Staphylococcus aureus

J Gen Microbiol, 1993 Jun, 139 ( Pt 6), 1301 - 6
Involvement of the accessory gene regulator (agr) in expression of type 5 capsular polysaccharide by Staphylococcus aureus; Dassy B et al.; The effect of an agr mutation on expression of type 5 capsular polysaccharide (CP) by Staphylococcus aureus Newman was investigated in different complex and synthetic media . CP expression by the agr mutant was strongly reduced in certain media but slightly in others, indicating that CP synthesis is positively controlled by agr . CP expression occurred in the post-exponential growth phase in both wild-type and mutant strains, suggesting that other regulatory systems could act in conjunction with agr.

Infect Control Hosp Epidemiol, 1993 Jun, 14(6), 331 - 6
Methicillin-resistant Staphylococcus aureus in a nursing home and affiliated hospital: a four-year perspective; Strausbaugh LJ et al.; OBJECTIVES: To determine the effect of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a nursing home on the subsequent MRSA caseload in a closely affiliated hospital . DESIGN: Observational and descriptive; routine and special MRSA surveillance data for nursing home and hospital were reviewed for a four-year period (1988 to 1991) as were records regarding patient transfers from nursing home to hospital . SETTING: The 120-bed nursing home care unit (NHCU) and the geographically separate 434-bed acute care facility (hospital) of the Portland Veterans' Affairs Medical Center (PVAMC) . PATIENTS: Veterans hospitalized in the acute care division of NHCU . RESULTS: Following the introduction of MRSA into the NHCU in December 1987, it quickly disseminated . Two to 32 newly colonized or infected patients were recognized in each quarter of the study period . Facility-wide prevalence surveys on two occasions disclosed MRSA colonization rates of 34% and 10% . During the study period, 15 to 54 (mean: 37.6) patients were transferred each quarter from the NHCU to the hospital of the PVAMC . The number of MRSA cases transferred ranged from 0 to 16 per quarter (mean: 5.4) . During the same period, the total number of MRSA cases in the hospital increased, rising from 7 cases in 1987 to 16 in 1988, 48 in 1989, 34 in 1990, and 35 in 1991 . The percentage of hospital MRSA cases accounted for by NHCU transfers was 0% in 1988, 38% in 1989, 12% in 1990, and 11% in 1991 . CONCLUSIONS: Despite the steady flow of patients between the NHCU and the hospital, the MRSA outbreak in the NHCU was associated with only a modest increase in the MRSA caseload at the affiliated hospital.

J Antimicrob Chemother, 1993 Jun, 31(6), 909 - 17
Treatment of familial staphylococcal infection--comparison of mupirocin nasal ointment and chlorhexidine/neomycin (Naseptin) cream in eradication of nasal carriage; Leigh DA et al.; Twenty-six families with recurrent staphylococcal infections were treated with either mupirocin nasal ointment (group M) or chlorhexidine neomycin (Naseptin) cream (group N) to the anterior nares, each combined with chlorhexidine soap for washing and chlorhexidine powder applied to other possible carriage sites . Patients receiving mupirocin following failure with chlorhexidine/neomycin (group M/N) were also treated . Treatment was given for seven days to 99 patients, 32 index (infected) patients and 67 family members . Follow-up swabs were collected by a study nurse 8, 14, 28, and 91 days after starting treatment . The carriage of Staphylococcus aureus in the anterior nares was 67%, in the axillae 22%, in the groin 23%, and perianal 19% . The carriage rates in the index patients was higher than family members, in all sites . The eradication of S . aureus from the nasal carriage site after therapy at 8 days was 95% in group M, 85% in group M/N and 61% in group N . Recolonization during the follow-up period was much less in those treated with mupirocin: 57% of patients in group M and 42% in group M/N were not carriers at 91 days, whereas 89% of patients group N were again colonized . Assessment clinically and in terms of prevention of further infective lesions showed that there was a higher response to mupirocin than to chlorhexidine/neomycin . Mupirocin nasal is a successful therapy for removing nasal carriage of S . aureus and has a prolonged effect on recolonization.

Biol Chem Hoppe Seyler, 1993 Jun, 374(6), 395 - 402
Limited proteolysis of chloroplast glyceraldehyde-3-phosphate dehydrogenase (NADP) from Spinacia oleracea; Zapponi MC et al.; The structural and functional properties of chloroplast glyceraldehyde-3-P-dehydrogenase I (D-Glyceraldehyde-3-phosphate: NADP oxidoreductase (phosphorylating) EC 1.2.1.13) from Spinacia oleracea were investigated by limited proteolysis . The enzyme is insensitive to trypsin and chymotrypsin, while Staphylococcus aureus V8 protease cleaves the C-terminal region of its subunits . Subunit A (36 kDa) is only partially cleaved at Glu 317 . No intact subunit B (39 kDa) is found at the end of the proteolytic experiment: two forms are originated from this subunit which is cleaved at Glu 342 and Glu 320 . Proteolytic cleavage at these sites does not significantly alter enzymatic activity, but leads to destabilization of the protein . Unlike the intact parent enzyme (600 kDa) the cleaved enzyme behaves as a 150-kDa species in size exclusion chromatography.

J Appl Bacteriol, 1993 Jun, 74(6), 637 - 44
Potential problems in the use of oligonucleotide probes for staphylococcal enterotoxin genes; Okoji CN et al.; Oligonucleotide probes unique to the five major enterotoxin genes of Staphylococcus aureus were synthesized and used to detect DNA sequences homologous to these genes in 27 non-clinical isolates of Staph . aureus isolated from nasal swabs of 74 healthy human volunteers . Genomic DNA from all 27 isolates reacted with at least one of the probes . In a phenotypic assay for toxin production by a reverse passive latex agglutination test however, only 15 of the 27 isolates produced enterotoxin in culture . The results raise the possibility that a number of Staph . aureus isolates harbour DNA sequences that are apparently silent or mutant copies of the enterotoxin genes . This complicates the identification of enterotoxin producers by tests which depend on oligonucleotide or DNA hybridization.

Am J Hematol, 1993 Jun, 43(2), 81 - 5
Heterogeneous proliferative effect of tumor necrosis factor-alpha and lymphotoxin on mitogen-activated B cells from B-chronic lymphocytic leukemia; Alvarez-Mon M et al.; The proliferative effect of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin on B cells from patients with B-chronic lymphocytic leukemia (B-CLL) was studied . Fresh purified B-CLL lymphocytes showed no proliferative response to either recombinant (r) TNF-alpha or r-lymphotoxin . However, after "in vitro" activation of B-CLL lymphocytes for 2 days with Staphylococcus aureus Cowan 1 (SAC), four of seven patients showed enhanced blastogenic response in the presence of either rTNF-alpha or r-lymphotoxin . We also found that the proliferative response of SAC-activated B-CLL lymphocytes to the two cytokines was independent of that found in the presence of interleukin-2 . These results demonstrate that TNF-alpha and lymphotoxin can heterogeneously support the proliferation of in vitro activated B cells from B-CLL patients and may reflect the biological heterogeneity of B-CLL disease.

Am J Hematol, 1993 Jun, 43(2), 149 - 50
Ultrastructure of neutrophilic phagosome of autologous platelet in vivo in specific granule deficiency; Sakura T et al.; The ultrastructure of neutrophilic phagosomes containing autologous platelets in vivo from a woman with specific granule deficiency is described . This phagosome formation was observed only when she had developed pneumonia due to Staphylococcus aureus . Therefore, the phenomenon might be induced by severe bacterial infection under an abnormal neutrophilic condition accompanied by specific granule deficiency.

Eur J Nucl Med, 1993 Jun, 20(6), 490 - 4
Improved detection of a staphylococcal infection by monomeric and protein A-purified polyclonal human immunoglobulin; Calame W et al.; The present study was undertaken to compare the technetium-99m labelled non-specific polyclonal human immunoglobulin (Ig) with 99mTc-labelled monomeric human immunoglobulin (m-Ig), 99mTc-labelled, protein A-purified, human immunoglobulin (A-Ig) and 99mTc-labelled monomeric, protein A-purified, human immunoglobulin (mA-Ig) as tracer agents for the detection of a thigh infection with Staphylococcus aureus . In vitro the binding of the various tracer agents to bacteria at various intervals was determined . For the in vivo evaluation, mice were infected and received one of the various labelled proteins . Scintigrams were made 0.25, 1, 4 and 24 h later . All 99mTc-labelled Igs bound to bacteria in vitro: the percentages of binding for the m-Ig (from 1 h onwards) and A-Ig and mA-Ig (from 3 h onwards) were significantly higher than that for Ig . The in vivo target-to-non-target (T/NT) ratios were significantly higher from 4 h onwards for all purified Igs than for Ig . Protein A-purified Igs yielded higher T/NT ratios than m-Ig . Furthermore, the amount of activity in the liver was significantly lower 24 h after administration of m-Ig, A-Ig and mA-Ig than after administration of Ig . It is concluded that in this experimental infection 99mTc-labelled monomeric Ig localizes a staphylococcal thigh infection better and faster than 99mTc-labelled unpurified Ig . However, the accumulation obtained with protein A-purified Ig or protein A-purified monomeric Ig was the highest of all tracer agents tested.

Kansenshogaku Zasshi, 1993 Jun, 67(6), 584 - 8
{Three cases with pelvic dead space infection after total cystectomy caused by methicillin-resistant Staphylococcus aureus (MRSA)--local injection of vancomycin}; Kiyota H et al.; We recently had three patients with pelvic dead space infection caused by methicillin-resistant Staphylococcus aureus (MRSA) after total cystectomy for urothelial cancer . All were male and aged from 67 to 74 years old . As for underlying diseases, two of them had bladder cancer and one of them had bladder cancer and right ureteral cancer . Total cystectomy and ileal conduit were performed for two patients with bladder cancer, and total cystectomy, nephroureterectomy and ureterocutaneoustomy were performed for a patient with bladder cancer and ureteral cancer . Pelvic dead space infections caused by MRSA appeared after 15-30 days postoperatively . All patients were cured after we locally administered 0.5 g of vancomycin twice a day for 10-11 days from the drains to the pelvic dead spaces . All patients had preoperative antitumor chemotherapy and the postoperative administrations of beta-lactams in common . From these results, we suggest that local administration of vancomycin is effective for the pelvic dead space infection caused by MRSA after total cystectomy.

Clin Infect Dis, 1993 Jun, 16(6), 766 - 71
Meningitis due to Staphylococcus aureus in children; Givner LB et al.; Meningitis due to Staphylococcus aureus is uncommon, occurring primarily in patients with known preexisting abnormalities of the CNS (including patients who have undergone previous neurosurgery or trauma) . We reviewed our experience with meningitis due to S . aureus in children seen at two medical centers . Among the 40 patients, 32 (80%) had a known predisposing abnormality of the CNS at the time of diagnosis of S . aureus meningitis; all of these 32 patients had had recent neurosurgery, most for placement or revision of a ventriculoperitoneal shunt . Eight patients had no known predisposing CNS abnormality . Four of these eight patients were known to be immunocompromised . The other four patients all had an occult CNS abnormality demonstrated during subsequent workup . Our series demonstrates that when the diagnosis of S . aureus meningitis is made in the absence of a known predisposing CNS abnormality or immunologic defect, then a timely search for an occult CNS abnormality should be undertaken.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1334 - 42
Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome; Walsh TJ et al.; Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals . Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance . The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin . We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy . Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable . Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups . Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18) . The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04) . Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 {83%} subjects) . Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01) . Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02) . Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen . T/S plus rifampin was less effective in clearing both pressure and other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds . There were no significant differences in toxicity between the two regimens . Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state . The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

Am J Physiol, 1993 Jun, 264(6 Pt 2), H1878 - 83
Thromboxane A2 analogue, U-46619, potentiates calcium-activated force in human umbilical artery; Crichton CA et al.; It has previously been shown that human umbilical artery (HUA) smooth muscle produces thromboxane A2 in response to increasing oxygen levels and that this thromboxane promotes contraction . To investigate the intracellular action of thromboxane A2, strips of HUA longitudinal smooth muscle were permeabilized using alpha-toxin from the bacterium Staphylococcus aureus . This treatment rendered the surface membrane permeable to low-molecular-weight substances but left functional thromboxane A2 receptors . Tension measurements were used to investigate the effect of the stable thromboxane A2 analogue, U-46619, on the Ca2+ sensitivity of smooth muscle contractile proteins . U-46619 (1 nM to 1 microM) potentiated submaximal Ca(2+)-activated force (generated by {Ca2+}, 50 nM to 3 microM) but not maximal Ca(2+)-activated force (generated by {Ca2+}, 10-100 microM) . The specific thromboxane A2 receptor antagonist, GR-32191B (1 microM), inhibited the action of U-46619 (0.1 microM) . The potentiation of submaximal Ca(2+)-activated force produced by the muscle in response to U-46619 (0.1 microM) was antagonized by guanosine 5'-O-(2-thiodiphosphate) (1 mM), the nonhydrolyzable analogue of GDP, and mimicked by guanosine 5'-O-(3-thiotriphosphate) (100 microM), the nonhydrolyzable analogue of GTP . These results suggest that U-46619 acts via the previously identified thromboxane A2 receptor to promote Ca2+ sensitivity of tension production in HUA smooth muscle . Furthermore, this effect appears to be mediated via a G protein.

Kidney Int, 1993 Jun, 43(6), 1357 - 62
Methicillin-resistant Staphylococcus aureus nasal carriage and infections in CAPD; Lye WC et al.; In view of the increasing concern about methicillin-resistant Staphylococcus aureus (MRSA) infections, we studied the characteristics and outcome of MRSA nasal carriage and infections in our CAPD program . All patients entering into the CAPD program from January 1989 to December 1991 were enrolled into the study . The patients' anterior nares were cultured before the implantation of the catheters . Peritoneal dialysis-related infections were diagnosed based on standard criteria . Data on MRSA nasal carriage, exit-site and tunnel infections and peritonitis were prospectively collected . A total number of 167 patients with 225.9 patient dialysis years were studied with a mean follow-up duration of 16.2 +/- 9.5 months . There were 28 patients with MRSA nasal carriage . The carrier state was unrelated to age, sex and presence of diabetes mellitus . MRSA nasal carriage was associated with a significant increase in the rate of peritonitis (P < 0.01) and exit-site infections (P < 0.01), the number of catheter losses, and CAPD patient dropout (P < 0.001) . A total of 30 patients had MRSA infections . In this group, 15 patients had 24 episodes of peritonitis; 20 had 22 episodes of exit-site infections; and 1 had tunnel infection . Fourteen patients had a combination and/or multiple episodes of infections . Treatment of MRSA infections with intraperitoneal vancomycin was unsuccessful in 12 patients (40.0%) resulting in catheter loss . Nine patients (30.0%) dropped out of CAPD after treatment failure for MRSA peritonitis . The patient dropout rate per infection for MRSA infections was comparable to Pseudomonas and fungal infections, but was significantly higher than MSSA infections (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Singapore Med J, 1993 Jun, 34(3), 221 - 4
A survey of postoperative wound infections in obstetrics and gynaecology--the Kandang Kerbau Hospital experience; Chia JY et al.; Postoperative wound infection is of great importance to both the surgeon and patient . This study covers 6,639 major operations in Kandang Kerbau Hospital, Singapore over a 12-month period . The overall wound infection rate was 2.26% . The highest wound infection rate occurred in hysterectomies and the lowest in laparoscopies . There was a good correlation between monthly caesarean wound infection rate and number of caesarean sections . Staphylococcus aureus was the most common organism isolated . The wound infection rate was also higher in crowded wards and among some surgeons . After distribution of the survey results, we noted a decrease in wound infection rate for some surgeons and a changing pattern in the use of antibiotics . A further study of other risk factors was encouraged.

J Dermatol Sci, 1993 Jun, 5(3), 150 - 64
Production of staphylococcal impetigo-like lesion on human skin explants in culture; Abe Y et al.; We produced a highly reproducible experimental impetigo-like lesion in normal human skin explants in culture . The three Staphylococcus aureus strains we used were an isolate from a human impetigo (E strain), an isolate from a human furunculosis (N strain) and ATCC 29213 strain . E strain was a protein A positive, coagulase type V, producer of exfoliative toxin (ET) and beta-toxin . N strain was a coagulase type IV, ET non-producer and alpha-toxin positive . ATCC 29213 was a coagulase type II, ET non-producer, and alpha-, beta-, and delta-toxin positive . Normal human skin samples were obtained from 8 adult skin surgery patients . One specimen was obtained from human oral mucosa . Small pieces of the samples were slightly abraded on the epidermal surface and cultured on lens paper rafts floating in Eagle's Minimum Essential Medium in an atmosphere of 5% CO2 and 95% air . Fifty microliters of the respective bacterial suspensions were applied to the epidermal surfaces of the explants . The inoculated surfaces were then occluded under sterile plastic plaster . Histologically, the formation of intraepidermal blisters at the granular layer level with acantholytic cells was observed in all 8 of the skin specimens at 10 h after inoculation with E strain . The specimen from an oral mucous membrane did not produce similar changes with any of the three S . aureus strains . Neither N or ATCC strains developed bullae in the epidermis at 6, 10 or 18 h after inoculation . Immunofluorescent examination revealed that the inner surfaces of blisters in the epidermis were lined with anti-ETA antibody . Under the electron microscope, the blisters of the specimens which had been inoculated with strain E contained only a few S . aureus cells . These results suggest that blister formation at the granular layer level with acantholytic cells is mediated by ET action at the granular layer level and occurs without invasion of lymphocytes or neutrophils, or the involvement of any serum components . Therefore, under appropriate conditions, impetigo could develop even in adults.

J Physiol, 1993 Jun, 465, 629 - 45
Effects of pH and inorganic phosphate on force production in alpha-toxin-permeabilized isolated rat uterine smooth muscle; Crichton CA et al.; 1 . Strips of longitudinal smooth muscle isolated from rat uterus were permeabilized using crude alpha-toxin from the bacterium Staphylococcus aureus . This treatment rendered the surface membrane permeable to small molecular weight substances . Simultaneous measurements of tension and calcium concentration ({Ca2+}) (using indo-1 fluorescence) were used to investigate the effects of pH and inorganic phosphate concentration ({Pi}) on Ca(2+)-activated force generated by the contractile proteins . 2 . Raising the {Pi} from 1 to 11 mM at a pH of 7.2 depressed both maximal and submaximal Ca(2+)-activated force . This effect of Pi was concentration dependent having the majority of its effect by 6 mM . 3 . Further experiments at a submaximal {Ca2+} showed that Ca(2+)-activated force was enhanced by raising {Pi} from 6 to 11 mM suggesting that Pi increased the Ca2+ sensitivity of tension production . Based on these results, calculations indicate that the apparent affinity constant of Ca2+ for the contractile proteins increased from 4 x 10(6) M-1 to 6 x 10(6) M-1 on raising {Pi} from 1 to 11 mM . 4 . Lowering pH from 7.2 to 6.7 at a {Pi} of 1 mM potentiated Ca(2+)-activated force with a small depression in the apparent Ca2+ sensitivity of tension production . This effect of pH on maximum (100 microM Ca2+) and submaximum (0.3 microM Ca2+) Ca(2+)-activated force was observed over a range of acidic pHs (7.0-6.7) . 5 . Increasing pH from 7.2 to 7.7 at a {Pi} of 1 mM depressed Ca(2+)-activated force with no effect on Ca2+ sensitivity of tension production . 6 . Spontaneous contractions in intact rat myometrium are abolished under hypoxic conditions . Under these same conditions intracellular {Pi} rises and pH falls . The results of this study suggest that taken individually neither the effect of a rise in {Pi} nor a fall in pH on Ca(2+)-activated force generated by the contractile proteins can account for the effect of hypoxia on spontaneous contractions.

Mikrobiol Z, 1993 Jun-Aug, 55(4), 68 - 74
{The carriage of Staphylococcus aureus among different population groups}; Malanchin IN; The level of carriage of Staphylococcus aureus in three biotopes (nose, fauces, hand skin) and categories of carriers among students and teachers of the Medical Institute, medical personnel of surgical department and maternity hospital as well as the workers of combine building plant have been studied . The higher percentage of Staphylococcus aureus carriers was established in the nasal cavity of the maternity hospital personnel (p < 0.001) and on the hand skin of the personnel of surgical stationary (p < 0.05) as compared to the students and teachers . Carriage frequency of Staphylococcus aureus among the workers several times exceeded its level in the control group . The strains of the third phage group predominated among the personnel of surgical department, those of the second and fourth phage, groups, among the maternity hospital workers . Representatives of the second phage group were isolated in the plant workers . High level of carriage among the workers creates preconditions for the development of purulent diseases of the hand and fingers after microtraumas at the plant . All this dictates a necessity to eliminate Staphylococcus aureus in the carriers of all three biotopes.

Zentralbl Bakteriol, 1993 Jun, 279(2), 214 - 24
Antibiogram typing of methicillin-resistant Staphylococcus aureus: a comparison with phage typing, biotyping and API Staph; Hamilton-Miller JM et al.; 68 strains of methicillin- and gentamicin-resistant Staphylococcus aureus (MRSA) have been characterized by four different methods . First, by their production of lecithinase, lipase, pigment and sheep haemolysin . Second, by API Staph code . Third, by their sensitivity to 9 antibiotics . Fourth, by phage typing using the International Set and Supplementary phages . The third method was the most discriminatory . The combination of the first three techniques provides a highly effective, cheap and simple system to type MRSA . 80 separate MRSA strains from 26 countries were found to belong to a wide variety of phage types . Most were of group III . The most commonly found types were 85 (6 strains), 84 (4 strains) and 47 (3 strains).

Antibiot Khimioter, 1993 Jun, 38(6), 30 - 4
{Antibiotic resistance plasmids in various strains of Staphylococcus aureus}; Gabisoniia TG et al.; Plasmids with the molecular weights of 1.6 to 21.0 MD were detected in Staphylococcus aureus . The plasmids determined resistance to benzylpenicillin, ampicillin, streptomycin, erythromycin, tetracycline, chloramphenicol, arsenate and arsenite . Strain p16 of Staphylococcus aureus contained plasmid pL16 with the molecular weight of 18.0 MD determining resistance to erythromycin, streptomycin, benzylpenicillin and ampicillin . The plasmid has two replication sites and is likely a natural recombinant of two plasmids.

Fukushima J Med Sci, 1993 Jun, 39(1), 35 - 42
The properties and mec A gene of the methicillin-resistant Staphylococcus aureus isolated in Fukushima Medical College Hospital; Tanabe F et al.; The 106 methicillin-resistant strains of Staphylococcus aureus (MRSA) isolated in Fukushima Medical College Hospital were examined for their properties and mecA gene . The strains produced four types of coagulase, of which type II was the most common, produced by 84 (79.2%) . Beta-lactamase was produced by 58 (50%) . Enterotoxins were produced by 45 (42.5%), most of which (39/106, 36.8%) were of type A . Thirty-four strains (32.1%) produced both enterotoxins and toxic shock syndrome toxin-1 . All strains were susceptible to vancomycin and arbekacin, although they were mostly resistant to many other antibiotics . Using the polymerase chain reaction (PCR) technique, the mecA gene was detected in 57 (91.9%) of the 62 strains used . In addition, one of the 42 methicillin-susceptible strains isolated had the mecA gene . These results indicate that detection of the mecA gene by the PCR technique is a rapid and accurate way to identify methicillin resistance.

J Hosp Infect, 1993 Jun, 24(2), 139 - 51
Strains of methicillin-resistant Staphylococcus aureus isolated in Australian hospitals from 1986 to 1990 . Australian Group for Antimicrobial Resistance; Vickery AM; Major teaching hospitals in each state of Australia participated in five annual surveys (1986 to 1990) of clinically significant isolates of Staphylococcus aureus . All isolates of methicillin-resistant S . aureus (MRSA) were phage typed with the Basic International Set and an Australian experimental set of typing phages . One or two predominant strains were isolated in individual states during each of the survey periods . Less than 3% (33 of 1243) of MRSA isolates were not typable and more than 86% (1070 of 1243) belonged to strains that were isolated on at least five occasions during a single survey period . Strains of phage types 83A/85/95/90/88@47T/90A/87M/13M and 85/90/88@47T/90A/87A were the most prevalent, but each was identified in only four of the five surveys . Isolates of phage type (83A/85/95) weak/88@87M persisted throughout the survey period.

Zentralbl Bakteriol, 1993 Jun, 278(4), 510 - 7
Unrelatedness of multiply resistant Staphylococcus aureus with resistance to methicillin and to quinolones (QR-MRSA) as evident from SmaI-digestion patterns of genomic DNA; Witte W et al.; Methicillin-resistant S . aureus with quinolone-resistance (QR-MRSA) isolated in Germany from three outbreaks of nosocomial infections and from sporadic nosocomial infections in five hospitals exhibited different SmaI-restriction patterns of their genomic DNA . Phage-typing and determination of plasmid profiles performed in parallel confirmed this differentiation, with one exception . These results indicate that there is obviously no overregional spread of one particular QR-MRSA clone and that quinolone resistance has developed independently in different MRSA.

Curr Microbiol, 1993 Jun, 26(6), 337 - 44
The membrane binding C-terminus of protein A from Staphylococcus aureus affects its cellular localization and causes structural deformation when expressed in Escherichia coli; Warnes A et al.; Protein A from Staphylococcus aureus is a powerful diagnostic reagent and has several uses in human disease therapy . Expression in non-pathogenic Escherichia coli containing recombinant plasmids coding for this protein has increased its availability, but can reduce the stability of the plasmid-bearing host . By employing immune electron microscopy, we have determined that E . coli containing stable plasmids coding for a truncated version of protein A, without the membrane binding site, secrete this protein through the cytoplasmic membrane and into the periplasmic space, where it accumulates . E . coli containing unstable plasmids, however, which code for the complete protein including the membrane-binding site, target the protein into the cytoplasmic membrane . This accumulation of protein A in the E . coli cytoplasmic membrane inhibits the formation of septa between dividing cells and results in aberrant elongated, multi-chromosomal forms.

Zentralbl Bakteriol, 1993 Jun, 279(2), 180 - 90
Binding of collagen, fibronectin, lactoferrin, laminin, vitronectin and heparan sulphate to Staphylococcus aureus strain V8 at various growth phases and under nutrient stress conditions; Liang OD et al.; We have examined how Staphylococcus aureus strain V8 cells interact with 125I-labelled extracellular matrix (ECM) and serum proteins (collagen type I and IV), fibronectin, lactoferrin, laminin, vitronectin, and heparan sulphate at various phases of the growth cycle . Maximal binding of these glycoproteins and heparan sulphate to the bacteria occurred after 17 to 20 h in the late stationary phase except for fibronectin-binding, which was maximal after 12 to 14 h . Binding of the glycoproteins and heparan sulphate to S . aureus V8 under nutrient stress conditions exhibited complex patterns based on different starving conditions and various binding ligands . In general, bacteria starved in distilled water and 0.02 M potassium phosphate buffer (pH 7.2) at room temperature showed high susceptibility to all binding ligands within the first 18 h, followed by entering a lower binding period (except for collagen-binding which still remained high) . The binding was not correlated to cell surface charge or hydrophobicity of the bacteria . Furthermore, extracellular and cell-associated proteolytic activity of starved cells against ECM and serum proteins was found to be greater than for non-starved cells . Thus, S . aureus could sustain its ability to bind various connective tissue and cell surface components during a long period of time even in the absence of energy-yielding substrates.

Presse Med, 1993 May 29, 22(19), 909 - 13
{Severe infections caused by methicillin-resistant Staphylococcus aureus . 62 cases}; May T et al.; A French multicentre study was conducted in 15 Infectious Diseases departments; 347 cases of severe staphylococcal infections were collected during one year (October 1989 to October 1990): Two-hundred and fifty-eight strains were analysed with complementary bacteriological studies, including 62 strains of methicillin-resistant Staphylococcus aureus . Epidemiological, clinical and therapeutic aspects were investigated . Nosocomial infection was responsible for 90 percent of the cases, and previous antibiotic therapy was reported in 74 percent . An invasive procedure was incriminated in 43 patients (69 percent); intravenous catheter (38 percent), mechanical ventilation (31 percent), surgery (22 percent), prosthetic device (20 percent) . Thirty-nine patients were treated with glycopeptides either alone or in combination with beta-lactams, aminoglycosides, fucidic acid, fosfomycin, rifampicin, quinolones or synergistines, showing the great diversity in the choice of antibiotics in methicillin-resistant S . aureus infections . More than 90 percent of these strains were resistant to gentamicin and quinolones, 80 percent of clindamycin and 70 percent to rifampicin . No resistance to glycopeptides (vancomycin or teicoplanin) was observed . Prognosis was severe, with a mortality rate of 35 percent, justifying educational and prophylactic measures in at risk medical departments.

Biochem Biophys Res Commun, 1993 May 28, 193(1), 6 - 12
Ins(1,4,5)P3 and glutathione increase the passive Ca2+ leak in permeabilized A7r5 cells; Missiaen L et al.; Thapsigargin depletes intracellular Ca2+ stores by its inhibitory effect on the Ca2+ pumps, which unmasks an aspecific Ca2+ leak from the stores . This aspecific Ca2+ permeability of the stores was further investigated using 45Ca2+ fluxes on intact and permeabilized A7r5 smooth-muscle cells . Stores in intact cells were found to be more leaky for Ca2+ than those in saponin-permeabilized or Staphylococcus aureus alpha-toxin-permeabilized cells, which suggests that a cytosolic factor may be involved . Supplementing the medium bathing the permeabilized cells with a submaximal Ins(1,4,5)P3 concentration increased the leakiness of the stores . Glutathione also increased the aspecific Ca2+ leak . This effect occurred with both the reduced and the oxidized form but reduced glutathione was more effective . Our data show that basal Ins(1,4,5)P3 levels and glutathione can contribute to the relatively high Ca2+ leak in intact cells . The washing out of these substances during permeabilization can reduce the aspecific leakiness of the stores.

J Biol Chem, 1993 May 25, 268(15), 11247 - 55
Phosphorylation weakens DNA binding by peptides containing multiple "SPKK" sequences; Green GR et al.; Sea urchin testis-specific H1 and H2B histones (Sp H1 and Sp H2B) are characterized by reversibly phosphorylated N-terminal regions consisting largely of multiple clustered "SPKK" tetrapeptides (serine-proline adjacent to two basic amino acids) . This report presents data showing differences in DNA affinities between peptides containing dephosphorylated and phosphorylated N-terminal regions . Sp H1 and its phosphorylated derivative (pSp H1) were purified by hydroxylapatite chromatography . Peptides containing the N-terminal regions of Sp H1 and pSp H1 (NP and pNP, respectively) were produced by digestion with Staphylococcus aureus protease . NP and two forms of pNP differing in phosphate content were purified by DNA-cellulose chromatography . The DNA affinities of the peptides were compared using several criteria . NP was bound more tightly by DNA-cellulose than pNPs . NP precipitated DNA under a broad range of NaCl concentrations; pNPs did not . Both NP and pNPs protected DNA against thermal denaturation, but NP created a more stable DNA-peptide complex . Thirty to sixty times more pNP than NP was required to obtain equivalent inhibition of Hoechst 33258 binding to DNA . NP did not behave as a competitive inhibitor of DNA binding by Hoechst 33258 binding to DNA . We conclude that during spermatogenesis, dephosphorylation of the Sp H1 N-terminal region increases its basicity and thus its affinity for DNA.

Med J Aust, 1993 May 17, 158(10), 671 - 4
Bacteraemia and fungaemia in an Australian general hospital--associations and outcomes; McGregor AR et al.; OBJECTIVE: To obtain a comprehensive overview of bacteraemia and fungaemia in a general hospital and thus to determine the incidence, primary sites of sepsis, organisms involved and associated mortality . DESIGN: A prospective laboratory and clinical evaluation of all episodes where microorganisms were cultured from blood over one year . SETTING: The two major hospitals in the Australian Capital Territory which have both community and referral functions . These hospitals provide obstetric and paediatric services along with adult medicine and surgery . PATIENTS: All those who acquired bacteraemia in hospital or presented with a blood-stream infection documented by a positive blood culture . RESULTS: During 1990, 474 clinical episodes of bacteraemia or fungaemia were detected in 446 patients . Significant isolates were identified in 317 of these episodes . The incidence of significant sepsis was 8.1 episodes per 1000 admissions . The most common organisms isolated were Staphylococcus aureus (75 episodes) and Escherichia coli (70 episodes) . One hundred and twenty-eight episodes were hospital acquired . Intravenous catheters were the primary sites of sepsis in 68 episodes . Fifty patients died . Higher mortality rates were associated with patients over 60 years of age, respiratory tract sepsis, endocarditis and the presence of an underlying malignancy . CONCLUSION: Bacteraemia and fungaemia are common problems . Nosocomial bacteraemia accounted for 40% of episodes . Half of these nosocomial infections were iatrogenic . Many of the episodes of intravenous catheter sepsis were potentially preventable . Ongoing programs of surveillance of bacteraemia, with the evaluation of primary site, associated features and mortality, are essential to monitor the dimensions of this problem and aid in implementing effective preventive strategies.

J Immunol, 1993 May 15, 150(10), 4261 - 9
Differential expression of IL-4 receptors in human T and B lymphocytes; Mozo L et al.; IL-4R have been described in unstimulated human T and B lymphocytes . However, a precise comparative study on the expression and regulation of IL-4R in isolated human T and B cell populations has not yet been fully assessed . We examined the mRNA levels and the cell membrane expression of IL-4R in freshly isolated T and B lymphocytes as well as in in vivo- and in vitro-stimulated cells . IL-4R protein expression and transcript levels were higher in tonsillar unstimulated B cells than in T cells . Splenic and peripheral blood B lymphocytes also expressed higher surface IL-4R in their membranes than T cells did . Large B lymphocytes from tonsils (in vivo-activated cells) obtained by Percoll gradient centrifugation displayed higher IL-4R levels than resting cells . On activation in vitro of T lymphocytes with IL-2 or PHA, slight increments on the IL-4R mRNA and protein levels were achieved . However, maximal levels of IL-4R expression were obtained on T cell incubation with IL-4 at a concentration of 100 U/ml . Similarly, the same concentration of this lymphokine up-regulated the surface IL-4R molecules and the IL-4R mRNA levels in purified B lymphocytes . Cross-linkage of surface Ig by insolubilized anti-IgM potentiated the effect of IL-4 in up-regulating IL-4R expression in B cells, probably by inducing outgrowth of IL-4R positive subpopulations . The B cell mitogen, Staphylococcus Aureus Cowan I, although inducing cell proliferation, was ineffective in promoting new receptor synthesis . Cell proliferation was not required for IL-4-dependent IL-4R up-regulation on both T and B lymphocytes.

Am J Cardiol, 1993 May 15, 71(13), 1186 - 97
Clinicopathologic features of active infective endocarditis isolated to the native mitral valve; Fernicola DJ et al.; Although a number of clinicopathologic studies in patients with active infective endocarditis (IE) have been reported, none have focused on patients studied at necropsy with active IE isolated to the mitral valve . We studied at necropsy 63 patients (aged 12 to 88 years {mean 50}, 44 males {70%}) with active IE limited to the native mitral valve: 21 (33%) had preexisting mitral valve disease (rheumatic in 8, prolapse in 3, hypertrophic cardiomyopathy in 1, and mitral annular calcium in 9), and the other 42 patients (67%) had previously normal mitral valves . Of the latter 42 patients, 22 (52%) had recognized predisposing factors to IE: opiate addiction in 14, habitual alcoholism in 6 and/or chronic hemodialysis in 4 . Staphylococcus aureus or epidermidis was the responsible organism in 32 patients (51%), and the active IE was associated with an infection elsewhere in the body in 31 patients (50%) . The active IE caused rupture of mitral chordae tendineae in 11 patients (18%), perforation of the anterior mitral leaflet in 7 patients (11%), and mitral ring abscess in 10 patients (16%) . Grossly visible systemic emboli were found in 44 patients (70%) and 33 (52%) had infarcts in 1 or more body organs . Thus, active IE isolated to the mitral valve in necropsied patients appears to be more common in males than females (2 to 1); the infection more commonly than not involves a preexisting anatomically normal valve rather than a preexisting abnormal one (2 to 1); the vegetations often do not cause or worsen valvular dysfunction; a predisposing factor is commonly present (2 of 3 patients), and the IE commonly is part of a generalized or systemic infection (1 of 2 patients).

FEMS Microbiol Lett, 1993 May 15, 109(2-3), 303 - 9
A murine IgG1 monoclonal antibody that binds specifically to outer surface protein A of Lyme disease spirochete Borrelia burgdorferi; Abolhassani M et al.; A murine monoclonal antibody, designated MA-2G9, directed against outer surface protein A (OspA) of the Lyme disease spirochete, Borrelia burgdorferi, has been produced . Antibody MA-2G9, IgG1 subclass, was purified by affinity chromatography on protein G Sepharose column and used for purification of OspA antigen from Borrelia burgdorferi cell lysate . Epitope specificity was studied by Western immunoblotting, using several strains of B . burgdorferi and non-Lyme disease bacteria such as Treponema pallidum and B . hermsii . The MA-2G9 monoclonal antibody reacted specifically with recombinant OspA as well as with native OspA in sonicated B . burgdorferi strains . No reaction was observed with T . pallidum, Escherichia coli, Staphylococcus aureus and B . hermsii lysates . The MA-2G9 antibody also recognized the denatured form of OspA indicating that it is directed against sequential epitope and not conformational epitope.

FEMS Microbiol Lett, 1993 May 15, 109(2-3), 279 - 82
Transformation and expression of a staphylococcal plasmid in Escherichia coli; Saha D et al.; A multiple antibiotic-resistant Staphylococcus aureus, was found to possess three plasmid bands in agarose gel electrophoresis . A plasmid of approximately 4.3 kb (pMC790/2) was found to code for ampicillin and tetracycline resistance and to have one EcoRI site when transformed into S . aureus RN 4220 . pMC790/2 in unmodified form was transformed into a recA- E . coli at a frequency of 1.2 x 10(4) transformants/micrograms of plasmid DNA . Plasmid (pMC790/2) replicated, maintained itself stably and expressed far better in the E . coli host than in S . aureus.

Appl Environ Microbiol, 1993 May, 59(5), 1515 - 9
Repair and enterotoxin synthesis by Staphylococcus aureus after thermal shock; Hernandez FJ et al.; To study repair and enterotoxin synthesis, four staphylococcal strains (FRI-100, FRI-137, FRI-472, and S6) were subjected to sublethal heat treatment, transferred to four liquid repair media (1% powdered skim milk in distilled water, complex medium, M9 minimal salt medium, and saline solution), and then incubated at different temperatures . Powdered skim milk proved to be the most efficient medium for promoting the repair of injured cells, particularly at 37 degrees C . Minimal salt medium also gave good results . Salt tolerance also increased at 4 degrees C, although it did not reach normal values . After 6 h of incubation at 37 degrees C in powdered skim milk, strain FRI-100 synthesized detectable amounts of enterotoxin A . After 10 h of incubation in the same medium at the same temperature, enterotoxins were detected in all of the strains.

Antimicrob Agents Chemother, 1993 May, 37(5), 1144 - 9
blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus; Hackbarth CJ et al.; For Staphylococcus aureus, it is hypothesized that two genes located upstream of the beta-lactamase gene, blaZ, are required for the inducible expression of beta-lactamase . blaR1 is predicted to encode a signal-transducing membrane protein, and blaI is predicted to encode a repressor protein . These same two genes may also regulate the production of penicillin-binding protein 2a (PBP 2a), a protein essential for expression of methicillin resistance . To confirm that these two genes encode products that can control both beta-lactamase and PBP 2a production, blaI, blaR1, and blaZ with a 150-nucleotide deletion at the 3' end were subcloned from a 30-kb staphylococcal beta-lactamase plasmid and three beta-lactamase-negative strains of methicillin-resistant S . aureus were transformed with the recombinant plasmid containing that insert . The production of PBP 2a and a nonfunctional beta-lactamase was detected by fluorography and by immunoblots with polyclonal antisera directed against each of the proteins . Whereas the parent strains did not produce beta-lactamase and constitutively produced PBP 2a, PBP 2a and a truncated beta-lactamase were now inducible in the transformants . Therefore, two plasmid-derived genes regulate the production of both PBP 2a and beta-lactamase.

J Antibiot (Tokyo), 1993 May, 46(5), 850 - 7
Cephalosporins having a heterocyclic catechol in the C3 side chain . II . Improvement of pharmacokinetic profile; Iimura S et al.; 7-{(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido}-3- {propen-1-yl}-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized . Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity . The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity . The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S . aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.

Eur J Vasc Surg, 1993 May, 7(3), 277 - 82
Bacterial adherence to synthetic vascular prostheses and influence of human plasma . An in vitro study; Zdanowski Z et al.; The in vitro adherence of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli to five commercially available prosthetic vascular graft materials was compared . The influence of precoating the segments with human plasma for 2 h was also studied . S35-methionine was used to radiolabel bacteria . The segments were exposed to bacterial suspensions of approximately 10(7) CFU/ml at 37 degrees C for 0.5-18h . Following repeated washing in phosphate buffered saline (PBS), radioactivity associated with the segments was measured . The adherence of the three clinically relevant bacterial species was higher to untreated Dacron than to gelatin or collagen impregnated/coated Dacron or to PTFE . Furthermore, precoating of grafts with human plasma reduced bacterial adherence to woven Dacron, had a little effect on gelatin coated Dacron, but increased the adherence to collagen treated Dacron and, in particular, to PTFE.

Biotechniques, 1993 May, 14(5), 800 - 9
A baculovirus-expressed fusion protein containing the antibody-binding domain of protein A and insect luciferase; Oker-Blom C et al.; A fusion construct encoding two antibody-binding sites of protein A from Staphylococcus aureus and click beetle, Pyrophorus plagiophthalamus, luciferase (LucGR) was designed and expressed using the baculovirus system . The construct was inserted under the transcriptional regulation of the polyhedrin gene promoter of the Autographa californica nuclear polyhedrosis virus (AcNPV) and expressed in the insect Spodoperta frugiperda cell line during viral infection . The properties of the resultant chimeric protein product, protA-LucGR, were studied both in vivo and in vitro by using i) luminometry, ii) immunoblot analysis, iii) immunoprecipitation, iv) metabolic labeling procedures and v) luminescent immunoassays . Together, the results clearly demonstrate that the light-emitting properties of the fused luciferase construct remain intact . Further, the antibody-binding domain of protein A retains its activity as it binds to both rabbit and goat as well as human immunoglobulins . Due to the dual biological function of this fusion protein, it should provide a potential reagent within the field of molecular biology and diagnostics.

J Infect, 1993 May, 26(3), 265 - 77
Interactions of drugs acting against Staphylococcus aureus in vitro and in a mouse model; Renneberg J et al.; Two combinations of antibiotics, clindamycin with rifampicin and cloxacillin with netilmicin, were investigated for their activity against two strains of Staphylococcus aureus (a sensitive reference strain and a methicillin-resistant clinical isolate) by means of the in vitro checkerboard technique and an in vivo infected mouse model . The mouse model allowed drug interactions to be evaluated both from the changes in the number of bacteria surviving treatment and from the measured exposure to antibiotics at the site of infection . Specimens from the latter were evaluated twice (day 0 and day 2) in each experiment . The combination of cloxacillin and netilmicin exhibited a synergistic effect against the reference strain both in vitro and in vivo, whereas synergism was obtained under in vitro conditions only against the methicillin-resistant strain . The clindamycin and rifampicin combination acted synergistically or indifferently against both strains in vitro and at day 0 of the in vivo experiments . In contrast, on day 2 of infection, this combination had significantly greater bactericidal effect (synergism) compared to the combination of cloxacillin and netilmicin . These results illustrate the difficulties of interpreting in vitro results for clinical use.

J Dairy Sci, 1993 May, 76(5), 1290 - 7
Effect of a Staphylococcus aureus bacterin on serum antibody, new infection, and mammary histology in nonlactating dairy cows; Nickerson SC et al.; The influence of a Staphylococcus aureus mastitis vaccine on immunologic status and rate of new IMI was evaluated . At drying off, cows were vaccinated, either intramuscularly or subcutaneously in the area of the supramammary lymph node, or were left as unvaccinated controls; vaccinates received booster injections at 6 wk . Serum antibody concentrations, bacteriologic status, and SCC of quarter milk samples were determined . Four weeks after revaccination, cows were challenged by intramammary infusion of S . aureus and then killed 24 to 72 h later . Mean serum antistaphylococcal antibody titer of vaccinated cows during the trial was 4.7-fold that of controls . Challenge resulted in IMI rates of 92, 36, and 60% for control cows, cows vaccinated intramuscularly, and cows vaccinated in the area of the supramammary lymph node . Vaccination by either route had no influence on mammary parenchymal tissue components compared with controls; however, leukocyte infiltration was greater in quarters from cows vaccinated in the area of the supramammary lymph node than in quarters from unvaccinated controls . Plasma cell populations producing IgG1, IgG2, IgA, and IgM were greatest in quarters of cows vaccinated in the area of the supramammary lymph node followed by those in quarters of cows vaccinated intramuscularly and control cows.

J Dairy Sci, 1993 May, 76(5), 1285 - 9
Opsonization of Staphylococcus aureus by bovine immunoglobulin isotypes; Guidry AJ et al.; The ability of specific bovine Ig isotypes to enhance phagocytosis of Staphylococcus aureus by polymorphonuclear neutrophils was studied . Polymorphonuclear neutrophils were isolated from the blood of 14 lactating Holstein cows . Antibodies against S . aureus M10 were produced by two Holstein cows immunized via intramuscular injections and injections in the area of the supramammary lymph node with M10 emulsified in dextran sulfate . The IgG1, IgG2, and IgM were prepared from immune sera . Fluorescein-labeled, formalin-killed S . aureus M10 were opsonized with the respective isotypes prior to incubation with polymorphonuclear neutrophils . Percentage of polymorphonuclear neutrophils phagocytosing averaged 37.4, 1.1, 15.9, and 9.4% for immune sera, IgG1, IgG2, and IgM, using a M10: polymorphonuclear neutrophils ratio of 10:1; and 77.1, 1.8, 32.1, and 57.9 using a 40:1 ratio . When IgG1 was incubated with either IgG2 or IgM, phagocytosis was reduced to 10.0 and 5.0%, respectively, using the 10:1 ratio and 24.2 and 44.7%, respectively, using the 40:1 ratio . Significant variation occurred among cows in the ability of polymorphonuclear neutrophils to undergo phagocytosis independent of isotype and S . aureus M10: polymorphonuclear neutrophil ratio . These data show that IgG2 and IgM are opsonic for bovine polymorphonuclear neutrophils and that IgG1 inhibits the activity of both . These results will be helpful to determine immunization protocols to solicit synthesis of bovine IgM and IgG2 specific for S . aureus.

Rheum Dis Clin North Am, 1993 May, 19(2), 311 - 31
Nongonococcal bacterial arthritis; Mikhail IS et al.; The most salient features of nongonococcal bacterial arthritis are reviewed . Factors such as life expectancy, prosthetic joints, arthroscopies, the spread of the AIDS epidemic, and of methicillin-resistant Staphylococcus aureus as modifiers of the course of these arthritides are discussed.

J Clin Microbiol, 1993 May, 31(5), 1275 - 9
Accuracy of reporting of methicillin-resistant Staphylococcus aureus in a provincial quality control program: a 9-year study; Mackenzie AM et al.; We report the results of a province-wide quality control program in which five methicillin-resistant Staphylococcus aureus strains were circulated to all Ontario laboratories (hospital, private, and public health laboratories) on nine occasions between 1980 and 1989 . The level of expression of methicillin resistance in each of the isolates was determined by performing viable colony counts on serial dilutions of methicillin in agar, and each isolate was assigned to an expression class according to previous published criteria (A . Tomasz, S . Nachman, and H . Leaf, Antimicrob . Agents Chemother . 35:124-129, 1991) . Over this time there was an improvement in the performance of laboratories in the recognition of three strains that were relatively easy to detect (strains B, C, and E) . These strains were of expression class II, and 98% of laboratories reported correct identifications in 1986 . Performance in identifying two strains (strains A and D) of expression class I remained poor . Strain A was circulated in two surveys in 1987 and 1989, and laboratories were sent a questionnaire requesting details of the methods used in those two surveys . The methods used by the laboratories were classified into three categories: disk diffusion, single-plate screening by agar incorporation, and automated methods, which included premanufactured MIC panels . Between the 1987 and 1989 surveys, there was no change in the performance of the disk diffusion test (60% correct on both occasions), but there was improvement in the sensitivity of the agar incorporation test (36% correct in 1987 and 84% correct in 1989) and in automated methods (43% correct in 1987 and 79% correct in 1989) . Over a decade, there was overall improvement in the performance of laboratories in detecting easy-to-detect strains, but there were difficulties in detecting organisms of low expression class, and an organism of very low expression class should be designated as a control organism for routine testing of methicillin-resistant s . aureus isolates.

Infect Control Hosp Epidemiol, 1993 May, 14(5), 260 - 4
Oxacillin- and quinolone-resistant Staphylococcus aureus in Sao Paulo, Brazil: a multicenter molecular epidemiology study; Sader HS et al.; OBJECTIVE: To investigate the possibility of interhospital spread of multiresistant Staphylococcus aureus in Sao Paulo, Brazil . DESIGN: We evaluated 13 nosocomial S aureus strains selected because of resistance to oxacillin and ciprofloxacin . SETTING: The strains were collected between March 1991 and September 1991 from four different hospitals in Sao Paulo . Two were teaching hospitals, and two were private hospitals . PATIENTS: Each strain was isolated from a different patient . All patients were hospitalized when the strains were isolated . INTERVENTIONS: The strains were typed by restriction endonuclease analyses of plasmid DNA (REAP) using EcoRI, HindIII, RsaI, and AluI and by extended antibiogram profile (34 drugs) . RESULTS: All strains had identical plasmid and antibiogram profile . They demonstrated the same plasmid pattern as previously described in one of the hospitals studied . CONCLUSIONS: Our results suggest the dissemination of a unique oxacillin- and quinolone-resistant strain of S aureus in several hospitals of Sao Paulo, Brazil.

Diagn Microbiol Infect Dis, 1993 May-Jun, 16(4), 343 - 9
Synergy assessed by checkerboard . A critical analysis; Hsieh MH et al.; The checkerboard dilution test is widely used for evaluation of in vitro synergy for multiple drugs, although problems in performance, standardization, and interpretation have been noted . A major problem inherent in this commonly used method is the use of twofold dilutions for the antibiotic concentrations . We evaluated an alternative method proposed by Horrevorts and colleagues that preserved the twofold dilution scheme . Giant checkerboards were constructed from a series of component checkerboards using rifampin and minocycline against Staphylococcus aureus . We found that this method improved the stability of the fractional inhibitory concentration (FIC) indices, but required substantially more labor and generated other problems . FIC interpretation and calculation remained compromised by the twofold dilution scheme . We have analyzed the theoretical basis of the checkerboard and its FIC calculation and conclude that the twofold dilution with its exponential increase in dilutions makes this method of synergy evaluation inherently unstable . The principle of examining growth at multiple dilutions of combined antibiotics is valid for assessment of synergy, but newer methods need to be devised.

Cell Immunol, 1993 May, 148(2), 291 - 300
The effects of retinoic acid on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells; Wang W et al.; Retinoic acid (RA) has attracted considerable attention as an agent with a broad range of physiologic and metabolic effects . The importance of RA in the susceptibility of vitamin A-deficient animals and humans to infection is well known . Initial studies from our laboratory showed that RA augmented the IgM response of cord blood mononuclear cells (CBMC) at concentrations ranging from 10(-5) to 10(-8) M, but not adult peripheral blood mononuclear cells (PBMC), to formalinized Cowan I strain Staphylococcus aureus (SAC), a T-cell-dependent polyclonal B-cell activator . In the present study, we demonstrate that RA augments the SAC-stimulated IgG synthesis of adult PBMC at very low concentrations (10(-11) to 10(-13) M) indicating that adult PBMC is 10(4) to 10(6) times more responsive to the augmenting effects of RA than CBMC . To evaluate the differences in dose-response characteristics between CBMC and adult PBMC, co-mixture experiments between T- and B-cells of CBMC and adult PBMC were performed . The dose-response characteristics of the augmenting effects of RA for a particular Ig isotype were related to the responding B-cell population . The results of an ELISA spot assay showed that the RA-induced enhancement in Ig synthesis was due to the "recruitment" of more B-cells to differentiate into Ig-secreting cells . When RA was added to CBMC stimulated by EBV, a T-cell-independent polyclonal activator, or to EBV-transformed B-cell clones, a small (twofold) augmentation in IgM synthesis was seen which suggested that RA may also have some direct effect on B-cells . However, if cord blood T-cells were preincubated with RA for 36 hr, washed, and added to cord blood B-cells with SAC, a 2.5- to 9-fold augmentation in IgM was obtained . These studies suggest that the principal mechanism(s) by which RA augments the Ig synthesis of SAC-stimulated cultures is mediated by the T-cell, or T-cell products, e.g., cytokines, which induces an increased proportion of B-cells to differentiate into Ig-secreting cells . RA may also have an effect, although minor, directly on B-cells . The differences in the dose-response characteristics between CBMC and adult PBMC appears to reside within the intrinsic capabilities of an Ig-producing B-cell subpopulation.

EMBO J, 1993 May, 12(5), 1887 - 95
Bacterial internalization mediated by beta 1 chain integrins is determined by ligand affinity and receptor density; Tran Van Nhieu G et al.; Binding of bacteria to beta 1 chain integrin receptors results in either bacterial adherence or uptake by cultured cells (Isberg, 1991) . In this report we show that Staphylococcus aureus coated with high affinity ligands for the beta 1 chain integrin family can be internalized efficiently, whereas bacteria coated with low affinity ligands are poorly internalized . Overproduction of the alpha 5 beta 1 integrin increased the efficiency of bacterial internalization, indicating that the uptake efficiency is directly related to the level of expression of the receptor . By using latex beads or S . aureus coated with mAbs directed against the alpha 5 beta 1 integrin, a roughly semi-logarithmic correlation was observed between the affinity of the receptor-ligand interaction and the rate of bacterial internalization . Evidence is presented that high affinity binding of the bacterium allows the microorganism to compete efficiently with receptor-ligand interactions at the basolateral surface of the cell.

J Intern Med, 1993 May, 233(5), 419 - 21
Pyomyositis in a patient with myeloma responding to antibiotics alone; Hoyle C et al.; Pyomyositis is a rare purulent infection of skeletal muscle with striking clinical features . It usually occurs in patients living in the tropics but is increasingly being reported in immunosuppressed patients . The traditional approach to management has been surgical with drainage and debridement of the multiple muscle abscesses . We report a patient with myeloma who developed multiple muscle and lung abscesses associated with a Staphylococcus aureus septicaemia . The case was successfully managed with intravenous antibiotics alone with no recurrence of the abscesses during a later episode of neutropenia . The advantages of avoiding surgical intervention in immunosuppressed and thrombocytopenic patients are obvious.

Proc Natl Acad Sci U S A, 1993 May 1, 90(9), 4271 - 5
Three-dimensional structure of a human immunoglobulin with a hinge deletion; Guddat LW et al.; X-ray analysis at 3.2-A resolution revealed that the Mcg IgG1 (lambda chain) immunoglobulin is a compact T-shaped molecule . Because of the hinge deletion, the Fc fragment lobe is pulled tightly upward into the junction of the Fab arms . Along the molecular twofold axis, the Fab arms are joined by an interchain disulfide bond between the two light chains . The antigen combining sites consist of large irregular cavities at the tips of the Fab regions . Potential complement (C1q) binding sites on Fc are sterically shielded by the Fab arms, but putative attachment sites are accessible for docking with the FcRI receptor on human monocytes and with protein A of Staphylococcus aureus.

J Exp Med, 1993 May 1, 177(5), 1239 - 46
Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo; Gonzalo JA et al.; Poly- and oligoclonal T cell stimuli like anti-CD3 epsilon monoclonal antibody or Staphylococcus aureus enterotoxin B (SEB), injected at doses that per se are not lethal, provoke acute death within less than 24 h, provided that endogenous glucocorticoids (GC) are depleted by adrenalectomy or by injection of saturating amounts of the GC receptor antagonist RU-38486 (mifepristone) . Pharmacological doses of the GC agonist dexamethasone (DEX) alter the in vivo response of splenic V beta 8+ T cells to SEB, thus impeding the expansion of such cells and causing their rapid (3 d) clonal deletion . In contrast, coadministration of RU-38486 counteracts a SEB-induced early (12 h) reduction of V beta 8+CD4+ and V beta 8+CD8+ spleen cells . In vivo T cell stimulation by injection of bacterial superantigen induces a rapid (peak at 90-120 min) increase in corticosterone serum levels, suggesting that endogenous GC might control early T cell activation . Accordingly, kinetic studies revealed that RU-38486 has to be administered within 2 h after superantigen administration to exert its lethal effect . Similarly, exogenous GC must be injected during this critical phase (2 h) to rescue animals from acute death induced by coinjection of SEB and D-galactosamine (GalN) . Adrenalectomy, injection of RU-38486 and priming with GalN per se provoke the programmed death of peripheral CD4+ and CD8+ T cells . Thus, three manipulations that sensitize mice for the lethal effect of T cell stimulation also exert a proapoptotic effect on peripheral T cells . In synthesis, endogenous and exogenous GC regulate T cell responses and determine the propensity of peripheral T cells to undergo apoptosis.

J Lab Clin Med, 1993 May, 121(5), 675 - 82
Staphylococcus aureus binding to cardiac endothelial cells is partly mediated by a 130 kilodalton glycoprotein; Johnson CM; Binding of Staphylococcus aureus to vascular endothelial cells may be an initiating event in the pathogenesis of endovascular infection, particularly infective endocarditis . In this study a competition assay between labeled and unlabeled bacteria was used to identify potential S . aureus-binding determinants on the surface of cultured porcine aortic valve endothelial cells . Concanavalin A inhibited 30% to 40% of the specific binding of S . aureus to membrane-associated components . Concanavalin A affinity chromatography of radiolabeled cell-surface proteins, followed by isolation of S . aureus-binding proteins, identified a 130,000-molecular-weight cell surface protein that may function as an endothelial cell S . aureus receptor . These data suggest that specific binding of S . aureus to cardiac valve endothelial cells is mediated in part by a 130 kd mannose-containing glycoprotein.

J Bacteriol, 1993 May, 175(9), 2779 - 82
Altered muropeptide composition in Staphylococcus aureus strains with an inactivated femA locus; de Jonge BL et al.; Tn551 inactivation of femA, a factor involved in methicillin resistance of Staphylococcus aureus, caused the production of peptidoglycan in which the fraction of monoglycyl- and serine-containing muropeptides was increased at the expense of pentaglycyl muropeptides . femA mutants have a specific block in the biosynthesis of pentaglycine cross bridges after the addition of the first glycine residue.

Infect Immun, 1993 May, 61(5), 2059 - 68
Staphylococcal enterotoxin type A internal deletion mutants: serological activity and induction of T-cell proliferation; Harris TO et al.; Previous findings indicate that the N-terminal region of staphylococcal enterotoxin type A (SEA) is required for its ability to induce T-cell proliferation . To better localize internal peptides of SEA that are important for induction of murine T-cell proliferation, SEA mutants that had internal deletions in their N-terminal third were constructed . A series of unique restriction enzyme sites were first engineered into sea; only one of these changes resulted in an amino acid substitution (the aspartic acid residue at position 60 of mature SEA was changed to a glycine {D60G}) . Because the D60G substitution had no discernible effect on serological or biological activity, the sea allele encoding this mutant SEA was used to construct a panel of mutant SEAs lacking residues 3 to 17, 19 to 23, 24 to 28, 29 to 49, 50 to 55, 56 to 59, 61 to 73, 68 to 74, or 74 to 85 . Recombinant plasmids with the desired mutations were constructed in Escherichia coli and transferred to Staphylococcus aureus . Staphylococcal culture supernatants containing the mutant SEAs were examined . Western immunoblot analysis with polyclonal anti-SEA antiserum revealed that each of the recombinant S . aureus strains produced a mutant SEA of the predicted size . All the mutant SEAs exhibited increased sensitivity to monkey stomach lavage fluid in vitro, which is consistent with these mutants having conformations unlike that of wild-type SEA or the SEA D60G mutant . In general, deletion of internal peptides had a deleterious effect on the ability to induce T-cell proliferation; only SEA mutants lacking either residues 3 to 17 or 56 to 59 consistently produced a statistically significant increase in the incorporation of {3H}thymidine . In the course of this work, two monoclonal antibodies that had different requirements for binding to SEA in Western blots were identified . The epitope for one monoclonal antibody was contained within residues 108 to 230 of mature SEA . Binding of the other monoclonal antibody to SEA appeared to be dependent on the conformation of SEA.

Infect Immun, 1993 May, 61(5), 1700 - 6
Induction of macrophage-mediated production of tumor necrosis factor alpha by an L-form derived from Staphylococcus aureus; Kuwano K et al.; We investigated the capability of an L-form derived from Staphylococcus aureus to induce tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal macrophages . The activity for TNF-alpha induction was found in the membrane fraction of the L-form but not in the cytoplasmal fraction purified by the sucrose step gradient centrifugation . TNF-alpha mRNA was also detected in macrophages stimulated with L-form membranes . L-form induced TNF-alpha production in macrophages from both lipopolysaccharide-responsive and -unresponsive mouse strains . Regardless of the presence of polymyxin B, the activity of TNF-alpha induction of L-form was mostly found in the phenol layer, but not in the aqueous layer, both of which were prepared by phenol extraction method . Fractions of L-form membranes representing molecular masses of approximately between 29 and 36 kDa were primarily responsible for inducing the production of TNF-alpha consistently . Moreover, this stimulatory effect was abolished by digestion with Streptomyces griseus protease . In Western blot (immunoblot) analysis with anti-lipoteichoic acid antibody, two bands (65 and 45 kDa) were observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the phenol layer, whereas one band (14 kDa) was observed in either the aqueous layer or lipoteichoic acid of S . aureus . These results suggest that the component in the membrane of the L-form, distinct from cell wall components such as teichoic acid or lipopolysaccharide, possesses the capability to stimulate TNF-alpha production by macrophages.

Antimicrob Agents Chemother, 1993 May, 37(5), 950 - 6
Oxidant-scavenging activities of ampicillin and sulbactam and their effects on neutrophil functions; Gunther MR et al.; Luminol-enhanced luminescence is a method used to measure formation of reactive oxygen intermediates important in the ability of neutrophils to kill microbes . Several studies have demonstrated that under some conditions of incubation, ampicillin can inhibit neutrophil-derived luminol-enhanced luminescence . We evaluated the mechanism(s) by which ampicillin inhibited the luminescent response of stimulated neutrophils . We also investigated sulbactam, a beta-lactamase inhibitor which has been given in combination with ampicillin and other beta-lactam antibiotics to increase their spectra, for possible similar effects . Both ampicillin and sulbactam attenuated luminol-enhanced luminescence by approximately 40% . Superoxide production was not prevented by added ampicillin, nor was superoxide scavenged by it . Myeloperoxidase reacts with H2O2 and Cl- to generate OCl-, which is believed to be the oxidizer of luminol that is primarily responsible for enhancement of neutrophil-derived luminescence . Hydroxyl radicals (HO.), which may also oxidize luminol, resulting in luminescence, can be formed from O2- and H2O2 via either myeloperoxidase-dependent (involving intermediate OCl-) or myeloperoxidase-independent (through a metal ion catalyst) reactions . Ampicillin scavenged H2O2 and OCl- and prevented 95% of Fenton reaction-generated HO . from reacting with 5,5-dimethyl-1-pyrroline-N-oxide . Sulbactam was found to scavenge OCl- and HO., but less avidly than ampicillin did . Neither ampicillin nor sulbactam inhibited myeloperoxidase activity . Sublethal concentrations of sulbactam had no significant effect on neutrophil killing of Staphylococcus aureus and Escherichia coli . Our results demonstrate a mechanism(s) by which ampicillin inhibits luminol-enhanced luminescence from stimulated neutrophils, namely, through scavenging of the oxidant(s) primarily responsible for the generation of luminescence.

J Clin Invest, 1993 May, 91(5), 1926 - 33
Plasma triglycerides determine low density lipoprotein composition, physical properties, and cell-specific binding in cultured cells; McKeone BJ et al.; The relationship between the plasma triglycerides and the LDL triglycerides of 30 normal and 48 hypertriglyceridemic subjects has been quantified; the data fit a simple adsorption isotherm, LDL triglyceride/(LDL triglyceride+LDL cholesterol ester) = 0.65 plasma triglyceride/(464 + plasma triglyceride) . In vitro transfer of triglyceride from concentrated VLDL to VLDL-depleted plasma produced triglyceride-rich LDL that had similar properties . LDL uptake by HepG2 cells increased with LDL triglyceride content whereas the reverse was found with skin fibroblasts . At 37 degrees C, the cores of both normal and hypertriglyceridemic LDL were isotropic liquids . Circular dichroic spectra revealed no difference in the secondary structure of normal and triglyceride-rich LDL . The affinity of monoclonal antibody MB47, which binds to the receptor ligand of apo B-100 was independent of LDL triglyceride content . MB3, which binds near residue 1022 of apo B-100, showed a triglyceride-dependent decrease in affinity for LDL from hypertriglyceridemic subjects and from in vitro incubations . LDL with an elevated triglyceride content formed in vitro had reduced proteolytic cleavage of apo B-100 by Staphylococcus aureus V8 protease . From these data, we infer that (a) LDL triglyceride is a predictable function of plasma triglyceride, (b) triglyceride induces subtle changes in apo B-100 structure at a site that is remote from the putative receptor binding ligand, and (c) the triglyceride-dependent receptor-binding determinants of apo B-100 are recognized differently by fibroblasts and HepG2 cells.

Mikrobiol Zh, 1993 May-Jun, 55(3), 47 - 53
{The interaction of pathogenic microorganisms with the sorbent polymethylsiloxane}; Dikova IG et al.; The method of electron microscopy has been used to study adhesion of the microbic cells of standard strains of Staphylococcus aureus, Escherichia coli and fungi of genus Candida on the organosilicon sorbent polymethylsiloxane (PMS) and medicamentous complex containing it . This complex contains furazolidone and metronidazole immobilized on silver ions-modified PMS . It is shown that the adhesion of microorganisms is accompanied by their destruction whose rate on pure PMS and medicamentous complex is different . Using experimental data the assumptions are advanced concerning the mechanism of the PMS interaction with Gram-positive and Gram-negative microorganisms as well as with fungi of genus Candida.

Clin Exp Rheumatol, 1993 May-Jun, 11(3), 263 - 70
Selective suppression of resting B cell function in patients with systemic lupus erythematosus treated with cyclophosphamide; Takeno M et al.; The immunological function of patients with inactive systemic lupus erythematosus (SLE) receiving chronically administered, low-dose cyclophosphamide (CY) together with prednisolone (PSL) was compared with that of inactive patients receiving PSL alone . A striking selective suppression of "genuine" resting, but not "partially" or "fully" activated, B cell function was noted in the patients receiving PSL + CY as measured by Staphylococcus aureus Cowan I (SAC)-induced proliferative responses by Percoll-separated small resting B cells of high density; the small resting B cells sedimenting in a high density fraction were more responsive to SAC in patients treated with PSL alone than those in normal controls . However, the spontaneous proliferation and spontaneous secretion of immunoglobulins by peripheral blood B cells were elevated in both the patient groups . The proliferative responses to phytohaemagglutinin and concanavalin A by T cells were not significantly different between both patient groups . The data indicate that the genuine resting B cells may be the major target for the CY effect in SLE, and thus such selective suppression may help explain the efficacy of CY and PSL together in treating SLE.

Arzneimittelforschung, 1993 May, 43(5), 607 - 9
Synergistic effect of ethanolic extract of propolis and antibiotics on the growth of staphylococcus aureus; Krol W et al.; Ethanolic extract of propolis (EEP), known to possess marked antibacterial activity, was incubated with 8 different common antibiotics in culture medium containing a fixed amount of a standard strain of Staphylococcus aureus . The antibiotic compounds used were: penicillin G, doxycycline, streptomycin, cloxacillin, chloramphenicol, cefradine, ampicillin and polymyxin B . They were used in varying levels, ranging between 0.000005-125.0 micrograms/ml or units, resp . Firstly, their minimal inhibitory concentrations were established in the absence of EEP, than EEP was added in concentrations up to 600 micrograms/ml . EEP had a marked synergistic effect on the antibacterial activity of streptomycin and cloxacillin, and a moderate synergistic effect on the others, except ampicillin.

Z Kardiol, 1993 May, 82(5), 287 - 92
{An unusual cause of myocardial infarct . Bacterial mitral valve endocarditis, valve ring and myocardial abscess with direct coronary lesion}; Volker U et al.; We report on a 45-year-old man with bacterial mitral valve endocarditis and valve-ring abscess following a staphylococcus aureus sepsis with septic shock and respiratory insufficiency . A thrombosis of the marginal branch of the left circumflex coronary artery with a myocardial infarction occurred as a consequence of the unusual location of the abscess which spread to the left ventricular lateral wall with an encasement of this blood vessel, and with destruction of the arterial wall . The patient died of biventricular heart failure because of septic shock and myocardial infarction . We discuss entrance spots of infection, predisposing diseases, and complications of valve-ring and myocardial abscesses.

J Orthop Res, 1993 May, 11(3), 404 - 11
Evaluation of biodegradable cefazolin sodium microspheres for the prevention of infection in rabbits with experimental open tibial fractures stabilized with internal fixation; Jacob E et al.; Immediate internal fixation of severe open tibial fractures usually is contraindicated due to the high risk of infection . The objective of this study was to evaluate the efficacy of local antibiotic therapy with biodegradable poly-(DL-lactide-co-glycolide) cefazolin-loaded microspheres for the prevention of infection in experimental open fractures stabilized with internal fixation . Rabbits with experimental tibial fractures that were contaminated with Staphylococcus aureus were treated with local application of cefazolin microspheres, an equivalent local dose of free Ancef powder, or systemic Ancef therapy . The bones then were fixed with a four-hole plate, and the animals were observed for 8 weeks . Clinically, deep infection was present in 86% of control animals that received no antibiotics and in 60% of animals that received a 7 day course of systemic Ancef therapy . In contrast, no infections were noted among any of the surviving rabbits that received local therapy with either cefazolin microspheres or free Ancef powder . Significantly higher levels of serum cefazolin were measured at 1 h for animals treated with free Ancef powder (18.7 +/- 6.1 micrograms/ml) than for those treated with cefazolin microspheres (0.57 +/- 0.27 micrograms/ml) . Follow-up studies are in progress to evaluate further the potential clinical benefits of local antibiotic therapy for the management of contaminated open fractures in humans.

Enferm Infecc Microbiol Clin, 1993 May, 11(5), 235 - 40
{Right endocarditis caused by Staphylococcus aureus in parenteral drug addicts: evaluation of a combined therapeutic scheme for 2 weeks versus conventional treatment}; Espinosa FJ et al.; BACKGROUND: Intravenous drug addicts (IVDA) are a group of patients in whom it is difficult to complete standard treatment of infectious endocarditis due to frequent antisocial behavior and in whom, once clinical improvement is achieved, voluntary discharge is frequently requested . This is why the evaluation of new treatment schedules tending to decrease the length of the same is of great interest . This non randomized study has the aim of knowing the efficacy of a short treatment with cloxacillin or vancomycin associated to gentamicin in right-sided endocarditis by methicillin-sensitive Staphylococcus aureus, comparing this with the standard schedule of 28 days . METHODS: This series was made up of IVDA patients diagnosed of right endocarditis by S . aureus . Inclusion criteria were the presence of intravenous drug addiction, isolation of methicillin-sensitive S . aureus in 2 or more blood cultures and achievement of the diagnostic criteria of right-sided endocarditis . Two schedules were used: a) standard: cloxacillin or vancomycin for 4 weeks, associating aminoglucoside in the first 3-5 days; b) short; cloxacillin or vancomycin associated to gentamicin for 2 weeks with no ulterior treatment . The study was not randomized and the treatment of 2 weeks was compared with historic controls treated for 4 weeks . The criteria evaluated were those of clinical cure, relapse, appearance of complications during treatment and mortality . RESULTS: Both the standard treatment and the combination of cloxacillin or vancomycin with gentamicin for 2 weeks cured 100% of the episodes of right endocarditis by S . aureus . There were no relapses and mortality was nul . Neither were there any differences between the two groups with regard to appearance of complications . CONCLUSIONS: In intravenous drug addict patients with right-sided endocarditis by methicillin S . aureus, the association of cloxacillin and gentamicin for 2 weeks is an effective alternative to long (4 week) treatments with only one antibiotic . The low number of cases treated with vancomycin does not allow conclusions to be drawn on its efficacy.

Arch Dis Child, 1993 May, 68(5 Spec No), 594 - 6
What cord care--if any?
Verber IG, Pagan FS.
The use of antiseptic treatment during cord care varies from unit to unit . Although it may reduce bacterial colonisation it may also delay cord separation . Where antiseptic treatment is used there is uncertainty as to the best agent . Hexachlorophane powder (0.3%) and 4% chlorhexidene detergent were each compared with dry cord care as a control on a two ward maternity unit in a six month open study . Of 133 infants treated with hexachlorophane 44 (33%) became heavily colonised with Staphylococcus aureus compared with 80 (47%) of 171 controls; a reduction of one third . Chlorhexidene reduced colonisation by more than half; 17 (16%) of 104 compared with 41 (42%) of 98 controls . Chlorhexidene was associated with cord attachment at 10 days in 29 (28%) infants compared with 31 of 515 (6%) infants when it was not used . Hexachlorophane was more acceptable to the nursing staff . The reduction in colonisation with the two compounds was largely due to the suppression of cross infection.

FEMS Microbiol Lett, 1993 May 1, 109(1), 19 - 23
Enhanced conjugative transfer of plasmid DNA from Escherichia coli to Staphylococcus aureus and Listeria monocytogenes; Trieu-Cuot P et al.; Transfer of mobilizable shuttle cloning vectors by conjugation from Escherichia coli to Staphylococcus aureus occurred at a very low frequency (10(-9) transconjugants per donor colony-forming unit after the mating period) . It was observed that subinhibitory concentrations of penicillins (oxacillin or penicillin G) in the mating medium resulted in increased transfer frequency by conjugation of the shuttle vector pAT18 from E . coli SM10 to S . aureus 80CR5 Str (54-fold) and to Listeria monocytogenes LO17RF (45-fold) . These results were interpreted as indicating that the cell wall of Gram-positive bacteria constitutes an important barrier for conjugative transfer of genetic information delivered from E . coli . It was also demonstrated that presence of a restriction system(s) in S . aureus recipients represented a major barrier to introduction of foreign DNA.

Am J Vet Res, 1993 May, 54(5), 732 - 7
Role of an intramammary device in protection against experimentally induced staphylococcal mastitis in ewes; Penades JR et al.; An intramammary device (IMD) was adapted for use in ewes; this device was made of abraded polyethylene material (1.7 mm in diameter, 47 mm long) and formed a 15-mm-diameter loop in the gland cistern . The IMD was inserted in 1 gland in each of 43 ewes . A significant (P < 0.0001) increase in milk somatic cell count (SCC) was observed in glands provided with an IMD . This increase was attributable to an increase in neutrophil numbers and was observed during the first 12 weeks after insertion . The IMD had a protective effect against experimentally induced staphylococcal mastitis (Staphylococcus aureus and S epidermidis), although different milk SCC were required for protection from each bacterial species in most ewes (10(6) and 2 x 10(5) cells/ml, respectively) . Histologic studies revealed that the IMD induced local squamous metaplasia in the glandular part of the lactiferous sinus . Erythrocytes were found in milk from glands provided with an IMD throughout the studied period (35 days of the 45-day lactation) and, in some cases, blood clots were observed during the first 2 weeks of lactation . Glands with IMD also had lower milk production and quality at 30 and 32 days of lactation . Eight ewes with IMD were studied throughout a subsequent lactation . Milk from the IMD-containing glands had an increase in SCC, as in the previous lactation period; did not contain blood clots or erythrocytes; and had normal composition (similar to that in glands without the IMD).

Rev Hosp Clin Fac Med Sao Paulo, 1993 May-Jun, 48(3), 112 - 5
{Tropical myositis}; Takayasu V et al.; The authors describe six cases of tropical myositis or pyomyositis treated in the Department of Internal Medicine of the University of Sao Paulo between 1985 and 1992 . Staphylococcus aureus was the causative agent . It was isolated from the muscular abscess in four cases and blood cultures in two cases . The treatment with appropriate antibiotics and drainage of the abscess(es) determined satisfactory evolution without mortality or residual deformity.

Cytokine, 1993 May, 5(3), 276 - 84
Prevention and treatment of Staphylococcus aureus infections with recombinant cytokines; Daley M et al.; Antibiotic therapy is only moderately efficacious for bovine Staphylococcus aureus mastitis . We have used recombinant bovine cytokines to activate the natural host defenses, to prevent and treat bovine mastitis . Uninfected mammary glands infused with GM-CSF or IL-2 increased the percentage of phagocytic cells in the milk by 2-3 fold . IL-1 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and had no effect on phagocytosis . Treatment with IL-2 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and enhanced their phagocytosis . GM-CSF had no effect on the number polymorphonuclear cells in the milk but enhanced their inducible oxygen radical formation, and enhanced their phagocytosis . All cytokines were effective in preventing S . aureus infections (20-100%) . 52% of all chronically infected mammary gland quarters treated with three doses of IL-2 responded to therapy and 32% of the treated quarters remained cured . 75% of all mammary glands treated with three doses of IL-1 beta responded to therapy by clearing the infection and 22% of the treated glands remained cured . These studies demonstrate that recombinant bovine cytokines can be used effectively to prevent infections as well as treat established chronic infection.

Lik Sprava, 1993 May-Jun, (5-6), 65 - 9
{The relationship of duodenal peptic ulcer and gastroduodenitis to a chronic staphylococcal infection}; Zavadiak MI; Tonsillar and pharyngeal smears revealed growth of pathogenic microorganisms, mainly of Staphylococcus aureus, in 58.0 +/- 3.7% of 174 patients with duodenal ulcer and gastroduodenitis during remission or unstable remission, in 40.0 +/- 5.3% of 85 patients with other gastroenterological diseases and in 17.5 +/- 6.0% of 40 subjects constituting control group . Urease activity ratio (biological marker of Helicobacter pylori) was found to be approximately the same in every group of patients vs 11.1 +/- 6.2% of 27 healthy persons . Pathogenetic mechanisms of relation between duodenal ulcer, chronic gastroduodenitis and chronic focuses of infection are discussed . Lymphatic pharyngeal ring is supposed to be biotopical for Helicobacter pylori.

J Hosp Infect, 1993 May, 24(1), 23 - 8
Infection due to a contaminated thoracic drainage system; Jacobs JA et al.; Infection and colonization of the pleural space in three patients was traced to contaminated thoracic drain equipment . The organisms implicated were Bacillus cereus, Staphylococcus aureus and various non-fermenting Gram-negative bacteria . A careful examination of cleaning and decontamination procedures revealed delay in replacing the drainage bottle jar to be the main factor responsible for the contamination of the drainage unit and the pleural space . Recent technical adaptation of the drainage apparatus had removed the need for daily changing of this jar . These findings confirm that thoracic drainage systems may be a potential source of contamination for the patient . We emphasize that technical improvements to existing operating apparatus should necessitate the adaptation of recommendations governing their use in accordance with approved hospital hygiene standards.

Immunol Lett, 1993 May, 36(2), 203 - 8
Cyclosporin A and FK506 block the negative signaling mediated by surface IgM cross-linking in normal human mature B cells; Yamaoka K et al.; Cross-linking of surface IgM (sIgM) or sIgD by anti-IgM Ab or anti-IgD Ab, respectively, induced DNA synthesis in peripheral blood B cells (PBL-B) . Cell division, determined by the increase in the number of M phase cells, was also induced when PBL-B were stimulated with anti-IgD Ab plus IL-4 or Staphylococcus aureus Cowan I (SAC), but far less by stimulation with anti-IgM Ab plus IL-4 . Anti-IgM Ab did not suppress the DNA synthesis induced by SAC or anti-IgD Ab plus IL-4, but it did suppress the cell division induced by them . Thus, sIgM cross-linking generates both positive and negative signaling to B-cell proliferation . Cyclosporin A (CSA) and FK506 suppressed DNA synthesis and cell division at relatively high concentrations . On the other hand, CSA and FK506 at lower concentrations blocked the anti-IgM Ab-generated inhibition of cell division without affecting DNA synthesis . Low concentrations of CSA did not affect the cell division induced by anti-IgD Ab plus IL-4 but did increase the cell division induced by SAC or anti-IgM Ab plus IL-4, suggesting that stimulation with SAC, as well as with anti-IgM Ab plus IL-4, generates both positive and negative signals to cell division, whereas sIgD lacks the ability to transduce negative signaling.

Proc Natl Acad Sci U S A, 1993 May 1, 90(9), 4032 - 6
Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells; Wang LM et al.; Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2 . Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth . The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I . These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation . IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS . However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS . Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection . These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.

Pharm World Sci, 1993 Apr 23, 15(2), 79 - 82
Pharmacokinetics and clinical study of cefotetan in bile: prophylactic use in biliary tract surgery; Cherrier P et al.; The excretion of cefotetan, a 7 alpha-methoxy-cephalosporin, was studied in 27 patients undergoing biliary surgery . Pharmacokinetic parameters were determined after a single intravenous bolus dose of 1 g (10 patients) or 2 g (17 patients) . Rapidly excreted in bile, cefotetan concentrations were considerably higher in bile {range: 92-2,594 mg.l-1 (1 g); 35-4,610 mg.l-1 (2 g)} than in plasma despite the presence of gall stones . Bile bactericidal activities against Staphylococcus aureus (MIC 8 mg.l-1) and Bacteroides fragilis (MIC 2 mg.l-1) correlated well with gall bladder cefotetan levels {r = 0.888 (1 g); r = 0.971 (2 g)} . No cefotetan was detected in the bile of 3 patients with nonfunctioning gall bladders . One other patient with very low activity and these three aside, the inhibitory quotients (cefotetan concentration/MIC) were > 4 for both doses against both bacteria.

Biochemistry, 1993 Apr 20, 32(15), 3842 - 51
The energetics and cooperativity of protein folding: a simple experimental analysis based upon the solvation of internal residues; Staniforth RA et al.; The reversible unfolding of two dissimilar proteins, phosphoglycerate kinase from Bacillus stearothermophilus (PGK) and Staphylococcus aureus nuclease (SAN), was induced with two denaturants, urea and guanidinium chloride (GuHCl) . For each protein, structural transitions were monitored by intrinsic fluorescence intensity changes arising from a unique tryptophan residue . In the case of SAN the single, native tryptophan residue was used, whereas for PGK two versions, one with a tryptophan at position 315 and one at 379, were constructed genetically . The resultant folding curves were analyzed by considering the change in the solvation free energy of internal amino acid residues as the denaturant concentration was varied . We derive the following simple relationship: -RT ln K = delta Gw + n delta Gs,m{D}/Kden . + {D}) where K is the equilibrium constant describing the distribution of folded and unfolded forms at a given denaturant concentration {D}, delta Gw is the free energy change for the transition in the absence of denaturant, and n is the number of internal side chains becoming exposed . delta Gs,m and Kden . are constants derived empirically from the solvation energies of model compounds and represent the behavior of an average internal side chain between 0 and 6 M GuHCl and 0 and 8 M urea . For proteins of known structure these values can easily be derived, and for others, average values in guanidinium chloride (delta Gs,m = 0.775 kcal/mol and Kden . = 5.4 M) or urea (delta Gs,m = 1.198 kcal/mol and Kden . = 25.25 M) can be used in the analysis . Results show that the parameters n and delta Gw are independent of the denaturant used for all 12 transitions studied . This supports the hypothesis that the unfolding activity of urea and GuHCl can be accounted for by their effect on the solvation energy of amino acid side chains which are buried in the folded but exposed in the unfolded protein . This simple analytical treatment allows the "cooperativity" of protein folding to be interpreted in terms of the number of side chains becoming exposed to the solvent in a given step and allows accurate estimation of the free energy irrespective of the denaturant concentration needed to induce the transition.

FEBS Lett, 1993 Apr 19, 321(1), 15 - 8
The two Staphylococcal bi-component toxins, leukocidin and gamma-hemolysin, share one component in common; Kamio Y et al.; Staphylococcal bi-component toxins, leukocidin and gamma-hemolysin, consist of two protein components, i.e . F and S for leukocidin and H gamma I and H gamma II for gamma-hemolysin . In this study we purified H gamma I and H gamma II to homogeneity from the culture medium of Staphylococcus aureus RIMD 310925 and compared their properties with those of F and S purified from the same source . The N-terminal 59- and C-terminal 2-residue amino acid sequences, apparent molecular mass, and isoelectric point of purified H gamma I were the same as those of F . In an Ouchterlony double diffusion test a fused line without spur was formed between F and H gamma I using either anti-F or anti-H gamma I antibodies . A synergistic action of F and H gamma II caused hemolysis of human red blood cells, and H gamma I acted synergistically with S to exhibit leukocidin activity . We conclude that the two toxins share one protein component (F = H gamma I) in common and leukocidin- and gamma-hemolysin-specific activities are determined by S and H gamma II, respectively . It is also reported that the N-terminal 58-residue sequence of H gamma II is 72% similar to the corresponding sequence of S.

J Immunol, 1993 Apr 15, 150(8 Pt 1), 3224 - 9
Staphylococcus aureus Wood 46 strain activates human B cells without affecting DNA synthesis or tyrosine phosphorylation; Saiki O et al.; Induction of Ig secretion in human tonsilar B cell by protein A-deficient Staphylococcus aureus WOOD 46 strain (SAW) was examined . SAW induced as much Ig secretion as protein A-rich S . aureus Cowan I strain (SAC) when IL-2 was present in the culture . Activated and resting B cells are separated by Percoll gradient to determine whether SAW stimulates either resting or activated B cells . In resting B cells, SAW plus IL-2 induced IgM secretion significantly, but neither IL-2 nor SAW alone induced IgM secretion . In activated B cells, however, IL-2 induced IgM secretion by itself and SAW plus IL-2 did not induce additional IgM secretion . These results suggest that SAW activates small resting B cells rather than preactivated B cells . Subsequently, mechanisms of B cell activation by SAW and SAC were compared . SAW did not induce {3H}-TdR incorporation through day 1 to 5, and the number of viable cells was not increased by SAW stimulation . Moreover, SAW did not induce significant tyrosine phosphorylation at any concentration tested, when tyrosine phosphorylation of B cells was examined . However, SAC induced both {3H}-TdR incorporation and tyrosine phosphorylation of B cell efficiently . In further experiments, induction of IL-2R and IgM mRNA expressions were examined . SAW by itself induced IL-2R and IgM mRNA expressions without affecting expression of membrane-type IgM mRNA . These results show that SAW activates human B cells in quite a different manner from SAC by up-regulating the expression of secretory type IgM mRNA without affecting cell proliferation nor tyrosine phosphorylation, proposing a distinct B cell activation model from SAC.

J Biol Chem, 1993 Apr 15, 268(11), 7646 - 9
Activation of protein kinases by insulin and non-hydrolyzable GTP analogs in permeabilized 3T3-L1 adipocytes; Klarlund JK et al.; The molecular events that lead from the interaction of insulin with its receptor to the activation of protein serine/threonine kinases are still unknown . In this study, we have examined the role of GTP-binding proteins in this signaling pathway using differentiated 3T3-L1 adipocytes permeabilized with alpha-toxin from Staphylococcus aureus . Addition of GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)) or insulin to such permeabilized cells markedly increases protein kinase activities in cell lysates using the microtubule-associated protein-2 kinase substrate peptide KRELVE-PLTPSGEAPNQALLR, which contains the threonine 669 phosphorylation site on the epidermal growth factor receptor . Similar stimulations of protein kinase activity by these agents are observed using the peptide KRRRLASLAA, which is selectively phosphorylated by ribosomal protein S6 kinases . The effects of insulin and GTP gamma S are not additive . Importantly, the GTP-binding protein antagonist GDP beta S (guanosine 5'-O-(2-thiodiphosphate)) inhibits the activation of the protein kinase activities by insulin in permeabilized 3T3-L1 adipocytes . These data are consistent with the hypothesis that activation of Ras or other GTP-binding proteins is a key element of the signaling mechanism whereby insulin receptor tyrosine kinase activates the microtubule-associated protein-2 kinase cascade.

Biochemistry, 1993 Apr 13, 32(14), 3549 - 56
Immunochemical mapping of domains in human interleukin 4 recognized by neutralizing monoclonal antibodies; Ramanathan L et al.; Human interleukin 4 is a highly pleiotropic cytokine secreted by activated T cells that exerts multiple biological effects on B and T lymphocytes and other cell types . Elucidation of structure-function relations was accomplished by epitope mapping of a panel of monoclonal antibodies and by mutagenesis of selected amino acid residues . Epitope mapping of these monoclonal antibodies was achieved through binding studies with recombinant human interleukin 4 (rhuIL-4), proteolytic fragments produced by digestion with Staphylococcus aureus V8 protease and synthetic peptides derived from the sequence of the parent molecule . Monoclonal antibodies 25D2, 35F2, and 11B4 neutralized the in vitro T-cell proliferation activity of rhuIL-4 and also prevented binding of rhuIL4 to its cell surface receptor . These antibodies recognized sequences 104-129, 70-92, and 61-82, respectively . These regions comprise the BC loop/helix C (residues 61-92) and helix D (residues 104-129) . A nonneutralizing monoclonal antibody (1A2) recognized a nonoverlapping region (residues 43-59) comprising almost entirely helix B . Mutagenesis of a cluster of residues within helix C showed that at least three residues (K84, R88, and N89) were potentially involved in receptor recognition . The existence of two distinct nonneighboring binding domains in the three-dimensional structure of rhuIL-4 provided preliminary evidence for a model of receptor interaction involving the formation of a ternary complex consisting of two molecules of the extracellular portion of the receptor and one molecule of rhuIL-4.

Biochemistry, 1993 Apr 6, 32(13), 3298 - 305
Rhodopsin mobility, structure, and lipid-protein interaction in squid photoreceptor membranes; Ryba NJ et al.; Treatment of outer segment membranes from Loligo forbesi with endoprotease-V8 from Staphylococcus aureus results in cleavage of the C-terminal extension of the squid rhodopsin, with accompanying reduction of the apparent molecular weight from 47,000 to 36,000 on sodium dodecyl sulfate/polyacrylamide gel electrophoresis . Negative-stain electron microscopy of the intact membranes shows that small clusters of the rhodopsin C-termini form structures extending from the membrane surface and that these are absent after protease treatment . Fourier transform infrared spectra of the amide I band of the protein indicate that removal of the C-terminal extension increases the relative alpha-helical content of squid rhodopsin to a level comparable to that for bovine rhodopsin in disk membranes, and to an extent which suggests that the alpha-helical structure lies mainly in the M(r) 36,000 (transmembrane) section of the protein . Saturation-transfer electron spin resonance (ESR) spectroscopy of the spin-labeled protein reveals that the rotational diffusion of squid rhodopsin in outer segment membranes that have been extensively washed with urea to remove peripheral proteins is much slower than that of bovine rhodopsin in rod outer segment disk membranes . This reduction in rotational mobility is also found with purified squid rhodopsin reconstituted in egg phosphatidylcholine and in urea-washed outer segment membranes which have been treated with endoprotease-V8 to remove the C-terminal extension of squid rhodopsin . In the latter case, the saturation-transfer ESR spectra are virtually identical to those of the non-proteolyzed membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1993 Apr 6, 32(13), 3511 - 8
The epitope for the inhibitory antibody M7-PB-E9 contains Ser-646 and Asp-652 of the sheep Na+,K(+)-ATPase alpha-subunit; Abbott A et al.; The binding of monoclonal antibody M7-PB-E9 to the alpha-subunit of Na+,K(+)-ATPase partially inhibits enzyme activity (35%) in competition with ATP, while in the presence of magnesium it stimulates the rate of ouabain binding severalfold {Ball, W . J . (1984) Biochemistry 23, 2275-2281} . These effects have been shown to result from an antibody-induced shifting of the enzyme's E1 <==> E2 conformational equilibrium to the right that affects all enzyme-ligand interactions except that with Mg2+ {Abbott, A.J., & Ball, W.J . (1992) Biochemistry 31, 11236-11243} . In order to identify the location of the M7-PB-E9 epitope, proteolytic fragments of the lamb kidney enzyme were generated and the immunoreactive alpha fragments were identified by Western blot analyses . These studies revealed a 47-kDa tryptic fragment, which bound both M7-PB-E9 and a -COOH terminus specific antisera and NH2-terminal sequencing showed to originate at Ala-590 . Digestion with Staphylococcus aureus V8 protease produced a 36-kDa -COOH-terminus fragment which originated at Gly-697 and did not contain the antibody epitope . Thus the intracellular sequence region Ala-590 to Gly-697 was shown to contain the antibody epitope . When M7-PB-E9's ability to recognize the alpha subunits from various species and tissues was determined and correlated with available sequencing data, only Ser-646 was present in the highly reactive lamb, pig, and avian kidney alpha 1 proteins and altered (Asn) in the poorly recognized Xenopus and rat kidney and Torpedo electroplax organ enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ugeskr Laeger, 1993 Apr 5, 155(14), 1047 - 9
{Purulent arthritis and bursitis after local injection of depot steroids}; Bak K et al.; The occurrence of severe joint and bursal infections preceded by local steroid injection was investigated in a retrospective survey . Of 37 consecutive patients with pyogenic arthritis or bursitis admitted to two hospitals over a three-year-period, nine (95% confidence limits 12-41%) had received previous intraarticular or intrabursal injections of steroid . Staphylococcus aureus was cultured in all cases . This incidence rate of endemic iatrogenic infection is at least 60 times higher than earlier reported . The alarming frequency may be attributed to insufficient aseptic precautions and/or the injection of depot steroids into cavities with overlooked established infection . An increased awareness of this complication seems warranted . Meticulous hygienic measures should be emphasized in drug information inserts . Health authorities and quality control bodies should monitor and analyze the occurrence of such accidents.

Jpn J Antibiot, 1993 Apr, 46(4), 310 - 7
{Therapeutic efficacy of cefodizime in combination with minocycline against systemic infection caused by methicillin-resistant Staphylococcus aureus in immunocompromised tumour bearing mice}; Furukawa T et al.; The in vivo synergistic effect of cefodizime (CDZM) in combination with minocycline (MINO) against methicillin-resistant Staphylococcus aureus (MRSA) was investigated . A study of fractional effective dose (FED) index showed that either synergistic or additive effect was observed between CDZM and MINO . The postantibiotic effect (PAE) of MINO was not altered by the addition of CDZM . However, a strong synergistic bactericidal effect of CDZM and MINO against MRSA CT-18 was observed for more than 14 hours in the presence of immunocompromised tumour bearing murine polymorphonuclear leukocytes (PMN) . These results suggest that the strong therapeutic efficacy of CDZM in combination with MINO was caused by synergistic bactericidal effect of the 2 drugs in the presence of PMN.

J Gen Microbiol, 1993 Apr, 139 ( Pt 4), 695 - 706
Recombination at the coagulase locus in Staphylococcus aureus: plasmid integration and amplification; McDevitt D et al.; The integrating plasmid pCOA18, comprising pUC18 linked to a mutated coagulase (coa) gene from Staphylococcus aureus, and constructed by substituting coa sequences with a tetracycline (Tc)-resistance marker (delta coa::Tcr), was transformed into Staphylococcus aureus RN4220, where it underwent recombination with the chromosomal coa locus . Allele-replacement mutants were recovered at a low frequency directly after transformation . The majority of transformants carried pCOA18 integrated in the chromosome by a single Campbell-type recombination event . The majority of integrants contained tandem repeats of pCOA18 and expressed high levels of resistance to Tc (> 30 micrograms ml-1) compared to the single-copy integrants and allele-replacement mutants (15 micrograms ml-1) . Transduction of a single-copy integrant to a Coa+ recipient allowed the cointegrant to be resolved and allele-replacement recombinants to be selected . In addition, growth of a single-copy integrant on high concentrations of Tc (> 30 micrograms ml-1) selected for amplified derivatives at a frequency of 10(-5) . It was estimated that up to 19 copies of pCOA18 could occur in a tandem array in the chromosome.

J Biochem (Tokyo), 1993 Apr, 113(4), 413 - 9
Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of Agkistrodon blomhoffii siniticus; Ohkura N et al.; Phospholipase A2 inhibitor (PLI) was purified from the blood plasma of Chinese Mamushi, Agkistrodon blomhoffii siniticus, by sequential chromatography on Sephadex G-200, Mono Q, and Blue-Sepharose CL-6B columns . The purified PLI was a glycoprotein with an apparent molecular mass of 75 kDa and was composed of a single subunit with a mass of about 20 kDa . From the results of a cross-linking experiment, the PLI was found to present as a homotrimer of the subunit . The fundamental properties of A . blomhoffii siniticus PLI were very similar to those of Habu Trimeresurus flavoviridis PLI {Kogaki et al . (1989) J . Biochem . 106, 966-971}, although the latter was composed of two homologous subunits, PLI-A and PLI-B {Inoue et al . (1991) J . Biol . Chem . 266, 1001-1007} . The amino acid sequence of the subunit of A . blomhoffii siniticus PLI was determined by alignment of the peptides obtained by lysyl endopeptidase digestion or Staphylococcus aureus V8 protease digestion . The subunit was composed of 147 amino acid residues with one residue, Asn103 being N-glycosylated . The molecular weight of its protein portion was calculated to be 16,444 Da . The amino acid sequence of A . blomhoffii siniticus PLI subunit showed about 75% homology to those of T . flavoviridis PLI subunits, and also showed significant homologies to those of the carbohydrate recognition domains of C-type lectins.

J Antimicrob Chemother, 1993 Apr, 31(4), 559 - 68
Enhanced Staphylococcus aureus susceptibility to immunodefences induced by sub-inhibitory and bactericidal concentrations of imipenem; Cuffini AM et al.; Recent evidence suggests that the selection of an antibiotic for the treatment of infection should take into account not only the drug's antimicrobial activity but also the way in which it interacts with host defence mechanisms, since this may influence the response to infection . In this study we have investigated the effects of imipenem on the activities of human macrophages against Staphylococcus aureus . Bacterial susceptibility to phagocytosis and intracellular killing were determined after S . aureus and macrophages were incubated both simultaneously with sub-inhibitory and bactericidal concentrations of imipenem and following pre-exposure of the organisms and the macrophages individually to the same concentrations of imipenem . At both concentrations and under both circumstances, imipenem potentiated the phagocytic and microbicidal activities of the macrophages.

J Antimicrob Chemother, 1993 Apr, 31(4), 533 - 41
Synergic activity of imipenem/cilastatin combined with cefotiam against methicillin-resistant Staphylococcus aureus; Oka S et al.; The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia model . Combinations of imipenem plus cefotiam in ratios from 1:5 to 1:160 were more effective than either imipenem alone or cefotiam alone (P < 0.05) . Synergy was observed against both beta-lactamase producing and beta-lactamase non-producing MRSA . Staggered combinations of imipenem with cefotiam (each drug was administered at a different time) were studied in an in-vitro pharmacokinetic system to clarify relationships between killing kinetics and pharmacodynamics of the combinations . In the in-vitro system, cefotiam (1 g over 30 min) administered 2 h after imipenem administration (250 mg over 30 min) reduced viable cell counts to an undetectable level and maintained this for 4 h, while the simultaneous administration of imipenem and cefotiam maintained an undetectable cell count for only 2 h . Furthermore, imipenem administered after cefotiam showed no synergy . These results indicate that the timing of dosing of each antibiotic influences synergy, and administration of cefotiam 2 h after imipenem is more effective than the other regimens.

Clin Infect Dis, 1993 Apr, 16(4), 574 - 9
Spectrum of extraintestinal disease due to Aeromonas species in tropical Queensland, Australia; Kelly KA et al.; During a 12-month period, the clinical spectrum of extraintestinal disease due to Aeromonas species was determined for 56 patients in tropical Queensland (Australia) . Forty-six patients acquired their infection in the community, six patients were infected in the hospital, and four patients were colonized . Demographic risk factors included male gender (67%) and Aboriginal ethnic background (35%) . The disease ranged from deep-seated infection (four cases) to soft-tissue infection of varying intensity (48 cases) . Among patients whose infections were community acquired, 22 required hospitalization and 27 suffered trauma-associated infection . Seventeen patients (63%) in the latter group had lacerations to the hands and feet that were contaminated with surface water or soil . The appearance of the wounds was not pathognomonic, and diagnosis was made by laboratory evaluation . Aeromonas was the sole pathogen in nine patients . Polymicrobial infections were due to Aeromonas and mainly Staphylococcus aureus and/or mixed enteric bacteria . Aeromonas hydrophila was the most common species isolated (71%), followed by Aeromonas sobria (25%) . In nine cases, the empirical antibiotic regimen prescribed did not adequately cover infection due to Aeromonas . Infection was seen regularly throughout the year, but a cluster of cases also occurred during the tropical Australian wet season.

J Vet Med Sci, 1993 Apr, 55(2), 297 - 300
Characteristics of Staphylococcus aureus isolated from peracute, acute and chronic bovine mastitis; Matsunaga T et al.; Fifty-eight Staphylococcus aureus strains isolated from bovine mastitic milk at 27 dairy farms in Japan during the period from November 1988 to May 1989 were examined for their productivity of virulence associated factors . The positive rates of the total isolates for various virulence factors were as follows: toxic shock syndrome toxin-1 (TSST-1, 27.6%), staphylococcal enterotoxins (SEs, 34.5%), alpha-haemolysin (74.1%), beta-haemolysin (65.5%), delta-haemolysin (12.1%), DNase (100%), egg-yolk factor (25.9%), clumping factor (70.7%) and protein A (58.6%) . All of S . aureus isolates from peracute mastitis produced TSST-1, SEC, alpha-haemolysin and beta-haemolysin . While none of clumping factor and protein A were detected among peracute isolates, these factors were produced at a relatively high frequency by isolates from chronic mastitis . In coagulase typing, the most predominant type was VI (36.2%), and types IV, V and VIII were not observed . TSST-1 positive isolates showed interesting characteristics which all of the isolates produce both SEC and coagulase type VI but lack egg-yolk factor, clumping factor and protein A except for one isolate . We could infer that TSST-1 and SEC contribute to bovine mastitis, especially to peracute mastitis from the present study.

J Vet Med Sci, 1993 Apr, 55(2), 259 - 63
Effects of active egg white product on neutrophil function in calves; Nakagawa J et al.; The effects of an active egg white product (AEWP) on neutrophil function in calves were investigated . Calves were administered AEWP orally at doses of 250 mg and 500 mg/kg either once or twice, with an interval of 5 days between doses in the latter case . The peripheral blood neutrophils of calves receiving a single 500 mg/kg dose displayed increased nitroblue tetrazolium reducing activity and increased intracellular killing of Staphylococcus aureus from 1 day after administration, with maximum levels being attained on the 3rd day . However, no such increase of these activities was observed after administration of 250 mg/kg . Calves receiving two doses of 500 mg/kg displayed the same changes as seen in the corresponding one-dose group, while the neutrophil activity of calves receiving 250 mg/kg also increased after the second dose . However, no increase in the peripheral blood neutrophil count was observed after AEWP administration . Thus, AEWP enhanced the nonspecific antibacterial activity of neutrophils when given to calves by the oral route.

Biomaterials, 1993 Apr, 14(5), 383 - 91
Adherence to a metal, polymer and composite by Staphylococcus aureus and Staphylococcus epidermidis; Verheyen CC et al.; Bacterial adherence on to several materials with a potential application in reconstructive surgery was studied . Polymer (poly(L-lactide)), composite (hydroxyapatite/poly(L-lactide)) and metal (316L stainless steel) were evaluated both as smooth and sandblasted specimens . All materials were incubated in phosphate-buffered saline, challenged with Staphylococcus aureus or S . epidermidis and evaluated for up to 24 h . S . aureus showed a preference for the metal and composite tested over the polymer used . For S . epidermidis no preference was found for one of the investigated materials . The influence of surface roughness on bacterial growth was demonstrated by increased colonization on the sandblasted specimens.

Fundam Appl Toxicol, 1993 Apr, 20(3), 280 - 7
Effects of 7,12-dimethylbenz{a}anthracene on the superantigen toxic shock syndrome toxin (TSST-1)-induced proliferation and antibody secretion by human lymphocytes; Wood SC et al.; Toxic shock syndrome toxin (TSST-1), a 22-kDa exotoxin secreted by Staphylococcus aureus, can act as a nominal antigen and induce proliferation and immunoglobulin secretion in human B-cells . The purpose of the present studies was to examine the effect of 7,12-dimethylbenz{a}anthracene (DMBA), a well-characterized immunosuppressant of both cell-mediated and humoral immunity in murine lymphocytes, upon the mixed lymphocyte reaction (MLR) and TSST-1-induced immune responses in human lymphocytes . The MLR, using human tonsillar lymphocytes (HTL) from four different donors, was inhibited in a dose-dependent manner from 1 to 100 microM . The IC50 for the suppression of the MLR ranged from 10 to 40 microM . TSST-1 is a potent stimulator of T-cells bearing specific VB regions on the T-cell receptor (TCR) . In contrast with the results from the MLR, DMBA inhibited TSST-1-induced T-cell proliferation only at 100 microM in HTL . A similar profile of activity was determined with splenic T-cells from a single donor . TSST-1 has also been demonstrated to induce specific B-cell proliferation and differentiation in the presence of irradiated T-cells . TSST-1-induced B-cell proliferation was only consistently and markedly inhibited by DMBA at 100 microM in tonsillar and splenic lymphocytes . In contrast, TSST-1-induced B-cell differentiation, as manifested by IgM and IgG secretion, was inhibited in a dose-dependent manner from 1 to 100 microM DMBA in B-cells from human tonsils and spleens.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antibiot (Tokyo), 1993 Apr, 46(4), 606 - 13
TAN-1057 A-D, new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus . Taxonomy, fermentation and biological activity; Katayama N et al.; Two Gram-negative bacteria were found to produce the new antibacterial antibiotics TAN-1057 A, B, C and D . The producing bacteria were characterized and designated as Flexibacter sp . PK-74 and PK-176 . These antibiotics were active against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus . TAN-1057 A inhibited protein biosynthesis in Escherichia coli and S . aureus . It showed excellent protective effects against an experimental methicillin-resistant S . aureus infection in mice.

Am J Infect Control, 1993 Apr, 21(2), 70 - 4
Higher overall nosocomial infection rate because of increased attack rate of methicillin-resistant Staphylococcus aureus; Stamm AM et al.; BACKGROUND: Methicillin-resistant Staphylococcus aureus has become a frequent cause of hospital-acquired infectious disease . However, the impact of methicillin-resistant S . aureus on the overall nosocomial infection rate has not been clearly defined . METHODS: The University of Alabama at Birmingham Hospital is a tertiary care facility and participant in the National Nosocomial Infections Surveillance system . Prospective, hospital-wide surveillance for nosocomial infections was conducted for 8 months per year during 1986 through 1991 . RESULTS: The total nosocomial infection rate increased from 4.5% in 1987 to 5.9% in 1990 . This was temporally associated with a rise in the attack rate of methicillin-resistant S . aureus from 0% to 0.4% . The remainder of the increase was caused by other gram-positive microorganisms, including methicillin-sensitive S . aureus . We identified methicillin-resistant S . aureus most commonly in the surgical intensive care unit and as a cause of lower respiratory tract infections . In contrast, methicillin-sensitive S . aureus was most frequently found in the neurologic intensive care unit and as the etiologic agent of surgical wound infections . CONCLUSIONS: Methicillin-resistant S . aureus has become a common nosocomial pathogen . There has been no decrease in the attack rate of methicillin-sensitive S . aureus or other gram-positive cocci . The total nosocomial infection rate has increased as a result equally of the emergence of methicillin-resistant S . aureus and of the renewed activity of other gram-positive pathogens . Methicillin-resistant S . aureus has added to the overall burden of nosocomial infectious disease.

J Nat Prod, 1993 Apr, 56(4), 571 - 82
Tricolorin A, major phytogrowth inhibitor from Ipomoea tricolor; Pereda-Miranda R et al.; The allelopathic potential of Ipomoea tricolor (Convolvulaceae), used in Mexican traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of organic extracts on seedling growth of Amaranthus leucocarpus and Echinochloa crus-galli . Bioactivity-directed fractionation of the active CHCl3 extract led to the isolation of the allelopathic principle, which turned out to be a mixture of the so-called "resin glycosides" of convolvulaceous plants . The structure of tricolorin A, the major phytogrowth inhibitor present in the active fraction, was elucidated as (11S)-hydroxyhexadecanoic acid 11-O-alpha-L-rhamnopyranosyl-(1-->3)-O-alpha-L-{2-O-(2S-methylbutyryl)-4 -O- (2S-methylbutyryl)} rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D-fucopyran oside- (1,3"-lactone){1}, based on chemical methods and spectral analysis including 1H-1H COSY, 1H-13CHETCOR, long range 1H-13C COLOC, and selective INEPT experiments . Bioassays showed that radicle elongation of the two weed seedlings tested was inhibited by tricolorin A {1} with IC50 values ranging from 12 to 37 microM . Staphylococcus aureus was sensitive to compound 1 with an MIC value of 1.8 micrograms/ml . Significant cytotoxic activity against cultured P-388 and human breast cancer cells (ED50 2.2 micrograms/ml) was demonstrated for compound 1, and it also inhibited phorbol 12,13-dibutyrate binding using calf brain homogenate as a source of protein kinase C (IC50 43 microM).

Immunology, 1993 Apr, 78(4), 563 - 7
Induction of macrophage parasiticidal activity by Staphylococcus aureus and exotoxins through the nitric oxide synthesis pathway; Cunha FQ et al.; Murine peritoneal macrophages stimulated in vitro with killed Gram-positive bacteria Staphylococcus aureus or its membrane components in the presence of interferon-gamma (IFN-gamma) expressed high levels of nitric oxide (NO) synthase and produced large amounts of NO in a dose-dependent manner . This is not due to the contamination by Gram-negative endotoxin because the stimulatory activity was not affected by the addition of polymyxin B . The expression of the NO synthase and the synthesis of NO by macrophages stimulated with toxic shock syndrome toxin-1 (TSST), lipoteichoic acid (LTA) or killed whole S . aureus together with IFN-gamma was inhibited by the glucocorticoid, dexamethasone or by the specific inhibitor of NO synthesis, L-N-iminoethyl-ornithine (L-NIO) . The exotoxins together with IFN-gamma also activated macrophages to kill the intracellular parasite Leishmania major . The leishmanicidal activity was completely inhibited by L-NIO.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 737 - 40
Pharmacokinetics and bactericidal activities of one 800-milligram dose versus two 400-milligram doses of intravenously administered pefloxacin in healthy volunteers; Petitjean O et al.; Pefloxacin pharmacokinetics and serum bactericidal activities (SBA) against Escherichia coli and Staphylococcus aureus were compared after intravenous infusion of either a single 800-mg dose or twice-daily 400-mg doses into 16 healthy volunteers . Plasma pefloxacin concentrations were measured for up to 60 h, and SBAs were determined 1, 12, and 24 h after the start of the infusion . The mean areas under the concentration-versus-time curve for plasma were not different (138 versus 136 h.mg/liter) . The mean clearances, volumes of distribution, and half-lives were also comparable . The mean (+/- standard deviation) maximal concentration after the 800-mg infusion was 12.11 +/- 1.35 versus 6.51 +/- 0.73 mg/liter after the first 400-mg infusion and 7.42 +/- 0.76 mg/liter after the second 400-mg infusion . Mean trough concentrations at 24 h were significantly different: 2.77 +/- 0.63 (800 mg) versus 1.93 +/- 0.49 (400 mg twice) mg/liter (P = 0.0007) . Mean SBAs against E . coli after 800 mg of pefloxacin were higher than 1/128 (1 h), 1/32 (12 h), and 1/16 (24 h) . Mean SBAs against S . aureus under the same conditions were higher than 1/64 (1 h), 1/16 (12 h), and 1/8 (24 h) . Mean SBAs at 1 and 12 h were significantly higher after the 800-mg infusion than after the 400-mg infusion but were similar at 24 h for both regimens . Comparison of SBAs according to National Committee for Clinical Laboratory Standards criteria showed a similar adequacy at 24 h for both regimens against both strains . Administration of 800 mg of pefloxacin once a day is bioequivalent to 400 mg twice a day, and bactericidal activity of the 800-mg infusion is not less than that of two 400-mg infusions.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 702 - 7
Efficacy of prophylaxis with beta-lactams and beta-lactam-beta-lactamase inhibitor combinations against wound infection by methicillin-resistant and borderline-susceptible Staphylococcus aureus in a guinea pig model; Kernodle DS et al.; Although some beta-lactams and beta-lactam-beta-lactamase inhibitor combinations exhibit activity against methicillin-resistant Staphylococcus aureus, there remains the concern that therapeutic failures may result from the selection of resistant subpopulations . The prophylactic use of these antibiotics in clean surgery, however, may prove adequate since wound infections arise from the inoculation of small numbers of bacteria . In this clinical setting, heterogeneity in the phenotypic expression of beta-lactam resistance may facilitate antibiotic efficacy . Similarly, beta-lactamase-mediated resistance in S . aureus is dependent on inoculum size, and it may be possible to prevent infection from small inocula with relatively labile beta-lactams . To test this hypothesis, antibiotics were administered to guinea pigs as prophylaxis against infection by two methicillin-resistant strains and one borderline-susceptible strain . Following prophylaxis with sulbactam or placebo, inoculation of only a dozen or fewer bacteria had a 50% probability of creating an abscess (50% infective dose {ID50}) . The efficacy of ampicillin was similar to that of cefazolin, exhibiting moderate activity against the borderline-susceptible strain (ID50s, greater than 300 bacteria) and minimal activity against the methicillin-resistant strains (ID50s, fewer than 100 bacteria) . Coadministration of sulbactam with ampicillin or cefazolin yielded better results than the beta-lactam alone for five of six strain-beta-lactam combinations, including an 80-fold increase in the efficacy of ampicillin-sulbactam compared with that of ampicillin for one methicillin-resistant strain (ID50s, 2,017 and 25 bacteria, respectively) . Prophylaxis with beta-lactams, especially beta-lactam-beta-lactamase inhibitor combinations, reduces the risk of wound infection by beta-lactam-resistant S . aureus.

Monatsschr Kinderheilkd, 1993 Apr, 141(4), 293 - 6
{"Tropical" pyomyositis in childhood}; Reutter-Simon G et al.; We report on a 14 year old boy, who developed bacterial pyomyositis (Staphylococcus aureus) in his left thigh . Ultrasound and magnetic resonance imaging were very helpful for the differential diagnosis and follow-up of this infection which in large skeletal muscles frequently is associated with abscess formation . Treatment consisted of antibiotics and surgical drainage.

Circ Shock, 1993 Apr, 39(4), 299 - 305
Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis; Vary TC et al.; The effect of inflammation and chronic sepsis on the activity of pyruvate dehydrogenase complex (PDH) in skeletal muscle was investigated in rats . Inflammation was induced by the placement of a catheter in the carotid artery . Sepsis was induced by repeated (every 48 hr) injections of an inoculum composed of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis organisms into a preformed subcutaneous abscess . Hindlimb muscle was sampled 7 or 14 days following the initial injection of the inoculum into the abscess . Total PHD activity was not altered by any of the conditions examined . There were no differences in the proportion of active PDH complex after 7 days in any of the conditions examined . In contrast, 14 days after the initial bacterial injection, the concentration of active PDH complex in skeletal muscle was reduced by 50% in the septic rats . The combination of intravascular catheterization and infection resulted in a further decrease in the concentration of active PDH complex . The decreased concentration of active PDH complex was associated with increased plasma lactate concentrations in septic rats . Catheterization exacerbated the rise in plasma lactate in sepsis . In this model of chronic sepsis, the magnitude of the hyperlactatemia and the inhibition of the PDH complex in skeletal muscle appear dependent upon the length of time of the septic insult and are potentiated by addition of an intravascular focus of inflammation.

Bone Marrow Transplant, 1993 Apr, 11(4), 261 - 9
Microbial carriage, sepsis, infection and acute GVHD in the first 25 BMT at the Royal Liverpool Children's Hospital; Rhodes LE et al.; The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991 . The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts . SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB) . Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage . Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33% . A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only) . A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01) . Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05) . It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD.

J Leukoc Biol, 1993 Apr, 53(4), 404 - 10
Functional alterations of human neutrophils by medium-chain triglyceride emulsions: evaluation of phagocytosis, bacterial killing, and oxidative activity; Bellinati-Pires R et al.; Medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) emulsions currently used in nutritional therapy were evaluated for their in vitro effect on neutrophil oxidative metabolism, phagocytosis, and bacterial killing activities . Neutrophils from healthy adult male volunteers were assessed after blood incubation with commercially available fat emulsions containing LCT, MCT, or a mixture of 50% MCT and 50% LCT at a final triglyceride concentration of 20 mg/ml . It was observed that MCT-containing emulsions stimulated nitroblue tetrazolium (NBT) dye reduction by neutrophils as determined by a cytochemical NBT test performed directly on whole blood . This effect was dose dependent . However, after lipid removal by cell washing, the MCT-treated neutrophils showed decreased production of hydrogen peroxide (H2O2) and NBT reduction in response to bacterial lipopolysaccharide or phorbol myristate acetate stimuli as well as impaired phagocytosis and killing of Staphylococcus aureus . In contrast, the LCT emulsion did not alter any of the neutrophil functions evaluated . The present data suggest that MCTs elicit the oxidative metabolism of neutrophils, probably by phagocytosis of fat particles and, depending on the lipid concentration, this effect may not be reversible, leading to impairment of the cellular response to subsequent membrane stimuli.

Am J Med, 1993 Apr, 94(4), 371 - 8
Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long-term-care facility with the use of mupirocin ointment; Kauffman CA et al.; PURPOSE: To assess the impact of the use of mupirocin ointment on colonization, transmission, and infection with methicillin-resistant Staphylococcus aureus (MRSA) in a long-term-care facility . PATIENTS AND METHODS: All 321 residents of a Veterans Affairs long-term-care facility from June 1990 through June 1991 were studied for MRSA colonization and infection . MRSA-colonized patients received mupirocin ointment to nares in the first 7 months and to nares and wounds in the second 5 months . The effect of mupirocin use on MRSA colonization and infection was monitored . All S . aureus strains isolated were tested for the development of resistance to mupirocin . RESULTS: A total of 65 patients colonized with MRSA received mupirocin ointment . Mupirocin rapidly eliminated MRSA at the sites treated in most patients by the end of 1 week . Weekly maintenance mupirocin was not adequate to prevent recurrences--40% of patients had recurrence of MRSA . Overall, MRSA colonization in the facility, which was 22.7% +/- 1% prior to the use of mupirocin, did not change when mupirocin was used in nares only (22.2% +/- 2.1%), but did decrease to 11.5% +/- 1.8% when mupirocin was used in nares and wounds . Although colonization decreased, roommate-to-roommate transmission and MRSA infection rates, low to begin with, did not change when mupirocin was used . Mupirocin-resistant MRSA strains were isolated in 10.8% of patients . CONCLUSIONS: Mupirocin ointment is effective at decreasing colonization with MRSA . However, constant surveillance was required to identify patients colonized at admission or experiencing recurrence of MRSA during maintenance treatment . Long-term use of mupirocin selected for mupirocin-resistant MRSA strains . Mupirocin should be saved for use in outbreak situations, and not used over the long term in facilities with endemic MRSA colonization.

J Bacteriol, 1993 Apr, 175(8), 2400 - 6
Choline transport activity in Staphylococcus aureus induced by osmotic stress and low phosphate concentrations; Kaenjak A et al.; Uptake of {14C}choline upon hyperosmotic stress of exponential-phase Staphylococcus aureus cultures in a complex medium occurred after a delay of 2.5 to 3.5 h . This uptake could be prevented by chloramphenicol, suggesting that it occurred via an inducible transport system . Radioactivity from {14C}choline was accumulated as {14C}glycine betaine . However, neither choline nor glycine betaine could act as the major carbon and energy source for the organism, suggesting that choline was not metabolized beyond glycine betaine . Assay of choline transport activity in cells grown under different conditions in defined media revealed that osmotic stress was mainly responsible for the induction, but choline gave a further increase in induction . The system was not induced in anaerobically grown cells . Choline transport activity was repressed by glycine betaine and proline betaine, suggesting that these compounds are corepressors . Choline transport activity was not induced in cells osmotically stressed by 1 M potassium phosphate or 0.5 M sodium phosphate, but was induced in cells grown in low-phosphate medium in the absence of osmotic stress . This suggests that there is a connection between the phosphate and osmotic stress regulons . Choline transport was energy and Na+ dependent and had a Km of 46 microM and a maximum rate of transport (Vmax) of 54 nmol/min/mg (dry weight) . The results of competition studies suggested that N-methyl and an alcohol group or aldehyde groups at the ends of the molecule were important in its recognition by the system . Glycine betaine was not a highly effective competitor, suggesting that its transport system and the choline transport system were distinct from each other . Choline transport was highly susceptible to a variety of inhibitors, which may be related to the greater dependence on respiratory metabolism of cells grown in the presence of high NaC1 concentrations.

J Clin Microbiol, 1993 Apr, 31(4), 982 - 5
Random amplified polymorphic DNA assay is less discriminant than pulsed-field gel electrophoresis for typing strains of methicillin-resistant Staphylococcus aureus; Saulnier P et al.; Twenty-six strains of methicillin-resistant Staphylococcus aureus with different pulsed-field gel electrophoresis fingerprints were tested by random amplified polymorphic DNA assay with three primers, resulting in 15 to 20 different random amplified polymorphic DNA fingerprints . By summing the results for the three primers, the number of different fingerprints increased to 25, but two strains could not be differentiated . We conclude that pulsed-field gel electrophoresis remains the best method of typing methicillin-resistant S . aureus strains.

Eur J Immunol, 1993 Apr, 23(4), 984 - 7
Interleukin 6 is not required for antigen-specific antibody responses by human B cells; Costelloe KE et al.; Interleukin-6 (IL-6) is a late-acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established . We show here that IL-6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus . A blocking IL-6 antibody also had no effect on antibody production, suggesting that endogenous IL-6 production was not required . In control experiments, this antibody inhibited PWM-stimulated immunoglobulin secretion and proliferation of the IL-6-dependent B cell line B9 . A requirement for IL-6 in responses of unfractionated TMC may have been disguised by the presence of T cells . To overcome this problem, we investigated the effect of IL-6 on specific antibody production by T-depleted B cells stimulated with antigen in the presence of IL-2, which is a T cell replacing factor (TRF) for human B cells . Specific antibody production was restored by IL-2, but not IL-6 . Neither IL-6 nor anti-IL-6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF . These experiments show that IL-6 does not have a significant role in antigen (influenza virus)-specific antibody responses by human B lymphocytes.

Infect Immun, 1993 Apr, 61(4), 1593 - 5
Reduction of bacterial titers by low-dose aspirin in experimental aortic valve endocarditis; Nicolau DP et al.; Using a rabbit model of Staphylococcus aureus endocarditis, we studied the effects of aspirin on the natural progression of this infection . Compared with untreated animals, the aspirin-treated animals showed a 30% (P = 0.11) reduction in the weight of the vegetations and an 84% (P = 0.03) reduction in the bacterial titer of the vegetations.

Infect Immun, 1993 Apr, 61(4), 1581 - 5
High sodium chloride concentrations inhibit staphylococcal enterotoxin C gene (sec) expression at the level of sec mRNA; Regassa LB et al.; Expression of the staphylococcal enterotoxin type C gene (sec) is regulated in response to both high NaCl concentrations (osmolarity) and the accessory gene regulator (agr) . agr is a global regulator that alters the expression of many genes in Staphylococcus aureus . In this report, we have demonstrated that osmoregulation of sec occurs at the level of mRNA independently of an intact agr allele . Northern (RNA) and Western blot (immunoblot) analyses of samples from cultures grown in low- (0 M NaCl) and high-osmotic-strength (1.2 M NaCl) media revealed that the low-osmotic-strength culture contained approximately 16-fold more SEC and sec mRNA than the high-osmotic-strength culture . sec expression in high-osmotic-strength medium was enhanced when osmoprotective compounds were added . Osmoregulation of sec expression in Agr- strains was also examined; SEC and sec mRNA levels decreased in response to high osmolarity in a manner similar to that seen in the Agr+ strains.

Cell Immunol, 1993 Apr 1, 147(2), 279 - 93
Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines; Abdelnour A et al.; We have recently described a murine model of Staphylococcus aureus-induced septic arthritis . One of the hallmarks of this disease is a striking hypergammaglobulinemia . In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain . In vivo, inoculation of live S . aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells . We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell-dependent phenomenon . Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells . To elucidate mechanisms responsible for S . aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S . aureus on the release of cytokines . Our results show that the S . aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties . The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator . Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S . aureus . Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL-6 but not TNF-alpha had potent B-cell differentiation properties in S . aureus-stimulated cell cultures.

J Infect Dis, 1993 Apr, 167(4), 810 - 7
Down-regulation of human immunodeficiency virus type (HIV-1) production after stimulation of monocyte-derived macrophages infected with HIV-1; Nottet HS et al.; Macrophages infected with human immunodeficiency virus (HIV) can be stimulated as a result of secondary infections . The effect of stimulation of HIV-1-infected monocyte-derived macrophages on HIV-1 production by these cells was studied . Exposure of macrophages to phorbol 12-myristate 13-acetate or to opsonized Escherichia coli, Staphylococcus aureus, or zymosan resulted in a decrease in HIV production . HIV production was inversely related to the degree of stimulation, measured as lucigenin-enhanced chemoluminescence . The production of reactive oxygen intermediates, however, did not seem to be the direct cause of the diminished HIV production, since oxygen-radical scavengers did not prevent the decrease in HIV production . Furthermore, oxygen-radical scavengers did not affect HIV production by nonstimulated macrophages . These results indicate that activation signals have an opposite effect and reactive oxygen intermediates have no effect on HIV production in macrophages compared with the effect described in T cells.

Alcohol Clin Exp Res, 1993 Apr, 17(2), 389 - 93
Alcohol-induced inhibition of alveolar macrophage oxidant release in vivo and in vitro; Antony VB et al.; Alcohol consumption is known to predispose the host to more frequent and severe bacterial infections, suggesting that alcohol compromises the normal immune function of the lung . The pulmonary alveolar macrophage is the resident host defense cell in the lung and forms the first line of defense against invading microorganisms . One of the mechanisms whereby alveolar macrophages kill bacteria is by releasing toxic oxygen radical species, such as superoxide anion and hydrogen peroxide . We hypothesized that chronic alcohol consumption caused alveolar macrophage dysfunction leading to inhibition of oxidant production when stimulated . Our data demonstrate that alveolar macrophages harvested from alcohol-treated rats release significantly lower quantity (p < 0.05) of both superoxide anion and hydrogen peroxide when stimulated with several different types of stimuli including heat-killed Staphylococcus aureus, soluble immune complexes or phorbol myristate acetate . Pair-fed control rats who received isocaloric quantities of maltose dextrin in their diet to compensate for the alcohol were able to produce oxidants in equal quantities when stimulated, to rats who were fed a normal diet . Similar results were noted in vitro experiments when alveolar macrophages harvested from normal rats were incubated in vitro in alcohol-containing media and then stimulated with the aforementioned stimuli . Alveolar macrophages, which had been incubated in alcohol for 4 hr, showed significant decreases in their ability to produce superoxide anion . This defect was noticeable for a period up to 8 hr following removal of alveolar macrophages from the alcohol-containing media.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Exp Immunol, 1993 Apr, 92(1), 164 - 8
The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells; Wang W et al.; In this study we examined the effects of retinol (ROH), a metabolic precursor of retinoic acid (RA), on Staphylococcus aureus Cowan I (SAC)-induced immunoglobulin synthesis of cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC) . ROH augmented SAC-induced IgM synthesis of CBMC by 5.9 +/- 1.5-fold (n = 7, mean +/- s.d.), and IgG synthesis of adult PBMC by 16.3 +/- 5.1-fold (n = 3) at optimal concentrations of 10(-6) M and 10(-11) M, respectively . No augmenting effects could be demonstrated for the other immunoglobulin isotypes . Time-course studies showed that the synthesis of IgM by CBMC was accelerated with detectable immunoglobulin in supernatant fluids starting on day 3 . ROH augmented immunoglobulin synthesis of CBMC stimulated by Epstein-Barr virus (EBV), a T cell-independent polyclonal activator, and of EBV-transformed B cell clones (2.5 +/- 0.2 and 4.1 +/- 1.5-fold increase, respectively), which suggests that ROH can act directly on B cells to enhance immunoglobulin synthesis . In contrast, when ROH was preincubated with cord blood T cells, washed and added to the B cell-enriched fraction with SAC, no increase (0.9-1.8-fold) in IgM synthesis was obtained . Thus, the principal mechanism(s) by which ROH augments immunoglobulin synthesis is by acting on B cells . This is in contrast to the immunoglobulin-enhancing effects of RA which is mediated by T cells, or T cell products, e.g . cytokine . Our studies suggest that RA and ROH may have different pathways of immunoglobulin-enhancing effects, perhaps mediated by different retinoid binding proteins resulting in gene activation and immunoglobulin synthesis.

Infect Immun, 1993 Apr, 61(4), 1281 - 7
Phagocytosis of Staphylococcus aureus induces a selective stress response in human monocytes-macrophages (M phi): modulation by M phi differentiation and by iron; Kantengwa S et al.; Phagocytosis of microorganisms represents a stress not only for the phagocytosed agent but also for the host cell . We have investigated the stress response induced in human monocytes-macrophages (M phi) phagocytosing inactivated Staphylococcus aureus . Exposure of human M phi to S . aureus induced in these cells (i) a threefold increase in superoxide dismutase activity, (ii) a selective and differentiation-dependent induction of host heat shock protein synthesis (HSP70 but not HSP65), and (iii) de novo synthesis of heme oxygenase, but only when exogenous iron was added to the cultures . The coordinate upregulation of two scavenging enzymes and of HSP70 suggests that all three are part of cellular protective mechanisms against phagocytosis-related oxidative injury to host cells.

Oral Microbiol Immunol, 1993 Apr, 8(2), 125 - 7
Salivary effects on polymorphonuclear leukocyte functions; Fumarulo R et al.; Respiratory burst, enzymatic degranulation and bacterial killing were investigated on peripheral blood polymorphonuclear leukocytes (polymorphonuclear leukocytes) incubated with a pool of salivary fluids elicited from healthy donors . Low saliva concentrations primed polymorphonuclear leukocytes for enhancement of O2 consumption, O2- and beta-glucuronidase release and Staphylococcus aureus killing . Whole saliva, on the contrary, depressed all tested phagocytic activities.

Immun Infekt, 1993 Apr, 21 Suppl 1, 40 - 2
{Preliminary results in a placebo-controlled, double-blind crossover clinical trial with human interleukin-2 (n-IL-2) in patients with variable immunodeficiency syndrome (CVID)}; Rump JA et al.; Ten CVID patients with an in vitro defect for IL-2-synthesis were treated for 12 months in a placebo-controlled double-blind crossover therapy study with human natural IL-2 s.c . There were no severe side effects of n-IL-2 recorded . Serum levels of soluble IL-2 receptors were unaffected by the therapy . Serum IL-2 levels were only measurable in single patients during the therapy phase . Since verum and placebo groups did not differ with respect to requirement for intravenous gammaglobulin substitutions, n-IL-2 therapy was uneffective in switching on IgG synthesis in vivo . Nevertheless, there was an elevation in vitro of IgM synthesis in 5 patients and of IgG synthesis in 4 patients during n-IL-2 therapy after stimulation of patients' lymphocytes with staphylococcus aureus Cowan I (SAC) plus n-IL-2 or with Pokeweed Mitogen (PWM) without n-IL-2 . Additionally, an elevated IL-2-synthesis in vitro was recorded after OKT3 stimulation for 3 CVID patients . There was a significant reduction of severe infections from 25 during the first 6 months of the study to 7 infections during the following 6 months, in the group of patients which received n-IL-2 first . In the second group, which received placebo first, there were no significant differences between placebo and n-IL-2 therapy phase detectable (25 infections during the first 6 months of the study and 24 severe infections in the second phase).(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Ophthalmol (Copenh), 1993 Apr, 71(2), 160 - 4
Central microbial keratitis in a Swedish city population . A three-year prospective study in Gothenburg; Neumann M et al.; An analysis of central microbial keratitis with respect to etiology, recovery, complications and visual outcome was carried out in Gothenburg, Sweden, during a 3-year period . Gram positive bacteria were found in 22 out of 48 cases; Staphylococcus aureus and Staphylococcus epidermidis accounted for more than 50% of these Gram positive cases . Pseudomonas was the most common Gram negative bacterium . No case with etiology of fungus was found . The contact lens wearers showed mainly the same bacterial spectrum as non-wearers . The initial 'shotgun' therapy with cefuroxime and gentamycin seemed adequate for this bacterial spectrum . Seventy percent of the eyes healed within 3 weeks . Contact lens wear and trauma were found to be the two major predisposing factors in the cases with microbial keratitis . The lens wearers had shorter recovery times than the non wearers . The visual results after one month were good in 50% of the eyes, and another 12% attained useful vision.

Comp Immunol Microbiol Infect Dis, 1993 Apr, 16(2), 173 - 8
Evidence for homology of buffalo and goat granular cationic peptides; Sarmah S et al.; Due to lack of studies on PMN granular cationic proteins to assess immunostatus of buffaloes, the peripheral PMN leukocytes were subjected to homogenization by sonication and centrifugation cycles in order to obtain pure pellet of granules . Acid extracted granules contained cationic proteins and peptides, which were further separated by exclusion Sephadex G-50 chromatography, the peptides were in the last peak and were found to be active against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria . The peptides were conjugated to ovalbumin in order to develop antibodies, which were further tested by Ouchterlony double immunodiffusion and enzyme linked immunosorbent assay . These tests demonstrated the antigenic relationship between buffalo and goats for the PMN cationic peptides as well as the peptide release which was also monitored in activated buffalo PMN leukocytes.

Acta Paediatr, 1993 Apr, 82(4), 404 - 7
Abnormal responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I and interleukin-2; Inoue Y et al.; Responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I (SAC) and recombinant interleukin-2 (rIL-2) varied in our study . T-cell function and IL-2 production were normal, and intrinsic B-cell defects were suggested . Some patients showed no increase in expression of IL-2 receptors on B cells with SAC stimulation, which may be due to impaired maturation stages . Two patients showed an increased level of B cells with IL-2 receptors, suggesting blocked development of intracellular mechanisms . One patient may have a defect in immunoglobulin isotype switching.

J Dermatol, 1993 Apr, 20(4), 198 - 202
Furuncle-like lesions in mouse experimental skin infections with Staphylococcus aureus; Abe Y et al.; The pathomechanism of furuncle has not been fully elucidated and should be investigated using an appropriate animal model . We observed the invasion of Staphylococcus aureus cells into hair follicles in mice, using a strain of S . aureus isolated from human furunculosis . Light microscopical examination revealed that S . aureus cells attached to corneocytes at 6 h after inoculation, proliferated around the ostium of the hair follicle and invaded the hair follicle at 12 h after inoculation . Electron microscopically, S . aureus cells attached to the horny layer of hair follicle with long, thick, string-like structures . At 12 h after inoculation, S . aureus cells invaded in a file between the inner root sheath and outer root sheath . We could not induce direct invasion from the follicle ostium . Our findings suggest that there are some regions of the hair follicle through which S . aureus cells can relatively easily invade deeper into the follicle . The most important question is what confines the invasion and inflammation of S . aureus to the hair follicle . We suggest that there is some locus minoris for invasion into hair follicles by S . aureus, such as an interface between the two sheaths.

J Dermatol, 1993 Apr, 20(4), 193 - 7
The incidence of isolation of methicillin-resistant Staphylococcus aureus (MRSA) strains from skin infections during the past three years (1989-1991); Nishijima S et al.; We did a statistical study of 294 strains of Staphylococcus aureus (S . aureus) isolated from skin infections during the period from January of 1989 to December of 1991 in the Department of Dermatology, Kansai Medical University Hospital . We especially examined methicillin-resistant S . aureus (MRSA) from the point of view of incidence, variety of skin infections with MRSA, coagulase type, phase type, and resistance against antimicrobial agents . The frequency of isolation of MRSA has been increasing . In 1991, the proportion of MRSA isolates among all S . aureus strains isolated from skin infections was 41.5% . MRSA was isolated most often from infectious decubitus . Coagulase type II and phage group NT (not typable) MRSA were most frequently isolated . The resistance of MRSA to OFLX and IMP/CS had remarkably increased . Notably, the resistance to MINO was low before 1991.

Rev Argent Microbiol, 1993 Apr-Jun, 25(2), 80 - 7
Effect of potassium sorbate and pH on the survival of Staphylococcus aureus in saturated sugar solutions; Chirife J et al.; Addition of 0.3% (w/w) of potassium sorbate (a permitted food additive) coupled with a reduction of pH from 7 to 6 or 5.5, resulted in a dramatic decrease in the survival of two S . aureus strains inoculated (10(8) c.f.u./ml) in laboratory media supplemented with sugar (227 g sugar/100 g water) and incubated at 35 degrees C . These in vitro results may be of potential value to improve the efficacy of sugar therapy for the treatment of certain infected wounds; however, clinical trials are needed to confirm these findings.

Pathol Biol (Paris), 1993 Apr, 41(4), 434 - 40
{Evaluation of three automated blood culture systems . Bio Argod, Bact T/Alert, bactec NR-860}; Aubert G et al.; In 1991 and 1992, three automated blood culturing systems were successively assessed ("Diagnostics Pasteur" Bio Argos: 1,120 Vials, "Organon Teknika" BacT/Alert: 1,400 vials and "Becton Dickinson" bactec NR-860: 2,146 standard vials 6 and 7 and 2,360 resin vials 26 and 27), and compared with the conventional system (C) (Roche aerobic BHI-S Liquoid, and Diagnostics Pasteur anaerobic prereduced Shaedler) . Duplicate blood cultures were collected in various hospital services . They were processed over a 7-day period by the automated instruments and were incubated for 10 days using conventional techniques . The percentage of positivity (clinically significant results) obtained with the automated instruments was similar to that obtained with conventional techniques . Bio Argos: 3.4 p . cent vs 3.8 p . cent with C, BacT/Alert: 3.9 p . cent vs 3.5 p . cent, Bactec standard 6 and 7 vials: 5.6 p . cent vs 6.4 p . cent, and resin 26 and 27: 4.2 p . cent vs 3.1 p . cent . A better sensitivity was found with Bactec resin 26 and 27 vials when compared to C for Staphylococcus aureus (22 p . cent of S . aureus strains were isolated only with resin vials 26 and 27) . False positives were as follow: 0.36 p . cent for BacT/Alert, 2.1 p . cent for Bio Argos and 3.5 p . cent for Bactec . The fastest detection rate was observed with the instrument which shakes the vials continuously (BacT/Alert): 73.6 p . cent of positive vials were detected on the day the vials were received at the laboratory . Ninety-four percent of the Bactec resin 26 and 27 positive vials, 90.6 p . cent of the BacT/Alert positive vials, 84 p . cent of the Bactec 6 and 7 positive vials and 73.7 p . cent of the Bio Argos positive vials were detected within twenty-four hours.

Pathol Biol (Paris), 1993 Apr, 41(4), 428 - 33
{Evaluation of the carriage of Staphylococcus aureus in patients and the personnel of a hemodialysis center for the prevention of infections}; Ternois I et al.; With the aim of improving the prevention of Staphylococcus aureus infections in hemodialysis patients, an evaluation of S . aureus nasal carriage was carried out at the hemodialysis center of CHU-Rouen between the 1st of January, 1991 and the 30th of June, 1991 . The S . aureus strains were classified according to their antibiotypes, serotypes and lysotypes . The carriage rate appears to be similar to that of the general population but inferior to what has been previously reported in hemodialysis centers . We report our findings on nasal carriage strains . The risk of infection is low . The standards of hygiene, adopted by hospital personnel, seem to be effective although cross colonization may have possibly occurred . Taking into account the different epidemiologic circumstances encountered in each hemodialysis center it is, therefore, necessary to determine the rate of carriage and identify the personnel at risk (persistent carriers, patients with a previous history of S . aureus septicemia, meti-R strains) in order to implement prophylaxis accordingly to epidemic characteristics of each center.

Rev Latinoam Microbiol, 1993 Apr-Jun, 35(2), 147 - 52
{Microbiological study of nosocomial lung infections}; Araque-Granadillo MC et al.; A total of 83 adult patients between 25 and 60 years of age who acquired pulmonary infectious disease within 48 hours after being admitted to the medical, surgical and/or intensive care units at the university hospital of the "Universidad de Los Andes" (Merida, Venezuela) were studied during a period of 18 months . The most frequent clinical entity observed was pneumonia (49.4%) . In all types of pulmonary samples obtained by secretion or puncture, more than half gave positive results to the microbiological analysis . Gram-negative bacilli prevailed as the etiological agents, with a preponderance of the species from Klebsiella (21.7%) and Pseudomonas (15.1%) genus . Staphylococcus aureus was also isolated in 13.3% of all cases . Satisfactory sensitivity to third generation cephalosporins and aminoglucosides was observed on these strains . Quinolones showed the highest antimicrobial activity . The application of an adequate antimicrobial therapy, according to the antibiotics sensitivity test results, allowed a successful clinical efficacy in 67.4% of all cases.

J Hosp Infect, 1993 Apr, 23(4), 279 - 85
Assessment of oxacillin salt agar for detection of MRSA identified by presence of the mecA gene; Kobayashi Y et al.; To assess the screening method for detection of methicillin-resistant Staphylococcus aureus recommended by Thornsberry and McDougal J . Clin Microbiol 1983; 18: 1084-1901, the growth of S . aureus and Staphylococcus epidermidis strains on Mueller Hinton agar containing 4% NaCl and 6 mg l-1 oxacillin, after 24 h incubation at 35 degrees C, was investigated . The strains used for this study were characterized for possession of the mecA gene by the polymerase chain reaction . All 39 strains of S . aureus with the mecA gene grew on this agar, and all 12 strains of S . aureus without the mecA gene did not grow . On the other hand, three of 12 strains of S . epidermidis did not grow on this agar, although all these strains possessed the mecA gene . These results suggest that Thornsberry and McDougal's screening method is suitable for detecting S . aureus strains with mecA gene . Introduction of this method, to detect methicillin-resistant S . aureus more precisely, is simple and cheap for any laboratory in any part of the world.

Aktuelle Traumatol, 1993 Apr, 23(2), 80 - 4
{Concentration of ciprofloxacin in bone tissue}; Meissner A et al.; After the administration of a 200 mg i.v . dose, the concentration of ciprofloxacin in bone and serum of 20 patients with coxarthrosis was determined before implantation of a total hip-joint endoprosthesis . Samples were taken from the cortical bone and cancellous bone either 1 hour, 2 hours, 3 hours, 4 to 5 hours, or 13 to 19 hours after administration . Blood samples for the determination of serum concentration were also taken at these times . The bone samples were extracted three times in phosphoric acid (10 mmol/l) at 4 degrees C for 20 hours, the volume of phosphoric acid being ten times that of the bone sample . The ciprofloxacin concentration was determined by high-performance liquid chromatography and fluorescence detection . The bone concentration was referred to bone volume by assuming a bone density of 1.9 g/l . The mean bone concentrations in cancellous and cortical bone after ciprofloxacin administration were, respectively, 2.16 mg/l and 1.42 mg/l after 1 hour; 0.82 mg/l and 0.56 mg/l after 2 hours; 2.50 mg/l and 1.04 mg/l after 3 hours; 1.16 mg/l and 0.42 mg/1 after 4-5 hours; and 0.27 mg/l and 0.15 mg/l after 13-19 hours . Ciprofloxacin quickly penetrated the bone . The ratio of areas under the curve (AUC) from bone to serum was 2.24 for cancellous and 0.99 for cortical bone . In 16 out of 19 bone samples, the ciprofloxacin concentration measured was higher than the MIC90 for Staphylococcus aureus.

J Med Microbiol, 1993 Apr, 38(4), 270 - 7
Analysis of an outbreak of variably methicillin-resistant Staphylococcus aureus with chromosomal RFLPs and mec region probes; Stewart PR et al.; An outbreak of infections with multi-resistant Staphylococcus aureus with unusual methicillin resistance at a Melbourne hospital was investigated by examining restriction fragment length polymorphisms (RFLPs) of total DNA digested with the rare-cutting endonuclease SmaI . The polymorphisms were identified by pulsed-field gel electrophoresis (PFGE) and were analysed numerically to give quantitative estimates of genetic distances between isolates . The majority of the isolates were found to belong to one group, with only minor genetic differences between the isolates that showed varying resistance to methicillin, thereby suggesting development of resistant variants from one clonal type during the outbreak . These results were confirmed by DNA hybridisation analysis with specific resistance gene probes for parts of a multi-resistance gene cluster (including methicillin) in the chromosome . Analysis of the RFLP patterns of S . aureus isolates is potentially a useful procedure in clinical epidemiology.

Infect Immun, 1993 Apr, 61(4), 1567 - 70
Antibodies to a range of Staphylococcus aureus and Escherichia coli heat shock proteins in sera from patients with S . aureus endocarditis; Qoronfleh MW et al.; Antibodies to a range of Staphylococcus aureus and Escherichia coli heat shock proteins were present in sera from patients with S . aureus endocarditis . This suggests the highly immunoreactive nature of a range of heat shock proteins in addition to the GroEL equivalent (common antigen) protein . In one case, antibodies to three proteins unique to the infecting S . aureus strain, which were more prominent in heat-shocked cells, were also detected.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 3 - 5
{Biosynthesis of the new antistaphylococcal antibiotic batumin}; Smirnov VV et al.; Levels of batumin biosynthesis by separate cells of the antibiotic-producing strain were investigated . The strain belongs to the genus Pseudomonas . It was found that the cell population was not homogeneous by that property . There were isolated highly active, active and low active clones . Specific selection of the most active clone made it possible to increase the number of the cells with high levels of the antibiotic biosynthesis in the population from 8.8 to 84.7 per cent . A clone was isolated which formed no zones of the growth inhibition of Staphylococcus aureus 209P . The data showed that the biosynthesis of batumin was genetically unstable which could be indicative of the plasmid localization of the genes controlling its production . However, with the basic methods of the plasmid DNA isolation it was demonstrated that the batumin-producing strain contained no extrachromosomal DNA which indicated to the chromosomal localization of the genetic locus responsible for the antibiotic synthesis.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 14 - 8
{Electron-radioautographic study of the action of "levosin" ointment and the ointment base (polyethylene oxide) on Staphylococcus aureus}; Pal'tsyn AA et al.; Morphological properties and intensity of RNA synthesis in the Staphylococcus aureus cells exposed to levosin ointment or it base alone (a mixture of polyethylene glycols) were studied with electron microscopy . It was found that the exposure to the substances led to various destructions in the microbial cells, marked inhibition of their viability evident from lower levels of RNA synthesis by the bacteria and a decrease in the count of the bacterial cells . There were certain differences in the effect of the substances on the morphological properties of the bacteria, while the level of their viability inhibition was the same.

Lett Appl Microbiol, 1993 Apr, 16(4), 203 - 6
A Staphylococcus aureus-specific oligonucleotide probe derived from 16S rRNA gene sequences; Bentley RW et al.; Genes encoding 16S rRNA were sequenced from 16 species of Staphylococcus . Sequence analysis highlighted a potential Staph . aureus-specific region and a complementary oligonucleotide probe was synthesized and its specificity tested . Northern blotting indicated molecular specificity, and dot blots to RNA from Staph . aureus, Staph . capitis, Staph . caprae, Staph . carnosus, Staph . caseolyticus, Staph . cohnii, Staph . epidermidis, Staph . gallinarum, Staph . haemolyticus, Staph . hominis, Staph . hyicus, Staph . saprophyticus, Staph . sciuri, Staph . simulans, Staph . warneri and Staph . xylosus indicated species-specificity.

Eur J Immunol, 1993 Apr, 23(4), 873 - 81
Identification of two distinct CD5- B cell subsets from human tonsils with different responses to CD40 monoclonal antibody; Dono M et al.; This study investigated the response of different CD5- B cell subsets to CD40 monoclonal antibody (mAb) in various combinations with interleukin (IL)-4 or rabbit anti-human mu chain antibody (a-mu-Ab) . The different CD5- B cell subsets were isolated from tonsillar B cell suspensions depleted of CD5+ B cells and subsequently fractionated on Percoll density gradients . While resting CD5+ B cells proliferated and produced IgM molecules in response to a-mu-Ab, IL-4 and CD40 mAb as well as to Staphylococcus aureus Cowan strain I (SAC) and IL-2, resting CD5- B cells, which were co-purified in the same 60% Percoll fractions, consistently failed to respond . These cells were, however, activated by the stimuli employed, as demonstrated by their capacity to express the surface activation markers CD69, CD25 and CD71 . Resting CD5+ B cells had the typical phenotype of mantle zone B cells (IgM+ IgD+ CD39+ CD38- CD10- CDw75dim), whereas resting CD5- B cells were CD38- CD39- CD10- CDw75 intermediate and expressed surface IgM but relatively little surface IgD and could not be classified as mantle zone or germinal center cells . The finding that purified germinal center cells (CD38+ CD10+ CD39- CDw75bright, IgG+) responded to CD40 mAb and IL-4 and also to SAC plus IL-2 further underlined the differences to resting CD5- B cells . However, some of the data collected suggest possible relationships between CD5- B cells and germinal center cells . The CD5- B cells isolated from the 50% Percoll fraction proliferated in response to a-mu-Ab, CD40 mAb and IL-4 as well as to SAC and IL-2 . These cells had the same mantle zone B cell phenotype as the CD5+ B cells, but their capacity to respond to the stimuli in vitro was unrelated to a possible contamination with CD5+ B cells, as documented by the appropriate controls . Furthermore, upon exposure to SAC or phorbol esters, the large majority of CD5- B cells from the 50% Percoll fraction did not express surface CD5 and there was very little if any accumulation of CD5 mRNA . Finally, most of the cycling cells in the stimulated CD5- B cells did not express CD5 . The CD5- B cells from the 50% Percoll fraction were comprised of a consistent proportion of cells that expressed surface activation markers.(ABSTRACT TRUNCATED AT 400 WORDS)

J Neurochem, 1993 Apr, 60(4), 1283 - 91
Limited proteolysis of myelin basic protein in a system mimetic of the myelin interlamellar aqueous space; Nicot C et al.; We have investigated the early steps of myelin basic protein (MBP) degradation in a membrane mimetic system (reverse micelles), resembling the interlamellar aqueous spaces where the protein is located in the myelin sheath . MBP, unfolded in buffer, refolds on incorporation into the micelles, resulting in reduced accessibility to three proteolytic enzymes, trypsin, cathepsin D, and Staphylococcus aureus V8 protease, in comparison with aqueous solution . Eleven cleavage sites seen in buffer are removed from proteolytic attack in micellar solution . These sites delineate a protected protein domain displaying a potential beta-sheet structure capable of interacting with the myelin membrane . An additional site not seen in buffer is attacked in the micelles . Experiments with a structure inducer, 15% 1-propanol in buffer, reveal that the refolding pattern of MBP in reverse micelles is specific to the membrane biomimetic system and is not produced by organic solvent per se . Micellar digestions of MBP generate long peptides, two of which, isolated after tryptic digestion, have been found to be immunodominant in multiple sclerosis patients . The findings suggest the structure induced in MBP by the micelles resembles that leading to production of the self-peptides recognized by T cells during proteolytic breakdown of MBP in autoimmune demyelinating diseases.

J Biol Chem, 1993 Mar 25, 268(9), 6641 - 8
Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils; Selsted ME et al.; A new family of cysteine-rich antimicrobial peptides from bovine neutrophils was isolated and characterized . Thirteen structurally homologous peptides were purified to homogeneity from a granule-rich cytoplasmic fraction of purified blood neutrophils . The complete sequences of the peptides were determined by a combination of enzymatic digestion, Edman degradation, and additional biochemical characterization of the carboxyl termini . The peptides are characterized by a highly cationic 38-42-residue chain which includes 6 invariantly spaced cysteines which form three disulfides . They share a highly conserved consensus sequence which is also found in a recently described epithelial antimicrobial peptide from bovine trachea . The in vitro antibacterial activities of the 13 neutrophil peptides, determined in assays using Staphylococcus aureus and Escherichia coli as test organisms, demonstrated that each peptide possessed antimicrobial activity, and that several were as active as the most potent neutrophil defensin, rabbit NP-1 . Though the structural and functional attributes of the bovine neutrophil peptides are similar to those of defensins, the two peptide families are distinguished by their unique consensus sequences and additionally by differing tridisulfide motifs . We therefore propose that this new defensin-like antimicrobial peptide family be named beta-defensins.

Biochemistry, 1993 Mar 23, 32(11), 2813 - 21
The carboxy terminus of sodium and potassium ion transporting ATPase is located on the cytoplasmic surface of the membrane; Thibault D; The positions, with respect to the plasma membrane, of lysine 905, contained in the peptide QRKIVE, and of lysine 1012, contained in the carboxy-terminal peptide, RPGGWVEKETYY, of ovine Na+/K(+)-transporting ATPase have been reported to be cytoplasmic and extracytoplasmic, respectively {Bayer, R . (1990) Biochemistry 29, 2551-2256} . These results from our laboratory have been reexamined using an extension of the same procedure . Sealed right-side-out vesicles were modified with pyridoxal phosphate and sodium {3H}borohydride in the presence and absence of saponin or cholate . The modified alpha polypeptide was isolated and digested with the proteinase from Staphylococcus aureus strain V8 or trypsin to produce one or the other of these two peptides . These digests were passed over immunoadsorbents, identical to those used by Bayer, directed against pyroglutamylRXIVE or -ETYY . Unlike in the earlier studies, however, in the present studies the modified, radioactive peptides bound and eluted from the immunoadsorbents were submitted to HPLC, and their respective mobilities were compared to those of the synthetic peptides that had also been modified with pyridoxal phosphate . In this manner, the correct, modified peptide could be positively identified, and its specific radioactivity could be estimated . When cholate was added to sealed vesicles, prior to modification, there was at least a 3-fold increase in the incorporation of radioactivity into lysine 1012, consistent with a cytoplasmic location for this residue.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Med, 1993 Mar 22, 94(3A), 177S - 181S
A pilot study of oral fleroxacin given once daily in patients with bone and joint infections; Putz PA; The object of this open-label, noncomparative, multicenter study was to evaluate the efficacy and safety of 400 mg of fleroxacin administered orally once daily for 2-12 weeks to patients with bone and joint infections (osteomyelitis, septic arthritis, and prosthetic joint infection) . A total of 90 adult patients (56 men and 34 women) were treated at 11 centers . Patients returned on days 5-9 of treatment, subsequently every 2 weeks during treatment, and 0-3 days and 28-42 days (compulsory follow-up) after treatment for assessment of bacteriologic, clinical, and safety parameters . A total of 19 patients (13 with osteomyelitis, 5 with septic arthritis, and 1 with prosthetic joint infection) were bacteriologically evaluable . Staphylococcus aureus was the predominant pathogen isolated in all evaluable infections . Of the 13 patients with osteomyelitis, 11 (85%) were bacteriologically cured and 10 (77%) were clinically cured . Three of the five patients with septic arthritis and the single patient with a prosthetic joint infection were both bacteriologically and clinically cured . Clinical adverse events related to fleroxacin were reported by 25 (28%) of the 90 patients . Most of these events involved the digestive system (primarily constipation and nausea) and the central nervous system (primarily insomnia and headache) . The majority of these were of mild or moderate intensity and occurred during the first 2 weeks of treatment . Adverse events led to premature discontinuation of treatment in seven patients . Bone and joint infections continue to represent a therapeutic challenge . Treatment is based mainly on surgical procedures (drainage, sequestrectomy, ablation of implants, and implantation of cement impregnated with antibiotics) and on parenteral administration of antibiotics, requiring hospitalization of the patient . Fleroxacin, a new fluoroquinolone, has proven in vitro activity against bacteria involved in bone and joint infections . Its oral, once-daily administration, which eliminates hospitalization and its attendant costs, makes this drug an effective outpatient treatment of bone and joint infections.

Am J Med, 1993 Mar 22, 94(3A), 174S - 176S
Efficacy of oral fleroxacin in bone and joint infections; Green SL; Bone and joint infections have traditionally required long-term parenteral antimicrobial therapy, which is often expensive and inconvenient . Because of their excellent absorption and tissue penetration, oral quinolones may provide an alternative to parenteral therapy . This multicenter study was designed to evaluate the efficacy and safety of oral fleroxacin in osteomyelitis and septic arthritis . A total of 96 patients with either septic arthritis or acute or chronic osteomyelitis from 17 U.S . centers were enrolled in a noncomparative study using oral fleroxacin 400 mg per day . Patients with implantable devices were excluded . Proof of infection for evaluability required clinical findings in addition to bacteriologic recovery of a susceptible organism from synovial fluid or bone . Treatment lasted 2-12 weeks . Clinical and bacteriologic outcomes were judged at the conclusion of therapy and in the 6-week follow-up period . A total of 30 patients qualified for efficacy analysis (26 osteomyelitis, 4 septic arthritis) . Bacteriologic cure was achieved in 77% of the osteomyelitis group and 50% of the septic arthritis group . Clinical cures were reported in 54% of the osteomyelitis group and 50% of the septic arthritis group . Staphylococcus aureus was the most frequently recovered pathogen (62% evaluable cases) . Safety was evaluated in 96 patients . The most common side effects were nausea, vomiting, and skin reactions . Oral fleroxacin may be a safe, effective, and certainly less expensive alternative to standard intravenous antimicrobial therapy in patients with bone and joint infections.

Am J Med, 1993 Mar 22, 94(3A), 159S - 165S
Comparative efficacy and safety of oral fleroxacin and amoxicillin/clavulanate potassium in skin and soft tissue infections; Tassler H; The objective of this open-label, randomized, multicenter study was to compare the efficacy and safety of fleroxacin, 400 mg administered orally once daily, and amoxicillin/clavulanate potassium (AMX/CP), 500 mg/125 mg administered orally three times daily, for 4-21 days to patients with skin and soft tissue infections (SSTIs) . The specific diagnoses in both groups were primarily skin abscess, impetigo, and skin ulcer, as well as wound infection erysipelas, folliculitis, cellulitis, and lymphangitis . A total of 285 patients were randomized to treatment in a 2:1 ratio, 190 in the fleroxacin group and 95 in the AMX/CP group . Adult male or female inpatients or outpatients were included in the trial and were followed up after 3-5 days of therapy and 3-9 days after completion of therapy for assessment of bacteriologic, clinical, and safety parameters . The most frequently isolated pathogen in both treatment groups was Staphylococcus aureus . Bacteriologic cures were observed in 87 (76%) of 115 evaluable patients in the fleroxacin group and in 41 (72%) of 57 evaluable patients in the AMX/CP group . Clinical cure was seen in 86 (75%) of 114 patients in the fleroxacin group and 45 (79%) of 57 patients in the AMX/CP group . Clinical adverse events related to the trial medication were reported by 40 (21%) of 189 patients in the fleroxacin group and by 16 (17%) of 95 patients in the AMX/CP group . In both groups, most adverse events were mild or moderate in severity and involved the digestive system (primarily diarrhea, nausea, and vomiting) . In the fleroxacin group, adverse events affecting the central nervous system (mainly dizziness, insomnia, somnolence) also were reported . In this study, both fleroxacin and amoxicillin/clavulanate potassium were effective and well tolerated in the treatment of skin and soft tissue infections.

Am J Med, 1993 Mar 22, 94(3A), 150S - 154S
Comparison of oral fleroxacin with oral amoxicillin/clavulanate for treatment of skin and soft tissue infections; Smith JW et al.; Oral fleroxacin, 400 mg once a day, and oral amoxicillin/clavulanate potassium (AMX/CP), 400 mg/125 mg three times a day, administered for 4-21 days, were compared for efficacy and safety in the treatment of skin and soft tissue infections . A total of 113 patients were enrolled in a multicenter, randomized, double-blind trial; 57 were assigned to fleroxacin and 56 to AMX/CP . A total of 22 and 33 patients in the fleroxacin and AMX/CP groups, respectively, were evaluable for efficacy . The most common diagnoses were skin abscess (14; 62%) and wound infections (5; 23%) in the fleroxacin group and skin abscess (17; 52%) and skin ulcer (9; 27%) in the AMX/CP group . A total of 20 (91%) of the fleroxacin-treated patients and 29 (88%) of the AMX/CP-treated patients were bacteriologically cured (two fleroxacin- and one AMX/CP-treated patients developed super-infection) . The eradication rate for Staphylococcus aureus was 100% (11 of 11) in the fleroxacin group and 89% (17 of 19) in the AMX/CP group; 18 (82%) of the fleroxacin group and 25 (76%) of the AMX/CP group were clinically cured . Adverse events were seen in 22% (12 of 54) of the fleroxacin group and 25% (13 of 53) of the AMX/CP group . None were serious . Bacteriologic and clinical cure rates and safety results for the two groups were similar . The small sample size precluded statistical analysis at the 95% confidence level.

J Immunol, 1993 Mar 15, 150(6), 2391 - 400
Lung surfactant suppresses oxygen-dependent bactericidal functions of human blood monocytes by inhibiting the assembly of the NADPH oxidase; Geertsma MF et al.; Surfactant is known to lower the surface tension in alveoli and affects the antibacterial functions of alveolar and peritoneal macrophages . We investigated the effects of surfactant on the bactericidal functions and oxidative metabolism of human blood monocytes and granulocytes . Monocytes incubated with surfactant ingest this material and subsequently exhibit an impaired ability to kill ingested bacteria . Granulocytes incubated with surfactant do not ingest this material, and their bactericidal functions are not affected . However, granulocytes that have ingested surfactant-coated Staphylococcus aureus display an impaired ability to kill these bacteria . Moreover, in monocytes and granulocytes that contain surfactant--the latter by ingestion of surfactant-coated S . aureus--the intracellular production of H2O2 is impaired due to inhibition of the assembly of the NADPH oxidase . Together these results demonstrate that surfactant inside monocytes and granulocytes inhibits the capacity of these cells to kill bacteria intracellularly by impairing oxygen-dependent killing mechanisms.

J Biol Chem, 1993 Mar 15, 268(8), 5866 - 71
Identification of a major binding site for complement C3 on the IgG1 heavy chain; Shohet JM et al.; Activation of the alternative pathway of complement by immune complexes involves the covalent attachment of the third component (C3) to the IgG heavy chain . In order to localize the site/sites of attachment, adducts of human C3.IgG were digested in situ with endoproteinase Lys-C and Staphylococcus aureus V8 protease, and the fragments were analyzed . The dimeric peptide containing the covalent bond, identified by alkylation of the free thiol group (Cys1010) with iodo{14C}acetamide, was isolated by high-performance liquid chromatography fractionation . A double sequence with NH2 termini corresponding to position 134 of IgG heavy chain and position 1002 of the C3 alpha' chain was found by analysis with automated Edman degradation . The intact dimeric peptide had a mass of 3453 Da and was composed of IgG and C3 fragments with predicted sizes of 23 and 12 residues, respectively . The IgG peptide includes a cluster of six potential acceptor sites for ester bond formation . Thus, it appears that C3 binding is limited to a single region within the CH1 domain of the IgG1 heavy chain.

J Immunol, 1993 Mar 15, 150(6), 2281 - 94
Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity; Patten PA et al.; We have used multiple-amino acid replacement mutagenesis to examine the roles of the TCR homologues of Ig complementarity-determining regions (CDR) and framework sequences in Ag-MHC and Staphylococcus aureus enterotoxin reactivity . In the three cases examined, transplantation of Ig CDR3 homologues between I-Ek-restricted TCR that recognize distinct peptides did not result in transfer of peptide reactivity . Thus the structural context of the CDR3 loops, e.g., both neighboring CDR and the V beta structure, must play a crucial, albeit supporting, role in ligand recognition . The extreme lability of this context was also shown by the fact that transplantation of the CDR1, -2, and -3 loops from the beta chain of 5C.C7 onto a V beta 1 framework failed to transfer MHC-peptide specificity even when the TCR-alpha chains were identical . In contrast, superantigen reactivity was readily transferred in several cases, with CDR2 transplants conferring strong staphylococcal enterotoxin B and A reactivity and CDR1 transplants yielding weak reactivities . This suggests that bacterial (and perhaps other) superantigens bind to many of the same regions of the TCR V beta that are believed to interact with MHC molecules . These regions of V beta may be ideal targets for superantigen binding precisely because they interact with MHC molecules and thus may be relatively conserved.

Presse Med, 1993 Mar 13, 22(9), 425 - 8
{Diagnosis of acute infectious epidural inflammation . Role of magnetic resonance imaging}; Claudel JP et al.; External pachymeningitis, usually caused by Staphylococcus aureus, is a rare pathological entity which is difficult to diagnose at an early stage, has a poor functional prognosis and often requires an emergency surgical treatment . We report three cases in which magnetic resonance imaging provided an early diagnosis of the epidural space infection before severe neurological deficits, such as paraparesis and/or paraplegia, set in . Following an anti-staphylococcal treatment with fluoroquinolone and beta-lactamase-resistant beta-lactam antibiotics with good bone penetration administered intravenously during 4 to 6 weeks, then orally for 5 to 6 months cure without functional sequelae was obtained in all three patients.

N Z Med J, 1993 Mar 10, 106(951), 72 - 4
Methicillin resistant Staphylococcus aureus (MRSA) in New Zealand 1988-90; Heffernan H et al.; AIMS . To survey methicillin-resistant Staphylococcus aureus (MRSA) in New Zealand during the three years 1988-90 . METHODS . Isolates and accompanying epidemiological data referred and reported to the New Zealand Communicable Disease Centre were analysed . RESULTS . MRSA was isolated from 255 persons, 235 patients and 20 healthcare staff, over the three years . The majority (84%) of persons were, or were recent, hospital patients or staff . Among hospital patients, males and patients aged 0 to 14 years were more likely to have MRSA . While most (88%) of the 145 strains identified occurred sporadically, three caused large outbreaks each involving more than 20 people . A third of the strains originated overseas, most commonly Australia or one of the Pacific Islands . The rate of MRSA isolation was higher in the North Island than the South Island . Two-thirds of the MRSA had only a low level of methicillin resistance and were not multiresistant . CONCLUSIONS . MRSA continues to be isolated only infrequently in New Zealand and has not become endemic in our hospitals.

Anticancer Res, 1993 Mar-Apr, 13(2), 439 - 42
Immunomodulation activity of phenothiazines, benzo{a}phenothiazines and benz{c}acridines; Molnar J et al.; Some non-differentiation-induction benzo{a}phenothiazines and mutagenic benz{c}acridines more potently inhibited the mitogen-induced blast transformation of human-peripheral blood lymphocytes than differentiation-induction and non-mutagenic counterparts and phenothiazines . Differential absorption spectrophotometry revealed tight complex formation between these drugs and bacterial endotoxin or mitogens . All of these compounds only slightly affected antibody dependent cellular cytotoxicity and natural killer cell activity, but significantly inhibited the endotoxin-or heat-killed Staphylococcus aureus induced tumor necrosis factor production by human mononuclear cells . Pretreatment of mice with these drugs protected them from lethal E . coli infection . Quantumchemical analysis suggests a correlation between the biological activity of these compounds and some molecular orbital parameters such as the charge at C7, and the ratio of polar/total surface areas.

Jpn J Antibiot, 1993 Mar, 46(3), 234 - 41
{Antibacterial activities of arbekacin against recently isolated methicillin-resistant Staphylococcus aureus (I)}; Deguchi K et al.; Against 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1990 to 1991, minimum inhibitory concentrations (MICs) of a total of 15 antibacterial agents including arbekacin (ABK) were determined . In addition coagulase types of the tested strains were determined and classified according on their origins . 1 . Among the coagulase types of 200 strains, type II were 63.5%, type IV 18.5%, type VII 11.0% and the other types 7.0% . Type II strains were prevailing among those isolated from the respiratory tract specimens and type IV among those from the surgical specimens . These results were in agreement with other recent reports including our previous ones . 2 . The MIC50 of methicillin, 6 cephalosporins (CEPs), imipenem, fosfomycin (FOM), gentamicin, tobramycin and clindamycin for 200 strains ranged from 50 to > 100 micrograms/ml . On the other hand, MIC50 and MIC90 of ABK, minocycline (MINO) and vancomycin (VCM) were 0.78 and 3.13 micrograms/ml for ABK, 0.39 and 50 micrograms/ml for MINO, and 0.78 and 1.56 micrograms/ml for VCM . 3 . The MIC90 of ABK against coagulase type IV strains was rather high, 12.5 micrograms/ml . However, the strains inhibited by 6.25 to 12.5 micrograms/ml of ABK were isolated even in our studies performed in 1986, 1988 and 1989 . Further studies are therefore required to confirm whether appearance of these strains used in the present study inhibited at relatively high concentrations of ABK is due to the use of ABK . 4 . It is reported that, at present, most of the MRSAs spreading in Japan are acceleratedly acquiring resistance to many drugs, and especially, they are developing high resistance against beta-lactams . ABK showed potent antibacterial activities even against these strains . Since ABK has been shown to display potent activities against MRSA in combination with beta-lactams or FOM, we believe ABK is one of the useful aminoglycoside antibiotics for the treatment of MRSA infections.

Jpn J Antibiot, 1993 Mar, 46(3), 222 - 33
{Enhancement of in vitro antimicrobial activity of cefmetazole and cefotiam in combination against methicillin-susceptible and -resistant Staphylococcus aureus studied using checkerboard MIC method and disc diffusion method with discs containing both drugs}; Matsuo K et al.; Antimicrobial activities of cefmetazole (CMZ) and cefotiam (CTM) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-susceptible strains and 47 methicillin-resistant strains) by the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl . MICs of CMZ and CTM individually against 9 methicillin-susceptible strains (MSSA) were 0.78 approximately 1.56 micrograms and 0.39 approximately 0.78 micrograms/ml without 4% NaCl, and 1.56 approximately 3.13 micrograms/ml and 0.78 approximately 1.56 micrograms/ml with 4% NaCl, respectively . In combination of CMZ and CTM, MICs of CMZ and CTM against these MSSA decreased to 0.20 approximately 0.39 micrograms/ml and 0.20 micrograms/ml without 4% NaCl, and 0.20 approximately 0.78 micrograms/ml and 0.10 approximately 0.78 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.313 to 0.628 . FIC indexes < or = 0.5 were observed against 7 out of 9 strains . MICs of CMZ and CTM individually against 47 methicillin-resistant strains (MRSA) were 6.25 approximately 100 micrograms/ml and 3.13 approximately 800 micrograms/ml in the absence of 4% NaCl, and 6.25 approximately 100 micrograms/ml and 50 approximately greater than 800 micrograms/ml in the presence of 4% NaCl, respectively . In combination of CMZ and CTM, MICs of these drugs against MRSA were reduced to 0.20 approximately 25 micrograms/ml without 4% NaCl and 0.39 approximately 25 micrograms/ml and 3.13 approximately 200 micrograms/ml with 4% NaCl, respectively . The strains studied showed minimum FIC indexes of 0.02 to 0.5 either with 4% NaCl or not . By the disc diffusion method, between CMZ disc and CTM disc a synergistic interaction against MRSA was well observed . In addition, discs containing both drugs showed a greater inhibitory zone than discs containing the equivalent amount of CMZ or CTM alone . These in vitro observations reported here suggest that the use of CMZ and CTM in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection . Prophylactic use of CMZ and CTM in combination for surgical infection would be also more effective than the use of these drugs individually . The synergistic enhancement of antimicrobial activity of CMZ and CTM in combination was assessed using discs containing various amounts of these drugs at various ratios . In this investigation, discs containing CMZ/CTM (20 micrograms/10 micrograms) was selected . Using discs containing CMZ/CTM (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CTM in combination.(ABSTRACT TRUNCATED AT 400 WORDS)

Eur J Clin Microbiol Infect Dis, 1993 Mar, 12(3), 170 - 6
Cefdinir-induced modification of the susceptibility of bacteria to the antibacterial activity of human serum and polymorphonuclear neutrophils; Pruul H et al.; The effect of serum on the bactericidal activity of cefdinir, and the ability of the antibiotic to modify the interaction of bacteria with human polymorphonuclear neutrophils were assessed . In the presence of antibiotic, serum-resistant Escherichia coli were sensitised to the bactericidal activity of normal human serum . Cefdinir enhanced opsonophagocytic killing of Escherichia coli and Staphylococcus aureus at suprainhibitory concentrations . Significant potentiation of killing occurred with the combination of inhibitory concentrations of cefdinir, neutrophils and sub-optimal levels of serum opsonins . Pre-exposure of Escherichia coli, but not Staphylococcus aureus, to cefdinir enhanced phagocytic uptake and killing of the antibiotic-damaged bacteria . These results indicate that cefdinir-mediated phenotypic modification of Escherichia coli renders the bacteria susceptible to serum antibacterial activity and phagocytic uptake and intracellular killing.

Indian J Med Res, 1993 Mar, 97, 64 - 6
Coagglutination test for detection of heat labile enterotoxin producing Escherichia coli strains; Ram S et al.; A simple particle immunoassay based on the coagglutination (CoA) of Staphylococcus aureus strain Cowan 1 coated with heat labile enterotoxin (LT) specific antibodies was evaluated to detect LT in the cell lysates of blood agar grown Esch . coli . Among strains of Esch . coli isolated from 2661 patients with acute diarrhoea, isolates from 609 patients demonstrated LT production by CoA test . Most prevalent serogroups were 020, 078, 0128, 04, 0117, 068, 0158, 07, 0114, 0148 and 0145 . A comparison of CoA with classical rabbit ileal loop and skin permeability factor assay for 100 strains showed 86, 69 and 83 LT positive strains respectively . CoA proved a more specific, simple, rapid and sensitive assay which may be useful for screening of large number of Esch . coli isolates in epidemiological investigations.

J Burn Care Rehabil, 1993 Mar-Apr, 14(2 Pt 1), 164 - 8
Methicillin-resistant Staphylococcus aureus eradication in a burn center; Snyder LL et al.; Methicillin-Resistant Staphylococcus aureus and its detection, virulence, and significance relative to morbidity, epidemics, and cost have been widely discussed in the literature . Although some experts recommend against attempting to eradicate the organism, our health center decided that under the circumstances this course should be pursued . This article describes the outbreak of Staphylococcus aureus, the rationale for pursuing its eradication, the measures successful in doing so, and the relative costs involved.

Kansenshogaku Zasshi, 1993 Mar, 67(3), 223 - 30
{Relationship between coagulase toxin-type and drug susceptibility in Staphylococcus aureus strains isolated in all the Japanese National University Hospitals}; Kimura A et al.; Drug susceptibility of 430 Staphylococcus aureus strains isolated in 1991 from clinical specimens at all of the Japanese national university hospitals was evaluated in relationship with the epidemiological markers, namely, coagulase typing, and staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 (TSST-1) production . There were five major methicillin-resistant Staphylococcus aureus (MRSA) groups in all the 252 MRSA strains: coagulase-type II-SEC + TSST-1- producing strains (II-SEC + TSST-1): 34.5%; coagulase-type II-no toxin-producing strains (II-): 15.4%; coagulase-type IV-SEA-producing strains (IV-SEA): 10.3%; coagulase-type II-SEA + SEC + TSST-1- producing strains (II-SEA + SEC + TSST-1): 8.7%; and coagulase-type III-no toxin-producing strains (III-): 7.1% . II-SEA + SEC + TSST-1 group was highly resistant to OFLX, whereas half of the other strain groups were sensitive to OFLX . Seventy-eight percent of the IV-SEA group was sensitive to FMOX, but there was no sensitive strain to FMOX in the II-SEA + SEC + TSST-1 group . More than 50% of the IV-SEA, III- and II-groups were sensitive to IPM, while the II-SEC + TSST-1 and II-SEA + SEC + TSST-1 groups were highly resistant to IPM . The III- and II-groups showed very good sensitivity to MINO, but the sensitivity to it of the II-SEA + SEC + TSST-1 group was very low . All of the strain groups were sensitive to ST except for the IV-SEA group . These results may provide useful information in the choice of antibacterial agents for MRSA infection.

J Orthop Res, 1993 Mar, 11(2), 256 - 62
Bioerodible polyanhydrides for antibiotic drug delivery: in vivo osteomyelitis treatment in a rat model system; Laurencin CT et al.; Acute and chronic osteomyelitis can be difficult to treat by conventional means . Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical debridement . Each method has specific drawbacks . We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis . We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin . Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus . After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone . The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period . Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of animals with a polyanhydride polymer implant alone (p < 0.01), and of animals with a PMMA/gentamicin implant (p = 0.03) . Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone.

J Orthop Res, 1993 Mar, 11(2), 250 - 5
Antibiotic-loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomyelitis in rats; Gerhart TN et al.; A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats . Osteomyelitis was established by inoculating S . aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders . The cylinders were left in place for 3 weeks . The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed . For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks . Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01) . Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture . At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 205 - 13
Occurrence of macrolide-lincosamide-streptogramin resistances among staphylococcal clinical isolates at a university medical center . Is false susceptibility to new macrolides and clindamycin a contemporary clinical and in vitro testing problem?
Sanchez ML, Flint KK, Jones RN.
A total of 2189 staphylococcal strains at the University of Iowa Hospitals and Clinics (Iowa City, IA) were initially screened to determine the incidence of constitutive (29.8%) and potential inducible macrolide-lincosamide-streptogramin (MLS) resistance (11.3%) . Staphylococcus haemolyticus and S . epidermidis (62.5% and 55.3%) showed the highest incidence of constitutive resistance . Staphylococcus hominis had the highest incidence of inducible resistance (40.6%), while S . aureus had the lowest rate for both resistance types . The overall ratio of constitutive-inducible MLS resistance was 4:1 . Among strains initially speciated using the Vitek System GPI card, there was only a 69% species identification reproducibility, and 78% accuracy versus a reference identification method . A random sample of 105 Staphylococcus spp . isolates with discordant macrolide (erythromycin resistant) and lincosamide (clindamycin susceptible) susceptibility patterns were tested against 16 antimicrobial agents by using a reference broth microdilution method . All erythromycin-resistant Staphylococcus spp . were also resistant to other 14-member macrolides and azithromycin, while all organisms remained susceptible to clindamycin, rifampin, vancomycin, and the streptogramin compounds (RP59500 and virginiamycin) . Resistance to teicoplanin was identified among some oxacillin-resistant S . haemolyticus strains . Of 105 isolates, 65 (62%) showed inducible MLS resistance, 28 (27%) were noninducible, and 12 (11%) were either fully susceptible or resistant to the MLS drugs (Vitek System interpretation errors) . MLS disk induction tests revealed two inducible resistance phenotypes: ML and MLS . Staphylococcus aureus showed the highest inducible resistance rate at 95% with an MLS-predominant pattern . In contrast, endemic S . haemolyticus isolates did not demonstrate inducible resistance that is, efflux-mediated erythromycin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

J Heart Lung Transplant, 1993 Mar-Apr, 12(2), 330 - 2
Surgical management of infective endocarditis after heart-lung transplantation; Hasan A et al.; Bacterial endocarditis after heart-lung transplantation has not been described . We report Staphylococcus aureus bacterial endocarditis in a 12-year-old boy after heart-lung transplantation . He was found to have an apparently free vegetation in his left ventricle, which was surgically removed . After a stormy postoperative period, he successfully recovered and remains well after 6 months.

Am J Emerg Med, 1993 Mar, 11(2), 134 - 8
The effect of scrubbing and irrigation with normal saline, povidone iodine, and cefazolin on wound bacterial counts in a guinea pig model; Howell JM et al.; This study examines the effects of povidone iodine, normal saline, and cefazolin alone and after scrubbing on bacterial counts in contaminated animal lacerations . Twelve albino guinea pigs each received four lacerations inoculated with a standard inoculum of Staphylococcus aureus . Twelve hours after inoculation, each wound was biopsied to ensure contamination and then either treated or left as an untreated control . One wound on each animal was an untreated control . The remaining three lacerations on six pigs were irrigated with cefazolin (CZ) solution, normal saline, or 1% (wt/vol) povidone iodine solution (PI) . Three lacerations on another six pigs were treated with 20% poloxamer 188 scrub (scrub) alone, scrub followed by PI irrigation (SCR/PI), or scrub followed by CZ irrigation (SCR/CZ) . Quantitative bacteriology was performed on tissue biopsies 2 hours (time 1), 7 hours (time 2), and 12 hours (time 3) after irrigation . Posttreatment counts for PI, CZ, and normal saline irrigation were not different from control or one another (P > .05) . Bacterial counts for SCR/PI were significantly lower than control (P < .05) for all posttreatment biopsies (1.8 to 2.9 mean log(10) decrease) . SCR/CZ was significantly lower than control (P < .05) at times 2 and 3 only (1.7 to 2.0 mean log(10) decrease) . In this guinea pig model, cleansing 12-hour-old lacerations contaminated with S aureus using SCR/PI or SCR/CZ significantly reduced bacterial counts over 12 hours.

J Pediatr Surg, 1993 Mar, 28(3), 345 - 8; discussion 348-9
Does the fibrin coat around a central venous catheter influence catheter-related sepsis?
Lloyd DA, Shanbhogue LK, Doherty PJ, Sunderland D, Hart CA, Williams DF.
The purpose of this study was to determine whether the fibrin sheath that develops around an intravenous silicone catheter influences catheter-related sepsis . A rat model with a central intravenous silicone catheter was used . Staphylococcus aureus, dose 1 x 10(7) colony forming units (cfu), were injected via the tail vein, either immediately after catheter insertion (group 1, n = 23) or after the catheter had been in situ for at least 7 days (group 2, n = 22) . Blood cultures were done on at 24 hours and 7 days . Animals were killed on day 7 and the catheter was removed for culture (Maki and broth) and scanning electronmicroscopy (SEM) . The was no significant difference (P > .05) between the number of positive blood cultures in groups 1 and 2 at 24 hours (16 v 9) and 7 days (12 v 6) . In group 1 there were significantly more positive catheter cultures by both methods (23 v 16 in group 2; P < .05) and more cfu/per centimeter catheter (group 1 mean, 520, range, 197 to 600; group 2 mean 195, range 9 to 600; P < .001) . In group 1, 12 animals had catheter sepsis compared with 5 in group 2 (P = NS) . On SEM a fibrinous sheath was identified on all catheters removed on day 7 but not on 5 catheters inserted and removed after 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Food Microbiol, 1993 Mar, 18(1), 25 - 36
Effect of low-dose irradiation on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy; Grant IR et al.; The effect of irradiation (2 kGy) on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy during storage at abuse temperatures (15 and 22 degrees C) was assessed by inoculation studies . Irradiation resulted in a 3-4 log10 reduction in numbers of both pathogens . Whenever B . cereus and S . aureus numbers reached 10(6) and 10(7) cfu/g, respectively, during storage their toxins were detectable . As the time taken to attain these levels was longer in irradiated than in unirradiated samples, toxin production by both pathogens was delayed by irradiation . When samples initially containing low levels (10(2)/g) of S . aureus were irradiated no toxin was produced during subsequent storage at 15 or 22 degrees C . Diarrhoeal toxin produced by B . cereus was detected after 2 days at 22 degrees C, but not at 15 degrees C, in samples containing 10(2) cells/g prior to irradiation . When higher numbers (10(6)/g) of either pathogen were present prior to irradiation, toxins were produced by both pathogens at 22 degrees C, but not at 15 degrees C . Microbial competition had an effect on the growth of B . cereus and S . aureus after irradiation when a low initial inoculum was applied . However, when a higher inoculum was used the pathogens outnumbered their competitors and competition effects were less important . It was concluded that low-dose irradiation would improve the microbiological safety of roast beef and gravy.

Infect Dis Clin North Am, 1993 Mar, 7(1), 69 - 80
Short-course combination and oral therapies of Staphylococcus aureus endocarditis; Chambers HF; The experimental basis for use of 2-week semisynthetic penicillin plus aminoglycoside combination therapy for Staphylococcus aureus endocarditis is reviewed . The use of oral therapy is examined . Short-course combination of oral regimens can be effective and may be suitable for selected patients with S . aureus endocarditis.

Infect Dis Clin North Am, 1993 Mar, 7(1), 53 - 68
Staphylococcus aureus bacteremia and endocarditis . New diagnostic and therapeutic concepts; Mortara LA et al.; Staphylococcus aureus is an important and prevalent cause of both uncomplicated bacteremia, as well as endocarditis . This article addresses the following controversial strategies: diagnosis of endocarditis in staphylococcemic populations; optimal treatment strategies for right-sided and left-sided S . aureus endocarditis; use of echocardiography in S . aureus endocarditis; and therapy options for catheter-associated staphylococcemias.

Hautarzt, 1993 Mar, 44(3), 135 - 42
{Staphylococcus aureus and atopic eczema}; Neuber K et al.; The bacterial skin flora of patients with atopic eczema is different from that in healthy normal persons . In addition, such patients more often suffer from microbial infections . Differences in sebum and sweat secretion and increased bacterial adhesion to epithelial cells in atopic eczema may predispose to enhanced amounts of Staphylococcus aureus, for example, on the skin . Defective host-defence mechanisms with dysfunction of cellular and humoral immune reactions have been suggested . On the other hand, bacterial antigens may induce allergic reactions, e.g . increased IgE synthesis and enhanced expression of the low-affinity receptor for IgE (CD23, Fc epsilon RII), and the release of inflammatory mediators such as leukotrienes and histamine . The production of bacterial toxins might be important for the pathophysiology of atopic eczema . This paper summarizes the present data and tries to integrate them into a model for the induction of atopic eczema.

Antimicrob Agents Chemother, 1993 Mar, 37(3), 554 - 8
Relative efficacies of broad-spectrum cephalosporins for treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis; Steckelberg JM et al.; The effects of treatment with broad-spectrum parenterally administered cephalosporins and cefuroxime, cefazolin, or nafcillin were compared in an experimental model of Staphylococcus aureus infective endocarditis, and the results in vivo were compared with the activities of the study drugs in vitro . After 3 days of treatment, all antimicrobial agents tested were more effective than no treatment in reducing the number of surviving bacteria in cardiac valve vegetations . Nafcillin was the most effective agent studied and was significantly more active than was ceftizoxime, ceftriaxone, cefotaxime, cefoperazone, cefuroxime, or cefazolin (P < or = 0.05) . Cefpirome and ceftazidime were the most effective broad-spectrum cephalosporins . The outcome of treatment with cefpirome or ceftazidime was similar to that of treatment with nafcillin and significantly better than that of treatment with ceftizoxime or cefotaxime (P < or = 0.05) . Treatment outcome correlated closely with the MICs of the antimicrobial agents for the study strain with the exception of ceftazidime, which was significantly more active in vivo in comparison with other agents than predicted by its MIC (P < or = 0.0003) . When ceftazidime was excluded as an outlier, treatment outcome correlated with the MICs of the remaining study drugs (Spearman's correlation coefficient, 0.95; P < or = 0.0004), as well as with the estimated percentage of time during which the concentration of total drug (correlation coefficient, -0.85; P < or = 0.007) or free drug (correlation coefficient, -0.90; P < or = 0.003) exceeded the MIC . A consideration of total or free drug concentrations in relation to MICs did not significantly improve the correlation with outcome observed with the MICs alone.

Antimicrob Agents Chemother, 1993 Mar, 37(3), 507 - 11
Activity of ampicillin-sulbactam and oxacillin in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus; Pefanis A et al.; Using a rat model of aortic valve infective endocarditis, we previously found that oxacillin was equally effective against an oxacillin-susceptible strain of Staphylococcus aureus and a beta-lactamase-hyperproducing borderline oxacillin-susceptible strain of S . aureus; also, ampicillin-sulbactam was less effective than oxacillin against both isolates and at low doses was less effective against the borderline-susceptible strain than against the fully oxacillin-susceptible strain (C . Thauvin-Eliopoulos, L . B . Rice, G . M . Eliopoulos, and R . C . Moellering, Jr., Antimicrob . Agents Chemother . 34:728-732, 1990) . In the present study, we extended this work, using alternative treatment schedules and additional bacterial strains . Extending treatment with low doses of ampicillin-sulbactam (500 and 250 mg/kg of body weight per day, respectively) to 6.5 days resulted in equalization of effectiveness against the previously studied strains BOSSA-1 and OSSA-1 (3.75 +/- 1.61 log10 and 4.71 +/- 1.79 log10 CFU of residual viable bacteria per g, respectively) . Against the borderline oxacillin-susceptible strain BOSSA-1, increasing the sulbactam dosage from 500 to 2,000 mg/kg/day while maintaining a fixed dose of ampicillin (1,000 mg/kg/day) by continuous infusion resulted in lower bacterial counts (4.93 +/- 1.84 log10 versus 3.65 +/- 1.26 log10 CFU of residual viable bacteria per g, respectively), but this difference was of only borderline significance; differences in efficacy between the low-dose and high-dose sulbactam regimens were exaggerated when intermittent intravenous administration was used (6.19 +/- 1.90 log10 versus 3.37 +/- 1.41 log10 CFU/g, respectively; P < 0.001) . However, for any individual sulbactam dosage, the model of administration (continuous versus intermittent infusion) did not affect the activity of the regimen . When additional strains were used in the model, oxacillin and ampicillin-sulbactam (1,000 plus 2,000 mg/kg/day) were equally effective against both oxacillin-susceptible and borderline oxacillin-resistant strains of S . aureus . These results support the predictions that oxacillin would be clinically effective in the treatment of infections caused by borderline oxacillin-susceptible strains of S . aureus and that, except at very low doses, ampicillin-sulbactam would also be as effective against borderline-susceptible strains as against fully oxacillin-susceptible strains of S . aureus.

Res Vet Sci, 1993 Mar, 54(2), 221 - 6
Experimental intramammary infection of ewes with Staphylococcus aureus subsp anaerobius; de la Fuente R et al.; The susceptibility of the ovine mammary gland to experimental infection with Staphylococcus aureus subsp anaerobius was studied in five lactating Churra ewes . The left mammary gland of each ewe was inoculated with bacteria while the right halves remained untreated and served as a control . A rapid cellular response was elicited in all inoculated glands . The reaction of inoculated mammary glands varied from that of clinical mastitis (ewes C and D) to subclinical mastitis (ewes B and E) or merely to a transient increase of somatic cell counts (ewe A) . S aureus subsp anaerobius is less pathogenic for ewes by the intramammary route than S aureus since doses of about 10(8) bacteria caused clinical mastitis in only two of the inoculated animals.

J Clin Microbiol, 1993 Mar, 31(3), 706 - 7
Production of enterotoxins and toxic shock syndrome toxin by bovine mammary isolates of Staphylococcus aureus; Kenny K et al.; The production of staphylococcal enterotoxin A (SEA), SEB, SEC, SED, and SEE and toxic shock syndrome toxin 1 by bovine mammary isolates of Staphylococcus aureus was evaluated . Enterotoxin secretion was detected by immunodiffusion using specific polyclonal antisera . Of 262 isolates examined, 75 (28.6%) produced one or more toxins . The most common pattern was secretion of both SEC and SED and toxic shock syndrome toxin 1 . No isolates secreted SEE, one produced SEA, and seven secreted SEB.

Biotechniques, 1993 Mar, 14(3), 436 - 41
Specific and quantitative immunoprecipitation of tropomyosin and other cytoskeletal proteins by magnetic separation; L'Ecuyer TJ et al.; Immunoprecipitation is a powerful technique for purifying many proteins for which specific antibodies exist . Magnetic separation has recently been demonstrated to be effective in the immunoprecipitation of cell-surface proteins . We have used magnetic separation with anti-immunoglobulin or protein A bound to magnetic particles to immunoprecipitate labeled muscle tropomyosin and several other cytoskeletal proteins for which specific antibodies exist . We have not found it necessary to bind antigen-specific antibody to the magnetic particles, increasing the versatility of the technique . The quantitative recovery of tropomyosin from muscle cultures using magnetic separation is superior to Staph A (protein A-positive Staphylococcus aureus cells) . The specificity of magnetic separation also compares favorably with Staph A for immunoprecipitation of muscle tropomyosin . Fibroblast tropomyosin, vimentin (from muscle and osteoblast) and myosin heavy chain are other cytoskeletal proteins that are easily recovered with magnetic separation . Magnetic separation, therefore, appears to be a valuable technique for the immunoprecipitation of cytoskeletal proteins from various cell types.

Am J Med, 1993 Mar, 94(3), 313 - 28
Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management; Mulligan ME et al.; Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in community hospitals, long-term-care facilities, and tertiary care hospitals . The basic mechanism of resistance is alteration in penicillin-binding proteins of the organism . Methods for isolation by culture and typing of the organism are reviewed . MRSA colonization precedes infection . A major reservoir is the anterior nares . MRSA is usually introduced into an institution by a colonized or infected patient or health care worker . The principal mode of transmission is via the transiently colonized hands of hospital personnel . Indications for antibiotic therapy for eradication of colonization and treatment of infection are reviewed . Infection control guidelines and discharge policy are presented in detail for acute-care hospitals, intensive care and burn units, outpatient settings, and long-term-care facilities . Recommendations for handling an outbreak, surveillance, and culturing of patients are presented based on the known epidemiology.

Chest, 1993 Mar, 103(3), 962 - 4
Thymic abscess with bacteremia and manubriosternal pyarthrosis in a geriatric patient; Rubinstien E et al.; We describe a geriatric patient with acute substernal chest pain thought to be due to coronary heart disease, who was subsequently found to have Staphylococcus aureus bacteremia associated with infection of the thymus and manubriosternal joint . To our knowledge, this is the first report of (1) a thymic abscess in a geriatric patient, (2) a thymic abscess associated with bacteremia, (3) extra-articular extension of manubriosternal pyarthrosis, and (4) manubriosternal pyarthrosis in the geriatric age group.

J Infect Dis, 1993 Mar, 167(3), 633 - 41
Fibronectin is more active than fibrin or fibrinogen in promoting Staphylococcus aureus adherence to inserted intravascular catheters; Vaudaux P et al.; To further define the role of fibrin(ogen) and fibronectin in Staphylococcus aureus adherence to central venous catheters, the amount, chemical integrity, and biologic activity of these proteins adsorbed on lines inserted in hospitalized patients were prospectively studied . Polyurethane cannulas promoted a significantly lower adherence of S . aureus than polyvinyl chloride (P < .01) or Hickman (P < .001) cannulas and contained the lowest amount of immunologically assayed fibronectin but not of fibrin(ogen) . Fibrinogen showed an extensive loss of adherence-promoting activity on inserted cannulas, which was related to its proteolytic breakdown, as detected by SDS-PAGE and immunoblots with antifibrinogen antibodies and confirmed by in vitro studies with purified protein fragments . In contrast, either intact or fragmented fibronectin, although present in much lower amounts than fibrin(ogen), could actively promote S . aureus adherence onto intravenous catheters.

Infect Immun, 1993 Mar, 61(3), 919 - 25
Phenotypic characterization of xpr, a global regulator of extracellular virulence factors in Staphylococcus aureus; Smeltzer MS et al.; We recently described a Tn551 insertion in the chromosome of Staphylococcus aureus S6C that resulted in drastically reduced expression of extracellular lipase (M . S . Smeltzer, S . R . Gill, and J . J . Iandolo, J . Bacteriol . 174:4000-4006, 1992) . The insertion was localized to a chromosomal site (designated omega 1058) distinct from the lipase structural gene (geh) and the accessory gene regulator (agr), both of which were structurally intact in the lipase-negative (Lip-) mutants . In this report, we describe a phenotypic comparison between strains S6C, a hyperproducer of enterotoxin B; KSI9051, a derivative of S6C carrying the Tn551 insertion at omega 1058; ISP546, an 8325-4 strain that carries a Tn551 insertion in the agr locus; and ISP479C, the parent strain of ISP546 cured of the Tn551 delivery plasmid pI258repA36 . Compared with their respective parent strains, ISP546 and KSI9051 produced greatly reduced amounts of lipase, alpha-toxin, delta-toxin, protease, and nuclease . KSI9051 also produced reduced amounts of staphylococcal enterotoxin B . Coagulase production was increased in ISP546 but not in KSI9051 . Using a mouse model, we also demonstrated that ISP546 and KSI9051 were far less virulent than ISP479C and S6C . We have designated the genetic element defined by the Tn551 insertion at omega 1058 xpr to denote its role as a regulator of extracellular protein synthesis . We conclude that xpr and agr are similar and possibly interactive regulatory genes that play an important role in pathogenesis of staphylococcal disease.

Infect Immun, 1993 Mar, 61(3), 793 - 9
Toxicity of recombinant toxic shock syndrome toxin 1 and mutant toxins produced by Staphylococcus aureus in a rabbit infection model of toxic shock syndrome; Bonventre PF et al.; Menstrually associated toxic shock syndrome (TSS) is attributed primarily to the effects of staphylococcal exotoxin toxic shock syndrome toxin 1 (TSST-1) . A region of the 194-amino-acid toxin spanning residues 115 through 144 constitutes a biologically active site . Several point mutations in the TSST-1 gene in that region result in gene products with reduced mitogenic activity for murine T cells . In this study we evaluated the toxicity of recombinant TSST-1 and several mutants of TSST-1 made by transformed Staphylococcus aureus during in vivo growth in a rabbit infection model of TSS . The toxicities of the transformed strains of S . aureus for rabbits correlated with the mitogenic activities of the recombinant toxins . An isolate originally obtained from a patient with a confirmed case of TSS (S . aureus 587) implanted in a subcutaneous chamber served as a positive control . TSST-1 produced in vivo led to lethal shock within 48 h, and a TSST-1-neutralizing antibody (monoclonal antibody 8-5-7) administered to rabbits challenged with S . aureus 587 prevented fatal illness . Rabbits infected with transformed S . aureus RN4220 expressing wild-type toxin (p17) or mutant toxins retaining mitogenic activity for T cells succumbed within a similar time frame . Blood chemistries of samples obtained from infected animals before death indicated abnormalities in renal and hepatic functions similar to those induced by parenteral injection of purified staphylococcal TSST-1 . Mutant toxin 135 (histidine modified to alanine at residue 135) possessed only 5 to 10% of the mitogenic activity of wild-type toxin . Rabbits challenged with transformed S . aureus RN4220 expressing mutant toxin 135 exhibited only mild transient illness . Mutant toxin 135 retained reactivity with monoclonal antibody 8-5-7 and by several criteria was conformationally intact . Toxin from a double mutant, 141.144, with alanine substitutions at residues 141 (histidine) and 144 (tyrosine), also was devoid of mitogenic activity . In this case, antibody recognition was lost . Mutant toxins 115 and 141 were found to possess approximately half-maximal mitogenic activity . Rabbits challenged with S . aureus RN4220 expressing either 115 or 141 toxin succumbed to lethal shock . We conclude that the ability of TSST-1 to activate murine T cells in vitro and its expression of toxicity leading to lethal shock in rabbits are related phenomena.

Arch Biochem Biophys, 1993 Mar, 301(2), 294 - 8
Purification and properties of Alligator mississipiensis cytochrome c; Barber MJ et al.; Cytochrome c has been purified to homogeneity from alligator liver (Alligator mississipiensis) using aluminum sulfate precipitation, CM-cellulose and gel-filtration chromatography, and reverse-phase HPLC . The protein exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an approximate molecular weight of 12,000 Da . Oxidized and reduced visible spectra yielded maxima at 408 (tau) nm and 315 (delta), 415 (tau), 520 (beta), and 550 (alpha) nm, respectively, while potentiometric titrations in the presence of dye-mediators yielded an Eo of +265 mV . N-terminal analysis of the protein yielded no sequence which indicates a blocked residue . A combination of amino acid sequencing, using peptides obtained from Staphylococcus aureus V8 protease, endoproteinase Lys-C, and CNBr digests of the protein and total amino acid analyses, using equine and avian cytochromes c as standards yielded the primary sequence GDVEKGKKIFVQKCAQCHTVEKGGKHKTGPNLHGLIGRKTGQAPGFSYTEANKNKGITWGEETLMEYLE NPKKYIPGTKMIFAGIKKKPERADLIAYLKEATSN . Comparison with sequences of other cytochromes c indicated the closest similarity to cytochrome c from snapping turtle (Chelydra serpentina) with substitutions at five positions corresponding to residues 32 (His-->Asn), 44 (Glu-->Pro), 89 (Ala-->Pro), 100 (Asp-->Glu), and 104 (Lys-->Asn), respectively . The presence of Pro and Asn residues at positions 89 and 104, respectively, are unique to alligator cytochrome c.

J Bacteriol, 1993 Mar, 175(6), 1612 - 20
Influence of femB on methicillin resistance and peptidoglycan metabolism in Staphylococcus aureus; Henze U et al.; The inactivation of FemB by insertion of Tn551 in the central part of the femB open reading frame was shown to increase susceptibility of methicillin-resistant Staphylococcus aureus strains toward beta-lactam antibiotics to the same extent as did inactivation of femA . Strains carrying the methicillin resistance determinant (mec) and expressing PBP 2' were affected to the same extent as were strains selected for in vitro resistance, which did not express PBP 2' . Both femA and femB, which form an operon, are involved in a yet unknown manner in the glycine interpeptide bridge formation of the S . aureus peptidoglycan . FemB inactivation was shown to reduce the glycine content of peptidoglycan by approximately 40%, depending on the S . aureus strain . The reduction of the interpeptide bridge glycine content led to significant reduction in peptidoglycan cross-linking, as measured by gel permeation high-pressure liquid chromatography of muramidase-digested cell walls . Maximum peptide chain length was reduced by approximately 40% . It is shown that the complete pentaglycine interpeptide bridge is important for the sensitivity against beta-lactam antibiotics and for the undisturbed activity of the staphylococcal cell wall-synthesizing and hydrolyzing enzymes, as was also apparent from electron microscopic examinations, which revealed aberrant placement of cross walls and retarded cell separation, leading to a pseudomulticellular phenotype of the cells for both femA and femB mutants.

Biol Pharm Bull, 1993 Mar, 16(3), 328 - 30
Labile 50S ribosome from partial macrolide-resistant Staphylococcus aureus; Endou K et al.; Staphylococcus aureus S704 and 8325MMT7 show constitutive resistance to macrolide antibiotics such as erythromycin (EM), oleandomycin, spiramycin, rosamicin and josamycin, except for tylosin, rokitamycin (RKM), and mycinamicin as well as lincosamide and streptogramin type B antibiotics (PM-resistance) . Whenever 70S ribosomes from either of them were dissociated into 30S and 50S subunits in a 10-28%(W/W) linear sucrose gradient, the latter subunit was further cleaved into two small apparently equal particles (about 40S) . RKM could no longer bind to either of the small particles . A prior exposure of 8325MMT7's 50S subunit to RKM (except EM) did not cause cleavage in any small particles . The largest component (M.W . 33.0kDa) of 50S ribosomal proteins was absent in at least the small particles . The first finding suggests that the lability of the 50S ribosome may be responsible for PM-resistance.

Vojnosanit Pregl, 1993 Mar-Apr, 50(2), 129 - 33
{Therapy of infected pseudarthroses of the lower leg}; Milankov M et al.; The retrospective study comprised 23 patients with infected pseudoarthrosis after osteosynthesis of of the lower log fracture treated at the Clinic of Orthopedic Surgery and Traumatology in Novi Sad . Staphylococcus aureus has been the most common causative agent of infection . In all patients debridment of infection foci was performed and reosteosynthesis with the external fixator and in 10 patients spongioplasty was performed in addition . At the control examination good results were achieved in 4, satisfying in 3 and poor in 16 patients . Amputation was performed in 5 patients.

Rinsho Byori, 1993 Mar, 41(3), 233 - 4
{Symposium "infections, recently worth noticing" . Introductory address}; Kobayashi K; There was once an idea that the extensive development of antibiotics and vaccines would cause most bacterial and viral infections to fade away someday . However, the occurrence of antibiotic resistant bacteria and variant viruses proved this to be illusion . The spread of HIV infection, since there is no way to cure it so far, is of great concern . The occurrence of methicillin resistant Staphylococcus aureus (MRSA) presents another difficulty in preventing nosocomial infections due to the existence of healthy carriers . The out-break of MRSA in wards is one of the most serious problems in hospital management . HCV is capable of inducing chronic hepatitis, hepatic cirrhosis and hepatoma . HCV is thus a more serious concern today than HBV, since preventive measures against HBV by vaccination and anti-HBV immunoglobulin are fully established . We, doctors, nurses and clinical technologists are apt to be exposed to these hazardous microorganisms and thus should take appropriate precautions during routine work . The present symposium was planned to present recent research on these microorganisms, HIV, MRSA and HCV, so that we can improve our measures to prevent them.

Am J Reprod Immunol, 1993 Mar, 29(2), 124 - 30
Mitogen induced production of polyclonal IgG is decreased in women with severe endometriosis; Gebel HM et al.; PROBLEM: The etiology and/or pathogenesis of endometriosis may involve aspects of both humoral and cellular immunity . METHOD: In this investigation, we analyzed the ability of B lymphocytes from distinct patient groups for production of IgG1, IgG2, and IgG3 following in vitro stimulation with polyclonal B-cell mitogens (pokeweed mitogen and Staphylococcus aureus Cowan strain I) after in vitro stimulation with polyclonal B-cell activators . RESULTS: We observed that the in vitro production of IgG1, IgG2, and IgG3 was identical among fertile controls (no endometriosis; N = 22), infertile women without endometriosis (N = 22), infertile women without endometriosis (N = 20) and patients with stage 1 or 2 endometriosis (N = 31) . In contrast, in vitro IgG2 production was significantly reduced among women with stage 3 or 4 endometriosis (N = 11) compared to controls (P < 0.001) . CONCLUSION: Since the number of circulating B cells was similar in each patient group studied, the reduced production of IgG2 in patients with stage 3 or 4 disease was not merely due to fewer antibody producing cells in those subjects, and we speculate that the observed decrease in polyclonal IgG2 production among these patients is due to a primary defect . In additional studies, we observed that polyclonal IgG2 production was normal among stage 3 or 4 patients treated with danazol (N = 11), but significantly reduced in patients treated with gonadotropin releasing hormone agonists (N = 8) . Although not conclusive, these data suggest that danazol may have the capacity to correct the defective production of polyclonal IgG2 in patients with severe endometriosis.

Diabetes Res Clin Pract, 1993 Mar, 19(3), 183 - 8
Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus; Marhoffer W et al.; In this study neutrophil (PMN) oxidative burst activity was investigated ex vivo and in vitro in comparison to the PMN-phagocytic functions ingestion and bacterial killing in poorly-controlled type 1 diabetic patients . Luminol enhanced chemiluminescence in response to phorbolesters as a measure of oxidative burst was assessed in a parallel detecting microtiterplate luminometer in 40 poorly-controlled type 1 diabetic subjects . PMN ingestion was measured with {3H}thymidine-labelled Staphylococcus aureus in a kinetic radiometric assay . Microbicidal activity was determined by pure plate counting of surviving bacteria (colony forming units, cfu) after defined pmn challenge . PMNs of type 1 diabetic subjects showed a highly significant reduction of peak CL response in response to PMA compared to nondiabetic controls (P < 0.001) and PMN ingestion (51.8 +/- 4.6%) and bacterial killing (28.6 +/- 3.2%) were reduced as well (78.2 +/- 5.2% (IN) and 18.4 +/- 4.1% (BK), P < 0.01, respectively) . The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations > or = 13.8 mmol/l whereas PMN IN and BK were significantly reduced at glucose levels > or = 27.75 mmol/l . In the control group there was a positive correlation of peak CL response and IN as well as BK (P < 0.05); in type 1 diabetic patients this was also true, but did not reach statistical significance . The data obtained in this study clearly demonstrated impaired PMN oxidative burst activity and markedly reduced ingestion and bacterial killing in type 1 diabetic patients ex vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

East Afr Med J, 1993 Mar, 70(3), 140 - 2
Surgical management of pyopericardium; Lema LE; Forty three patients with pyopericardium were managed over a six year period . Pyomyositis and septic arthritis were the most common associated conditions and Staphylococcus aureus the commonest microorganism isolated . Mycobacterium tuberculosis was isolated in only three of the cases . Pericardiocentesis and various forms of pericardial windows were found to be associated with high rates of recurrences, inadequate drainage and subsequent constrictive pericarditis . Pericardiectomy should be done as an initial form of surgical treatment where the general condition of the patient permits, since this procedure is not associated with the adverse sequelae of aspiration and pericardial window procedures.

Eur J Med, 1993 Mar, 2(3), 143 - 7
Recovery from staphylococcal septicaemia in neutropenic patients without removal of the previously inserted central venous catheter; Karmochkine M et al.; OBJECTIVES: An open clinical study was conducted in the haematological department of an intensive care unit to investigate cure of staphylococcal septicaemia in neutropenic central venous catheter carriers without removal of the line . METHODS: Thirteen neutropenic patients with a central venous catheter were investigated . These patients were under treatment for haematological malignancies and had at least 2 blood cultures positive for Staphylococcus aureus or coagulase-negative staphylococcus . Antibiotherapy including vancomycin was given through the catheter . Each case was re-evaluated on day 3 of treatment . The catheter was removed if blood cultures remained positive or if clinical signs of bloodstream infection persisted or worsened . RESULTS: Clinical recovery was obtained in ten patients and bacterial eradication in twelve . Three patients died from septic shock: two deaths were not related to staphylococcal septicaemia; one death was due to a staphylococcal septic shock which occurred within a few hours of admission, despite of prompt removal of the central venous catheter . CONCLUSIONS: With appropriate antibiotherapy, leaving the central venous catheter in place would appear possible in cases of staphylococcal septicaemia . Response to treatment, however, must be carefully monitored.

Tohoku J Exp Med, 1993 Mar, 169(3), 179 - 86
Protection of BALB/c mice against methicillin-resistant Staphylococcus aureus infection by intraperitoneal administration of nucleoside-nucleotide mixture; Adjei AA et al.; The effect of intraperitoneally administered nucleic acid components (nucleoside-nucleotide mixture) on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice . Two experiments were conducted in which BALB/c mice were fed a nucleotide-free 20% casein diet for 30 days . On the 10th day, the mice were inoculated intravenously with viable MRSA organisms . The mice were intraperitoneally administered nucleoside-nucleotide mixture or saline (control) daily from the onset of the experiment (experiment 1) or from the day of inoculation (experiment 2) . The survival rate in the nucleoside-nucleotide group in experiment 1 (70%) was significantly higher than that in the saline group (20%) (p < 0.05) . In experiment 2, the survival rate in the nucleoside-nucleotide group (55%) tended to be higher than that in the saline group (36%) without statistically significant difference; furthermore, in the surviving mice, the viable MRSA organisms recovered from the spleen and the kidney were fewer in the former group than in the latter group (p < 0.05) . The studies showed that the intraperitoneal administration either before or after the MRSA challenge of the nucleoside-nucleotide mixture was effective for the recovery of the mice from the infection.

Ukr Biokhim Zh, 1993 Mar-Apr, 65(2), 63 - 8
{Effect of staphylococcal peptidoglycan on the activity of Ca2+-ATP-ase from the sarcoplasmic reticulum in the early stages of ionizing radiation effect}; Voitsits'kyi VM et al.; It is established that peptidoglycan of Staphylococcus aureus possess superficial activity and can render influence on the functional activity of biomembranes . It tends to increase Ca(2+)-ATP-ase activity in the sarcoplasmic reticulum membranes, but no changes have been observed in case of the enzyme solubilization . The effect of peptidoglycan was more expressed, if it was used in the early period of acute radiation injury (1 and 24 h) in a dose of 0.21 Cl/kg for samples with irradiation-induced decrease of Ca(2+)-ATP-ase activity.

Exp Dermatol, 1993 Mar, 2(2), 70 - 4
Enhancing effect of protein A on the interaction between opsonized corneocytes and neutrophils in staphylococcal infection; Kato T et al.; Formation of subcorneal pustules characterizes skin lesions infected by Staphylococcus aureus . To elucidate the mechanism underlying the subcorneal pustule formation as well as that of anti-bacterial host defence, we studied the effect of staphylococcal protein A on the interaction between the stratum corneum (SC) and neutrophils . We found that protein A significantly promoted opsonized SC-induced chemiluminescence (CL) in neutrophils . This was specific to SC because no enhancement was observed with opsonized zymosan . It took place even with the serum obtained from a patient with agammaglobulinemia, ruling out the possibility of the involvement of Fc-receptors of neutrophils in this phenomenon . Microscopic observation of such SC revealed an increase in the number of neutrophils adhering to the surface of the protein A-coated corneocytes . Ultrastructural observation showed a distinct deformation of the neutrophils adhering to the surface of the corneocytes, suggesting that they are in an activated state . Such an enhanced interaction between protein A-attached SC and neutrophils seems to play an important role in the host defence mechanism against the invading S . aureus and in the production of the characteristic pustules by the neutrophil-mediated damage of the surrounding epidermal tissue.

J Hosp Infect, 1993 Mar, 23(3), 211 - 22
Outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit; Haddad Q et al.; An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred in a neonatal intensive care unit (NICU) over a period of 2 months involving 16 babies, mainly of low birth weight . Arbitrary grouping of the isolates showed that there were apparently three different strains involved in the outbreak, as determined only by antibiogram . Twenty-three out of 27 isolates were allocated to 'group 1' based on antibiotic sensitivity pattern . Control of spread of the MRSA in the unit was difficult because of some technical constraints but eradication was finally achieved by cohort nursing and treatment with topical mupirocin in paraffin base . All MRSA isolates were resistant to gentamicin, erythromycin, tetracycline and at least four other antibiotics but sensitive to vancomycin . Overcrowding, limited space, inadequate cleaning of the equipment and initial lack of correct attitude to scrupulous handwashing techniques, all appeared to contribute to the ease of spread of the strains involved.

Vet Immunol Immunopathol, 1993 Mar, 36(2), 137 - 51
Suppression of proliferative response of BoCD4+ T lymphocytes by activated BoCD8+ T lymphocytes in the mammary gland of cows with Staphylococcus aureus mastitis; Park YH et al.; Investigations were conducted to determine the mechanisms that account for differences in the responses of BoCD4+ lymphocytes from mammary gland secretions (MGS) in healthy cows and in cows with Staphylococcus aureus infection . The proliferative response to lectins and S . aureus antigens of mammary gland lymphocytes from healthy, S . aureus immunized cows was less than the response of peripheral blood lymphocytes . The lower responses of mammary gland lymphocytes were attributable both to less efficient antigen presentation by mammary gland antigen-presenting cells (APC) than by peripheral blood APC, and to lower responsiveness of mammary gland lymphocytes to lectins and antigen . In addition, the proliferative response of infected mammary gland lymphocytes was less than the response of uninfected mammary gland lymphocytes . This difference resulted from decreased proliferation of BoCD4+ lymphocytes in infected MGS . Flow cytometric analysis revealed that infected MGS contained increased numbers of BoCD8+ cells which coexpressed an activation molecule, ACT2, relative to BoCD8+ cells from uninfected MGS . Removal of BoCD8+, ACT2+ lymphocytes resulted in increased antigen responsiveness by lymphocytes from infected mammary glands . Also, when purified BoCD4+ lymphocytes were stimulated with antigen in the presence of varying numbers of ACT2+, BoCD8+ lymphocytes, antigen responsiveness was decreased in a dose-related manner . These data demonstrate that hyporesponsiveness of mammary gland lymphocytes to lectins and S . aureus antigen is, in part, mediated by activated BoCD8+ lymphocytes and suggest that this population enhances persistent intramammary infection by S . aureus.

J Med Microbiol, 1993 Mar, 38(3), 203 - 8
Genetic analysis of methicillin-resistant Staphylococcus aureus from a Nigerian hospital; Udo EE et al.; Methicillin-resistant strains of Staphylococcus aureus isolated during 1985 and 1987 at a Nigerian hospital were compared by resistance profiles, plasmid analysis, and pulsed-field gel electrophoresis of chromosomal DNA . The results indicated that the isolates from the two periods were unrelated with regard to all three aspects . None of the isolates was similar to the classical MRSA nor to the epidemic MRSA of Australia or the UK . The MRSA isolated in 1985 had a similar plasmid to MRSA isolates from Singapore, but differed from them when compared by pulsed-field gel electrophoresis.

J Bacteriol, 1993 Mar, 175(5), 1493 - 9
Isolation and characterization of autolysis-defective mutants of Staphylococcus aureus created by Tn917-lacZ mutagenesis; Mani N et al.; Two autolysis-defective mutants (Lyt-1 and Lyt-2) of Staphylococcus aureus have been isolated by transposon Tn917-lacZ mutagenesis . The mutants exhibited normal growth rate, cell division, cell size, and adaptive responses to environmental changes . No autolytic activities were detected in a crude autolytic enzyme preparation from the Lyt- mutants . The rate of autolysis of whole cells and cell walls in the mutants were negligible, but mutant cell wall preparations were degraded by crude enzyme preparations from the wild-type strain . Zymographic analyses of enzyme extracts from the mutants showed a single autolytic enzyme band, compared with more than 10 autolytic enzyme bands from the parent strain . Analyses of intracellular and exoprotein fractions gave results similar to those in experiments with total-cell extracts . Southern blot analysis indicated the insertion of a single copy of the transposon into the chromosome of Lyt mutants . Isogenic Lyt mutants constructed by phage phi 11 transduction showed similar phenotypes . Because both Lyt- mutants had Tn917-lacZ inserted in the appropriate orientation, it was possible to determine gene activity under various conditions by measuring beta-galactosidase activity . The gene activity was found to be induced by low pH, low temperature, and high sucrose and high sodium chloride concentrations . From these data, we propose that the mutation lies in either a master regulatory gene or a structural gene which is responsible for the synthesis or processing of a majority of the autolytic enzyme bands.

Exp Dermatol, 1993 Mar, 2(2), 75 - 83
Helium-neon laser irradiation induces effects on cytokine production at the protein and the mRNA level; Funk JO et al.; The construction of an in vitro model allowed an investigation of the basic functions of immunocompetent cells after laser irradiation . Among low-energy laser sources, the helium-neon (He-Ne) laser, with a wavelength of 632.8 nm, has often been found to produce photobiological effects including evidence of interference with immunological functions . Previous experiments revealed an influence of He-Ne laser irradiation on concentrations of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) in supernatants of cultures of human peripheral blood mononuclear cells (PBMC) with increased cytokine concentrations after irradiation of 18.9 J/cm2 and decreased concentrations after irradiation of 37.8 J/cm2 . Now, the mechanisms involved were studied . Results showed that cytokine production of cells stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) was altered significantly after laser irradiation but not after stimulation with staphylococcus aureus enterotoxin B (SEB) . In situ hybridization of IFN-gamma mRNA producing PBMC revealed that the number of positive cells was modulated similarly . The results were identical in cultures of enriched monocytes (M phi) or enriched T cells . Cells of the human monocytic cell line Mono Mac 6 were also influenced after LPS stimulation, whereas constitutively IL-2-producing Jurkat cells were not influenced by laser irradiation at any energy density . Analysis of the IL-2 receptor (IL-2R) and intercellular adhesion molecule-1 (ICAM-1) expression in PBMC showed partial down-regulation of both receptors at 37.8 J/cm2, but only after stimulation with PHA.(ABSTRACT TRUNCATED AT 250 WORDS)

JPEN J Parenter Enteral Nutr, 1993 Mar-Apr, 17(2), 148 - 52
The effects of oral RNA and intraperitoneal nucleoside-nucleotide administration on methicillin-resistant Staphylococcus aureus infection in mice; Adjei AA et al.; The effects of oral RNA and intraperitoneal nucleoside-nucleotide mixture administration on methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection were studied in mice . BALB/c mice were fed a nucleic acid-free diet or nucleic acid-free diet supplemented with 0.5% or 2.5% ribonucleic acid (RNA) for 30 days . Nucleoside-nucleotide mixture or saline (control) was intraperitoneally administered daily to these rats except for the 2.5% RNA group, which received saline only . On the 10th day of this treatment, the mice were inoculated intravenously with the viable MRSA organisms . Susceptibility to the MRSA was determined by animal survival and recovery of the MRSA from the organs . The survival rates in the three groups that were administered saline were 29%, 35%, and 40% for nucleic acid-free diet, 0.5% RNA, and 2.5% RNA groups, respectively, whereas in the two groups that received the nucleoside-nucleotide mixture the rates were 69% for the nucleic acid-free diet group and 55% for 0.5% RNA group . The susceptibility of the mice to the MRSA challenge was not affected by dietary RNA, which indicates the ineffectiveness of oral RNA . The combined survival rate in the two nucleoside-nucleotide groups (64%) was statistically different (p < .01) from that in the three saline groups (34%) . There was a greater reduction in viable organism recovery in the kidney and spleen of the surviving mice that had been administered the nucleoside-nucleotide mixture than in those administered saline.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Invest, 1993 Mar, 91(3), 853 - 61
Tolerance to endotoxin-induced expression of the interleukin-1 beta gene in blood neutrophils of humans with the sepsis syndrome; McCall CE et al.; The induction of genes of host cells stimulated by microbial products such as endotoxin and the tolerance of cells to endotoxin excitation play critical roles in the pathogenesis of microbial-induced acute disseminated inflammation with multiorgan failure (the sepsis syndrome) . One gene that is induced in phagocytic cells by endotoxin and that appears to play an essential role in the pathogenesis of the sepsis syndrome is IL-1 beta . We report here that blood neutrophils (PMN) of patients with the sepsis syndrome (sepsis PMN) are consistently tolerant to endotoxin-induced expression of the IL-1 beta gene, as determined by decreased synthesis of the IL-1 beta protein and reductions in IL-1 beta mRNA . This down-regulation of the IL-1 beta gene in sepsis PMN occurs concomitant with an upregulation in the constitutive expression of the type 2 IL-1 receptor (IL-1R2) . These phenotypic changes do not persist in PMN of patients recovering from the sepsis syndrome . Tolerance has stimulus and response specificity since sepsis PMN tolerant to endotoxin can respond normally to Staphylococcus aureus stimulation of IL-1 beta production and they normally secrete elastase . Uninfected patients with severe trauma or shock from causes are not tolerant to endotoxin and tolerance is not limited to patients infected with Gram-negative bacteria . The mechanism responsible for tolerance involves pretranslational events and is not due to loss of the CD14 surface protein, a receptor required for endotoxin induction of IL-1 beta in PMN . The physiological significance of the tolerance to endotoxin and increased expression of IL-1R2 on sepsis PMN is unknown, but may represent an attempt by the host to protect itself from the deleterious effects of disseminated inflammation.

Eur J Immunol, 1993 Mar, 23(3), 702 - 8
APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression; Mapara MY et al.; We studied induction of apoptosis in several human malignant B cells from chronic lymphocytic leukemias (BCLL) by triggering the APO-1 antigen . The APO-1 antigen was found to be expressed on the surface of malignant B cells . In BCLL cells from most patients, APO-1 antigen expression increased following in vitro activation by Staphylococcus aureus Cowan I (SAC) or interleukin-2 (IL-2) . In certain cases of BCLL co-stimulation with SAC plus IL-2 resulted in a synergistic up-regulation of the APO-1 antigen on the cell surface and prepared BCLL cells for monoclonal antibody anti-APO-1 mediated apoptosis . Interestingly, bcl-2 mRNA expression decreased upon stimulation with SAC plus IL-2, whereas SAC or IL-2 alone did not affect the level of bcl-2 expression . Thus, in these BCLL cells induction of anti-APO-1-mediated apoptosis appeared to be correlated with bcl-2 mRNA down-regulation . One informative BCLL, however, with a similar pattern of APO-1-antigen expression, did not show SAC plus IL-2-dependent bcl-2 down-regulation . Surprisingly, these cells proliferated in response to anti-APO-1 only when cells were co-stimulated with SAC plus IL-2 . Our data suggest that down-regulation of bcl-2 prepares BCLL cells for induction of APO-1-mediated apoptosis . In addition they demonstrate that triggering of the APO-1 antigen may also lead to the induction of proliferation in special cases of BCLL.

Eur J Immunol, 1993 Mar, 23(3), 664 - 8
Activation of mucosal V beta 3+ T cells and tissue damage in human small intestine by the bacterial superantigen, Staphylococcus aureus enterotoxin B; Lionetti P et al.; Staphylococcus aureus enterotoxin B (SEB) was added to explants of fetal human intestine in organ culture or administered into the lumen of fetal small intestine prior to culture . Both routes produced a massive increase in lamina propria T cells expressing V beta 3, and to a lesser extent, those expressing V beta 5 and V beta 12 . SEB-activated lamina propria T cells produced interleukin-2 and interferon-gamma and T cell activation was accompanied by tissue damage, which was inhibited by FK506.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Mar-Apr, (2), 122 - 4
{Staphylococcus aureus-induced antigen-specific immunosuppression}; Gusev EIu et al.; In experiments made on noninbred white mice the manifestations of delayed hypersensitivity and the number of antibody-producing cells in regional lymph nodes or the spleen were determined on day 5 after the subcutaneous or intraperitoneal immunization of the animals with sheep red blood cells (SRBC) . At the same time the injection of S . aureus antigens simultaneously with SRBC raises the threshold of antigenic sensitivity and decreases the manifestations of cell-mediated and humoral immune response to SRBC . This suppressive effect was even more pronounced in the local immune process and was partially mediated by the hyperproduction of prostaglandins.

Tidsskr Nor Laegeforen, 1993 Feb 20, 113(5), 581 - 4
{Bacterial arthritis}; Gran JT et al.; During the years 1980-89, 13 patients were hospitalized because of bacterial arthritis of the peripheral joints . There were five juvenile patients (under 15 years of age) . The remaining eight patients were adults, of whom seven were older than 50 years . The mean delay in establishing the diagnosis was four days (0-10 days) . Monarthritis was found in 12 patients, and in one patient two joints were involved . The most commonly affected joints were the shoulder (four cases), knee (four cases), ankle (three cases), hip (two cases) and toe (one case) . A predisposing condition was found in five patients, and three cases suffered from reduced mobility of the joint at follow-up . Staphylococcus aureus was the most common etiologic agent.

J Immunol, 1993 Feb 15, 150(4), 1276 - 85
Immunoregulatory role of CD40 in human B cell differentiation; Splawski JB et al.; CD40 is a member of a family of surface molecules with homology to the nerve growth factor receptor and is expressed on B cells . The role of CD40 in regulating human B cell differentiation and the production of specific Ig isotypes was examined . In the absence of other stimuli, anti-CD40 and IL-4 induced the secretion of IgM, IgG, and IgE by purified human peripheral blood B cells . However, addition of formalinized Staphylococcus aureus (SA) enhanced the response . In the presence of SA, anti-CD40 and IL-4 induced the secretion of IgM, IgG1, IgG2, IgG3, and IgG4 in addition to IgE . No consistent effect on IgA secretion was demonstrated . The combination of SA, anti-CD40, and IL-4 induced one tenth of the total Ig production that was stimulated by SA and IL-2, with a different distribution of Ig H chain isotypes . B cells stimulated with SA, anti-CD40, and IL-4 secreted a greater percentage of IgG4 and IgE and a decreased percentage of IgG1 and IgA, compared with that secreted in response to SA and IL-2 . Anti-CD40 did not induce Ig production in combination with IL-2 and did not alter the Ig secreted in response to SA and IL-2 . Stimulation with SA, anti-CD40, and IL-4 caused Ig H chain isotype switch, inasmuch as IgG and IgE secretion could be induced from preimmune cord blood B cells and IgD+ naive adult B cells and IgE secretion could be induced from IgE- adult B cells . Ig secretion by purified B cells stimulated with SA, IL-4, and anti-CD40, but not with SA and IL-2, was significantly enhanced by anti-CD18 or anti-ICAM-1 mAb, suggesting that homotypic aggregation induced by anti-CD40 might limit Ig production . Finally, anti-CD40 was found to inhibit Ig production by B cells cultured with anti-CD3-activated T cells . These results suggest that engagement of the CD40 molecule on B cells provides signals that permit IL-4 to induce Ig isotype switching . This response is limited by LFA-1-mediated homotypic interactions of B cells . Engagement of CD40 by the ligand expressed by activated T cells appears to be important for the activation of B cells during T cell-B cell collaboration and the production of all isotypes of Ig.

Biochim Biophys Acta, 1993 Feb 13, 1161(2-3), 194 - 200
Identification of a novel 4 kDa immunoglobulin-A-binding peptide obtained by the limited proteolysis of jacalin; Kabir S et al.; Jacalin, an IgA-binding lectin from jackfruit (Artocarpus heterophyllus) seeds, was isolated by the passage of PBS extracts of seeds over an affinity matrix containing IgA-Sepharose-4B . It was further purified by HPLC . When analyzed by SDS-PAGE under both reducing and nonreducing conditions, the native jacalin was dissociated into two subunits of 12 and 15.4 kDa . Both the subunits could bind IgA . Peptide mapping performed with radioiodinated jacalin indicated that both the subunits were susceptible to proteolysis by Staphylococcus aureus V8 proteinase . One degradation product was a small peptide of 4 kDa . This small proteolytic fragment also bound IgA . The amino-termini of the two major IgA binding subunits, 12 and 15.4 kDa, were identical . The 4 kDa IgA-binding proteolytic fragment of jacalin had a different amino-terminal sequence, suggesting that the region of jacalin which binds IgA does not remain close to the amino-terminus of the peptide.

Med Clin (Barc), 1993 Feb 13, 100(6), 205 - 9
{Clinical epidemiology of an outbreak of nosocomial infection caused by Staphylococcus aureus resistant to methicillin and aminoglycosides: efficacy of control measures . Comité de Control de Infecciones}; Trilla A et al.; BACKGROUND: The appearance of outbreaks of nosocomial infections due to methicillin resistant Staphylococcus aureus (MRSA) is a current problem in Spain . The clinical and molecular epidemiology of these outbreaks as well as the efficacy of their control measures are a matter of controversy . METHODS: An outbreak of MRSA nosocomial infections in the Hospital Clinic i Provincial of Barcelona, a 953-bed University Hospital, with a total of 347 cases from September 1989 to October 1991 is described . The control measures used include prospective and continued surveillance of all MRSA isolations, identification of the reservoir, use of different types of isolation and control of nasal carriers among health care workers . The MRSA strains isolated were studied by standard microbiological procedures, phage-typing and extrachromosomal (plasmid) DNA analysis by means of restriction endonuclease analysis (REAP) . RESULTS: From the Intensive Care Units, the outbreak extended to the medical and surgical wards . Seventy-one percent of the cases corresponded to infected patients and 29% to asymptomatic carrier patients . The MRSA strain responsible of the outbreak had a notable antibiotic multiple-resistance pattern . The studies performed showed that most of the strains belonged to phage group III and were lysed by phage 77 . Plasmid DNA analysis showed that 95% of the strains isolated had a unique homogeneous profile . Despite the different control measures used, the MRSA infection has acquired a medium level endemic rate in the Hospital Clinic i Provincial . CONCLUSIONS: The introduction and spread of methicillin-resistant MRSA in a teaching hospital with more than 500-bed may be rapid and affecting large number of patients . Effective control measures carries multiple problems, which must be addressed with the collaboration of all hospital employees . The molecular typing techniques used (REAP) further identified that the outbreak is due to one single MRSA strain, with an epidemiologic behavior identical to the one showed by the epidemic strains previously described in the United Kingdom and Australia.

J Biol Chem, 1993 Feb 5, 268(4), 2610 - 5
Purification and characterization of a membrane-bound protein carboxyl methyltransferase from rat kidney cortex; Boivin D et al.; Class II protein carboxyl methyltransferases (EC 2.1.1.77) are known to exist predominantly in a soluble form in all cells studied so far . These enzymes have been purified to homogeneity from the cytosols of many mammalian tissues but not from membranes . We describe here the purification to apparent homogeneity of a membrane-associated protein carboxyl methyltransferase from the brush border membrane of rat kidney . The enzyme was purified by fast protein liquid chromatography on Superdex 75 and Mono-Q and by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and consists of a single 27,300 polypeptide . The purified enzyme recognizes exogenous substrate proteins such as ovalbumin and gamma-globulins as well as synthetic peptides containing a L-isoaspartyl residue but not a synthetic peptide containing a farnesylated C-terminal cysteine (S-farnesyl-LARYKC) . The Km for S-adenosyl-L-methionine with ovalbumin as the substrate is 1.5 microM and the purified enzyme is sensitive to inhibition by S-adenosyl-L-homocysteine (Ki = 0.3 microM) . Peptide map obtained after Staphylococcus aureus V8 protease digestion of brush border membrane protein carboxyl methyltransferase showed a fragmentation pattern that was identical to that obtained for a soluble protein carboxyl methyltransferase purified according to the same procedure, indicating a high degree of homology . These results support the notion that class II protein carboxyl methyltransferases are not restricted to a cytosolic localization and show that the membrane-bound form of this enzyme shares many characteristics with known cytosolic protein carboxyl methyltransferases.

Semin Arthritis Rheum, 1993 Feb, 22(4), 252 - 64
Hypogammaglobulinemia and rheumatic disease; Lee AH et al.; Primary hypogammaglobulinemia describes a heterogeneous group of immunoglobulin disorders mainly composed of X-linked agammaglobulinemia, common variable immunodeficiency, and selective immunoglobulin (Ig) A deficiency . The most serious problems are related to recurrent infections with high-grade encapsulated bacteria . However, a wide variety of rheumatologic disorders also occur in association with hypogammaglobulinemic states . Septic arthritis with usual bacterial pathogens such as Staphylococcus aureus, and unusual bacteria such as Mycoplasma and Ureaplasma species, have been described in these patients . An aseptic nonerosive polyarticular arthritis that resembles rheumatoid arthritis is seen in 10% to 30% of hypogammaglobulinemic patients . Autoimmune disorders such as immune thrombocytopenic purpura, immune hemolytic anemia, juvenile rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, essential mixed cryoglobulinemia, chronic active hepatitis, and sarcoidosis have been reported in hypogammaglobulinemic patients . Finally, to complicate matters, many disease-modifying antirheumatic drugs, including gold, D-penicillamine, sulfasalazine, azathioprine, and cyclophosphamide, cause symptomatic hypogammaglobulinemia in some patients.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Feb, 41(2), 295 - 9
{Successful surgical management for chronic sternal osteomyelitis and anterior mediastinal abscess after double valve replacement by total sternectomy and pectoralis major muscle flaps}; Kaneda K et al.; A 63-year-old woman underwent double (aortic and mitral) valve replacement in February, 1987 . Thirty days later, purulent drainage developed at the sternotomy incision with high fever . Wound cultures revealed staphylococcus aureus . She was treated by local wound care with antibiotics . About one month later, she had a satisfactory wound healing . But three cutaneous fistulas with discharge emerged at the sternotomy incision in November (9 months later) and the cultures grew the same species . The fistulogram showed the communication between these tracts and the mediastinum . The diagnosis of chronic sternal osteomyelitis and anterior mediastinal abscess was made . At first the resection of the xiphoid process and the mediastinal drainage were carried out in March, 1988 . Inspite of this procedure, she still had persistent purulent discharge . Then, en bloc excision of the infected sternum and the adjacent costal cartilage were performed in April . The defect was obliterated with the bilateral pectoralis major muscle flaps . After the radical operation, her wound was completely healed, even though the ventilatory support was needed for 24 days because of flail chest due to the anterior chest wall instability . Now she has been free from recurrence for four years . Total sternectomy and pectoralis major muscle plombage seem to be a very effective management in chronic sternal osteomyelitis.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Feb, 41(2), 273 - 6
{A case of the successful treatment of pulmonary artery pseudoaneurysm after PA banding}; Egawa Y et al.; Pulmonary artery pseudoaneurysm after PA banding is a rare complication and its mortality is very high . The authors successfully operated on this sort of lesion . To our knowledge, this is the first successful case in Japanese literature . The second of twins was found to be suffering asplenia, dextro cardia, TAPVC, atrioventricular septal defect, corrected TGA and PDA . On the 19th day of life, increasingly pulmonary congestion forced us to operate . We performed PDA ligation, correction of TAPVC, together with extrathoracically adjustable PA banding . 5 months following this operation, spike fever and swelling of anterior thorax were noted . PA angiography was performed, and it showed that the pulmonary artery had been cut through by the band and a pseudoaneurysm had developed . The PA banding was removed and an end-to-end anastomosis of the PA was performed using cardiopulmonary bypass and deep hypothermia with surface cooling . The diameter of the PA anastomosis was designed to be one half that of her aorta . Staphylococcus aureus was cultured from the specimen of the PA band . It was thought to have contributed to the development of this aneurysm . The post operative course was uneventful.

J Antibiot (Tokyo), 1993 Feb, 46(2), 310 - 5
Structures of enzymatically modified products of arbekacin by methicillin-resistant . Staphylococcus aureus; Kondo S et al.; Only a limited number of strains of methicillin-resistant Staphylococcus aureus (MRSA) moderately resistant to arbekacin (ABK) have been isolated clinically . Three inactivated products of ABK have been obtained by reaction with excess amounts of a crude enzyme preparation extracted from an ABK-resistant MRSA strain (MIC, 25 micrograms/ml) . The 2"-O-phosphate was the major product together with small amounts of the 6'-N-acetate and the double modification product . The structures of these modification products were determined by MS and NMR spectral analyses.

Diagn Microbiol Infect Dis, 1993 Feb, 16(2), 99 - 104
Use of chemiluminescent DNA probes in the rapid detection of oxacillin resistance in clinically isolated strains of Staphylococcus aureus; Youmans GR et al.; Chemiluminescent DNA probes (AccuProbe, species specific; and FlashTrack, bacterial generic) were used to determine oxacillin resistance in Staphylococcus aureus . Ribosomal RNA was measured at designated intervals in the presence and absence of antibiotic . A total of 48 (AccuProbe assay) and 24 (FlashTrack) S . aureus isolates with known oxacillin susceptibility patterns were inoculated into Bactec 6A bottles both with and without 4 micrograms/ml oxacillin and incubated at 35 degrees C for 4 h . Aliquots were removed at 0 and 4 h, and pellets of bacteria were obtained via selective centrifugation . Probe assay counts (relative light units, RLUs) were performed . Of 21 oxacillin-resistant S . aureus (ORSA) strains, 20 showed a > 5-fold RLU increase during the incubation period (Accu-Probe assay): 25 of 27 oxacillin-susceptible strains demonstrated a < or = 4-fold increase . AccuProbe test sensitivity and specificity were 95% and 92%, respectively . With the generic FlashTrack probe assay, all nine ORSA isolates showed a > or = 4- to 10-fold increase in RLUs, and all 15 oxacillin-susceptible strains showed a < or = 4-fold increase in RLUs during the 4-h incubation . The FlashTrack test sensitivity and specificity were both 100% . Probe assays were completed within 5 h . This study suggests that rapid and reliable determination of oxacillin resistance in S . aureus clinical isolates can be accomplished using commercially available DNA probes.

Int J Food Microbiol, 1993 Feb, 17(4), 289 - 301
Effect of three preservatives on the growth of Bacillus cereus, Vero cytotoxigenic Escherichia coli and Staphylococcus aureus, on plates with gradients of pH and sodium chloride concentration; Thomas LV et al.; The effect of temperature, pH, sodium chloride concentration and a preservative (sodium benzoate, sodium nitrite or potassium sorbate) on the growth of three foodborne bacterial pathogens (Bacillus cereus, Vero cytotoxigenic Escherichia coli and Staphylococcus aureus) was studied using gradient gel plates . Growth, expressed in optical density units, was recorded using image analysis techniques, and was expressed as three-dimensional grids . These gave a visual indication of the effects of any three of the environmental factors on bacterial proliferation . Sorbate was completely effective against E . coli at all temperature/pH/NaCl combinations, and was the most effective preservative tested against B . cereus . Increase in the acidity and/or the NaCl concentration improved the effect of all the preservatives, except nitrite when used against St . aureus . Nitrite was the least effective preservative, particularly against St . aureus . At < 25 degrees C, sorbate was more effective than benzoate against St . aureus when used with higher concentrations of NaCl . At 35 degrees C benzoate was the most effective preservative against St . aureus, especially when used at pH < 6.

Rev Clin Esp, 1993 Feb, 192(3), 112 - 5
{Infections in the postoperative period of a liver transplant . A comparison of 2 protocols for anti-infectious prophylaxis}; Cisneros Alonso C et al.; We discuss the incidence of infection in 198 liver transplants during the immediate post-surgical period . All of them were treated with protocols with anti-infective prophylaxis, and have been divided in two groups regarding the antibiotic scheme used, in the second of said groups we have included parenteral vancomycin . Global incidence of infection was different for both groups (46.9% in group A and 15.3% in group B) (p < 0.01) . We stress that the most frequent germ found in the cultures of the group without vancomycin was Staphylococcus aureus, with a great difference between groups (p < 0.01); global incidence of pneumonias was also different between both groups (p < 0.05) . After the introduction of vancomycin in the second group the most frequent found germ was Candida but with a low percentage . Gram-negative germs appear preferably in both groups when hospital stay was over 10 days . It is important to stress that transplanted patients who did not show rejection got significantly lesser infected (p < 0.05) than patients who shown rejection . We think that parenteral prophylaxis with ceftazidime and vancomycin, associated with oral-rhino-gastric decontamination, is useful for the control of early infections in patients with liver transplant.

J Vet Med Sci, 1993 Feb, 55(1), 169 - 71
Platelet abnormalities in a dog suffering from gangrenous mastitis by Staphylococcus aureus infection; Hasegawa T et al.; Severe gangrenous mastitis due to Staphylococcus aureus infection was diagnosed in a 7 year-old intact female beagle which was presented with swelling of mammary glands after dystocia . Leukocytosis (25,200-48,600/microliters), decreased platelets (107,000-179,000/microliters), and abnormal platelet pattern continued during the critical condition . Consistent with platelet pattern, large platelets were observed in the blood smear . The number of leukocytes and platelets rapidly returned to normal during treatment, and the platelet pattern was also restored . The number and pattern of platelet may provide a clue for the evaluation of the clinical condition and/or severity of the lesions in the dog with mastitis.

J Chemother, 1993 Feb, 5(1), 10 - 3
Comparison of the antibacterial activity and synergistic activity towards antibiotics of different mammalian sera; Miglioli PA et al.; The antibacterial activity against Escherichia coli ATCC 10798 and Staphylococcus aureus Mag 90 of normal sera from nine species of mammals was investigated by Avantage (Abbott) . Human and rat sera showed the highest antibacterial activity against E . coli ATCC 10798, while all investigated sera did not exhibit, till the maximum concentration tested (20%), spontaneous antibacterial activity against S . aureus Mag 90 . Heat inactivated sera (56 degrees C for 30 min) of all investigated species lost their antibacterial activity, but maintained their synergistic effect with sub-MICs of some antibacterial drugs, principally against E . coli ATCC 10798.

Stat Med, 1993 Feb, 12(3-4), 301 - 10
Evaluation of protocol change in burn-care management using the Cox proportional hazards model with time-dependent covariates; Ichida JM et al.; Survival analysis methods are valuable for detecting intervention effects because detailed information from patient records and sensitive outcome measures are used . The burn unit at a large university hospital replaced routine bathing with total body bathing using chlorhexidine gluconate for antimicrobial effect . A Cox proportional hazards model was used to analyse time from admission until either infection with Staphylococcus aureus or discharge for 155 patients, controlling for burn severity and two time-dependent covariates: days until first wound excision and days until first administration of prophylactic antibiotics . The risk of infection was 55 per cent higher in the historical control group, although not statistically significant . There was also some indication that early wound excision may be important as an infection-control measure for burn patients.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 339 - 41
Synergy of levofloxacin (L-ofloxacin) and oxacillin against quinolone-resistant Staphylococcus aureus, measured by the time-kill method; Patel JA et al.; The synergistic activity of levofloxacin and oxacillin against levofloxacin-resistant isolates of methicillin-resistant Staphylococcus aureus was tested by the time-kill method . The combination of levofloxacin at 1/4 the MIC for the isolate plus oxacillin at 8 micrograms/ml (< 1/4 the MIC) was synergistic against seven of nine isolates at 8 h, although no significant synergy was demonstrated at 24 h . This combination may prove to be effective against multidrug-resistant methicillin-resistant S . aureus, and further studies are warranted.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 203 - 6
beta-Lactamase-mediated inactivation and efficacy of cefazolin and cefmetazole in Staphylococcus aureus abscesses; Fields MT et al.; 12694668 Clinical reports and animal models have demonstrated that cefazolin may have decreased efficacy against some strains of Staphylococcus aureus because of type A beta-lactamase-mediated hydrolysis . We sought to measure biologically active cefazolin concentrations within abscesses with high concentrations of S . aureus and compare the concentrations with those of cefmetazole, a beta-lactamase-stable cephamycin . A type A beta-lactamase-producing strain of S . aureus with a demonstrated inoculum effect against cefazolin (MIC at an inoculum of 5 x 10(5) CFU/ml, 1.0 micrograms/ml; MIC at an inoculum of 5 x 10(7) CFU/ml, 32.0 micrograms/ml) but not cefmetazole (MICs at inocula of 5 x 10(5) and 5 x 10(7) CFU/ml, 2.0 micrograms/ml) was used . Cefazolin or cefmetazole (100 mg/kg of body weight every 8 h for 8 days) was administered to rabbits with infected tissue cages . No differences in the concentrations of the two drugs in the uninfected tissue cages were observed . Higher concentrations of cefmetazole than cefazolin were found in infected tissue cages at day 3 (5.9 +/- 0.7 versus 2.2 +/- 0.3 micrograms/ml; P < 0.01), day 5 (9.1 +/- 2.6 versus 3.6 +/- 0.7 micrograms/ml; P = 0.02), and day 8 (9.4 +/- 1.4 versus 4.8 +/- 0.9 micrograms/ml; P = 0.01) after infection . Cefazolin and cefmetazole were equally effective in reducing the bacterial concentration in the abscess . In vitro experiments demonstrated greater cefazolin than cefmetazole degradation by S . aureus, but the differences were greater in serum than in abscess fluid supernatants . We conclude that abscess cefazolin concentrations are diminished by type A beta-lactamase-producing S . aureus, but this did not affect drug efficacy in this model.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 191 - 8
Expression of the tetK gene from Staphylococcus aureus in Escherichia coli: comparison of substrate specificities of TetA(B), TetA(C), and TetK efflux proteins; Guay GG et al.; The tetK gene, which encodes a tetracycline efflux pump from Staphylococcus aureus, was expressed in Escherichia coli by using an inducible, low-level expression system . The tetK gene, as well as the tetA(B) gene from the transposon Tn10 and the tetA(C) gene from plasmid pBR322, was subjected to the regulatory control of the lac repressor, and resistance to tetracycline was measured as a function of the isopropyl-beta-D-thiogalactopyranoside concentration . The maximum resistance of the E . coli strain containing the tetK construct was comparable to the maximum resistance of the strain containing the tetA(C) construct but was less than the resistance of the strain containing the tetA(B) construct . Overexpression of the tetK, tetA(B), or tetA(C) genes was toxic . When expression was regulated so that resistance to tetracycline was comparable, then the TetA(B) and TetA(C) proteins conferred very similar levels of resistance to a variety of tetracycline derivatives . In contrast, the TetK protein was less capable of conferring resistance to the tetracycline derivatives minocycline, 6-deoxy-6-demethyltetracycline, and doxycycline . The implications for the recognition of various tetracycline substituents by the TetK protein are discussed.

Vet Microbiol, 1993 Feb, 34(2), 139 - 53
Influence of adjuvants on the immune response of sheep to a novel Staphylococcus aureus vaccine; Watson DL et al.; Sheep were immunized twice with two Staphylococcus aureus vaccines which contained either killed bacterial cells shrouded with pseudocapsules or toxoided beta haemolysin, together with various adjuvants . Circulating antibody responses were monitored using an ELISA (anti-pseudo-capsule responses) and an anti-beta haemolysin assay . Combining a killed cell/pseudocapsule/dextran sulphate (DXS) vaccine and the toxoid vaccine did not cause any diminution of antibody responses compared with separate injection of the two preparations . Addition of calcium phosphate to DXS as an adjuvant for the combined vaccine did not extend the duration of anti-pseudocapsule responses compared with those obtained with dextran sulphate alone . Nor was there any benefit in terms of durability of the response by increasing the amount of DXS: doses of DXS of 10-20 mg/kg liveweight provoked significantly higher peak responses but caused acute clinical reactions at the vaccination site and did not prolong the antibody response . In contrast, the combined vaccine given with DXS and emulsified in Freund's Incomplete Adjuvant (FIA) resulted in a large anti-pseudocapsule response with elevated levels of antibody being sustained for at least one year; there was a significant IgG2 anti-pseudocapsule response in animals receiving the vaccine with DXS and FIA . In the above experiments, 10(10) pseudocapsule-shrouded bacterial cells were used in the vaccine . Reducing the concentration of cells to 10(9) caused a slightly reduced anti-pseudocapsule response (not significant) whereas increasing the concentration to 10(11) did not increase the response.

J Pharm Sci, 1993 Feb, 82(2), 170 - 3
Survival of Staphylococcus aureus in oral administration liquid medicaments and influence of count medium on survival; Vivar C et al.; The survival of Staphylococcus aureus was studied in 30 oral administration liquid medicaments (15 syrups and 15 solutions) to determine the effectiveness of the preservatives, the influence of the culture medium used in the enumeration of the surviving microorganisms, and the loss of the enzyme coagulase, phosphatase, DNase (deoxyribonuclease), and thermonuclease . Samples were inoculated with 6.3-6.5 x 10(5) viable cells per milliliter and were stored at room temperature for 60 days . Aliquots were taken for analysis at 0, 15, 22, 30, and 60 days after samples were inoculated . The enumeration of S . aureus was made by most probable number method (MPN) with six liquid culture media: triptone soy (TS), TS with 10% NaCl (TSS), TS and TSS with 0.2% catalase, Mannitol salt, and Tellurite-mannitol-glycine . The survival of S . aureus was lower in solutions than in syrups, decreased with the storage time, and depended on the culture medium utilized in the enumeration . Nonselective media were more sensitive than selective ones; that is, a better percentage of recovery was achieved with TS and the catalase medium . The preservative was effective in 93.3% of the samples . Coagulase was the most stable enzyme and phosphatase, DNase, and thermonuclease disappeared during the storage period.

Clin Infect Dis, 1993 Feb, 16(2), 288 - 9
Menstrual toxic shock syndrome complicated by persistent bacteremia: case report and review; Crowther MA et al.; An unusual case of menstrual toxic shock syndrome (TSS) is described in which the patient had persistent Staphylococcus aureus bacteremia despite therapy with iv cloxacillin . There was no demonstrable evidence of endocarditis or an abscess as a focus for persisting bacteremia . The strain of S . aureus isolated from the blood and vagina produced toxic shock syndrome toxin 1 (TSST-1) and enterotoxin A . Bacteremia occurs uncommonly in association with TSS; however, aggressive high-dose antistaphylococcal therapy should be instituted for treating this possible complication.

Gastroenterol Jpn, 1993 Feb, 28(1), 18 - 24
Interleukin 6 production by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection and primary biliary cirrhosis; Kakumu S et al.; IL-6 production by peripheral blood mononuclear cells (PBMC) was studied in patients with chronic hepatitis B virus (HBV) infection and primary biliary cirrhosis (PBC) using the ELISA method . Spontaneous production of IL-6 was significantly increased in patients with HBeAg+ chronic hepatitis (CH) . The cultures stimulated with lipopolysaccharide and lectin-free interleukin-2 (IL-2) showed enhanced IL-6 production both in controls and all patient groups compared with culture without any stimulation . IL-6 production in response to IL-2 was higher in patients with HBeAg+ CH and PBC than in controls . In PBMC with increased IL-6 production, monocyte function was increased in patients with HBeAg+ CH and PBC, while B cells from PBC showed elevated response to Staphylococcus aureus Cowan 1 . IL-6 production in the presence of HBeAg was greater in anti-HBe+ patients than in HBeAg+ ones . These results suggest that IL-6 response is involved in the immune response in patients with chronic liver disease.

J Biomed Mater Res, 1993 Feb, 27(2), 233 - 7
Application of the quinolone antibiotic ciprofloxacin to Dacron utilizing textile dyeing technology; Phaneuf MD et al.; Prosthetic arterial graft infection continues to be a significant and often devastating complication of vascular surgery . The organisms Staphylococcus aureus (S . aureus) and Staphylococcus epidermidis (S . epidermidis) are the primary pathogens causing acute and late graft infections, respectively . The objective of this study was to develop an infection-resistant prosthetic arterial graft by applying the bacteriocidal quinolone antibiotic ciprofloxacin to polyethylene terepthalate (Dacron) via thermofixation (pad/heat), a new application method founded on established textile procedures . We hypothesize that the limited fibrophilic characteristics of ciprofloxacin will permit binding to Dacron and at the same time allow persistent controlled release over an extended period of time . Using pad/heat technology, 33 micrograms (+/- 2.97 micrograms, n = 12) of ciprofloxacin was successfully bound to a 1-cm2 piece of woven Dacron . A full complement of microbiologic assays demonstrated superior, sustained antistaphylococcal activity of the pad/heat Dacron when compared to Dacron dipped into an equivalent concentration of ciprofloxacin . The sustained antimicrobial efficacy of ciprofloxacin pad/heat-treated Dacron opens new avenues in the development of infection-resistant biomaterials based on an understanding of textile chemistry.

Eur J Biochem, 1993 Feb 1, 211(3), 843 - 9
The primary structure of turtle Cu,Zn superoxide dismutase . Structural and functional irrelevance of an insert conferring proteolytic susceptibility; Schinina ME et al.; A copper,zinc superoxide dismutase, has been isolated from the marine turtle Caretta caretta and the complete amino acid sequence obtained . The sequence was determined by isolation and analysis of peptides obtained after cleavage of the carboxymethylated apoenzyme with trypsin or Staphylococcus aureus protease . Turtle superoxide dismutase consists of 166 amino acid residues, which represents the largest number to date for a cytosolic copper,zinc superoxide dismutase . The comparison of this amino acid sequence with that of bovine superoxide dismutase revealed a one-residue C-terminal extension, two single residue insertions and a 12-residue insertion in the N-terminal region, in turtle superoxide dismutase . The new segment consists of a threefold repeating sequence and was found to be the site for selective proteolytic attack by trypsin under native conditions . The biochemical characteristics, the spectroscopic and catalytic properties as well as the thermal stability and the resistance to irreversible denaturation, were carefully examined and were very similar to those of other superoxide dismutases . These results indicate that the presence of the new polypeptide segment does not affect the main folding of the chain and the quaternary structure, nor the functional parameters of turtle superoxide dismutase . The possibility that the new insert constitutes a loop excluded from the protein scaffold providing the framework of the active site is also discussed.

Scand J Immunol, 1993 Feb, 37(2), 245 - 50
Leukaemic T cells from patients with chronic lymphocytic leukaemia of T-cell origin respond to Staphylococcus aureus enterotoxin superantigens; Metzger R et al.; We investigated the in vitro responsiveness of peripheral blood lymphocytes from two patients with T-cell chronic lymphocytic leukaemia (T-CLL) to Staphylococcus aureus enterotoxin (SE) superantigens . T-cell receptor (TcR) alpha beta (V beta 7.1)-expressing CD4+ leukaemic T cells from patient HE (white blood cell count 480,000/microliters) proliferated in response to SEA and, only at 1000-fold higher concentrations, to SEB, SED, and SEE . CD4+CD8+ TcR alpha beta (V beta 12.1)-expressing leukaemic T cells from patient KO (white blood cell count 120,000/microliters) were activated by SEB but not by the other tested SEs . In both instances, the activation of leukaemic T cells by SE was dependent on the presence of HLA-DR+ cells . Southern blot analysis of TcR beta gene rearrangement confirmed that the proliferating cells were derived from the leukaemic T-cell clone and not from contaminating normal T cells . These data indicate that leukaemic T cells from patients with T-CLL exert a clonally variable responsiveness to SE superantigens . We conclude that recognition of specific antigen and subsequent signal transduction can be initiated via the TcR of leukaemic T-CLL cells.

J Clin Microbiol, 1993 Feb, 31(2), 467 - 9
Type 5 and 8 capsular polysaccharides are expressed by Staphylococcus aureus isolates from rabbits, poultry, pigs, and horses; Poutrel B et al.; A total of 103 Staphylococcus aureus isolates from rabbits (n = 37), poultry (n = 33), pigs (n = 27), and horses (n = 6) and 14 Staphylococcus intermedius isolates from wild animals were serotyped for capsular polysaccharide types 5 and 8 by an enzyme-linked immunosorbent assay using polyclonal rabbit antibodies . About 98% of the S . aureus isolates were typeable . Type 5 was predominant in the poultry (75.8%) and pig (66.7%) isolates, whereas type 8 was more frequent among the isolates from rabbits (59.5%) and horses (83.3%) . By contrast, none of the 14 S . intermedius isolates was typeable.

J Clin Microbiol, 1993 Feb, 31(2), 227 - 32
Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships; Schlichting C et al.; Sixty-nine Staphylococcus aureus isolates from two epidemiologically unrelated sources were typed by pulsed-field gel electrophoresis after SmaI digestion of chromosomal DNA (genome typing), and the results were compared with those obtained by other typing methods: phage typing with the international set of phages, capsular serotyping with monoclonal antibodies against capsular polysaccharides type 5 and 8, and zymotyping by polyacrylamide agarose electrophoresis for esterase polymorphism . A good correlation of S . aureus types was found by these four typing methods . Differentiation increased in the order capsular typing < zymotyping < phage typing < genome typing, yielding 2, 10, 20, and 26 different S . aureus types, respectively . Five of the 26 genome types were further divided into several subtypes revealing clonal relationships . When 36 French S . aureus isolates were compared with 33 German S . aureus isolates, 3 strains representing clonal populations were identical in both groups . S . aureus isolates from patients with cystic fibrosis were also typed at the beginning and the end of a 4-week summer camp for these patients . The results suggested a possible strain transmission during the summer camp . We conclude that genome typing by pulsed-field gel electrophoresis is a powerful tool not only for strain identification but also for the resolution of the clonal relationships of S . aureus strains.

Epidemiol Infect, 1993 Feb, 110(1), 79 - 86
Crystal violet reactions of Staphylococcus aureus strains colonizing infants in the first six weeks; Hudson SJ et al.; Nasal colonization with Staphylococcus aureus occurred in 18% of babies leaving a maternity unit and had risen to 40% by 6 weeks after birth . S . aureus was first acquired by 34.5% of babies after discharge . Female infants were more likely to be colonized than males . Colonization was not significantly different between babies receiving standard postnatal care and those nursed on the Special Care Baby Unit . Crystal violet (CV) tests showed that purple-reacting isolates accounted for approximately 60% of strains, whether first detected at hospital discharge or subsequently acquired . Purple-reacting strains, once acquired, were significantly better able to persist than non purple-reacting strains and formed a cumulatively higher proportion of the strains isolated at 6 weeks after birth than at hospital discharge . CV purple-reactions were significantly associated with lysis by phages of groups III and I and non-purple-reactions were significantly associated with lysis by phages of group II and/or 94/96 . Maternity units remain a significant route whereby strains of S . aureus with some characteristics associated with a hospital origin gain access to the community.

Arthritis Rheum, 1993 Feb, 36(2), 234 - 42
Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin-4; Chomarat P et al.; OBJECTIVE . To assess CD23 status in rheumatoid arthritis (RA) patients, as defined by the levels of CD23 expression on peripheral blood mononuclear cells (PBMC), the levels of soluble CD23 (sCD23) in sera, and the production of sCD23 by PBMC cultures and its regulation by interleukin-4 (IL-4) . METHODS . CD23 expression as determined by double fluorescence-activated cell sorter analysis and sCD23 production as determined by immunoradiometric assay were investigated in 24 RA patients and 21 controls . Soluble CD23 was measured in sera and supernatants of PBMC, activated with polyclonal activators (pokeweed mitogen {PWM} or Staphylococcus aureus Cowan strain 1, {SAC}) used either alone or in combination with IL-2 or IL-4 . RESULTS . The percentage of B cells expressing CD23 and serum levels of sCD23 were increased in patients with RA . IL-4 was a potent inducer of sCD23 production in supernatants, whereas IL-2 was inactive . Costimulation with SAC or PWM did not increase the effect obtained with IL-4 alone . When sCD23 levels in RA and control supernatants were compared, spontaneous production was found to be increased in RA PBMC . This difference from control values was even more pronounced when sCD23 levels in PBMC and purified B cells in response to IL-4, either alone or in combination with SAC or PWM, were tested . In the same supernatants, the increased secretion of sCD23 induced by IL-4 was associated with an inhibitory effect of IL-4 on Ig production, a phenomenon that was more pronounced in RA PBMC than in controls . CONCLUSION . CD23 status in RA is characterized by increased expression of CD23 on B cells, increased production of sCD23 in sera and supernatants, and increased sensitivity of RA PBMC and B cells to IL-4.

Clin Exp Immunol, 1993 Feb, 91(2), 249 - 56
Defective IL-6 secretion in HIV-infected haemophilia patients; Weimer R et al.; To study the role of IL-6 in HIV-induced B cell defects, in vitro B cell responses and IL-6 secretion were determined simultaneously in 67 haemophilia patients . Twenty-three patients were HIV- (Group 1), 27 HIV+ stage CDC II, III (Group 2), and 17 were HIV+ stage CDC IV (Group 3) . Pokeweed mitogen (PWM) was used for T cell-dependent and Staphylococcus aureus Cowan I (SAC I) for T cell-independent B cell stimulation . B cell differentiation was assessed in a reverse haemolytic plaque assay and by ELISA determination of IgG and IgM in culture supernatants . An ELISA was used to measure IL-6 in plasma and culture supernatants . HIV- patients showed impaired immunoglobulin-secreting cell (ISC) responses after T cell-independent and T cell-dependent stimulation (P < 0.0001 and P < 0.01, respectively), whereas IL-6 secretion, IgM and IgG responses were comparable to those in healthy controls . HIV+ patients at stage CDC II, III or IV demonstrated significantly reduced mitogen-stimulated IL-6 secretion (P < 0.05, PWM; P < or = 0.001, SAC I) as well as impaired ISC and IgG responses (P < 0.01, PWM; P < or = 0.0001, SAC I) . CDC IV patients showed reduced IgM responses in addition (P < 0.02, PWM; P < 0.0005, SAC I) . Plasma IL-6 levels were elevated both in HIV+ patients (CDC II, III patients: 165 +/- 73 pg/ml, P < 0.005; CDC IV patients: 58 +/- 18 pg/ml, P < 0.0001) and in HIV- patients (283 +/- 65 pg/ml, P < 0.0001) which appeared to be a T cell effect induced by treatment with haemophilia factor concentrates . Our data provide evidence for different types of B cell deficiencies in HIV- patients (impaired ISC response only) and HIV+ patients (impaired ISC as well as IL-6 and IgM/IgG responses) . The defective IL-6 secretion in HIV+ patients is likely to affect terminal B cell differentiation and this may explain the reduced immunoglobulin secretion in these patients in response to antigenic challenge.

Am J Surg, 1993 Feb, 165(2), 203 - 7
Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock; Livingston DH et al.; Standard doses of antibiotic administered by intermittent infusions after hemorrhagic shock have decreased efficacy in combating infection . This study compared identical quantities of cefazolin administered after shock as intermittent doses or as continuous infusions in a subcutaneous abscess model . One hour after resuscitation from shock, rats were inoculated with 2 x 10(8) Staphylococcus aureus subcutaneously on the dorsum and divided into three groups: (1) control rats, which received no drug treatment; (2) rats in the intermittent group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, then every 8 hours for three doses, and (3) rats in the continuous infusion group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, followed by cefazolin, 90 or 180 mg/kg, intraperitoneally by continuous infusion more than 24 hours after inoculation . Seven days after the inoculation, abscess number, diameter, and weight were measured . Rats that received either dosage of cefazolin intermittently had the same abscess rate after shock as control rats . Rats that received a continuous infusion of cefazolin at either dose had 56% fewer abscesses than control rats . Abscess diameter and weight decreased with increasing quantities of cefazolin, and abscesses were always smaller in rats receiving the continuous infusion . There were no differences in peak subcutaneous cefazolin levels between the intermittent and continuous groups . Continuous infusion provided significantly more cefazolin to the tissue than an equivalent quantity of cefazolin delivered as intermittent doses . These data demonstrate that continuous infusion of cefazolin provided more antibiotic to the tissue and was superior to intermittent injection in reducing infection after hemorrhagic shock.

J Exp Med, 1993 Feb 1, 177(2), 523 - 7
Interferon gamma inhibits interleukin 10 production by monocytes; Chomarat P et al.; Interleukin 10 (IL-10) was first described for its ability to inhibit interferon gamma (IFN-gamma) production . Herein, we studied the balance between IFN-gamma and IL-10 production by human peripheral blood mononuclear cells (PBMC) in response to Staphylococcus aureus Cowan (SAC) or lipopolysaccharide (LPS) . Monocyte depletion reduced IL-10 production by 90% and resulted in an increased IFN-gamma production . Addition of anti-IL-10 antibody to PBMC cultures also strongly increased IFN-gamma production . In contrast, among various cytokines, only IFN-gamma strongly reduced IL-10 synthesis by SAC- or LPS-activated PBMC and monocytes . Thus, IFN-gamma has proinflammatory effects through the combination of two mechanisms: (a) induction of early tumor necrosis factor alpha (TNF-alpha) and IL-1 beta synthesis; and (b) inhibition of the delayed production of IL-10, an inhibitor of TNF-alpha and IL-1 beta synthesis . Taken together, the present data indicate that IFN-gamma and IL-10 antagonize each other's production and function.

J Exp Med, 1993 Feb 1, 177(2), 511 - 6
Lipopolysaccharide-induced selective priming effects on tumor necrosis factor alpha and nitric oxide production in mouse peritoneal macrophages; Zhang X et al.; Preculture of thioglycollate-elicited C3HeB/FeJ mouse peritoneal macrophages in vitro with subthreshold stimulatory concentrations of lipopolysaccharide (LPS) can induce hyporesponsiveness (desensitization) to both tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) production when these cells are subsequently stimulated with 100 ng/ml of LPS . We have established, however, that the primary dose of LPS required for inducing downregulation of NO production is significantly lower than that required for inducing downregulation of TNF-alpha production . Further, when LPS-pretreated macrophages become refractory to subsequent LPS stimulation for NO production, the secondary LPS-stimulated TNF-alpha production is markedly enhanced, and vice versa . These results indicate that LPS-induced TNF-alpha and NO production by macrophages are differentially regulated, and that the observed desensitization process may not reflect a state in which macrophages are totally refractory to subsequent LPS stimulation . Rather, our data suggest that LPS-pretreated macrophages become selectively primed for differential responses to LPS . The LPS-induced selective priming effects are not restricted to LPS stimulation, but extend as well to stimuli such as zymosan, Staphylococcus aureus, and heat-killed Listeria monocytogenes.

Infect Immun, 1993 Feb, 61(2), 768 - 71
The gamma-hemolysin locus of Staphylococcus aureus comprises three linked genes, two of which are identical to the genes for the F and S components of leukocidin; Cooney J et al.; The Staphylococcus aureus gamma-hemolysin comprises two polypeptides, whereas the gamma-hemolysin locus (hlg) contains three open reading frames . The hlgA and hlgB genes encode the gamma 1 and gamma 2 components, respectively . The HlgB protein (gamma 2) has 27% residue identity with S . aureus alpha-toxin . Surprisingly, hlgB and hlgC are 98.5 and 99.1% identical to the lukF and lukS genes, respectively, encoding the F and S components of the Panton-Valentine leukocidin.

Infect Immun, 1993 Feb, 61(2), 580 - 7
Sequencing of leucocidin R from Staphylococcus aureus P83 suggests that staphylococcal leucocidins and gamma-hemolysin are members of a single, two-component family of toxins; Supersac G et al.; A 2,813-bp HincII-ClaI DNA fragment encodes the two S and F components (LukS-R and LukF-R) of leucocidin R (Luk-R) which are secreted by Staphylococcus aureus P83 . The two genes (lukS-R and lukF-R) belong to a single operon . Two peptidic sequences were deduced: LukS-R is a 35,721-Da polypeptide of 315 amino acids, including a signal sequence of 29 residues, and LukF-R is a 36,838-Da polypeptide of 325 amino acids, including a signal sequence of 25 residues . LukS-R and LukF-R were expressed in Escherichia coli and purified from the periplasmic space . Luk-R exerts biological activities on polymorphonuclear cells and on erythrocytes from various animals . Comparison of the amino acid sequence of LukF-R with that of the B component of gamma-hemolysin (HlgB), those of the F and S components of another recently sequenced staphylococcal leucocidin, and those of a few peptides of the F component from Panton-Valentine leucocidin suggests that all four toxins belong to a single, two-component family of toxins.

J Infect Dis, 1993 Feb, 167(2), 312 - 22
Adhesion of Staphylococcus aureus to surface-bound platelets: role of fibrinogen/fibrin and platelet integrins; Herrmann M et al.; Platelets adhering to artificial or biologic surfaces have been implicated in the pathogenesis of catheter infections or endocarditis; however, the ligands involved in Staphylococcus aureus interaction with adherent platelets remain incompletely understood . Radiolabeled S . aureus Cowan I were incubated with purified platelets adherent to polymethylmethacrylate (PMMA) coverslips and washed, and adhesion was determined . Platelets promoted adhesion of S . aureus approximately 30-fold compared with adhesion to albumin-PMMA . In the presence of both plasma (1% vol/vol) and platelets, adhesion was extensively promoted, with 30% (of inoculated) S . aureus adherent (150-fold increase) . Platelet pretreatment with anti-GPIIb/IIIa monoclonal antibodies or inhibitors of platelet activation decreased plasma-enhanced adhesion, suggesting a role of platelet activation in S . aureus adhesion . Plasma-enhanced adhesion was sensitive to thrombin antagonists, proteinase inhibitors, heparin, or antifibrinogen antibodies, indicating that fibrinogen/fibrin is necessary for bridging between adherent platelets and S . aureus . In conclusion, S . aureus adhesion to immobilized platelets may play a role in the pathogenesis of invasive bloodstream infections or endocarditis.

Leukemia, 1993 Feb, 7(2), 226 - 34
Interleukin-2 enhances the production of tumor necrosis factor-alpha in activated B-type chronic lymphocytic leukemia (B-CLL) cells; Larsson LG et al.; Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a regulator growth and differentiation of normal and malignant B cells . We utilized a selected clone (I-83) of primary resting B-type chronic lymphocytic leukemia (B-CLL) cells, inducible to activation, growth and differentiation in vitro, as a model system to study the possible role of TNF-alpha as an autocrine growth factor for such cells . Our results show that unstimulated I-83 B-CLL cells produced a low level of TNF-alpha mRNA, as shown by Northern blot analysis, and cytoplasmic TNF-alpha, determined in individual cells by immunocytochemistry . Secreted TNF-alpha could, however, not be detected in the medium by ELISA . TNF-alpha synthesis and secretion was, however, induced to high levels by stimulation of the B-CLL cells with interleukin-2 (IL-2) after activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) or Staphylococcus aureus Cowan strain I (SAC) and B-cell stimulatory factor-MP6 (thioredoxin) . A moderate increase in TNF-alpha secretion was also induced by TPA or IL-2 alone . IL-4 did not have any major effects on the production of TNF-alpha in activated cells, but inhibited the IL-2-induced production of TNF-alpha in SAC-activated cells . The cell surface expression of TNF-alpha receptors (TNF-R), as determined by binding assay using 125I-labelled recombinant TNF-alpha (rTNF-alpha), was also induced after SAC or TPA activation, but shed receptors (TNF-binding proteins) were only observed after TPA activation . Exogenously added rTNF-alpha in combination with TPA or SAC induced a high level of DNA synthesis in I-83 B-CLL cells . The increased endogenous production and secretion of TNF-alpha during induced growth stimulation, the induced expression of TNF-R, and the mitogenic effect of TNF-alpha on activated B-CLL cells raise the question whether TNF-alpha may function as an autocrine co-stimulator of B-CLL cell growth as recently suggested . anti-TNF-alpha and anti-TNF-R antibodies, however, failed to inhibit the IL-2- and IL-4-induced proliferation of activated I-83 B-CLL cells.

Jpn J Antibiot, 1993 Feb, 46(2), 154 - 8
{Transferability of vancomycin to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus}; Haruta T et al.; The transferability of vancomycin (VCM) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus . VCM was administered intravenously for 30 minutes at a dose level of 30 mg/kg . Serum concentration reached a maximum of 75 +/- 3.80 micrograms/ml (mean +/- S.E.) at the completion of administration (i.e., 30 minutes) and CSF concentration reached a maximum of 2.4 +/- 0.39 micrograms/ml at 60 minutes . Pharmacokinetic parameters calculated from this concentration-time curve were as follows: Cmax (CSF/Serum) 3.21%, AUC (CSF/Serum) 2.39% between 15 and 60 minutes, 3.99% between 15 and 120 minutes, and 4.40% between 15 and 150 minutes . T 1/2 for VCM in CSF: 143 minutes, T1/2 (CSF/Serum):2.09 . Based on this investigation, VCM appears to be effective in the treatment of meningitis caused by MRSA (Methicillin-resistant S . aureus).

Jpn J Antibiot, 1993 Feb, 46(2), 142 - 53
{In vitro effects of combinations of antibiotics against highly-fosfomycin-resistant, methicillin-resistant Staphylococcus aureus . With special reference to efficacies of combinations of imipenem/cilastatin and cephems}; Kouda M; The author evaluated in vitro effects of combinations of antibiotics against 27 clinical isolates of highly-fosfomycin (FOM)-resistant, methicillin-resistant Staphylococcus aureus (MRSA) . In combinations of FOM and cephems (CEPs), MICs of CEPs were decreased by FOM significantly, and synergistic effects were observed when the MIC of FOM was below 50 micrograms/ml . Combinations of imipenem/cilastatin (IPM/CS) and CEPs, however, was superior to those of FOM and CEPs in terms of synergistic effects . In these combinations, good synergism was found when the MIC of IPM/CS was below 25 micrograms/ml and those of CEPs were relatively low . In combinations of aminoglycoside and CEPs, no apparent synergism was observed . Most significant synergistic effect was achieved in the combination between IPM/CS and cefamandole . We believe that both fractional inhibitory concentration indices and achievement rates of effective serum concentrations should be taken into account to determine an effective combination of antibiotics.

Jpn J Antibiot, 1993 Feb, 46(2), 130 - 41
{Enhancement of in vitro antimicrobial activity of cefmetazole and cefazolin in combination against methicillin-resistant Staphylococcus aureus studies by checkerboard MIC method and disc diffusion method using discs containing both drugs}; Matsuo K et al.; Antimicrobial activities of cefmetazole (CMZ) and cefazolin (CEZ) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-sensitive and 47 methicillin-resistant strains) using the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl . MICs of CMZ and CEZ individually against 9 methicillin-sensitive strains (MSSA) were 0.78-1.56 micrograms/ml and 0.39-0.78 micrograms/ml without 4% NaCl, and 1.56-3.13 micrograms/ml and 0.39-0.78 micrograms/ml with 4% NaCl, respectively . In combination of CMZ and CEZ, the MICs of CMZ and CEZ against these MSSA decreased to 0.012-0.39 micrograms/ml and 0.10-0.20 micrograms/ml without 4% NaCl, and 0.20-0.78 micrograms/ml and 0.20-0.39 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.385 to 1.013 . Minimum FIC indexes < or = 0.5 were seen in 7 out of 9 strains . MICs of CMZ and CEZ individually against 47 methicillin-resistant strains (MRSA) were 3.13-100 micrograms/ml and 3.13-400 micrograms/ml without 4% NaCl, and 6.25-50 micrograms/ml and 50-400 micrograms/ml with 4% NaCl, respectively . In combination of CMZ and CEZ, MICs of these drugs against MRSA were reduced to 0.10-50 micrograms/ml and 0.39-200 micrograms/ml without addition of 4% NaCl and 0.39-12.5 micrograms/ml and 3.13-100 micrograms/ml with 4% NaCl, respectively . Minimum FIC indexes observed were 0.047 to 0.625, and those with values < or = 0.5 were observed in 43 out of 47 strains . By the disc diffusion method, between the CMZ disc and CEZ disc, a synergistic interaction against MRSA was well observed . In addition, discs containing both drugs showed a greater inhibitory zone diameter than discs containing the equivalent amount of CMZ or CEZ alone . These in vitro observations reported here suggest that the use of CMZ and CEZ in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection, as well as for surgical prophylaxis . Therefore, further study was carried out to assess the synergistic enhancement of antimicrobial activity of CMZ and CEZ in combination using discs containing various amounts of these drugs at various ratios . Using discs containing CMZ/CEZ (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CEZ in combination . From inhibitory zone diameters obtained with these combination discs, enhanced MICs of CMZ or CEZ in combination can be assessed.

Jpn J Antibiot, 1993 Feb, 46(2), 123 - 9
{Bacteriological evaluations of combination effects with cefotiam and other antimicrobial agents against methicillin-resistant Staphylococcus aureus . II . Synergistic actions of cefotiam with arbekacin and minocycline}; Deguchi K et al.; We assessed the bacteriological efficacies of cefotiam (CTM) plus arbekacin (ABK) and CTM plus minocycline (MINO) therapies against methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro system . The results are summarized as follows . 1 . Both of CTM+ABK and CTM+MINO demonstrated almost perfect antibacterial activities against MRSA strains at ABK and MINO concentrations of MIC levels as clinically expected plasma ABK or MINO levels, and also showed antibacterial activities at ABK or MINO concentrations of sub-MIC levels . But no results suggesting antagonism were obtained . 2 . The potent antibacterial effect of CTM+ABK or CTM+MINO against MRSA strains was considered to be the result of damage to the cellular membrane of target strains by ABK or MINO with ABK or MINO concentrations at MIC or sub-MIC levels and by the subsequent antibiotic effect of CTM . 3 . A combination of drugs which are different from each other in mechanisms of action and points of action is likely to show a consistent antibacterial effect, but a combination of drugs which are competitive to each other because they share mechanism and point of action possibly cause antagonism.

Jpn J Antibiot, 1993 Feb, 46(2), 115 - 22
{Bacteriological evaluations of combination effects with cefotiam and other antimicrobial agents against methicillin-resistant Staphylococcus aureus . I . Synergistic actions of cefotiam with imipenem and vancomycin}; Deguchi K et al.; We assessed the bacteriological efficacies of cefotiam (CTM) plus imipenem (IPM) and CTM plus vancomycin (VCM) therapies against methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro system . The results are summarized as follows . 1 . It appeared that the bacteriological efficacies of CTM+IPM therapy against MRSA strains were different against different target MRSA strains . In other words, the FIC indices of CTM+IPM were distributed in a wide range of < or = 0.5- > 2.0 . The strains showing MIC levels of < or = 8 micrograms/ml in IPM concentrations showed a strong correlation with FIC index values of < or = 0.5, and the strains showing the MIC level of > or = 128 micrograms/ml in IPM concentration showed a strong correlation with FIC index values of > 2.0 . Hence, the strains showing FIC indices < or = 0.5 were considered to be newborn strains with penicillin-binding protein 2' (PBP-2'), those showing FIC indices > 0.5- < or = 2.0 were considered to be strains with increasing production in PBP-2', and those showing FIC indices > 2.0 were considered to be strains with increasing productions in both PBP-2' and PBP-m2 . In strains with FIC indices higher than 2.0, the 2 drugs may possibly share the action mechanism and the activity center thus they compete with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Aust N Z J Surg, 1993 Feb, 63(2), 116 - 9
Septic arthritis of the hip in infancy; Little DG et al.; A retrospective study was undertaken of 24 infants with septic arthritis of one or both hips who presented to the Children's Hospital, Camperdown, during the 15 year period from 1973 to 1989 . Staphylococcus aureus was found to be the most common pathogen . Umbilical catheterization was a significant aetiological factor in seven of 10 neonates studied . Young premature infants had the poorest outcome in regard to permanent bony changes in the upper femur, hip instability and leg length discrepancy . In patients with unstable and severely damaged upper femora, late salvage procedures were found to be unsatisfactory.

Lik Sprava, 1993 Feb-Mar, (2-3), 95 - 7
{The diagnostic importance of antibodies to the cell wall peptidoglycan of Staphylococcus in the blood serum of children with a staphylococcal infection}; Pozur VK et al.; High titers of antibodies to peptidoglycan of staphylococcus aureus were found in children with purulent-inflammatory diseases of staphylococcal etiology . This may be used for the diagnosis of staphylococcal infection.

Cell Immunol, 1993 Feb, 146(2), 238 - 48
Regulation of human B cell responsiveness by interferon-alpha: interferon-alpha-mediated suppression of B cell function is reversed through direct interactions between monocytes and B cells; Oka H et al.; Previous studies have revealed that interferon-alpha (IFN-alpha) suppresses the B cell responses stimulated with Staphylococcus aureus (SA) + IL-2 in the complete absence of monocytes but enhances the responses of B cells contaminated with monocytes . The current studies therefore examined in detail the combined effects of IFN-alpha and monocytes on the B cell responses induced by SA + IL-2 . Monocytes overcome the suppressive effects of IFN-alpha on the IgM production induced by SA + IL-2 . Thus, in the presence of monocytes, IFN-alpha enhanced the IgM production by B cells stimulated with SA + IL-2 . IFN-alpha still enhanced the IgM production induced by SA + IL-2 in the presence of monocytes and indomethacin . The IFN-alpha-mediated suppression of B cell responsiveness was not overcome by addition of factors generated from SA-activated monocytes, or any of IL-1 beta, IL-6, and TNF-alpha . Of note, the IFN-alpha-mediated suppression of B cell responsiveness was overcome only when B cells and monocytes were allowed to contact with each other . This reversal of the IFN-alpha-mediated suppression of B cell function was not blocked by any of the mAb to CD11a, CD18, CD54, or monomorphic determinants of HLA-DR . These results indicate that IFN-alpha enhances the B cell responses induced by SA + IL-2 through direct interactions between monocytes and B cells that do not involve lymphocyte-function-associated-1 molecules, intercellular adhesion molecule-1, or HLA-DR antigens . Thus, the data demonstrate the presence of unique direct interactions between B cells and monocytes that regulate human B cell responsiveness.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1993 Feb, 26(1), 44 - 50
Crusted scabies in systematic lupus erythematosus: a case report; Chen DY et al.; Crusted scabies (Norwegian scabies) is uncommon in clinical practice and may present as papulosquamous dermatosis . A case of crusted scabies in systemic lupus erythematosus (SLE) is described . The skin lesions simulated those of subacute cutaneous lupus erythematosus of the papulosquamous type, and became the source of epidemic scabies in the hospital . The colonization with Staphylococcus aureus within crusted lesions may have contributed to the patient's sepsis . This case illustrates the pitfalls in recognition of crusted scabies and the importance of rapid diagnosis.

Mol Mar Biol Biotechnol, 1993 Feb, 2(1), 28 - 40
Purification and properties of a catechol oxidase from blood cells of the ascidian Pyura stolonifera; Watters D et al.; A catechol oxidase (EC 1.10.3.1) was purified to homogeneity from blood cells of the ascidian Pyura stolonifera using gel filtration on Sephadex G-50 and hydrophobic interaction chromatography on PhenylSuperose . Two peaks of activity were eluted from PhenylSuperose, one with a decreasing salt gradient and the other with nonionic detergent . The latter represents an aggregated form of the enzyme . The enzyme has a molecular weight of 56 kd and shows a preference for catechols with uncharged hydrophobic side chains (e.g., 4-t-butylcatechol) but does not hydroxylate free tyrosine . Inhibition of the enzyme by diethyldithiocarbamic acid and thiol reagents implicate copper at the active site . Sequence analysis of a peptide generated by incubation with Staphylococcus aureus V8 protease demonstrated considerable homology to one of the conserved copper binding regions of tyrosinases . This enzyme is found in the same cells as the dopa-containing protein ferreascidin . When ferreascidin is incubated with the enzyme, its spectrum changes rapidly, indicating that the catechol oxidase uses it as a substrate . The P . stolonifera enzyme differs from an enzyme involved in adhesion, isolated from the mussels, M . edulis and G . demissa: it is isolated as a soluble enzyme that does not appear to exist as a latent precursor.

J Formos Med Assoc, 1993 Feb, 92(2), 110 - 6
Valve ring abscess associated with infective endocarditis: echocardiographic features and clinical observations; Hwang JJ et al.; The presence of a valve ring abscess in patients with infective endocarditis adds appreciably to the expected rates of morbidity and mortality . From January 1989 to October 1991, a total of 43 consecutive patients with infective endocarditis seen at National Taiwan University Hospital were enrolled in this study . There were 30 men and 13 women, ranging in age from 14 to 75 years (mean +/- SD 38.5 +/- 15.0 years) . The presence of infective endocarditis was documented by surgery in 26 patients and was based on a clinical diagnosis in the remaining 17 patients . A valve ring abscess was detected in five patients, either by transthoracic or transesophageal echocardiography, and all were confirmed at surgery . Aortic valve endocarditis was more frequently found in patients with valve ring abscesses (100% vs 31.6%, p < 0.01), and the infecting organism was most often Staphylococcus aureus (60.0% vs 15.8%, p < 0.05) . The proportion of urgent operations was also higher in the group with abscesses (80.0% vs 23.7%, p < 0.05) . The hospital mortality was 40.0% in patients with abscesses and 5.3% in patients without abscesses, but the difference did not reach significance (p = 0.056) . Transthoracic echocardiography identified valve ring abscesses in the first three patients, but transesophageal echocardiography was more useful in detecting abscesses located in the posterior aspect of the aortic root in the other two patients, in which the lesion was overlooked or only suspected by the transthoracic approach.(ABSTRACT TRUNCATED AT 250 WORDS)

J Hosp Infect, 1993 Feb, 23(2), 123 - 31
Catheter-related Staphylococcus aureus infections; Knudsen AM et al.; Among 3394 patients with Staphylococcus aureus bacteraemia from the years 1986-89, 88 patients were found whose intravenous catheter and blood grew organisms of the same phage type . Strains of phage type 95 were more frequent among the patients with confirmed catheter-related bacteraemia than among other bacteraemia cases . Strains with particular phage-type patterns occurring with increasing frequency in Denmark during recent years also occurred with significantly higher frequencies among the confirmed catheter-related bacteraemias . No major differences in antibiotic resistance were observed . Patients with catheter-related bacteraemia had, in spite of a higher frequency of underlying diseases, a lower mortality compared with other bacteraemia patients, and endocarditis occurred less frequently (2% vs . 6%) . Among 201 S . aureus isolates from catheters in 1988 only strains of group I occurred with increased frequency . The possible role of catheters as selection pressure on the S . aureus population is discussed.

Biull Eksp Biol Med, 1993 Feb, 115(2), 178 - 80
{Characteristics of antilysozyme activity of Staphylococcus aureus in various types of experimental infection course}; Bukharin OV et al.; The connection between the level of Staphylococcus Aureus anti-lysozyme activity (ALA) and the character of the experimental infection course has been revealed . The subsiding type of infection was developed by infecting by clones with the low ALA and at the same time there was a shift in the structure of population at the final stage of infectious process to the reduction of its heterogeneity in respect of ALA and the preservation of the colonies only with the zero and low ALA . The protracted form of infection was provoked by the clone with the high ALA and the dynamics of microbial dissemination had rhythmical nature and a high heterogeneity in respect of ALA in the structure of population of staphylococcus was preserved and the selection of colonies with the high ALA was observed . ALA of staphylococcus is an important link of pathogenesis of persistence as it determines the duration and dynamics of the survival of the pathogen in the organism.

Biol Pharm Bull, 1993 Feb, 16(2), 178 - 81
Mode of action of an antimicrobial peptide, tachyplesin I, on biomembranes; Katsu T et al.; An antimicrobial peptide, tachyplesin I, isolated from hemocytes of the horseshoe crab, Tachypleus tridentatus, increased the K+ permeability of Staphylococcus aureus and Escherichia coli cells, concomitantly reducing cell viability . At a higher concentration range, this peptide also enhanced the permeability of human erythrocytes . Tachyplesin decreased the phase transition temperature of an artificial membrane composed of dipalmitoylphosphatidylglycerol and, further, broadened it extensively, while it did not affect that of dipalmitoylphosphatidylcholine membrane . The latter result related closely to the fact that this peptide acted weakly on erythrocytes in which acidic lipids constitute a minor portion . Tachyplesin altered the normal discoid shape of human erythrocytes to a crenated form, suggesting that the peptide accumulated predominantly in the outer half of the membrane bilayer and destabilized the membrane structure, thus causing the change in permeability . The mode of action of tachyplesin was compared with that of gramicidin S, a peptide forming an amphiphilic structure analogous to tachyplesin.

Cell Struct Funct, 1993 Feb, 18(1), 53 - 60
Inhibition of cell adhesion by proteolytic fragments of type V collagen; Hatai M et al.; Type V collagen inhibits the cell-substratum adhesion of many types of cells . In this study, inhibitory effects of type V collagen on the adhesion of mouse melanoma B16-F10 cells to fibronectin, laminin and vitronectin were investigated . When the culture dishes were coated with a mixture of fibronectin and type V collagen, adhesion of the cells was inhibited by 50% at a fibronectin/collagen molar ratio of 10/1 . At a similar molar ratio, adhesion of the cells to laminin was inhibited moderately, but that to vitronectin was not significantly affected . Type V collagen added into culture medium was less effective in inhibiting cell adhesion . The antiadhesive activity of type V collagen was partially retained in the alpha 1 (V) chain of heat-denatured collagen . The alpha 1 (V) chain was split into two large fragments, 90 kDa and 60 kDa, by limited digestion with Staphylococcus aureus V8 proteinase . The 90-kDa fragment, which was derived from the C-terminal half of the alpha 1 (V) chain, inhibited the cell adhesion more profoundly than alpha 1 (V) . However, little fibronectin bound to the 90-kDa fragment, while fibronectin bound to the 60-kDa fragment, which was less antiadhesive than the 90-kDa fragment, with the same extent as alpha 1 (V) . We therefore concluded that the antiadhesive effect of type V collagen was not due to its specific binding to the fibronectin molecule.

Eur J Clin Microbiol Infect Dis, 1993 Feb, 12(2), 121 - 4
Enhancement of in vitro bactericidal activity of neutrophils from trauma patients in the presence of granulocyte colony-stimulating factor; Anding K et al.; In order to determine whether granulocyte colony-stimulating factor (G-CSF) can enhance the bactericidal activity of polymorphonuclear leukocytes (PMNL) in trauma patients, PMNL obtained from severely injured patients one or two days after trauma were incubated with G-CSF and Staphylococcus aureus for different periods of time . G-CSF at a concentration of 6000 units/ml significantly improved the antibacterial activity of PMNL in trauma patients (n = 10) and healthy volunteers (n = 12) during the incubation period of 180 min . No difference in the bactericidal function of PMNL could be found between severely injured patients and healthy donors.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 270 - 5
Immunomodulatory effect of fosfomycin on human B-lymphocyte function; Morikawa K et al.; Fosfomycin (FOM) is an unique antibiotic which is chemically unrelated to any other known antimicrobial agent . Recent investigations have demonstrated that FOM inhibits histamine release from basophils . In this study, we examined the effect of FOM on human B-cell functions . FOM inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan 1 in a dose-dependent manner . FOM interfered with the transition from the G0 to the G1 phase of the cell cycle, leading to cell arrest . The proliferative response of in vivo-activated B cells and lymphokine-induced B-cell proliferation were also affected by FOM . In addition, FOM suppressed immunoglobulin secretion by antibody-producing B cells . Interestingly, FOM did not affect the expression of activation antigens such as the CD25 (interleukin-2 receptor) and CD71 (transferrin receptor) antigens . Moreover, FOM sustained the increased Ia expression on B-cell membranes induced by S . aureus Cowan 1 stimulation, which suggests that FOM may not block the role of B cells in antigen presentation in T-cell-B-cell interaction.

Graefes Arch Clin Exp Ophthalmol, 1993 Feb, 231(2), 61 - 5
Cellular fibronectin and tenascin in an orbital nylon prosthesis removed because of infection caused by Staphylococcus aureus; Paallysaho T et al.; An orbital nylon prosthesis was removed because of an infection caused by Staphylococcus aureus that was resistant to antimicrobials . It was processed for histopathology and immunohistochemistry . Within 3 weeks the implant had an extensive ingrowth of fibrovascular tissue containing chronic inflammatory cells, foreign body giant cells, and myofibroblasts . By using the indirect immunofluorescent method, this tissue was found to react with monoclonal antibodies (Mabs) against extradomain A of cellular fibronectin (EDA-cFN) and tenascin (TN) . The presence of EDA-cFN and TN within the implant are indicative of an active healing process, since both of these proteins, scarce in adult tissues, have been shown to be reexpressed during tissue regeneration . The findings suggest that fibronectin plays a definite role in bacterial adherence and foreign body infections.

Pediatr Res, 1993 Feb, 33(2), 209 - 13
A study of the binding of immunoglobulin G and immunoglobulin E from children with bronchial asthma to peptides derived from group II antigen of Dermatophagoides pteronyssinus; Oshika E et al.; The peptides that were produced by the treatment of the purified group II antigen of Dermatophagoides pteronyssinus with cyanogen bromide, lysylendopeptidase, Staphylococcus aureus V8 protease, or N-tosyl-L-phenylalanylchloromethyl ketone-treated trypsin were examined for their binding with IgG and IgE from children with bronchial asthma by immunoblotting analysis . Both IgG and IgE bound to the peptides from the amino terminus to the 76th residue and the carboxyl terminal side from the 13th or 15th residue; on the other hand, both Ig failed to bind to the carboxyl terminal side from the 39th, 56th, or 77th residue . The data demonstrated that peptides lacking residues 1 to 15 possessed the ability to bind Ig, whereas those lacking residues 1 to 39 had lost it . The present study indicates that the amino terminal half of the group II antigen of Dermatophagoides pteronyssinus is more important for the binding of IgG and IgE than the carboxyl terminal half and suggests that the residues 15 to 39 may be directly related to the binding of both IgG and IgE.

Sci Total Environ, 1993 Jan 29, 128(2-3), 141 - 9
Impact of repackaging hazardous (infectious) hospital waste on the indoor air quality of a hospital; Brenniman GR et al.; With landfill bans on the disposal of hazardous (infectious) hospital wastes, many hospitals in the United States are faced with selecting alternative means of disposal . One alternative method of disposal is to repackage the waste and ship it off site for incineration . This paper reports on a study in which airborne bacteria were sampled in an area where waste was repackaged . Results of the sampling showed bacteria concentrations ranging from not detectable (central supply room) to 105 colonies/m3 air (approximately 40 feet from the incinerator room door) . This would seem to indicate that the source of the bacteria was at or near the incinerator room door where the repackaging operation took place . Although some human pathogens were identified, most of the bacteria identified do not represent a serious health threat . However, Staphylococcus aureus was found in air samples collected from locations in the hospital served by the same ventilation system in the area of the repackaging operation . The waste handling practices used in hospitals need to be reevaluated, and the definition of 'sick building syndrome' needs to be expanded beyond chemicals to include microorganisms . More research is needed to characterize bacteria in air and to determine the impact of airborne bacteria on human health.

Biochemistry, 1993 Jan 19, 32(2), 725 - 34
Sequence-specific deamidation: isolation and biochemical characterization of succinimide intermediates of recombinant hirudin; Bischoff R et al.; Natural hirudin variant 2 with a lysine residue in position 47 (rHV2-Lys47) was produced in a genetically engineered strain of Saccharomyces cerevisiae as a secreted protein of 65 amino acids and purified to greater than 99% homogeneity . Only reversed-phase high-performance liquid chromatography (RP-HPLC) using very shallow acetonitrile gradients indicated the presence of a component in the final product (approximately 1% of total protein) with a slightly increased retention time . Using successive RP-HPLC purification steps, this hydrophobic impurity was isolated and separated into two constituents defined as components A1 and A2 which differed from the parent molecule by mass reductions of 17.2 Da (A1) and 17.6 Da (A2), respectively, as determined by electrospray mass spectrometry (ESMS) . Proteolytic digestion with endoprotease Glu-C from Staphylococcus aureus (V8 protease) and analysis of the peptide mixture by ESMS showed that the mass difference between rHV2-Lys47 and component A1 was due to a modification between amino acids 1 and 43, while the corresponding mass difference with component A2 was the result of a modification within the peptide fragment comprising residues 50-61 . Further analyses using amino acid sequencing and ESMS in combination with collision-activated dissociation (CAD) detected modifications at residues Asn33-Gly34 in component A1 and at Asn53-Gly54 in component A2 . Both of these sites were previously shown to be susceptible to spontaneous deamidation under slightly basic pH conditions . Thus, the mass reductions of approximately 17 Da and the fact that both asparagines, Asn33 in component A1 and Asn53 in component A2, proved to be resistant to Edman degradation provided strong support for them being stable succinimide intermediates of the corresponding deamidation reactions . Both intermediates were shown to have inhibition constants for human alpha-thrombin on the order of 1 pM, identical to that of rHV2-Lys47 . The isoelectric point of component A2 was determined to be within 0.01 pH unit of that of the parent molecule by isoelectric focusing in an immobilized pH gradient.

Biochim Biophys Acta, 1993 Jan 18, 1145(1), 51 - 7
Assembly and channel-forming activity of a naturally-occurring nicked molecule of Staphylococcus aureus alpha-toxin; Tomita T et al.; From the culture supernatant of Staphylococcus aureus Wood 46, we obtained a naturally-occurring nicked molecule of staphylococcal alpha-toxin . The nicked alpha-toxin consisted of non-covalently-linked 8-kDa and 25-kDa polypeptides, which were derived, respectively, from the N-terminal and the C-terminal part of the toxin nicked at the peptide bond between Glu-71 and Gly-72 . The nicked toxin, as well as native alpha-toxin, bound to and oligomerized in the liposome membranes composed of choline-containing phospholipids (i.e., phosphatidylcholine and sphingomyelin) and cholesterol, and formed membrane channel in the liposome membranes . However, the channel-forming activity of the nicked toxin, assessed as a toxin-induced carboxyfluorescein leakage from the liposomes, was approx . 20-fold lower than that of native alpha-toxin . Channel-forming activity of the nicked toxin as well as native toxin was inhibited by divalent cations including Zn2+, Cd2+, Ca2+ and Mg2+, and degree of the inhibitory effect of the divalent cations was in the following order: Zn2+ > Cd2+ > Ca2+ > Mg2+ . Thus, although the cleavage of alpha-toxin at the position between Glu-71 and Gly-72 drastically reduced channel-forming activity of the toxin, the nicked toxin retained the ability to oligomerize in phospholipid-cholesterol membranes and the characteristics of channel-forming activity in terms of the specificity for phospholipids and the susceptibility to divalent cations.

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