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Nippon Rinsho, 1992 May, 50(5), 1016 - 9
{The structure and function of the mecA gene in methicillin-resistant Staphylococcus aureus}; Kanno H; Penicillin binding protein (PBP) 2' is the most important mechanism of the resistance to beta-lactams in methicillin-resistant Staphylococcus aureus (MRSA) . And the mecA gene is the coding gene of PBP2', and located in the SmaI fragment G of the chromosome map by Pattle P.A., . A part of the structure of mecA is similar to that of the penicillinase gene . The resistance of MRSA to beta-lactams were influenced by the presence of penicillinase plasmid and the alternation of femA gene.

Nippon Rinsho, 1992 May, 50(5), 1010 - 5
{An attempt to control nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection}; Miyachi N et al.; A strain of Methicillin-Resistant Staphylococcus aureus (MRSA) was first isolated in our hospital in March 1986 . Since then, MRSA has become a difficult pathogen and a cause of sepsis, bacterial endocarditis, and pneumonia in 1988 . Rigorous hospital-wide control measures have been planned . The major control measures, based on the various investigations reported, consist of the following three points; improvement of environmental control, reinforcement of handwashing practices during care and control usage of antibiotics . The frequency of isolation of MRSA among the S . aureus isolates was 43.3% in 1988 and this was further reduced to 31.7% in 1990 . The total number of MRSA isolates from decubitus, bile, and blood samples have also declined . This decline resulted in a reduction of cases of severe MRSA infection . As yet, MRSA strain are still isolated on incubation . There may be a limit to complete control by measures in a single hospital . It is desired that regional measures and national consensus on nosocomial infection be established.

Nippon Rinsho, 1992 May, 50(5), 1004 - 9
{An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA) isolated from medical staffs, inpatients and hospital environments at our hospital}; Nishijima S et al.; Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms which is causative of the nosocomial infections . Recently the incidence of isolation of MRSA is increasing from year to year in Japan . Especially MRSA isolated from inpatients are much higher than from outpatients . Therefore we have done epidemiological studies about MRSA isolated from medical staffs, inpatients and hospital environments in our hospital . Thereafter we examined phage typing and coagulase typing of those MRSA . MRSA were isolated more frequently from anterior nares of inpatients in compare with doctors and nurses . MRSA were isolated more frequently from the environments of MRSA carriers . Coagulase type II and phage type N.T . (not typable) were dominant type of MRSA in our hospital (69% and 61%) . Our studies have revealed that the isolation frequency of MRSA is very high in our hospital . It seems to suggest that inpatients who are carrying MRSA are spreading MRSA out hospital environments and medical staffs.

Intern Med, 1992 May, 31(5), 678 - 81
Lupus nephritis associated with bacterial panperitonitis and lung alveolar hemorrhage; Yano N et al.; A 36-year-old woman was admitted to the hospital with the diagnosis of nephrotic syndrome due to lupus nephritis . The patient had panperitonitis caused by Staphylococcus aureus as a complication, and an emergency laparotomy was performed . After the operation, the patient developed a massive lung alveolar hemorrhage . Methylprednisolone pulse therapy showed a marked effect on the lung hemorrhage . It is known that lung alveolar hemorrhages associated with systemic lupus erythematosus have a very high mortality; the present case is relatively rare because of the good response to steroid pulse therapy.

Cytokine, 1992 May, 4(3), 227 - 31
Interleukin 2 treatment of Staphylococcus aureus mastitis; Reddy PG et al.; A study was conducted in dairy cows to evaluate the efficacy of recombinant bovine interleukin 2 (rBoIL-2) as an adjunct to antibiotic therapy in Staphylococcus aureus mastitis . In normal, non-mastitic cows, intramammary infusion of rBoIL-2 caused a tenfold increase in somatic cell counts (SCC) in milk . Co-administration of 2 mg of rBoIL-2 and sodium cephapirin in cows with established S . aureus mastitis decreased SCC and shedding of S . aureus compared with values from cows that were given only sodium cephapirin or 10 mg rBoIL-2 with sodium cephapirin . Cows in the 2 mg rBoIL-2 group cleared the infection earlier and at 2 weeks after treatment had not relapsed with staphylococcal mastitis . These data suggest that rBoIL-2 may be useful as an immunotherapeutic agent in controlling mastitis.

J Struct Biol, 1992 May-Jun, 108(3), 238 - 44
The three-dimensional structure of trypsin-treated Staphylococcus aureus alpha-toxin; Olofsson A et al.; Trypsin treatment of staphylococcal alpha-toxin cleaves the molecule into two roughly equally sized parts, which results in inactivation of the toxin . Tetragonal arrays of oligomers, closely resembling the native ones, can however be formed on lipid layers . From tilted views of negatively stained crystals a 3D structure to 23 A resolution has been determined by electron microscopy and image processing . On comparison with the 3D structure of the native alpha-toxin (Olofsson et al., J . Mol . Biol . 214, 299-306, 1990) the subdomains are more separated, confirming the differences found when comparing the projection maps (Olofsson et al., J . Struct . Biol . 106, 199-204, 1991) . The tryptic cleavage takes place in a postulated hinge region . The results are consistent with the hypothesis that the conformational change required for inducing the membrane permeabilizing property takes place in this region . Furthermore, we present a refined projection map at approximately 10 A resolution based on the analysis of a large number of crystals using unbending methods.

G Ital Cardiol, 1992 May, 22(5), 567 - 71
{Sepsis and endocarditis: two rare complications following pacemaker implantation . Description of a case and review of the literature}; Vecchi MR et al.; A case of Staphylococcus aureus tricuspid valve endocarditis in a patient with permanent transvenous VVI pacemaker and recurrent febrile episodes is described . Medical treatment was not effective, and only with surgical removal of the lead was the infection successfully treated.

Ann Acad Med Singapore, 1992 May, 21(3), 354 - 60
Infection in continuous ambulatory peritoneal dialysis (CAPD): aetiology, complications and risk factors; Lee GS et al.; Continuous ambulatory peritoneal dialysis (CAPD) was started in the Singapore General Hospital in 1980 . Peritonitis and exit site infections have been the major cause of morbidity and catheter loss in CAPD . In 1990, 130 patients were on CAPD and the peritonitis rate was one episode in 20.4 patient months . Gram positive organisms accounted for 54% of the infections of which Staphylococcus epidermidis was the commonest (24%) . Catheter removal was required in 14% of the cases and 9% of the patients discontinued CAPD as a result of peritonitis . The exit site infection rate was one episode in 27.5 patient months and the commonest organism was Staphylococcus aureus (54%) . Twenty-three (47%) of the cases of exit site infection required catheter removal and 83% of the cases were the result of S . aureus infections . Patients with preexisting exit site infections experienced more episodes of peritonitis . Patients above the age of 50 years experienced more episodes of peritonitis and exit site infection . Sex, diabetes and the duration on CAPD did not influence the frequency of infections . Patients using the UV Germicidal Exchange Device had fewer episodes of peritonitis than those using the conventional spike system.

Chem Pharm Bull (Tokyo), 1992 May, 40(5), 1309 - 12
Relationship between the effects on bacterial activity of selected disinfectants and the hydrophobic characters of dibasic acid diesters; Furuta T et al.; We prepared test solutions which contained 80% (v/v) ethanol and 0.2% (w/v) chlorhexidine (CH) or benzalkonium chloride (BC) with or without a dibasic acid diester . After complete evaporation of the ethanol from the solution on filter paper, an overnight broth culture (Staphylococcus aureus) was repeatedly inoculated onto the filter paper, and viable bacterial counts were measured at 5 min after the last inoculation . By comparison with viable counts for CH or BC alone, we estimated the potentiating effects of dibasic acid diester on the bactericidal activity of CH or BC, and confirmed that this activity of the two disinfectants was potentiated in the presence of certain compounds in the homologs of di-n-butyl esters of aliphatic dibasic acid, and di-alkyl esters of adipic and phthalic acid . Diisobutyl adipate, one of the most effective diesters, substantially enhanced the bactericidal activities of benzethonium chloride, cetyl pyridinium chloride and didecyl dimethyl ammonium chloride, as well as CH and BC, but not those of polyhexamethylene biguanide or alkyldiaminoethyl glycinate . The potentiating effects of dibasic acid diesters observed for both CH and BC seemed to be affected by the hydrophobic character of these diesters themselves and are also expressed well by a particular quadratic equation as a function of these characters: namely, capacity factors, as determined by high-performance liquid chromatography.

Br Heart J, 1992 May, 67(5), 409 - 11
Endocarditis with aneurysm involving an aortic homograft used to correct a truncus arteriosus: medical-surgical salvage; Engle MA et al.; An aneurysm of an aortic homograft conduit, used to correct a type I truncus arteriosus anomaly in a four month old infant, developed when the patient was 15 . Blood cultures grew Staphylococcus aureus . The aneurysm was detected by magnetic resonance imaging and digital subtraction angiocardiography . An emergency open heart operation, guided by these investigations, was performed to remove the original homograft and replace it with another valved aortic homograft . Postoperative antibiotic treatment had to be stopped when profound neutropenia developed . This responded to treatment with recombinant human granulocyte colony stimulating factor . Three years later she was symptom free and did not require medication . Chest x rays and echocardiograms showed a normally functioning heart and conduit valve.

J Hosp Infect, 1992 May, 21(1), 15 - 28
Characterization of methicillin-resistant Staphylococcus aureus associated with nosocomial infections in the University Hospital, Kuala Lumpur; Hanifah YA et al.; Methicillin-resistant Staphylococcus aureus (MRSA) as a hospital pathogen has presented many clinical problems in the University Hospital, Kuala Lumpur, Malaysia since 1978 . The need for control of spread of these organisms became evident by 1985 when it was noted that the incidence of MRSA among S . aureus isolated from hospital inpatients had increased from 11.5% in 1979 to 18.8% in 1985 . The characteristics of 50 MRSA isolates associated with nosocomial infections in the hospital are described here . The predominant strains produced Type IV coagulase and 84% of isolates studied showed moderate to high resistance to methicillin with MIC values of 25 mg l-1 or higher . All the MRSA isolates that could be phagetyped were susceptible to Group III phages, with 76.6% of the isolates being susceptible to phage 85 . At least 10 different patterns were distinguishable by plasmid typing, the majority of isolates harbouring up to four small plasmids.

J Investig Allergol Clin Immunol, 1992 May-Jun, 2(3), 146 - 53
Functional evaluation of human neutrophils . Is the bactericidal activity correlated with nitroblue tetrazolium reduction?
Bellinati-Pires R, Carneiro-Sampaio MM, Colletto GM.
The cytochemical nitroblue tetrazolium (NBT) reduction test continues to be used in clinical laboratories to detect defects in the oxidative metabolism of phagocytes . However, the specificity of the test is controversial, and it is not clear whether NBT reduction really reflects the microbicidal activity of these cells . In the present study, we evaluated the killing of Staphylococcus aureus by neutrophils from healthy adult individuals and from patients with phagocyte dysfunctions using a fluorochrome phagocytic assay, and compared the results with those obtained with a cytochemical NBT test performed simultaneously . The ability of neutrophils to reduce NBT (expressed as percent reducing neutrophils) with or without a lipopolysaccharide stimulus was not correlated with the bactericidal activity of these cells (expressed as percent killed bacteria per 100 neutrophils) . The age and sex of the healthy adults did not influence the results of either assay . It seems that the superoxide anion played a small role in NBT reduction by normal neutrophils, since superoxide dismutase did not significantly inhibit this reaction . Only the absolute absence of NBT reduction reflected the low bactericidal activity of neutrophils, as seen in patients with chronic granulomatous disease (CGD) . We conclude that the only clinical usefulness of the NBT test is for the screening of CGD, and that bacterial phagocytic assays are more appropriate for assessing the microbicidal function of neutrophils.

J Investig Allergol Clin Immunol, 1992 May-Jun, 2(3), 141 - 5
The ability of granulocytes to absorb latex particles and Staphylococcus aureus in patients hypersensitive to aspirin; Matusiewicz R et al.; An examination of the ability of granulocytes to absorb latex particles and Staphylococcus aureus was performed in 32 patients with atopic asthma, 27 patients with atopic asthma and hypersensitive to aspirin, and 20 patients hypersensitive to aspirin only . The control group included 20 healthy subjects . The results of our investigation demonstrate a defect of the ability of granulocytes to absorb latex particles and S . aureus in patients with atopic asthma and hypersensitivity to aspirin.

Eur J Med, 1992 May, 1(2), 113 - 5
Comparative study of community versus hospital-acquired Staphylococcus aureus bacteraemia; Maradona JA et al.; OBJECTIVES: We prospectively investigated 274 consecutive Staphylococcus aureus septicaemias in adult patients between January 1983 and December 1989 to evaluate outcome in hospital acquired and community acquired episodes . METHODS: Epidemiologic, clinical, laboratory and therapeutic parameters were analyzed with univariate and multivariate statistical tests . RESULTS AND CONCLUSIONS: Ninety episodes of Staphylococcus aureus bacteraemia were acquired in the community and 184 in hospital . Diabetes mellitus and renal failure were accompanied by a clear increase in bacteraemia related death in the community-acquired category . Correct antibiotic therapy showed a better response in the community-acquired group . Bacteraemia related death was 22.6% for episodes acquired in the hospital and 18.8% for those originating in the community.

Arq Bras Cardiol, 1992 May, 58(5), 383 - 5
{Infection of polytetrafluorethylene prosthesis in modified Blalock-Taussig anastomosis}; Thome LG et al.; A 16 month-old baby submitted to systemic-pulmonary shunt with a polytetrafluorethylene prosthesis, who presented hyperthermia, radiologic signs of pulmonary opacifications and positive culture for staphylococcus aureus . Reoperation disclosed a prosthesis pseudoaneurysm, with disconnection of the anastomosis and evidences of infection . This complication has a low diagnostic rate and a high mortality and should always be suspected when signs of systemic infection become apparent in the postoperative period of polytetrafluorethylene systemic-pulmonary shunt.

Antimicrob Agents Chemother, 1992 May, 36(5), 1109 - 14
Pharmacokinetics and bactericidal rates of daptomycin and vancomycin in intravenous drug abusers being treated for gram-positive endocarditis and bacteremia; Rybak MJ et al.; The pharmacokinetics and bactericidal killing rates (BR) of daptomycin (D) and vancomycin (V) in 12 intravenous drug abusers (6 treated with daptomycin and 6 treated with vancomycin) were evaluated . Pharmacokinetic parameters were determined from multiple serum samples drawn at steady state over a 12-h dosing interval after intravenous infusions of 3 mg of D per kg of body weight and 1,000 mg of V . The BRs were determined from the 1- and 6-h serum samples by using four isolates of Staphylococcus aureus (three methicillin susceptible and one methicillin resistant) obtained from the patients enrolled in the study . Peak serum daptomycin concentrations were lower and volumes of distribution were higher than reported in healthy volunteers . Although not statistically different, D clearance was 22% higher than reported in healthy volunteers . V pharmacokinetics were similar to those reported in previous studies . Daptomycin's BRs, although comparable to those of V in patients' serum, were significantly decreased compared with those found in broth . This may be related to the high degree of protein binding of D (93% versus 50% for V) . Conversely, the BRs of V in serum were significantly greater than those in broth . The BRs of D and V in broth were greater when killing curves were performed with test strains in logarithmic versus stationary-phase growth . The ability to kill organisms in stationary phase may be an important factor in determining the performance of an antibiotic in deep-seated infections such as endocarditis.3+

Antimicrob Agents Chemother, 1992 May, 36(5), 1053 - 6
Uptake and intracellular activity of sparfloxacin in human polymorphonuclear leukocytes and tissue culture cells; Garcia I et al.; The penetration of sparfloxacin into human neutrophils (PMN) and different tissue culture cells (HEp-2 and McCoy) was evaluated . The cellular to extracellular concentration ratios (C/E) of sparfloxacin were always higher than 4 at extracellular concentrations ranging from 0.5 to 25 mg/liter . The uptake of sparfloxacin by PMN was rapid, nonsaturable, reversible, not energy dependent, and significantly reduced at pH 8 . The penetration of this agent into PMN was similar when viable and Formalin-killed cells were used and was not affected by environmental temperature . Ingestion of opsonized zymosan significantly increased the amount of PMN-associated sparfloxacin . Sparfloxacin at a concentration of 0.5 mg induced a significant reduction in the survival of intracellular Staphylococcus aureus . It is concluded that sparfloxacin reaches intracellular concentrations within leukocytic cells much higher than extracellular concentrations, while remaining active intracellularly.

Nippon Rinsho, 1992 May, 50(5), 1042 - 8
{Characterization of the Staphylococcus aureus norA gene, which confers resistance to hydrophilic quinolones}; Yoshida H; The norA gene cloned from chromosomal DNA of a quinolone-and methicillin-resistant Staphylococcus aureus strain conferred resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but no or less resistance to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S . aureus and Escherichia coli . Nucleotide sequence analysis of the cloned DNA fragment revealed that the norA gene could code for a protein consisting of 388 amino acid residues with a molecular weight of 42,265, which was consistent with the experimental value of about 49,000 obtained on DNA-directed translation . The deduced NorA polypeptide has 12 hydrophobic membrane-spanning regions and is partly homologous to tetracycline resistance protein and sugar transport proteins . The uptake of a hydrophilic quinolone, enoxacin, by S . aureus harboring a plasmid carrying the norA gene was about 50% of that by the parent strain lacking the plasmid, but it increased to almost the same level as that by the latter strain with carbonyl cyanide m-chlorophenyl hydrazone . On the other hand, the uptake of a hydrophobic quinolone, sparfloxacin, was hardly affected by the norA gene . These results suggest that the NorA polypeptide may constitute a membrane-associated active efflux pump of hydrophilic quinolones.

Nippon Rinsho, 1992 May, 50(5), 1036 - 41
{Aminoglycosides resistance of methicillin-resistant Staphylococcus aureus}; Okamoto R et al.; In the last decade, there has been a dramatic increase in the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) in Japan . Especially, a high incidence of multiple resistant MRSA strains has been reported . These strains are resistant not only to beta-lactams but to aminoglycosides and macrolides . About 90% of MRSA strains were resistant to gentamicin (GM) and/or tobramycin (TOB), producing an aminoglycoside modifying enzyme, mainly, APH (2")/AAC (6) and/or AAD (4',4") . Based on these modifying enzymes produced, MRSA strains were classified into three groups; group 1 produced APH (2")/AAC (6), belonging to phage group I and coagulase IV, group 2 produced AAD (4',4"), belonging to phage group III and coagulase II, and group 3 produced APH (2")/AAC (6) and AAD (4',4"), belonging to phage group III and coagulase II . The epidemiological results suggest that MRSA strains changed from group 1 to group 2, and then to group 3 . Recently, arbekacin (ABK), a new anti-MRSA aminoglycoside, has been introduced into clinical practice . ABK shows a potent activity to GM-resistant strains, due to poorly modification by APH (2")/AAC (6') . However, there were few ABK- and GM-resistant strains in clinical isolates . These strains produced a higher amount of the enzyme than ABK-susceptible and GM-resistant strains . This observation suggests that ABK-resistant strains might be derived from GM-resistant strains by mutation of the gene coding APH (2")/AAC (6').

Nippon Rinsho, 1992 May, 50(5), 1026 - 35
{Multiple resistance to drugs by MRSA}; Inoue M et al.; Most methicillin-resistant Staphylococcus aureus (MRSA) isolates are multiply resistant to various antimicrobial agents . Therefore, MRSA strains have become a serious problem in the clinical setting . However, it should be noted that the frequency of isolation of strains resistant to aminoglycoside and minocycline was not significantly different between low- and high-MRSA isolates and the isolation frequency of high-MRSA strains, less susceptible to not only beta-lactam antibiotics but also to macrolide antibiotics and quinolones, was significantly higher than the corresponding values for low-MRSA strains . These results suggest that high-MRSA strains were selected by antimicrobial agents for the treatment with the patients.

Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4), 307 - 11
The utility of restriction endonuclease analysis and phage typing in the epidemiologic investigation of a Staphylococcus aureus outbreak in a neonatal nursery; Pekkala DH et al.; Outbreaks of Staphylococcus aureus infections in neonatal units require prompt investigation and implementation of control measures . From January to March 1990, a marked increase in the number of S . aureus infections was observed in a neonatal nursery . Twenty-seven S . aureus isolates from 23 patients were analyzed by phage typing and restriction endonuclease analysis (REA) . Only nine strains were differentiated by phage type . However, REA with HindIII, CfoI, and ClaI differentiated 20 strains . The REA results indicated that the outbreak was due to several different S . aureus strains and did not represent transmission of a single epidemic strain . REA may enable more accurate determination of the presence or absence of an epidemic strain during an outbreak than would traditional methods such as phage typing.

Scand J Immunol, 1992 May, 35(5), 561 - 7
B lymphoblasts show oxidase activity in response to cross-linking of surface IgM and HLA-DR; Furukawa K et al.; Human B lymphocytes express components of the superoxide generating system of phagocytes, NADPH oxidase . We studied regulation of this 'B-cell oxidase' during in vitro blast transformation, using Lucigenin-amplified chemiluminescence (CL) to detect superoxide release . While freshly isolated tonsil B lymphocytes showed no CL responses, culture with phorbol myristate acetate (PMA) and ionomycin induced susceptibility to CL triggering by anti-IgM and anti-HLA-DR . Maximal effects were observed after 3 days of culture with 0.4 ng/ml PMA + 1 microgram/ml ionomycin . Cells from such B lymphoblast cultures showed no CL responses to opsonized zymosan . In contrast, peripheral blood mononuclear cells, where monocytes are the predominant oxidant source, showed CL responses to opsonized zymosan but not to anti-IgM and anti-HLA-DR, either before or after culture with PMA + ionomycin . Culture of B cells with the surface immunoglobulin cross-linking agent staphylococcus aureus Cowan I also led to emergence of a CL, response to anti-IgM, which was enhanced by interferon-gamma . Interestingly, markedly fewer B blasts than freshly isolated B lymphocytes expressed cytochrome b-558 surface antigen . Thus, the B-cell oxidase is up-regulated during blast transformation and can be triggered via surface IgM and HLA-DR; however, this appears to be restricted to a subset of B lymphoblasts.

Protein Sci, 1992 May, 1(5), 654 - 66
Reversible unfolding and refolding behavior of a monomeric aldolase from Staphylococcus aureus; Rudolph R et al.; Thermal and GdmCl-induced unfolding transitions of aldolase from Staphylococcus aureus are reversible under a variety of solvent conditions . Analysis of the transitions reveals that no partially folded intermediates can be detected under equilibrium conditions . The stability of the enzyme is very low with a delta G0 value of -9 +/- 2 kJ/mol at 20 degrees C . The kinetics of unfolding and refolding of aldolase are complex and comprise at least one fast and two slow reactions . This complexity arises from prolyl isomerization reactions in the unfolded chain, which are kinetically coupled to the actual folding reaction . Comparison with model calculations shows that at least two prolyl peptide bonds give rise to the observed slow folding reactions of aldolase and that all of the involved bonds are presumably in the trans conformation in the native state . The rate constant of the actual folding reaction is fast with a relaxation time of about 15 s at the midpoint of the folding transition at 15 degrees C . The data presented on the folding and stability of aldolase are comparable to the properties of much smaller proteins . This might be connected with the simple and highly repetitive tertiary structure pattern of the enzyme, which belongs to the group of alpha/beta barrel proteins.

Zhonghua Wai Ke Za Zhi, 1992 May, 30(5), 270 - 1, 316
{Topical use of lysostaphin for Staphylococcus aureus infection of burn wounds in mice}; Huan JN; The effect of lysostaphin on the burn wounds infected with Staphylococcus aureus was studied in mice . The results showed that the mortality and incidence of bacterial isolation in wounds were 17.2% and 8.3%, respectively, in mice treated by lysostaphin, and the figures were significantly lower than that treated by SD-Ag (40.6% and 100%) or base (44.1% and 94.7%) . In lysostaphin group the bacterial count of subeschar tissue was 1325 cfu/g, compared with more than 10(9) cfu/g in both SD-Ag and base groups . The results demonstrate that lysostaphin has powerful killing effect on S . aureus, and may be used as atopical antimicrobial to control burn wound infection with S . aureus.

Biochem Biophys Res Commun, 1992 Apr 30, 184(2), 640 - 6
Molecular cloning and nucleotide sequence of leukocidin F-component gene (lukF) from methicillin resistant Staphylococcus aureus; Rahman A et al.; A lukF gene encoding F-component of Staphylococcal leukocidin from methicillin resistant Staphylococcus aureus (MRSA) was cloned . The nucleotide sequence of lukF gene was determined . The sequence data have revealed an open reading frame, which encodes a polypeptide with 323 amino acid residues . Inspection of the amino acid sequence deduced from nucleotide sequence of lukF and that from F-component of leukocidin from S . aureus V8 clarified that pre-matured F-component contains a typical signal peptide at the NH2 terminus and ATG starting codon for pre-matured F-component was present one base downstream to the TGA which is translation termination codon for S-component of leukocidin {A . Rahman et al . (1991) Biochem . Biophys . Res . Commun . 181, 138-144} . The nucleotide sequence of 5'-flanking region of lukF showed the presence of the consensus sequence of ribosome binding site in the internal region of the structural gene of S-component . The lukF was transcribed in the same direction as that of lukS . No Pribnow box can be discerned in the intercistronic region between the lukS and lukF genes . The amino acid sequence homology between S- and F-components was 31% . F-component was expressed in Escherichia coli DH5 alpha harboring plasmid pFRK92 which contained lukF gene.

Biochemistry, 1992 Apr 21, 31(15), 3738 - 50
Mapping the lipid-exposed regions in the Torpedo californica nicotinic acetylcholine receptor; Blanton MP et al.; To identify regions of the Torpedo nicotinic acetylcholine receptor (AchR) interacting with membrane lipid, we have used 1-azidopyrene (1-AP) as a fluorescent, photoactivatable hydrophobic probe . For AchR-rich membranes equilibrated with 1-AP, irradiation at 365 nm resulted in covalent incorporation in all four AchR subunits with each of the subunits incorporating approximately equal amounts of label . To identify the regions of the AchR subunits that incorporated 1-AP, subunits were digested with Staphylococcus aureus V8 protease and trypsin, and the resulting fragments were separated by SDS-PAGE followed by reverse-phase high-performance liquid chromatography . N-terminal sequence analysis identified the hydrophobic segments M1, M3, and M4 within each subunit as containing the sites of labeling . The labeling pattern of 1-AP in the alpha-subunit was compared with that of another hydrophobic photoactivatable probe, 3-trifluoromethyl-3-(m-{125I}iodophenyl)diazirine ({125I}TID) . The nonspecific component of {125I}TID labeling {White, B., Howard, S., Cohen, S . G., & Cohen, J.B . (1991) J . Biol . Chem . 266, 21595-21607} was restricted to the same regions as those labeled by 1-AP . The {125I}TID residues labeled in the hydrophobic segment M4 were identified as Cys-412, Met-415, Cys-418, Thr-422, and Val-425 . The periodicity and distribution of labeled residues establish that the M4 region is alpha-helical in nature and indicate that M4 presents a broad face to membrane lipid.

Biochem J, 1992 Apr 15, 283 ( Pt 2), 385 - 9
The complete sequences of trout (Salmo gairdneri) thymosin beta 11 and its homologue thymosin beta 12; Yialouris PP et al.; Two forms of beta-thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen . This suggests that the presence of two beta-thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species . Both trout beta-thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s . Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e . Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e . at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala) . Comparison of the known six sequences of beta-thymosins together with the sequences reported here showed that the sequence similarity of the two beta-thymosins in trout (86%) is greater than that of the two beta-thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-thymosins, the longer conserved segments located at positions 16-26 and 31-38.

Eur J Biochem, 1992 Apr 15, 205(2), 653 - 60
Amino acid sequence of calmodulin from Euglena gracilis; Toda H et al.; The complete amino acid sequence of calmodulin from Euglena gracilis was determined by isolation and sequence analyses of peptides derived from calmodulin by digestion with trypsin and Staphylococcus aureus V8 protease . Euglena calmodulin consists of 148 amino acid residues; it lacks tryptophan and cysteine and contains one tyrosine, three histidine and two NE-trimethyllysine residues/molecule of the protein . Its N-terminus was blocked with an acetyl group and C-terminal lysine was trimethylated . Euglena calmodulin is the first calmodulin so far examined in which the C-terminal lysine is trimethylated . The comparison of amino acid sequences between Euglena and human brain calmodulins indicated 17 amino acid substitutions in Euglena calmodulin.

Proc Natl Acad Sci U S A, 1992 Apr 15, 89(8), 3185 - 9
Targeted cleavage of mRNA in vitro by RNase P from Escherichia coli; Li Y et al.; External guide sequences (EGSs) complementary to mRNAs that encode beta-galactosidase from Escherichia coli and nuclease A from Staphylococcus aureus can target these RNAs for cleavage in vitro by RNase P from E . coli . Specific cleavage occurs at locations predicted by the nucleotide sequences of the EGSs . EGSs with regions complementary to the mRNAs that are as short as 13 nucleotides function efficiently and turn over slowly during incubation with the target substrate and the enzyme . EGSs composed of deoxyribonucleotides as well as those composed of ribonucleotides are effective, but cleavage of the targeted substrate with DNA as an EGS is about 10-fold less efficient than that with RNA as an EGS . An RNA EGS inhibited the formation of beta-galactosidase activity in a crude extract (S30) of E . coli that was capable of catalyzing coupled transcription-translation reactions.

Biochim Biophys Acta, 1992 Apr 14, 1138(4), 297 - 304
Proteolytic susceptibility of the central domain in chicken gizzard and skeletal muscle dystrophins; Augier N et al.; We investigated proteolytic susceptibility of the central domain in dystrophin molecules from chicken smooth and skeletal muscles . Dystrophin-enriched preparations from both muscles were made as described in Pons et al . (Proc . Natl . Acad . Sci . USA (1990) 87, 7851-7855) . These preparations contained other protein components in addition to dystrophin . Three enzymes (Staphylococcus aureus proteinase, chymotrypsin and trypsin) having different proteolytic specificities were used . Time-courses of proteinase degradation were examined by the Western immunoblot technique using a specific polyclonal serum directed against a fragment (residues 1173-1728) of the dystrophin central domain . We observed accumulation of some major proteinase-resistant fragments, in the 110-160 kDa range originating from that central region of the molecule . Cleavage patterns of the smooth and skeletal muscle preparations were quite similar, but molecular weights of the breakdown products differed slightly . Interpretation of the results was based on two predictive structural models of the dystrophin central domain (Koenig and Kunkel (1990) J . Biol . Chem . 265, 4560-4566 and Cross et al . (1990) FEBS Lett . 262, 87-90) . Skip residues at the end of repeat 13 (around the 1740th residue of the dystrophin amino acid sequence), as hypothesized in the Cross model, constitute probably the most sensitive site within the dystrophin central domain for any exogenous (or even endogenous) proteinase . Variations observed between dystrophins from skeletal and smooth muscles also suggest that the structures of both dystrophins differ slightly even within the dystrophin central domain . This precise identification of proteinase-resistant dystrophin fragments of variable lengths is a first step towards further physicochemical studies on the very large and rare dystrophin molecule.

Med Clin (Barc), 1992 Apr 11, 98(14), 527 - 30
{Septic arthritis induced by pyogenic germs in patients without parenteral drug addiction . Analysis of 44 cases}; Rozadilla A et al.; BACKGROUND: The aim of this study was to evaluate the clinical-microbiological characteristics presented in the area of influence of the Hospital de Bellvitge-Princeps d'Espanya, of articular infection induced by pyogenic germs in patients without intravenous drug addiction . METHODS: All the cases of microbiologically confirmed articular infection in patients without intravenous drug addiction diagnosed during the period of 1981-1990 were evaluated by protocol . RESULTS: Five cases (11%) with gonococcal arthritis and 39 cases (89%) of non gonococcal arthritis were observed with Staphylococcus aureus being the causal germ in 27 cases . Sixty percent of the patients presented one or more predisposing factors for the appearance of infectious arthritis . Monoarticular involvement was seen in 84% of the cases . At the time of diagnosis fourteen patients presented radiological signs compatible with septic involvement, with the isotopic study with 99mTc being positive in the 27 cases in which it was carried out . Delay in diagnosis was of 20 +/- 25 days . Functional results were considered as satisfactory in 57% of the cases . CONCLUSION: In the area of influence of the Hospital de Bellvitge-Princeps d'Espanya, the prevalence of gonococcal arthritis is low . Gram positive germ are the most frequent causal agents in all the age groups studied . Gammagraphy with 99mTc presented high profitability in the diagnosis of articular infections . The functional results observed were not optimal and improvement of the same probably requires a shortening in the time of delay in diagnosis.

Med Clin (Barc), 1992 Apr 11, 98(14), 521 - 6
{Infective endocarditis in heroin addicts in the province of Cádiz . A multicenter study of 150 cases}; Torres Tortosa M et al.; BACKGROUND: Given the progressive increase in infectious endocarditis (IE) in intravenous drug addicts (IVDA) in the province of Cadiz the present study was designed with the aim of studying the epidemiologic and clinical characteristics of this disease in our environment . METHODS: One hundred fifty episodes of IE occurring in 133 IVDA admitted to 6 hospitals in the province of Cadiz were studied in an open, multicentric study with a protocol of gathering of common data . Well known diagnostic criteria were used for this process and a univariant technique was employed in the analysis of prognostic factors . RESULTS: Fifty-three percent of the episodes occurred in the county of Campo de Gibraltar and 32% in the area of the Bay of Cadiz . The increase of the disease has been progressive since 1984 and marked over the last two years . All the patients presented fever, abnormal chest radiography in 90% and the process was produced by Staphylococcus aureus in 88% . Echography was abnormal in 85% of the episodes and vegetation was identified in 75% . The IE was located as right in 90%, mixed in 5% and left in 5% . Surgical treatment was required in 4 patients . Mortality was of 9% . Mixed or left location (p = 0.00003) and the development of the respiratory distress syndrome of the adult (p = 0.00001) were significantly associated with greater mortality . CONCLUSIONS: Infectious endocarditis in intravenous drug addicts maintains a well defined pattern of clinical expressivity and presents identifiable factors of prognostic influence . The increase in its prevalence in the province of Cadiz is probably due to a parallel increase in the addiction to intravenous heroin in this area.

J Biol Chem, 1992 Apr 5, 267(10), 7148 - 53
Purification of uridine diphosphate-galactose:glucosyl ceramide, beta 1-4 galactosyltransferase from human kidney; Chatterjee S et al.; A galactosyltransferase that transfers galactose from UDP-galactose to glucosylceramide was purified 440-fold to apparent homogeneity from normal human kidney "buffy coat" preparation employing detergent extraction, ultrafiltration, and Sepharose Q column chromatography . On reducing and nonreducing gels, the enzyme resolved into two bands with apparent molecular weights on the order of 60,000 and 58,000, respectively . The activity of the enzyme was also associated with these two bands following separation on polyacrylamide gels . Analytical isoelectric focusing revealed that the pI of this enzyme is approximately 4.55 . Product characterization and substrate specificity studies employing chromatography, enzymatic digestion with various glycosidases, and use of a variety of glycosphingolipid substrates revealed that the major product synthesized by this enzyme was Cer1-1 beta Glc4-1Gal, and Cer1-1 beta Glc was the preferred substrate . Digestion of the 60- and 58-kDa proteins with Staphylococcus aureus (V-8) protease revealed at least six peptides having identical electrophoretic migration . This finding suggests that the two proteins may be related to each other . Western immunoblot assays revealed that the antibody against UDP-galactose:GlcCer, beta 1-4 galactosyltransferase (GalT-2) but not galactosyltransferase UDP-Gal:N-acetyl-D-glucosaminyl-glycopeptide 4-beta-D-galactosyltransferase (EC 2.4.1.38) (B-GT) immunoprecipitated (recognized) the kidney GalT-2 . In contrast, antibody against B-GT did not immunoprecipitate GalT-2 . Thus our data indicate that GalT-2 and B-GT are two distinct enzymes . The availability of the enzyme GalT-2 and corresponding antibody will allow functional studies in the near future.

Pathology, 1992 Apr, 24(2), 99 - 101
Comparison of Roche blood culture bottle with an in-house conventional blood culture system; Phua RT et al.; A comparison was made of the in-use performance of an in-house broth blood culture in a general hospital during 8 mths in 1988 with that of a commercial biphasic culture (BCB system, Roche Products Pty Ltd, Sydney) for the corresponding period in 1989 . The clinical services and the number of blood samples tested were comparable . The yields of organisms after 48 hrs incubation were similar in both systems . Staphylococcus aureus showed up 3 times as often after 24 hrs incubation in the conventional system as in the BCB system . Agitation of the BCB facilitated macroscopic detection of growth in the initial 24 hrs incubation.

Pathology, 1992 Apr, 24(2), 102 - 8
Detection of teichoic acid antibodies in Staphylococcus aureus infections; Wise KA et al.; A commercially available agar gel diffusion (AGD) assay was used to investigate the teichoic acid antibody (TAA) response in 183 patients with proven Staphylococcus aureus (SA) infections . Two control groups were also investigated . One consisted of 100 hospitalized patients with a variety of medical and surgical conditions other than SA infection and the other consisted of 116 healthy hospital staff members . The sensitivity of the AGD assay varied markedly depending on the site of infection in the patients with proven SA infections . All patients with SA endocarditis developed positive TAA titres (greater than or equal to 1:4), although more than one third of these were initially negative . In patients with chronic osteomyelitis or septic arthritis, 41% had positive TAA titres, whereas no positive titres were detected in patients with acute osteomyelitis or septic arthritis . Lower rates of positive TAA titres were found in patients with deep abscesses (27%), pneumonia (14%) and post-operative infections (9%), but no positive titres occurred in patients with acute uncomplicated bacteremia, cellulitis or meningitis . In 100 hospitalized control patients, no positive titres were detected, and only 1 of 116 (0.9%) healthy hospital staff controls was positive . Suggested guidelines for the use of the AGD assay are discussed.

Hum Antibodies Hybridomas, 1992 Apr, 3(2), 93 - 106
Characterization of an antibody to the integrin beta 3 subunit (GP IIIa) from a patient with neonatal thrombocytopenia and an inherited deficiency of GP IIb-IIIa complexes in platelets (Glanzmann's thrombasthenia); Jallu V et al.; Patient A.F . is a 28-year-old polytransfused woman with an inherited bleeding disorder, Glanzmann's thrombasthenia . An abnormal platelet function is linked to severe decreases in the platelet content of the integrins GP IIb and GP IIIa . In 1987 the patient gave birth to a child with severe anemia and thrombocytopenia . Serological tests revealed the presence of anti-platelet antibody together with an anti-Rhesus D . Western blotting identified a major antibody that reacted with a protein of 90-95 kDa present in platelets and endothelial cells . This was identified as the beta 3 integrin subunit (GP IIIa) . Antibody-binding required intact disulfides, while controlled digestion with proteases showed the determinant(s) to be retained within chymotrypsin- (50, 63 kDa) and Staphylococcus aureus V8 protease-derived (25-38 kDa) fragments of GP IIIa . Direct binding assays performed in the presence of monoclonal antibodies specific for different epitopes on GP IIb-IIIa complexes confirmed that the epitope was exposed on intact platelets and revealed a specific inhibition of A.F . IgG binding by the monoclonal antibody, AP-3 . Other tests confirmed that the antibody reacted independently of the PlA or Pen polymorphisms carried by GP IIIa . IgG purified from A.F . plasma by adsorption and elution from paraformaldehyde-fixed normal platelets or electrophoretically separated GP IIIa was an inhibitor of ADP-induced platelet aggregation . Unexpectedly, Western blotting showed trace amounts of abnormally migrating GP IIIa in A.F . platelets, which retained an ability to react with her antibody . This suggests that the patient has formed an autoantibody reactive with an active site of the beta 3 integrin subunit and linked to the development of neonatal thrombocytopenia.

Microb Pathog, 1992 Apr, 12(4), 289 - 98
Evidence for three different fibrinogen-binding proteins with unique properties from Staphylococcus aureus strain Newman; Boden MK et al.; Binding of extracellular components of Staphylococcus aureus strain Newman to fibrinogen and prothrombin was investigated . Affinity-purified material from fibrinogen- and prothrombin-Sepharose was analysed on immunoblots, and two proteins with coagulase activity were identified . The two coagulases were produced in a sequential manner during staphylococcal growth . An 87 kDa fibrinogen-binding coagulase was produced mainly during the exponential growth phase and was replaced by a 60 kDa fibrinogen- and prothrombin-binding coagulase which was produced mainly during the post-exponential growth phase . In addition, a 19 kDa fibrinogen-binding protein was constitutively produced . Analyses of immunogenic properties and NH2-terminal sequences suggested that the 19, 60 and 87 kDa fibrinogen-binding proteins are not closely related . The NH2-terminal sequence of the 87 kDa protein is identical to a previously described coagulase from Staphylococcus aureus strain 8325-4 . The 19 kDa fibrinogen-binding protein, which spontaneously aggregates into dimers and larger molecular weight complexes, had a unique NH2-terminal sequence.

J Chemother, 1992 Apr, 4(2), 67 - 71
Frequency and transferability of trimethoprim and sulfonamide resistance in methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis; Then RL et al.; A total of 374 Staphylococcus aureus and 126 Staphylococcus epidermidis strains from 14 countries were studied for their resistance to methicillin, trimethoprim (Tp) and sulfonamides (Su), alone and combined (TpSu) . The frequency of resistance to Tp, Su and TpSu was much higher in methicillin-resistant S . epidermidis (MRSE) than in methicillin-resistant S . aureus (MRSA) . Considerable differences, however, existed in isolates from different countries . Resistance to Tp, Su or TpSu in MRSA was low or absent in isolates from Switzerland, Spain, Japan, Mexico, Argentina and Chile, but high in isolates from Germany and Brazil . High level Tp resistance mostly resided on large plasmids . It could be transferred in 17 out of 97 strains . Su resistance was never cotransferred . Strains cured of their large Tp resistance plasmids remained Su-resistant, which suggests a chromosomal location of Su resistance.

Acta Paediatr Jpn, 1992 Apr, 34(2), 151 - 6
Methicillin-resistant Staphylococcus aureus empyema in children; Fujita K et al.; Over a 14 year period, there were 20 patients who presented with staphylococcal empyema from whom methicillin-resistant Staphylococcus aureus (MRSA) was isolated . Twelve cases were community-acquired and 8 were hospital-acquired infections . Patients were treated with penicillinase-resistant penicillin, cephalosporin or carbapenem in combination with or without aminoglycoside . They were also treated with drainage or thoracentesis . However, they were refractory to treatment and 7 patients, 6 of whom were suffering from bacteremia, died . One bacteremic patient was treated with vancomycin and was cured . In an area of endemic MRSA, vancomycin may be the first choice in the initial treatment of staphylococcal empyema until antimicrobial susceptibility can be determined.

Proteins, 1992 Apr, 13(2), 152 - 7
Crystallization and preliminary X-ray diffraction analysis of staphylococcal enterotoxin type C; Bohach GA et al.; The Type C staphylococcal enterotoxin produced by Staphylococcus aureus strain FRI-909 has been crystallized using a combination of two precipitants, ammonium sulfate and polyethylene glycol 400, with the addition of small amounts of detergent . Two related crystal forms have been obtained, one triclinic, and one tetragonal, both with one toxin molecule per asymmetric unit . These crystals are stable for at least 75 hr in the X-ray beam and diffract to at least 2.2 and 2.6 A, respectively . The triclinic crystals have unit cell parameters a = 38.5 A, b = 43.7 A, c = 36.9 A, and interaxial angles alpha = 99.9 degrees, beta = 95.8 degrees, and gamma = 98.5 degrees . The tetragonal crystals are of space group P4(1)22 with unit cell parameters a = 43.4 A and c = 278.0 A.

J Biochem (Tokyo), 1992 Apr, 111(4), 537 - 45
Primary structure and disulfide bridge location of arrowhead double-headed proteinase inhibitors; Yang HL et al.; Two arrowhead proteinase inhibitors (inhibitors A and B) were characterized and their primary structures were determined . Both inhibitors A and B are double-headed and multifunctional protease inhibitors . Inhibitor A inhibits an equimolar amount of trypsin and chymotrypsin simultaneously and weakly inhibits kallikrein . Inhibitor B inhibits two molecules of trypsin simultaneously and inhibits kallikrein more strongly than does inhibitor A . The amino acid sequences of inhibitors A and B were determined by sequencing the reduced and S-carboxamidomethylated proteins and their peptides produced by cyanogen bromide or proteolytic lysylendopeptidase or Staphylococcus aureus V8 protease cleavage . Inhibitors A and B consist of 150 amino acid residues with three disulfide bonds (Cys 43-Cys 89, Cys 110-Cys 119, and Cys 112-Cys 115) and share 90% sequence identity, with 13 different residues . Since the primary structures are totally different from those of all other serine protease inhibitors so far known, these inhibitors might be classified into a new protease inhibitor family.

Zentralbl Bakteriol, 1992 Apr, 276(4), 487 - 92
Characteristics of bovine Staphylococcus aureus with special regard to clumping factor activity; Hummel R et al.; The occurrence of the following groups of bovine Staphylococcus aureus with characteristic patterns of biochemical reactions and sensitivities to phages was confirmed by the present investigation of 662 isolates from the udders of cows in 53 dairy herds: (1) host-specific variety (v) bovis, (2) not alloted strains with the basic marker, crystal violet type A (group na CV A), (3) group na CV C . The latter was split into three subgroups clearly differing in phage susceptibility patterns: I/119, I without 119 and III, respectively . Lack of clumping factor activity occurred in 323 out of 346 (93%) phage pattern I/119 strains examined while most or all isolates of the other groups of bovine strains proved to be clumping-positive.

Hybridoma, 1992 Apr, 11(2), 239 - 43
Chicken anti-protein A for the detection and capturing of protein A from Staphylococcus aureus in the presence or absence of mammalian IgG; Larsson A et al.; A sandwich-ELISA for the detection of protein A from Staphylococcus aureus (SpA) is described, using chicken anti-protein A as a capture antibody and its alkaline phosphatase conjugate for the detection of bound protein A . Traditionally, protein A is detected by its binding to the Fc part of a detector antibody . This binding will be influenced by the presence of other IgG in the protein A solution . However, SpA does not react with the Fc part of chicken IgG, and it is thus possible to detect protein A in IgG containing solutions, such as eluates from protein A-columns . The method can be used to detect 1 x 10(-7) g protein A/l in the presence of serum . The method is more sensitive if no serum or IgG is present in the solution.

Microbiologica, 1992 Apr, 15(2), 191 - 5
Antibiotic resistance and plasmids of some human nasal isolates of Staphylococcus aureus; Salamah AA; The Staphylococcus aureus isolates were all susceptible to vancomycin . More than 90% of the isolates were susceptible to rifampicin, ampiclox, methicillin, erythromycin and clindamycin . The isolates were highly resistant to the beta-lactamase-sensitive penicillins, that is 91, 93.2 and 70.4% of the isolates were resistant to penicillin, ampicillin and carbinicillin . Twelve plasmids were found in the isolates, the 35 and 11 Mdal plasmids coded for aminoglycosides and tetracycline resistances, respectively.

Microbiologica, 1992 Apr, 15(2), 125 - 33
Production of toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus strains isolated from humans, animals and foods in Nigeria; Adesiyun AA et al.; The production frequency of toxic shock syndrome toxin-1 (TSST-1) amongst Staphylococcus aureus strains isolated from humans, animals and foods in Nigeria was investigated . Of 1015 strains tested, 120 (11.8%) were positive for TSST-1 . Thirty one (16.0%) of 194 strains from human diarrhoea and wounds were positive compared to 47 (7.1%) of 666 isolates from eight animal species . Goat strains were most often positive for this toxin (17.0%) . A total of 42 (27.1%) of 155 strains from foods were positive for TSST-1 . Regardless of source, phage non-typable strains (48.3%) were most common amongst TSST-1 producers followed by strains sensitive to phages in several groups (mixed), 18.3%, and phage group III strains (17.5%) . Only 6 were phage group I strains (5.0%) . TSST-1 producing strains were mostly resistant to penicillin . Eighty-four (70.0%) TSST-1 producers were also enterotoxigenic with staphylococcal enterotoxin C (SEC) most frequently elaborated as 46 (38.9%) strains were positive . However, 42 (35.5%) and 39 (32.5%) strains producing TSST-1 were also positive for SEA and SEB, respectively . It was concluded that TSST-1 producing strains of S . aureus are widespread in humans, animals and foods in Nigeria and such distribution may play some role in the epidemiology of toxic shock syndrome, the prevalence of which is currently unknown in the environment.

Rinsho Ketsueki, 1992 Apr, 33(4), 532 - 6
{Sick sinus syndrome caused by amyloidosis associated with multiple myeloma}; Kirito K et al.; A 65-year-old man, who had been treated for multiple myeloma (MM) since 1986, was admitted because of loss of consciousness in September 1989 . An electrocardiogram taken just before admission showed a sinus arrest, junctional escaped rhythm, and marked bradycardia . The diagnosis of sick sinus syndrome (SSS) was made . Soon a temporary pacemaker was inserted, and the dyspnea ameliorated . However on the second day in the hospital, he had a high fever and Staphylococcus aureus was detected in the cultured blood . A diagnosis of septicemia was made, and the pacemaker was removed . He was then treated with beta-stimulants, but died in November 1989 . Necropsy revealed cardiomegaly and microscopic examination showed amyloid deposits in the sinoatrial node, and the walls of the ventricles and coronary arteries . Although amyloidosis is often a complication of MM and the heart is frequently affected, SSS caused by amyloidosis associated with MM is quite unusual . In such patients, the use of a pacemaker is controversial, because amyloid deposits are occasionally accelerated by insertion of a pacemaker and for patients with hematological disorders, septicemia associated with pacemaker insertion may prove fatal.

J Wildl Dis, 1992 Apr, 28(2), 215 - 22
Starvation, staphylococcosis, and vitamin A deficiency among mallards overwintering in Saskatchewan; Wobeser G et al.; During January to March 1991, 38 mallards (Anas platyrhynchos) found dead from a group of approximately 600 overwintering on the South Saskatchewan River were examined . Thirty birds died from starvation, four had disseminated Staphylococcus aureus infection, and the cause of death of four birds was not determined . All six birds from which the esophagus was examined microscopically, including the four birds with staphylococcosis, had squamous metaplasia of the submucosal glands, a lesion pathognomonic for vitamin A deficiency . Vitamin A deficiency may occur in mallards and other waterfowl that overwinter north of traditional wintering areas and rely on grains deficient in carotenoids.

Eur Heart J, 1992 Apr, 13(4), 446 - 52
Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis; Rohmann S et al.; Infective endocarditis is associated with significant morbidity and mortality, with valvular destruction and congestive heart failure being more common in patients with echocardiographically discernible vegetations . The transoesophageal approach affords consistently high quality images with excellent structural resolution . Two-hundred and eighty-one patients with clinically suspected infective endocarditis were studied, to evaluate the prognostic value of ascertaining the site of vegetations . Among them were 118 patients with vegetations attached to the aortic or mitral valve . These patients were followed for a mean period of 14 months . Mitral valve vegetations were associated with a significantly higher incidence of embolic events than vegetations on aortic valves (25% vs 9.7%) . The incidence of abscess formation was higher in aortic than in mitral valve endocarditis (6% vs 0%), as were the need for surgical intervention (11% vs 5.5%) and mortality (1.6% vs 0%) respectively) . Bivalvular endocarditis was associated with an increased rate of complications: embolism (50%), abscess formation (15%), surgery (35%) and mortality (10%) . By multivariate analysis, echocardiographically accessible risk factors for subsequent embolism were a vegetation size of more than 10 mm and mitral valve involvement . Risk factors associated with in-hospital fatality were embolism, a vegetation size of more than 10 mm, and Staphylococcus aureus infection . Our data suggest that the site influences both the rate and the type of complications . Precise echocardiographic visualization of vegetations helps to stratify patients into a high-risk sub-group, perhaps warranting early prophylactic surgical intervention . Transoesophageal echocardiography may play an important role in assessing the clinical outcome for these patients.

Clin Podiatr Med Surg, 1992 Apr, 9(2), 425 - 42
Vancomycin, metronidazole, and tetracyclines; Ellison MJ; Over the last 30 years, the impurities in the vancomycin product have been reduced, perhaps resulting in a lower rate of adverse reactions . Vancomycin is bactericidal against most susceptible organisms, but is bacteriostatic against the enterococcus . Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus . Vancomycin attains good tissue and bone penetration and must be administered intravenously for systemic infections . It is eliminated renally with a half-life of about 6 hours; this half-life is prolonged with advanced age and reduced renal function . Significant adverse reactions can be minimized with careful attention to administration technique . Metronidazole has excellent tissue penetration; its antibacterial site of action is within anaerobic bacterial cells . Metronidazole is cleared by hepatic metabolism with a half-life of about 7 to 8 hours . The half-life is unchanged with renal dysfunction but is prolonged in patients with hepatic function impairment . Although adverse effects are relatively minor, there is an important interaction with warfarin . For podiatric infections, metronidazole can be used in skin- and soft-tissue infections; anaerobes in bone and joint infections are rare . Topical metronidazole has been used successfully in the treatment of decubitus ulcers, and this needs further evaluation . The most commonly used tetracyclines are tetracycline, doxycycline, and minocycline . The tetracyclines are broad spectrum antimicrobial agents, but their usefulness is limited by resistant strains . Tetracycline's absorption is significantly impaired by food, and it is cleared renally and fecally . Doxycycline has the highest protein binding and the longest half-life; it is cleared both renally and fecally without hepatic metabolism . Minocycline has the best absorption and tissue penetration; the unchanged drug is cleared renally and fecally, and it also undergoes hepatic metabolism . All tetracyclines have important adverse reactions with respect to teeth and bones, and they are contraindicated during pregnancy and for children under age eight.

Am J Vet Res, 1992 Apr, 53(4), 585 - 91
Arthrotomy versus arthroscopy and partial synovectomy for treatment of experimentally induced infectious arthritis in horses; Bertone AL et al.; To evaluate the clinical, laboratory, and histologic effects of 2 methods of treatment for infectious arthritis in horses, Staphylococcus aureus (3.4 to 3.9 x 10(3) colony-forming units) was inoculated into the tarsocrural joints of 8 horses on day 0 . Each horse was treated with phenylbutazone (2 g, PO, q 24 h) and gentamicin sulfate (2.2 mg/kg of body weight, IV, q 8 h) for 14 days . On day 2, general anesthesia was induced, and each horse had 1 tarsocrural joint treated by arthrotomy, with removal of accessible fibrin and lavage with 3 L of sterile balanced electrolyte solution . An indwelling plastic drain was placed in the standing horse to provide a means for lavage with 3 L of balanced electrolyte solution twice daily for 72 hours . The contralateral tarsocrural joint was treated via arthroscopic debridement, synovectomy, and lavage with 3 L of balanced electrolyte solution . Arthrotomy and arthroscopic portals were allowed to heal by second intention . Lameness and thermographic examinations, analysis and bacteriologic culture of synovia, CBC, and WBC differential count were performed prior to inoculation and on days 1, 3, 6, 8, and 13 . On day 14, each horse was euthanatized, and the joints were measured, opened, and photographed . Synovium and articular cartilage were obtained for semiquantitative histologic (H&E stain) and histochemical (safranin O fast green stain) evaluation . Lameness and joint circumference were significantly (P less than 0.05) greater in limbs treated by arthroscopy, synovectomy, and lavage . Arthrotomy with lavage eliminated the S aureus infection significantly (P less than 0.05) earlier than arthroscopy, synovectomy, and lavage, however, both treatments eliminated the infection in all but a single joint.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiol Infect, 1992 Apr, 108(2), 287 - 98
An epidemic methicillin-resistant strain of Staphylococcus aureus in Spain; Aparicio P et al.; During 1990, a strain of methicillin-resistant Staphylococcus aureus became epidemic in Spain and spread in a manner analogous to that of EMRSA-1 in England . Isolates of this strain produced little protein A and were resistant to a number of antibiotics including ciprofloxacin . Beta-lactamase production was encoded by a c . 39 kb plasmid, which also conferred resistance to mercury, cadmium, ethidium bromide and propamidine isethionate . Investigation showed that two variants, separable by supplementary and Fisk phage typing, were circulating . The B variant appeared to spread more readily than the A variant . The opportunity was taken to compare the discriminatory power of traditional typing methods with molecular techniques . The discriminatory power of the molecular techniques used only reached the same level as the traditional methods when double enzyme digestion of total cellular DNA by EcoR I and Cla I was performed.

Arch Dermatol, 1992 Apr, 128(4), 530 - 4
An unusual presentation of secondary syphilis in a patient with human immunodeficiency virus infection . A case report and review of the literature; Glover RA et al.; BACKGROUND--Syphilis has been reported to assume unusual clinical appearances and to exhibit unusual courses in patients infected with the human immunodeficiency virus (HIV) type 1 . We recently observed a distinct manifestation of syphilis in an HIV-infected patient with features not previously described . OBSERVATIONS--A 38-year-old HIV-seropositive homosexual man presented with fever, chills, malaise, and a cutaneous eruption consisting of indurated, shiny, erythematous plaques that were confluent on the face and scalp leading to alopecia and extreme tautness of the skin . Initial clinical diagnoses included lymphoreticular malignancy and infection . Although cultures yielded Staphylococcus aureus, a skin biopsy specimen was diagnostic of syphilis . CONCLUSIONS--This case demonstrates an unusual clinical manifestation of syphilis in a patient with HIV infection and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of virtually any inflammatory cutaneous disorder in HIV-seropositive individuals.

J Clin Microbiol, 1992 Apr, 30(4), 967 - 73
DNA fingerprinting by pulsed-field gel electrophoresis is more effective than ribotyping in distinguishing among methicillin-resistant Staphylococcus aureus isolates; Prevost G et al.; Pulsed-field gel electrophoresis (PFGE) after SmaI restriction of DNA from 239 methicillin-resistant Staphylococcus aureus isolates (from 142 patients) produced 26 different fingerprints . The deduced chromosome sizes ranged from 2,200 to 3,100 kb (+/- 100 kb) . A total of 81 isolates taken from 65 patients were then typed by PFGE and ribotyping with ClaI, EcoRI, and HindIII . Ribotypes were less discriminating than PFGE . Ribotyping did not discriminate isolates from a given PFGE fingerprint into different subsets . PFGE may be a more effective epidemiological tool than ribotyping for the typing of methicillin-resistant S . aureus strains.

Clin Nucl Med, 1992 Apr, 17(4), 269 - 73
Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc-99m SC marrow imaging; Palestro CJ et al.; Seventy-three patients with various underlying disorders that could potentially alter distribution of bone marrow underwent In-111 labeled autologous leukocyte and Tc-99m SC marrow imaging to exclude musculoskeletal infection . There were 22 cases of infection among the 73 patients studied . When interpreted in isolation, labeled leukocyte images were considered positive for infection when uptake of labeled cells in the region of interest exceeded uptake in the corresponding contralateral side . The sensitivity, specificity, and accuracy of the study using this criterion were 86%, 12%, and 34%, respectively . When interpreted in conjunction with sulfur colloid marrow images, studies were considered positive for infection when uptake in the region of interest on leukocyte and marrow images was spatially incongruent . The sensitivity, specificity, and accuracy of this dual tracer modality were 100%, 94%, and 96%, respectively . Three patients with infection and abnormal leukocyte/marrow images underwent repeat imaging after appropriate therapy . Images were interpreted as normal in two of them; both were infection free at subsequent surgery . Images of the third patient were interpreted as consistent with persistent infection, and operative cultures grew out Staphylococcus aureus . In summary, combined leukocyte/marrow imaging is a highly accurate method for diagnosing musculoskeletal infection and overcomes certain inherent limitations of labeled leukocyte imaging alone.

Clin Exp Immunol, 1992 Apr, 88(1), 23 - 8
Impaired phagocytosis of Staphylococcus aureus by granulocytes and monocytes of AIDS patients; Pos O et al.; In the present study the microbicidal activities of granulocytes and monocytes from AIDS patients (CDC group IV) were assessed and compared with those of healthy controls . The phagocytosis and intracellular killing of Staphylococcus aureus by patient and control cells were measured using a method in which the rate of intracellular killing can be assessed independently of the rate of phagocytosis . Both granulocytes and monocytes of AIDS patients showed a decreased phagocytosis of S . aureus in comparison to phagocytes of healthy individuals . The rates of intracellular killing of S . aureus by granulocytes and monocytes did not differ significantly between these patients with late-stage HIV infection and controls.

J Med Microbiol, 1992 Apr, 36(4), 293 - 8
Modification of bactericidal fatty acids by an enzyme of Staphylococcus aureus; Mortensen JE et al.; Certain strains of Staphylococcus aureus produce an enzyme capable of inactivating the bactericidal fatty acids produced in staphylococcal abscesses by esterification to various alcohols . The enzyme, called FAME (fatty acid modifying enzyme), has a pH optimum between 5.5 and 6.0 and a temperature optimum of about 40 degrees C . Enzyme activity is not affected by edetic acid or by the presence or absence of sodium and potassium ions . Although FAME can utilise methanol, ethanol, 1-propanol, 2-propanol, 1-butanol or cholesterol as substrates, cholesterol appears to be the preferred substrate . FAME esterifies without being an esterase operating in reverse . Strains capable of producing the enzyme can synthesise it in trypticase soy broth and in a chemically defined medium, but not necessarily in equal amounts . FAME production is correlated with the ability of a strain to grow and survive within the tissues.

J Med Microbiol, 1992 Apr, 36(4), 288 - 92
The production of bactericidal fatty acids from glycerides in staphylococcal abscesses; Shryock TR et al.; Staphylococcal abscesses contain two types of lipids which are bactericidal for Staphylococcus aureus . These include a group of long chain unsaturated free fatty acids and another as yet unidentified lipid with unique properties . When abscess homogenates are incubated with S . aureus culture filtrates, the amount of bactericidal activity is increased . This phenomenon is called activation . To determine the source of increased bactericidal activity during activation, individual types of lipid were isolated from abscess homogenates and examined for their ability to be activated . Activation was found to result from the release of long chain unsaturated fatty acids from glycerides, presumably by the action of staphylococcal lipase.

J Bacteriol, 1992 Apr, 174(8), 2711 - 6
Staphylococcus aureus osmoregulation: roles for choline, glycine betaine, proline, and taurine; Graham JE et al.; Choline, glycine betaine, and L-proline enhanced the growth of Staphylococcus aureus at high osmolarity (i.e., they acted as osmoprotectants) on various liquid and solid defined media, while an osmoprotective effect of taurine was shown only for cells growing on high-NaCl solid medium that lacked other osmoprotectants . Potassium pool levels were high, and there was little difference in levels in cells grown at different osmolarities . Glycine betaine accumulated to high levels in osmotically stressed cells, and choline was converted to glycine betaine . Proline and taurine also accumulated in response to osmotic stress but to lower levels than glycine betaine.

J Bacteriol, 1992 Apr, 174(8), 2702 - 10
Proline transport in Staphylococcus aureus: a high-affinity system and a low-affinity system involved in osmoregulation; Townsend DE et al.; L-Proline enhanced the growth of Staphylococcus aureus in high-osmotic-strength medium, i.e., it acted as an osmoprotectant . Study of the kinetics of L-{14C}proline uptake by S . aureus NCTC 8325 revealed high-affinity (Km = 1.7 microM; maximum rate of transport {Vmax} = 1.1 nmol/min/mg {dry weight}) and low-affinity (Km = 132 microM; Vmax = 22 nmol/min/mg {dry weight}) transport systems . Both systems were present in a proline prototrophic variant grown in the absence of proline, although the Vmax of the high-affinity system was three to five times higher than that of the high-affinity system in strain 8325 . Both systems were dependent on Na+ for activity, and the high-affinity system was stimulated by lower concentrations of Na+ more than the low-affinity system . The proline transport activity of the low-affinity system was stimulated by increased osmotic strength . The high-affinity system was highly specific for L-proline, whereas the low-affinity system showed a broader substrate specificity . Glycine betaine did not compete with proline for uptake through either system . Inhibitor studies confirmed that proline uptake occurred via Na(+)-dependent systems and suggested the involvement of the proton motive force in creating an Na+ gradient . Hyperosmotic stress (upshock) of growing cultures led to a rapid and large uptake of L-{14C}proline that was not dependent on new protein synthesis . It is suggested that the low-affinity system is involved in adjusting to increased environmental osmolarity and that the high-affinity system may be involved in scavenging low concentrations of proline.

Arch Otolaryngol Head Neck Surg, 1992 Apr, 118(4), 392 - 6
Ciprofloxacin . Use as a topical otic preparation; Brownlee RE et al.; Most common topical otic preparations have been shown to cause sensorineural hearing loss and hair-cell damage in experimental animals . Ciprofloxacin is a relatively new fluoroquinolone with excellent activity against Pseudomonas and methicillin-resistant Staphylococcus aureus . Recent studies have shown oral ciprofloxacin to be effective in the treatment of chronic serous otitis media and malignant external otitis . However, this drug has never been used as a topical otic preparation . Thirty-five albino female guinea pigs were used to investigate the ototoxicity of topical ciprofloxacin hydrochloride . Bilateral transbullae drug delivery tubes were placed and auditory brain-stem response thresholds were recorded at 20, 16, 8, and 4 kHz before treatment and 21 days after the completion of treatment . Two groups of guinea pigs were used . In group 1 (positive controls), five guinea pigs had 0.1 mL of neomycin sulfate administered in one ear while the opposite (control) ear received 0.1 mL of 0.9% sodium chloride solution; in group 2, 30 guinea pigs received 0.75% ciprofloxacin ophthalmic solution and 0.9% sodium chloride solution in the control ear . All drugs were given twice a day for 7 consecutive days . All results were evaluated with paired, two-tailed t test and Hotelling's T2 test, and calculation of power was performed on all nonsignificant results . No significant ototoxic reaction was observed; small increases in hearing thresholds occurred at 4 (5.65 +/- 8.25 dB {mean +/- SD}) and 8 kHz (3.70 +/- 6.63 dB {mean +/- SD}) in the ciprofloxacin-treated ears; however, no significant hair-cell loss was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

J Infect Dis, 1992 Apr, 165(4), 749 - 53
Staphylococcus aureus microcapsule expression attenuates bacterial virulence in a rat model of experimental endocarditis; Baddour LM et al.; The virulence of the Staphylococcus aureus strains that differed only in capsule expression was compared in a rat model of catheter-induced experimental endocarditis . The ID50 of all the strains was low (less than 3 x 10(3) cfu of S . aureus), suggesting that this model may be more sensitive than other animal models to differences in bacterial virulence . Compared with the wild-type strains that expressed type 5 or type 8 capsular polysaccharides, mutant strains devoid of capsule had significantly lower ID50 values . In contrast, a mutant that produced scant amounts of the type 5 polysaccharide had an ID50 similar to that of the parental type 5 isolate . As the bacterial inoculum was increased, each of the S . aureus strains reached final concentrations of 10(10)-10(11) cfu/g of vegetation; however, the nonencapsulated mutants colonized the left-sided vegetations at lower inocula than did the wild-type strains . This study indicates that microcapsule expression attenuates bacterial virulence in a rat model of catheter-induced endocarditis.

Eur J Immunol, 1992 Apr, 22(4), 1007 - 11
Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin-2 pathway; Gonzalo JA et al.; Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB-reactive T cells bearing T cell receptor (TcR) V beta 8 gene products . Given that interleukin 2 (IL-2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL-2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL-2 modulate SEB responses in vivo . Surprisingly, neither IL-2 nor CsA were able to change the in vivo kinetics and magnitude of SEB-induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB-reactive TcR V beta 8 gene family . In accord with these in vivo observations, IL-2 is incapable of reversing "anergy" and apoptotic cell death of V beta 8+ SEB-reactive T cells isolated from SEB-primed mice in vitro . Accordingly, upon SEB injection V beta 8+ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)alpha chains in vivo, although SEB induces IL-2R alpha in vitro . Altogether, these results indicate that the IL-2/IL-2R-mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens . Moreover, the data suggest that unresponsiveness of V beta 8+ T cells from SEB-primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death . Absence or presence of IL-2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.

Infect Immun, 1992 Apr, 60(4), 1642 - 7
Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo; Onderdonk AB et al.; Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge . Subsequent studies with the rat model for intra-abdominal sepsis indicated that intramuscular doses of 10 to 100 micrograms per animal 24 and 4 h prior to surgical implantation of the bacterial inoculum reduced the early mortality associated with the peritonitis phase of this experimental disease process . Quantitative cultures of blood obtained from challenged rats showed that significantly fewer organisms were present in the blood of PGG glucan-treated animals than in that of untreated animals . Quantitative studies of leukocytes of rats and mice following a single injection of PGG glucan showed a modest transient increase in the total leukocyte count . The possible mechanisms by which protection occurs in the animal model system are discussed.

Infect Immun, 1992 Apr, 60(4), 1514 - 23
Genetic evidence that bound coagulase of Staphylococcus aureus is not clumping factor; McDevitt D et al.; Staphylococcus aureus Newman cells carry a surface receptor for fibrinogen called clumping factor . The bacteria also express coagulase, an extracellular protein that binds to prothrombin to form a complex with thrombinlike activity which coverts fibrinogen to fibrin . We have confirmed a recent report (M . K . Boden and J.-I . Flock, Infect . Immun . 57:2358-2363, 1989) that coagulase can bind to fibrinogen as well as to prothrombin and also that a fraction of coagulase is firmly attached to the cell . A mutant with a deletion in the chromosomal coa gene was isolated by allelic replacement . Allelic replacement either was directly selected by electrotransformation of S . aureus R3N4220 with a nonreplicating suicide plasmid, pCOA18, carrying the delta coa::Tcr mutation or occurred after transduction of the integrated pCOA18 plasmid . The coa mutant was completely devoid of coagulase activity but interacted both with soluble fibrinogen and with solid-phase fibrinogen with the same avidity as the parental strain . This strongly suggests that the bound form of coagulase is not clumping factor and is not responsible for the adherence of S . aureus Newman to solid-phase fibrinogen . The fibrinogen binding determinant of coagulase was located in the C terminus of the protein, by analyzing truncated fusion proteins, in contrast to the prothrombin-binding region which was located in the N terminus.

Infect Immun, 1992 Apr, 60(4), 1358 - 62
Phagocytic killing of encapsulated and microencapsulated Staphylococcus aureus by human polymorphonuclear leukocytes; Xu S et al.; Phagocytosis by human polymorphonuclear leukocytes (PMNs) is an important host defense against infections caused by Staphylococcus aureus . Using an in vitro assay, we compared the opsonic requirements for phagocytic killing of prototype strains of encapsulated (type 1) and microencapsulated (type 5 and type 8) S . aureus by human PMNs . More than 85% of broth-grown, logarithmic-phase type 5 and 8 S . aureus organisms were killed by PMNs incubated with fresh normal human, rabbit, or guinea pig serum with complement activity . Under similar conditions, the highly encapsulated type 1 strain was not killed . Both encapsulated and microencapsulated strains were opsonized for phagocytosis by heat-inactivated serum raised in rabbits to killed bacteria . Opsonization by homologous serum was required for phagocytosis of the type 1 strain . In contrast, microencapsulated type 5 and 8 S . aureus organisms were killed by heat-inactivated rabbit serum raised to type 5, type 8, or nonencapsulated isolates; this result suggested that antibodies to the capsule or to cell wall components other than the capsule could opsonize these organisms for phagocytosis . The specificity of the assay was confirmed with capsule type 5-specific monoclonal antibodies, which were opsonic only for the type 5 S . aureus isolate . These studies indicate that, unlike the highly encapsulated type 1 strain, broth-grown microencapsulated S . aureus strains do not resist opsonophagocytic killing in vitro by normal serum.

Cell Immunol, 1992 Apr, 140(2), 331 - 44
Functional properties of human germinal center B cells; Butch AW et al.; Germinal centers (GCs) are histologically defined areas where B cells undergo extensive proliferation and maturation, or die of apoptosis . GC B cells isolated from human tonsils can be phenotypically identified by expression of peanut agglutinin (PNA)-binding sites and can be further divided into subpopulations based on their expression of CD77 . To assess the functional potential of GC B cells, we studied CD77+ PNA+ B cells isolated from tonsils by examining their differentiation status and their ability to proliferate in vitro to various cytokines and costimulants . We found that CD77+ GC B cells are less differentiated than CD77- GC B cells; GC B cells less frequently express cytoplasmic IgG and IgM, and spontaneously secrete less Ig compared to CD77- GC B cells . To identify conditions capable of inducing GC B cell proliferation, we examined IL-4, IL-2, IFN-gamma, low molecular weight BCGF (LMW-BCGF), and an MLR supernatant along with costimulants such as anti-IgM antibody, Staphylococcus aureus Cowan I (SAC), PMA, and pokeweed mitogen (PWM) . While non-GC B cells proliferate strongly in response to these stimuli, GC B cells did not proliferate . However, CD77+ as well as CD77- GC B cells mounted a rapid and strong proliferative response upon stimulation with IL-4, but only in the presence of anti-CD40 antibody . Moreover, although nine additional cytokines were examined, only IL-4 was capable of supporting CD77+ GC B cell proliferation in the presence of anti-CD40 antibody . When cells were stimulated with IL-4 and anti-CD40 antibody, we also found that IFN-gamma consistently decreased the proliferative response of CD77+ GC B cells without affecting the response of non-GC B cells . Taken together, these data indicate that GC B cells have characteristic growth requirements and that IL-4 may be important for GC B cell growth in vivo.

FEMS Microbiol Immunol, 1992 Apr, 4(4), 193 - 200
Interaction of staphylococcal fibronectin binding protein (FnBP), TSST-1 and alpha-toxin with murine lymphocytes; Rozalska B et al.; The most restrictive factor in the inductive phase of immune response is the contact and adhesion of antigen-presenting cells and responding lymphocytes . We report the in vitro formation of aggregates (clusters) of murine T lymphocytes and dendritic cells (DC) pulsed with highly purified staphylococcal toxins (TSST-1, alpha-toxin) and gene-cloned surface fibronectin binding protein (gal-FnBP) . A high percentage of T lymphocytes were involved in clustering with TSST-1-pulsed DC . Lymphocytes of mice infected with Staphylococcus aureus (strain Cowan 1) 21 days before testing, clustered with the same ability as cells of mice infected 3 days before . Dendritic cells pulsed with alpha-toxin formed a moderate number of clusters only when co-cultured with T lymphocytes of mice infected 3 days before the test . FnBP-pulsed DC aggregated strongly with T lymphocytes . This response peaked at 3-4.5 h-cultures and increased again after 24 h . We concluded that at the beginning of co-culture, FnBP amplified the cells' adhesion process on antigen-independent way . This conclusion is supported by the observation that DC pulsed with formalin-modified FnBP (with a 65% decreased ability to bind fibronectin) formed fewer clusters with T-immune cells than dendritic cells pulsed with native, non-treated FnBP.

Immunol Invest, 1992 Apr, 21(2), 123 - 42
Phenotypic and functional analysis of mucosal lymph node T cell subpopulations proximal and distal to chronic staphylococcal antigen challenge; Dobrzanski MJ et al.; We investigated the functional and subset surface marker characteristics of supramammary lymph node T cell populations at sites proximal and distal to the mammary region of goats repeatedly injected with heat-treated Staphylococcus aureus antigen (HK-SAC) . Flow cytometric studies showed quantitative differences in CD4+ and CD8+ T cell subsets among large and small lymphocyte populations in ipsilateral and contralateral supramammary lymph nodes of these animals . Although ipsilateral (draining) lymph nodes were enriched with CD4+ and CD8+ T cells, CD4/CD8 ratios were comparatively lower than those of contralateral (non-draining) lymph nodes (2.30 vs 2.60, respectively) . Cell size analysis by flow cytometry showed that nearly 70% of the lymphocytes in ipsilateral nodes were of large cell phenotype with CD4/CD8 ratios of 2.52 . In contrast, there were only 56.1% large lymphocytes in contralateral lymph nodes but with similar CD4/CD8 ratios of 2.55 . The number of large lymphocytes in corresponding nodes of uninoculated control animals was significantly lower (50%) with much lower CD4/CD8 ratios (2.08) . Alloantigenic responses of both ipsilateral and contralateral lymph node T cells were greater than those of uninoculated controls . Antigen-specific proliferation studies showed that ipsilateral lymph node T cells greatly enhanced both primed and non-primed lymph node B cell responses to HK-SAC, whereas those from contralateral lymph nodes were less stimulatory . In contrast, contralateral lymph node T cells had greater enhancing effects on PWM-induced polyclonal B cell responses . These studies indicate that repeated local infection with bacterial antigen induce changes in the numbers, ratios and antigen-specific and non-specific responses among ipsilateral (draining) and distal contralateral (non-draining) lymph node T cell populations in mucosal-associated immune systems such as the mammary gland.

J Appl Bacteriol, 1992 Apr, 72(4), 289 - 93
Nucleotide sequence and structural relationships of a chloramphenicol acetyltransferase encoded by the plasmid pSCS6 from Staphylococcus aureus; Cardoso M et al.; The 4.6 kb chloramphenicol resistance (Cm) plasmid, pSCS6, isolated from a naturally occurring Staphylococcus aureus biotype C encoded an inducible chloramphenicol acetyltransferase (CAT) . The respective cat gene and its regulatory region were cloned . Sequence analyses revealed two open reading frames: one for a 9-amino acid leader peptide and the other for the 215-amino acid CAT monomer . Comparisons of the predicted CAT amino acid sequences revealed a high degree of similarity between CAT from pSCS6 and the CAT variants encoded by Cm plasmids of the pC221 family . These close structural relationships suggested an intraspecific exchange of Cm-determinants between Staph . aureus of human and bovine biotype.

J Nutr Sci Vitaminol (Tokyo), 1992 Apr, 38(2), 221 - 5
Effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus strain 8985N infection in mice; Adjei AA et al.; The effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice . Mice fed nucleic acid-free 20% casein diet were administered intraperitoneally with a nucleoside-nucleotide mixture or with saline (control group) daily for 30 days . On the tenth day on this treatment, mice were challenged with the bacteria . The survival rates were 25% and 72% for the control and nucleoside-nucleotide groups, respectively . The recovery of the survived mice from the infection was confirmed by the increment of body weight and the reduction of the bacteria in the organs . The results show the effectiveness of the intraperitoneal administration of the nucleoside-nucleotide mixture for the recovery from the MRSA strain 8985N infection in mice.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 876 - 8
Tet determinants provide poor protection against some tetracyclines: further evidence for division of tetracyclines into two classes; Oliva B et al.; Atypical tetracyclines were active against Escherichia coli and Staphylococcus aureus strains containing determinants that mediate resistance to typical tetracyclines by efflux (Tet B and Tet K) or ribosomal protection (Tet M) mechanisms . The results support recently published data that tetracyclines are divisible into at least two classes on the basis of their modes of action.

Indian J Med Res, 1992 Apr, 96, 109 - 11
In vitro effect of intravenous immunoglobulin supplementation on serum opsonic activity in tracheostomised patients; Chandra RS et al.; An in vitro study of the effect of immunoglobulins (mainly IgG) on opsonophagocytic activity of polymorphs was carried out in 17 tracheostomised patients admitted in medical intensive care unit of our hospital . The opsonic and phagocytic activities were tested against Staphylococcus aureus by modified polymorphonuclear leucocyte overlay method; and serum IgG and serum IgM levels were estimated by single radial immunodiffusion technique . As compared to healthy volunteers, opsonophagocytic activity was significantly lower in tracheostomised patients . However, this activity improved markedly after immunoglobulin supplementation (P less than 0.01) . The same degree of enhancement was also observed in normal controls.

Protein Eng, 1992 Apr, 5(3), 267 - 71
A new protein conjugate that replaces the use of secondary antibodies engineered from the two staphylococcal enzymes protein A and 6-phospho-beta-galactosidase; Witt E et al.; The lacG gene encoding the 6-phospho-beta-galactosidase (E.C.3.2.1.85) of Staphylococcus aureus was fused to the protein A gene in the plasmid pRIT2T . Escherichia coli cells containing this plasmid produce a fusion protein with both IgG binding and 6-phospho-beta-galactosidase activities after heat induction . The recombinant gene was overexpressed and the hybrid protein was purified to homogeneity in high yield . The chimeric protein was shown to have almost identical enzymatic characteristics to pure 6-phospho-beta-galactosidase . This result leads to the conclusion that a free N-terminus of the 6-phospho-beta-galactosidase is not required for biological activity . The hybrid protein of protein A and 6-phospho-beta-galactosidase was used as an enzyme conjugate in enzyme-linked immunosorbent assays (ELISA) . The experiments presented demonstrate that the 6-phospho-beta-galactosidase is a suitable fusion partner in various diagnostic applications where an unique biological activity is required.

Int Angiol, 1992 Apr-Jun, 11(2), 113 - 6
Interaction between vascular prostheses and rifampicin in the prevention of the grafts infection . An experimental study; Freyrie A et al.; Infections caused by synthetic prostheses are relatively rare (1.5-6%) but serious complication in vascular surgery . There is no doubt that during and immediately after surgery bacterial contamination may occur . An in vitro study was carried out in the Vascutek laboratories, which revealed a high affinity between prostheses in Dacron gel and Rifampicin . This affinity, the result of an ionic bond, was demonstrated by the fact that after 5 days Rifampicin was still present on the prostheses . Encouraged by this result, an experimental study was carried out in sheep . Five sheep were operated on making a prosthetic graft in both of the common carotid arteries: on one side a Gelseal Dacron prosthesis was implanted after being soaked for 15 minutes in a solution containing 1 mg/ml Rifampicin . A Knitted Dacron prosthesis was implanted in the contralateral carotid artery, again after pretreatment with Rifampicin . Explants were made after 2, 24, 48, 72 and 96 hours, and the concentration of Rifampicin on the prostheses was assessed on the basis of the diameter of the inhibition area on Staphylococcus aureus cultures . The results showed that the Gelseal Dacron prostheses maintained Rifampicin concentrations with an antibacterial activity up to 72 hours; this property disappears with the Knitted Dacron prostheses after only 24 hours . These results confirm the high affinity of Gelseal Dacron and Rifampicin also in in vivo experimental models.

Eur J Clin Microbiol Infect Dis, 1992 Apr, 11(4), 364 - 71
Activity of cefpirome combined with beta-lactamase inhibitors and affinity for the penicillin-binding proteins of methicillin-resistant Staphylococcus aureus; Piddock LJ et al.; The susceptibility of 47 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to cefpirome, ceftazidime and methicillin was determined with Isosensitest media, with/without 5% NaCl and incubation at 30 degrees, 37 degrees and 44 degrees C for 24 and 48 h . At 24 h the MIC50 of cefpirome was 8 mg/l compared to 64 mg/l ceftazidime; at 48 h this increased to 32 mg/l cefpirome . The addition of 10 mg/l clavulanic acid or sulbactam lowered the MIC of cefpirome (at 48 h) by greater than four-fold in 23% and 11% of the strains, respectively . Cefpirome had primary affinity for penicillin-binding protein (PBP) 1 and 2 in five MRSA and one methicillin-susceptible Staphylococcus aureus . PBP 2a was present in all MRSA and was not saturated by 64 mg/l cefpirome . Clavulanic acid at a concentration of 10 mg/l bound to PBP 2 by greater than 50% in all strains, and when combined with cefpirome, the density of PBP 2a was also reduced but not completely abolished . The data from this study suggests that the mechanism of synergy of a beta-lactamase inhibitor plus a cephalosporin for MRSA may be due to an additive effect against PBPs and not just inhibition of a beta-lactamase . No cefpirome-resistant mutants could be selected from a methicillin-susceptible Staphylococcus aureus, but mutants were selected from an MRSA (expressing homogeneous methicillin resistance) for which MICs of cefpirome were 8 to 32 mg/l.

Cent Afr J Med, 1992 Apr, 38(4), 161 - 5
Neonatal septicaemia in Calabar, Nigeria; Antia-Obong OE et al.; In a twelve-month prospective study of 132 neonates suspected of having septicaemia in the Special Care Babies Unit (SCBU) of the University of Calabar Teaching Hospital (UCTH), Calabar, 79 were confirmed by positive blood cultures . Forty (50.6 pc) of these were preterm infants . The incidence was 19.3 per 1,000 hospital live births, while the mortality rate was 30.3 pc . The main predisposing factors were birth asphyxia, birth outside hospital, prolonged rupture of membranes, prolonged labour and poor water supply in hospital . The predominant pathogens were coliform organism and Staphylococcus aureus . The antibiotic sensitivity pattern of the pathogens suggest the use of gentamicin as a sole agent in the initial treatment of septicaemia while awaiting culture results . In view of the role of inadequate antenatal care, poor water supply and unhygienic delivery practices in the aetiology of newborn septicaemia, it is suggested that improved antenatal care, water supply and childbirth practices will reduce the incidence of septicaemia.

Cent Afr J Med, 1992 Apr, 38(4), 136 - 9
Empyema in children: a review of 52 cases; Mahalu W et al.; A prospective study was undertaken to assess the clinical pattern, management and outcome in children admitted with empyema at Harare Hospital . Fifty-two children were seen and followed up during the three-year period, 1984-1987 . All patients were managed with intrapleural drain and antibiotics . Two needed decortication . The predominant pathogen isolated from the pleural cavity was Staphylococcus aureus . All survived and on follow up only one child was found to have persistent radiological abnormality and poor exercise tolerance . Early intrapleural drainage and appropriate antibiotics should be the mainstay of treatment for empyema for the majority of children in Zimbabwe.

Cell Immunol, 1992 Apr, 140(2), 381 - 9
The major rheumatoid factor cross-reactive idiotype is dominantly expressed by Staphylococcus aureus Cowan strain I-activated CD5+ control B cells; Bonagura VR et al.; Some seropositive (RF+) and seronegative (RF-) rheumatoid arthritis (RA) patients selectively express high concentrations of the major RF cross-reactive idiotype (RCRI) in their sera and generate high frequencies of RCRI+ pokeweed mitogen (PWM)-induced plasma cells from their peripheral blood mononuclear cells (PBM) . To determine if normal individuals can express RCRI in vitro, B cells from controls were activated with Staphylococcus aureus Cowan strain I (SAC) bacteria to identify RCRI and RF production . In addition, we studied the relationship of RCRI expression with the subset of B cells bearing CD5 . Control CD5+ B cells are responsible for RCRI expression following SAC activation . We also observed that RCRI is dominantly expressed by control SAC-induced B cells in frequencies comparable to that expressed by some RA and juvenile rheumatoid arthritis patients' PBM activated by PWM . Therefore, the frequency of RCRI+ B cells in control and arthritis patients' PBL may be similar, or the selection and/or regulation of RCRI+ B-cell expression in vitro and in vivo may be different in arthritis patients compared to normal individuals.

Vet Immunol Immunopathol, 1992 Apr, 32(1-2), 1 - 11
Local immunity in the mammary gland; Lee CS et al.; The mammary glands of pregnant and non-pregnant sheep were stimulated by infusion of killed Staphylococcus aureus, and the lymphoid cell response delineated with a panel of monoclonal antibodies . Seven days after antigen infusion, the mammary glands of both pregnant and non-pregnant sheep displayed a striking feature, characterised by the presence of numerous CD45R+ MHC class II+ B cells in the periductal connective tissues . These cells were seen to be clustering around blood capillaries with very prominent endothelial cell lining . Some CD5+ CD4+ lymphocytes were scattered among the B-cell clusters, whereas a few CD8+ lymphocytes were seen mainly at the periphery of the B-cell clusters . Fourteen days after antigen infusion, numerous plasma cells were observed, most of them being of the IgA isotype . Seven days after parturition (approximately 40 days after antigen infusion) the number of lymphocytes and plasma cells in the infused glands had declined dramatically . These data indicate that B cell and helper T-cell interaction can take place at the local sites of antigen stimulation in the mammary gland.

J Hosp Infect, 1992 Apr, 20(4), 233 - 45
Typing of methicillin-resistant Staphylococcus aureus with an M13 repeat probe; Wei MQ et al.; A bacteriophage M13 tandem repeat has been used to probe EcoRI digested genomic DNA of methicillin-resistant Staphylococcus aureus (MRSA) . The patterns generated were found to be useful in typing MRSA and generally confirmed the relationships that had previously been recognized in other studies based on antimicrobial resistance and plasmid profiles . The epidemic MRSA of London hospitals (EMRSA) and the majority of the epidemic MRSA of eastern Australian hospitals (EA MRSA) gave the same pattern . However, two isolates previously classified as EA MRSA gave a different pattern and a third another pattern . One isolate from Dublin, two isolates from Nuneaton and two isolates from Singapore gave the same pattern as the two EA MRSA . With the exception of the early or classic MRSA all the other isolates examined gave their own distinctive patterns . With one exception the classic MRSA belonged to a separate group . The exception was of particular interest because it gave the same pattern as the majority of the EA MRSA . This suggests that there may be an evolutionary relationship between some of the classic MRSA and the EMRSA of London and the EA MRSA of Australia.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 894 - 7
Relative beta-lactamase- and transpeptidase-inhibitory activities of the new quinolone WIN-57273 in Staphylococcus aureus; Furet YX et al.; The new quinolone WIN-57273 was shown to inhibit Staphylococcus aureus beta-lactamase activity noncompetitively in vitro with an apparent Ki value of 0.5 mM . MICs of penicillin G for a highly quinolone-resistant, beta-lactamase-negative strain in the presence of exogenous beta-lactamase decreased considerably when subinhibitory concentrations of WIN-57273 were added . Furthermore, the attachment transpeptidase reaction, investigated on whole cells of S . aureus, was impeded by WIN-57273 concentrations of greater than or equal to 30 microM . While these interactions suggest a novel mechanism of action for this compound, they are probably not relevant to the overall antibacterial potency of WIN-57273.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 883 - 5
Lack of effect of carbonyl cyanide m-chlorophenylhydrazone on KB-5246 accumulation by Staphylococcus aureus; Kotera Y et al.; The accumulation of KB-5246 in a quinolone-susceptible strain of Staphylococcus aureus was about 70 times that of norfloxacin . Carbonyl cyanide m-chlorophenylhydrazone increased the accumulation of norfloxacin about eightfold, but it did not influence that of KB-5246 . The low efflux of KB-5246 from S . aureus may contribute to its potent antibacterial activity.

Bol Med Hosp Infant Mex, 1992 Apr, 49(4), 241 - 9
{Intrahospital infections at a neonatal service}; Larracilla-Alegre J et al.; This study is about the importance and mechanisms of the nosocomial infections, specially in newborn babies of the "Hospital General del Centro Medico La Raza del IMSS" . We studied 461 newborns of which 53 (11.49%) developed one or more intrahospitalary infections . The rate of intra-hospital infections was 18.40%, mainly due by septicemia, infections of the surgical wounds, and respiratory tract infections . The gramnegative bacterias were predominant . Also were found Staphylococcus aureus and Staphylococcus epidermidis frequently . We give some preventive advice.

Rev Argent Microbiol, 1992 Apr-Jun, 24(2), 73 - 80
{Prevalence of Staphylococcus aureus isolated from subclinical bovine mastitis in dairies of the city of San Luis}; Puig de Centorbi ON et al.; In order to detect subclinical mastitis by means of California Mastitis Test and recounting of somatic cells, 163 cows from the dairies of San Luis city, Argentina, were examined . Seventy six individuals (46.6%) exhibited an inflammatory response ranging > or = 2+ grade and a cellular recounting value of > or = 5 x 10(5), data compatible with those of subclinical mastitis . Staphylococcus aureus was isolated from 39 (51.3%) cultures as estimated by the sum of the two last values listed in Table 1 . Organisms were isolated by plating on brain heart infusion agar with 5% of sheep blood and on Baird-Parker media . One hundred and three S . aureus isolates recovered from 51 of 63 cows were characterized by coagulase activity by the tube method using human and bovine plasma; clumping factor; glucose and mannitol fermentation; thermonuclease (TNase), pigment, gelatinase, fibrinolysin, acetoin, hemolysin production; egg yolk, tellurite and catalase reaction and crystal violet types . All isolates were susceptible to cephalothin, clindamycin, methicillin, gentamycin and vancomycin; 94.1% were susceptible to chloramphenicol and 53.8% to G penicillin . Sixty three isolates (61.1%) were classified according to Hajek and Marsalek scheme as biotype C (bovine and ovine ecovar), 33 isolates (32.0%) were classified as biotype B (swine and poultry ecovar); 1 isolated (0.9%) as intermediate between B and D; 5 isolates (4.8%) as biotype A (human ecovar) and 1 isolated (0.9%) as biotype D (ecovar silvestres spp) (Table 2) . Production of enterotoxins A to E and toxic shock syndrome toxin-1 (TSST-1) was determined by the optimal susceptibility plate method on 27 isolates (26.2%) which were coagulase 3+ to 4+ and TNase highly positive . None of them produced enterotoxins including TSST-1 . The subclinical mastitis data and the prevalence of S . aureus coincide with those of other authors, both from Argentina and from other countries.

Biochim Biophys Acta, 1992 Mar 23, 1105(1), 125 - 30
Calcium ion-mediated regulation of the alpha-toxin pore of Staphylococcus aureus; Tokunaga H et al.; The water-soluble alpha-toxin monomers of Staphylococcus aureus become hexamers forming the transmembrane pore when exposed to the membranes . This pore is freely permeable to small hydrophilic molecules, e.g . carboxyfluorescein, and becomes less permeable in the presence of calcium ions . Calcium ion-mediated decrease of the carboxyfluorescein leakage could not be eliminated by EDTA added in the medium, but the carboxyfluorescein could be freed by EDTA added in the intraliposomal space . This result suggests that the alpha-toxin pore changes its conformation as the calcium ion is bound and that the binding site is exposed to the intraliposomal side of the membrane . The interaction between the alpha-toxin hexamer and 8-anilino-1-naphthalene-sulfonic acid (ANS) was monitored by determining the fluorescence in the presence and absence of calcium chloride . The mean distances between the tryptophan residues of the alpha-toxin hexamer and the bound ANS were calculated to be 1.90 and 1.80 nm in the absence and presence, respectively, of calcium ions . The results showed the calcium ion mediated conformational change of the membrane-embedded alpha-toxin hexamer.

Harefuah, 1992 Mar 15, 122(6), 369 - 71, 406
{Septic cavernous sinus thrombosis}; Avraham S et al.; Septic cavernous sinus thrombosis is a rare complication of facial infections, particularly of the dangerous triangle (nose and upper lip) and less often of the orbit, middle ear, pharynx or teeth . Staphylococcus aureus is the most frequent causative agent . Prompt diagnosis and early aggressive antibiotic therapy, with or without anticoagulants, is required . A 49-year-old woman developed this complication following multiple nasal abscesses . Despite intensive antibiotic and anticoagulant therapy she became permanently blind . We present this case to stress the fact that this disease is still fraught with high morbidity, and even mortality.

J Immunol, 1992 Mar 15, 148(6), 1797 - 803
Regulation of cell division of mature B cells by ionomycin and phorbol ester; Kim KM et al.; The growth of a human B lymphoma cell line B104, an experimental model for mature B cells, was inhibited by ionomycin but not 12-O-tetradecanoylphorbol-13-acetate (TPA) . Ionomycin inhibited B104 cells from entering into the M phase of the cell cycle without affecting DNA synthesis . The inhibition of cell division of B104 cells by ionomycin occurred within 24 h after stimulation . Because such a mode of action resembles that of anti-IgM antibodies, signals transduced by Ca2+ may be responsible for the inhibition of cell division of B104 cells by anti-IgM antibodies . Indeed, EGTA suppressed the inhibition of cell division of B104 cells caused not only by ionomycin, but also by anti-IgM antibody . Although TPA itself did not have any ability to promote the growth of B104 cells, it could cancel the inhibition of cell division of B104 cells by ionomycin and increase the proportion of B104 cells entering into the M phase of the cell cycle . Staphylococcus aureus Cowan I causes the greatest proliferation of normal human peripheral blood B cells during the period from 48 to 72 h after stimulation . When ionomycin was added to S . aureus Cowan I-stimulated peripheral blood B cells at 48 h of culture, it inhibited cell division during this period without affecting DNA synthesis . In the presence of TPA, this activity of ionomycin was suppressed, and the proportion of M-phase cells increased . These results suggest that cell division of mature B cells is regulated by the signals mediated by Ca2+ and protein kinase C in a mode quite different from that of regulation of DNA synthesis.

J Immunol, 1992 Mar 15, 148(6), 1759 - 63
Synthetic peptides of human CD4 enhance binding of Ig to monocyte/macrophage cells . I . Characterization and mapping studies; Lenert P et al.; Human T cell glycoprotein CD4 binds to class II MHC molecules and to HIV envelope protein gp120 . We have shown that CD4 and synthetic peptides corresponding to amino acid residues 21-49 of the first extracellular domain of CD4, also bind Ig and, with greater avidity, antibody:Ag complex . We investigated the effect of CD4 synthetic peptides on the binding and uptake of human Ig by monocyte/macrophage U937 cells . We found that a synthetic peptide corresponding to amino acid residues 21-49 enhanced binding to U937 cells of both aggregated and nonaggregated Ig . The enhancement was concentration dependent, occurred both in normal and low ionic strength conditions, and varied with the time and the temperature of the preincubation step . The enhancement was maximal after preincubation for 3 h at 37 degrees C . A peptide concentration of 20 micrograms/ml was sufficient for optimal binding of both nonaggregated and aggregated Ig . CD4 peptide 21-49 also enhanced binding of Ig to Staphylococcus aureus protein A . These studies open a new perspective in the way monocyte/macrophage cells handle Ig, antibody:Ag or Id:anti-Id complex, in particular when present at threshold amounts in a nonprecipitating form.

Proc Natl Acad Sci U S A, 1992 Mar 15, 89(6), 2051 - 5
Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line; Zembowicz A et al.; Toxic shock syndrome toxin 1 (TSST-1) is a Mr 22,000 protein produced by Staphylococcus aureus . It is thought to be the cause of toxic shock syndrome . We investigated the hypothesis that TSST-1 induces nitric oxide (NO) synthase and that the NO formed may be involved in the pathogenesis of toxic shock syndrome . We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1 and also expresses NO synthase activity upon immunological stimulation . J774.2 macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown product of NO, and induced concentration-dependent elevations of cGMP in the pig kidney epithelial cell line (LLC-PK1) . This latter effect was due to the generation of L-arginine-derived NO for it was (i) abolished by oxyhemoglobin (10 microM), a scavenger of NO, or by methylene blue (10 microM), an inhibitor of NO-activated guanylate cyclase; (ii) potentiated by superoxide dismutase (100 units/ml), which prolongs the life of NO; (iii) inhibited by NG-monomethyl-L-arginine (0.3 mM), an inhibitor of NO synthase; (iv) significantly decreased when L-arginine (0.4 mM) in the medium was replaced by D-arginine (0.4 mM) . Moreover, TSST-1 (100 nM) enhanced the activity of cytosolic NO synthase in J774.2 cells . Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1 . The effects of hydrocortisone were partially reversed by coincubation with RU 486 (1 microM), an antagonist of glucocorticoid receptors . Thus, TSST-1 and perhaps other exotoxins produced by Gram-positive bacteria induce NO synthase and the increased NO formation may contribute to toxic shock syndrome and possibly to changes in the immune responses that accompany infection.

J Immunol, 1992 Mar 15, 148(6), 1753 - 8
Gangliosides suppress tumor necrosis factor production in human monocytes; Ziegler-Heitbrock HW et al.; Both normal and malignant cells contain gangliosides as important cell membrane constituents that, after being shed, may influence cells of the immune system . We have studied the impact of gangliosides on the expression of TNF in blood monocytes and in the monocytic cell line Mono Mac 6 . Although under standard culture conditions, bovine brain gangliosides (100 micrograms/ml) suppressed LPS-stimulated TNF production 5-fold in PBMC and 10-fold in Mono Mac 6 cells, suppression was more efficient under serum-free conditions . Looking at highly purified gangliosides, GD3, GD1a, GM3, GM2, and GM1 were all effective in reducing TNF production in PBMC, and in Mono Mac 6 by factor 10 to 50 . The suppressive activity was lost in molecules, lacking the sugar moiety or the lipid moiety . Gangliosides appear to act at an early step of activation in that TNF transcripts were reduced and the mobilization of the nuclear factor kappa B was blocked . Furthermore, in time kinetics, gangliosides were effective for up to 30 min after addition of LPS, but not thereafter . However, the expression of the CD14 Ag, a receptor molecule for LPS-LPS binding protein complexes, was unaffected by gangliosides . Finally, when using Staphylococcus aureus or platelet activating factor as a stimulus, gangliosides were able to suppress TNF production in Mono Mac 6 cells by factor 5 to 10, as well . On the other hand, phorbol ester-induced production of O2- was similar in cells treated with and without gangliosides . Taken together, our data demonstrate that TNF gene expression in monocytes induced by different types of stimuli can be blocked by gangliosides at an early step of signal transduction.

Blood, 1992 Mar 15, 79(6), 1563 - 73
Subcellular distribution of the Rap1A protein in human neutrophils: colocalization and cotranslocation with cytochrome b559; Quinn MT et al.; Rap1A, a low molecular weight guanosine triphosphate-binding protein (LMWG), has been shown previously by us to be associated with purified cytochrome b from stimulated human neutrophils . In the present studies, we show that Rap1A is also associated with affinity-purified cytochrome b from unstimulated neutrophils and use specific anti-Rap1 peptide antibodies to biochemically and immunocytochemically determine the subcellular distribution of Rap1A in resting and activated human neutrophils . Analysis of the subcellular fractionation of unstimulated cells by Western blotting of isopycnic sucrose density gradient fractions with anti-Rap1 peptide antibodies indicated that Rap1A colocalized with cytochrome b in the plasma membrane as well as in the specific granule membranes and that it was translocated, along with cytochrome b, to the plasma membrane when the cells were stimulated with phorbol myristate acetate (PMA) . No evidence for a cytosolic localization of Rap1A was found in our studies; however, if the cells were disrupted by sonication, rather than N2 cavitation, a fraction of the Rap1A was released from the membrane . Electron microscopy of thin sections of cryofixed, molecular-distillation dried neutrophils labeled with anti-Rap1 antibody alone or double-labeled with anti-Rap1 and anti-cytochrome b peptide antibodies confirmed our biochemical localization, and quantitation showed that more than half of the specific granule-associated Rap1A was translocated to the plasma membrane in PMA-stimulated cells . Ultrastructural analysis of neutrophils phagocytosing Staphylococcus aureus also demonstrated the translocation of Rap1A with cytochrome b . Approximately 70% of the total Rap1A labeling was associated with the phagolysosomal membrane, the site of assembly of the superoxide-generating system . The colocalization and cotranslocation of Rap1A with cytochrome b in resting and activated neutrophils is consistent with a functional association of these two molecules in the intact cell and provides further evidence for a role of this LMWG in the structure or function of the neutrophil superoxide-generating system.

J Biol Chem, 1992 Mar 5, 267(7), 4292 - 5
Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils; Selsted ME et al.; A potent and structurally novel antimicrobial peptide was purified from the cytoplasmic granules of bovine neutrophils . Suspensions of Staphylococcus aureus and Escherichia coli were virtually sterilized by the peptide at a concentration of 10 micrograms/ml . The peptide was found to be comprised of 13 amino acids, 5 of which were tryptophan residues, and the carboxyl-terminal arginine was carboxamidated . The primary structure of the peptide, which we have named indolicidin, is H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH2 . The mole percent of tryptophan in indolicidin is the highest observed among known protein sequences . The multiple tryptophan residues presumably play an important role in the function of this unique antibiotic peptide.

J Biol Chem, 1992 Mar 5, 267(7), 4766 - 72
Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin; Patti JM et al.; Some strains of Staphylococcus aureus bind collagen with a high degree of specificity and affinity . This interaction can represent a mechanism of substrate adhesion and may be an important step in the pathogenesis of osteomyelitis and infectious arthritis . We now report on the cloning, sequencing, and expression of a gene name cna, encoding a S . aureus collagen adhesin . The cna gene was isolated from a lambda GT11 S . aureus genomic library and encodes an 1185 amino acid polypeptide . The deduced amino acid sequence reveals several structural characteristics similar to previously described Gram-positive bacterial cell surface proteins . Antibodies raised against the native collagen adhesin from S . aureus recognize the recombinant collagen adhesin . Collagen binding activity can be detected in a lysate obtained from Escherichia coli cells, which harbor the cloned cna gene on an expression plasmid . Collagen-binding proteins can be detected in the lysate when analyzed by a Western blot type assay in which the membrane-transferred proteins are probed with radioactively labeled collagen . Finally, the bacterial lysate containing the recombinant adhesin can effectively inhibit the binding of soluble collagen to cells of S . aureus.

Biochim Biophys Acta, 1992 Mar 2, 1104(2), 325 - 30
Effect of fatty acyl domain of phospholipids on the membrane-channel formation of Staphylococcus aureus alpha-toxin in liposome membrane; Tomita T et al.; By use of carboxyfluorescein-loaded multilamellar liposomes prepared from synthetic phosphatidylcholine (PC) or sphingomyelin and cholesterol in a molar ratio of 1:1, we studied whether or not fatty acyl domain of the phospholipids affects the membrane-damaging action (or channel formation) of Staphylococcus aureus alpha-toxin on the phospholipid-cholesterol membranes . Our data indicated: (1) that toxin-induced carboxyfluorescein-leakage from the liposomes composed of saturated fatty acyl residue-carrying PC and cholesterol was decreased with increasing chain length of the acyl residues between 12 and 18 carbon atoms, although toxin-binding to the liposomes was not significantly affected by the length of fatty acyl residue; (2) that unsaturated fatty acyl residue in PC or sphingomyelin molecule conferred higher sensitivity to alpha-toxin on the phospholipid-cholesterol liposomes, compared with saturated fatty acyl residues; and (3) that hexamerization of alpha-toxin, estimated by SDS-polyacrylamide gel electrophoresis, occurred more efficiently on the liposomes composed of PC with shorter fatty acyl chain or unsaturated fatty acyl chain . Thus, hydrophobic domain of the phospholipids influences membrane-channel formation of alpha-toxin in the phospholipid-cholesterol membrane, perhaps by modulating packing of phospholipid, cholesterol and the toxin in membrane.

Kansenshogaku Zasshi, 1992 Mar, 66(3), 400 - 6
{A clinical study of respiratory tract infection due to Staphylococcus aureus detected by transtracheal aspiration}; Mikasa K et al.; A clinical study of 24 patients with respiratory tract infection due to S . aureus detected by transtracheal aspiration (TTA) was conducted, and the following results were obtained . 1) The detection frequency of S . aureus was relatively low (4.6%) . 2) Pneumonia was the principal clinical manifestation . 3) Approximately one half of the patients had previously received antimicrobials . 4) Multiple organisms were frequently detected, particularly in cases of hospital-acquired infection . H . influenzae was the most frequently simultaneously detected organism . 5) On sputum examination, approximately 20 ml of purulent sputum was found in most cases, and S . aureus was detected in sputum specimens from 20 of the patients . 6) The largest number of cases was found in 1987 . Onset was most common from autumn to spring . 7) Undernutrition was the most frequently associated host factor . As indicated by the above findings, the clinical expression of S . aureus infection is variable, and it is important that it be diagnosed accurately.

Kansenshogaku Zasshi, 1992 Mar, 66(3), 376 - 81
{Effect of methylrosanilinium chloride to MRSA nasal carriers}; Ogino J et al.; Since the end of 1987, we have noticed an increasing incidence of Methicillin resistant Staphylococcus aureus (MRSA) among the inpatients of Yamanashi Medical College Hospital . MRSA strains were identified in 70-80 percent of the specimens obtained from patients with Staphylococcus aureus . From 1988 we performed yearly bacteriological examinations of the nares of medical personnel at Yamanashi Medical College Hospital . We treated nasal carriers with OFLX drop lotion or Povidone-iodine applied to the nares . In 1991 we treated eight nasal carriers, who had been unsuccessfully treated with Povidone-iodine, with 0.01% Methylrosanilinium Chloride ointment which was applied to the nares once a day for two weeks . A post-bacteriological examination again revealed that MRSA vanished from the nares of six nasal carriers . The minimum inhibitory concentration (MIC) of Methylrosanilinium Chloride was determined by the agar plate dilution method . The 100% MICs of MSSA were 1.0 microgram/ml and of MRSA were 1.0 microgram/ml by Methylrosanilinium Chloride . Moreover we examined the MICs of Methylrosanilinium Chloride against MRSA under the existing 5% Albumin, and consequently the 100% MICs were 4.0 micrograms/ml . Therefore a 0.01% Methylrosanilinium Chloride has sufficient efficacy against MRSA . The reaction of the skin and nasal mucosa to Methylrosanilinium Chloride was examined by using three groups of guinea pigs . 0.1% and 0.01% Methylrosanilinium Chloride ointment and hydrophylic poloid were applied to the nares and skin once a day for two weeks . Post-observation with an opticmicroscope revealed no significant findings . Methylrosanilinium Chloride shows good anti-Staphylococcus aureus ability . Further investigation is needed to determine if Methylrosanilinium Chloride has additional clinical application.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 656 - 61
Characterization of penicillin-binding protein 2 of Staphylococcus aureus: deacylation reaction and identification of two penicillin-binding peptides; Chambers HF et al.; Penicillin-binding protein (PBP) 2 is the major PBP of five that have been identified in susceptible strains of Staphylococcus aureus . Beta-lactam antibiotic binding to PBP 2 is important for the antibacterial effect . Antibiotic binding to PBP 2 in strain 209P was examined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in competition assays using {3H}penicillin as the radiolabel . Clavulanic acid, which is specifically bound by PBP 2, and cefaclor, which is specific for PBP 3, were studied . Cefaclor, which alone appeared not to bind PBP 2, in combination inhibited PBP 2 binding of clavulanic acid . By varying the temperature during radiolabeling with {3H}penicillin in cefaclor competition assays and in direct radiolabeling assays with {3H}cefaclor, it was shown that cefaclor was bound by PBP 2 with high affinity (50% inhibitory concentration, less than or equal to 0.1 microgram/ml) and that the apparent low-affinity binding (50% inhibitory concentration, greater than 10 micrograms/ml) in competition assays performed at 37 degrees C was due to rapid deacylation . Two penicillin-binding peptides of PBP 2 also were identified in fluorographs of PBPs separated by nonequilibrium pH gradient gel and two-dimensional electrophoresis . Rapid deacylation for some antibiotics and the presence of two penicillin-binding peptides are two properties of PBP 2 that should be considered when correlating results of binding assays with effects of beta-lactam antibiotics on S . aureus.

Pflugers Arch, 1992 Mar, 420(3-4), 259 - 63
Fever response of sheep in the peripartum period to gram-negative and gram-positive pyrogens; Goelst K et al.; We have measured body temperatures and serum iron concentrations of sheep in the peripartum period following administration of endotoxin and Staphylococcus aureus cell walls . Both the rise in rectal temperature and the fall in serum iron concentration following intravenous injection of S . aureus were the same immediately pre- and postpartum as they were 5 weeks after parturition . The rise in rectal temperature following intravenous endotoxin injection immediately pre- and postpartum was significantly less than that of the same ewes 5 weeks later . However, the fall in serum iron concentration following endotoxin injection was significantly suppressed only prepartum . We conclude that fever is not suppressed in sheep in the peripartum period, but the response to endotoxin is suppressed, through complex processes incidental to the mechanism responsible for the maintenance of gestation and induction of labour.

Vet Immunol Immunopathol, 1992 Mar, 31(3-4), 301 - 12
Lysostaphin: immunogenicity of locally administered recombinant protein used in mastitis therapy; Daley MJ et al.; A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts . Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response . Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein) . Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass . Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin . Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule . Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy.

J Burn Care Rehabil, 1992 Mar-Apr, 13(2 Pt 1), 198 - 202
Susceptibility testing of topical antibacterials against methicillin-resistant Staphylococcus aureus; Smoot EC 3rd et al.; Methicillin-resistant Staphylococcus aureus (MRSA) isolates that were collected from 44 consecutive patients during 1 year in a community hospital were tested for susceptibility to five commonly used topical antibacterial agents . Agar-well susceptibility testing, which was based on zones of inhibition, was used to compare the effectiveness of the antibacterials against MRSA . Nitrofurazone was effective in inhibition of bacterial growth and was relatively inexpensive . Mupirocin was found to be effective but more costly for treatment of MRSA . Varying degrees of susceptibility to silver sulfadiazine, mafenide acetate, and bacitracin were noted in the cultures that were obtained at this medical center . On the basis of our findings from susceptibility tests compared with those of another center, we recommend that all hospitals undertake topical sensitivity testing of their MRSA isolates . Appropriate and effective topical antibacterial therapy can then be planned within each center.

Res Vet Sci, 1992 Mar, 52(2), 260 - 1
Pathogenicity of Fusobacterium necrophorum biovar B; Smith GR; Previous studies showed that the high minimum infective dose (more than 10(6) organisms) of biovar A strains of Fusobacterium necrophorum for mice by subcutaneous inoculation could be greatly reduced, often to less than 10 organisms, by suspending the fusobacteria in sublethal doses of broth cultures of certain other bacterial species, such as Staphylococcus aureus . The present study showed that no such enhancement of infectivity occurred with two biovar B strains . This observation, together with the low pathogenicity of pure cultures of these strains for mice, suggests that biovar B plays no more than a minor role in the aetiology of necrobacillosis.

Diagn Microbiol Infect Dis, 1992 Mar-Apr, 15(3), 195 - 9
Application of restriction endonuclease analysis of chromosomal DNA in the study of Staphylococcus aureus colonization in continuous ambulatory peritoneal dialysis patients; Pignatari A et al.; The relationship between nasal and skin colonization with Staphylococcus aureus and subsequent infection in continuous ambulatory peritoneal dialysis (CAPD) patients in Brazil has been documented by restriction endonuclease analysis of plasmid DNA . However, S . aureus strains without detectable plasmids have been identified . Using restriction endonuclease analysis of chromosomal DNA hybridized with an rRNA gene probe, we document the diversity of S . aureus strains without detectable plasmids colonizing CAPD patients . Ten paired strains without detectable plasmids from five patients were studied by restriction endonuclease analysis of chromosomal DNA and by phage typing . Five different profiles were obtained by restriction endonuclease analysis of chromosomal DNA . Although four of the ten paired isolates were nontypeable by phage typing, all were discriminated by restriction endonuclease analysis of chromosomal DNA . These results demonstrate that restriction endonuclease analysis of chromosomal DNA is a useful epidemiologic tool and complements the restriction endonuclease analysis of plasmid DNA of S . aureus by providing a means of typing strains without detectable plasmids.

Ceylon Med J, 1992 Mar, 37(1), 12 - 4
Methicillin resistant Staphylococcus aureus; Perera J et al.; Out of 308 isolates of Staphylococcus aureus isolated from specimens processed at the Department of Microbiology, Faculty of Medicine, Colombo 66 (21.5%) were resistant to methicillin . A significantly higher proportion of methicillin resistant Staphylococcus aureus (MRSA) were isolated from special care units, namely the Premature Baby Unit (PBU) and the Plastic Surgery Unit (PSU) when compared with other general medical and surgical units . Most of these strains were also resistant to many other antibiotics . The patients with MRSA infections had a longer mean hospital stay when compared to patients with methicillin sensitive Staphylococcus aureus (MSSA) infections . MRSA strains are as virulent as MSSA strains and these infections are mainly nosocomial.

J Burn Care Rehabil, 1992 Mar-Apr, 13(2 Pt 2), 293 - 7
Burn and trauma units as sources of methicillin-resistant Staphylococcus aureus; Phillips LG et al.; At the time that methicillin-resistant Staphylococcus aureus (MRSA) began to achieve clinical prominence, it was thought to be spread by exogenous vectors . Institution of rigorous infection control efforts, including isolation procedures, was found to have little effect on the frequency of MRSA colonization of burn wounds . It was later found that handwashing was sufficient to prevent cross-contamination . Subsequently, it has been shown that patients can be harboring MRSA at the time of admission to the burn unit and that multiple antimicrobial resistance can develop among organisms that reside in the patient through plasmid-mediated transfer of resistance genes . Excessive use of such agents as the synthetic penicillins and second- and third-generation cephalosporins has selected for the survival of these organisms . Currently, the only available agent for systemic treatment of MRSA infection is vancomycin, the use of which is expensive and associated with significant toxicity . Muciprocin is a topical antimicrobial that promises to be useful in the treatment of such infections . Other agents for systemic use are needed, since use of a single drug to combat MRSA infections seems likely to encourage the emergence of resistant organisms.

J Antibiot (Tokyo), 1992 Mar, 45(3), 297 - 305
Galacardins A and B, new glycopeptide antibiotics; Takeuchi M et al.; A strain of actinomycetes identified as Saccharothrix sp . SANK 64289 was found to produce new antibiotics, galacardins A and B . Their physico-chemical properties showed that they were new members of glycopeptide antibiotics . They were structurally related to beta-avoparcin but differed from it only in sugar composition . Though beta-avoparcin does not contain galactose, galacardins A and B did contain two and one moles of galactose, respectively . They showed strong antimicrobial activity against Gram-positive bacteria and also showed excellent in vivo protective activity against Staphylococcus aureus infection in mice.

Enferm Infecc Microbiol Clin, 1992 Mar, 10(3), 143 - 7
{The effect of clindamycin on intraphagocytic Staphylococcus aureus in leukocytes from patients with chronic osteomyelitis}; Burgaleta C et al.; BACKGROUND: Osteomyelitis are infections difficult to be completely cured, and its optimal therapy had not clearly been established . METHODS: We study the bactericidal activity of polymorphonuclear leukocytes and also of serum from 13 patients with Staphylococcus aureus chronic osteomyelitis . We also studied the activity of clindamycin against intraphagocytic S . aureus . The study was done in vitro using control S . aureus strain ATCC 25923 and also microorganisms recovered from infected bone . RESULTS: S . aureus two hours survival rates in polymorphonuclear leukocytes were 13.5 +/- 4.4 x 10(6), 10.5 +/- 4.0 x 10(6), 11.0 +/- 4.0 x 10(6), using polymorphonuclear leukocytes from controls and patients, with control and autologous sera respectively (p greater than 0.05) . We have observed a bactericidal activity defect in polymorphonuclear leukocytes from one patient and in the sera of 7 other patients . The incubation with clindamycin (10 MIC) reduces the number of cfu/ml to 2.1 +/- 0.9 x 10(6), 1.1 +/- 0.7 x 10(6) y 1.9 +/- 1.1 x 10(6), and we also detected and additional inhibition of 81.7 +/- 7%, 70.7 +/- 17% and 79.0 +/- 4% respectively . CONCLUSION: The results of our study confirm that clindamycin has an intracellular action against intraphagocytic S . aureus and also showed the ability of this antimicrobial agent to cover defects in defensive mechanism of the host . Both statements give support the potential usefulness of clindamycin as therapy for bone infections due to S . aureus.

Zentralbl Hyg Umweltmed, 1992 Mar, 192(6), 544 - 53
Adaptation of two commercially available DNA probes for the detection of E . coli and Staphylococcus aureus to selected fields of dairy hygiene--an exemplary study; Kneifel W et al.; The application of two commercially available colorimetric DNA hybridization tests (GENE-TRAK E . coli and Staphylococcus aureus) to selected aspects of dairy hygiene was investigated . Bacterial isolates of different origin, naturally contaminated cheese varieties, nonfat dry milk, milk concentrates, artificially contaminated milk and raw milks from udder quarters were examined . Based on the observation that the sensitivity of the E . coli DNA probe was comparable to that of the beta-D-glucuronidase-based fluorescence reaction (with 4-methyl-umbelliferyl-beta-D-glucuronide) of E . coli strains in Fluorocult lauryl sulfate broth, a Most Probable Number technique for enumerating E . coli in cheese using the DNA probe was developed . Another specific DNA probe was applied for the detection of S . aureus as a mastitis agent . By using a modified sample preparation, specific diagnosis of this microorganism in milk from udder quarters was enabled within 6 hours . This procedure is recommended to be used in screening tests . Based on the examples presented the potential of these tests in several fields of hygiene was illustrated.

Ann Rheum Dis, 1992 Mar, 51(3), 378 - 83
Staphylococcal infections in childhood dermatomyositis--association with the development of calcinosis, raised IgE concentrations and granulocyte chemotactic defect; Moore EC et al.; There is a high incidence of staphylococcal infection in children with dermatomyositis, which is limited to those children who either already have or subsequently develop calcinosis . Of 15 children followed up for 3-10 years after diagnosis, all nine who developed calcinosis had infections with Staphylococcus aureus compared with none of six without calcinosis . Of these nine, the occurrence of staphylococcal infections before calcinosis was observed in four, suggested by history in two, and unclear in three children . Granulocyte chemotaxis to Staphylococcus aureus was more severely depressed in those children with calcinosis, whereas those without calcinosis did not differ significantly from controls . The chemotactic defect was due to a serum factor (patients' serum depressed control chemotaxis and control serum corrected the patients' chemotaxis) . The nine children with calcinosis also had significantly higher serum IgE concentrations than non-atopic age matched controls; the six without calcinosis did not differ from controls . The increased IgE concentrations appeared to develop after staphylococcal infection and before calcinosis . Two of five patients with calcinosis had increased antistaphylococcal IgE antibodies; neither of the two patients without calcinosis had such increased antibodies . This suggests preceding immunological differences in patients with dermatomyositis who do and do not subsequently develop calcinosis, either increasing susceptibility to Staphylococcus aureus infection or potentially resulting from such infections.

Appl Environ Microbiol, 1992 Mar, 58(3), 1067 - 9
Enterotoxigenicity of Staphylococcus strains isolated from Spanish dry-cured hams; Marin ME et al.; The ability of 135 Staphylococcus strains isolated from Spanish dry-cured hams to produce enterotoxins in culture was investigated by the reversed passive latex agglutination method . A high percentage of enterotoxigenic Staphylococcus aureus strains (85.9%) was recorded, and 54.3% of these produced enterotoxin A . One of the two Staphylococcus epidermidis strains produced enterotoxin C . The reversed passive latex agglutination method yielded satisfactory results.

J Am Board Fam Pract, 1992 Mar-Apr, 5(2), 193 - 200
Implications of methicillin-resistant Staphylococcus aureus on nursing home practice; Coll PP et al.; BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is being isolated with increasingly frequency from nursing home patients . There is a limited choice of antibiotics available to treat infections caused by the organism . Control measures for nursing homes have not been well established . METHODS: Using the key words "methicillin," "homes for the aged," and "long-term care," and also using the text term "MRSA," the MEDLINE files were searched from 1966 to 1989 using a CD ROM system . Articles occurring subsequent to this search, until the manuscript was submitted, were accessed using a monthly update from the MEDLINE database using the same key words . RESULTS: MRSA prevalence rates as high as 34 percent have been reported from long-term care settings . Risk factors for developing MRSA include being sick, debilitated, and functionally impaired . Frequent use of antibiotics and invasive devices, such as catheters, are also identified risk factors . The implication of MRSA colonization on patient outcomes is not clear . Vancomycin remains the drug of choice for treating MRSA infections . Control measures include surveillance of new and established cases and the introduction of isolation procedures . Patients colonized with MRSA should not be refused admission to a nursing home because of their MRSA status . CONCLUSIONS: MRSA in nursing homes will continue to increase . There are resulting implications for patient care, health care costs, and admission and discharge policies . Research should first establish what effect MRSA colonization has on clinical outcomes in this setting and, if necessary, go on to develop clinical and cost effective methods of prevention and control.

Mol Microbiol, 1992 Mar, 6(6), 703 - 13
Protein A-calmodulin fusions: a novel approach for investigating calmodulin function in yeast; Stirling DA et al.; A novel gene fusion approach which may be of more general use has been developed for investigating the function of calmodulin in the budding yeast Saccharomyces cerevisiae . By fusing a portion of the Staphylococcus aureus spa gene (encoding protein A) to CMD1, the S . cerevisiae gene encoding calmodulin, we have generated a yeast calmodulin with an affinity tag able to bind immunoglobulins . The chimaeric protein A-calmodulin (ProtA-CaM) polypeptide functions in vivo and shows Ca(2+)-dependent binding to calmodulin target proteins . The spa-CMD1 fusion has been used (i) to prepare (by affinity chromatography) a fraction of yeast proteins which interact with calmodulin, (ii) to isolate genes encoding calmodulin target proteins by direct screening of an expression library, and (iii) to visualize calmodulin-binding proteins in crude extracts by Western blot analysis.

Immunology, 1992 Mar, 75(3), 420 - 6
B-cell maturation in chronic lymphocytic leukaemia . IV . T-cell-dependent activation of leukaemic B cells by staphylococcal enterotoxin 'superantigens'; Duan X et al.; Staphylococcal enterotoxins (SE) are potent T-lymphocyte activators that stimulate T cells by directly cross-linking HLA-DR molecules on antigen-presenting cells with the V beta gene products of the T-cell receptor . The different SE activate all T cells expressing a given V beta, and, therefore, have been termed 'superantigens' . Here we show that SE are potent activators of leukaemic B cells from patients with chronic lymphocytic leukaemia (CLL) . Purified B cells from seven of eight CLL patients with high WBC counts (greater than 80,000/microliters) responded to one or several of the tested SE (SEA, SEB, SEC1, SED, SEE) by proliferation ({3H}TdR incorporation) and/or Ig secretion . In several instances, the response of leukaemic B cells to SE was much stronger than was the response to other known B-cell activators including EBV, pokeweed mitogen (PWM), phorbolester (TPA), and Staphylococcus aureus Cowan I (SAC) . The activation of leukaemic B cells by SE was strictly dependent on the addition of irradiated T cells isolated from healthy donors . FACS analysis of cultured cells ensured that the proliferating cells were indeed B cells . Taken together, these results demonstrate that SE are strong T-cell-dependent B-cell activators that, in some cases, can stimulate maturation of leukaemic B cells which are refractory to other activation signals.

Pediatr Infect Dis J, 1992 Mar, 11(3), 184 - 8
Multiple methicillin-resistant Staphylococcus aureus strains as a cause for a single outbreak of severe disease in hospitalized neonates; Noel GJ et al.; Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infection . Outbreaks of infection caused by these pathogens are generally considered to be traceable to introduction of single strains into a hospital population . A large outbreak of bacteremic disease that recently occurred in our neonatal intensive care unit (11 episodes in 10 patients) involved 9 low birth weight infants and was associated with serious infection (4 episodes of meningitis) . To determine the role of a single point source in this outbreak, isolates were characterized based on phenotypic and genotypic analyses . Phenotypic analysis included assessing hemolytic activity, phage typing, antimicrobial susceptibility testing and methicillin resistance population analysis . Genotypic analysis included assessment of plasmid profiles, dot-blot hybridization, restriction enzyme fragment pattern analysis and hybridization analysis of chromosomal DNA using a panel of staphylococcal gene probes . This analysis established that at least two distinct strains of MRSA were responsible for disease during this outbreak . This experience demonstrates the potential for MRSA to cause severe disease in the neonatal intensive care unit and indicates that the epidemiology of MRSA outbreaks is more complex than the spread of a single strain of bacteria.

Infect Control Hosp Epidemiol, 1992 Mar, 13(3), 151 - 9
Antimicrobial therapy for methicillin-resistant Staphylococcus aureus colonization in residents and staff of a Veterans Affairs nursing home care unit; Strausbaugh LJ et al.; OBJECTIVE: To evaluate the effect of antimicrobial therapy on patients and staff colonized with methicillin-resistant Staphylococcus aureus (MRSA) in a skilled nursing facility and to assess the role of the environment as a potential reservoir for MRSA in the nursing home setting . DESIGN: As part of a comprehensive program to control an MRSA outbreak in a nursing home, patients and staff colonized with MRSA received 1 of 3 antimicrobial decolonization regimens depending upon the site and extent of colonization . Followup cultures were performed during therapy and on days 2, 7, 14, and 30 following the completion of therapy . Cultures of the patients' inanimate environment (pajamas, sheet, and floor) were obtained during and after therapy . Antimicrobial susceptibility tests were performed on 54 MRSA isolates obtained before and 44 MRSA isolates recovered after therapy . SETTING: A 120-bed Veterans Affairs nursing home care unit . PARTICIPANTS: Thirty-six patients and 7 staff nurses colonized with MRSA at 1 or more sites . INTERVENTION: Decolonization therapy with rifampin, trimethoprim-sulfamethoxazole, and clindamycin used alone or in various combinations for 5 or 10 days in conjunction with other infection control measures employed to combat the MRSA outbreak . RESULTS: Twenty (56%) of the 36 NHCU patients were either persistently colonized or became recolonized with MRSA during the 30-day followup period . Positive cultures on day 3 during therapy frequently identified patients who subsequently exhibited persistent or recurrent colonization . Before therapy, 92% of MRSA isolates were susceptible to rifampin, whereas only 43% of the isolates obtained after therapy were susceptible . Sixteen (80%) of 20 patients with persistent or recurrent colonization had rifampin-resistant strains of MRSA isolated after therapy . Twenty-three (18%) of 125 environmental cultures obtained during and after therapy from patients who exhibited persistent or recurrent colonization were positive for MRSA, in contrast to 9 (8%) of 107 from patients who were successfully decolonized . CONCLUSIONS: The decolonization component of the outbreak control program was judged to be ineffective and potentially hazardous because colonization persisted or recurred in more than half of the patients, and substantial antimicrobial resistance was noted in MRSA stains isolated after therapy . Resistance, especially to rifampin, and possibly re-acquisition of MRSA from other human or environmental sources were 2 factors that appeared to impede the decolonization effort.

J Steroid Biochem Mol Biol, 1992 Mar, 41(3-8), 291 - 9
Effect of ligand binding and DNA binding on the structure of the mouse oestrogen receptor; Emmas CE et al.; We have investigated the effects of ligand and DNA binding on the structure of the oestrogen receptor by performing limited proteolysis and analysing DNA binding activity by gel shift analysis . The effects of oestradiol, 4-hydroxytamoxifen and ICI 164,384 have been examined and we have found that despite differences in the DNA binding activity or relative mobility of the receptor-DNA complex we were unable to detect differences in the cleavage pattern produced by trypsin, chymotrypsin, Staphylococcus aureus V8, papain or elastase . Inhibition of DNA binding by ICI 164,384 was lost in receptor fragments that lacked the hormone binding domain . In contrast to the full-length receptor, proteolytic fragments produced by chymotrypsin differed in their ability to bind to an oestrogen response element (ERE) vs a thyroid response element (TRE) . Evidence is presented that this difference can be accounted for by the inability of fragments lacking the hormone binding domain to dimerise on a TRE.

J Clin Immunol, 1992 Mar, 12(2), 92 - 100
Hyper-IgM immunodeficiency syndrome: influence of lymphokines on in vitro maturation of peripheral B cells; Gougeon ML et al.; Peripheral B cells from six patients affected with the hyper-IgM immunodeficiency syndrome, characterized by an absence of IgG and IgA in serum with a concomitant elevated level of IgM, were analyzed for phenotypic and functional characteristics . We report that although the membrane antigenic pattern expression was characteristic of mature B cells, B cells from most patients exhibited an impairment in their in vitro response to several lymphokines, such as recombinant interleukin 2 (rIL-2) and low molecular weight B-cell growth factor (BCGF), that induce proliferation of anti-mu-activated B cells . This impairment was also found in response to a lymphokine mixture from a CD2-activated T-cell clone . The decrease in lymphokine-induced B-cell proliferation was accompanied by a low B-cell differentiation, whether patients' B cells were stimulated by the T-cell clone supernatant or rIL-2 and rIL6, lymphokines able to support differentiation of Staphylococcus aureus Cowan I (SAC)-activated B cells . In addition, none of the lymphokines tested were able to induce patients' B cells to switch from IgM-secreting cells to IgG- and IgA-secreting cells . We conclude that this syndrome is associated with a defect in lymphokine-dependent maturation of B lymphocytes, although the T- or the B-cell origin of the defect still cannot be determined.

Mol Gen Genet, 1992 Mar, 232(1), 49 - 57
Osmotic and growth-phase dependent regulation of the eta gene of Staphylococcus aureus: a role for DNA supercoiling; Sheehan BJ et al.; Transcriptional fusions were constructed between the promoter for the epidermolytic toxin A (eta) gene of Staphylococcus aureus and the luxAB and xylE reporter gene systems . The expression of the fusion products was found to be dependent upon the accessory gene regulator (agr) locus and was observed to increase significantly during the transition from the exponential to the stationary phase of growth . Furthermore the expression of the eta gene promoter was found to be osmotically regulated, with the expression levels of the eta fusions being inversely related to the osmolyte levels . The ability of environmental factors to influence DNA topology (and thence gene expression) was investigated . High osmolarity (0.7 M NaCl) resulted in an increase in the degree of negative supercoiling of plasmid DNA in the S . aureus strain 8325-4 (Agr+) but not in strain ISP546 (Agr-) . Furthermore the eta promoter was strongly induced in S . aureus cultures grown in the presence of sub-inhibitory concentrations of novobiocin, a DNA gyrase inhibitor . However this induction was independent of agr, suggesting that the eta promoter is subject to both agr-dependent (osmolarity, growth phase) and-independent (DNA topology) regulatory processes.

J Clin Microbiol, 1992 Mar, 30(3), 670 - 4
Recurrent Staphylococcus aureus bacteremia; Hartstein AI et al.; Sequential blood isolates from eight patients with 10 episodes of recurrent Staphylococcus aureus bacteremia were typed by restriction endonuclease analysis of plasmid DNA (REAP DNA fingerprinting) and immunoblotting . There were six early recurrences (within 2 months of stopping antimicrobial therapy) and four late recurrences . All early recurrences isolates were identical to initial isolates . These recurrences were defined as possible relapses . Three of four late recurrence isolates were different from the preceding isolates recovered from four patients . This was considered indicative of new infections . There was complete concordance between REAP DNA fingerprinting and immunoblot typing results . However, four isolates lacked plasmid DNA and could be typed only by immunoblotting . All initial isolates from different patients were different types by immunoblotting and by REAP DNA fingerprinting (except for those lacking plasmid DNA) . The bacterial traits detected by these methods appear to be stable in vivo for up to 3 months . Relapsing infections were associated with the presence of intravascular foreign bodies and vancomycin therapy of the preceding episodes.

Semin Dermatol, 1992 Mar, 11(1), 11 - 8
Staphylococcal toxin-mediated syndromes in childhood; Resnick SD; Staphylococcal toxic shock syndrome (TSS) and staphylococcal scalded skin syndrome (SSSS) are two distinct toxin-mediated syndromes with prominent cutaneous features . The exanthematous presentation of these syndromes places them in the broad category of childhood exanthems, and the ability to recognize these potentially devastating illnesses is essential for pediatricians and dermatologists who may encounter children with fever and rash . Recent advances in the understanding of the pathogenesis of these entities has helped to explain the distinctive clinical presentations of TSS and SSSS . Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are the secretory products of Staphylococcus aureus that lead to TSS . Many of the clinical features of TSS (fever, shock, multiple organ dysfunction) can be explained by the effects of cytokines (especially interleukin-1 and tumor necrosis factor) induced by TSST-1 . TSS is not an exclusively menstrual event associated with tampon use . Nonmenstrual pediatric TSS may be associated with a wide variety of staphylococcal infections . Infected burn wounds in hospitalized children and bacterial tracheitis (in some cases following influenza B infection) are relatively high-risk settings for pediatric TSS . The epidermolytic toxins (A and B) directly produce subgranular epidermolysis leading to SSSS . SSSS encompasses a clinical spectrum from bullous impetigo to the widespread exfoliation of the Ritter disease variant of SSSS . This entity usually occurs in children under 5 years of age, and is primarily explained by lack of immunity to the toxins as well as renal immaturity leading to poor clearance of toxin . The newborn nursery is an important setting where epidemics of SSSS have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Oncogene, 1992 Mar, 7(3), 549 - 52
The difference in p53 antioncogene transcription in human monocytes and lymphocytes; Osipovich OA et al.; The p53 gene is associated with malignant transformation as well as 'antioncogene' activity . In this report expression of p53 in resting and activated human blood monocytes and lymphocytes was studied . It is shown that human monocytes freshly isolated by continuous Percoll-gradient centrifugation contain detectable levels of p53 mRNA . Stimulation of monocytes by the potent activation inducer Staphylococcus aureus Cowan I (SAC) for 3-5 h caused the disappearance of p53 mRNA . In contrast, induction of a high level of tumor necrosis factor alpha mRNA was detected . The addition of cycloheximide did not increase the p53 mRNA content in stimulated monocytes, and decreased the mRNA level in resting cells . p53 mRNA was absent in freshly isolated lymphocytes and in resting cells cultured for 20 h . Activation of lymphocytes by phytohemagglutinin caused accumulation of p53 mRNA . We suggest that p53 gene regulation and functions might be different in human monocytes and lymphocytes.

J Med Microbiol, 1992 Mar, 36(3), 177 - 83
Identification of a human lactoferrin-binding protein in Staphylococcus aureus; Naidu AS et al.; Human lactoferrin (HLf) is an iron-binding protein with antimicrobial activity that is present in high concentrations in milk and various exocrine secretions . HLf is also an acute-phase protein secreted by polymorphonuclear leucocytes, and its binding to a large number of clinical isolates of Staphylococcus aureus has been described recently from our laboratory . We have now characterised the HLf-staphylococcal interaction in S . aureus strain MAS-89 . The binding of 125I-HLf to strain MAS-89 reached saturation in less than 90 min and was maximal between pH 4 and 9 . Unlabelled HLf displaced 125I-HLf binding . Various plasma and subepithelial matrix proteins, such as IgG, fibrinogen, fibronectin, collagen and laminin, which are known to interact specifically with S . aureus, did not interfere with HLf binding . A Scatchard plot was non-linear; this implied a low affinity (1.55 x 10(7) L/mol) and a high affinity (2.70 x 10(8) L/mol) binding mechanism . We estimated that there were c . 5700 HLf binding sites/cell . The staphylococcal HLf-binding protein (HLf-BP) was partially susceptible to proteolytic enzymes or periodate treatment and was resistant to glycosidases . An active HLf-BP with an apparent Mr of c . 450 Kda was isolated from strain MAS-89 cell lysate by ion-exchange chromatography on Q-sepharose . In SDS-PAGE, the reduced HLf-BP was resolved into two components of 67 and 62 Kda . The two components demonstrated a positive reaction with HLf-HRPO in a Western blot . These data establish that there is a specific receptor for HLf in S . aureus.

J Med Microbiol, 1992 Mar, 36(3), 164 - 71
Comparison of enterotoxins and haemolysins produced by methicillin-resistant (MRSA) and sensitive (MSSA) Staphylococcus aureus; Coia JE et al.; A collection of 201 isolates of Staphylococcus aureus was examined: 152 methicillin-sensitive S . aureus (MSSA) comprised 48 blood culture isolates (BC) and 58 isolates from routine diagnostic specimens (RD) from Glasgow Royal Infirmary (GRI), and 46 strains from nasal swabs of patients attending a general practitioner (GP); 49 isolates were of methicillin-resistant S . aureus (MRSA) from GRI . We have previously shown that the MRSA could be divided into two sub-groups on the basis of sensitivity or resistance to aminoglycoside antibiotics . Production of enterotoxins A, B, C and D, and alpha-, beta-, gamma- and delta- haemolysins was detected by reverse passive latex agglutination (RPLA) and agar overlay methods respectively: 60% of BC MSSA and a similar proportion of MSSA from other sources produced enterotoxin; 87% of aminoglycoside-sensitive MRSA produced enterotoxin (89% of these produced enterotoxin A alone) whereas only 27% of aminoglycoside-resistant MRSA were enterotoxin-positive, significantly less than either MSSA or aminoglycoside-sensitive MRSA . The proportion of haemolysin-producing isolates did not differ amongst the isolates of MSSA and MRSA; there was no difference in the distributions of haemolysins between aminoglycoside-sensitive and -resistant strains of MRSA . GP MSSA had higher and lower numbers of gamma- and delta-haemolysin producers respectively than other S . aureus isolates . alpha-Haemolysin producers were commoner amongst MRSA isolates, which were also more likely than MSSA isolates to produce several haemolysins . Differences in enterotoxin production between aminoglycoside-sensitive and -resistant MRSA isolates reflect subgroups previously defined by biotype, phage type, immunoblot and restriction enzyme fragmentation pattern data, and provide further evidence for the existence of two major MRSA clones in GRI.

J Bacteriol, 1992 Mar, 174(6), 1844 - 7
In vivo processing of Staphylococcus aureus lipase; Rollof J et al.; The Staphylococcus aureus lipase gene encodes a 76-kDa protein . Extracellular lipase purified from culture supernatants is only 45 to 46 kDa, however . We show that the lipase is secreted in vivo as an 82-kDa protein with full enzymatic activity . It is then sequentially processed, both in culture and in cell-free supernatants, to a mature, 45- to 46-kDa protein . Protein sequencing demonstrates that the N-terminal region of the 82-kDa prolipase, comprising 295 amino acids, is cleaved from the central and C-terminal moieties, which contain the active site . A metallocysteine protease is probably responsible for initiating this processing . The extremely hydrophobic, mature lipase is resistant to further protease degradation and retains the full catalytic activity of the prolipase.

Infect Immun, 1992 Mar, 60(3), 944 - 50
Platelet-activating factor modulates endotoxin-induced macrophage procoagulant activity by a protein kinase C-dependent mechanism; Kucey DS et al.; Macrophage procoagulant activity is an important mediator of extravascular fibrin deposition at sites of infection and appears to contribute to the pathogenesis of several infectious disease processes . Previous studies have shown that the inflammatory mediator platelet-activating factor was able to prime macrophages for induction of procoagulant activity by bacterial lipopolysaccharide . The present studies were designed to examine the mechanism of this priming effect . Platelet-activating factor (100 nM) primed macrophages for procoagulant activity generation in response to endotoxin at concentrations as low as 100 ng/ml and also following exposure to Escherichia coli, Bacteroides fragilis, and Staphylococcus aureus . The priming effect occurred following a pretreatment with platelet-activating factor for as short as 1 min, suggesting a rapid activation event . Two different doses of the calcium ionophore ionomycin were used to mimic the peak and sustained effects of platelet-activating factor on cytoplasmic calcium levels (1 microM and 100 nM, respectively) . Neither dose was able to mimic the priming effect . However, extracellular calcium was necessary for induction of procoagulant activity and the priming effect . By contrast, the protein kinase C agonist phorbol myristate acetate reproduced the priming phenomenon observed for platelet-activating factor . In further support of the concept that protein kinase C activation mediated the effect of platelet-activating factor, the specific protein kinase C inhibitor staurosporine reversed the ability of platelet-activating factor to augment induction of macrophage procoagulant activity by endotoxin . These data suggest mechanisms by which inflammatory mediators within the microenvironment of infection might modulate the host response to bacterial pathogens.

Infect Immun, 1992 Mar, 60(3), 899 - 906
Binding of heparan sulfate to Staphylococcus aureus; Liang OD et al.; Heparan sulfate binds to proteins present on the surface of Staphylococcus aureus cells . Binding of 125I-heparan sulfate to S . aureus was time dependent, saturable, and influenced by pH and ionic strength, and cell-bound 125I-heparan sulfate was displaced by unlabelled heparan sulfate or heparin . Other glycosaminoglycans of comparable size (chondroitin sulfate and dermatan sulfate), highly glycosylated glycoprotein (hog gastric mucin), and some anionic polysaccharides (dextran sulfate and RNA) inhibited heparan sulfate binding to various extents . Heat treatment (80 degrees C for 10 min) and treatment of the bacteria with pronase E, proteinase K, pepsin, and chymotrypsin considerably reduced their ability to bind 125I-heparan sulfate, but treatment with trypsin and neuraminidase did not affect binding . Scatchard plot analysis indicated the presence of cell surface components with low affinity (Kd = 3 x 10(-5) M) for heparan sulfate . Cell surface components were released by stirring bacteria with 1 M LiCl at 37 degrees C for 2 h . Proteins of this extract that competitively inhibited binding of 125I-heparan sulfate to S . aureus were isolated by affinity chromatography on heparin-Sepharose . Two proteins having molecular masses of approximately 66 and 60 kDa and the ability to bind 125I-heparan sulfate were obtained . The first 9 amino-terminal amino acid residues of the 66-kDa protein are Asp-Trp-Thr-Gly-Trp-Leu-Ala-Ala-Ala, and the first 4 amino-terminal amino acid residues of the 60-kDa protein are Met-Leu-Val-Thr.

J Vasc Surg, 1992 Mar, 15(3), 487 - 94
Evaluation of muscle flaps in the treatment of infected aortic grafts; Mehran RJ et al.; Standard therapy for abdominal aortic graft infection involving resection of the graft and extraanatomic bypass carries significant morbidity and mortality rates . The present study evaluates the feasibility of combining in situ graft replacement with a highly vascular tissue flap as an alternative to this problem . In 52 pigs a segment of a polytetrafluoroethylene graft was interposed in the infrarenal abdominal aorta . Staphylococcus aureus was used to infect the graft . One week later the animals were divided into six treatment groups . Group 1 (control) had debridement of the retroperitoneum only; group 2 had debridement with replacement of the graft; group 3 consisted of animals with the infected graft left in place and the graft wrapped with a rectus abdominis flap; group 4 is similar to group 3 except the seromuscularis of the jejunum was used to wrap the infected graft; in group 5 the graft was changed, and a rectus abdominis island flap was wrapped around the graft; and finally, group 6 was similar to group 5 except that the flap was obtained from the seromuscularis of the jejunum . Two weeks later, graft patency and infection status were assessed at reoperation . The incidence of graft infection was significantly reduced in groups 5 (0 of 10; p less than 0.01) and 6 (1 of 10; p less than 0.02) compared with group 1 (7 of 10), and the incidence of graft thrombosis was also greatly reduced in groups 5 (2 of 10) and 6 (1 of 10) versus group 1 (10 of 10; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

J Immunol, 1992 Mar 1, 148(5), 1423 - 30
Production of granulocyte-macrophage colony-stimulating factor but not IL-3 by normal and neoplastic human B lymphocytes; Zupo S et al.; The ability of human B cells to produce granulocyte-macrophage (GM)-CSF and IL-3 was investigated . B cells, isolated from tonsils or from the peripheral blood of patients with B cell chronic lymphocytic leukemia using mAb and immune rosettes, were cultured with or without Staphylococcus aureus Cowan strain I . GM-CSF and IL-3 were measured in the culture supernatants using a bioassay based on the selective proliferative response of the MO7e megakaryoblastic cell line to IL-3 or GM-CSF . S . aureus Cowan I-stimulated normal B cells released measurable amounts of GM-CSF but not of IL-3 as determined in neutralization assays with specific mAb in the MO7e cell line test . Some of the unstimulated normal B suspensions also produced GM-CSF, albeit in lower quantities . When normal B cells were fractionated into small (resting) and large (activated) B cells by Percoll density gradients, spontaneous GM-CSF production was detected only in the large cell fractions, but small cells were induced to produce GM-CSF upon S . aureus Cowan I stimulation . On a per cell basis, tonsillar B cells were found capable of releasing more GM-CSF than activated peripheral blood monocytes . The amount of GM-CSF produced by B cells was always inferior to that released by stimulated peripheral blood T cells or NK cells . The purified B cell suspensions from all 14 B cell chronic lymphocytic leukemia patients studied released GM-CSF but not IL-3 in the culture supernatants, sometimes even in the absence of stimuli . Northern blot analysis on total or poly(A)+ RNA confirmed the presence of GM-CSF, but not of IL-3, mRNA transcripts in both normal and malignant B cells . The results of these studies support the notion that activated human B lymphocytes release sufficient GM-CSF to play a role in the control of both hematopoiesis and the inflammatory process.

Diagn Microbiol Infect Dis, 1992 Mar-Apr, 15(3), 247 - 51
In vitro activity of teicoplanin compared with vancomycin against methicillin-resistant Staphylococcus aureus derived from cystic fibrosis sputum; Arrieta AC et al.; We evaluated the in vitro activity of teicoplanin compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) derived from cystic fibrosis (CF) sputum . Teicoplanin had a slightly lower median minimum inhibitory concentration (MIC) for these strains (0.25 micrograms/ml) than did vancomycin (0.5 micrograms/ml) . Inoculum size increased the MICs similarly for both drugs, and pH variations did not significantly affect their activity . The presence of serum and sputum in the growth media decreased the activity of both drugs, although this was more pronounced for teicoplanin which is highly protein bound . We conclude that teicoplanin has activity against this pathogen and might be evaluated in clinical protocols designed to address this emerging clinical problem.

In Vivo, 1992 Mar-Apr, 6(2), 161 - 5
Effects of Catuaba extracts on microbial and HIV infection; Manabe H et al.; Pretreatment of mice with hot water and alkaline extracts of Catuaba casca (Erythroxylum catuaba Arr . Cam.) effectively protected them from lethal infection of Escherichia coli and Staphylococcus aureus . The extracts significantly inhibited both the human immunodeficiency virus (HIV)-induced cytopathic effect and the expression of HIV antigen in HIV-1HTLV-IIIB or HIV-2ROD infected human lymphotropic virus type I (HTLV-1) positive MT-4 cells . The 50% effective concentrations of the active fractions (21-263 micrograms/ml) were 1/4 - 1/43 of their 50% cytotoxic concentrations . Their anti-HIV activity was shown to be induced, at least in part, via the inhibition of HIV adsorption to the cells . The data suggest a medicinal potential of Catuaba extracts against opportunistic infection in HIV patients.

Pol Arch Med Wewn, 1992 Mar, 87(3), 168 - 72
{Bactericidal activity of plasma and leukocytes in patients after kidney transplantation}; Hrycek A et al.; In renal transplant patients the plasma and leukocytes bactericidal activity was estimated towards the vivid bacterial cells of the standard strain of Staphylococcus aureus Oxford 209P . Considering the kind of the immunosuppression used, the patients were divided into two subgroups . The first subgroup comprised the patients treated with cyclosporin A and prednisone (12 persons) and the second one--the patients treated with azathioprine and with prednisone (19 persons) . The control group consisted of 20 healthy persons . In the renal transplant patients significantly more bacterial cells survived the incubation with plasma and peripheral blood leukocytes and the reduction of bactericidal activity of the leukocytes alone was also found . The reduction of bactericidal activity of the peripheral blood leukocytes observed in the patients of the group tested may have resulted from the inefficient microbicidal systems of those cells . The kind of the immunosuppressive treatment did not seem to affect the bactericidal activity of the leukocytes and plasma examined in the renal transplant patients peripheral blood . It may be supposed that the increased susceptibility of those patients to bacterial, viral and mycotic infections is due in part to the reduced bactericidal capability of the peripheral blood leukocytes.

East Afr Med J, 1992 Mar, 69(3), 123 - 5
Raw milk as a source of enterotoxigenic Staphylococcus aureus and enterotoxins in consumer milk; Ombui JN et al.; Staphylococcus aureus strains were isolated from 183 of 300 raw milk samples collected at the Kenya Co-operative Creamery (Dandora) . 97 of these 183 trains were assayed for the production of enterotoxin A, B, C and D . Seventy two (74.2%) of these were found to produce either a single or a combination of enterotoxins . Raw milk is a potential source of enterotoxigenic S . aureus in milk and milk products, especially if there is defective pasteurisation.

J Med Assoc Thai, 1992 Mar, 75 Suppl 2, 24 - 30
Cross-infection of gentamicin-methicillin-resistant Staphylococcus aureus in a male surgical ward at Rajavithi General Hospital; Rahule S et al.; Between January and December 1987, gentamicin-methicillin-resistant strains of Staphylococcus aureus (GMRSA) were isolated from 7 patients in a male surgical ward at Rajavithi General Hospital . Six patients developed significant infection which included sepsis (2), pneumonia (1), infection in the eye, ear and wound (1), wound infection (2), and one patient had GMRSA isolated from his sputum . The strains were untypable with standard phage type and were resistant to methicillin, gentamicin, amikacin, kanamycin, streptomycin, tetracycline, erythromycin and chloramphenicol, but susceptible o vancomycin and cotrimoxazole . GMRSA were also isolated from bed-rail and the used rubber gloves left in the affected room . The GMRSA strains contained 5 plasmids of molecular weight of 18, 11, 2, 1.8 and 1.7 Md . The 2Md plasmid coded for chloramphenicol resistance and the 1.8 Md plasmid for erythromycin resistance.

Pediatr Med Chir, 1992 Mar-Apr, 14(2), 151 - 4
{Teicoplanin therapy in neonatal and pediatric intensive therapy}; Tuo P et al.; We administered teicoplanin as specific antibiotic therapy for nosocomial "ICU specific" infections with methicillin-resistant Staphylococcus aureus and epidermidis (MRSA-MRSE) . The above mentioned drug has been given to 20 patients (15 newborns and 5 not-newborns) admitted into intensive care unit during the years 1988, 1989, 1990 with MRSA-MRSE localized and/or systemic infection, affected by severe disease (RDS, pulmonary edema, congenital cardiac disease, cystic fibrosis) undergoing invasive procedures which presented high nosocomial infective risk (tracheal intubation, mechanical ventilation, venous and arterial cannulation, total parenteral nutrition, etc.) . Complete recovery from systemic or localized infection (sepsis, low respiratory tract infection, high respiratory tract infection) occurred in 19 out of 20 patients, with a rate of success of 95% . Teicoplanin treatment lasted from a minimum of nine days to a maximum of thirty days . The dose was 5-6 mg/kg/die in one administration for the first three days, then 4 mg/kg/die . The tolerability of teicoplanin has proven satisfactory, since we had no major side effects during treatment and follow up.

Endocrinology, 1992 Mar, 130(3), 1533 - 8
Insulin stimulates the tyrosine phosphorylation of a 61-kilodalton protein in rat adipocytes; Mooney RA et al.; Insulin stimulated the tyrosine phosphorylation of a 61-kilodalton (kDa) protein in rat adipocytes prelabeled for 2 h with {32P}orthophosphate . Tyrosine phosphorylation of this 61-kDa protein displayed very similar insulin concentration dependency to receptor autophosphorylation and tyrosine phosphorylation of a high molecular mass receptor substrate of 160 kDa . Phosphorylation of the 61-kDa protein was very rapid with maximum labeling attained at 30 sec, paralleling that of the other two proteins . Phosphoamino acid analysis revealed that each of the insulin-responsive phosphoproteins contained phosphoserine as well as phosphotyrosine, though the ratio of two phosphoamino acids recovered from each protein differed . The 61-kDa protein yielded relatively equal proportions of phosphoserine and phosphotyrosine . In contrast, the insulin receptor yielded relatively more label on phosphotyrosine than phosphoserine, whereas label incorporated into the 160-kDa protein was recovered primarily on phosphoserine . Cleveland peptide maps using either Staphylococcus aureus V8 proteinase or chymotrypsin revealed no similarities between the 61-kDa protein and the other tyrosine phosphorylated proteins . With subcellular fractionation, the 160-kDa protein was found in equal proportions in the high speed pellet (100,000 g) and supernatant . The 61-kDa protein had a similar distribution to that of the 160-kDa protein but was also detected in the low speed pellet (10,000 g) . The insulin receptor was localized to the low speed pellet . In summary, rat adipocytes contain an insulin-dependent phosphotyrosyl protein of 61 kDa which is distinct from the more prominent high molecular mass receptor substrate . This 61-kDa protein has characteristics consistent with it being a substrate for the insulin receptor tyrosine kinase.

J Med Microbiol, 1992 Mar, 36(3), 172 - 6
Use of contour-clamped homogeneous electric field (CHEF) electrophoresis to type methicillin-resistant Staphylococcus aureus; Wei MQ et al.; Strains of methicillin-resistant Staphylococcus aureus (MRSA) from Australia and the UK were compared by digesting their chromosomal DNA with the low-frequency-cutting restriction enzyme SmaI and separating the restriction fragment length polymorphisms (RFLPs) by contour-clamped homogeneous electric field (CHEF) electrophoresis . The numbers of restriction fragments produced were in the range 14-17 and the sizes of the bands were 7-700 kb . Generally, the results confirmed previous conclusions based on antimicrobial resistance and plasmid profiles . The earlier MRSA isolates were different from more recent isolates, and the epidemic MRSA from eastern Australia (EA MRSA) was the same as the epidemic MRSA (EMRSA) found in London hospitals . However, contrary to previous results, the EA MRSA did not constitute a homogeneous group . The results showed that comparison of RFLPs by CHEF electrophoresis is a useful technique for studying the epidemiology of MRSA.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 566 - 72
Autolysis of methicillin-resistant and -susceptible Staphylococcus aureus; Gustafson JE et al.; The autolytic activities, including unstimulated, Triton X-100-stimulated, and daptomycin-induced, of various sets of methicillin-resistant and related methicillin-susceptible strains were compared . Faster rates of autolysis were noted in two heterogeneous methicillin-resistant transductants than in their methicillin-susceptible parental recipients, in a heterogeneous resistant strain than in a susceptible derivative created by chemical mutagenesis, and in a homogeneous resistant strain than in a derivative that had decreased methicillin resistance and was created by transposon Tn551 mutagenesis . These results suggest that the presence of the methicillin resistance region, mec, either directly or indirectly through an interaction with other host genes, confers a faster rate of autolysis on strains . Various auxilliary genes are known to affect methicillin resistance expression, and one of these genes, femA, was necessary for the expression of this faster rate of autolysis . These differences in autolytic activities were not observed in isolated crude cell walls retaining autolytic activities, suggesting different modes of regulation of autolysins in intact cells and isolated walls . In contrast, one homogeneous, highly resistant strain, DU4916, had a lower autolytic activity than did derived heterogeneous resistant and susceptible strains created by chemical mutagenesis and a strain that had decreased resistance and was created by transposon mutagenesis . Our observations suggest that methicillin resistance expression is associated with an enhanced rate of autolysis, in heterogeneous resistant strains at least.

Eur J Clin Microbiol Infect Dis, 1992 Mar, 11(3), 243 - 6
Spontaneously occurring staphylococcal mutants resistant to clinically achievable concentrations of ciprofloxacin and temafloxacin; Barry AL et al.; The frequency of spontaneously occurring mutants resistant to 0.5, 1, 2, 4 and 8 micrograms of temafloxacin or ciprofloxacin per milliliter was documented with four Staphylococcus aureus and four Staphylococcus epidermidis strains . Resistant mutants were recovered at two- to four-fold the MIC of either drug, and they displayed cross-resistance to other fluoroquinolones . Resistance to temafloxacin occurred at frequencies lower than those observed with equal concentrations of ciprofloxacin . Resistance to greater than four-fold the MIC of either drug was not detected (frequencies less than 10(-10).

Cell Immunol, 1992 Mar, 140(1), 237 - 47
Cholera toxin promotes the proliferation of anti-mu antibody-prestimulated human B cells; Anastassiou ED et al.; The predominant effect of cholera toxin (CT) on cell growth has been postulated to be inhibitory as a result of its induction of intracellular cAMP . We have recently reported that CT selectively enhances surface DR expression while it inhibits anti-mu antibody-induced B lymphocyte proliferation . In the present series of experiments we studied the effect of CT on in vitro preactivated highly purified (greater than 95% CD20+) human B cells . Cholera toxin enhanced thymidine incorporation of anti-mu antibody-preactivated but not of Staphylococcus aureus Cowan I or PMA + ionomycin-preactivated B cells . Concentrations of 100 pg/ml CT stimulated an enhancement of thymidine incorporation equivalent to that of optimal doses of BCGF . The growth factor-like effect of CT required the complete molecule, since binding of purified B subunit (B-CT) to GM1 ganglioside by itself did not reproduce the holotoxin effect . Moreover, B-CT pretreatment of anti-mu antibody-primed cells completely neutralized the holotoxin-enhancing effect . Both PGE2, a physiological agent that stimulates intracellular cAMP elevation, and the cAMP analogue, 8-bromo-cAMP, mimicked the growth-promoting effect of CT . However, the ED50 of CT required to augment proliferation in anti-mu antibody-preactivated human B cells was approximately 100 times less than the ED50 for cAMP formation . These results demonstrate a specific growth factor-like promoting effect of CT on sIg-preactivated highly purified human B cells that may be mediated at least in part through elevation in intracellular cAMP levels . Increased DR expression and stimulation of growth of sIg preactivated B cells may explain some of the adjuvant properties of CT following orally or parenterally administered antigens.

J Commun Dis, 1992 Mar, 24(1), 46 - 8
Nasal carriage of Staphylococcus aureus in hospital staff and its antibiotic sensitivity in Enugu, Nigeria; Onyemelukwe N et al.; The nasal carriage of Staphylococcus aureus was investigated in 475 hospital staff of different categories . The overall carriage was 34.42 per cent with a significantly higher rate in females (67.53 per cent) than in males (23.81 per cent) . Nurses, orderlies and attending physicians had a higher carriage rate than other categories of staff investigated . The rate was higher in personnel working in accident, neonatal and postnatal wards than in other wards . As many as 51.94 per cent of the strains of S . aureus were resistant to penicillin while 22.72 per cent of them were resistant to ampicillin.

Commun Dis Rep CDR Rev, 1992 Feb 28, 2(3), R25 - 9
Methicillin-resistant Staphylococcus aureus in England and Wales; Marples RR et al.; Methicillin-resistant Staphylococcus aureus (MRSA) were detected soon after the introduction of methicillin in 1960, and reports of their isolation increased up to 1971 . Changes in antibiotic usage were associated with a fall and then, in the early 1980s, a further rise in the number of reports . This article reviews the various surveys that have been conducted to establish the frequency, distribution and strain varieties of MRSA . The first strain to be recognised as epidemic (ie, affecting more than one hospital), was defined by phage typing and antibiogram, confirmed with molecular typing, and designated EMRSA-1 . It was first detected in 1981 and became progressively more widespread until it began to decline in 1987 . Only three health regions reported this strain in the first quarter of 1991 . EMRSA-2 has remained restricted to the South East and South West Thames regions . EMRSA-3 appeared in the South East Thames region in 1987 and has since spread, being reported from eight health regions in the first quarter of 1991 . At least 11 other strains of MRSA affecting more than one hospital have been detected and ten endemic strains (restricted to single hospitals) have been identified . Imported strains of MRSA, often introduced following the repatriation of road traffic accident victims, may include strains with epidemic potential and local spread has followed importation in at least two incidents . Continued surveillance of epidemic MRSA strains and the search for simple and widely applicable markers, such as unusual antibiotic resistance patterns or biochemical features, are needed for the prompt application of control measures.

FEBS Lett, 1992 Feb 24, 298(2-3), 237 - 9
The complete primary structure of bovine stefin B; Krizaj I et al.; A new stefin B-type low-Mr CPI was isolated from bovine thymus and subjected to structural analysis . The inhibitor consisted of 98 amino acids and its Mr was calculated to be 11,178 . The NH2-terminal amino acid residue was blocked . The sequence was determined by automated sequencing of peptides derived by cleavage with cyanogen bromide and fragments of the inhibitor resulting from enzymatic digestion with beta-trypsin and Staphylococcus aureus V-8 proteinase . The NH2-terminal blocking group was established with mass spectrometry . The inhibitor exhibits considerable sequence homology with inhibitors from the stefin family . Furthermore, a highly conserved QVVAG region within the stefin family is for the first time replaced by the QLVAG sequence.

FEBS Lett, 1992 Feb 24, 298(2-3), 133 - 6
Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA); Hiramatsu K et al.; Molecular cloning and nucleotide sequence analysis were performed for the identification of the regulator genes of methicillin resistance in the genome of a MRSA strain N315 . Two open reading frames (orfs) were identified in the 5'-flanking region of the mecA gene . Predicted amino acid sequences of these orfs showed extensive homology to the co-inducer and the repressor protein of the penicillinase (PCase) production in Staphylococcus aureus as well as in Bacillus licheniformis . These orfs are considered to encode putative co-inducer and repressor proteins specific for the regulation of methicillin resistance in MRSA.

Blood, 1992 Feb 15, 79(4), 990 - 6
Antiproliferative effects of interleukin-4 on freshly isolated non-Hodgkin malignant B-lymphoma cells; Defrance T et al.; The pattern of in vitro growth response of freshly isolated non-Hodgkin malignant lymphoma B cells (NHML) to cytokines was investigated . Ten tumor specimens of low- or intermediate-grade malignancy were selected for study . To assess their proliferative capacity in vitro, B-lymphoma cells were activated through ligation of their surface Ig receptor with insolubilized anti-IgM antibodies or Staphylococcus aureus strain Cowan I (SAC) . In the great majority of cases, interleukin-2 (IL-2) was the sole factor that significantly and reproducibly stimulated DNA synthesis in NHML activated through their surface Igs . Other B-cell tropic factors, including IL-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha), failed to elicit a growth response in most of the IL-2-responsive neoplastic samples . However, one specimen among 10 exhibited the opposite pattern of response and proliferated following culture with IL-4 and anti-Ig reagents, but not after IL-2 stimulation . Three specimens could also be induced for DNA synthesis on cross-linking of their surface Igs in the absence of exogenous growth factors . Although IL-4 could not support the in vitro growth of the majority of NHML cases, it strongly suppressed the proliferative signals delivered to these cells by anti-Ig reagents used alone or in combination with IL-2 . Our data suggest that, in most cases, IL-4 essentially provides growth-inhibitory signals to NHML when they are activated through their surface Ig receptors and as such may be considered to be a valid candidate for future therapy of this type of mature B-cell malignancy.

Biochem J, 1992 Feb 15, 282 ( Pt 1), 129 - 37
Evidence that a secondary binding and protecting site for factor VIII on von Willebrand factor is highly unlikely; Layet S et al.; A binding domain for Factor VIII (F.VIII) has been previously identified on the N-terminal portion of human von Willebrand Factor (vWF) subunit {amino acids (AA) 1-272} . In order to characterize other possible structures of vWF involved in its capacity to bind and to protect F.VIII against human activated protein C (APC), we used a series of purified vWF fragments overlapping the whole sequence of the subunit . Among those were fragments SpIII (dimer; AA 1-1365), SpII (dimer; AA 1366-2050) and SpI (monomer; AA 911-1365) generated by Staphylococcus aureus V8 proteinase, a P34 species (monomer; AA 1-272) obtained with plasmin, a monomeric 39/34 kDa dispase fragment (AA 480-718) and a tetrameric III-T2 fragment (AA 273-511/674-728) produced from SpIII by trypsin . Three other fragments without precise extremities were located using selected monoclonal antibodies to vWF . Two C-terminal fragments of 270 and 260 kDa, overlapping SpI and SpII, were respectively generated from vWF with trypsin and protease 1 from Crotalus atrox venom . An N-terminal 120 kDa fragment, overlapping P34 and 39/34 kDa fragments, was produced by protease 1 . Our results show that vWF bound to F.VIII and protected it from degradation by APC in a dose-dependent way . Among the C-terminal and central vWF fragments (SpII, tryptic 270 kDa, 260 kDa, SpI, 39/34 kDa and III-T2), none had the capacity to bind or to protect F.VIII, even at high concentrations . The three N-terminal fragments (SpIII, 120 kDa and P34) bound to F.VIII in a dose-dependent and saturable fashion . SpIII and the 120 kDa fragment had the capacity to protect F.VIII in a dose-dependent way . In contrast, the P34 species did not significantly protect F.VIII, even when using high concentrations of the fragment . In conclusion, the N-terminal end of vWF subunit (AA 1-272) plays a crucial role in binding to F.VIII, but requires additional structures of the 120 kDa fragment to protect it against APC . In addition, the presence of a secondary binding and/or protecting domain on other portions of the vWF subunit (potentially destroyed during the proteolysis of vWF) is highly unlikely.

Immunol Lett, 1992 Feb 15, 31(3), 259 - 65
Cleavage of human immunoglobulins by serine proteinase from Staphylococcus aureus; Prokesova L et al.; The serine proteinase (SP) released into the environment by most strains of S . aureus cleaves human IgG, IgM and IgA of both subclasses--IgA 1 and IgA 2 . SP cleaves H chains of all immunoglobulin classes and the SC of S-IgA, the L chains are degraded partially . The SP-induced cleavage results in a large spectrum of fragments under reducing conditions within a broad range of Mr (approx . 41,000 to less than 12,400) . This indicates that the enzyme does not affect the Ig molecule in the hinge region only . The degree of cleavage depends on the enzyme:substrate ratio and on the duration of incubation . The generation of small fragments is associated with the loss of antigenic determinants that results from the decreased binding of the cleaved material in the ELISA method . Partial cleavage of L chains suggests that the enzyme alters part of the molecule that is involved in antigen binding . Even if the ability of antigen binding remains preserved after cleaving Ig with SP, the antibody function is disturbed by splitting off the Fc region or by its degradation into small fragments . SP has to be considered as one of the virulence factors of S . aureus that may protect bacteria against the defence mechanisms of the host.

Eur J Biochem, 1992 Feb 15, 204(1), 165 - 71
Isolation and amino acid sequence of a glutamic acid specific endopeptidase from Bacillus licheniformis; Svendsen I et al.; An endopeptidase cleaving specifically at the carboxyl side of acidic amino acid residues, preferentially at glutamic acid, has been isolated from a commercial extract obtained by fermentation with Bacillus licheniformis . Using ion-exchange chromatography and affinity chromatography on bacitracin-Sepharose, it was possible, from 100 ml commercial extract, to isolate 100 mg homogeneous enzyme in a yield of 50% . It is the first description of a large-scale isolation of a Glu/Asp-specific enzyme . The preparation was essentially free of contaminating activities . The isolated enzyme consists of one peptide chain of 222 amino acid residues and has a calculated molecular mass of 23,589 Da . The determined amino acid sequence shows similarity to the Glu/Asp-specific enzymes previously isolated from Staphylococcus aureus V8, Actinomyces sp . and Streptomyces thermovulgaris . The substrate preference of the enzyme has been investigated . Although non-specific cleavages were observed after prolonged hydrolysis at high enzyme concentrations the enzyme appears to be essentially specific for Glu-Xaa and Asp-Xaa, with strong preference for the former . The isolated enzyme exhibits a bell-shaped pH/activity profile with an optimum at pH 7.5-8.0 . The activity is adversely affected by high ionic strength and beneficially affected by the inclusion of calcium ions in the assay medium . The enzyme is completely inhibited by diisopropylfluorophosphate, suggesting that it is a serine endopeptidase . It is partially inhibited by EDTA.

Biochem Biophys Res Commun, 1992 Feb 14, 182(3), 1075 - 81
Partial characterization of the 30 kD Ig-binding protein from Pseudomonas maltophilia; Grover S et al.; We have previously demonstrated that Pseudomonas maltophilia (ATCC 13637) possess a 30 kDa cell wall protein which binds various subclasses of IgG's and IgA by their Fc region . The protein was solubilized by papain and purified by affinity chromatography on cyanogen bromide activated sepharose beads conjugated with human IgG . The eluent was electrophoresed on a 12% polyacrylamide gel under denaturing conditions, and the immunoactive bands identified by Western blot analysis, a second gel was stained with Coomassie blue . The affinity purified eluent was electrophoresed on a one-dimensional 15% polyacrylamide gel and stained with Coomassie blue . The protein band of interest was cut . The protein band was then digested in situ with Staphylococcus aureus V-8 protease . The peptide bands were separated by electrophoresis on a second one dimensional 15% polyacrylamide gel and then electroblotted into a polyvinylidine difluoride membrane . The bands were visualized by staining with Coomassie blue, cut out, and sequenced using an automated gas phase sequencer . Minimal amino acid composition was determined in a similar fashion . We have thus obtained partial N-terminal amino acid sequence data from the above method.

Surg Gynecol Obstet, 1992 Feb, 174(2), 103 - 8
Hemoaccess site infection; Padberg FT Jr et al.; Infectious complications involving a hemoaccess graft or fistula are a significant cause of morbidity in patients on chronic hemodialysis . A review of 274 consecutive hemoaccess procedures identified 28 infections (an incidence of 10 per cent) . Infections occurred in 27 polytetrafluoroethylene (PTFE) grafts . The predominant organism was Staphylococcus aureus . Partial excision resolved 14 of the 27 graft infections . The remaining 13 required complete removal . Surgical management required six arterial ligations and seven autogenous reconstructions . No limb ischemia or mortality was directly attributable to these procedures . One infection occurred in 48 autogenous fistulas (an incidence of 2 per cent) . Although partial removal of an infected prosthesis was often sufficient, brachial artery ligation was well tolerated when required to control anastomotic infection.

Plast Reconstr Surg, 1992 Feb, 89(2), 268 - 71
The effect of fibrin glue on skin grafts in infected sites; Jabs AD Jr et al.; Fibrin bonding of skin grafts to wounds is an essential part of the graft-adherence process . Bacteria, in concentrations greater than 10(5)/gm of tissue, are associated with graft failure . Sixty-five rats were randomly divided into three groups, dorsal split-thickness skin grafts were harvested, and the sites were inoculated with Staphylococcus aureus . After incubation, each wound was quantitatively biopsied and treated with saline, fibrin glue with aprotinin, or fibrin glue alone . We found that the addition of commercially available fibrin glue with or without the antifibrinolytic agent aprotinin is capable of restoring graft adherence to normal levels in graft sites infected with greater than 10(5) bacteria/gm of tissue . Fibrin glue may have potential for increasing skin-graft take in the clinical situation where the graft bed is infected.

FEBS Lett, 1992 Feb 3, 297(1-2), 183 - 5
Induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells; Auguet M et al.; Inducible vascular nitric oxide synthase accounts for the contractile impairment observed in endotoxemia . We provide evidence that lipoteichoic acid (LTA) from Staphylococcus aureus, a micro-organism without endotoxin, also induces nitric oxide synthase . Our study demonstrates that on endothelium-free rings of rat aorta . LTA-like lipopolysaccharide induces a loss of contractility restored by Methylene blue and NG-nitro-L-arginine-methyl ester (LNAME) . Moreover in cultured vascular smooth muscle cells, LTA produces a dose-dependent increase in intracellular cyclic GMP which is antagonized by LNAME and prevented by dexamethasone.

Equine Vet J Suppl, 1992 Feb, (11), 18 - 23
Evaluation of sodium hyaluronate therapy in induced septic arthritis in the horse; Brusie RW et al.; This study was conducted to determine the efficacy of sodium hyaluronate (SH) with antibiotic therapy and joint lavage for reducing acute inflammatory and degenerative changes induced by septic arthritis . Septic arthritis was induced in six adult horses by inoculating the tarsocrural joints with 1 x 10(4) colony-forming units of Staphylococcus aureus . When clinical signs appeared, trimethoprim-sulphamethoxazole (30 mg/kg bodyweight {bwt} daily) and phenylbutazone (4.4 mg/kg bwt sid) were administered and continued until termination of the study (Treatment Day 18) . Twenty-four hours post inoculation, all joints were lavaged with sterile lactated Ringer's solution . Following lavage, one joint of each horse was injected with 10 mg of SH, and the contralateral joint served as the control . Sodium hyaluronate treated joints showed significant reductions in lameness, tarsal circumference and synovial fluid protein and WBC concentrations . The synovial membrane of the SH-treated joints contained less cellular infiltrate, less granulation tissue formation and retained a more normal villous structure compared with controls . The total glycosaminoglycan loss from the articular cartilage in the SH treated joints was consistently less than that from the control joints; however, this difference was not statistically significant . Sodium hyaluronate with joint lavage appears to be more beneficial than lavage alone for treatment of septic arthritis.

Pediatr Infect Dis J, 1992 Feb, 11(2), 82 - 7
Bone and joint infections caused by multiply resistant Staphylococcus aureus in a neonatal intensive care unit; Ish-Horowicz MR et al.; Twenty cases of osteomyelitis and/or septic arthritis caused by multiply resistant Staphylococcus aureus were documented in an Australian tertiary neonatal unit between 1981 and 1987 . Eighteen (90%) occurred in the 3 years 1985 to 1987, an incidence of 9.6/1000 admissions in that period . All osteomyelitis and/or septic arthritis occurred in sick premature infants requiring intensive support . Eleven (55%) had a birth weight of less than 1500 g . An intravascular device was the most common portal of entry (14 of 20, 70%) . Systemic symptoms were prominent at presentation, with local signs developing later in 18 (90%), usually within a week . Radiologic changes were almost always present by 10 days; radionuclide bone scanning was insensitive and did not hasten diagnosis . Osteomyelitis was multifocal in 11 cases (55%), with the long bones, particularly of the upper limb, most commonly affected . Large joint involvement was uncommon (15%) . Intravenous vancomycin for a mean of 32 days was associated with low mortality (1 of 20) and toxicity; surgical drainage was not performed . Follow-up at a minimum of 4 months (mean, 25.5 months) showed residual signs in the affected limb in 30%, none with significantly impaired function . Skeletal infection should be searched for rigorously in neonatal multiply resistant S . aureus sepsis . In the absence of large joint disease, vancomycin therapy alone for a minimum of 3 weeks gives good short term results with minimal toxicity.

J Surg Res, 1992 Feb, 52(2), 127 - 30
The critical relationship of antibiotic dose and bacterial contamination in experimental infection; Citak MS et al.; Even though the usefulness of prophylactic antimicrobial administration for potentially contaminated operations is widely accepted, infection continues to occur in a finite number of cases . This study examined whether potential infection due to an increasing bacterial inoculum can be prevented or controlled by increasing antimicrobial doses . In an initial set of experiments, Sprague-Dawley rats were given various doses of cefazolin (15, 30, 60, 120 mg/kg) intraperitoneally, then serum and tissue levels were quantified . Serum and tissue drug concentrations correlated with the dose given . In another set of experiments, rats were given doses of either 0, 30 (standard dose), 60, or 120 mg/kg of cefazolin 30 min prior to subcutaneous inoculation of various doses of Staphylococcus aureus . After 6 days, inoculum sites were examined for abscess formation and size . At low levels of contamination, increasing in antibiotic dose to 30, 60, and 120 mg/kg, abscess formation was eliminated at 50, 80, and 92% of inoculum sites, respectively . At moderate levels of contamination, abscesses formed at all inoculum sites, but abscess size was significantly smaller as the dose increased . When a high inoculum of S . aureus was given, large doses of antibiotics provided no additional benefit . These data suggest that the risk of infection in this model of experimental infection is significantly related to the size of the bacterial inoculum . Increasing the dose of an effective antimicrobial increases drug concentration at the site of contamination and reduces the risk of infection . Administration of higher doses of prophylactic antimicrobials may be more effective when larger amounts of bacterial contamination are anticipated.

Arch Intern Med, 1992 Feb, 152(2), 353 - 6
Mupirocin treatment of nasal staphylococcal colonization; Scully BE et al.; The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study . Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus . Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains . Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains . At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized . Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates . None of the subjects had serious adverse effects . Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated.

Am J Kidney Dis, 1992 Feb, 19(2), 162 - 6
Polymicrobial peritonitis in patients on continuous peritoneal dialysis; Holley JL et al.; Little data are available about the characteristics, outcome, and risk factors for polymicrobial peritonitis in patients on continuous peritoneal dialysis . We therefore reviewed the 43 episodes of polymicrobial peritonitis that occurred in 39 of our patients over the 11.5 years of our program . Polymicrobial peritonitis represented 9% (43/492) of all peritonitis episodes . Only three episodes of polymicrobial peritonitis were associated with an enteric source . Sixteen percent (7/43) of the polymicrobial peritonitis episodes were associated with catheter infections . Staphylococcus aureus was one of the cultured organisms in 33% of the polymicrobial peritonitis episodes . Patients with polymicrobial peritonitis had higher rates of tunnel infection (0.28/yr v 0.18/yr) and overall peritonitis (1.23/yr v 0.81/yr) than patients with single-organism peritonitis . Black patients were more likely to have polymicrobial peritonitis (12/56 v 27/338 whites, chi 2 = 9.8, P less than 0.005) . Patient age, gender, time on peritoneal dialysis, insulin dependence, and cause of end-stage renal disease had no influence on polymicrobial peritonitis . Significantly more catheters were removed for polymicrobial peritonitis than for single-organism peritonitis (17/42 v 89/420, chi 2 = 7.05, P less than 0.01), but in 60% of the episodes, the polymicrobial peritonitis was successfully treated without catheter removal . Polymicrobial peritonitis often occurs without gram-negative organisms and extension of catheter infection may be involved in some cases . For unclear reasons, black patients are at higher risk of polymicrobial peritonitis.

Acta Orthop Scand, 1992 Feb, 63(1), 4 - 6
Oral cefadroxil prophylaxis in hip fracture surgery . Serum concentrations studied in 17 patients; Nungu KS et al.; Serum concentration-time curves were determined in seventeen 82 (60-90) year-old patients undergoing trochanteric hip fracture surgery after receiving 1 g of cefadroxil per os . All the patients attained a serum level of antibiotic high enough to inhibit the growth of Staphylococcus aureus and S . epidermidis . When orally administered, cefadroxil should be given within 2 hours before surgery.

Int J Cardiol, 1992 Feb, 34(2), 216 - 8
Aortic coarctation endarteritis and aneurysm: diagnosis by transoesophageal echocardiography; Skinner JR et al.; A 17-year-old girl developed infective endarteritis, caused by Staphylococcus aureus, at the site of a previously undiagnosed aortic coarctation . Transoesophageal echocardiography revealed a clinically unsuspected false aneurysm . Foreknowledge of the presence of the aneurysm proved to be life saving when an acute deterioration required emergency surgery.

Biochim Biophys Acta, 1992 Feb 1, 1118(3), 223 - 30
Proteinase-catalyzed activation of porcine heart muscle pyruvate dehydrogenase and identification of its cleavage site; Koike K et al.; Porcine heart muscle pyruvate dehydrogenase (PDH, EC 1.2.4.1) with subunit composition alpha 2 beta 2 catalyzes the initial decarboxylation step of an oxidative decarboxylation sequence of pyruvate . Highly purified PDH, was further activated several-fold by limited digestion with trypsin, Staphylococcus aureus V8 proteinase (V8) or papain . The activation with these proteinases required about 10 min to attain a maximal level, lasted 1/2-2 h and thereafter decreased gradually . Addition of an inhibitor of each proteinase resulted in an immediate cessation of any further changes in the enzymatic activity . The optimal pH of the proteinase-activated PDH was not affected . Proteinases increased the maximum velocity and the apparent Km values for pyruvate, but the Hill coefficients for pyruvate were unchanged . Proteinase-activated PDH was capable of associating two other component enzymes to produce large unit resembling the native complex . The Coomassie brilliant blue stained gels after SDS-PAGE showed that the PDH alpha subunit (41 kDa) was cleaved by trypsin or V8 into two major fragments (31 and 10 kDa), whereas PDH beta was unaffected . By amino-terminal sequence analyses of these fragments the trypsin cleavage sites were identified as Arg-273 and Arg-282 and the V8 cleavage sites were Glu-277 and Glu-280.

Chest, 1992 Feb, 101(2), 583 - 5
Nontraumatic acute anterior mediastinitis in two HIV-positive heroin addicts; Dreyfuss D et al.; We present the cases of two young heroin addicts seropositive for HIV who had life-threatening spontaneous acute anterior mediastinitis due to Staphylococcus aureus . This was the consequence of the spreading to the mediastinum of an infection of the chest wall . Complete cure was achieved with antibiotics and surgical drainage . Spontaneous mediastinitis should arouse suspicion of the possibility of HIV infection.

Chest, 1992 Feb, 101(2), 574 - 6
Pulmonary manifestations of Staphylococcus aureus septicemia; Tsao TC et al.; This study includes 140 episodes (138 cases) of Staphylococcus aureus septicemia, made up mostly of community-acquired, nonintravenous drug abuse (nonIVDA) cases . Unlike other series, injury wounds and skin or soft tissue infections were the most common sites of primary infection . In spite of a different patient population and lack of cases with tricuspid valvular endocarditis, the lungs were still the most common site of secondary infectious foci and most developed within two weeks of onset of the septicemia.

Chest, 1992 Feb, 101(2), 490 - 5
Infected radial artery pseudoaneurysms occurring after percutaneous cannulation; Falk PS et al.; During a ten-month period in 1988 at our institution, we identified three infected radial artery pseudoaneurysms (RAPAs) associated with arterial lines . A retrospective chart review to 1983 identified three additional cases, all occurring in 1986 . In the six-year period of 1983 through 1988, during which approximately 12,500 radial artery catheters were placed, the incidence of RAPA formation was 6/12,500 (0.048 percent) . Five of the six cases were associated with Staphylococcus aureus infection . The duration of radial artery cannulation was significantly longer in patients who developed a pseudoaneurysm (12.5 days) than in those patients who did not suffer this complication (4.3 days) . Patients in whom infected RAPAs occurred also tended to be older (mean, 71.6 years) than the average age (54 years) for all patients admitted to the intensive care unit (ICU) . They also tended to have long stays in the ICU prior to development of RAPA, the shortest stay being 11 days and the average being 51 days . Risk factors for the development of this complication may include advanced age, longer duration of catheterization and hospitalization, and infection with S aureus.

Arthritis Rheum, 1992 Feb, 35(2), 168 - 75
Regulation of B cell function by lobenzarit, a novel disease-modifying antirheumatic drug; Hirohata S et al.; OBJECTIVE . Lobenzarit (disodium 4-chloro-2,2'-iminodibenzoate {CCA}) is a novel disease-modifying drug for the treatment of rheumatoid arthritis (RA) . Although its clinical efficacy has been demonstrated, its mechanism of action remains unclear . We therefore examined the effects of CCA on in vitro IgM and IgM rheumatoid factor (IgM-RF) production by human B cells . METHODS . IgM and IgM-RF production was induced from highly purified B cells from 8 healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus factors generated from mitogen-activated T cells (TCF) or with immobilized anti-CD3-activated CD4+ T cells . RESULTS . CCA suppressed the production of IgM-RF as well as IgM at concentrations of 25-50 micrograms/ml (therapeutic serum concentrations of the drug), although the IgM-RF production induced by SAC plus TCF was suppressed at lower concentrations of CCA (1-3 micrograms/ml) . Whereas CCA suppressed interleukin-2 (IL-2) production by anti-CD3-activated CD4+ T cells, its suppressive effects on B cells were not overcome by addition of IL-2 or TCF . CCA did not inhibit the initial stages of B cell activation in either culture system, but rather, suppressed the maturation of previously activated B cells . Cell cycle analysis by acridine orange staining indicated that CCA-mediated inhibition of B cell responsiveness induced by anti-CD3-activated CD4+ T cells was the result of a block at the G1-S interphase . CONCLUSION . These results indicate that CCA suppresses the production of IgM and IgM-RF by directly inhibiting activated B cells . Thus, one of the actions of CCA in RA may be the suppression of the function of activated B cells.

Enferm Infecc Microbiol Clin, 1992 Feb, 10(2), 107 - 10
{Hospital personnel who are nasal carriers of methicillin-resistant Staphylococcus aureus . Usefulness of treatment with mupirocin}; Gaspar MC et al.; BACKGROUND: The evaluation of health care workers role in methicillin-resistant Staphylococcus aureus outbreaks and the efficacy of mupirocin as a topical agent for nasal carriers . METHOD: Microbiologic study of nasal microflora of 1547 health care workers from the San Carlos University Hospital and 108 health care workers from related hospitals while an outbreak of methicillin-resistant Staphylococcus aureus nosocomial infections is in progress at San Carlos University Hospital . Assessment of the efficacy of mupirocin nasal ointment for nasal carriers using microbiologic controls of nasal and pharyngeal swabs at the end of treatment and two weeks after . RESULTS: In San Carlos University Hospital a total of 53 health care workers with nasal carriage of methicillin-resistant Staphylococcus aureus were found . That figure represents a 3.4% of all health care workers studied and also a 15.4% of methicillin-resistance among all S . aureus isolated . Among health care workers from related hospitals, only one nasal carrier was found . Forty-seven of all 53 methicillin-resistant Staphylococcus aureus isolated from San Carlos University Hospital health care workers and the strain isolated from the related hospitals health care worker were similar to the epidemic strain responsible for the outbreak . Mupirocin, as nasal ointment, was useful in eliminating nasal colonization in all cases . CONCLUSIONS: When a nosocomial outbreak of methicillin-resistant Staphylococcus aureus infections is detected, health care workers are one of the most important reservoirs . Topical treatment with mupirocin (nasal ointment) is useful for eliminating the nasal carrier status.

J Nat Prod, 1992 Feb, 55(2), 221 - 4
Isolation and identification of xochitloldione and isoxochitlolone from Cnidosculus urens; Dominguez XA et al.; Major components of MeOH extracts from the plant roots of Cnidosculus urens purified by cc and tlc and crystallization were lupeol acetate and the previously unreported compounds isoxochitlolone {1} and xochitloldione {2}, which were identified through mass, ir, nmr, and uv spectroscopy and X-ray crystallography . In preliminary testing, isoxochitlolone has been found to be active against Escherichia coli and Staphylococcus aureus.

J Electron Microsc (Tokyo), 1992 Feb, 41(1), 1 - 6
Ultrastructure of Staphylococcus aureus as revealed by microwave fixation; Morioka H et al.; The ultrastructure of the cell wall of Staphylococcus aureus was examined at electron microscopic level using new chemical fixation techniques during microwave irradiation and the results obtained were compared with those obtained by other conventional techniques . By using microwave fixation the concentric circular or zipper-like structure was observed in the cell wall . This structure was observed also with the spray-freeze-etch technique but not in thin section of the cells chemically fixed by conventional technique . For chemical fixative, glutaraldehyde is more advantageous than OsO4 as a concomitant fixative during microwave irradiation and postfixation by OsO4 is unnecessary and rather harmful for the preservation of the ultrastructure . The function of the observed structure is briefly discussed.

Jpn J Antibiot, 1992 Feb, 45(2), 197 - 207
{A multicenter study on panipenem/betamipron in dermatology}; Arata J et al.; Panipenem/betamipron (PAPM/BP), a new carbapenem, was studied in dermatology . PAPM/BP was used clinically in the treatment of skin and skin structure infections in a multicenter trial . Fifty three patients were enrolled in the trial . Clinical evaluations were made in 50 patients . Most patients received intravenous infusion of PAPM/BP in a dose of 500 mg twice daily . Other dosages were used in some patients . The overall clinical efficacy rate was 78% . When 15 cases of secondary infections were excluded, the rate was 85.7% . Adverse responses were nausea and/or vomiting in 3 patients, redness with itching in 1 patient, headache or head heaviness in 2 patients and diarrhea in 1 patient . The patient with redness and itching had also nausea and vomiting . This occurred 1 hour after the start of the first infusion of this drug . After the discontinuation of the treatment the symptoms went away on the next day . Abnormalities in laboratory test results were observed in 7 out of 53 patients . One patient with liver cirrhosis and hepatocellular carcinoma developed anemia (RBC 372 x 10(4)/mm3----275 x 10(4)/mm3, Hb 11.9 g/dl----8.8 g/dl, 35.1%----26.0%) . Other abnormalities were all mild . Penetration of the drug into skin tissues after intravenous infusion of 500 mg of this drug in skin surgery patients was studied . Skin/serum concentration ratios ranged from 0.20 to 0.97 . Skin concentrations were higher than the concentration of PAPM inhibiting 80% of clinical isolates over a period of 6 hours . In rats, skin concentrations were much lower than serum concentrations probably due to the difference in in vivo metabolism of PAPM . A few resistant strains of Staphylococcus aureus against PAPM and imipenem (IPM) were isolated . However, PAPM and IPM showed good antibacterial activities compared to other drugs tested . In conclusion, PAPM/BP is considered to be a useful drug in the treatment of skin and skin structure infections.

Appl Environ Microbiol, 1992 Feb, 58(2), 471 - 5
Identification of two proline transport systems in Staphylococcus aureus and their possible roles in osmoregulation; Bae JH et al.; The food-borne pathogen Staphylococcus aureus is distinguished from other food-borne pathogens by its ability to grow at water activity values below 0.90 . Previous studies have indicated that proline accumulation mediated by transport represents a primary osmoregulatory strategy utilized by this bacterium (C . B . Anderson and L . D . Witter, Appl . Environ, Microbiol . 43:1501-1503, 1982; I . Koujima, H . Hayashi, K . Tomochika, A . Okabe, and Y . Kanemasa, Appl . Environ . Microbiol . 35:467-470, 1978; K . J . Miller, S . C . Zelt, and J.-H . Bae, Curr . Microbiol . 23:131-137, 1991) . In this study, we demonstrate the presence of two proline transport systems within whole cells of S . aureus, a high-affinity transport system (Km, 7 microM) and a low-affinity transport system (Km, 420 microM) . Our results indicate that the low-affinity proline transport system is osmotically activated and is the primary system responsible for the accumulation of proline by this pathogen during growth at low water activity.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 458 - 62
Efficacy of ticarcillin-clavulanic acid for treatment of experimental Staphylococcus aureus endocarditis in rats; Catherall EJ et al.; The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis . Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log10 CFU/g), or delayed until 24 h after infection, when the vegetations usually contained greater than 9 log10 CFU/g . Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses . Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by beta-lactamase-producing strains of S . aureus, illustrating the beta-lactamase-inhibitory activity of clavulanic acid in vivo . Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal beta-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active . These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 440 - 5
Characterization of four beta-lactamases produced by Staphylococcus aureus; Zygmunt DJ et al.; Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D) . To investigate the effect of specific beta-lactamase type upon staphylococcal resistance, each beta-lactamase was purified to homogeneity, and the Michaelis constants (Km values) and turnover numbers (kcat values) for various penicillin and cephalosporin substrates were determined . Whereas Km values of the four beta-lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta-lactamases for nitrocefin, cefazolin, and cephapirin . Conversely, the type B and C beta-lactamases exhibited greater kcat values than the type A and D enzymes against most of the cephalosporin agents, excluding nitrocefin . In contrast to earlier reports suggesting that the type B beta-lactamase is relatively inefficient in hydrolyzing penicillin G, we found only minor differences in the specific activities and kcat values of the type A, B, and C beta-lactamases . The type D beta-lactamase was distinctly less active against penicillin G, however, exhibiting only 15 to 25% of the kcat values of the other beta-lactamases . More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists . This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme . Whereas the isoelectric points of the type A, B, and C beta-lactamases were similar, the value for the type D beta-lactamase was distinguishably lower (10.1 for types A, B, and C and 9.7 for type D).We conclude that marked differences in the stability of commonly used beta-lactams to hydrolysis by the staphylococcal beta-lactamases are present . This heterogeneity and the clinical implication thereof need to be considered in the antibiotic management of staphylococcal infection.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 287 - 90
Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains; Dagan R et al.; Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions, and in several recent studies, it was present in the majority of the cases . Since recently a large proportion of S . aureus strains in our community showed erythromycin resistance, we undertook a prospective double-blind controlled study comparing topical mupirocin with oral erythromycin to determine (i) the prevalence of erythromycin-resistant S . aureus strains in impetigo and (ii) whether an increased rate of failure of erythromycin treatment was associated with such resistance . A total of 102 patients 3 to 185 months old (median = 49 months) were enrolled . Culture was positive for 97 of 102 (95%) patients, and S . aureus was present in 93% of the patients for whom cultures were positive . S . aureus was the single pathogen in 64% of these patients . Erythromycin-resistant S . aureus strains were present in 27 of 91 (28%) patients for whom cultures were positive . In all cases but one, S . aureus was resistant to penicillin, and in all cases it was sensitive to mupirocin . A marked difference was observed in favor of mupirocin in the clinical courses of the disease . However, only patients with erythromycin-resistant S . aureus strains had unfavorable courses compared with those treated with mupirocin (failure rate, 47 versus 2%, respectively) . Patients with erythromycin-susceptible S . aureus strains who received erythromycin had a failure rate of 8% . In four patients, S . aureus strains initially susceptible to erythromycin became resistant during treatment . We conclude that erythromycin-resistant S . aureus strains are commonly isolated from impetigo in our region.(ABSTRACT TRUNCATED AT 250 WORDS)

Invest Radiol, 1992 Feb, 27(2), 111 - 3
Ultrasonic detection of osteomyelitis . Pathologic correlation in an animal model; Abiri MM et al.; The authors correlated sonographic findings with histologic findings in a rabbit model of osteomyelitis . Staphylococcus aureus osteomyelitis was induced in the femora of 11 New Zealand white rabbits . The opposite leg was used as a control . Sonographic findings showed fluid adjacent to the bone in 11 cases . The fluid was believed to be an inflammatory exudate, and its presence suggested osteomyelitis . Pathologic analysis showed extraperiosteal purulent fluid adjacent to the cortex as well as histopathologic changes of osteomyelitis in the 11 rabbits . There was one false-positive sonographic diagnosis of osteomyelitis in a rabbit that had a soft tissue abscess adjacent to the cortex.

Pathol Res Pract, 1992 Feb, 188(1-2), 254 - 8
What's new in exogenous osteomyelitis?
Bohm E, Josten C.
By the increase in road and occupational accidents during the past few decades posttraumatic osteomyelitis has become not only the most important type of exogenous but of all inflammatory bone processes . The major morphologic, bacteriologic and immunologic studies about posttraumatic bone inflammation will be outlined in this survey . The histologic classification of chronic osteomyelitis has proved useful for the observation of the course and for the selection of the treatment in 1,500 patients . Detailed morphological studies have shown that posttraumatic osteomyelitis often begins with a necrosis of the outer tangential lamella of the tubular bone partly promoted by partial periosteal retrogression, possibly followed by a necrosis of the fracture ends caused by a disturbance of the medullary blood circulation . Type and extent of osteomyelitis are determined by several traumatic, therapeutic and endogenous factors . Bacteriologically an infection with staphylococcus aureus is still prevailing . Comparative studies about the causative agents shortly after the trauma and during the following osteomyelitis have basically shown an identical range of causative agents . Immunologic studies with monoclonal antibodies in the actual site of inflammation have on the one hand found a decrease in the number of T-lymphocytes and the T-helper cells and on the other hand an increase in the T-suppressor cells, natural killer cells, macrophages in the osteomyelitic site . The impact of these findings on the therapy of osteomyelitis can presently not be estimated . However, they will become important after immunohistochemical studies of the bone and soft tissue Lager in osteosynthetic material after aseptic bone surgery have been carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

Nippon Kyobu Geka Gakkai Zasshi, 1992 Feb, 40(2), 294 - 8
{Methicillin-resistant Staphylococcus aureus endocarditis following patch closure of ventricular septal defect}; Imoto Y et al.; Mediastinitis due to methicillin-resistant Staphylococcus aureus was found on the ninth postoperative day after patch closure of ventricular septal defect (VSD) in a six-month-old girl . Intravenous administration of vancomycin and debridement of the wound followed by irrigation with povidone iodine and vancomycin led to wound disinfection, but blood cultures continued positive . On the 22nd postoperative day, an echocardiographic examination revealed vegetations in the right ventricle . An emergency open heart operation was undergone . The largest vegetation was 1 x 2 cm in size, originating from the intracardiac patch used for closure of the VSD . The pulmonary and tricuspid valves were also involved . After removal of the infected tissues, including the two cusps of the pulmonary valve and a part of the tricuspid valve, the ventricular septal defect was closed again with a woven Dacron patch . The defect in the tricuspid valve was repaired . Postoperative examinations revealed severe pulmonary regurgitation and mild tricuspid regurgitation, but the cardiac function was good and neither vegetation nor leakage around the patch was recognized.

Nippon Kyobu Geka Gakkai Zasshi, 1992 Feb, 40(2), 290 - 3
{MRSA pyothorax due to bronchopleural fistula after grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta--a successful treatment by open drainage and omentopexy}; Yuasa H et al.; Treatment of postpneumonectomy pyothorax due to bronchopleural fistula (BPF) is troublesome, especially with methicillin-resistant staphylococcus aureus (MRSA) infection . Moreover, in a bypass-grafting case, the management becomes more complicated . We reported a successful treated case of MRSA pyothorax due to BPF after grafting and pneumonectomy . In a 48-year-old woman performed grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta, MRSA pyothorax due to BPF occurred . BPF was successfully closed by fibrin-glueing under bronchofiberscopy . However pyothorax was not improved by thoracic irrigation for a month . Therefore, open pleural drainage underwent . At the same time, bronchial stump and graft surface was covered with the omental pedicle flap . The open wound had become sterile in two months, and the thoracic window was closed three months after the open drainage.

Indian Pediatr, 1992 Feb, 29(2), 161 - 5
Clinical and bacteriological study of normal and inflamed neonatal conjunctivae; Rao K et al.; Maternal vaginal and neonatal conjunctival flora were prospectively studied in a 117 mother baby pairs . The commonest isolates from both vaginal and conjunctival flora were E . coli, Staphylococcus aureus and Klebsiella species . In 85% of mother-baby dyads, isolates from vagina and conjunctiva were similar . The commonest bacterial isolates in neonates with conjunctivitis were Staphylococcus aureus (37.4%), E . coli (27.9%) and Klebsiella species (19.3%) . Maternal coitus, infections, rupture of membranes and baby's birth weight and sex did not influence the occurrence of conjunctivitis.

Acta Paediatr Jpn, 1992 Feb, 34(1), 80 - 3
A case report of purulent pericarditis with cardiac tamponade: echocardiographic findings; Abo K et al.; A five year old girl with cardiac tamponade due to purulent pericarditis caused by Staphylococcus aureus was treated successfully with a combination therapy of appropriate antibiotics and surgical open drainage . Right atrial collapse was observed during early systole using two-dimensional echocardiography . This case illustrated the usefulness of echocardiography for early detection and treatment of cardiac tamponade in pediatric patients.

Zentralbl Veterinarmed B, 1992 Feb, 39(1), 65 - 8
Lack of growth of heat-shocked Staphylococcus aureus surviving cells in common media and enterotoxin release; Javier Hernandez F et al.; The ratio of the different types of S . aureus surviving cells immediately after sub-lethal heat treatment (52 degrees C for 15 min) was studied . A high ratio of cells which are unable to form colonies even in a common medium such as TSA was observed . This fact has not been reported previously for common media through recovery after heat shock has been widely studied . After the treatment, staphylococcal protein A, but no enterotoxin, was seen to be released into the extracellular environment.

FEMS Microbiol Lett, 1992 Feb 1, 70(1), 1 - 8
A structurally novel staphylococcal protein A from the V8 strain; Finck-Barbancon V et al.; Protein A from the Staphylococcus aureus strain V8 has a molecular mass about 8000 Da less than that of known proteins A . The corresponding gene was cloned and expressed in Escherichia coli . Sequence analysis of this structurally new protein A revealed that it lacked an IgG-binding domain (58 amino acids), and that it also lacked two octapeptide repetitions located in the membrane/wall attaching region . Contrary to what had been proposed previously, the first translated amino acid is probably not a leucine, but very likely a methionine located 12 residues upstream.

Kokyu To Junkan, 1992 Feb, 40(2), 183 - 8
{Management of infected transvenous permanent pacemakers}; Shibata T et al.; Between November, 1980, and January 1991, a total of 115 transvenous pacemakers were implanted in 102 patients at our hospital . Infection at the site of implantation developed in three cases or 2.6% . The median time of the onset of infection postoperatively was eleven and a half months, the range being two and a half to twenty-four months . Coagulase positive Staphylococcus aureus was cultured from the infected site of one patient and coagulase negative Staphylococcus epidermidis and saprophyticus in two patients . Staphylococcus aureus septicemia developed in one patient . Conservative medical treatment consisting of the application of two or more antibiotics was unsuccessful in all three cases . In two patients, removal of the infected pacemaker generator and implantation of a completely new pacemaker system at a new, clean site were conducted . In one of these two patients, the septic pacemaker electrode was withdrawn 3 months after removal of the infected pacemaker generator . In the other patient, limited thoracotomy with incision of the left brachiocephalic vein was performed for removal of the electrode three weeks after removal of the infected pacemaker generator.

J Gen Microbiol, 1992 Feb, 138 ( Pt 2), 275 - 81
Characterization of the chloramphenicol acetyltransferase variants encoded by the plasmids pSCS6 and pSCS7 from Staphylococcus aureus; Cardoso M et al.; The two 4.6 kb chloramphenicol resistance (CmR) plasmids pSCS6 and pSCS7, previously identified in Staphylococcus aureus from subclinical bovine mastitis, both encoded an inducible chloramphenicol acetyltransferase (CAT, EC 2.3.1.28) . The pSCS6- and pSCS7-encoded CAT variants were purified by ammonium sulphate precipitation, ion-exchange chromatography and fast protein liquid chromatography (FPLC) . Both native enzymes showed Mr values of 70,000 on FPLC and were composed of three identical subunits, each of Mr approximately 23,000 . The CAT variants from pSCS6 and pSCS7 differed in their net charges and in their isoelectric points . The isoelectric point of the CAT from pSCS6 was pH 5.7 and that of the CAT from pSCS7 pH 5.2 . Both CAT variants exhibited highest enzyme activities at pH 8.0 . The Km values for chloramphenicol and acetyl-CoA of the CAT from pSCS6 were 2.5 microM and 58.8 microM, respectively, while those of the CAT from pSCS7 were 2.7 microM and 55.5 microM . Both CAT variants were relatively thermostable . The CAT from pSCS6 was less sensitive to mercuric ions than the CAT from pSCS7.

Ann Cardiol Angeiol (Paris), 1992 Feb, 41(2), 63 - 8
{Endocarditis caused by heart valve prosthesis . Apropos of 35 cases}; Papola P et al.; 35 cases of prosthetic valve endocarditis are reported . The diagnostic is based on clinical, echocardiographic, bacteriological and anatomical aspects . Heart failure, neurologic complications, positive culture of prosthesis, Staphylococcus aureus infection and perivalvular abscess are factors of a bad prognosis . The current therapeutic trends associate antibiotic treatment and infected prosthetic valve replacement rather for hemodynamic indications than bacteriological factors . General prognosis has a mortality of 40 p . cent . Prophylaxis of infection, although simple is necessary.

Z Lebensm Unters Forsch, 1992 Feb, 194(2), 124 - 8
Effect of six organic acids on staphylococcal growth and enterotoxin production; Domenech A et al.; Four Staphylococcus aureus strains were incubated at 37 degrees C for 24 h in broth progressively acidified with lactic, citric, ascorbic, acetic, pyruvic and propionic acids, and their survival rate and enterotoxin producing ability was studied . Acids were chosen based on their frequent use by the food industry . Periodically, samples were withdrawn to determine counts, pH and the presence of enterotoxins A, B, C, and D . For a given acid, the effect on growth and enterotoxin synthesis was different . The most inhibitory acid for the growth of strains FRI-100 and FRI-472 was pyruvic acid, for strain FRI-137 was lactic acid, all six acids were equally effective on strain S6 . Lactic acid was very inhibitory to enterotoxin synthesis, but the effect on this parameter of acetic and citric acids was almost nil . Enterotoxins were seen to be inactivated at acid pH values; enterotoxin B was the most resistant to inactivation.

J Dairy Sci, 1992 Feb, 75(2), 596 - 605
The economic implications of bioengineered mastitis control; Miles H et al.; This paper estimates the cost of mastitis for the New York dairy sector . The average cost is found to be $125 per cow from reduced milk production, treatment, and increased culling . At the 1988 cow inventory, this translates to approximately $100 million annually for the entire dairy farm sector . When quality and production losses for the processing sector are added, the cost to the New York industry alone is nearly $150 million annually . Two promising new treatments, a bacteriocin and a vaccine, are evaluated . Both have shown effectiveness in preliminary trials against Staphylococcus aureus . Assuming that further development will allow the treatments to be effective against the major bacterial sources of mastitis infections, the treatments are projected to increase the annual income of the New York dairy industry by $18.8 to $39.7 million . The bacteriocin could replace antibiotic usage, a desirable goal in the opinion of many, and the vaccine promises to immunize cows against mastitis very effectively.

J Dairy Sci, 1992 Feb, 75(2), 423 - 34
Use of an enzyme-linked immunosorbent assay to monitor the control of Staphylococcus aureus mastitis; Grove TM et al.; Conventional culture methods were used to evaluate the ability of an ELISA to identify Staphylococcus aureus IMI . The test was 96% accurate; sensitivity was 90%, and specificity was 97% . The test was used to screen preserved milk samples rapidly in 10 cooperator herds . Prevalence of IMI was greater than 10% in 6 herds at the first test . Average prevalence of cows scoring +2 (suspect) and +3 (positive) was 12.6% . Prevalence declined during the 12-mo study . Incidence of new IMI decreased from 7.9% at 6 mo to 3.6% at 12 mo . Rinsing teat cup liners with a 25-ppm iodophor or 100-ppm chlorine solution reduced the presence of S . aureus on the milking machine liners by 97% . Elevated scores were correlated with increases in lactation number . Milk antibody concentrations changed quadratically with increasing SCC . The SCC increased as milk antibody concentration increased . In 38 dairy herds, bulk tank antibody tests reflected herd prevalence of S . aureus infection . The average prevalence was 15.0% in 87 herds in which all lactating cows were tested.

J Vet Med Sci, 1992 Feb, 54(1), 145 - 8
Protein characterizations and immunological properties of the low-molecular-mass protein A isolated from Staphylococcus aureus KS 1034; Kusunoki H et al.; The extracellular low-molecular-mass protein A isolated from Staphylococcus aureus KS 1034 was analyzed for its amino acid contents and terminal amino acid sequences . The C-terminal and the N-terminal amino acid sequences of the low-molecular-mass protein A were -Asn-Ala-Phe and Ala-Gln-His-Asp-Glu-Ala-Gln-, respectively . For immunochemical properties, the low-molecular-mass protein A was similar to protein A isolated from S . aureus Cowan I . Extracellular protease activity of KS 1034 strain was considerably lower than S . aureus C-30 isolated from chicken that produced the extracellular low-molecular-mass protein A.

Vet Microbiol, 1992 Feb, 30(2-3), 223 - 32
Chloramphenicol resistance plasmids in Staphylococcus aureus isolated from bovine subclinical mastitis; Cardoso M et al.; Chloramphenicol resistance (CmR) could be detected in 11 of 217 Staphylococcus aureus isolates from bovine subclinical mastitis . All isolates were assigned to biotypes A or C . The CmR-determinants were found to be located exclusively on small plasmids of approximately 4.6 kb as revealed by protoplast transformation . The 11 CmR-plasmids could be differentiated on the basis of restriction endonuclease analyses . The restriction maps of these CmR-plasmids identified two separate groups . One group demonstrated homology to the plasmid pC 221, the other to the plasmid pC 223 . Both prototype plasmids, pC 221 and pC 223, had been isolated from S . aureus of human origin.

Nippon Hinyokika Gakkai Zasshi, 1992 Feb, 83(2), 197 - 204
{Methicillin-resistant Staphylococcus aureus (MRSA) infection in urological field--clinical backgrounds and clinical course}; Koroku M et al.; The Staphylococcus aureus in this study were isolated from 33 outpatients and 38 inpatients of the Department of Urology from August 1989 to April 1991 . Twenty one patients (29.5%), three outpatients, had the MRSA type . Significant correlations were found between the incidence of MRSA infection and such factors as diabetes mellitus and the isolation of MRSA within 7 days of the administration of antibiotic agents . Out of 14 MRSA which were investigated for coagulase type, 9 were type VII . This indicates an outbreak of MRSA in the urological ward . Seven cases of MRSA and 5 cases of MRSA had high grade fever (over 38 degrees C), but all patients experienced much relief by using susceptible antibiotic agents . Our study shows that the isolation frequency of MRSA has increased in urological field . Therefore, we think it is important to treat patients with MRSA infection adequately, especially when there are compromised hosts in the same room.

Ann Pharmacother, 1992 Feb, 26(2), 209 - 10
Aerosolized vancomycin therapy facilitating nursing home placement; Gradon JD et al.; OBJECTIVE: To demonstrate a novel method of eliminating nasopharyngeal colonization by methicillin-resistant Staphylococcus aureus (MRSA) in a debilitated, hospitalized patient . DESIGN: Single-patient, nonblind, nonplacebo, case study . SETTING: Community hospital, Brooklyn, NY . PATIENT: Hospitalized patient with recalcitrant nasopharyngeal MRSA colonization that could not be eliminated by conventional therapeutic interventions . INTERVENTIONS: Aerosolized vancomycin hydrochloride 120 mg q6h administered in room air via face mask together with vancomycin nasal drops, 2 drops to each nostril q6h . MAIN OUTCOME MEASURE: Elimination of MRSA from the nasopharynx of the patient . RESULTS: Successful elimination of MRSA colonization after four days of therapy . CONCLUSIONS: Aerosolized vancomycin in combination with vancomycin nasal drops is beneficial in eliminating nasopharyngeal colonization by MRSA . Clinical trials are warranted to confirm this clinical observation.

Ophthalmology, 1992 Feb, 99(2), 180 - 4
Role of Staphylococcus aureus in chronic allergic conjunctivitis; Tuft SJ et al.; A study was undertaken to test the hypothesis that Staphylococcus aureus colonization of the lid margins could determine the expression of allergic eye disease in atopic patients . The authors compared lid isolates of S . aureus from 23 adults who had both atopic dermatitis and chronic conjunctivitis and isolates from 14 patients who had atopic dermatitis but who lacked ocular disease . No significant difference was found in either the staphylococcal protein A or hemolytic toxin production by isolates from the two disease groups, and there was no difference between groups in the quantity of serum IgG nor IgE antibodies to staphylococcal ribitol-teichoic acid . In seven patients with chronic allergic conjunctivitis who were challenged with staphylococcal protein A or heat-killed S . aureus, delayed-type hypersensitivity was not enhanced . These results suggest that although S . aureus colonization of the lids is common in atopic patients, neither the pattern of toxin production nor humoral or cell-mediated immunity to S . aureus play a role in the expression of chronic allergic conjunctivitis.

Diabetes Care, 1992 Feb, 15(2), 256 - 60
Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes; Marhoffer W et al.; OBJECTIVE--In this study, ingestion of Staphylococcus aureus and "bacteria killing" (BK) were measured to evaluate polymorphonuclear leukocyte (PMN) phagocytic functions and chemiluminescence response (CL) to phorbol-myristic acetate (PMA) as respiratory burst activity with regard to metabolic control parameters in diabetic patients . RESEARCH DESIGN AND METHODS--PMN phagocytic functions were assessed in 40 diabetic patients, all receiving insulin and in poor metabolic control, with 3H-thymidine-labeled Staphylococcus aureus in a modified radiometric assay . Bacteria killing was determined by pure-plate counting of surviving bacteria (colony-forming units {cfu}) and luminol-enhanced CL in response to PMA as a measure of respiratory burst . PMN function data were correlated to HbA1 as parameter of recent metabolic control . RESULTS--PMN of diabetic patients showed a significant reduction in Staphylococcus aureus (50.7 +/- 4.1%) and BK (29.4 +/- 4.2%) compared with healthy nondiabetic control subjects (76.6 +/- 4.6% and 16.3 +/- 3.1%, respectively, P less than 0.001), and PMN CL response was markedly reduced in diabetic patients also . Linear regression analysis showed a highly significant negative correlation of HbA1 versus Staphylococcus aureus (r = -0.67, P = 0.001) and a positive correlation for BK (r = 0.73, P less than 0.001) . This was also true for CL, although this did not reach statistical significance (P = 0.06) . CONCLUSIONS--The data obtained demonstrate impaired PMN phagocytic functions and CL response in diabetic patients . These findings suggest inhibitory effects of elevated glucose concentrations on PMNs, a possible role of protein glycosylation for impairing PMN function, thus contributing in part to altered host defense.

Br J Dermatol, 1992 Feb, 126 Suppl 39, 56 - 60
Clinical relevance of the antibacterial activity of terbinafine: a contralateral comparison between 1% terbinafine cream and 0.1% gentamicin sulphate cream in pyoderma; Nolting S et al.; The antibacterial efficacy of 1% terbinafine cream and 0.1% gentamicin sulphate cream was evaluated in 33 patients with superficial staphylococcal pyoderma in a double-blind contralateral comparison . After 12 days of active treatment, Staphylococcus aureus could be grown from only one out of 33 patients using terbinafine vs no patient using gentamicin . At the end of the study, a marked improvement in clinical symptoms was observed with no significant difference between the two therapies . Despite reviewing the patients three times during the course of the study, no adverse events were reported . The results of this study demonstrate that terbinafine has clinically relevant antibacterial properties which may be useful not only in pyoderma, but also in mixed fungal/bacterial infections, such as athlete's foot.

Am J Med Sci, 1992 Feb, 303(2), 121 - 2
Case report: inflammatory bronchial flap and 'check valve' bronchial obstruction; Rumbak MJ et al.; The authors report the case of a patient in whom check valve bronchial obstruction was the result of an inflamed bronchial mucosal flap . Bronchoscopic examination showed that the mucosal flap opened with inspiration and closed with expiration . Protective brush and semiquantitative bronchoalveolar lavage cultures grew Staphylococcus aureus and Pseudomonas spp . An inflammatory mucosal flap and check valve bronchiolar obstruction has been described previously in only one patient and this was on postmortem examination.

Zentralbl Veterinarmed B, 1992 Feb, 39(1), 39 - 47
Lytic activities, protein profiles and morphologic characteristics of new bacteriophages isolated from canine and human Staphylococcus aureus strains; Adesiyun AA et al.; The lytic activity, protein profile and morphology of five newly isolated phages from canine Staphylococcus aureus strains and one from a human S . aureus strain were compared with those of selected phages in the international phage sets (IPS) . Five canine phages lysed 57 (76.0%) of 75 canine isolates of Staphylococcus aureus from Nigeria at routine test dilution (RTD) while 34 (IPS) phages typed only 31 (41.3%) strains at RTD or/and 100-RTD . The new human phage lysed 11 (14.7%) of 75 strains isolated from human diarrhoea . The new phages were readily propagated, specific in activity and stable during storage at 4 degrees C . Prominent proteins detected by SDS-PAGE indicated similarities between some of the phages but one canine phage was distinctly different, as was its morphology which was an isometric head with a short tail compared to oval heads and long tails which characterized others . IPS phages in the same serologic group had similar protein profiles but no correlation was observed with lytic groups . The use of protein profile and electron micrographs allowed classification of the phages into serogroups . It is concluded that the newly isolated canine phages could be very useful in typing Nigerian canine strains of S . aureus.

East Afr Med J, 1992 Feb, 69(2), 78 - 82
Clinical and bacteriological study on childhood empyema in south eastern Nigeria; Asindi AA et al.; Forty-eight children with empyema thoracis were seen over a seven-year period (December, 1982 to November 1989) in the University of Calabar Teaching Hospital, Calabar, Nigeria . This number accounted for 0.2% of all paediatric admissions during the period . The peak age incidence was 2 years and under . Pneumonia was the antecedent illness in about all cases, but surprisingly, measles played an insignificant role . Late consultation and severe morbidity were constant feature with anaemia and cardiac failure as frequent complications of the disease . Staphylococcus aureus, the predominant causative organism was resistant to penicillin and ampicillin but sensitive to gentamicin, cloxacillin and erythromycin . The initial use of the parenteral gentamicin or cloxacillin in treating children with empyema is therefore recommended . This study demonstrates the rarity and low fatality (6%) of childhood empyema in Calabar, but protracted hospitalisation and exorbitant medication involved make it an important disease . Perhaps, it can be completely eliminated if parents are educated enough to avoid late reporting of childhood respiratory diseasePIP: Physicians analyzed December 1982-November 1989 data on 48 2-60 month old children with empyema thoracis at the University of Calabar Teaching Hospital in southeastern Nigeria to determine the incidence and etiology of empyema thoracis in this region . The incidence rate stood at 2/1000 pediatric admissions . 3 children died (6.3%), all of heart failure . 47 children suffered from fever, cough, and breathlessness, the symptoms for pneumonia . Even though bronchopneumonia is a common complication of measles which occurs frequently in Calabar, only 3 children (6.25%) also had measles . The most frequent complication of this accumulation of pus in the thoracic cavity was congestive heart failure (16 cases) . 47 patients suffered from anemia (hemoglobin levels 11 gm/dl) . Hemoglobin levels of 54% of all patients decreased over time to 8 gm/dl . In fact, 2 children had hemoglobin levels of 4.4 gm/dl and they experienced cardiac failure . Laboratory personnel were only able to examine pleural aspirates from 37 patients . They did not detect any organisms in 27% of these aspirates . This may have been due to parent's widespread practice of giving medication to all the children before coming to the hospital . 45.9% of the aspirates only grew Staphylococcus aureus while another 8.1% grew it and other pathogens . About 90% of the pathogens were resistant to ampicillin and penicillin and almost 90% were sensitive to cloxacillin, gentamicin, and erythromycin . Cloxacillin was very expensive and parenteral erythromycin was unavailable . Nevertheless the pediatricians used parenteral gentamicin and cloxacillin . The parents were responsible for buying the antibiotics which tended to be costly . All the patients required emergency closed tube thoracostomy drainage within 24 hours of admission . 83.3% remained in the hospital for 2 weeks and 33.3% for 1 month . Despite the rarity of empyema, long hospitalization and expensive drugs make it an important disease in Calabar .

Zh Mikrobiol Epidemiol Immunobiol, 1992 Feb, (2), 57 - 9
{The characteristics of the polyclonal action and immunomodulating activity of bacterial peptidoglycans in oppositely reacting mouse strains}; Pozur VK et al.; The data on the specific features of the polyclonal action of gram-negative bacteria on primary immune response to sheep red blood cells in oppositely reacting mouse strains are presented . Staphylococcus aureus and Bacterium flavum peptidoglycans have been found to increase the amount of antibody producing cells to thymus-dependent antigen only in the spleen of low-responsive mice . At the same time differences in the amino acid composition of these heteropolymers do not affect their stimulating activity . Differences between the capacity of B . flavum peptidoglycans to induce the activation of B cells in mice of different strains have been established.

Zh Mikrobiol Epidemiol Immunobiol, 1992 Feb, (2), 54 - 7
{The chemoluminescence of the primary focus of a suppurative infection and of isolated neutrophils exposed to dimephosphon}; Ziganshina LE et al.; The influence of dimephosphone at concentrations of 0.001 M-0.75 M on the chemiluminescence of tissues at the focus of purulent infection in the ear of a guinea pig, on the survival rate of the experimental animals injected with the lethal dose of Staphylococcus aureus, as well as on the spontaneous and stimulated chemiluminescence of blood neutrophils in patients with wound infection, was studied . The study showed that different concentrations of dimephosphone oppositely influenced the intensity of the chemiluminescence of neutrophil suspensions and tissues at the focus of infection: low concentrations were found to produce stimulating action and high concentrations, suppressive action . At the highest concentration used in this study (0.75 M) dimephosphone prevented the death of the animals receiving lethal doses of S . aureus.

J Leukoc Biol, 1992 Feb, 51(2), 164 - 71
Chronic granulomatous disease with partial deficiency of cytochrome b558 and incomplete respiratory burst: variants of the X-linked, cytochrome b558-negative form of the disease; Roos D et al.; Five male patients from four different families presented with a clinical record of chronic granulomatous disease (CGD): recurrent infections of the skin and/or respiratory tract with catalase-positive microorganisms, sometimes in combination with granulomata and/or abscesses in various organs . These patients differed from "classical" forms of the disease in that their neutrophils, although deficient in killing in vitro of Staphylococcus aureus, contained a decreased but measurable amount of cytochrome b558 (10-60% of normal on a heme basis), causing weak staining in the nitroblue tetrazolium dye test and a depressed respiratory burst after contact of the cells with fluid or particulate activators of the NADPH:O2 oxidoreductase . In the cell-free activation system, the defect in the patients' cells was localized in the membrane fraction . In each of the four families, the cellular abnormalities showed an X-linked inheritance . Fusion experiments performed with the monocytes from these patients and those from patients with classical X-linked, cytochrome b558-negative (Xb(0)) or autosomal, cytochrome b558-positive (Ab+) CGD showed complementation of NADPH:O2 oxidoreductase activity in the latter but not in the former combination . Thus, the unusual CGD patients represent variant forms of Xb(0) CGD, with mutations in the gene coding for the beta subunit of cytochrome b558 that do not cause complete loss of this protein.

J Clin Microbiol, 1992 Feb, 30(2), 362 - 9
Epidemiologic typing of Staphylococcus aureus by DNA restriction fragment length polymorphisms of rRNA genes: elucidation of the clonal nature of a group of bacteriophage-nontypeable, ciprofloxacin-resistant, methicillin-susceptible S . aureus isolates; Blumberg HM et al.; Analysis of DNA restriction fragment length polymorphisms of rRNA genes (ribotyping) was employed to assist in the epidemiologic investigation of the emergence and spread of ciprofloxacin-resistant Staphylococcus aureus at the Atlanta VA Medical Center because many isolates of interest were nontypeable by phages and harbored few plasmids useful as strain markers . Chromosomal DNAs of selected S . aureus isolates were digested initially with 20 different restriction enzymes . EcoRI appeared to give the best discrimination of hybridization banding patterns (ribotypes) and was used with all study isolates . Overall, 15 different ribotypes were seen among the 50 S . aureus isolates studied (7 ribotypes among 13 methicillin-susceptible S . aureus {MSSA} isolates and 9 ribotypes among 37 methicillin-resistant S . aureus {MRSA} isolates) . Seven of eight ciprofloxacin-resistant MSSA (CR-MSSA) patient isolates had identical antibiograms, were nontypeable by phages, and had a single 22-MDa plasmid . Six of these seven CR-MSSA isolates had an identical ribotype pattern . Ribotyping distinguished this CR-MSSA strain or clone from MRSA and other MSSA isolates, including nontypeable isolates that contained a 22-MDa plasmid . Five ciprofloxacin-susceptible MSSA isolates studied had five ribotypes; one pattern was identical to the CR-MSSA clone . Twenty-three CR-MRSA isolates recovered from the Atlanta VA Medical Center had four different ribotypes . Ribotyping proved to be a useful molecular epidemiologic tool in the study of S . aureus because it differentiated isolates which were indistinguishable by more traditional methods . In addition, this technique demonstrated that at our institution, ciprofloxacin resistance emerged in multiple strains of MRSA, as opposed to primarily a single strain or clone of MSSA.

J Hosp Infect, 1992 Feb, 20(2), 113 - 9
Ten years' experience with methicillin-resistant Staphylococcus aureus in a large Australian hospital; Faoagali JL et al.; The Royal Brisbane Hospital (RBH) is a 1200-bed teaching hospital with acute, general and specialist units for adult patients . Methicillin-resistant Staphylococcus aureus (MRSA) was first detected at the RBH in 1975 and the number of new patients colonized and infected increased from one in 1975 to 720 in 1989, with a peak of 811 in 1987 . Virulence may be inferred from blood culture isolates . Between 1979 and 1989 the number of patients with S . aureus bacteraemia increased from 40 to 138 per year . The percentage of these isolates which were MRSA varied from a low of 4% in 1980 to a peak of 37% in 1984 with 28% in 1989 . The control attempts, sensitivity patterns, sources of the isolates and their probable impact and importance will be discussed.

Cell Immunol, 1992 Feb, 139(2), 478 - 92
Effects of interferon-alpha on human B cell responsiveness: biphasic effects in cultures stimulated with Staphylococcus aureus; Oka H et al.; Although interferon-alpha (IFN-alpha) has been found to be involved in the immune regulation in vivo, the effects of IFN-alpha on human B cells have not yet been clarified because of conflicting results in the literature . The present study therefore examined the effects of several subtypes of IFN-alpha (natural, alpha 1, alpha 2a, alpha 2b) on B cell responsiveness in detail by comparing different experimental conditions . Highly purified B cells from normal human individuals were cultured with Staphylococcus aureus (SA) + IL-2 or with immobilized anti-CD3-activated T4 cells in the presence or absence of IFN-alpha . IFN-alpha enhanced the immunoglobulin (Ig) production induced by immobilized anti-CD3-activated T4 cells . By contrast, IFN-alpha (5-50,000 IU/ml) suppressed the Ig production induced by SA + IL-2 . The suppression by IFN-alpha was dependent on the concentration of SA . The inhibitory effects of IFN-alpha in SA-stimulated cultures were exerted in the first 72 hr of cultures and required the presence of IL-2, whereas IFN-alpha enhanced the maturation of B cells when it was added after 72 hr of cultures . The suppressive effects of IFN-alpha were overcome by addition of immobilized anti-CD3-preactivated T cells that had been treated with mitomycin C, but not by the addition of fresh T cells or soluble factors produced by activated T cells . Of interest, IFN-alpha did not inhibit the expression of IL-2R, but inhibited that of intercellular adhesion molecule-1 (ICAM-1) on B cells after stimulation with SA + IL-2, suggesting that the suppressive effects of IFN-alpha might be related to the regulation of B cell-B cell contacts through ICAM-1 . There was no significant difference in effects on B cells among various subtypes of IFN-alpha . These results suggest that the effects of IFN-alpha on human B cell responsiveness may be different depending on the nature of stimulation . Moreover, the data indicate that IFN-alpha enhances the differentiation of activated B cells irrespective of the activation signals.

J Neurosurg, 1992 Feb, 76(2), 307 - 11
Spinal subdural abscess . Case report; Bartels RH et al.; Only 44 cases of spinal subdural abscess have been reported to date . The authors present another case and review the relevant literature . The findings of intraspinal gassification on computerized tomography scans and Escherichia coli as the causative organism have not previously been described in relation to spinal subdural abscess . Most frequently, Staphylococcus aureus is the responsible organism . Hematogenous spread of infection from a distant source often takes place . In a surprising number of incidences, iatrogenic causes are the primary foci of spinal subdural abscess . Spinal subdural abscess is an unpredictable disease, with an unfavorable outcome if left untreated . If there is suspicion of a spinal subdural abscess, urgent radiological examination followed by immediate surgical drainage and appropriate antibiotic therapy is warranted.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 505 - 7
Antibacterial activity of sparfloxacin against experimental renal infections in mice; Georgopoulos A et al.; In a murine model of renal infection (Staphylococcus aureus and Escherichia coli), sparfloxacin was compared with ciprofloxacin and fleroxacin . After intrarenal inoculation, mice were treated orally for 5 days . The drugs were administered at five different dosages, ranging from 3.125 to 50 mg/kg of body weight per day for S . aureus and from 0.78 to 12.5 mg/kg/day for E . coli . Evaluation of efficacy was based on the proportional reduction of bacterial counts in the kidney tissues of treated animals compared with those of untreated control animals . For S . aureus, the doses required to clear the infection in 50% of mice were as follows: sparfloxacin, 10 mg/kg/day; ciprofloxacin, 33 mg/kg/day; and fleroxacin, 16 mg/kg/day . For E . coli renal infection, the corresponding dosages were as follows: sparfloxacin, 1.5 mg/kg/day; ciprofloxacin, 2.45 mg/kg/day; and fleroxacin, 1.8 mg/kg/day . Sparfloxacin and fleroxacin have a lower effective dose than ciprofloxacin in these models, probably because ciprofloxacin has a shorter serum half-life than the other two compounds.

Vet Immunol Immunopathol, 1992 Jan 31, 30(4), 399 - 410
Function of bovine mammary macrophages as antigen-presenting cells; Politis I et al.; The ability of mammary macrophages treated with Staphylococcus aureus to induce antigen-specific T-cell proliferation was compared to that of the autologous blood monocytes . Induction of T-cell proliferation has been correlated with changes in major histocompatibility complex (MHC) class II antigen expression and interleukin 1 (IL-1) production by mammary macrophages and blood monocytes . The present study showed that both monocytes and mammary macrophages treated with S . aureus induced T-cell proliferation . However, there was a 3-fold decrease (P less than 0.05) in T-cell proliferation in macrophage cultures compared to those of blood monocytes, when these cells were treated with S . aureus . Mammary macrophages, the cells less effective in stimulating T-cell proliferation, expressed lower levels (2-fold) of MHC class II molecules and produced less IL-1 (3-fold) than blood monocytes . These data suggest that S . aureus may affect macrophage-T cell interaction by modulating the expression of MHC class II molecules and the synthesis of IL-1 by macrophages.

Biochemistry, 1992 Jan 28, 31(3), 911 - 20
Solution studies of staphylococcal nuclease H124L . 1 . Backbone 1H and 15N resonances and secondary structure of the unligated enzyme as identified by three-dimensional NMR spectroscopy; Wang JF et al.; The backbone 1H and 15N resonances of unligated staphylococcal nuclease H124L (recombinant protein produced in Escherichia coli whose sequence is identical to the nuclease produced by the V8 strain of Staphylococcus aureus) have been assigned by three-dimensional (3D) 1H-15N NOESY-HMQC NMR spectroscopy at 14.1 tesla . The protein sample used in this study was labeled uniformly with 15N to a level greater than 95% by growing the E . coli host on a medium containing {99% 15N}ammonium sulfate as the sole nitrogen source . The assignments include 82% of the backbone 1HN and 1H alpha resonances as well as the 15N resonances of non-proline residues . Secondary structural elements (alpha-helices, beta-sheets, reverse turns, and loops) were determined by analysis of patterns of NOE connectivities present in the 3D spectrum.

J Biol Chem, 1992 Jan 25, 267(3), 1910 - 7
Constitutive presence of a catalytic fragment of protein kinase C epsilon in a small cell lung carcinoma cell line; Baxter G et al.; Protein kinase C (PKC) has been implicated in a variety of cellular responses such as proliferation, differentiation, and secretion . We assessed the role of PKC in the mitogenic effects of gastrin-releasing peptide (in a small cell lung cancer (SCLC) cell line . Using antisera that specifically recognize the PKC isoforms alpha, beta, gamma, delta, and epsilon, we determined that PKC epsilon is the major isoform in the SCLC cell line NCI-N417, followed by PKC alpha and delta . In addition to the 90-kDa PKC epsilon, our anti-PKC epsilon antiserum specifically detected a 40-kDa immunoreactive protein . Treatment of the cells with either 20 nM phorbol myristate acetate or 50 nM GRP enhanced significantly the level of the 40-kDa protein in a time-dependent (1-8 h), cycloheximide-sensitive fashion . Subcellular fractionation revealed that 90% of PKC epsilon was in particulate form, while the 40-kDa immunoreactive protein was cytosolic . To test the hypothesis that the 40-kDa soluble protein represented a catalytically independent PKC epsilon fragment, cytosolic extracts were assayed for kinase activity . 45-50% of the activity was apparent in the absence of the PKC activators phosphatidylserine and diacylglycerol . This effector-independent kinase activity was further purified by affinity chromatography using a synthetic peptide corresponding to the pseudosubstrate region of PKC epsilon (ERMRPRKRQGAVRRRV) coupled to Sepharose . The partially purified protein, recognized by the anti-PKC epsilon antiserum, exhibited histone kinase activity with kinetics similar to those of the tryptically generated catalytic fragment of brain PKC epsilon . This activity was inhibited by staurosporine (IC50 = 1 x 10(-8) M) and by the pseudosubstrate inhibitor peptide (IC50 = 7.7 x 10(-8) M) . The SCLC kinase and the brain PKC epsilon catalytic fragment were similar as indicated by the relative sizes of the PKC epsilon immunoreactive peptides generated with protease V8 from Staphylococcus aureus (Mr approximately 37,000, 34,000, 28,000, 26,000, and 25,000) . Taken together, we conclude that a variant SCLC cell line expresses a constitutively active catalytic fragment of PKC epsilon . Regulation by 12-O-tetradecanoyl-13-acetate or GRP via de novo protein synthesis suggests a novel mechanism of control of PKC diversity with implications for small cell lung cancer and possibly other malignancies.

J Biol Chem, 1992 Jan 25, 267(3), 1546 - 53
The purification of a Rap1 GTPase-activating protein from bovine brain cytosol; Nice EC et al.; Two GTPase-activating proteins (GAPs) have been detected in extracts from bovine brain: GAP-1, which is specific for the activation of ras GTPases, and GAP-3, which is specific for the activation of the rap1 GTPases . We present a strategy for the purification to homogeneity of a cytosolic form of GAP-3 from bovine brain . The 100,000 x g supernatant from homogenized brains was chromatographed sequentially on DEAE Fast Flow, green H-E4BD Sepharose, Bio-Gel A1.5, hydroxyapatite, and phenyl-Sepharose prior to high resolution separation on Mono Q HR 5/5, phenyl-Superose HR 5/5, Mono Q PC 1.6/5, and Superose 12 PC 3.2/30 . This procedure resulted in an approximately 18,000-fold purification, yielding 50 micrograms of GAP-3 from 1.6 kg of tissue . Purified cytosolic GAP-3 migrated as a single band of apparent Mr 55,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis . However, on gel filtration cytosolic GAP-3 chromatographed as a dimer with an apparent Mr 92,000 . Purified GAP-3 does not activate ras or rho GTPases and possesses no intrinsic GTPase activity . Amino acid sequence data indicated a proline-rich N terminus . The amino acid sequences of peptides generated by Staphylococcus aureus V8 digestion of reduced and pyridine-ethylated GAP-3 showed no similarity to the predicted primary structure of GAP-1 or any other proteins in the nucleic acid or protein data bases . By comparison with the data of Rubinfeld et al . (Rubinfeld, B., Munemitsu, S., Clark, R., Conroy, L., Watt, K., Crosier, W.J., McCormick, F., and Polakis, P . (1991) Cell 65, 1033-1042), it appears that the membrane-associated (Mr 85,000-95,000) and cytosolic forms of GAP-3 are derived from equivalent, or closely related, genes.

Brain Res, 1992 Jan 20, 570(1-2), 21 - 6
Identification of a B-50-like protein in frog brain synaptosomes; Janssen U et al.; Vestibular compensation in the frog following unilateral labyrinthectomy is accompanied by distinct changes in the endogenous phosphoprotein patterns in total frog brain homogenate and isolated synaptosomes . The purpose of this study was to characterize one of these proteins, an acidic 45-kDa synaptosomal protein, resembling in some of its features the growth-associated protein GAP-43/B-50 . Our results demonstrate by comparative analysis with purified rat B-50/GAP-43 that the 45-kDa protein (IP 4.8) in synaptosomal membranes of frog brain is phosphorylated by added purified PKC, cross-reacts with affinity-purified rabbit antibodies to rat B-50 and exhibits a Staphylococcus aureus V8 protease peptide digestion pattern corresponding to rat B-50 . Therefore, we conclude that the acidic 45-kDa synaptosomal protein is a growth-associated B-50-like protein, probably involved in processes responsible for compensatory reorganization of the vestibular structures after hemilabyrinthectomy in the frog.

Vet Rec, 1992 Jan 18, 130(3), 54 - 5
High incidence of clinical mastitis due to Staphylococcus aureus in two dairy herds with low milk cell counts; Torgerson PR et al.; Five dairy herds with a high incidence of clinical mastitis were investigated . Two of these herds had a high incidence of mastitis caused by Staphylococcus aureus yet had a relatively low rolling mean cell count . The mean cell counts of samples from clinical cases submitted by the dairymen from these two farms were significantly lower than the counts of similar samples submitted from the other farms . It is suggested that a possible explanation of the low cell count on these two farms was the proficiency of the dairy-men in detecting clinical mastitis.

Biochim Biophys Acta, 1992 Jan 16, 1138(1), 20 - 6
Niemann-Pick type II fibroblasts exhibit impaired cholesterol esterification in response to sphingomyelin hydrolysis; Byers DM et al.; Fibroblasts from patients with Niemann-Pick Type II disease, including the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) forms, exhibit reduced or delayed stimulation of cholesterol esterification by low density lipoprotein (LDL) . Based on recent evidence that cholesterol esterification can also be stimulated by cell surface sphingomyelin hydrolysis, we have compared the response of normal, NPC and NPD fibroblasts to treatment with exogenous sphingomyelinase (SMase) . Staphylococcus aureus SMase (greater than 0.05 U/ml) hydrolyzed over 90% of endogenous sphingomyelin within 1 h and increased incorporation of {3H}oleic acid into cholesterol-{3H}oleate after an initial lag in all three cell types . However, normal levels of cholesterol esterification were not observed for NP Type II fibroblasts: four NPD cell lines exhibited an average of 32% of normal response while cholesterol esterification was only 20% in two well-characterized NPC lines . A third NPC line exhibited normal response to SMase despite greater than 90% impairment of LDL-stimulated cholesterol esterification . Incubation of fibroblasts with LDL followed by SMase produced a synergistic response, particularly in NPC cells where there was little response to either treatment alone . Chloroquine abolished LDL-stimulated cholesterol esterification in normal fibroblasts but had no effect on the response to SMase, indicating that lysosomal enzymes may not be involved in SMase-mediated cholesterol esterification . These results suggest that intracellular processing of cholesterol derived from either LDL or release from the plasma membrane (by sphingomyelin hydrolysis) is affected in Niemann-Pick Type II cells and that these pathways can complement one another in the stimulation of cholesterol esterification.

J Immunol, 1992 Jan 15, 148(2), 491 - 7
Human recombinant IL-3 is a growth factor for normal B cells; Xia X et al.; IL-3 is a well known hemopoietic cell growth and differentiation factor . However, its functional role in normal B cell differentiation has not been established . We have investigated the effect of IL-3 on the growth and differentiation of human B cells . IL-3 enhanced the proliferation of Staphylococcus aureus Cowan 1 strain-stimulated B cells . The optimal time of IL-3 to stimulate B cell growth was on day 2 to day 3, suggesting that IL-3 was a B cell growth factor acting in the late stage . IL-3 synergized with IL-2 to enhance B cell proliferation and differentiation . Pretreatment of B cells with IL-3 for more than 3 days increased the expression of IL-2R on B cells . However, pretreatment of B cells with IL-2 did not alter the subsequent response to IL-3, suggesting that the synergy between IL-2 and IL-3 may be attributed to the up-regulation of IL-2 response by IL-3 . In addition, pretreatment of B cells with IL-4 decreased subsequent response of B cells to IL-3 as well as IL-2, suggesting that IL-3- and IL-2-responding cells passed a similar way during the early stage of B cell activation . It appears that IL-3 and IL-6 mediate normal B cell differentiation via separate mechanisms . IL-3-induced B cell differentiation was mainly mediated by increasing cell growth, whereas IL-6 induced B cell differentiation without affecting proliferation.

Vet Immunol Immunopathol, 1992 Jan 15, 30(2-3), 233 - 46
Effect of a milk-derived factor on the inflammatory response to Staphylococcus aureus intramammary infection; Owens WE et al.; Daily injections of an anti-inflammatory milk-derived factor (MDF) into mice increased resistance to Staphylococcus aureus challenge, and reduced leukocyte infiltration . Intraperitoneal injection of MDF into lactating mice prior to S . aureus intramammary challenge resulted in greater milk secretory activity and less inflammation compared with untreated controls, but had little effect on the number of S . aureus recovered from mammary tissue . Infusion of MDF directly into mouse mammary glands prior to challenge reduced S . aureus recovered after challenge . Incubation of bovine mammary macrophages in medium supplemented with MDF enhanced phagocytosis of opsonized S . aureus . In addition, infusion of 5 mg MDF into uninfected bovine mammary glands 24 h prior to S . aureus challenge resulted in fewer infections (five of ten) than in control quarters (seven of nine) . Repeated daily injections of 5 mg MDF into S . aureus-infected quarters increased the percent of mammary neutrophils and decreased the recovery of S . aureus, but did not eliminate infections . Intravenous injection of 8 g MDF into cows resulted in pronounced leukopenia while the accompanying effect on mammary leukocytes was less marked but followed a similar course . Results suggest that the use of MDF in mice enhanced resistance to experimental infection and was beneficial in maintaining mammary secretory activity and reducing inflammation after bacterial challenge . In the cow, MDF promoted phagocytosis in vitro and was effective against challenge when infused intramammarily.

J Immunol, 1992 Jan 15, 148(2), 381 - 7
Uncoupling of cytokine mRNA expression and protein secretion during the induction phase of T cell anergy; Schall TJ et al.; The CD4+ T cell clone HA1.7 may be made specifically nonresponsive, or anergic, to its cognate Ag, an influenza hemagglutinin peptide (HA), by pretreatment with the superantigen Staphylococcus aureus enterotoxin B or with high concentrations of HA itself . We compare the patterns of mRNA expression and protein production of selected T cell cytokines during the first 24 h after treatments that induce anergy in HA1.7 and during the same period after treatments that simulate normal cellular activation . The cytokines examined include TNF-alpha, IL-8/neutrophil activating protein-1 and the RANTES/SIS cytokines, a family of small secreted proteins with inflammatory and potential antiproliferative and leukocyte regulating activities . Messenger RNA for TNF-alpha, human MIP-1 alpha, human MIP-1 beta, and IL-8 are all induced during the development of clonal anergy in HA1.7, and these levels are significantly higher than those seen during activation of the clone using an anti-CD3 antibody and IL-2 . These high levels of mRNA also persist longer than those seen after anti-CD3 and IL-2 activation . However, the increased levels of mRNA are not typically accompanied by increased protein secretion . In all cases but one, the amount of cytokine secreted by HA1.7 cells was greater after anti-CD3 and IL-2 treatments than after anergy-inducing treatments . Thus, the induction of T cell anergy in HA1.7 does not appear to require a general inhibition of T cell cytokine mRNA expression, and, in fact, anergy treatments appear to superinduce certain cytokine transcripts, but anergy-specific posttranscriptional mechanisms may exist by which cytokine release is regulated.

Cancer Lett, 1992 Jan 10, 61(2), 105 - 10
Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin; Kumar S et al.; Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I . Its antitumour activity is proven in various tumour models . Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis . Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA . The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone) . Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth . Our data indicate that protein A has anticarcinogenic properties.

J Mol Biol, 1992 Jan 5, 223(1), 377 - 80
Crystallization and preliminary crystallographic data on Escherichia coli TEM1 beta-lactamase; Jelsch C et al.; Two crystal forms of Gram- bacteria TEM beta-lactamase have been obtained . The tetragonal form has a very large unit cell and diffracts to 3.0 A resolution . Orthorhombic crystals, grown using ammonium sulfate and a small amount of acetone as precipitating agents, belong to space group P2(1)2(1)2(1) with cell parameters a = 43.1 A, b = 64.4 A, c = 91.2 A and diffract to 1.7 A resolution . A seeding procedure has been designed that ensures reproducibility of the crystal properties . Molecular replacement, using a model reconstructed from the C alpha co-ordinates from Staphylococcus aureus PC1 beta-lactamase, gives a solution that satisfies crystal packing constraints.

J Mol Biol, 1992 Jan 5, 223(1), 145 - 58
Specificity of origin recognition by replication initiator protein in plasmids of the pT181 family is determined by a six amino acid residue element; Wang PZ et al.; We have investigated the specificity of replication origin recognition by the initiator proteins of a set of six closely related Staphylococcus aureus plasmids, the pT181 family . These plasmids replicate by an asymmetric rolling-circle mechanism using plasmid-coded initiators that nick the replication origins and form a phosphotyrosine bond at the 5' nick terminus . Five of the plasmids are in different incompatibility groups and their initiator proteins do not cross-complement the cloned origins of any but their own plasmid . One pair is weakly incompatible and their initiator proteins and origins do cross-complement for replication in vivo . This pattern of cross-reactivity led to the prediction that the determinant of specificity would correspond to a homologously positioned set of six residues in the C-terminal domain of the protein, some 80 residues away from the active site tyrosine, that are divergent for all of the compatible plasmids and identical for the incompatible pair . Site-directed mutagenesis was used to exchange these six residues among three pairs of plasmids and these exchanges brought about the predicted switching of origin recognition specificity . Single substitution within this six residue set reduced or eliminated the activity of the protein but did not alter the origin recognition specificity . These six and flanking residues cannot form an amphipathic alpha-helix nor do they conform to the classical helix-turn-helix or other known DNA binding motifs . A novel type of interaction is suggested in which the protein binds to its recognition site, bends and melts the DNA, and causes or enhances the extrusion of an adjacent cruciform containing the nick site . This configuration would juxtapose the nicking target and the active site tyrosine residue and would unwind the highly G + C-rich replication origin.

J Biol Chem, 1992 Jan 5, 267(1), 126 - 32
Transport of phagosomal components to an endosomal compartment; Pitt A et al.; The participation of phagosomes in interorganellar protein and membrane exchange is important to the maturation of phagosomes into phagolysosomes . To investigate this process, we have developed an assay to measure protein transport from phagosomes to other vesicle populations . J774-E clone macrophages phagocytosed 125I-anti-dinitrophenol IgG-coated Staphylococcus aureus for 3 min followed by chase for intervals of 0-30 min . Following cell fractionation, the intracellular distribution of radioiodinated protein was assayed . We observed a time-dependent increase radioiodinated protein in a non-phagosome vesicle fraction which displayed endosome characteristics . Concomitantly, radioiodinated protein within phagosomes decreased over the chase period . As assessed via Percoll density gradient fractionation, the phagocytosed radioiodinated protein migrated to both heavy (lysosome density) and light (endosome density) vesicle populations . Characterization of the fusogenic properties of the transport vesicles demonstrated that they are capable of in vitro fusion with early endosomes . Furthermore, this fusion event shares many of the biochemical requirements identified for phagosome-endosome and endosome-endosome fusion . Morphological analysis of phagosome maturation provides additional evidence for phagosome to endosome transport . These results suggest phagocytosed material is transferred from phagosomes to endosomes and then recycled out of the cell.

J Biol Chem, 1992 Jan 5, 267(1), 323 - 30
Activation of NADPH oxidase in human neutrophils permeabilized with Staphylococcus aureus alpha-toxin . A lower Km when the enzyme is activated in situ; Bauldry SA et al.; The NADPH oxidase is a multicomponent enzyme system that produces the reduced oxygen species essential for bacterial killing by polymorphonuclear leukocytes (PMN) . Study of the oxidase has typically been carried out in cell-free systems in which Km values of 20-150 microM NADPH have been reported . However, when compared with affinities reported for other flavoprotein dehydrogenases and when considering the cellular concentration of NADPH/NADP+ of approximately 35 microM, the reported affinity of the oxidase for NADPH appears low . To investigate this apparent discrepancy we have studied the kinetics of NADPH oxidase activation in situ in human PMN permeabilized with Staphylococcus aureus alpha-toxin . alpha-Toxin permeabilization of human PMN did not initiate NADPH oxidase activation at physiologic concentrations of NADPH . If permeabilized cells were stimulated with 1 microM formyl-methionyl-leucyl-phenylalanine, 10 microM guanosine 5'-O-(3-thiotriphosphate), 0.5 mM Ca2+, 5 micrograms/ml cytochalasin B in the presence of varying concentrations of NADPH, we were able to demonstrate activation of the oxidase complex as shown by superoxide dismutase-inhibitable reduction of cytochrome c . In this system we determined that the Km for oxidase activation was 4-7 microM NADPH, a 4-10-fold decrease from reported values . The oxidase was the enzyme being studied as shown by the absence of enzymatic activity in patients with chronic granulomatous disease . In addition, if the enzyme was initially activated in permeabilized cells, the cells homogenized, and the Km for the oxidase determined in a cell-free system, the observed Km reverted to previously reported values (36 microM) . These results indicate that NADPH oxidase, studied in situ, has a significantly higher substrate affinity than that observed in isolated membranes and, moreover, indicate that substrate affinity is optimal for catalysis at reported concentrations of cytosolic NADPH.

J Environ Pathol Toxicol Oncol, 1992 Jan-Feb, 11(1), 43 - 6
Protective and therapeutic efficacies of protein A on 7,12-dimethylbenz(alpha)anthracene-induced rat mammary adenocarcinoma; Bansal MR et al.; Protein A of Staphylococcus aureus Cowan I is a powerful immunostimulating agent . Female Swiss Portan rats fed 7,12-dimethylbenz(alpha)anthrancene (DMBA) exhibited increased serum alkaline phosphatase activity, which returned to normal levels following eight weeks of treatment with 12 micrograms protein A subcutaneously . Protein A reduced the potential of tumor induction by DMBA as observed by the noninduction of tumors until three months after discontinuation of protein A administration . The total leukocyte count was not affected . Protein A treatment for six weeks of DMBA-induced mammary adenocarcinoma-bearing rats caused the increased serum alkaline phosphatase activity to decrease but not to normal levels, indicating regression but no disappearance of the tumors . The total leukocyte count of the tumor bearers was stimulated by protein A and increased 24 hours after protein A administration; however, in the fourth week of treatment it returned to normal levels . The leukocytosis suggests that protein A could cause tumor necrosis by an inflammatory reaction, edema, and cell destruction and thus tumor regression.

J Antimicrob Chemother, 1992 Jan, 29(1), 35 - 9
Antibiotic resistance and plasmids in Staphylococcus aureus from normal populations; Virani Z et al.; Antibiotic resistance, plasmid profiles and plasmid structures were examined in nasal Staphylococcus aureus collected from a random sample of normal individuals in the mid 1960s and from women at an antenatal clinic in 1989 . The results were generally similar except for an increase in the resistance to penicillin in the later sample . The plasmid population had changed little though more uncategorized plasmids were evident in the 1960s samples.

J Clin Microbiol, 1992 Jan, 30(1), 63 - 6
Controlled evaluation of BACTEC PLUS 27 and Roche Septi-Chek anaerobic blood culture bottles; Wilson ML et al.; Becton Dickinson Diagnostic Instrument Systems (Sparks, Md.) recently introduced BACTEC high-volume aerobic and anaerobic bottles that accept up to 10 ml of blood for use on their nonradiometric blood culture instruments . Both bottles contain 25 ml of tryptic soy broth, 0.05% sodium polyanetholesulfonate, and mixed resins . We compared the anaerobic bottle, designated BACTEC PLUS 27 (BP27), with the Roche Septi-Chek (RSC) Columbia broth anaerobic bottle in a collaborative evaluation at three university hospitals . A total of 5,152 adequately filled blood cultures were obtained from adult patients with suspected bacteremia or fungemia . Staphylococcus aureus was recovered significantly more often (P less than 0.03) from BP27 bottles alone; there were no other significant differences in yield . When microorganisms were recovered from both anaerobic bottles, growth was detected earlier in BP27 than it was in RSC (P less than 0.001), especially for S . aureus (P less than 0.001) and Staphylococcus epidermidis (P less than 0.02) . We conclude that the yield from BP27 bottles is equivalent to or better (S . aureus) than that from RSC anaerobic bottles with Columbia broth and that speed of detection is superior with BP27 bottles.

J Clin Microbiol, 1992 Jan, 30(1), 252 - 4
Phage pattern-specific oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus in U.S . hospitals: epidemiological significance; Zierdt CH et al.; For a 13-year period (1978 through 1990), oxacillin-resistant (MIC, greater than 4 micrograms/ml) Staphylococcus aureus (ORSA) strains were collected from Clinical Center (National Institutes of Health) patients and patients from five other U.S . hospitals . From Clinical Center patients, 251 of 253 isolates (99%) were bacteriophage typed as phage group III . Five other hospitals contributed 203 ORSA strains, of which 188 (93%) were group III . The group III ORSA strains predominantly included a characteristic core pattern of phages, 7/47/53/54/75/77 . For the low-level (borderline) oxacillin-resistant strains (MIC, 2 to 4 micrograms/ml), amoxicillin-clavulanic acid combination (Augmentin) testing disclosed 62 hyper-beta-lactamase producers, of which 59 (95%) were of a separate, distinct S . aureus strain, with the phage pattern 92/94/96/292/D-11 (group V) . Thus, ORSA and hyper-beta-lactamase producing S . aureus are distinct epidemic strains.

Clin Exp Immunol, 1992 Jan, 87(1), 53 - 7
Hyper-response of serum IgG1 to Staphylococcus aureus peptidoglycan in patients with hyper-IgE syndrome; Ishizaka A et al.; The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis and recurrent infections . To determine whether an impairment of the antibody response to Staphylococcus aureus contributes to infections in this syndrome we measured total serum IgG subclass, specific IgG1 and IgG2 levels against peptidoglycan (PG), the immunodominant cell wall component of S . aureus and serum opsonic activity to PG . Of the 14 patients with HIE syndrome, nine had increased level of serum IgG1 and six had IgG2 subclass deficiency . In regard to specific response of IgG1 and IgG2 antibodies to PG, patients were divided into five groups related to ages and compared with 10 control subjects for each age cohort . Patients with HIE syndrome had significant high levels of serum-specific IgG1 to PG and significant decreased levels of serum-specific IgG2 to PG in all five groups . Additionally, serum opsonic activity in patients was significantly higher than that in normal control subjects . It is concluded that IgG2 deficiency or poor IgG2 antibody response to S . aureus is not the explanation of the abnormal susceptibility to S . aureus infections of HIE patients.

Biochem J, 1992 Jan 1, 281 ( Pt 1), 191 - 6
Identification of the site of covalent attachment of nafcillin, a reversible suicide inhibitor of beta-lactamase; Tan AK et al.; Nafcillin was shown to reversibly inhibit beta-lactamase from Staphylococcus aureus PC1 with characteristics indicative of a type A inhibitor {Citri, Samuni & Zyk (1976) Proc . Natl . Acad . Sci . U.S.A . 73, 1048-1052} . At nafcillin concentrations above 80 mM, complete inactivation occurred within 200 s . Upon removal of the excess nafcillin the inhibited enzyme was re-activated completely, with a rate constant of 2.0 x 10(-3) s-1 (25 degrees C) . The inhibited enzyme was shown to be in the form of a covalent acyl-enzyme intermediate . Digestion by pepsin and trypsin yielded a single nafcillin-labelled peptide fragment which was isolated, sequenced and shown to be: Ala-Tyr-Ala-Ser-Thr-Ser-Lys . This sequence corresponds to the region surrounding the active-site serine residue, Ser-70, indicating that the inhibitor is covalently attached to the same residue as productive substrates.

J Med Microbiol, 1992 Jan, 36(1), 56 - 60
Resistance to desiccation and skin fatty acids in outbreak strains of methicillin-resistant Staphylococcus aureus; Farrington M et al.; Resistance to desiccation and to skin fatty acids was measured in three groups of methicillin-resistant Staphylococcus aureus (MRSA) strains and a group of control strains . Organisms from a large outbreak on a special care baby unit (SCBU), where MRSA had been isolated from staff hands but not from the environment, were significantly more sensitive to drying than strains from a burns unit where extensive environmental contamination had been demonstrated . MRSA from other wards, in the same hospital but not associated with large outbreaks, gave heterogeneous results . Fatty-acid resistance, determined by an agar dilution method, was not associated with strain origin . Some epidemic strains of MRSA were relatively sensitive to desiccation, and the abilities of such strains to spread widely on a SCBU by the hand-borne route could not be explained by enhanced resistance to skin fatty acids.

J Med Microbiol, 1992 Jan, 36(1), 52 - 5
Aggregation of human granulocytes by Staphylococcus aureus lipase; Rollof J et al.; The effects of purified extracellular lipase from Staphylococcus aureus on human granulocytes were studied in vitro with a turbidimetric technique . Within the concentration range 0.6-4.4 micrograms/ml, lipase caused monophasic aggregation accompanied by the release of lactoferrin; the corresponding concentrations of the solvent in which it was suspended, Triton X100, had no effect . Lipase-induced aggregation did not occur in the presence of autologous plasma.

Proc Natl Acad Sci U S A, 1992 Jan 1, 89(1), 290 - 4
Replication of single-stranded plasmid pT181 DNA in vitro; Birch P et al.; Plasmid pT181 is a 4437-base-pair, multicopy plasmid of Staphylococcus aureus that encodes tetracycline resistance . The replication of the leading strand of pT181 DNA initiates by covalent extension of a site-specific nick generated by the initiator protein at the origin of replication and proceeds by an asymmetric rolling circle mechanism . The origin of the leading strand synthesis also serves as the site for termination of replication . Replication of pT181 DNA in vivo and in vitro has been shown to generate a single-stranded intermediate that corresponds to the leading strand of the DNA . In vivo results have suggested that a palindromic sequence, palA, located near the leading strand termination site acts as the lagging strand origin . In this paper we report the development and characterization of an in vitro system for the replication of single-stranded pT181 DNA . Synthesis of the lagging strand of pT181 proceeded in the absence of the leading strand synthesis and did not require the pT181-encoded initiator protein, RepC . The replication of the lagging strand required RNA polymerase-dependent synthesis of an RNA primer . Replication of single-stranded pT181 DNA was found to be greatly stimulated in the presence of the palA sequence . We also show that palA acts as the lagging strand origin and that DNA synthesis initiates within this region.

Infect Immun, 1992 Jan, 60(1), 249 - 56
Effect of specific antibody on adherence of Staphylococcus aureus to bovine mammary epithelial cells; Olmsted SB et al.; Staphylococcus aureus is a major pathogen in the bovine mammary gland . The ability of S . aureus to adhere to epithelial cells in the ductules and alveoli of the bovine mammary gland is believed to add greatly to its virulence and may be necessary for colonization . Two in vitro methods were developed for the purposes of quantifying adherence and of determining the effect which specific antibody may have in inhibiting the adherence of this organism . Both methods utilize bovine mammary epithelial primary cells as targets for labeled bacteria . In one assay, the bacteria are labeled with {methyl-3H}thymidine and incubated on the primary epithelial monolayers . The second assay involves labeling the bacteria with biotin . An enzyme-linked immunosorbent assay is then performed with streptavidin conjugated to horseradish peroxidase . Both methods have proven to be reliable and allow for the testing of many criteria in one assay . Cows were immunized with a whole-cell vaccine, and immune serum and milk were collected . The bacteria were then incubated in the presence of serum or milk as a test for antiadherent capability . By using the methods described, distinct antiadherent activity in both serum and milk was demonstrated.

Chest, 1992 Jan, 101(1), 199 - 203
Etiology and diagnosis of pneumonia requiring ICU admission; Potgieter PD et al.; The spectrum of pathogens and the microbiologic investigations used to obtain a diagnosis in 178 patients with severe pneumonia (88 percent requiring intermittent positive-pressure ventilation) are reviewed . Ninety-five patients had primary pneumonia, 31 had nosocomial pneumonia, 24 were immunocompromised patients, and 28 had aspiration pneumonia . While the spectrum of isolates conformed to the usual patterns for the different types of pneumonia, the incidence of Gram-positive infections (15 percent), predominantly Klebsiella pneumoniae, Staphylococcus aureus, (8 percent), and Legionella pneumophila (5 percent) in primary pneumonia was much higher than in community or general hospital-based studies, and only one case of Mycoplasma pneumoniae was identified . Gram stain of sputum or tracheal aspirate taken on intubation in primary pneumonia was reliably predictive of the causative organisms in both Gram-positive and Gram-negative infections when compared with infections proven by blood culture . Serologic studies were valuable in patients in whom no positive microbiologic diagnosis was evident; however, fiberoptic bronchoscopy contributed minimally to the microbiologic diagnosis in this group of patients . The cause of severe primary pneumonia differs from less severe disease, and this should be recognized when selecting empiric antibiotic therapy.

J Vasc Surg, 1992 Jan, 15(1), 35 - 41; discussion 41-2
Cefuroxime versus cefazolin as prophylaxis in vascular surgery; Edwards WH Jr et al.; Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication . In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures . To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin . Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation . Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation . Both agents were continued every 6 hours after operation for 24 hours . Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2) . Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients . In vitro evaluation of six of the study isolates plus an additional eight S . aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05) . Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin . Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections . In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Gastroenterol, 1992 Jan, 87(1), 58 - 61
Percutaneous endoscopic gastrostomy as an unrecognized source of methicillin-resistant Staphylococcus aureus colonization; Nunley D et al.; Methicillin-resistant Staphylococcus aureus (MRSA) caused colonization or infection around the gastrostomy site of seven hospitalized patients, five of whom were in the long-term care unit . All cultures of gastrostomy sites were retrospectively reviewed, and 28% had MRSA . The gastrostomy site was responsible for 6.3% of all MRSA cultures, and 12.5% of all MRSA-positive patients with gastrostomy site cultures had involvement at that site . The implications of MRSA and gastrostomy tubes are discussed.

J Immunol, 1992 Jan 1, 148(1), 29 - 34
Anti-IgM but not anti-IgD antibodies inhibit cell division of normal human mature B cells; Kim KM et al.; Insolubilized anti-IgD antibody markedly increased DNA synthesis in and cell division of normal peripheral blood B cells (PBL-B) when used in combination with IL-4 . Anti-IgM antibodies also induced DNA synthesis of PBL-B, but their ability to induce cell division was less than that of anti-IgD antibodies even when used in combination with IL-4 . Moreover, anti-IgM antibodies inhibited cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4 without affecting DNA synthesis . Anti-IgM antibodies also inhibited Staphylococcus aureus Cowan I-induced cell division of PBL-B without affecting DNA synthesis . These results indicate that cross-linkage of surface IgM (sIgM) in mature B cells generates negative signals to inhibit cell division of mature B cells . Because anti-IgD antibodies did not inhibit cell division at all, the role of sIgD in the regulation of cell division of mature B cells may be quite different from that of sIgM . IFN-alpha/beta promoted cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4 . They also counteracted the inhibitory effect of anti-IgM antibody on cell division of PBL-B.

Radiology, 1992 Jan, 182(1), 195 - 9
Diagnosis of bone, joint, and joint prosthesis infections with In-111-labeled nonspecific human immunoglobulin G scintigraphy; Oyen WJ et al.; The diagnostic accuracy of scintigraphy performed after injection of indium-111-labeled nonspecific human immunoglobulin G (IgG) was studied in 113 patients with 120 foci of suspected infection in bone (52 chronic and eight acute infections), joints (15 localizations), joint prostheses (37 prostheses), and soft tissue of the locomotor system (eight localizations) . All patients also underwent standard three-phase scintigraphy after injection of technetium-99m-labeled methylene diphosphonate . A scan obtained with In-111-labeled IgG was considered positive if focal increasing accumulation was noted over time . In 51 patients (45.1%), the results of scintigraphy were verified with intraoperative cultures, and in 21 patients (18.6%), with needle aspiration . The prevalence of infection was 59%; overall sensitivity, 97%; and specificity, 85% . Use of In-111-labeled IgG enabled correct identification of the presence, site, and extent of infection in 69 of 71 proved foci of infection; 41 of 48 negative studies were correct . Only two infections proved with culture were missed; in both patients, the cultures revealed growth of Staphylococcus aureus in low counts.

Srp Arh Celok Lek, 1992 Jan-Feb, 120(1-2), 31 - 3
{Osteomyelitis after malleolar fractures}; Milankov M et al.; Over a ten-year period, 485 patients suffering from malleous fracture were operated at the Department for Orthopaedic Surgery and Traumatology in Novi Sad . Postoperative infection appeared in ten cases (2.06%) . Eight of these patients primarily had open fractures, and two of them had closed ones . Osteosynthesis of the lateral malleous had most frequently been treated by the use of panel and screws . Staphylococcus aureus was isolated as symptom of the infection in eight cases . In treatment of malleous osteomyelitis, the debridement of focus of infection together with fixation material extraction was the most frequently performed operative method . During a two-year period no exacerbation, seven patients was observed while at control examination three patients had secretion from fistula . Mobility of ankle joint was limited in most cases, while walking imposed no pain.

Jpn J Ophthalmol, 1992, 36(1), 84 - 90
Increased lysosomal enzyme activity of keratocytes after endocytosis of foreign particles; Mishima H et al.; It has been reported that keratocytes endocytose foreign particles both in vitro and in vivo, suggesting the active participation of keratocytes in corneal wound healing and host defense mechanism . To understand the cellular response and the fate of engulfed foreign particles, we investigated the changes in the lysosomal enzyme activities after keratocytes endocytosed latex beads or glutaraldehyde-fixed Staphylococcus aureus . Acid phosphatase activity in the cells endocytosing either latex beads or fixed bacteria increased significantly as compared with that in the control over the period of 12 hours . Changes in acid phosphatase activity depended on both the incubation periods and the amount of latex beads or bacteria added . The activity reached a plateau after 6 hours of incubation . When keratocytes endocytosed latex beads, the activity of N-acetyl-beta-D-glucosaminidase in the cells showed an increase similar to that of acid phosphatase . However, the N-acetyl-glucosaminidase activity in the cells endocytosing fixed bacteria did not increase significantly . These findings suggest that endocytosing keratocytes increase degrading enzyme activities in the cells to break down engulfed foreign particles . It is also suggested that the intracellular response is varied according to the character of the engulfed materials.

In Vivo, 1992 Jan-Feb, 6(1), 13 - 6
Effect of pine seed shell extract on microbial and viral infection; Sakagami H et al.; Pretreatment of mice with ammonia extract of seed shell of Pinus Koraicenis, via the intraperitoneal or intravenous route, effectively protected them from lethal infection of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus . The pine seed shell extract also moderately inhibited syncytium formation and cytopathogenic effect induced by human immunodeficiency virus (HIV) infection in cultured human lymphotropic virus type I (HTLV-1) positive MT-4 cells . These data suggest a medicinal potential of pine seed shell extract against opportunistic infection in HIV patients.

J Biochem (Tokyo), 1992 Jan, 111(1), 109 - 12
Amino acid sequence of sweet-taste-suppressing peptide (gurmarin) from the leaves of Gymnema sylvestre; Kamei K et al.; The complete amino acid sequence of a sweet-taste-suppressing peptide, gurmarin, from the leaves of Gymnema sylvestre was determined by the Edman analysis of peptides derived from digests obtained with Staphylococcus aureus V8 protease, pyroglutamyl aminopeptidase, and lysyl endopeptidase . Gurmarin consists of 35 amino acid residues with an amino-terminal pyroglutamyl residue and has the molecular weight of 4,209 . Gurmarin has no significant homology with other known proteins.

Microbiol Immunol, 1992, 36(3), 231 - 4
Studies on osmotic stability of liposomes prepared with bacterial membrane lipids by carboxyfluorescein release; Nagamachi E et al.; The authors measured the osmotic stability of liposomes prepared with membrane lipids of bacteria, using the osmotic-shock release of entrapped carboxyfluorescein as an indicator . The sub-second physical changes of liposomes suspended in a solution of low osmotic pressure were examined by stopped flow spectrophotometry . The entrapped carboxyfluorescein was released when the liposomes burst on inflow of excess water . Liposomes prepared with the lipids of a stable Staphylococcus aureus L-form strain were more resistant to low osmotic pressure than those prepared from the wild strain of S . aureus, and liposomes prepared from Mycoplasma orale were even more resistant . Cardiolipin enhanced the lipid membrane stability in S . aureus and cholesterol in M . orale . The stability of lipid membranes to low osmotic pressure could be precisely determined by the present method.

Immunopharmacol Immunotoxicol, 1992, 14(1-2), 73 - 103
Protein A potentiates lymphokine-activated killer cell induction in normal and melanoma patient lymphocytes; Singh KP et al.; The effects of purified protein A from Staphylococcus aureus Cowan I stain on induction of lymphokine (IL-2) activated killer (LAK) activity were studied in normal as well as melanoma patient's lymphocyte . The coculture of peripheral blood mononuclear cells (PBMC) with various doses of protein A (0.001, 0.01 and 0.1 microgram/ml) and IL-2 (100 U/ml) for 4 days produced synergistic effect on the LAK cells mediated cytotoxicity . The potentiation of cytotoxicity and lytic ability of LAK cells against NK sensitive (K-562) and NK-resistant (M14) tumor cells were observed . Further there was potentiation of DNA synthesis in PBMC after 4 days culture . Similar results were found when PBMC from melanoma patients were cultured with PA and IL-2 . The potentiation of LAK cell induction associated with its cytotoxic and lytic potential by low doses of IL-2/PA regiment may be helpful in the development of LAK immunotherapy of the cancer patients.

Chemotherapy, 1992, 38(2), 107 - 11
An alkaloid, cepharanthine, potentiates the bactericidal effect of methylglyoxal bis (cyclopentylamidinohydrazone) on Staphylococcus aureus; Hibasami H et al.; Antiproliferative effects of combined treatment with methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine biosynthesis inhibitor, and cepharanthine, a biscoclaurine alkaloid, on methicillin- and gentamicin-resistant Staphylococcus aureus were investigated . The bactericidal effect of MGBCP on S . aureus was potentiated by the cepharanthine treatment . Cellular polyamine levels of the bacteria treated with both MGBCP and cepharanthine were much lower than those of the bacteria treated with MGBCP alone . On the contrary, the cellular MGBCP concentration was much higher in the cepharanthine-treated bacteria . Thus, cepharanthine was considered to enhance the incorporation of MGBCP into the bacteria . The combination of MGBCP and cepharanthine resulted in greater suppression of macromolecular synthesis in the bacteria that might have caused greater suppression of bacterial growth.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 6 - 9
Comparison of a polymerase chain reaction assay and a conventional microbiologic method for detection of methicillin-resistant Staphylococcus aureus; Tokue Y et al.; The presence or absence of a methicillin resistance gene in 58 clinical isolates of Staphylococcus aureus was examined by the polymerase chain reaction (PCR) and Southern blot analyses . The results were analyzed in relation to those of the MIC assay of methicillin and oxacillin . PCR assay results were identical to those of Southern blot analysis of genomic DNA digested with HindIII (positive, 28 strains; negative, 30 strains) . Among the 28 PCR-positive strains, 6 strains showed methicillin susceptibility by the conventional susceptibility test (MICs, less than or equal to 8 micrograms/ml) . Culturing of the six strains with ceftizoxime led to an increase in the phenotypic level of resistance to methicillin and oxacillin, indicating that these strains should be classified as methicillin-resistant S . aureus (MRSA) . The PCR assay was found to be a sensitive and reliable procedure for the rapid diagnosis of MRSA infection, even in cases in which the conventional MIC assay failed to detect MRSA.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 17 - 24
Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics; Tawara S et al.; The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia . The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated . In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum . A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values . On the other hand, in mice with pneumonia caused by K . pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue . There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum . The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung . These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.

Microbiol Immunol, 1992, 36(1), 35 - 41
Some improved versions of methods for the indirect detection of staphylococcal protein A gene expressed in Escherichia coli; Sakurada J et al.; Several versions of methods for the indirect detection of expression of staphylococcal protein A gene (spa) in Escherichia coli (E . coli) were devised by making use of biological properties of staphylococcal protein A (SpA) . i) Hemagglutination of sheep red blood cells (SRBC) sensitized with anti-SRBC-antibodies using heat-treated spa-transformed E . coli organisms; Native spa-transformed E . coli organisms did not agglutinate the sensitized SRBC . The heat-treatment (60 C, 4 hr) of the transformants, however, caused positive hemagglutination like SpA-positive Staphylococcus aureus (S . aureus) organisms . ii) Halo formation around colonies on agar plates containing normal dog serum, which is originally used for the detection of SpA of S . aureus . A mutant strain NMJ was isolated, which showed formation of the halo of precipitate due to interaction between immunoglobulin and SpA . iii) A new version of immunodetection; After lysis of the transformants grown on a nitrocellulose membrane by alkali, SpA could be directly detected by immuno-detection procedures after inactivation of endogenous peroxidase in bacteria by phenylhydrazine and hydrogen peroxide.

Khirurgiia (Mosk), 1992 Jan, (1), 47 - 51
{Phagocytic link of immunity in patients surgically treated for chronic calculous cholecystitis}; Antipov IA et al.; Twenty-two females, 38 to 75 years of age, who underwent planned operation for chronic uncomplicated calculous cholecystitis were examined in the pre- and postoperative period . Postoperative pneumonia developed in 4 (13.4%) patients, no other complications occurred . Functional neutrophil activity was studied according to the following parameters: spontaneous and induced NBT test, myeloperoxidase activity, amount of cationic proteins, expression of Fc receptors, spontaneous and induced luminol-dependent chemiluminescence, neutrophil bactericidal action against H-thymidine-labelled Staphylococcus aureus (strain 209), amount of blood immunoglobulins, and the modulating effect of serum of patients on the chemiluminescence of neutrophils of healthy donors . The control group consisted of 35 volunteers whose ages ranged from 18 to 50 years . Basic differences were revealed between the indices of neutrophil activity in patients with an uneventful postoperative period and those of patients with infectious complications in the preoperative period which became much graver in the early postoperative period . This suggests that neutrophilic dysfunctions play a significant role in the development of postoperative infectious complications in this category of patients.

Chem Pharm Bull (Tokyo), 1992 Jan, 40(1), 177 - 81
Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes; Takeda Y et al.; The regulatory effects of lobenzarit disodium (CCA), a therapeutic agent for treating rheumatoid arthritis (RA), on polyclonal immunoglobulin production by human lymphocytes were investigated in vitro . CCA inhibited the production of immunoglobulin in all the classes examined at a clinically relevant concentration . Moreover, it inhibited the immunoglobulin production as well as lymphocyte proliferation even when purified B lymphocytes preactivated by Staphylococcus aureus COWAN I were cultured with recombinant lymphokines such as IL2 and IL6 . These results suggest that CCA acts directly on B lymphocytes . The analysis at each of two different stages of B lymphocyte activation lineage, i.e., the primary activation stage and a stage of proliferation and differentiation to antibody secreting cells, has indicated that CCA inhibits the proliferation-differentiation stage of B lymphocytes . CCA does not inhibit B lymphocytes at the primary activation stage; actually, it augments them, resulting in the subsequent enhancement of immunoglobulin production.

Clin Infect Dis, 1992 Jan, 14(1), 75 - 82
Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review; Raad II et al.; Over the last two decades, the optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia has become the subject of controversy . A review of the literature revealed an occasional association between relapse of the infection and a short course of therapy (less than 10 days of iv antibiotic therapy) . From records kept between 1983 and 1989 at the University of Florida's affiliated hospitals, we identified 55 patients with catheter-related S . aureus bacteremia . Nine patients (16%) developed acute early complications (e.g., endocarditis or osteomyelitis) while receiving antibiotics . The results of multivariate analysis showed that an early complicated course was characterized by fever and/or bacteremia that persisted for greater than 3 days after catheter removal (P = .02) . The remaining 46 patients were followed up for at least 3 months . During follow-up, three of the 18 patients treated for less than 10 days with iv antibiotics developed relapsing septicemia, whereas none of the 28 patients treated for a longer period developed this condition (P = .05) . Fever and/or bacteremia that persists for greater than 3 days after catheter removal and initiation of antibiotic therapy suggests an acutely complicated course requiring prolonged treatment . The duration of iv antibiotic therapy in uncomplicated cases should not be less than 10 days but need not be greater than 2 weeks.

Microsurgery, 1992, 13(2), 84 - 91
Effect of treated infection on microvascular anastomosis; Luk KD et al.; The effect of established infection with penicillin-resistant Staphylococcus aureus on microarterial and microvenous anastomosis was studied in a rat experimental model . The infection was treated with wound debridement and systemic antibiotics at the time of the surgical procedure . It was found that the patency rate of microarterial repairs at 10-14 days was 95.1% . Veins were less resistant to infection than arteries . Two types of vein involvement were found . These were classified according to the degree of thrombosis resulting from endophlebitis . The patency rate of anastomoses performed on the more mildly infected veins was 56.5% and that on the more severely infected veins was 0%.

Eur J Clin Microbiol Infect Dis, 1992 Jan, 11(1), 47 - 51
Comparison of ampicillin/sulbactam and amoxicillin/clavulanic acid for detection of borderline oxacillin-resistant Staphylococcus aureus; Liu H et al.; Borderline oxacillin-resistant Staphylococcus aureus (BORSA) may be misidentified as intrinsically methicillin-resistant Staphylococcus aureus (MRSA) in the clinical laboratory . Under disk diffusion testing conditions designed to maximize detection of MRSA (incubation at 32 degrees C, pre-induction with methicillin, or plating on 4% NaCl-supplemented agar), BORSA strains also tend to appear resistant to semisynthetic penicillins . Under these conditions, ampicillin/sulbactam appears to be more accurate than amoxicillin/clavulanic acid for differentiating BORSA from MRSA.

Eur J Clin Microbiol Infect Dis, 1992 Jan, 11(1), 43 - 7
Immediate and long-term efficacy of systemic antibiotics for eradicating nasal colonization with Staphylococcus aureus; Lipsky BA et al.; The efficacy of nine antibiotics used in different nonrandomized regimens for eradicating nasal colonization with Staphylococcus aureus was investigated in 72 patients . Dicloxacillin, erythromycin and three cephalosporins had eradicated colonization in about 75% of cases at early follow-up (less than or equal to 20 days) and in less than or equal to 50% at late follow-up (greater than or equal to 20 days) . Clindamycin had eradicated colonization in all 13 patients at both follow-up times . One of two patients was successfully treated with fleroxacin, as were three of five with enoxacin . Among 21 patients treated with ofloxacin, colonization was eradicated in 20 (95%) at early follow-up and in all six of those from whom late follow-up cultures were obtained . Thus, clindamycin and ofloxacin appear to be useful systemic antibiotics for eradicating nasal colonization with Staphylococcus aureus.

Eur J Clin Microbiol Infect Dis, 1992 Jan, 11(1), 4 - 8
Restriction endonuclease analysis of Staphylococcus aureus plasmid DNA from three continents; Doebbeling BN et al.; Staphylococcus aureus isolates (n = 1201) from 20 centers in Europe, the USA and Brazil were evaluated for the presence of epidemiologic markers . Plasmid typing and restriction endonuclease analysis of plasmid DNA confirmed the presence of an apparently identical plasmid in 13% of clinical isolates . The plasmid was recovered from all 20 hospitals studied, with an overall frequency of greater than 10% on each of the three continents . Since relatively few staphylococcal plasmids may be shared by epidemiologically unrelated strains, there are inherent limitations to this otherwise useful technique . Additionally, these data demonstrate the importance of including unrelated strains of Staphylococcus aureus from the local region as controls when molecular typing methods are performed.

Clin Pharmacokinet, 1992 Jan, 22(1), 32 - 46
Ofloxacin clinical pharmacokinetics; Lamp KC et al.; Ofloxacin is a new fluoroquinolone with a spectrum of activity similar to other fluoroquinolones with activity which includes Chlamydia trachomatis, Mycobacterium spp., Mycoplasma spp . and Legionella pneumophila . Through its additional mechanisms of action, ofloxacin may be less susceptible to the development of resistance from Staphylococcus aureus commonly seen with currently available fluoroquinolones . The impact of these findings cannot be evaluated without further clinical experience . The pharmacokinetics of ofloxacin are characterised by almost complete bioavailability (95 to 100%), peak serum concentrations in the range of 2 to 3 mg/L after a 400mg oral dose and an average half-life of 5 to 8h . In comparison with other available quinolones, elimination is more highly dependent on renal clearance, which may lead to more frequent dosage adjustments in patients with impaired renal function . Ofloxacin appears less likely to affect the pharmacokinetics of drugs (e.g . theophylline) which commonly interact with fluoroquinolones such as ciprofloxacin and enoxacin . The properties of ofloxacin make it a therapeutic alternative to currently available fluoroquinolones.






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