Staphylococcus aureus

FEMS Microbiol Lett, 1993 Jan 15, 106(2), 147 - 55
Serotype F double- and triple-converting phage insertionally inactivate the Staphylococcus aureus beta-toxin determinant by a common molecular mechanism; Carroll JD et al.; The precise molecular mechanism of Staphylococcus aureus beta-toxin inactivation by the serotype F triple-converting phage phi 42, phi A1 and phi A3 was investigated . Sequence analysis of the phi 42 (attP) and Staphylococcus aureus (attB) attachment sites and the left (attL) and right (attR) chromosomal/bacteriophage DNA junctions of individual lysogens, each harbouring a triple-converting phage, revealed the presence of a common 14-bp core sequence in all four sites . These findings indicate that the genomes of the triple-converting phage integrate into the 5'-end of the beta-toxin gene (hlb) by a site- and orientation-specific mechanism identical to that previously described for the serotype F double-converting phage phi 13.

FEMS Microbiol Lett, 1993 Jan 15, 106(2), 123 - 7
Cloning of the replication region on the bacteriocinogenic plasmid pRJ9 of Staphylococcus aureus; de Oliveira SS et al.; A 5.8-kb ClaI fragment of pRJ9, a bacteriocinogenic plasmid of Staphylococcus aureus, was cloned in the unique ClaI site of pRJ5 . The recombinant plasmid obtained, pRJ23, failed to confer bacteriocin production and immunity to bacteriocin on host cells . The cloned fragment was shown to contain the complete replicon of pRJ9 . Attempts to clone the 4.4-kb ClaI fragment of pRJ9 were unsuccessful, apparently due to the inactivation of the basic replicon of the cloning vector . Therefore, plasmid pRJ5 cut at its ClaI site appears to be a suitable vector for cloning replication regions of plasmids that can replicate in S . aureus.

Gene, 1993 Jan 15, 123(1), 99 - 103
The use of degenerate, sensor gene-specific, oligodeoxyribonucleotide primers to amplify DNA fragments from Staphylococcus aureus; Bayles KW; The sensor proteins of bacterial two-component regulatory systems comprise a large family of proteins that are involved in environmental sensing and signal transduction . To study these proteins in the Gram+ pathogen, Staphylococcus aureus, two pairs of degenerate oligodeoxyribonucleotides (oligos) that corresponded to conserved sequences contained within sensor protein-encoding genes were synthesized . Using these oligo primers, DNA fragments from S . aureus were amplified by polymerase chain reaction (PCR), cloned in Escherichia coli, and sequenced . Comparison of the deduced amino acid sequences from these cloned fragments to the sequences contained in the GenBank database suggest that some of the PCR products were derived from sensor protein-encoding genes . However, several other fragments were identified that encoded peptides with up to 65% identity to transport proteins . Given the biochemical and functional properties of some of these proteins, these data suggest that sensor and transport proteins may be evolutionarily related.

Blood, 1993 Jan 15, 81(2), 454 - 61
Subtractive cDNA cloning of a novel member of the Ig gene superfamily expressed at high levels in activated B lymphocytes; Kozlow EJ et al.; Using subtractive cDNA cloning we have isolated a series of cDNA clones that are exclusively or selectively expressed in B lymphocytes . mRNA transcripts from one such cDNA clone, referred to as BL11, were found to be expressed at low levels in RNA from normal B lymphocytes, but at very high levels in RNA from in vitro activated B lymphocytes . One major 2.5-kb BL11 mRNA transcript was detected, while low levels of 4.8-, 1.8-, and 1.6-kb transcripts were also found . BL11 mRNA transcripts were absent or present at low levels in RNA prepared from resting or mitogen activated T cells, a variety of lymphoid cell lines including several B-cell lines, and several different tissues . Low levels of BL11 transcripts were found in poly(A) RNA purified from brain and lung . A study of the kinetics of BL11 mRNA accumulation in B lymphocytes stimulated in vitro with Staphylococcus aureus Cowan strain I showed a rapid induction of BL11 mRNA within 2 hours of stimulation with peak expression by 16 hours and a mild decrease with time following the peak levels . Consistent with the in vitro data, in situ hybridization using antisense BL11 RNA probes and human tonsillar tissue localized BL11 transcripts in B-cell-enriched areas . Multiple BL11 cDNA and genomic clones were isolated and sequenced to complete and verify the BL11 cDNA sequence (2,404 bp) . A 615-nucleotide open reading frame predicted to encode for a 205-amino acid protein with a molecular weight of 23 Kd was identified . Search of protein data bases with the predicted BL11 protein showed homologies to several members of the Ig superfamily . Analysis of the predicted protein showed a likely signal peptide, a single membrane spanning region, and one V-like Ig domain with three predicted n-glycosylation sites . Southern blot analysis of human genomic DNA suggested that BL11 is a single copy gene without evidence of rearrangement . Primer extension and S1 nuclease mapping identified four tightly clustered transcriptional start sites approximately 40 bp upstream of the predicted translation start site . The first 270 bp of the promoter region were sequenced and found to contain a CATAA box rather than a TATAA box and several DNA motifs found in activation genes . BL11 should prove to be an interesting gene that likely encodes for a protein involved in B-cell activation.

Med Clin (Barc), 1993 Jan 9, 100(1), 9 - 13
{Relationship between nosocomial infection and hospital mortality . Multicenter study}; Rodriguez-Rumayor G et al.; BACKGROUND: Hospital mortality related to infections acquired in the hospital setting has not been well studied in Spain . We carried out a study of seven hospitals in order to assess and quantify the problem . METHODS: The study period included three months of observations (between November 1, 1989 and January 31, 1990), and data pertaining to all deaths of patients hospitalized for a minimum of 24 hours were collected . The number of people admitted within the study period was 16,025, and the number of deaths registered and included in our study was 488 (3%) . The data were obtained from the patient's medical history one week after death as well as from the hospital physicians on the case . In order to quantify the interobserver variability derived from the classification criteria, the simple kappa index was calculated and averaged to form an ordinal scale . RESULTS: 216 (44.3%) of 488 deaths included in our study had no infection, 138 (28%) had an infection no-hospital-associated, and 134 (27%) had nosocomial infection (50-10%--"causally related to death", 59-12%--"contributing to death", and 25-5%--"not related to death") . The lower respiratory tract infections, bacteremias and surgical wound infections were the most related to cause of death . Staphylococcus aureus was the pathogen most frequently associated with the infections found at the time of death . CONCLUSIONS: Those patients admitted with non-fatal diseases made up the greatest percentage (39.9%) of deaths from nosocomial infections . The infection was considered the direct cause of death in 18.8% of these cases, although the differences found had no statistical significance.

Science, 1993 Jan 8, 259(5092), 227 - 30
Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus; Kreiswirth B et al.; Soon after methicillin was introduced into clinical practice in the early 1960s, resistant strains of Staphylococcus aureus (MRSA) appeared, bearing a newly acquired resistance gene, mecA, that encodes a penicillin binding protein, PBP2a . MRSA have spread throughout the world, and an investigation of the clonality of 472 isolates by DNA hybridization was performed . All 472 isolates could be divided into six temporally ordered mecA hybridization patterns, and three of these were subdivided by the chromomosomal transposon Tn554 . Each Tn554 pattern occurred in association with one and only one mecA pattern, suggesting that mecA divergence preceded the acquisition of Tn554 in all cases and therefore that mecA may have been acquired just once by S . aureus.

J Immunol Methods, 1993 Jan 4, 157(1-2), 225 - 31
Comparative analysis of using MTT and XTT in colorimetric assays for quantitating bovine neutrophil bactericidal activity; Stevens MG et al.; Two different tetrazolium compounds were compared for use in a colorimetric assay for quantitating bovine neutrophil bactericidal activity against Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, and Brucella abortus . The tetrazolium compounds tested included 3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide (MTT) and sodium 3,3'-{1{(phenylamino)carbonyl}-3,4- tetrazolium}-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) . The MTT and XTT colorimetric bactericidal assays were conducted by incubating antibody-opsonized bacteria with neutrophils in microtiter plates for 30 and 60 min at ratios of ten and 100 bacteria per neutrophil . Neutrophils were then lysed with saponin and samples were incubated 30 min with MTT or XTT plus coenzyme Q (CQ) . Dead bacteria and lysed neutrophils did not react with MTT or XTT plus CQ . Live bacteria converted XTT to water soluble orange formazan in the presence of CQ and MTT to insoluble purple formazan . Absorption of formazan produced by bacteria from XTT was measured at 450 nm . Formazan produced by bacteria from MTT was solubilized by adding isopropanol and measured by absorption at 560 nm . Absorption of both types of formazan was directly related to viable bacteria cell number and used to determine the number of bacteria not killed by neutrophils . The percentage of bacteria killed by neutrophils was determined by extrapolation from a standard formazan curve that was derived by incubating MTT or XTT plus CQ with known numbers of bacteria . The XTT and MTT colorimetric bactericidal assays produced comparable results when used to measure bovine neutrophil bactericidal activity against S . aureus, E . coli, L . monocytogenes, and B . abortus . However, the assay using XTT was quicker and easier to perform because bacteria converted XTT to a formazan that did not need to be solubilized before measuring absorption.

Bull Hosp Jt Dis, 1993-95, 53(4), 7 - 9
Septicemia in a child undergoing callotasis limb lengthening; Minty I et al.; We report a patient undergoing femoral callotasis lengthening using the dynamic axial fixator to correct a post-infective leg length discrepancy of 7.8 cm . Seventeen days after the operation, the patient developed a pin site infection, which was successfully treated by oral antibiotics . On the 34th post-operative day, the infection reoccurred, and was accompanied by generalized malaise, vomiting and pyrexia . Serology identified Staphylococcus aureus enterotoxin . Following removal of the fixator, the child recovered, but only four cm of lengthening was achieved . The pins probably acted as a persistent foreign body, with local inflammation creating favorable ground for bacterial infection . The role of the previous multifocal osteomyelitis unclear, but it could have acted as a continuous source of pathogens . The resulting toxemia was not immediately suspected, and could have resulted in the loss of the patient had the fixator not been removed promptly.

Vojnosanit Pregl, 1993 Jan-Feb, 50(1), 39 - 42
{Analysis of bacterial flora in burn patients}; Tomanovic B et al.; Bacterial flora of burn wound smears and hemocultures of 25 patients with burns have been followed up and analysed in the period of one year . Pseudomonas auruginosa have been most commonly isolated from burn wound smears, in 406 (5.6%) and Staphylococcus aureus, in 371 (47.14) samples . The most important hemoculture isolates has been Staphylococcus aureus found in 34 (57.6%) of samples . One multiresistant strain of Staphylococcus aureus represented 91% of all Staphylococcus aureus strains isolated from hemocultures and 84% from burn wound smears . Serologic and pyocin typing of Pseudomonas auruginosa proved the presence of several epidemic strains.

Biochem Mol Biol Int, 1993 Jan, 29(1), 149 - 59
Comparative study of the properties of plasmid mediated staphylococcal beta-lactamase as expressed in Escherichia coli; Saha D et al.; An unmodified natural plasmid of Staphylococcal origin having beta-lactamase determinant was introduced by transformation into Gram-negative Escherichia coli HB101 recA-SmR (plasmidless) . Beta-lactamase of Staphylococcus aureus is extracellular . In recipient transformed E . coli HB101, the enzyme shows periplasmic location . The enzyme is expressed well in E . coli, and the basal level of enzyme production in E . coli, is approximately 3-4 fold higher than that of S . aureus . Beta-lactamase is inducible both in S . aureus and E . coli . Enzymatic properties as indicated by substrate profile and Km values are found to be similar.

J Physiol, 1993 Jan, 460, 247 - 71
The effects of MgADP on cross-bridge kinetics: a laser flash photolysis study of guinea-pig smooth muscle; Nishiye E et al.; 1 . The effects of MgADP on cross-bridge kinetics were investigated using laser flash photolysis of caged ATP (P3-1(2-nitrophenyl) ethyladenosine 5'-triphosphate), in guinea-pig portal vein smooth muscle permeabilized with Staphylococcus aureus alpha-toxin . Isometric tension and in-phase stiffness transitions from rigor state were monitored upon photolysis of caged ATP . The estimated concentration of ATP released from caged ATP by high-pressure liquid chromatography (HPLC) was 1.3 mM . 2 . The time course of relaxation initiated by photolysis of caged ATP in the absence of Ca2+ was well fitted during the initial 200 ms by two exponential functions with time constants of, respectively, tau 1 = 34 ms and tau 2 = 1.2 s and relative amplitudes of 0.14 and 0.86 . Multiple exponential functions were needed to fit longer intervals; the half-time of the overall relaxation was 0.8 s . The second order rate constant for cross-bridge detachment by ATP, estimated from the rate of initial relaxation, was 0.4-2.3 x 10(4) M-1 s-1 . 3 . MgADP dose dependently reduced both the relative amplitude of the first component and the rate constant of the second component of relaxation . Conversely, treatment of muscles with apyrase, to deplete endogenous ADP, increased the relative amplitude of the first component . In the presence of MgADP, in-phase stiffness decreased during force maintenance, suggesting that the force per cross-bridge increased . The apparent dissociation constant (Kd) of MgADP for the cross-bridge binding site, estimated from its concentration-dependent effect on the relative amplitude of the first component, was 1.3 microM . This affinity is much higher than the previously reported values (50-300 microM for smooth muscle; 18-400 microM for skeletal muscle; 7-10 microM for cardiac muscle) . It is possible that the high affinity reflects the properties of a state generated during the co-operative reattachment cycle, rather than that of the rigor bridge . 4 . The rate constant of MgADP release from cross-bridges, estimated from its concentration-dependent effect on the rate constant of the second (tau 2) component, was 0.35-7.7 s-1 . To the extent that reattachment of cross-bridges could slow relaxation even during the initial 200 ms, this rate constant may be an underestimate . 5 . Inorganic phosphate (Pi, 30 mM) did not affect the rate of relaxation during the initial approximately 50 ms, but accelerated the slower phase of relaxation, consistent with a cyclic cross-bridge model in which Pi increases the proportion of cross-bridges in detached ('weakly bound') states.(ABSTRACT TRUNCATED AT 400 WORDS)

Bioorg Khim, 1993 Jan, 19(1), 75 - 80
{Cloning the Staphylococcus aureus enterotoxin B gene, obtained by polymerase chain reaction, and its expression in Escherichia coli cells}; Ignatov KB et al.; To determine the Staphylococcus aureus enterotoxigenicity, we have developed an approach based on polymerase chain reaction (PCR) . Using this method several S . aureus strains have been screened for the presence of the enterotoxin B gene . A DNA fragment of the selected strain (FRI 722H) containing enterotoxin B gene has been obtained by the PCR method and cloned in the pUC19 vector . It is shown that enterotoxin B with the leader peptide forms insoluble complexes in E . coli cells, whereas the mature toxin is present in cytoplasmic fraction in a soluble form . The recombinant toxin made up for 1.7% of the total cellular protein in E . coli JM 109 cells.

Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S13 - 8
Genetic control of population structure in heterogeneous strains of methicillin resistant Staphylococcus aureus; de Lencastre H et al.; Cultures of heterogeneous strains of methicillin resistant Staphylococcus aureus are composed of several subpopulations of cells that differ in their level of antibiotic resistance and frequencies . Experimental evidence is presented indicating that the number of these subpopulations, their resistance level and the frequency with which they are represented in a culture are strain-specific and reproducible with a surprising degree of precision from one culture to another . This implies a genetic control of population structure in these bacteria.

Microbiol Immunol, 1993, 37(1), 29 - 34
Efficient adsorption of lysostaphin on bacterial cells of lysostaphin-resistant Staphylococcus aureus mutant; Sakurada J et al.; A simple and efficient method for the purification of staphylolytic endopeptidase (lysostaphin) contained in culture supernatant of Staphylococcus simulans biovar staphylolyticus strain by adsorption of the enzyme on bacterial cells of lysostaphin-resistant S . aureus mutant was successfully devised . Lysostaphin was sufficiently absorbed on the heat-killed mutant cells derived from S . aureus Cowan I and efficiently eluted by 3 M KSCN . Enzyme preparation obtained by a single procedure of the affinity purification was pure enough for practical use . The yield of the enzyme was 25 mg from 1 liter culture and recovery rate was 64%.

Monaldi Arch Chest Dis, 1993, 48(1), 29 - 33
Thymomodulin enhances phagocytic and intracellular killing activities of polymorphonuclear leucocytes without increasing release of chemotactic factors; Lantero S et al.; Thymomodulin, a calf thymus derivative, is able to stimulate T-lymphocytes and monocytes, and to activate phagocytes and their precursors . However, it is not fully understood whether the effect of thymomodulin on phagocytic cells is a direct stimulation, or a phenomenon mediated by cytokines released by mononuclear cells . To answer this question, we first evaluated the effects of thymomodulin on the phagocytosis and intracellular killing of Staphylococcus aureus by blood polymorphonuclear cells (PMNs), cultured with or without autologous mononuclear cells . Secondly, during the processes of phagocytosis and intracellular killing, we evaluated the release by PMNs of chemotactic factors for PMNs, lymphocytes and monocytes . No difference was found in the phagocytosis and killing processes when PMNs were incubated alone or with autologous mononuclear cells (p > 0.05, each comparison) . Thymomodulin was able to increase the phagocytosis process when PMNs were incubated with lymphocytes and monocytes (p = 0.05), and to enhance the killing by PMNs cultured alone (p = 0.05), or cultured with autologous mononuclear cells (p < 0.05) . The release of chemotactic factors for PMNs, lymphocytes and monocytes in the supernatants of the phagocytosis experiments, was higher when PMNs were incubated with mononuclear cells, compared to cultures of PMNs alone (p < 0.05, each comparison); and thymomodulin did not increase their release without the presence of autologous mononuclear cells in the cultures (p > 0.05 each comparison) . These data suggest that thymomodulin acts upon PMNs, inducing mononuclear cells to release factors able to stimulate the phagocytosis and the intracellular killing of exogenous organisms, but does not amplify the immune reaction enhancing further leucocytes recruitment.

Biofizika, 1993 Jan-Feb, 38(1), 37 - 46
{Molten globule unfolding by strong denaturing agents occurs by the "all or nothing" principle}; Uverskii VN et al.; The equilibrium Gu-HCl-induced denaturation of bovine carbonic anhydrase B and beta-lactamase from Staphylococcus aureus was studied at 4 degrees C by the multiparametric approach . With the use of fast protein size-exclusion chromatography (FPLC) it has been shown that in the region of the molten globule-random coil transition the distribution function of the protein molecules on size is bimodal, i.e . the protein molecules (which are already denatured) can only in one of two conformational states . Consequently the unfolding of the molten globule can be of "all-or-none" character . This means that a protein molecule can be at least in three discrete states: the native, the molten globule and unfolded.

Surg Today, 1993, 23(1), 4 - 8
A study on postoperative enteritis caused by methicillin-resistant Staphylococcus aureus; Takesue Y et al.; We investigated the production of staphylococcal enterotoxin (SE) with respect to coagulase types by methicillin-resistant Staphylococcus aureus (MRSA) . A total of 138 strains of MRSA, which were isolated from clinical materials in the surgical ward between 1983 and 1990, were studied . Coagulase type IV strains produced SE A only, whereas coagulase type II strains were classified into four groups by SE production: SE B producing strains (32.7%), SE C producing strains (29.8%), SE B and C coproducing strains (12.5%), and SE A and C coproducing strains (25.0%) . Almost all of the organisms (nine of ten) which were isolated from the feces of patients with MRSA enteritis were SE A and C coproducing strains . The coincidence in time of the prevalence of MRSA enteritis and the isolation SE A and C coproducing strains also demonstrated that these strains caused MRSA enteritis . Although SE C producing strains and SE A and C coproducing strains were simultaneously prevalent in 1990, the former tended to be sensitive while the latter tended to be resistant to minocycline . Considering the variety of antibiotic sensitivity in coagulase type II strains, it is thus considered to be of critical importance for epidemiologic purposes to further characterize isolates by SE typing.

Scand J Infect Dis, 1993, 25(1), 123 - 32
Activity of erythromycin and clindamycin in an experimental Staphylococcus aureus infection in normal and granulocytopenic mice . A comparative in vivo and in vitro study; Hoogeterp JJ et al.; The activity of 2 bacteriostatic antibiotics, erythromycin and clindamycin, against Staphylococcus aureus was studied in vitro and in an experimental infection in granulocytopenic as well as normal mice . In vivo, on the basis of dosage, erythromycin was 2.20 times more potent than clindamycin in normal mice and 1.95 times more potent in irradiated granulocytopenic mice . Tissue concentrations were calculated from the plasma concentrations, taking plasma protein and tissue binding into account . On the basis of the area under the curve for the free tissue concentrations, clindamycin was 1.48 times more potent than erythromycin in normal mice and 1.64 times more potent in irradiated mice, which is somewhat less than expected from the comparison in vitro . It is concluded that the relative antistaphylococcal efficacies of erythromycin and clindamycin in vivo can be predicted from the in-vitro values if the relevant pharmacokinetics are taken into account . Irradiation decreased the efficacy of both antibiotics such that an about 8-fold increase in dose led to an antibacterial effect similar to that in non-irradiated animals . This could imply that these drugs will not be sufficiently effective against staphylococcal infections in granulocytopenic patients.

Scand J Infect Dis, 1993, 25(1), 107 - 13
The value of surveillance cultures in neutropenic patients receiving selective intestinal decontamination; de Jong PJ et al.; 230 neutropenic episodes in 84 patients with acute myeloid leukemia receiving selective intestinal decontamination were studied to evaluate the ability of surveillance cultures to monitor the efficacy of microbial suppression, to identify causative organisms in case of fever, and to predict infection due to potential pathogens (i.e . Staphylococcus aureus and aerobic Gram-negative bacteria) . Most cultures became negative soon after the administration of prophylactic antibiotics and there were only few persistent colonizations . 14 potential pathogens resistant to the intestinal decontamination regimen were isolated in surveillance cultures, none of which caused infection . Of the 212 febrile episodes, only 22 were caused by a microbiologically documented infection with potential pathogens . Most microbiologically documented infections were caused by organisms not routinely identified by surveillance cultures, indicating efficient selective intestinal decontamination . Only 9 (41%) of the 22 infections with potential pathogens were predicted by surveillance cultures . We conclude that surveillance cultures are of limited use in predicting infection or identifying causative organisms of fever in neutropenic patients receiving selective intestinal decontamination . However, they are useful in monitoring the efficacy of microbial suppression . One set of surveillance cultures each week after the disappearance of potential pathogens would be sufficient.

Nephron, 1993, 63(4), 409 - 15
Depressed phagocytosis in hemodialyzed patients: in vivo and in vitro mechanisms; Vanholder R et al.; Infection is a frequent complication and the major cause of death among end-stage renal patients . Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis . In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients . Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples . These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C . This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA . PMNL response remains intact during dialysis with non-complement-activating dialyzers . In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood . We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure . The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions . These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.

Jpn J Antibiot, 1993 Jan, 46(1), 8 - 17
{Effects of a combination therapy consisting of arbekacin and ampicillin of methicillin-resistant Staphylococcus aureus}; Deguchi K et al.; Investigations were made on effects of a combination therapy consisting of arbekacin (ABK) and ampicillin (ABPC) against methicillin-resistant Staphylococcus aureus (MRSA) . The following conclusions were drawn . 1 . A frequency of FIC index to be < or = 0.5 upon a combination therapy consisting of ABK and ABPC against MRSA was 48.7%, hence this therapy showed better antibacterial effects than the other 8 combination therapies consisting of ABK and other antibiotics previously studied . 2 . A combination therapy consisting of ABK and ABPC against MRSA was better than any other combination therapy because ABPC had a higher binding affinity with penicillin-binding protein 3 of MRSA, and because a high antibacterial activity of ABPC was maintained during the combination therapy . ABPC did not lose antibacterial activity largely because MRSA dose not produce beta-lactamase, or most of MRSA produces little beta-lactamase activity . 3 . Our data indicate that the success of a combination therapy against MRSA depends upon the effects of the drug under sub MIC concentrations.

J Burn Care Rehabil, 1993 Jan-Feb, 14(1), 55 - 7
Development of septic arthritis by hematogenous seeding in a pediatric patient with burns; Smoot EC et al.; We describe a pediatric patient with burns who experienced a septic hip joint from hematogenous seeding by sustained Staphylococcus aureus bacteremia . A search for a central vascular focus of the bacteremia included the use of an indium scan, which localized purulence within the left hip joint . The physical findings, radiographic findings, and subsequent aspiration of the hip joint were diagnostic for a septic arthritis . This case alerts the physician that the pediatric hip is a potential site for infection in the presence of bacteremia . Once infected, the joint may become a secondary source of an ongoing bacteremia . The diagnostic work-up and treatment for a septic hip have been discussed . This occult site of infection is easy to overlook because a painful hip joint in the pediatric patient with burns may be confused for painful burn wounds . The prerequisites to joint infections in this population were all present: bacteremia, intercurrent illness, unique vascular anatomy, and an impaired immune response.

Acta Paediatr, 1993 Jan, 82(1), 113 - 5
Pyomyositis and staphylococcal scalded skin syndrome; Wong GW et al.; Pyomyositis is a rare musculoskeletal infection in non-tropical countries . We report a child who had pyomyositis complicated by staphylococcal scalded skin syndrome . This complication has not previously been described in patients with pyomyositis . Early diagnosis of pyomyositis was made by ultrasound examination, and percutaneous needle drainage under ultrasound guidance was performed . Pus aspirated and blood cultures grew Staphylococcus aureus . No open surgical drainage was required and resolution of the abscess was documented by serial ultrasound examinations.

Kansenshogaku Zasshi, 1993 Jan, 67(1), 45 - 52
{Hospital infection with methicillin-resistant Staphylococcus aureus (MRSA) in Saga Medical School Hospital, a rapid increase in coagulase type-VIII strains}; Nagasawa Z et al.; Hospital infection with MRSA has increased in Saga Medical School Hospital . The causative MRSA consisted predominantly of coagulase type-II strain before 1989, but after 1990, coagulase type-VII MRSA increased rapidly . This type-VII strain has marked multiple drug-resistance, and the pattern of drug sensitivity of MRSA in this hospital was different from that of MRSA detected in other facilities, which are clinically serious problems, therefore, we conducted an etiological study of the background of the increase in MRSA infection in our hospital . The results of the study are summarized as follows: 1) The proportions of MRSA (on strain from one patient) to all types of S . aureus detected in the hospital were 26% for 1986, 23% for 1988, 37% for 1989, 30% for 1990 and 60% for 1991 . The proportion increased greatly in 1991 . 2) Coagulase type VII-MRSA was first detected only in 5 patients in 1989, then it tended to spread, and this type (probably derived from the same strain) accounted for 47% of MRSA infection in patients examined in 1991 . 3) The study of the drug sensitivity pattern and etiological survey of the infection showed that coagulase type VII-MRSA prevalent in the hospital consisted of two types: CLDM, and EM-sensitive, IPM/CS, and MINO-resistant and TSST-1 non-producing and enterotoxin non-producing type, and CLDM, and EM-sensitive, IPM/CS, and MINO-resistant and TSST-1 non-producing type with enterotoxin serotype A . 4) Coagulase type VII-MRSA (Probably derived from the same strain) was detected in physicians and nurses working in affected wards and also in the patients's room.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Immunol Immunopathol, 1993 Jan, 66(1), 43 - 51
Regulation of B cell function by bucillamine, a novel disease-modifying antirheumatic drug; Hirohata S et al.; Bucillamine {N-(2-mercapto-2-methylpropionyl)-L-cysteine} (BUC) is a thiol compound that differs from D-penicillamine (DPC) in that it contains two free sulfhydryl groups . Clinical trials have demonstrated that its efficacy in rheumatoid arthritis is superior to that of DPC, but its mechanism of action remains unclear . We therefore examined the effects of BUC on the in vitro function of human B cells in comparison to those of DPC . IgM production was induced from highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus factors generated from mitogen-activated T cells (TF) or interleukin-2 (IL-2) or with immobilized anti-CD3-activated CD4+ T cells . BUC suppressed the production of IgM at concentrations of 0.3-100 micrograms/ml irrespective of the presence of CuSO4 . Whereas BUC suppressed the production of IL-2 and interferon-gamma by immobilized anti-CD3-activated CD4+ T cells, its suppressive effects on the production of IgM in anti-CD3-stimulated cultures were not overcome by addition of TF or IL-2, indicating that the action of BUC involves direct inhibition of B cell function . BUC suppressed the initial stages of B cell activation, but not the maturation of previously activated B cells . In contrast to DPC, the suppressive activities of BUC did not require the presence of copper and were not overcome by the addition of monocytes or catalase . The effects of SA981, a metabolite of BUC with an intramolecular disulfide, on B cell function were more marked than those of BUC, whereas the effects of SA679, another metabolite of BUC with one of the two sulfhydryl bonds methylated, were similar to those of DPC . SA672, a metabolite of BUC with both of the two sulfhydryl bonds methylated, did not suppress B cell function . These results indicate that BUC as well as some of its metabolites inhibit cytokine production by T cells and also suppress the production of IgM at least in part by directly inhibiting B cells . These compounds exert immunosuppressive effects that are similar to those of DPC, but also unique inhibitory effects that depend upon the capacity of BUC to form an intramolecular disulfide between its two sulfhydryl groups.

Mol Gen Genet, 1993 Jan, 236(2-3), 187 - 92
LamB as a carrier molecule for the functional exposition of IgG-binding domains of the Staphylococcus aureus protein A at the surface of Escherichia coli K12; Steidler L et al.; One, two or four IgG-binding domains of the Staphylococcus aureus Protein A (SPA) were inserted into the LamB protein which was expressed under control of the tac promoter . The chimeric proteins were shown to be exposed at the cell surface by analysis of isolated outer membranes and also by testing their functional interaction with IgG molecules . We hereby show that the LamB protein can accept as many as 232 amino acids (four SPA domains) and still be incorporated into the Escherichia coli outer membrane, while maintaining the functional conformation of the inserted SPA polypeptides.

Int J Pept Protein Res, 1993 Jan, 41(1), 74 - 84
Sequence and solution conformation of the 20-residue peptaibols, saturnisporins SA II and SA IV; Rebuffat S et al.; Saturnisporins SA II and SA IV are the major components of the 20-residue peptaibol mixture isolated from a culture of the fungus Trichoderma saturnisporum . These peptides exhibit antibiotic activity against Staphylococcus aureus . Their sequences were derived from unequivocal methodology implying the combined use of positive ion FAB mass spectrometry and NMR: the majority of the sequences result from mass spectrometry fragmentations and the location of isomeric residues arises either from analysis of ROESY cross-peaks between contiguous amide protons or from heteronuclear 2J or 3J 1H-13C couplings detected in long-range 1H-13C COSY experiments . The sequence specific 1H and 13C NMR assignments are described . Saturnisporins SA II and SA IV exhibit similar secondary structures, as deduced from their ROESY patterns and 3JNHC alpha H coupling constant values, together with amide hydrogen-deuterium exchange rates and temperature coefficients of amide and carbonyl groups . An overall alpha-helical structure is proposed, maintaining two regions of distortion to this regular structure; i) the N-terminal part, which contains 3(10) and mixed alpha-3(10) turns, and ii) the Aib10-Val15 region, including a Pro residue which accommodates a bend stabilized by two 3(10) H-bonds.

Antimicrob Agents Chemother, 1993 Jan, 37(1), 32 - 8
High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases; Gilbart J et al.; Mupirocin resistance in Staphylococcus aureus results from changes in the target enzyme, isoleucyl-tRNA synthetase (IRS) . Twelve strains of S . aureus comprising four susceptible (MICs < or = 4 micrograms/ml), four intermediate level-resistant (MICs between 8 and 256 micrograms/ml), and four highly resistant (MICs > or = 512 micrograms/ml) isolates were examined for their IRS content and the presence of a gene known to encode high-level mupirocin resistance . Ion-exchange chromatography of cell extracts showed a single IRS active peak in mupirocin-susceptible strains, with 50% inhibitory concentrations (IC50s) of 0.7 to 3.0 ng of mupirocin per ml . In strains showing intermediate mupirocin resistance, similar single IRS activity peaks were observed, but these were less sensitive to inhibition, and the mupirocin IC50s for them were 19 to 43 ng/ml . Strains that were highly resistant to mupirocin displayed two distinct peaks; one was similar to that found with susceptible strains (IC50, 0.9 to 2.5 ng/ml), but an additional peak with an IC50 of 7,000 to 10,000 ng/ml was also observed . A strain cured of the plasmid encoding high-level mupirocin resistance lacked the resistant IRS peak . Restriction digests, produced by endonuclease NcoI, of total bacterial DNA isolated from the highly resistant strains hybridized with a mupirocin resistance gene probe, whereas DNA isolated from the intermediate level-resistant and susceptible strains did not . These results demonstrate that two different IRS enzymes were present in highly mupirocin-resistant S . aureus strains . In strains expressing intermediate levels of resistance, only a chromosomally encoded IRS which was inhibited less by mupirocin than IRS from fully susceptible strains was detected.

J Steroid Biochem Mol Biol, 1993 Jan, 44(1), 1 - 11
Expression and functional analysis of steroid receptor fragments secreted from Staphylococcus aureus; Cao X et al.; Fragments of the DNA-binding domain of the rat glucocorticoid receptor (rGR) and the human estrogen receptor (hER) were expressed in Staphylococcus aureus as a chimeric fusion to protein A by using a modified expression vector with an artificial factor X-cleavage site . The secreted product was isolated by hydrophobic chromatography on Phenyl-Sepharose and purified on DNA-cellulose or by anion-exchange chromatography . After cleavage of the protein A moiety, the purified rGR DNA-binding domain from amino acids 406 to 523 (rGR406-523), binds specifically to a glucocorticoid responsive element as a homodimer but cannot form heterodimers with the DNA-binding domain of the hER . Amino acids 510 to 523 following the zinc finger region, as well as free sulfhydryl-groups are necessary for DNA-binding, which is more efficient when the tripeptide Gly-Gly-Cys is added to the carboxy terminal end . Despite its specific interaction with DNA, rGR406-523 does not activate transcription from the MMTV promoter in a cell-free system that efficiently responds to addition of native GR, suggesting that regions essential for transcriptional activation in vitro are located outside of the DNA-binding domain.

Eur J Immunol, 1993 Jan, 23(1), 191 - 9
Regulation of T helper cell cytokine expression: functional dichotomy of antigen-presenting cells; Schmitz J et al.; A bias to either cell-mediated or antibody-mediated effector mechanisms is induced in an immune response against a pathogen, if activated T helper cells (Th) predominantly express Th1 {interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta} or Th2 (IL-4, IL-5, IL-6 and IL-10) cytokines . Here we provide evidence that, due to the capability to secrete IL-1, macrophages, but not B cells, as antigen-presenting cells (APC) induce production of IFN-gamma in resting Th cells . Normal murine splenic Th cells were activated in vitro with the superantigen Staphylococcus aureus enterotoxin B (SEB) presented by macrophages as compared to other APC from murine spleen . As determined by immunofluorescence, Th cells producing IL-2 but almost none producing IL-4 and IL-5 are generated, irrespective of the type of APC . Generation of IFN-gamma-producing Th cells is largely dependent on presentation of SEB by macrophages . The requirement for macrophages, however, is overcome if IL-1 is provided . Expression of IFN-gamma by Th cells is not induced, if production of IL-1 by macrophages is inhibited by IL-10 . Our results suggest a functional dichotomy of APC: normal resting Th cells differentiate into IL-2 and IFN-gamma secreting cells (Th1 cells) if antigen is presented by macrophages, whereas presentation by B cells generates Th cells secreting IL-2, which might differentiate into Th2 cells upon re-stimulation.

Cutis, 1993 Jan, 51(1), 43 - 4
Linear bacterial dissection; Shelton R; An unusual case of an erythematous indurated arcuate plaque with a curvilinear appearance was noted after a patient manipulated an ingrown beard hair . During removal of a biopsy specimen, a purulent discharge was expressed that had evidently dissected through the dermis forming this interesting shape . This may be similar to a recently reported entity described by Shelley and Shelley as linear bacterial dissection . Culture of the discharge grew Staphylococcus aureus and Klebsiella pneumoniae . Complete resolution occurred after drainage and antibiotic therapy . Cellulitis and erysipelas typically do not show central clearing or form arcuate plaques . Aside from lymphangitis, thrombophlebitis, and sinus tracts of carbuncles, dermal infectious processes rarely present as linear or arcuate plaques . The differential diagnosis and a review of the literature are presented.

Intensive Care Med, 1993, 19(5), 285 - 9
Resistance to methicillin and virulence of Staphylococcus aureus strains in bacteriemic cancer patients; Marty L et al.; OBJECTIVE: To estimate the relation between resistance to methicillin and virulence in strains of Staph . aureus by estimating the survival at day 30 . DESIGN: Case control analysis . SETTING: Inpatients at a major Cancer Referral Center . PATIENTS: 21 patients with methicillin-resistant Staph . aureus (MRSA) bactaeremia and 45 patients with methicillin-susceptible Staph . aureus (MSSA) bactaeremia, all treated with vancomycin . MEASUREMENTS AND MAIN RESULTS: Fewer MRSA than MSSA patients were neutropenic (p = 0.04), but more MRSA patients were hospitalized in intensive care units (p = 0.03), had had surgical episodes (p = 0.06) . MRSA patients also had more microbiological samples cultured (p = 0.007) . The outcome of the bacteriemic episodes in 14 MRSA and 14 MSSA patients matched for these four factors showed that blood cultures from MRSA patients remained positive significantly longer (p = 0.04), but that survival and length of hospital stay were not significantly different . CONCLUSIONS: These results do not indicate that methicillin-resistance in Staph . aureus is associated with increased virulence.

Perit Dial Int, 1993, 13 Suppl 2, S79 - 80
Establishing an experimental infection model for peritoneal dialysis: effect of inoculum and volume; Calame W et al.; The effect of the number of bacteria and the volume of the inoculum was studied in an experimental infection model to establish a peritoneal dialysis model in the rat . Staphylococcus aureus was used in all experiments, and Staphylococcus epidermidis only in the volume experiments . A bacterial number between 10(8) and 10(9) colony-forming units (cfu) resulted in a time-dependent decrease of bacteria collected from the peritoneal cavity . Higher concentrations resulted in the death of animals, while lower concentrations were rapidly cleared . There was a positive correlation between the volume in which 3 x 10(8) cfu were dissolved and the number of bacteria isolated from the peritoneal cavity 24 hours after infection . The results of this study led to an experimental dialysis model using 10 mL of dialysis fluid and 0.5 mL of a suspension containing 3 x 10(8) cfu of Staphylococcus aureus.

Perit Dial Int, 1993, 13 Suppl 2, S332 - 4
Staphylococcus aureus peritonitis is associated with Staphylococcus aureus nasal carriage in peritoneal dialysis patients; Piraino B et al.; Although the definition of S . aureus nasal carriage in peritoneal dialysis patients is variable, carriage is often defined as 2 or more positive cultures for S . aureus . We investigated the relationship between S . aureus infections and nasal carriage (defined as 1 or more positive nose cultures) in 138 patients on peritoneal dialysis . By this definition, approximately 50% of the patients were carriers . The rates of S . aureus exit-site infection (0.28/year vs 0.43/year, p < 0.001) and peritonitis (0.08/year vs 0.20/year, p < 0.001) were lower in the noncarriers (patients with no positive nose cultures) than in those patients who had 1 or more positive nose cultures . Patients with only 1 positive nose culture had a similar S . aureus exit-site infection rate (0.31/year vs 0.28/year), but a higher peritonitis rate (0.24/year vs 0.08/year, p < 0.001) compared to those patients with no positive nose cultures . However, patients with 2 or more positive nose cultures were at increased risk for both S . aureus exit-site infections and peritonitis . This relationship held even when only patients with frequent nose cultures were included in the analysis . Thus patients with even 1 positive nose culture for S . aureus are at risk for S . aureus peritonitis and should not be classified as noncarriers.

Exp Clin Immunogenet, 1993, 10(1), 16 - 20
Defective calcium-dependent signal transduction in B lymphocytes of a certain common variable immunodeficiency; Kondo N et al.; Two different common variable immunodeficiency patients were studied . Patient 1 showed hypogammaglobulinemia in all major classes of gammaglobulins and slightly reduced percentages of circulating CD19+ cells, CD20+ cells and surface IgG-or IgA-bearing cells with a normal percentage of surface IgM-bearing cells . Patient 2 showed normal levels in IgM with IgG and IgA deficiencies and almost normal percentages of circulating CD19+ cells, CD20+ cells and surface IgM-, IgG- or IgA-bearing cells . The proliferative responses of peripheral blood mononuclear cells to B cell mitogen, Staphylococcus aureus Cowan I, were reduced in patient 1 but not in patient 2 . The intracellular calcium concentrations in lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus from patient 2 were increased after anti-mu stimulation . The concentrations were scarcely increased in LCLs from patient 1 . These results suggest that B cells of patient 1 have a defective Ca(2+)-dependent signal transduction pathway, resulting in a failure of cell activation and cell proliferation . The defect in B cells of patient 2 may exist on immunoglobulin gene switching or expression rather than the Ca(2+)-dependent signal transduction pathway.

Nephrol Dial Transplant, 1993, 8(3), 235 - 9
Nasal mupirocin ointment decreases the incidence of Staphylococcus aureus bacteraemias in haemodialysis patients; Boelaert JR et al.; The incidence of S . aureus bacteraemia in a haemodialysis unit was studied over 2 years (167.75 patient-years of follow-up) during which nasal calcium mupirocin was used to eradicate nasal S . aureus carriage; this incidence was compared to that previously observed in the same unit before the use of nasal mupirocin (185.8 patient-years) . Nasal mupirocin led to eradication of nasal S . aureus carriage in 96.3% of surveillance cultures and to a fourfold reduction in the incidence of S . aureus bacteraemia per patient-year, from 0.097 before mupirocin to 0.024 with mupirocin use (P = 0.008) . Once or thrice weekly maintenance regimens of mupirocin were equally efficacious . The incidence of bacteraemia caused by other micro-organisms was not significantly affected . One single mupirocin-resistant isolate was identified in a nasal surveillance culture . Eradication of S . aureus from the nares did not lead to overgrowth by other micro-organisms . Chemoprophylaxis with nasal mupirocin in haemodialysis patients is cost-effective.

Nephrol Dial Transplant, 1993, 8(2), 157 - 62
Adherence of Staphylococcus aureus to cultures of human peritoneal mesothelial cells; Glancey G et al.; Strains of Staphylococcus aureus, isolated from the effluent of patients with peritonitis on CAPD (continuous ambulatory peritoneal dialysis), adhered well to both cultured human mesothelial cells and to fibronectin, but not to laminin or gelatin . Mesothelial cells grown in medium M199 exhibited more surface fibronectin compared to cells grown in MEM-Dval and demonstrated higher levels of S . aureus adherence . Soluble fibronectin concentrations up to 10 micrograms/ml increased the adherence of S . aureus to cultured mesothelial cells . The dose-response curve was consistent with the binding of fibronectin to a saturable receptor of apparent dissociation constant (KD) = 1.7 x 10(-10) M . This corresponds closely to the KD (2 x 10(-10) M) of the staphylococcal fibronectin-binding protein . S . aureus adherence was increased following the preincubation of mesothelial cell monolayers with interleukin-1 and was maximal after 6 h preincubation . Treating mesothelial cells with interferon-gamma for 48-72 h reduced the adherence of S . aureus.

Mol Microbiol, 1993 Jan, 7(1), 99 - 107
A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage; Switalski LM et al.; Staphylococcus aureus strains isolated from patients with septic arthritis or osteomyelitis possess a collagen receptor present in two forms, which contains either two or three copies of a 187-amino-acid repeat motif . Collagen receptor-positive strains adhered to both collagen substrata and cartilage in a time-dependent process . Collagen receptor-specific antibodies blocked bacterial adherence, as did preincubation of the substrate with a recombinant form of the receptor protein . Furthermore, polystyrene beads coated with the collagen receptor bound collagen and attached to cartilage . Taken together, these results suggest that the collagen receptor is both necessary and sufficient to mediate bacterial adherence to cartilage in a process that constitutes an important part of the pathogenic mechanism in septic arthritis.

Infect Control Hosp Epidemiol, 1993 Jan, 14(1), 29 - 35
Restriction endonuclease analysis of plasmid DNA from methicillin-resistant Staphylococcus aureus: clinical application over a three-year period; Trilla A et al.; OBJECTIVE: To investigate trends in plasmid types of methicillin-resistant Staphylococcus aureus over a 3-year period and determine the clinical impact of plasmid typing . DESIGN: Restriction endonuclease analysis of plasmid DNA (REAP) was used to type 270 clinical isolates . SETTING: A Veterans Affairs Medical Center . RESULTS: Forty-four different REAP types were identified and, of these, 23 appeared only once . Types designed as V1 and V2 were more commonly found in nosocomial cases than in community-acquired cases (p < .05); whereas the K and D types were more common in isolates from community-acquired cases (p < .05) . In 30 (11%) isolates, no plasmid was detected . When combined with epidemiological data, REAP typing revealed 4 small outbreaks that would have been missed using traditional epidemiological methods alone . In large outbreaks involving 10 or more cases, REAP typing data revealed unsuspected patterns of transmission . CONCLUSIONS: Multiple plasmid types were present in this endemic setting . Restriction endonuclease analysis of plasmid DNA was a practical and valuable adjunct to traditional epidemiological methods.

Diagn Microbiol Infect Dis, 1993 Jan, 16(1), 9 - 16
Molecular epidemiology and antimicrobial susceptibility testing . Testing of quinolone-resistant Staphylococcus aureus strains isolated in Brazil; Rodrigues JN et al.; An outbreak of 20 oxacillin-resistant Staphylococcus aureus (ORSA) bloodstream infections (BSIs) was detected in the intensive care unit (ICU) at Hospital Sao Paulo, Brazil . In a surveillance study, 10% of ICU personnel were defined as chronic nasal carriers of ORSA . Thirteen BSIs and five nasal isolates were available for phage typing, restriction endonuclease analysis of plasmid (REAP) and chromosomal DNA hybridized with 32P rRNA gene probe . Susceptibility testing against select antimicrobial agents, including 11 quinolones, six glycopeptides, and five topical agents, was performed by broth microdilution and the disk diffusion tests . Ten of the 13 BSI isolates and four of the five nasal strains were oxacillin and quinolone resistant . The new fluoroquinolones CI-960 and WIN57273, the glycopeptides, and the topical agents ramoplanin, bacitracin, mupirocin, and novobiocin were most active . Fourteen strains, 12 BSI isolates, and three nasal isolates showed the same REAP profile . Moreover, the same REAP and chromosomal profile was detected in at least nine BSI isolates and in two nasal isolates . These strains were nontypable by phage typing . We concluded that nosocomial cross-transmission of a single, multiresistant strain of S . aureus occurred and that the epidemic reservoir was nasal carriage by ICU personnel.

Cell Immunol, 1993 Jan, 146(1), 117 - 30
Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes . I . Stimulation of PKC-dependent and -independent pathways by LMW-BCGF; Kolb JP et al.; The low molecular weight B cell growth factor (LMW-BCGF) induces the G1 --> S transition in human B lymphocytes activated by a first signal, Staphylococcus aureus Cowan (SAC) or anti-mu antibody . It also stimulates proliferation of normal long-term B cell lines and some B cell tumors . We have previously reported that LMW-BCGF induces the hydrolysis of polyphosphoinositides (PI) and a rise in intracellular free calcium concentration, through the generation of inositol trisphosphate (InsP3) (Renard et al., J . Immunol . 18, 1705, 1988) . In the present work we have analyzed the possible association between early signaling events elicited by LMW-BCGF in SAC-activated B cells and its ability to provoke DNA synthesis, notably at the level of phospholipase C (PLC) and protein kinase C (PK-C) activation . Inhibitors of PLC and of InsP3-induced calcium release were found to block LMW-BCGF-dependent DNA synthesis . An increase in membrane-associated protein kinase C (PK-C) activity was detected after the addition of the growth factor and the mitogenic effect of LMW-BCGF was partially suppressed when B cell blasts were incubated with staurosporine or H-3, two inhibitors of PK-C activity . In addition, the mitogenic effect due to the addition of LMW-BCGF was not modified by the incubation of B cell blasts with high concentrations of TPA, even if this treatment inhibited cellular response to a low concentration of TPA . LMW-BCGF also increased intracellular pH in B cell blasts and lymphokine-induced mitogenic activity was reduced when the Na+/H+ amiloride or ethylisopropyl amiloride (EIPA) antiport blockers were added . These results suggest that (i) LMW-BCGF-induced PI breakdown and CA2+ mobilization and cell alkalinization are associated with the induction of cell proliferation, and (ii) the activation of PK-C does not appear to be the sole pathway activated by LMW-BCGF.

Biochem J, 1993 Jan 1, 289 ( Pt 1), 289 - 97
Deglycosylation and fragmentation of purified rat liver angiotensin II receptor: application to the mapping of hormone-binding domains; Desarnaud F et al.; We report new structural data about the rat liver angiotensin II receptor, which belongs to the AT1 subclass . This receptor has been purified at analytical or semi-preparative levels by a previously described strategy involving its photolabelling with a biotinylated azido probe and selective adsorption of the covalent probe-receptor complexes to immobilized streptavidin {Marie, Seyer, Lombard, Desarnaud, Aumelas, Jard and Bonnafous (1990) Biochemistry 29, 8943-8950} . Chemical or enzymic deglycosylation of the purified receptor has shown a shift in its molecular mass from 65 kDa to 40 kDa . Fragmentation of the purified receptor was carried out with V8 protease from Staphylococcus aureus, CNBr and trypsin . It was possible to find trypsin-treatment conditions which allowed production of a 6 kDa probe-fragment complex with a satisfactory yield . Attempts to localize this small fragment (5 kDa after subtraction of the probe contribution) in the recently published rat AT1 receptor sequence are reported . As expected, this fragment is not glycosylated; moreover, its further fragmentation by CNBr induces a very slight decrease in its size . These data support the hypothesis that a receptor sequence comprising the third transmembrane domain and adjacent portions of extra- and intracellular loops is involved in photolabelling by the C-terminal azidophenylalanine of the angiotensin-derived probe . These preliminary results are discussed in terms of future prospects for the characterization of hormone-binding domains of angiotensin II receptors.

Vasa, 1993, 22(3), 241 - 6
{Pathogenesis and size development of infected saccular aneurysms--an animal experiment study}; Bosse U et al.; Both femoral arteries of 56 Wistar rats were intersected and re-anastomosed by microsurgical technique . 24 anastomoses were performed under aseptic conditions and 88 were contaminated with a standard suspension of staphylococcus aureus . All the contaminated anastomoses which had remained patent developed true saccular aneurysms that reached their maximum volume during the acute period of infection between the 10th and 50th postoperative day . None of the anastomoses performed under aseptic conditions developed an aneurysm . This experiment represents an animal model for the reproduction of true saccular aneurysms of the arterial wall . It may help to investigate the etiology of arterial aneurysm formation.

Microbios, 1993, 75(302), 17 - 21
Survival ability of clinical isolates of methicillin-resistant Staphylococcus aureus; Sasatsu M et al.; The survival abilities of methicillin-resistant strains of Staphylococcus aureus were compared with those of sensitive strains . Absorbent cotton was inoculated with 10(8) cells of each strain tested and stored at 30% humidity at 25 degrees C . The numbers of cells of sensitive strains decreased significantly to well below those of resistant strains after 4 weeks, while cells of resistant strains remained above 10(3) after 14 weeks.

Cytobios, 1993, 75(300), 21 - 32
Morphological changes of Carcinoscorpius rotundicauda amoebocyte and Escherichia coli during their interaction; Ding JL et al.; Interaction between Carcinoscorpius rotundicauda amoebocytes and Escherichia coli or Staphylococcus aureus has shown that whilst E . coli was observed to lyse, S . aureus remained intact . The heavily granulated amoebocytes were activated by the lipopolysaccharide of E . coli to undergo dramatic morphological changes with time, leading to degranulation which caused lysis of the E . coli . Degranulation of the amoebocytes involved maturation of the larger electron dense granules (0.7-2.0 micron) which were apparently mobilised towards the cell membrane whilst undergoing a loss in electron density . Some of these larger granules were expelled at 15-30 min while other intracellular granules underwent further degranulation, where parallel filaments appearing like microtubules were evident, giving the granules a striated and less dense form . By 60 min, there was complete depolymerisation of the microtubular filaments giving rise to undefined, fused and homogeneously packed striations and particulate material in the cytoplasm; the smaller electron dense granules (0.3-0.7 micron) remained unchanged . This asynchronous degranulation and preferential expulsion of granules from only some amoebocytes while maintaining others intact, implies that the horseshoe crab has safeguards in its defence mechanism, hence ensuring its continued survival as a 'living fossil'.

Biotechnol Ther, 1993, 4(1-2), 31 - 42
Functional interaction between interleukin-9/P40 and interleukin-4 in the induction of IgE production by normal human B lymphocytes; Dugas B et al.; Interleukin-4 (IL-4) has been shown to induce a high rate of IgE production by normal B lymphocytes from peripheral blood without preactivation of these cells . In the present study, significant IgE production was observed at the concentration of 30 U/mL IL-4 (0.5 ng IgE/mL), and a plateau value was reached at 300 U/mL (1.2 ng IgE/mL) . In these experiments, recombinant human (rh) and murine (rm) interleukin-9/P40 (IL-9/P40) were unable to induce such an IgE production by human B lymphocytes . However, in the presence of a suboptimal dose of IL-4 (100 U/mL), both rh and rm IL-9/P40 enhanced the IgE production in a dose-dependent manner (from 3 to 1000 U/mL) . Under these experimental conditions, the slight but significant (p < 0.01, Student's t test) production of IgG (50 ng/mL) was also potentiated when the cell cultures were performed in the presence of 300 U/mL of IL-9/P40 . The IL-4-induced IgG and IgM production by purified B lymphocytes preactivated with Staphylococcus aureus Cowan strain I was also potentiated in the presence of 300 U/mL of rh IL-9/P40, indicating a direct effect of this cytokine on this cell type . In contrast, IgE production by Staphylococcus aureus Cowan strain I-activated B lymphocytes was never observed . Taken together these data suggested a direct role for IL-9/P40 in the regulation of immunoglobulin production by B lymphocytes.

Perit Dial Int, 1993, 13(3), 224 - 7
Survival of 138 surgically placed straight double-cuff Tenckhoff catheters in patients on continuous ambulatory peritoneal dialysis; Weber J et al.; OBJECTIVE: To determine the natural history of a surgically placed Tenckhoff catheter in patients on continuous ambulatory peritoneal dialysis (CAPD) . DESIGN: Prospective 7-year study analyzing catheter survival of all catheters using the Kaplan-Meier life table methodology . SETTING: Teaching hospital, department of nephrology . PATIENTS: One hundred and fifteen unselected patients beginning CAPD . INTERVENTIONS: Removal of the catheter required for the following complications: exit-site or tunnel infections or relapsing peritonitis, outflow obstruction, pericatheter leak, and development of hernias . MAIN OUTCOME MEASURES: Period between insertion and removal of the catheter . RESULTS: The cumulative survival of all catheters after 1, 2, and 3 years of CAPD was 87%, 69% and 65% . Catheter survival of the first versus the second catheter after 1 year was significantly longer (p = 0.03) . The difference was not significant in relation to diabetes, age, and sex . Infectious complications caused 61% (n = 19) of all 31 catheter failures, mainly due to tunnel infections caused by Staphylococcus aureus (n = 12) . "Mechanical" complications accounted for 49% (n = 12) of catheter failures . Eight of 12 mechanical complications were outflow failures . Seven patients had to be transferred to hemodialysis . CONCLUSIONS: The straight Tenckhoff catheter is a reliable peritoneal access device for CAPD in an unselected patient population.

Perit Dial Int, 1993, 13(3), 198 - 200
Chronic tunnel infections in children: removal and replacement of the continuous ambulatory peritoneal dialysis catheter in a single operation; Schroder CH et al.; OBJECTIVE: Chronic tunnel infections often necessitate the removal of the continuous ambulatory peritoneal dialysis (CAPD) catheter . Most published studies advocate postponing the insertion of a new catheter for several weeks . For young children it will be particularly difficult to wait this length of time, since vascular access may be cumbersome, and hemodialysis may not be well tolerated . The present study describes the results of the simultaneous removal and replacement of the CAPD catheter . DESIGN: Twenty-three Toronto Western Hospital II catheters were inserted in 17 children because of infectious complications (21 chronic tunnel infections; 2 recurrent peritonitis) in a single operation under appropriate antibiotic prophylaxis . The new catheter was inserted at the contralateral side of the abdomen with the deep cuff in the midline, using the same entrance to the peritoneal cavity . Dialysis was resumed immediately after the operation . SETTING: A university pediatric dialysis unit . PATIENTS: Seventeen children (mean age 3.7 years; range 1.0-8.5 years) were studied . In this group 23 catheters were replaced . RESULTS: In four cases a relapse of the tunnel infection was observed within 3 months . All other cases remained free of infection for a period of at least 6 months . The main causative microorganism was Staphylococcus aureus (15 occurrences) . CONCLUSION: It is not necessary to interrupt peritoneal dialysis for the replacement of a CAPD catheter because of infectious complications.

Eur J Haematol Suppl, 1993, 54, 14 - 7
Teicoplanin in home therapy of the terminally ill child; Ball LM et al.; Children discharged in the terminal phase of illness were offered the possibility of having central venous line infections treated with teicoplanin at home by their parents after suitable instruction . The decision to begin antibiotic treatment was subjective, based on a history of rigors and/or raised temperature in an otherwise "well" child . No difficulties were encountered in instructing the chosen parents . In all, five treatment periods of 7 days were required in the five children selected . The review time was 31 weeks (mean duration, 6.2 weeks/patient; range, 4-12 weeks), ended in all cases by death . Infection occurred a mean of 3.2 weeks after discharge (range, 1-8 weeks), and all episodes were successfully treated at home without hospital admission or ward-based support . No deaths occurred as a result of antibiotic therapy failure, and there were no clinically relevant side-effects . Autopsy confirmed the absence of central venous line infection in one patient, but blood culture was positive for Staphylococcus aureus in another . This study shows that home treatment of line infections with teicoplanin is effective and well tolerated, and offers advantages in terms of quality of life and parent-child relationships.

J Clin Lab Anal, 1993, 7(4), 209 - 13
Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy; Watanabe A et al.; The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM) . H2O2 production by PMN after stimulation was measured using flow cytometry . Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function . H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls . This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation . Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function . It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.

Ann Fr Anesth Reanim, 1993, 12(1), 72 - 4
{Nosocomial Aeromonas hydrophila pneumonia complicating toxic coma}; Poirier T et al.; A 24-year-old male homosexual drug addict was admitted in coma and circulatory failure after a 10 g overdose of acebutolol . The usual resuscitative measures were undertaken, together with administration of adrenaline and gastric lavage . Six hours of external cardiac massage and pacing, and high catecholamine doses (36 mg.h-1 of adrenaline and 60 micrograms.kg-1 x min-1 of dobutamine) were required before the circulatory system became again spontaneously efficient . After this acute episode, the patient improved despite acute tubular necrosis . On the third day, bilateral alveolar and interstitial lesions were found on the chest film . Bronchoalveolar lavage and protected distal brushings were carried out . Both Aeromonas hydrophila and Staphylococcus aureus were found in the cultured brushings . Treatment with ceftriaxone, vancomycin and amikacin was introduced . This nosocomial pneumonia was very haemorrhagic, resulting in several bloody casts responsible for several episodes of atelectasis . The patient was definitely extubated on the 18th day, and left the ICU 23 days later without any sequela . His HIV status was negative . Four other infections with the same strain of Aeromonas hydrophila occurred at the same time as this patient's . The common source for this germ was found to be soft water . Several measures have since been undertaken: removal of a centralized water softener, filtration and higher chlorine content in the water circuit, and updating of intensive care protocols for disinfection of equipment.

Acta Neurochir (Wien), 1993, 122(1-2), 130 - 3
Pyogenic parenchymatous and nidus infection after embolization of an arteriovenous malformation . An unusual complication . Case report; Mourier KL et al.; Infectious complications of cerebral angiography and of therapeutic angiographic procedures are very seldom reported . The case of an infected embolized arteriovenous malformation (AVM) by staphylococcus aureus is reported . Abscess formation became manifest seven months after the endovascular procedures . Antibiotherapy was initially started after puncturing the abscess, but finally the cure of the lesion could only be obtained by radical excision of the infected and embolized AVM, as if the persisting embolization material was promoting the infection . The modalities of infection after cerebral endovascular procedures are discussed.

Vet Res, 1993, 24(1), 33 - 45
{Modeling of the bactericidal effect of spiramycin . Choice of a pharmacodynamic model}; Renard L et al.; The modelling of in vitro growth curves of Staphylococcus aureus ATCC 6538P at different pHs, of spiramycin killing curves and of the dose-effect relationship was performed . The growth curve was characterised by a Volterra-Kostitzin differential model, the main parameters of which were the bacterial growth rate constant of 0.95 +/- 0.13 h-1 and a lag-time of 0.74 +/- 0.36 h . The Zhi model used for bactericidal kinetics showed the same bacterial killing rate constant from a minimum concentration characteristic of "time-dependent" antibiotics . This differential model incorporated with pharmacokinetic models could lead to a rationale for proper dosage regimens.

Med Dosw Mikrobiol, 1993, 45(2), 159 - 62
{Treatment with neomycin and Na2EDTA for skin infections in rabbits caused by Staphylococcus aureus}; Rudy M et al.; The rabbits were infected intradermally with a strain of S . aureus resistant to neomycin . They were treated with neomycin, Na2EDTA and by combination of these substances, which were applied as a cream with differing concentrations of these factors . Simultaneous application of neomycin and Na2EDTA for treatment of experimental staphylococcal infections caused in rabbits with a strain resistant to neomycin, resulted in acceleration of healing of pustular changes, when compared with results obtained in animals treated with these substances alone.

Am J Cardiovasc Pathol, 1993, 4(4), 367 - 70
Isolated right-sided endocarditis in Hong Kong Chinese; Dickens P et al.; Thirteen histologically-proven cases of endocarditis confined to the right side of the heart were found in 9406 consecutive autopsies . Eleven cases involved the tricuspid valve and two the atrial endocardium . Nine cases were in males and 4 in females . Only one case showed underlying valvular/endocardial disease . Eight cases were infective, with Staphylococcus aureus being the predominant organism, and 5 non-infective . For the infective cases, intravenous drug abuse was the commonest predisposing factor, and malignancy the commonest association for the non-infective . The commonest overall complication was lung abscess due to septic emboli in the 3 drug addicts, a common association in other reported series . These latter cases are particularly important to recognize, being generally more responsive to treatment than left-sided infective endocarditis.

Acta Haematol Pol, 1993, 24(4), 333 - 8
{Production of activity stimulating an increase of clonal granulocytic precursors by normal B lymphocytes under the influence of various mitogens}; Kozlowska-Skrzypczak M et al.; The effect of mitogen-stimulated (concanavalin A, Con A; phytohemagglutinin, PHA; pokeweed mitogen, PWM; Staphylococcus aureus Cowan I, SAC I) normal B lymphocytes on the clonal proliferation of granulocytic progenitors from marrow of healthy subjects (CFU-dG) was studied in diffusion chamber culture . PWM-, SAC- and Con A-stimulated B lymphocytes produced an humoral activity that increased the CFU-dG-derived colony formation . The highest growth-stimulating effect was induced by SAC I-preincubated B lymphocytes and to a lesser degree by PWM- or Con A-stimulated B cells . In contrast, PHA-preincubated and unstimulated B lymphocytes revealed no effect on the CFU-dG proliferation.

Surg Today, 1993, 23(10), 880 - 4
The significance of methicillin-resistant Staphylococcus aureus infection in general surgery: a multivariate analysis of risk factors and preventive approaches; Shimada M et al.; To investigate the characteristics, risk factors, and prevention of methicillin-resistant Staphylococcus aureus (MRSA), a total of 3,627 patients were studied . Among these, 1,336 patients with various infections were used in a risk factor analysis of MRSA to determine the relationship between the use of antibiotics and the incidence of MRSA . Only 3.0% of infections were attributed to MRSA, the esophagus and colorectal region being highly involved, as anastomotic or pelvic abscesses, while the lung had a lower incidence . Almost half the patients with MRSA infections (47.6%) had concomitant infection . A univariate analysis revealed the following significant factors: The coexistence of gastrointestinal or metastatic malignancy, sepsis, tracheostomy, and the prior use of antibiotics such as the beta-lactam compounds or aminoglycosides . A multivariate analysis showed that gastrointestinal malignancy, sepsis, and the prior use of aminoglycosides, tetracycline, macrolides, and carbapenems were independently significant factors . To promote the education of doctors and nurses, regular in-service meetings on MRSA were held in the ward . Moreover, preventive approaches such as patient isolation, strategically placed hand washing equipment, and the use of disposable gloves and contaminated waste bags, have been initiated, and the incidence of MRSA has decreased significantly since then . Thus, to control MRSA, the following steps should be taken: (1) constant and careful surveillance, (2) regular risk factor analyses, (3) the optimal administration of antibiotics, and (4) the education of all hospital staff.

Microbiol Immunol, 1993, 37(11), 853 - 9
Potent in vitro bactericidal activity of polymyxin B against methicillin-resistant Staphylococcus aureus (MRSA); Yoshida T et al.; Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carried by inpatients or healthy hospital personnel by topical use of antibiotics is an important step for preventing outbreak of MRSA nosocomial infection . In the screening of the antibiotic best suited for this purpose, we have found that polymyxin B, a commonly used antibiotic for gram-negative infection, had an unexpected strong cytokilling activity towards MRSA clinical strains, which was more potent than that of vancomycin or gentamicin . The data suggested that polymyxin B could be an antibiotic of choice in the treatment of topical carriage of or infection caused by MRSA.

Medicina (B Aires), 1993, 53(2), 124 - 8
{Evaluation of alternative hemoculture tests for the diagnosis of early neonatal sepsis}; Celadilla ML et al.; In order to evaluate the diagnostic usefulness of coadjuvant tests such as external auditory canal swab culture and cultures from nasopharyngeal and gastric aspirates, and to determine the incidence and etiology of early neonatal sepsis (ENS) at our Unit, 90 newborn cases whose mothers experienced premature rupture of the membranes (PRM) were studied prospectively . Although a firm diagnosis requires positive blood cultures, the difficulty in recovering microorganisms and the trauma induced by sample collection in the baby justify the search for alternative diagnostic tests . Out of 2293 childbirths during 1991, 90 mothers (4%) had PRM more than 24 hours pre-partum, while 6.9/1000 (16/2293) developed ENS . In newborns from PMR mothers, ENS percentage was 3.3%, but increased to 5.5% in association with chorionamnionitis and reached 8.8% in premature cases . Among etiological ENS agents, Gram-positive microorganisms predominated (Table 1), particularly Staphylococcus aureus . Despite the finding that none of the coadjuvant assays (Table 2) had sufficient sensitivity or positive predictive value to identify all septic cases, they may prove useful to pinpoint newborns at high risk due to amniotic fluid exposure to infection or to chorioamnionitis.

Surg Today, 1993, 23(11), 947 - 53
Methicillin-resistant Staphylococcus aureus infections following esophageal surgery in patients with impaired defense mechanisms; Saito T et al.; This study was conducted to determine whether or not compromised host defense mechanisms prior to surgery are related to postoperative infections with methicillin-resistant Staphylococcus aureus (MRSA) . Neutrophil cytocidal activities, serum complement and immunoglobulin levels, the in vivo antibody-producing capacity against pneumococcal polysaccharide (PPS), and cell-mediated immunity (CMI) were evaluated in 22 patients who underwent esophagectomy for esophageal cancer between 1989 and 1990 . Postoperatively, nine patients developed MRSA infections . Anti-PPS IgG was found to be significantly lower in patients with MRSA infections than in those without (P < 0.01) . All the patients with MRSA infections showed a titer < 600 EU, while all but one of the non-infected patients showed a titer > 600 EU . Impairment in other components of the defense mechanisms, apart from a partial deficiency of CMI, did not differ between the groups . Thus, a preoperative evaluation of the antibody-producing capacity may serve to predict the development of MRSA-related infections following major surgery such as esophagectomy.

J Mol Neurosci, 1993 Fall, 4(3), 161 - 72
Synthesis and characterization of a bioactive 82-residue sphingolipid activator protein, saposin C; Weiler S et al.; The sphingolipid activator protein, saposin C (also termed SAP 2), was chemically synthesized, purified, and characterized . The fully protected 82-residue protein was synthesized by automated solid-phase methods, with multiple recoupling steps resulting in a high average coupling efficiency of 98.8% . The overall yield was estimated to be approx 40% . Deprotection and cleavage of the peptide from the resin was followed by folding in the absence of chaotropic agents at pH 8.5 . The protein was purified by reversed-phase high pressure liquid chromatography (HPLC) and its purity determined by capillary electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) . The composition of the synthetic saposin C was determined by amino acid analysis . Its sequence was verified by Edman sequence analysis of overlapping peptide fragments generated by chymotryptic and Staphylococcus aureus V8 digestions . The sequence at the C-terminus was determined by digestion with carboxypeptidase P, followed by phenylthiohydantoin (PTH) derivitization and HPLC analysis of the released amino acid residues . Deglycosylated native saposin C appeared as a lower molecular-weight species than synthetic saposin C on SDS-PAGE . This has been explained by amino acid and C-terminal analysis showing native saposin C to be two amino acids shorter at the C terminus than a deduced sequence (from cDNA) previously published . Synthetic saposin C displayed 85% of full biological activity as determined by its ability to stimulate glucocerebrosidase activity in vitro: Synthetic and native saposin C increased glucocerebrosidase catalyzed hydrolysis of 4-methylumbelliferyl beta-D-glucoside by factors of 6.0 and 7.1, respectively . Furthermore, synthetic and native saposin C share similar K(act) values (0.5 and 1.5 microM respectively) indicating that they bind to glucocerebrosidase with similar affinities.

Postgrad Med J, 1993, 69 Suppl 3, S78 - 83
Action of povidone-iodine against methicillin-sensitive and -resistant cultures of Staphylococcus aureus; Lacey RW et al.; Forty clinical isolates of methicillin-resistant and methicillin-sensitive Staphylococcus aureus were studied for their susceptibility to povidone-iodine (available iodine 11%) under a variety of conditions . The cultures varied in properties, notably in their sensitivity to other therapeutic agents . No differences were observed between the resistant and sensitive cultures in destruction by povidone-iodine . When bactericidal activity occurred, > 99% of the bacterial cells were lethally damaged within 10 seconds of exposure to povidone-iodine . The bacterial cells that had been washed and resuspended thrice in distilled water were most susceptible, with as little as 1 x 10(-16) G (2.36 x 10(5) atoms) of iodine being required to destroy one bacterial cell . Attempts were made to select variants resistant to iodine from the surviving minority population in such experiments . These experiments failed to select resistance, and it is concluded that any apparent variation in vulnerability to povidone-iodine results from aggregation of the bacteria and differences in penetration of povidone-iodine . Substances were studied for their ability to inactivate povidone-iodine . The most potent agents were the free sulphur-containing amino acids, cysteine and methionine . These are present in high concentrations in nutrient broth and most other culture media . This explains the reports of 'pseudo-resistance' to povidone-iodine in certain laboratory experiments . Suggestions are made for the optimum use and formulation of povidone-iodine.

Postgrad Med J, 1993, 69 Suppl 3, S66 - 9
Comparison of bactericidal activities of various disinfectants against methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus; Yasuda T et al.; Various disinfectants were compared in terms of the duration of bactericidal activity against methicillin-sensitive Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA), among S . aureus isolated in our hospital . Strains of S . aureus which showed minimum inhibitory concentrations of cloxacillin of less than 1.56 micrograms/ml and of 3.13 micrograms/ml or higher were designated MSSA and MRSA respectively . There was no difference in sensitivity to disinfectants between MSSA and MRSA . There was a great variation in the duration of bactericidal activity of chlorhexidine gluconate against these species with the majority requiring contact times of between 2 minutes and over 20 minutes . All strains except for one strain of MRSA were killed within 20 seconds after disinfection with benzalkonium chloride . All strains were killed within 20 seconds after disinfection with alkyldiaminoethylglycine hydrochloride or povidone-iodine.

Postgrad Med J, 1993, 69 Suppl 3, S62 - 5
In vitro efficacy of povidone-iodine solution and cream against methicillin-resistant Staphylococcus aureus; Goldenheim PD; Methicillin-resistant Staphylococcus aureus (MRSA) has emerged worldwide as a significant and difficult-to-treat source of nosocomial infection, emphasizing the ever-present need for reliable and effective antisepsis . Betadine Solution (10% povidone-iodine; PVP-I) and Betadine Cream (5% povidone-iodine) are broad-spectrum microbicides widely used for topical cleansing, wound treatment, and antisepsis . There have been no reports of bacterial resistance to Betadine preparations . In the present study in vitro killing times were determined for PVP-I solution and PVP-I cream against five hospital isolates of MRSA and one methicillin-sensitive strain (MSSA) . Isolates were incubated for 24 hours in trypticase soy broth and 0.5 ml, containing 10(6)-10(7)/ml bacteria, was then removed and added to each test agent containing PVP-I . At intervals of 30 seconds, 1 min, 2 min, 3 min, 5 min, 10 min, and 15 min, 10 microliters aliquots were removed and added to 10 ml of culture broth containing 0.1% sodium thiosulphate, the neutralizing agent for PVP-I . After neutralization the samples were incubated for 48 hours and then observed for growth (turbidity) or its absence . PVP-I solution was effective against all isolates, killing each strain within 30 seconds . PVP-I cream killed four of the MRSA isolates within 30 seconds, and required a 2-3 minute killing time for one strain of MRSA and the strain of MSSA . These results are supported by four published in vitro studies which show that PVP-I is highly effective in killing MRSA . In addition, each study shows that PVP-I is more effective than chlorhexidine against MRSA.

Postgrad Med J, 1993, 69 Suppl 3, S27 - 32
Efficacy and safety of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution; Kirita T et al.; The efficacy and safety of a quick drying rubbing type disinfectant (HAD Hand Wash) composed of a povidone-iodine (PVP-I) and ethanol were evaluated in the disinfection of transient skin flora on fingers of 30 medical staff of our department . Three millilitres of HAD solution was rubbed onto the hands for three minutes several times a day over a four week period . Bacteriological effects were evaluated twice, on the first day and after four weeks, by the palm stamp method . The rate of colonies sterilized (bacterial reduction rate) after the use of HAD Hand Wash was 86.9 +/- 21.2% (mean +/- SD) on the first measurement, and 91.5% +/- 12.8% at four weeks . Staphylococcus epidermidis was isolated most frequently and this was eradicated in 83.3% of subjects, the bacterial reduction rate 99.7% . Staphylococcus aureus was originally isolated in 14 subjects and was eradicated in 13; the bacterial colony reduction rate was 99.9% showing high antiseptic efficacy . Although the bacterial reduction rate for Bacillus sp . was a rather low, 75.8-100%, this result was not considered problematic from the clinical standpoint . There were no side effects like chapping in spite of an average 104 applications of HAD Hand Wash during the 4-week test period . From these results, HAD Hand Wash was considered highly effective and safe.

Postgrad Med J, 1993, 69 Suppl 3, S126 - 9; discussion S130
Epidemic methicillin-resistant Staphylococcus aureus (EMRSA): experience from a health district of central England over five years; Rahman M; A series of outbreaks of EMRSA occurred in three hospitals of a Health District in the years 1986 and 1987, affecting 64 patients and 6 staff members . By the antibiotic sensitivity pattern (methicillin-resistance and resistance to many others) and phage typing, the organism resembled the epidemic strains involved in London outbreaks . In this series of outbreaks, different circumstances led to adaptation of different control measures with their cost implications . As failure with chlorhexidine was experienced, it was replaced with povidone-iodine for routine handwashing and topical application to patients in affected wards . Heavy environmental contamination involving mattress, bed, floor, table, chair, locker, television etc . was shown . Repeated failures of a phenolic disinfectant led to use of formaldehyde or a higher concentration of the phenolic disinfectant which caused side effects in staff members . Various anti-bacterial agents had been used in treating different conditions in different cases . Mupirocin was found to be the best agent in treating infections or colonization of superficial accessible sites . For non-accessible sites fusidic acid and rifampicin were found to be satisfactory . Continued surveillance in the District for three years after the last case did not detect re-emergence of EMRSA.

Postgrad Med J, 1993, 69 Suppl 3, S122 - 5
Efficacy of intranasal application of povidone-iodine cream in eradicating nasal methicillin-resistant Staphylococcus aureus in neonatal intensive care unit (NICU) staff; Masano H et al.; We investigated the staff in our neonatal intensive care unit (NICU) for the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the nasal cavity, and then applied intranasal povidone-iodine cream to the physicians and nurses working on the unit . Prior to the application of povidone-iodine cream, the isolation rate of S . aureus from the nasal cavity was 30% for the physicians and nurses in contact with NICU patients (contact group), not significantly different from the 33.3% rate for other hospital staff (control group) . The isolation rate for the contact group decreased to 10.5% after application of the cream . Although MRSA was not isolated from the nasal cavity of those in the control group, it was isolated from 13.3% of those of the contact group before application of the cream . Nasal MRSA disappeared after use of the cream . No adverse reactions or abnormalities in serum levels of thyroid hormone-related substances were observed in any of the subjects . These results indicated that the nasal application of povidone-iodine cream is safe and effective for eradicating MRSA in the nasal cavity.

Postgrad Med J, 1993, 69 Suppl 3, S117 - 21
Prevention and control of nosocomial infection caused by methicillin-resistant Staphylococcus aureus in a premature infant ward--preventive effect of a povidone-iodine wipe of neonatal skin; Aihara M et al.; In early 1983 we experienced a small scale epidemic of Staphylococcus aureus coagulase type IV in the premature infants unit . Children had bacteraemia or impetigo . The microorganism was resistant to methicillin, erythromycin and lincomycin and was susceptible to tetracycline, chloramphenicol and cefmetazole . The results of coagulase typing and antimicrobial sensitivities indicated that these cases represented nosocomial infection with MRSA . The source and route of the infection were investigated, and measures were taken to prevent bacterial spread from carriers and to keep instruments and environments clean . As the source of infection was not identified, we tried wiping the body surface of the premature infants with a diluted IsodineR solution (10% povidone-iodine; 1:100 dilution) in order to prevent colonization of the microorganism on the body surface . As a result, no additional MRSA infection occurred in the premature infant unit . During the subsequent 6 years of frequent surveys of carriers and wiping the appropriate body surface with diluted IsodineR solution we have had no recurrence of MRSA . None of the premature infants wiped with IsodineR solution showed any objective abnormalities, although laboratory testing disclosed an elevated blood iodine level and a transient mild reduction of T4 in some infants.

Postgrad Med J, 1993, 69 Suppl 3, S106 - 16
Clinical significance of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in UK hospitals and the relevance of povidone-iodine in their control; Gordon J; This review summarizes the natural history, clinical relevance and basis of control of Staphylococcus aureus infection in UK hospitals, stressing the central role of asymptomatic carriage by patients and staff in persistence of this prolific and versatile nosocomial pathogen . The clinical relevance of methicillin-resistant and methicillin-sensitive S . aureus (MRSA and MSSA) is considered in terms of prevalence and spectrum of invasive and toxigenic infections produced, correlated with host and parasite risk factors . An assessment is made of arguments why the acquisition of methicillin-resistance or multiple antibiotic resistance might justify more than conventional methods of containment and how the control policy is influenced by the expression of enhanced virulence and epidemicity . Guidelines for control of epidemic MRSA (EMRSA) are discussed with reference to justification, feasibility and efficacy . As elimination of carriage is crucial to the success of any rational control policy the relative merits of topical antibiotics and antiseptic agents are compared . The bacterial efficacy of povidone-iodine, chlorhexidine and mupirocin are evaluated as a basis for eradication of MRSA.

Scand J Infect Dis, 1993, 25(5), 647 - 53
Changing pattern of phage group II Staphylococcus aureus infections: from community to hospital; Faber M et al.; Changes in Staphylococcus aureus strains of phage group II were evaluated over a 30-year period . Strains of this group were previously known to be mainly community-acquired, to be rather sensitive to antibiotics and to occur in infections with better clinical outcome . During the period 1961 to 1990 a total of 551, 563 S . aureus strains was characterized according to antibiotic resistance, phage type and site of isolation . Clinical information was obtained on 16,781 bacteraemia cases . Strains of group II occurred until 1983 with a rather constant frequency around 16% of the S . aureus population . Since then, a constant increase in frequency has taken place and since 1990 they are the most frequently isolated phage pattern (22%) . Bacteraemia caused by these strains occurs today with the same frequency in hospital and community as strains of other phage patterns . Moreover, these strains have changed from being highly susceptible, to being more resistant to penicillins and tetracycline than the rest of the population . Resistance to methicillin remained low in group II strains throughout the period (about 0.2%) . Mortality rate and the proportion of patients with underlying diseases have been the same in recent years regarding group II strains as with other strains . This study indicates that the previous distinction between community-acquired and hospital-acquired S . aureus infections is no longer valid.

Microbiol Immunol, 1993, 37(9), 695 - 703
A factor found in aged tungstate solution enhanced the antibacterial effect of beta-lactams on methicillin-resistant Staphylococcus aureus; Tajima Y et al.; We have found a factor (Factor T) in aged mixtures of tungstate and phosphate which greatly enhances the antibacterial effects of beta-lactams on both inducible and constitutive methicillin-resistant Staphylococcus aureus, but not on methicillin-susceptible S . aureus . Factor T alone did not strongly inhibit bacterial growth . There was no synergism of Factor T with other classes of antibiotics, nor with other groups of bacteria, and it reduced the efficacy of amino-glycosides and tetracycline . Upon preparation of Factor T, acidifying and heating the mixture of tungstate and phosphate resulted in a high yield and reproducibility, and no enhancing effect was observed when other anions such as sulfate or molybdate were used instead . Factor T is heat- and acid-stable but labile to alkalization, and is probably a complex of phosphate and tungstate.

Microbios, 1993, 76(306), 19 - 28
Cell wall-active antibiotics induce specific alterations of the electrophoretic profile of membrane proteins in a Staphylococcus aureus strain; Najioullah F et al.; The effect of six representative cell wall-active antibiotics upon the membrane proteins of Staphylococcus aureus CIP 65-25 was studied . The profiles of whole membrane proteins and of penicillin-binding proteins of strain CIP 65-25 grown on an antibiotic-free medium were analysed and compared with those of nine other S . aureus strains . Both profiles were found to be very similar for all strains examined . Cell wall-active antibiotics brought about definite changes dealing with a few membrane proteins of strain CIP 65-25 . Some polypeptide bands of the control profiles decreased or vanished after exposure to antibiotics whereas others rose only in antibiotic-treated bacteria . None of these modified polypeptides was a penicillin-binding protein . Their possible involvement in the antibacterial effects of antibiotics or in the determinism of bacterial resistance to antibiotics is discussed.

Nord Med, 1993, 108(11), 286 - 8
{Hvidovre Hospital . Measures to control the spread of imported multiresistant Staphylococcus aureus}; Kolmos HJ; Methicillin-resistant Staphylococcus aureus (MRSA) are endemic in many hospitals abroad . Patients transferred from these hospitals may give rise to a spread of MRSA in Scandinavian hospitals, where MRSA only occur sporadically . A spread of MRSA may have great therapeutic and economic consequences for the local health care system and should therefore be met by strict hygienic measures . In Hvidovre Hospital patients transferred from or recently admitted to hospitals outside Scandinavia, are screened for MRSA . Patients carrying MRSA are isolated and discharged as soon as possible . Attempts are made to eliminate the carrier state by means of chlorhexidine.

Med Dosw Mikrobiol, 1993, 45(1), 37 - 40
{Modulation of lymphocytes and immunoglobulins by serine proteinase of Staphylococcus aureus}; Porwit-Bobr Z; Serine proteinase of S . aureus binds with surface of peripheral blood lymphocytes and by proteolysis of polypeptides on the membrane and transduction of signals, changes in polyclonal activation of T and B lymphocytes occur . Cleavage of immunoglobulins tested in three classes and evaluated by electrophoresis in polyacrylamide gel (SDS-Page) of Ig fragments, was differing . IgG and IgG fragments were degraded in higher degree than IgM, H and L chains or i Fc and i Fab fragments . Influence of proteolytic modulation of IgG particles on fixation antigenic fractions homogenized by ultrasound cells of S . aureus was evaluated in ELISA test . Basing on detailed results postulated mechanism of modification effect of immunoglobulins and lymphocyte reaction under influence of serine proteinase of S . aureus in microenvironment of after-inflammatory reaction in staphylococcal infection, has been accepted.

Med Dosw Mikrobiol, 1993, 45(1), 19 - 23
{Increase of pathogenicity of Staphylococcus aureus strains caused by lysogenic conversion by phages of serologic group F}; Mlynarczyk G et al.; The substantial influence of presence of the double converting prophages of the serological group F on the decrease of intensity of human leukocytes stimulation with lysogenic cells of S . aureus was determined . The end values of chemiluminescence in the six experimental systems containing lysogenic bacteria were only from 15.4 to 37.2% of the value in the control sample . The end values of the intercellular killing of the two lysogenic variants were twofold lower than in controls . Third of the investigated variants was completely resistant to intracellular killing in the applied system, and revealed 27% of growth stimulation.

Jpn J Ophthalmol, 1993, 37(2), 165 - 70
Ophthalmic diseases in bedridden patients with severe dementia; Kiuchi Y et al.; Ophthalmologic examinations were performed on the 176 eyes of 88 bedridden patients with severe dementia . There were some pathologic changes in the external and anterior segments of 93 eyes . We observed infectious external and anterior segment eye diseases in 80 of these 93 eyes (86.0%) . Fundus diseases were found in 34 eyes, but treatment was not necessary . Infectious eye diseases appeared to be the most prevalent ocular problem in these patients . Cultures of conjunctival swabs commonly demonstrated Staphylococcus aureus . No differences were noted in tear secretion rate or lysozyme concentrations in tears between eyes with and without infection . The blinking frequency was significantly reduced in infected eyes compared to normal eyes . Failure of the lacrimal drainage system was observed more often in infected eyes than in normal eyes . This study demonstrated that bedridden patients with severe dementia develop infectious eye diseases easily, to which stasis of tear flow seems to predispose . In caring for bedridden patients with severe dementia, ophthalmologists must be concerned with controlling infectious eye diseases.

Drugs Exp Clin Res, 1993, 19(2), 59 - 64
Microbicidal effects of ozone solution on methicillin-resistant Staphylococcus aureus; Yamayoshi T et al.; Methicillin-resistant Staphylococcus aureus has become an important problem in chemotherapy in the past decade because of its resistance to commonly used disinfectants . The usefulness of ozone solutions to disinfect against strains of this bacterium has been evaluated . Ozone strongly oxidizes the cell walls and cytoplasmic membranes of bacteria . The microbicidal effect of ozone solutions took place within the first five seconds of treatment . An ozone concentration 1.5 times that needed to kill the one methicillin-sensitive strain tested was sufficient to kill the resistant clinical isolates . Such an ozone solution could be used to disinfect medical instruments and similar equipment . Ozone solutions should be useful in reducing the number of bacterial infections caused by inadequate disinfection against new resistant strains.

Respiration, 1993, 60(3), 182 - 5
Conservative treatment of empyema in children; Gocmen A et al.; Seventy-two children with no underlying diseases were treated for empyema . Radical surgical approaches like decortication were necessary for only 3 children . In 66 children tube drainage was applied . Staphylococcus aureus was cultured or was shown in Gram's stain in 32 (44%) and children with this microorganism had longer duration of tube drainage (p < 0.05) . The period for normalization of chest X-ray was positively related with the age of the patient (p < 0.05) . In 60 of 72 children, chest X-ray was normal after 3 months . Follow-up of the patients 18 months after the infection revealed that pulmonary radiograms were normal in all cases and pulmonary function tests were within normal limits in all of the tested children (n = 25) . It is emphasized that avoiding major surgical approaches must be encouraged in childhood empyema.

Rev Med Interne, 1993, 14(7), 733 - 6
{Staphylococcus aureus endocarditis: an unusual clinical picture}; Acar P et al.; We describe an unusual presentation of bacterial endocarditis due to Staphylococcus aureus in a 50 year-old woman with mitral insufficiency . The disease began by a vascular purpura without fever and a digital embolism . The source of infection was anal ulcerations . Diagnosis of endocarditis was made possible by trans-oesophagus echocardiography but not by trans-thoracic echocardiography . The patient was successfully treated by surgery associated with antibiotherapy . This observation emphasizes the indications of surgery at the acute phase of endocarditis . The anal source of endocarditis is original, no other case has been found in the literature.

Acta Microbiol Hung, 1993, 40(2), 91 - 9
Multiple effects of promethazine in Staphylococcus aureus; Molnar J et al.; The antibiotic resistance of 6 Staphylococcus aureus strains was eliminated with a frequency from 1.2 to 10% in the presence of subinhibitory concentrations of promethazine . The pigment production of the cells was also eliminated by the promethazine to an extent of 0 to 5% . The cell size was increased and the protein A production was markedly decreased in S . aureus cells cultured in the presence of promethazine . Complex formation between protein A and promethazine was detected by differential spectrophotometry . The biological activity of staphylococcus protein A was abolished by promethazine in the passive haemagglutination of rabbit antiserum treated sheep red blood cells . Evidence has been found that plasmid-encoded functions of S . aureus cells can be altered in the presence of promethazine, and the chromosomally controlled synthesis of protein A, one of the weakest virulence factor of S . aureus is also lowered by promethazine.

Am J Nephrol, 1993, 13(6), 435 - 6
Retropharyngeal infection with Staphylococcus aureus in a haemodialysis patient; Hughes J et al.; The case of a 55-year-old female Asian haemodialysis patient is described . She developed a septicaemic illness and retropharyngeal soft-tissue infection secondary to Staphylococcus aureus infection.

J Mal Vasc, 1993, 18(4), 327 - 30
{Aortic thrombosis during acute endocarditis caused by Staphylococcus aureus}; Pistorius MA et al.; The authors report a case of acute bacterial (Staphylococcus aureus) endocarditis in a 70-year-old woman, revealed by a febrile cerebral ischemic accident . Ultrasonography confirmed the presence of a large posterior mitral valve vegetation interfering with left ventricular filling . The sudden onset of complete paraplegia and acute ischemia of the lower limbs suggested thrombosis of the abdominal aorta, which was confirmed by aortography . These features indicated that a vegetation fragment had migrated, obstructing the aortic bifurcation and causing secondary thrombosis . This led in turn to involvement of the medullary arteries and the onset of paraplegia . Unfortunately, acute renal insufficiency and major left heart failure rapidly developed, and the patient died . Autopsy confirmed the diagnosis of aortic thrombosis with involvement of the renal arteries . Multiple visceral infarcts were noted as well as the large mitral vegetation . This case illustrates the potential severity of systemic embolism complicating endocarditis due to Staphylococcus aureus . The accident was remarkable because of the aortic acute occlusion and the association with paraplegia, an unusual neurologic complication.

Trop Geogr Med, 1993, 45(6), 294 - 6
Bacterial pathogens in malnourished children with pneumonia; Fagbule DO; Lung puncture aspirates were obtained from 99 malnourished children aged 9 months to 5 years with pneumonia, in order to identify the causative bacterial agents . Klebsiella species, Staphylococcus aureus and Escherichia coli were identified in 39.4%, 30.3% and 8.8% of aspirates, respectively . Approximately half to two-thirds of the children in each aetiological group had the same organisms isolated in both lung aspirates and blood . The bacterial agents reflected the immunocompromised status of the patients . Isolation of Klebsiella species was associated with age (p < 0.01), and type of malnutrition (p < 0.05); while that of Staphylococcus aureus was only statistically associated with type of malnutrition (p < 0.01) . Gentamicin and cloxacillin represent a safe antibiotic regime for pneumonia in children with moderate to severe malnutrition.

J Ocul Pharmacol, 1993 Winter, 9(4), 311 - 20
Bioassays for quantitating ciprofloxacin and tobramycin in aqueous humor; Engel LS et al.; Development of new therapies for bacterial keratitis requires assays of antibiotics in infected ocular tissues; however, methods for such drug quantitation can be expensive and can lack precision and sensitivity . To develop a more suitable assay for quantitating tobramycin and ciprofloxacin in the aqueous humor, sixteen bioassays were compared . Variables assessed included: the strain of bacteria used as indicator (Staphylococcus aureus ATCC 25923 versus Klebsiella pneumoniae ATCC 10031), the application of bacteria to the agar surface versus inclusion in molten agar, the volume of the agar, and the application of antibiotic on paper discs versus instillation into agar wells . The best results were obtained when the appropriate indicator organism (S . aureus for tobramycin and K . pneumoniae for ciprofloxacin) was applied to the surface of the agar, antibiotic solution was put into agar wells, and the volume of agar was 30 ml per plate . The best sensitivity for assays of tobramycin and ciprofloxacin diluted in water were 0.98 and 0.12 micrograms/ml, respectively . These sensitivities improved as much as fourfold when antibiotics were diluted in aqueous humor or normal saline . The precision of all assays tested was high as determined by regression coefficients (r > 0.90) . The sensitivity and precision of these assays indicate their utility for quantitating fluoroquinolones and aminoglycosides in aqueous humor.

Adv Perit Dial, 1993, 9, 248 - 50
Hypertonic saline compresses: therapy for complicated exit-site infections; Strauss FG et al.; We review our experience with hypertonic saline compress therapy in 17 patients with complicated peritoneal dialysis catheter exit-site infections (ESIs) . Compresses consisted of exit-site application of 4-5 gauze pads soaked with warm 3% saline for 5-10 minutes, three times daily, for 2-4 weeks, followed by once-daily use thereafter . The mechanism of action involves inhibition of bacterial growth by a hypertonic medium . Eleven patients with cultures positive for Staphylococcus aureus or Pseudomonas were treated with local exist-site measures (cleansers, antiseptics, antibiotic ointments) . Therapy, which included multiple courses of systemic antibiotics, failed in 8 patients; in 3 patients, who were intolerant to antibiotics, ESI remained unresolved after local care only . Six patients with culture-negative ESIs received no systemic antibiotics and were unimproved following local therapy . Factors associated with therapy failure included malnutrition, diabetes, obesity, and dermal sensitization and injury associated with prolonged topical agent use . Following hypertonic saline compress therapy, we observed resolution of ESI in all patients without recurrence for follow-up intervals of 3-12 months (mean 6.5 months) . Advantages of this therapy include excellent patient acceptance, ease of use, lack of adverse effects on exit site, adjacent skin, catheter or systemic reaction, and minimal expense . Future potential applications include routine daily use for infection prophylaxis and as therapy combined with antibiotics for established ESIs.

Adv Perit Dial, 1993, 9, 236 - 9
Breaking-in after the insertion of Tenckhoff catheters: a comparison of two techniques; Lye WC et al.; Breaking-in after catheter implantation may be an important factor in the development of early catheter-related infections in continuous ambulatory peritoneal dialysis (CAPD) patients . We carried out a prospective study comparing two break-in techniques after catheter implantation . All patients entering the CAPD program from March 1991 to December 1992 were enrolled into the study . Data on diabetes mellitus status, Staphylococcus aureus nasal carriage, and peritoneal dialysis-related infections were gathered . After catheter implantation, the patients were assigned to either have their catheter rested until the fourteenth postoperative day (group 1) or immediate use of the catheter for intermittent peritoneal dialysis (group 2) . Exit-site care was identical for both groups . A total of 32 patients in group 1 and 74 in group 2 were studied . Age, sex, and S . aureus nasal carriage were not significantly different between the two groups . There were more patients with diabetes mellitus in group 2 . Four patients in group 2 dropped out of the CAPD program because of refractory peritonitis . There was no significant difference in the number of exit-site infections between groups 1 and 2 . There were more patients who had pericatheter leakage and catheter migration in group 2 compared to group 1, although the difference was not statistically significant.

Adv Perit Dial, 1993, 9, 195 - 7
A prospective study of peritoneal dialysis-related infections in CAPD patients with diabetes mellitus; Lye WC et al.; Data comparing peritoneal dialysis (PD)-related infection rates between diabetic and nondiabetic patients on chronic peritoneal dialysis are conflicting . We carried out a prospective study comparing PD-related infection rates between diabetic and nondiabetic patients treated with continuous ambulatory peritoneal dialysis (CAPD) in our center . All patients commencing CAPD between January 1989 and June 1992 were enrolled into the study . Patients were followed up until death, CAPD dropout, or until December 1992 . Data on diabetes mellitus status, Staphylococcus aureus nasal carriage, and PD-related infections were gathered . Infection rates were analyzed using life tables and the negative binomial test . One hundred and seven diabetic patients and 72 nondiabetic patients were studied . Patients with diabetes mellitus were not at increased risk of being S . aureus nasal carriers . The peritonitis rate was significantly higher in the diabetic group (1.2 vs 0.8 episodes/patient/year, p < 0.05) . The exit-site and tunnel infection, catheter loss, and patient dropout rates were not significantly different between the two groups . Life-table analysis did not show a significant difference in the time to first episode of peritonitis and catheter-related infection.

Comp Biochem Physiol C, 1993 Jan, 104(1), 37 - 42
Morphological aspects of Achacin-treated bacteria; Otsuka-Fuchino H et al.; 1 . The morphology of bacteria treated with the bactericidal glycoprotein, Achacin, purified from the giant African snail, Achatina fulica Ferussac, has been studied . 2 . Achacin lengthens the bodies of Escherichia coli by three to seven times . 3 . Achacin damages the surface of Staphylococcus aureus and sinks the cytoplasmic membranes into the cytoplasm . 4 . Achacin causes neither the leakage nor the destruction of cells.

Comp Biochem Physiol C, 1993 Jan, 104(1), 187 - 91
GTP-binding protein amplifies contractile responses of alpha-toxin-permeabilized uterine smooth muscle to Ca2+; Suga O et al.; 1 . alpha-toxin of Staphylococcus aureus readily permeabilized rat uterine smooth muscle after incubation for a short time . 2 . The permeabilized muscle responded to Ca2+ dose-dependently and repeatedly in the same manner . 3 . The threshold concentration of Ca2+ for contraction was 0.1-0.3 microM and the maximal contraction was achieved with 1 or 3 microM Ca2+ . 4 . GTP gamma S or GTP augmented the contractile response to Ca2+ . 5 . GDP beta S or GDP suppressed the contraction . 6 . The role of GTP-binding protein in sensitization of Ca(2+)-induced contractile response of smooth muscle is discussed.

Diabetes Res, 1993, 22(3), 135 - 44
Vertebral bone metastasis of small cell carcinoma of lung in a diabetic patient, initially diagnosed as pyogenic vertebral osteomyelitis; Nagasaka A et al.; A 40-year-old man with a 3-year history of uncontrolled NIDDM, 2-pack/month cigarette smoking habit and alcohol abuse, was admitted to our university hospital . He presented with severe back pain, persistent cough and fever . A left lung infiltrate was noted on chest X-ray film . Staphylococcus aureus was isolated from arterial blood . Thoracic bone destruction with pleural mass lesion confirmed by computed tomography (CT) and magnetic resonance image (MRI) . These findings mislead our diagnosis to pyogenic osteomyelitis associated with NIDDM . An absence of marked clinical and roentgenological improvement after antibiotic therapy and strict glycemic control with insulin was noted . This suggested to us the need for needle biopsy of the osteolytic and mass lesions confirmed by imaging techniques . This resulted in making the diagnosis of metastasis of small cell carcinoma from the left lung . The correlation between NIDDM and pulmonary small cell carcinoma possibly induced by genetic abnormality remains to be resolved . By making the most of imaging techniques and needle biopsy, the possibility of pulmonary small cell carcinoma complicating NIDDM can be appropriately evaluated.

J Med Liban, 1993, 41(2), 90 - 4
{Right-sided endocarditis caused by Staphylococcus aureus during the neonatal period . (A case report)}; Melki I et al.; Right-sided infectious endocarditis in the neonate, due to staphylococcus aureus, is a rare entity . A high index of suspicion should be used when dealing with a very sick neonate, especially with aggressive reanimation . Although the diagnosis is clinical, echocardiography is essential to confirm the diagnosis and also is an excellent mean to follow the evolution of the disease . The pathogenesis of the infection is due to bacteremia with implantation of the staphylococcus on a normal endothelium . The prognosis is poor with a high mortality rate and possibility of sequelae (essentially cardiac and neurologic) . The prognosis depends essentially on early diagnosis and treatment which should last for at least 4-6 weeks . The authors present the case of a 2-week-old girl who developed a right-sided staphylococcal endocarditis following treatment of neonatal jaundice with i.v . perfusion of albumin . The patient survived with cardiac and central nervous system sequelae.

Plant Cell Physiol, 1993 Jan, 34(1), 83 - 91
Identification of surface-exposed parts of red-light- and far-red-light-absorbing forms of native pea phytochrome by limited proteolysis; Nakazawa M et al.; Peptide fragments were obtained by limited proteolysis with trypsin and Staphylococcus aureus V 8 protease from either the PR or the PFR form of 121-kDa phytochrome purified from etiolated pea (Pisum sativum L.) shoots . Patterns of bands after polyacrylamide gel electrophoresis in the presence of SDS of the digests were different, with some bands appearing preferentially when the digestions were carried out with the PR or the PFR form . Amino-terminal sequences of the fragments were analyzed to determine the exact locations of the amino-termini of the fragments within the amino acid sequence of the apoprotein of pea phytochrome . The amino acid compositions of some of the sequenced fragments were determined in order to confirm the carboxy-terminal amino acids . Three cleavage regions were identified as kinetically favored sites of cleavage of PFR (Arg-746 to Lys-752, around Glu-877 and around Arg-1010), whereas only one was identified for PR (Glu-38 to Arg-62) . Regions of Glu-255, Arg-383, Arg-583 to Glu-620 and Lys-1093 to Glu-1115 were also identified as potential sites of proteolytic cleavage in both forms of the phytochrome . Other cleavage sites, the specificities of which have not yet been determined, are Glu-404, Glu-695 and Lys-1045 . Surface-exposed parts of phytochrome in the PR and PFR forms are discussed.

Biosci Biotechnol Biochem, 1993 Jan, 57(1), 102 - 6
Amino acid sequence of chymotrypsin inhibitor ECI from the seeds of Erythrina variegata (Linn.) var . Orientalis; Kimura M et al.; The amino acids of the chymotrypsin inhibitor (ECI) from the Erythrina variegata seeds have been sequenced . The sequence was solved by analysis of peptides derived from the protein by enzymatic digestions with trypsin and Staphylococcus aureus V8 proteinase, as well as by chemical cleavage with o-iodosobenzoic acid . The ECI consists of 179 amino acid residues with a pyroglutamic acid as the N-terminal residue and has a calculated molecular weight of 19,791 . Comparison of this sequence with the sequences of the two trypsin inhibitors, ETIa and ETIb, from the E . variegata seeds shows that about 60% of the residues of ECI are identical to those of ETIa and ETIb and that the reactive sites, Arg63, in ETIa and ETIb change to Leu64 in ECI.

J Infect Dis, 1993 Jan, 167(1), 98 - 106
Efficacy of antibiotic-coated catheters in preventing subcutaneous Staphylococcus aureus infection in rabbits; Sherertz RJ et al.; Vascular catheters coated with antiinfective compounds were evaluated as to their ability to prevent Staphylococcus aureus catheter infection in a rabbit model . Zones of inhibition of agar surface-plated S . aureus demonstrated the following hierarchy: dicloxacillin and clindamycin were each better than fusidic acid or chlorhexidine, which were better than ciprofloxacin, cefotaxime, or cefuroxime . In vivo half-lives of inhibitory activity for clindamycin and dicloxacillin were 5.6 and 17.7 h, respectively, with apparent first-order kinetics . Chlorhexidine disappeared in vivo with apparent two-compartment kinetics: first-compartment t1/2, 16.8 h; second-compartment t1/2, 115.6 h . In a rabbit model, dicloxacillin, clindamycin, fusidic acid, and chlorhexidine decreased the risk of infection compared with uncoated control catheters (P < .05) . For dicloxacillin, clindamycin, and chlorhexidine, this was true even if the S . aureus inoculation was delayed 48 or 96 h after catheter implantation . These data suggest that vascular catheters with antiinfective coatings should be investigated further in hospitalized patients.

Respiration, 1993, 60 Suppl 1, 25 - 31
Cephalosporins and inflammatory host reactions; Scheffer J et al.; The oral cephalosporins cefaclor, cefetamet, Ro 40-6890 and cefpodoxime were studied with regard to their effects to modulate the chemiluminescence response, the rate of phagocytosis, bactericidal action and leukotriene formation from human granulocytes, the release of histamine from human basophils and the induction and release of tumor necrosis factor (TNF) and interleukin-6 (IL-6) from a preparation of human lymphocytes, monocytes and basophils . The cephalosporins increased the histamine release induced by Escherichia coli and Staphylococcus aureus whereas the synthesis of leukotrienes from human neutrophils was decreased . The studies with regard to adherence and phagocytosis showed a significant increase in phagocytosis for E . coli . The bactericidal activity of human granulocytes was also enhanced . Furthermore, the studied cephalosporins decreased the release of IL-6 and TNF.

Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S9 - 12
Basic mechanisms of bacterial tolerance of antimicrobial agents; Goessens WH; Although it has been known for many years that beta-lactam antibiotics inhibit the synthesis of peptidoglycan, it was the phenomenon of tolerance which allowed elucidation of the mode of action of beta-lactam antibiotics particularly with respect to the lysis of the bacteria . By studying tolerant pneumococci it was shown that penicillin triggers the production of autolytic enzymes which degrade the peptidoglycan to such an extent that lysis and killing of cells occurs . Since this discovery many studies have shown that various microorganisms are capable of preventing the lysis and/or killing action of beta-lactams . In Staphylococcus aureus strains, for instance, tolerance appears to be due to the lower specific activity of autolytic enzymes, extracted after exposure to a high concentration of methicillin (64 micrograms/ml) . At these high concentrations of beta-lactams the same strains also show inhibition of RNA and protein synthesis . This inhibition of macromolecular synthesis is probably due to a feed-back mechanism which synchronizes synthesis rates of protein, RNA, peptidoglycan and the activity of autolytic enzymes.

Drugs, 1993 Jan, 45(1), 29 - 43
Osteomyelitis . Common causes and treatment recommendations; Dirschl DR et al.; Infections involving bone continue to be a common problem . In children this is usually an acute haematogenous osteomyelitis . Early diagnosis with culture of an aspiration specimen is of paramount importance . Treatment with antibacterial agents is often successful unless pus is obtained in aspiration . In cases with an established abscess, surgical drainage is often needed in addition to antibiotic treatment . Staphylococcus aureus is the most common causative organism, although other microbes are often found in special circumstances such as in neonates, patients with sickle cell disease and those with nail puncture wounds . In adults, a pyogenic osteomyelitis is often due to direct trauma and generally is chronic in nature . Surgical debridement is the mainstay of treatment in these cases . Antibiotic treatment is often helpful but not curative by itself . Fungal and mycobacterial osteomyelitis is especially common in immunocompromised hosts . Amphotericin B remains the preferred treatment for fungal infections . Long term antituberculous multiple drug therapy is often sufficient to treat mycobacterial osteomyelitis.

Arch Biochem Biophys, 1993 Jan, 300(1), 327 - 34
alpha-Macroglobulin domain structure studied by specific limited proteolysis; Thomsen NK et al.; Limited proteolysis was used to probe the domain structures of rat alpha 1-inhibitor 3, human pregnancy zone protein, and rat alpha 1-macroglobulin representing monomeric, dimeric, and tetrameric members, respectively, of the alpha-macroglobulin family . Specific limited digestion with trypsin, chymotrypsin, elastase, subtilisin, or Staphylococcus aureus V8 proteinase produced well-defined fragments as monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The fragments were electroblotted to polyvinylidene difluoride membranes and subjected to NH2-terminal sequence analysis to locate the cleavage sites by comparison with the known primary structures of these proteins . Based on these results and the sizes of the generated fragments the 180-kDa alpha-macroglobulin subunit is proposed to contain seven relatively large domains resistant to proteolytic digestion, constituted by approximate residues 1-200 (I), 290-400 (II), 415-660 (III), 710-860 (IVa), 920-1160 (IVb), 1203-1305 (Va), and 1314-1451 (Vb) (human alpha 2-macroglobulin numbering) . The overall domain organization is similar to that recently proposed by D . S . Rubenstein, J . J . Enghild, and S . V . Pizzo (1991, J . Biol . Chem . 266, 11252-11261) from studies of rat alpha 1-inhibitor 3, but the present results suggest that the large domains IV and V proposed by these authors are each composed of two domains . The present study emphasizes that domain Vb contains the determinants necessary for receptor recognition.

Infect Immun, 1993 Jan, 61(1), 356 - 9
Staphylococcal enterotoxin A gene (sea) expression is not affected by the accessory gene regulator (agr); Tremaine MT et al.; The goal of this work was to determine whether staphylococcal enterotoxin type A gene (sea) expression is regulated by an accessory gene regulator (agr) . The Tn551 insertionally inactivated agr allele of Staphylococcus aureus ISP546 was transferred to three Sea+ S . aureus strains . Each of the Agr- strains produced as much staphylococcal enterotoxin A (SEA) as its parent strain . These results suggest that sea expression is regulated differently from that of seb, sec, and sed, which previously have been shown to require a functional agr system for maximal expression.

J Immunol, 1993 Jan 1, 150(1), 96 - 105
Insulin regulates serine/threonine phosphorylation in activated human B lymphocytes; Valentine MA et al.; Activation of either dense tonsilar B lymphocytes or the B lymphoblastoid cell line T5-1 with Staphylococcus aureus, Cowan strain I, induced surface expression of insulin receptors . Addition of insulin to these activated cells resulted in subsequent phosphorylation of the B cell surface protein CD20, the functions to regulate B cell activation . The cytoplasmic domains of CD20 contain multiple serine and threonine residues, of which at least two are followed by acidic sequences typical of substrate sites favored by casein kinase II . Tryptic mapping of CD20 isolated from intact cells treated with insulin showed increased phosphorylation on peptides having similar migration to those phosphorylated by casein kinase II in vitro . Treatment of tonsilar B cells or T5-1 cells with phorbol esters or in vitro phosphorylation by purified protein kinase C did not result in phosphorylation of peptides phosphorylated by casein kinase II, suggesting that protein kinase C is not directly involved in CD20 phosphorylation in the response to insulin . Phosphorylation of CD20 cannot be triggered by insulin in resting B cells, as the insulin receptor is expressed only after entry into the G1 phase of the cell cycle . Thus, distinct regulation of activation pathways are available to resting as opposed to activated B lymphocytes.

Acta Microbiol Pol, 1993, 42(3-4), 235 - 41
Phage-related conversion of enterotoxin A, staphylokinase and beta-toxin in Staphylococcus aureus; Zabicka D et al.; The conversion of enterotoxin A, staphylokinase and beta-toxin in Staphylococcus aureus is related with lysogeny stage . Bacteriophages able to convert enterotoxin A were used for lysogenization of the standard NCTC 8325-4 strain . Lysogenic, enterotoxigenic derivatives of this strain were characterized . The conversion of enterotoxin A was obtained in 7 examined derivatives, the conversion of enterotoxin A and staphylokinase at the same time was obtained in one case and the loss of beta hemolysin production ability was observed in all of 8 examined derivatives of the NCTC 8325-4 standard strain.

Ann Biol Clin (Paris), 1993, 51(6), 637 - 9
Identification of Staphylococcus aureus using a DNA probe: Accuprobe; Freney J et al.; A non-isotopic nucleic probe (Accuprobe) has been presented recently by Gen-Probe for the direct specific 1-h identification of Staphylococcus aureus isolated from culture . 50 S aureus strains previously characterized by conventional methods as well as 26 atypical strains (absence of coagulase, thermonuclease and fibrinogen affinity factor) were tested . Moreover, the Accuprobe system was evaluated using 29 other staphylococcal type strains representing all the species described to date . Only the strains that belonged to the S aureus species, including the 26 atypical strains, were detected by Accuprobe, which proved to be a rapid specific mean of identifying S aureus strains, particularly those that are not readily identified by conventional methods.

J Tongji Med Univ, 1993, 13(4), 209 - 12
Establishment and application of SPA-co-operated ELISA for detection of anti-HCV-IgM; Li FH et al.; A staphylococcus aureus protein A co-operated ELISA (SPA-ELISA) for the detection of anti-HCV-IgM has been established using HCV antigenic polypeptide, SPA-bearing germs and horseradish peroxidase labelled anti-human IgM . The specificity of SPA-ELISA has been confirmed by some substitution tests, blocking tests and destroying test with 2-mercaptoethanol . The results showed that the rate of anti-HCV-IgG in a group of patients with acute hepatitis and there were significant difference in anti-HCV-IgM was higher than that of anti-HCV-IgM detected rates between patients with acute hepatitis and those with chronic hepatitis (32.26%, P < 0.01) . On the other hand, the positive rates of anti-HCV-IgM were 53.66% and 63.41% in transfusion associated hepatitis, 38.10% and 42.86% in sporadic hepatitis, 6.11% and 16.33% in people who have had active social activities, 40.00% and 10.00% in a group of blood donors respectively . Furthermore, taking into account the characteristics of HCV polypeptide used, its easiness of manipulation, and elimination of the interference of anti-HCV-IgG in sera, the new SPA-ELISA is believed to be of practical value in clinical and epidemiological studies of hepatitis C.

Acta Microbiol Pol, 1993, 42(1), 23 - 8
Comparison of simple methods of methicillin-resistance detection and evaluation of some properties of methicillin-resistant Staphylococcus aureus strains; Trzcinski K et al.; Population analysis of methicillin-resistant Staphylococcus aureus and determination of their sensitivity to antimicrobial agents were performed . It was found, that the methicillin-resistant strains belonged to resistance classes II and III . All methicillin-resistant S . aureus were susceptible to ciprofloxacin, ofloxacin, vancomycin and teicoplanin . Differences between classes were observed in susceptibility to erythromycin and gentamicin.

Gene, 1992 Dec 15, 122(2), 361 - 5
Production and secretion of a bifunctional staphylococcal protein A::antiphytochrome single-chain Fv fusion protein in Escherichia coli; Gandecha AR et al.; A bifunctional molecule was genetically engineered which contained the secretory signal and four Fc-binding domains of Staphylococcus aureus protein A (FcA), fused to a single-chain Fv (scFv) derived from an immunoglobulin (Ig) G1 mouse monoclonal antibody (AS32) directed against the plant regulatory photoreceptor protein, phytochrome . The FcA::AS32scFv sequence was encoded in a single synthetic gene and expressed as a 60-kDa periplasmic protein in Escherichia coli . The bifunctionality of the fusion protein was established by its ability to bind to both IgG-agarose and phytochrome-sepharose . Growth of cultures, producing the FcA::AS32scFv, at 37 degrees C, resulted in a decrease in the periplasmic accumulation of the fusion protein, and an increased accumulation of an assumed degradation product which retained Fc-binding activity . Growth of cultures at lower temperatures favoured the accumulation of undegraded fusion protein . The recombinant fusion protein could be purified to homogeneity by a simple, rapid chromatography procedure.

FEMS Microbiol Lett, 1992 Dec 15, 79(1-3), 75 - 9
Investigation of microbial growth in vivo: evaluation of a novel in vivo chamber implant system; Arbuthnott JP et al.; An intraperitoneal chamber implant system has been used to investigate the phenotype of Staphylococcus aureus growing in the rat and the effect of the antibiotic flucloxacillin on bacterial growth in vivo . Titanium chambers were implanted in the peritoneum: a period of 3-4 days equilibration allowed diffusion of host proteins into the chamber fluid prior to inoculation with bacteria . S . aureus inoculated into the chamber fluid, grew rapidly over a 72 h period, reaching counts of > 10(9) per ml . Organisms harvested from chambers were analysed by SDS-PAGE and showed significant differences in polypeptide profiles from the same strain grown in nutrient broth in vitro . Analysis of whole cell extracts by Western-blotting revealed that protein A expression was repressed in S . aureus grown in vivo . Following subcutaneous administration, flucloxacillin levels in serum peaked earlier and were higher than those detected in chamber fluid . The inhibitory effect of the antibiotic on the growth of S . aureus in chambers in treated animals could be monitored easily by sequential sampling of the chamber fluid . These results indicate the potential of the chamber implant model for investigation of microbial phenotype in vivo and development of alternative methods for assessment of antimicrobial efficacy in vivo.

J Biol Chem, 1992 Dec 15, 267(35), 25141 - 52
Activation of NADPH oxidase and phospholipase D in permeabilized human neutrophils . Correlation between oxidase activation and phosphatidic acid production; Bauldry SA et al.; A major function of human neutrophils (PMN) during inflammation is formation of oxygen radicals through activation of the respiratory burst enzyme, NADPH oxidase . Stimulus-induced production of both phosphatidic acid (PA) and diglyceride (DG) has been suggested to mediate oxidase activity; however, transductional mechanisms and cofactor requirements necessary for activation are poorly defined . We have utilized PMN permeabilized with Staphylococcus aureus alpha-toxin to elucidate the signal pathway involved in eliciting oxidase activity and to investigate whether PA or DG act as second messengers . PMN were permeabilized in cytoplasmic buffer supplemented with ATP and EGTA for 15 min before addition of NADPH and various cofactors . Oxidase activation was assessed by superoxide dismutase inhibitable reduction of ferricytochrome C; PA and DG levels were measured by radiolabeled product formation or by metabolite mass formation . Both superoxide (O2-) and PA formation were initiated by 10 microM GTP gamma S; addition of cytosolic levels of calcium ions (Ca2+, 120 nM) enhanced O2- and PA formation 1.5-2 fold . DG levels showed little change during these treatments . PA formation preceded O2- production and varying GTP gamma S levels had parallel effects on O2- and PA formation . However, while PA formation and oxidase activation occurred in tandem at Ca2+ levels of < 1 microM, higher calcium enhanced PA formation but inhibited O2- production . Removal of ATP completely blocked O2- production but had little effect on PA formation; in contrast, if ATP was replaced with ATP gamma S, parallel production of PA and O2- occurred in the absence of other cofactors . Finally, while inhibition of PA production by ethanol pretreatment led to inhibition of O2- formation in PMN treated with GTP gamma S alone, in cells stimulated with a combination of GTP gamma S and Ca2+, ethanol continued to inhibit PA formation but had no effect on O2- production . Our results do not support a role for DG in the signal transduction path leading to oxidase activation and, while we show a close correlation between oxidase activation and PA production under many physiologic conditions, we also demonstrate that PA is not sufficient to induce oxidase activation and O2- formation can occur when PA production is inhibited.

Blood, 1992 Dec 15, 80(12), 3173 - 81
Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors; Fluckiger AC et al.; Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells . In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines . Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation . Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system . Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation . This Ig response was potentiated by IL-2 and antagonized by IL-4 . Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells . No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation . Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents . In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells.

FEBS Lett, 1992 Dec 14, 314(2), 187 - 90
cDNA sequence analysis of an antibiotic dodecapeptide from neutrophils; Storici P et al.; The full-length cDNA of a neutrophil antibiotic dodecapeptide has been cloned by reverse transcription/PCR from bovine bone marrow RNA . This peptide was originally isolated from bovine neutrophils, and shown to exert a potent antimicrobial activity in vitro on both Escherichia coli and Staphylococcus aureus . The cDNA codes for a polypeptide of 155 amino acid residues with a predicted mass of 17,629 Da and a pI of 8.03 . The deduced sequence comprises a putative signal peptide of 29 amino acids, a 114 residue pro-region, and a carboxy-terminal dodecapeptide corresponding to the mature antibiotic . The pro-sequence displays extensive identity to corresponding regions of other structurally unrelated antibiotic peptides of bovine neutrophils recently cloned.

J Vet Pharmacol Ther, 1992 Dec, 15(4), 351 - 63
Vancomycin kinetics in plasma and synovial fluid following intravenous administration in horses; Orsini JA et al.; Vancomycin hydrochloride was infused intravenously (i.v.) over a 30-min period in five horses at doses of 6.6, 11.0 and 15.4 mg/kg . Vancomycin concentration in plasma and synovial fluid samples was measured using a polarization immunoassay . A pharmacokinetic model was developed to accommodate the special features of the present study . The data were described by a two compartment open model with synovial fluid as an additional compartment in exchange with plasma . Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were measured for Staphylococcus aureus and Enterococcus sp . using isolates from hospital patients . Based on the pharmacokinetic model and MIC/MBC data, a practical therapeutic protocol for vancomycin administration was established at doses of 4.3-7.5 mg/kg given as a 1-h infusion every 8 h.

Plast Reconstr Surg, 1992 Dec, 90(6), 1031 - 5
The effect of denervation on soft-tissue infection pathophysiology; Alison WE Jr et al.; Pressure is the sine qua non in the etiology of pressure sores; however, ischemia, denervation, edema, and infection also have been implicated . The role of denervation in tissue infection was studied in an isolated in vivo ovine flap model . Twenty-six adult ewes, divided into three groups, had 29 island pedicle flaps raised on their buttocks . In group I, the cutaneous nerve remained intact, while group II had its nerve divided acutely . Group III had prolonged denervation, where the nerve was divided 7 days before flap elevation . All flaps received intradermal inoculations of 10(7) Staphylococcus aureus . Ninety-six hours later, quantitative bacteriology showed counts of 10(7), 10(7), and 10(9) colony-forming units (CFU) per gram of tissue in groups I, II, and III, respectively . Septic foci were larger in group III, and there was a significant increase in tissue edema between groups I and III . A 25-fold increase in bacterial counts seen in the prolonged denervation group may help explain why neurologically injured patients are more susceptible to infection and pressure ulcerations.

Dtsch Med Wochenschr, 1992 Dec 11, 117(50), 1907 - 12
{Incidence, frequency and resistance characteristics of methicillin-oxacillin resistant Staphylococcus aureus strains in Germany}; Voss A et al.; In a multicentre study, the methicillin-resistant Staphylococcus aureus (MRSA) isolates in 19 large clinics in Germany were recorded, and the resistance characteristics of these strains were studied . Oxacillin-mannitol-salt agar plates were distributed to all participants to ensure uniformity of screening, and each laboratory used these plates to investigate 200 consecutive Staphylococcus aureus isolates for oxacillin-methicillin resistance . Of the 3,794 evaluable Staphylococcus aureus isolates, 71.5% were penicillin and 3.7% (142) oxacillin resistant; four study centres reported methicillin-oxacillin resistance rates of more than 5% . Of the MRSA isolates, 75% were also resistant to ciprofloxacin, 61% to fosfomycin, 52% to imipenem, 50% to trimethoprim/sulfamethoxazole and 36% to clindamycin . All isolates were sensitive to vancomycin and teicoplanin . Of the Staphylococcus aureus strains isolated from patients in intensive therapy units, 10.4% were methicillin-oxacillin resistant . Drains and catheter tips (9.8% and 5.2% respectively) were the materials with the highest proportions of MRSA . Of the MRSA isolates in this study, 58.2% belonged to lysis group II.

J Mol Biol, 1992 Dec 5, 228(3), 983 - 6
Purification, crystallization and preliminary X-ray analysis of toxic shock syndrome toxin-1 from Staphylococcus aureus; Passalacqua EF et al.; High yields of toxic shock syndrome toxin-1, from Staphylococcus aureus, have been purified (> 99%) using a novel, simple, two-step procedure involving dye ligand chromatography . Crystals suitable for X-ray diffraction work were obtained by vapour diffusion using ammonium sulphate and polyethylene glycol as precipitants . They belong to the orthorhombic space group C222(1), with unit cell dimensions a = 108.6 A, b = 177.6 A and c = 97.5 A, with three molecules per asymmetric unit . The crystals diffract to at least 2.5 A resolution and are suitable for three-dimensional X-ray structural analysis.

J Biol Chem, 1992 Dec 5, 267(34), 24538 - 43
Six amino acids determine the sequence-specific DNA binding and replication specificity of the initiator proteins of the pT181 family; Dempsey LA et al.; The replication of pT181 and related plasmids of Staphylococcus aureus proceeds by a rolling circle mechanisms . The initiator proteins encoded by the plasmids of the pT181 family have sequence-specific DNA binding and topoisomerase activities . These proteins nick one strand of the DNA at the origin of replication . The free 3'-hydroxyl end at the nick is then used as a primer for the replication of the leading strand of the DNA . Although these initiator proteins are highly homologous, they show specificity in DNA binding and replication for their cognate DNAs . In this study, we have generated hybrid initiator proteins and studied their various biochemical activities in vitro . Our results show that 6 amino acids are sufficient to determine the DNA binding and replication specificities of such initiator proteins.

Eur J Cell Biol, 1992 Dec, 59(2), 458 - 63
Interleukin-1 from baboon peripheral blood monocytes: altered response to endotoxin (lipopolysaccharide) and Staphylococcus aureus stimulation compared with human monocytes; von Bulow GU et al.; The baboon Papio ursinus does not elicit a febrile response upon injection with endotoxin, but fever is produced when injected with Staphylococcus aureus particles (Zurowsky, Y., H . Laburn, D . Mitchell, Can . J . Physiol . Pharmacol . 65, 1402-1407 (1987)) . We address the question whether baboon peripheral blood monocytes produce interleukin-1 (IL-1) when stimulated with endotoxin or S . aureus particles in culture . Results show that little IL-1 biological activity was produced from endotoxin-stimulated baboon peripheral blood monocytes, compared with S . aureus-stimulated cells . Measurements of IL-1 beta by radioimmunoassay supported these data . This is contrary to data from human monocytes, which show greater sensitivity to endotoxin . Examination of IL-1 beta mRNA from endotoxin-stimulated and S . aureus-stimulated baboon monocytes, however, showed that more mRNA for IL-1 beta was present in endotoxin-stimulated monocytes than in cells stimulated with S . aureus . This illustrates the possibility that the production and/or the secretion of IL-1 beta is not as efficient in baboon monocytes as it is in human monocytes.

Brain Behav Immun, 1992 Dec, 6(4), 409 - 17
Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes; Matera L et al.; Prolactin (PRL) has been shown to contribute to the development of lymphoid tissues and maintenance of physiological immune function . Here we show that the role of the hormone extends to the control of the effector phase of the immune response . In addition to triggering resting lymphocytes to cell division, the hormone can also control the magnitude of their response to polyclonal stimuli . Concentrations of PRL in the physiological range increased the {3H}thymidine, {3H}uridine, and {3H}leucine incorporation of unstimulated NK cells cultured in serum-free conditions . The same concentrations of the hormone increased the response of NK, T, and B cells to the mitogenic stimuli interleukin 2 (IL2), phytohemagglutinin (PHA), and staphylococcus aureus cowan, respectively, the effect being maximally evident in the presence of suboptimal concentrations of the mitogens . By contrast concentrations of PRL five- to tenfold the physiological levels inhibited the mitogenic response to IL2 and PHA . These data indicate a double-faceted regulatory role of this hormone in vivo.

J Gen Microbiol, 1992 Dec, 138 ( Pt 12), 2515 - 8
Glycine betaine transport by Staphylococcus aureus: evidence for two transport systems and for their possible roles in osmoregulation; Pourkomailian B et al.; The transport of glycine betaine by Staphylococcus aureus was investigated . Two transport systems were found that could be differentiated on the basis of their affinity for glycine betaine and their activation by osmotic pressure . The high-affinity system was relatively independent of osmotic pressure and exhibited a Km of approximately 3 microM . This system was not inhibited by proline, for which a separate high-affinity transport system has been recently discovered . The low-affinity system was activated approximately 35-fold by an increase in osmotic pressure and exhibited a Km of approximately 130 microM for glycine betaine . This system is partially inhibited by excess proline and may be identical to the low-affinity system recently described for proline . Both glycine betaine transport systems are Na(+)-dependent.

J Laryngol Otol, 1992 Dec, 106(12), 1051 - 4
Clinical and bacteriological profile of the ear in otogenic tetanus: a case control study; deSouza CE et al.; Twenty two patients presented with otogenic tetanus . Seventeen patients had acute histories with only a single episode of otitis media with otorrhoea . Fifteen patients had unilateral central perforations, five had bilateral central perforations and two had no perforations but had acutely congested tympanic membranes which were bulging suggesting the presence of purulent fluid behind them . All patients with perforations had a purulent pulsatile discharge . A coexisting aerobic infection was seen in 85 per cent of the cultures and 59 per cent of these were due to staphylococcus aureus (versus 25 per cent in the controls) . Only one patient had received partial immunization . Tetanus resulting from otitis media is not an indication for surgery.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2729 - 35
Antimicrobial activities of clofazimine and B669 are mediated by lysophospholipids; Van Rensburg CE et al.; The susceptibilities of a range of gram-positive and gram-negative microbial pathogens to clofazimine and its analog B669 (0.1 to 32 micrograms/ml), as well as the effects of these agents on membrane phospholipid metabolism in Staphylococcus aureus and Escherichia coli, have been investigated in vitro . Gram-positive bacteria were found to be generally susceptible to these agents, whereas gram-negative organisms were uniformly resistant . Exposure of S . aureus to both agents (1 to 5 micrograms/ml), especially B669, caused dose-related enhancement of the activity of phospholipase A2, according to an increase in the release of 3H-radiolabeled arachidonate and lysophosphatidylethanolamine ({3H}LPE) from bacterial-membrane phospholipids . Treatment of E . coli with the riminophenazines also increased the release of {3H}arachidonate and {3H}LPE . Growth of gram-positive but not gram-negative bacteria was inhibited by LPE and lysophosphatidylcholine . Moreover, coincubation with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase protected gram-positive bacteria against the riminophenazines as well as against lysophospholipids . The results from this study are consistent with a mechanism whereby lysophospholipids mediate the activities of the two drugs.

Am J Physiol, 1992 Dec, 263(6 Pt 2), R1339 - 46
Modulation of sleep by cortisone in normal and bacterially infected rabbits; Toth LA et al.; Infectious disease is known to alter both sleep patterns and hydrocortisone (cortisol) concentrations in rabbits . Moreover, the sleep-altering effects of microbial infections are likely to be mediated via endogenous immune modulators whose actions are attenuated by glucocorticoids . To evaluate the relationships between sleep and glucocorticoids during infectious disease, the effects of cortisone administration (20 mg/kg, im) on sleep were examined before and after inoculation of rabbits with Staphylococcus aureus or Escherichia coli . When administered alone, cortisone did not alter the amount of time spent in slow-wave sleep (SWS) but did reduce electroencephalographic (EEG) slow-wave amplitudes during SWS, the number of bouts of SWS and the amount of time spent in rapid-eye-movement sleep . The duration of individual bouts of SWS was increased after cortisone treatment . Bacterially infected rabbits developed biphasic changes in sleep patterns that were characterized by an initial increase and a subsequent decrease both in SWS time and in EEG slow-wave amplitudes during sleep . Cortisone treatment attenuated these effects in S . aureus-inoculated rabbits . In contrast, cortisone treatment did not alter the initial phase of enhanced sleep in E . coli-inoculated rabbits but did attenuate the subsequent sleep suppression . These data indicate that glucocorticoid administration is associated with an attenuated sleep response in bacterially inoculated rabbits.

J Dairy Sci, 1992 Dec, 75(12), 3330 - 8
Potentiation of antibiotic therapy for bovine mastitis by recombinant bovine interleukin-2; Daley MJ et al.; Adjunct therapy with recombinant bovine interleukin-2 and antibiotics for Staphylococcus aureus IMI was investigated in an attempt to improve the therapy of antibiotics alone . Treatment of established S . aureus IMI with Na-cephapirin or Cefa-Lak produced average cures of 32.0 and 41.8%, respectively . When Na-cephapirin treatment was combined with recombinant bovine interleukin-2 at either 3.3 or 10 mg, the therapeutic efficacy was improved by an average of 20 to 30% . When Cefa-Lak treatment was combined with recombinant bovine interleukin-2 at 10 mg, the therapeutic efficacy was improved on average by 20% . Recombinant bovine interleukin-2, formulated in the excipient of the commercial Cefa-Lak, also improved the therapeutic efficacy by 16% compared with Cefa-Lak alone . Recombinant bovine interleukin-2, formulated in Cefa-Lak, maintained biological activity at room temperature for at least 21 d . After intramammary infusion of recombinant bovine interleukin-2, no biologically active interleukin-2 was detected in milk 48 h (four milkings) after administration . These data suggest that cytokines may be used as adjunct therapy with existing mastitis antibiotics or formulations of existing commercial products to improve the therapeutic efficacy.

South Med J, 1992 Dec, 85(12), 1176 - 80
Pleural effusions in right-sided endocarditis: characteristics and pathophysiology; Sexauer WP et al.; The incidence, characteristics, and pathogenesis of pleural effusions in patients with right-sided endocarditis (RSE) are poorly defined . We have recently observed four patients with a history of intravenous drug abuse and bacteremia due to Staphylococcus aureus who had pleural effusions during an episode of RSE . We report the pleural fluid characteristics of five effusions in these four patients and attempt to define the pathogenesis of each . We found that (1) an exudative, sterile, serosanguineous, or bloody effusion is common in RSE, (2) empyema occurred in only one patient, and (3) transudative effusions due to CHF were not observed . Possible mechanisms of pleural fluid formation in RSE include parapneumonic effusion, septic pulmonary emboli with or without infarction, and empyema . Congestive heart failure does not appear to be a common cause of pleural effusion in pure right-sided endocarditis.

Epidemiol Infect, 1992 Dec, 109(3), 413 - 21
Occurrence of quinolone resistance in Staphylococcus aureus from nosocomial infection; Witte W et al.; Among 63 Staphylococcus aureus isolates (one isolate per one patient) counted from infections (from August to November 1991) in hospital T., eight exhibited resistance to fluoroquinolones . Seven of these quinolone-resistant isolates were multiply- and methicillin-resistant S . aureus (QR-MRSA) . The results of phage-, plasmid- and genotyping (pulsed field electrophoresis) revealed that six different strain-clones of these MRSA were spread in the hospital . In vitro spontaneous mutants resistant to fluoroquinolones are 10-100-fold more frequent in MRSA than in other S . aureus when selected on isosensitest-agar containing 1 microgram/ml of ciprofloxacin . However, the same mutant frequencies were found in strain 8325-4 with and without the mecA-determinant . The resistance phenotype was stable over 30 generations of subculture in nutrient broth as well in natural quinolone resistant MRSA as in mutants of other types of S . aureus selected in vitro . The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA . Data of chemotherapy prior to the isolation of S . aureus show that three of seven patients from whom QR-MRSA were isolated were treated with a quinolone . In eight cases of infections with non-MRSA and quinolone treatment the isolated S . aureus strains were in vitro sensitive to quinolones.

Br J Anaesth, 1992 Dec, 69(6), 647 - 52
Extradural abscess complicating extradural anaesthesia for caesarean section; Kee WD et al.; Extradural abscess has been described infrequently as a complication of extradural anaesthesia and analgesia . We describe an abscess that developed 5 days after operation in a patient who had extradural anaesthesia for Caesarean section and postoperative analgesia, and review the literature on extradural abscess complicating extradural catheterization, including a discussion on pathogenesis, clinical presentation, diagnosis and management . There have now been 16 reported cases of extradural catheter-related extradural abscess . Only one previous case has been in obstetric practice, despite the widespread use of these techniques in this specialty . A disproportionate number of cases have involved thoracic catheters . Duration of catheterization ranged from 40 h to 6 weeks, the majority of catheters being in place for 5 days or less . The time from catheter placement to development of symptoms ranged from 72 h to 5 months . The causative organism was isolated in 11 cases: Staphylococcus aureus was identified in nine (82%) and Staphylococcus epidermidis in two (18%) . Outcome was reported in 15 cases, of which seven (47%) had a full or near full recovery and eight (53%) had a persistent neurological deficit . One case was managed successfully without surgery . Fifty percent of all cases have been reported in the past 5 years . With the increasing use of extradural techniques for anaesthesia and analgesia, this serious complication may be seen more frequently in the future.

J Med Microbiol, 1992 Dec, 37(6), 376 - 81
Immunological response to a Staphylococcus aureus fibronectin-binding protein; Ciborowski P et al.; A protein (gal-FnBP), constructed by fusion of the genes encoding beta-galactosidase of Escherichia coli and the binding domains of fibronectin-binding protein (FnBP) of Staphylococcus aureus was used . FnBP is a surface protein responsible for attachment of bacteria to extracellular matrix of various host tissues . Gal-FnBP is more stable and can be produced in larger quantities than native FnBP . The binding specificity of this fusion protein was established in a Western blot analysis . Treatment of gal-FnBP with formalin inactivated the binding capacity of the protein but immunogenicity was retained . Immunisation of mice with formalin-treated gal-FnBP resulted in high antibody titres against the fibronectin-binding part of this fusion protein . These antibodies were measured by their ability to block the specific binding of fibronectin to gal-FnBP in a blocking assay . Sera raised against formalin-treated gal-FnBP and non-treated gal-FnBP blocked this binding to 40 and 25% respectively, thereby indicating the usefulness of gal-FnBP as a vaccine component.

Clin Immunol Immunopathol, 1992 Dec, 65(3), 286 - 93
Parathyroid hormone inhibits immunoglobulin production without affecting cell growth in human B cells; Jiang Y et al.; The effect of parathyroid hormone (PTH) on immunoglobulin (Ig) production and proliferation in the human B-cell lines CBL, SKW, and CESS was studied . PTH inhibited Ig production from all the B-cell lines in a dose-dependent manner during 5 days of culture . As little as 0.1 ng/ml was inhibitory . PTH also inhibited Ig production from cell lines stimulated by vasoactive intestinal peptide (VIP), interleukin 2 (IL-2), and IL-6 . This inhibition was not due to decreased cell growth since proliferation was not affected and cell viability was always greater than 98% . In contrast to PTH, inactivated PTH or triiodothyronine failed to affect Ig production . Inhibition by PTH was blocked by anti-PTH serum, but not by control serum . Of the various cytokines tested, IL-4 reduced the PTH-induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-3, IL-5, interferon alpha (IFN-alpha), IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF), failed to do so . The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control antibody . Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4 . PTH also inhibited IgG, IgM, and IgA production by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation . This inhibition was blocked by anti-IL-4 antibody but not by control antibody . These results indicate that, in addition to its regulatory effect on calcium metabolism, PTH also acts as an immunoregulatory factor, and that it interacts with the cytokine, IL-4.

Surg Gynecol Obstet, 1992 Dec, 175(6), 548 - 50
Microbiologic factors of stump wound infection; Brook I et al.; Specimens from 52 patients with stump wound infection (SWI) were studied for aerobic and anaerobic bacteria . Bacterial growth was present in 44 specimens . Only aerobic or facultative bacteria were recovered in 19 specimens, only aerobic bacteria in 12 and mixed aerobic, facultative and anaerobic bacteria in 13 . One hundred and three isolates were recovered (2.3 per specimen)-58 aerobic or facultative (1.3 per specimen) and 45 anaerobic (1.0 per specimen) . The predominant isolates were anaerobic cocci (17), Bacteroides species (13 isolates), Staphylococcus aureus (12) and Escherichia coli (11) . Polymicrobial infection occurred in 36 instances . S . aureus was more commonly isolated and anaerobic bacteria were less commonly isolated in SWI of the arms, compared with legs . These data highlight the polymicrobial aerobic-anaerobic cause of SWI.

Am J Cardiol, 1992 Dec 1, 70(18), 1449 - 52
A comparison of hospital and community-acquired infective endocarditis; Chen SC et al.; The epidemiology, clinical features, microbiology and outcome of 30 episodes of nosocomial endocarditis occurring over a 13-year period were reviewed and compared with 148 cases of community-acquired endocarditis . Twenty-eight patients (93%) had been in hospital for > 1 week and 10 patients (33%) for > 1 month when they developed endocarditis . Left-sided infection was most frequent; only 3 cases involved the tricuspid valve . Compared with community-acquired infection, patients tended to be older, had a greater incidence of congestive cardiac failure (p = 0.001) or hypotension (p = 0.0008) at presentation and were more likely to have bacteremia after an invasive procedure (83 vs 31%; p < 0.00001) . Intravascular devices were the presumed source of bacteremia in 11 cases (37%); the same organism was isolated from both the blood and the suspected source of infection . Staphylococcus aureus was the most frequent causative organism, accounting for 17 episodes (57%), including 4 (13%) due to methicillin-resistant strains . Nosocomial endocarditis had a significantly higher mortality than did community-acquired infection (40 vs 18%; p = 0.02) . Eight patients (27%) needed valve replacement . Proper adherence to protocols for management of intravascular devices and appropriate antimicrobial prophylaxis before procedures may have prevented endocarditis in 15 of 30 patients.

J Neurochem, 1992 Dec, 59(6), 2030 - 9
Inhibition of phosphorylation of synapsin I and other synaptosomal proteins by beta-bungarotoxin, a phospholipase A2 neurotoxin; Ueno E et al.; Some snake venom neurotoxins, such as beta-bungarotoxin (beta-BuTX), which possess relatively low phospholipase A2 (PLA2) activity, act presynaptically to alter acetylcholine (ACh) release both in the periphery and in the CNS . In investigating the mechanism of this action, we found that beta-BuTX (5 and 15 nM) inhibited phosphorylation, in both resting and depolarized synaptosomes, of a wide range of proteins, including synapsin I . Naja naja atra PLA2, which has higher PLA2 activity, also inhibited phosphorylation but was less potent than beta-BuTX . At 1 nM, beta-BuTX and N . n . atra PLA2 inhibited phosphorylation of synapsin I only in depolarized synaptosomes . Synaptosomal ATP levels were not affected by 5 or 15 nM beta-BuTX or by 5 nM N . n . atra PLA2 . Limited proteolysis, using Staphylococcus aureus V-8 protease, indicated that beta-BuTX inhibited phosphorylation of synapsin I in both the head and the tail regions . The inhibition of phosphorylation was not antagonized by nordihydroguaiaretic acid or indomethacin, suggesting that arachidonic acid derivatives do not mediate this inhibition . Furthermore, inhibition of phosphorylation by beta-BuTX and N . n . atra PLA2 was not altered in the presence of the phosphatase inhibitor okadaic acid, suggesting that stimulation of phosphatase activity is not responsible for this inhibition . Inhibition of protein phosphorylation by PLA2 neurotoxins and enzymes may be associated with an inhibition of ACh release.

J Hosp Infect, 1992 Dec, 22(4), 299 - 305
An outbreak of infection due to Staphylococcus aureus phage type 52 in a neonatal intensive care unit; Chowdhury MN et al.; An outbreak of infection due to Staphylococcus aureus phage-type 52, resistant only to penicillin, occurred in children's wards primarily in a neonatal intensive care unit . The outbreak involved 86 infants; the majority presented with conjunctivitis, wound infections, boils, omphalitis and otitis externa . Seven per cent of these infants (six of 86) also had septicaemia . In addition, 6% (five of 86) were colonized by this phage type and the most common site of carriage was the umbilicus . The outbreak was contained by eradication of nasal carriage among the staff members and also by standard infection control measures.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2617 - 21
Survey of the methicillin resistance-associated genes mecA, mecR1-mecI, and femA-femB in clinical isolates of methicillin-resistant Staphylococcus aureus; Hurlimann-Dalel RL et al.; The restriction site polymorphism of the chromosomal femAB region and the first appearance of the regulatory element mecR1-mecI associated with the methicillin resistance determinant (mec) were analyzed in 192 initially methicillin resistant (Mcr) Staphylococcus aureus clinical isolates collected between 1965 and 1990 in the Zurich area . Forty-three of the strains lost the resistance spontaneously . All isolates that were still Mcr hybridized with mecA, the gene for the low-affinity penicillin-binding protein PBP 2' . Mcr strains isolated before 1977 lacked sequences that hybridized with mecR1-mecI, a regulatory element controlling the expression of mecA; exceptions to this were one strain isolated in 1966 and one strain isolated in 1972 . The size of the EcoRV fragment carrying femA, a chromosomally encoded factor involved in pentaglycine side chain formation of the peptidoglycan and essential for the expression of methicillin resistance, was conserved in all strains but one, which was susceptible to methicillin even though it carried a functional mecA gene . The methicillin susceptibility of this particular strain was presumably due to a spontaneous femA-like mutation . The 192 strains belonged to seven different EcoRV restriction fragment patterns recognizable with a 10.5-kb probe covering the femAB region . Some 93% of the 149 Mcr strains belonged to pattern A, and the remaining Mcr strains shared patterns A' and B . The 42 isolates which spontaneously lost their resistance upon storage and revival represented all seven different patterns . This strong conservation of femA suggests an important role for femA in cell wall metabolism and methicillin resistance.

Protein Sci, 1992 Dec, 1(12), 1613 - 21
The calmodulin-binding site of the plasma membrane Ca2+ pump interacts with the transduction domain of the enzyme; Falchetto R et al.; Calpain proteolysis of the plasma membrane Ca2+ pump removes a C-terminal 14-kDa portion which includes the calmodulin-binding domain . This produces a fully activated 124-kDa fragment, which can be inhibited by synthetic versions of the calmodulin-binding domain . The inhibition is strongest when Trp-8 in the latter domain is replaced by a Tyr residue (Falchetto, R., Vorherr, T., Brunner, J., & Carafoli, E., 1991, J . Biol . Chem . 266, 2930-2936) . In the present study, the N-terminus of the 28-residue synthetic calmodulin-binding domain was acetylated with 3H-acetic anhydride, and Phe in position 25 was replaced by a phenylalanine derivatized with a diazirine-based, photoactivatable carbene precursor . This peptide (C28WC*) inhibited the fully active 124-kDa fragment of the pump and became cross-linked to it upon photolysis . After proteolysis of the fragment with Asp-N or Staphylococcus aureus V8 (Glu-C) protease, labeled peptides were isolated by reversed-phase high-performance liquid chromatography and subjected to Edman sequence analysis . The peptides originated from a region of the pump located within the unit protruding into the cytoplasm between transmembrane domain two and three . This unit has been proposed to be the site of the energy transduction domain, which would couple the ATP hydrolysis to Ca2+ translocation.

FEMS Microbiol Lett, 1992 Dec 1, 78(2-3), 175 - 80
Typing of methicillin-resistant Staphylococcus aureus with IS256; Wei MQ et al.; A simple one-step procedure is described for specifically amplifying and labelling insertion element IS256 which is associated with the gentamicin-resistance transposon Tn4001 . The product has been used to probe DNA digests of methicillin-resistant Staphylococcus aureus . The resulting restriction fragment length polymorphisms were found to be able to distinguish isolates which were indistinguishable by other typing methods . The probe also hybridised with methicillin-resistant Staphylococcus aureus which were isolated before the emergence of gentamicin resistance, demonstrating its usefulness in typing species other than those that are gentamicin-resistant.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2709 - 14
In vitro pharmacodynamic effects of concentration, pH, and growth phase on serum bactericidal activities of daptomycin and vancomycin; Lamp KC et al.; Clinical trials with daptomycin were halted in December 1990 because of treatment failures including two resistant Staphylococcus aureus strains . High protein binding of daptomycin (> 90%) and the lower-than-expected concentrations in serum with the dosage regimen of 3 mg/kg of body weight every 12 h may have contributed to these failures . To evaluate the effect that higher concentrations would have on bactericidal activity measured by time-kill curves, peak and trough concentrations were estimated for dosage regimens of 3, 5, and 10 mg/kg every 12 h . MICs, MBCs, and killing curves for daptomycin and vancomycin were performed by using the estimated concentrations with four S . aureus strains obtained from patients who failed daptomycin therapy for endocarditis . MICs and MBCs of daptomycin demonstrated a greater inoculum effect than those of vancomycin; MICs and MBCs of daptomycin increased three- to fourfold, but those of vancomycin increased only one- to twofold when the inoculum was increased from 5 x 10(5) to 5 x 10(7) CFU/ml . No pH-dependent effect on MICs or MBCs was seen . Strenuous experimental conditions were chosen: high inoculums (5 x 10(7) CFU/ml), extremes of pH (6.4, 7.4, and 8), and stationary and exponentially growing organisms; and all experiments completed in the presence of pooled human serum . Daptomycin exhibited concentration-dependent killing and statistically faster kill rates than vancomycin against stationary- or exponential-growth-phase organisms . A pH-dependent decrease in activity with daptomycin was also demonstrated . Daptomycin and vancomycin produced higher kill rates against exponentially growing organisms . A pH-dependent decrease in activity with daptomycin was also demonstrated . Daptomycin and vancomycin produced higher kill rates against exponentially growing organisms . The results indicate that the use of higher dosage regimens with compounds similar to daptomycin may be capable of overcoming the effects of pH, high inoculum, and protein binding.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2693 - 7
Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin; O'Reilly T et al.; We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis . Clindamycin was used as a comparison drug . Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity . After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started . The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin) . Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g) . Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones) . Therapy with rifampin or clindamycin alone was associated with the emergence of resistance . Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens . Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Arch Oral Biol, 1992 Dec, 37(12), 991 - 5
Expression of Fc-gamma-RIII and fibronectin in peripheral polymorphonuclear neutrophils with increased response to Fc stimulation in patients with juvenile periodontitis; Asman B et al.; The nature of increased luminol-enhanced chemiluminescence (CL) in peripheral polymorphonuclear neutrophils (PMN) in juvenile periodontitis is of pathophysiological interest and may serve as a model for tissue damage caused by granulocytes . Activation of PMNs by opsonized Staphylococcus aureus was compared with that of Actinobacillus actinomycetemcomitans and Bacteroides gingivalis, regarded as being more specific for juvenile periodontitis . The CL was higher in the PMNs from the patients, independently of bacteria and mode of opsonization (autologous serum or gamma-globulin) . Fc-gamma-RIII assessed on the washed fragments from peripheral PMNs was significantly (p < or = 0.005) lower in the patients with juvenile periodontitis than in their pair-matched healthy controls, while the content of fibronectin was higher (p < or = 0.032) . However, when Fc-gamma-RIII and fibronectin were studied in fresh PMNs by flow cytometry no difference could be found between the two groups . The increased generation of CL of peripheral PMNs found in patients with juvenile periodontitis seems to be independent of humoral factors and of bacterial species and may be related to the properties of the PMN cell membranes.

Zhongguo Zhong Yao Za Zhi, 1992 Dec, 17(12), 747 - 9, 764
{Anti-inflammatory and anti-bacterial functions of bezoar antipyretic tablets}; Meng HQ et al.; Bezoar Antipyretic Tablets can inhibit markedly acute exudative inflammation . It can also inhibit markedly drug-resistant Staphylococcus aureus, etc . It has no influence on Bacillus pyocyaneus, etc.

Mol Cell Endocrinol, 1992 Dec, 90(1), 1 - 6
Localization of the heparin binding site of follistatin; Inouye S et al.; To define the heparin-binding site of follistatin, the reduced and S-carboxymethylated recombinant human follistatin containing 288 amino acids was digested by Staphylococcus aureus V8 . The digested product was subjected to sulfate cellufine column chromatography and the adsorbed peptide fragments eluted with a stepwise gradient of sodium chloride . The recovered column fractions were further purified by reversed-phase high-performance liquid chromatography (HPLC) and the HPLC peaks subjected to amino-terminal sequence analysis . All of the sulfate cellufine-retarded peptide fragments gave the same N-terminal amino acid sequence, which started at residue-68 of human follistatin, suggested that those fragments starting from residue-68 contain the heparin binding site . The multiple fragments might represent the oxidized, non-glycosylated or glycosylated forms of follistatin(68-113) resulting from the V8 digestion . A synthetic peptide corresponding to the region having the amino acid sequence 72-86 of follistatin was able to bind both heparin and sulfate cellufine, as well as compete with recombinant follistatin for binding to heparin . These findings further define the location of the heparin and heparan sulfate-binding site of follistatin at the basic amino acid-rich region comprising the amino acid sequence Lys75-Lys-Cys-Arg-Met-Asn-Lys-Lys-Asn-Lys-Pro-Arg86.

J Rheumatol, 1992 Dec, 19(12), 1960 - 2
Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection; Rivera J et al.; We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection . Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection . Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients . Staphylococcus aureus was the most commonly isolated organism in both groups . We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection . Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.

J Helminthol, 1992 Dec, 66(4), 305 - 9
Radiolabelling of the excretory-secretory and somatic antigens of Anisakis simplex larvae; Sugane K et al.; Anisakis simplex larvae were cultured in vitro in medium containing 35S-methionine for ten days . The medium and the larval tissues were analysed for biosynthetically labelled polypeptide by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography . Immunoprecipitates with positive and negative human antisera were similarly analysed, using Staphylococcus aureus to absorb immuno-complexes . ES products of Anisakis larvae contained many polypeptides with molecular weights of less than 200 K . 180 KDa and 40 KDa polypeptides in ES products reacted with IgG in Anisakis-infected human sera . Somatic extracts also contained many polypeptides with molecular weights of less than 200 K . One of these polypeptides with a molecular weight of 130 K reacted with IgG in Anisakis-infected human sera . These polypeptides did not react with other nematode-infected human sera.

Hiroshima J Med Sci, 1992 Dec, 41(4), 79 - 85
Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents . II . Isolation of arbekacin-resistant strain; Inouye Y et al.; Resistance patterns against 24 antimicrobial agents were examined for 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital during the period October 1990 and July 1991 . Overall resistance (the percentage of highly and moderately resistant strains) to the antimicrobial agents is summarized as follows: methicillin 100%, flomoxef 100% (beta-lactams); kanamycin 94%, tobramycin 94%, amikacin 100%, isepamicin 94%, gentamicin 80%, dibekacin 94%, arbekacin 2% (basic oligosaccharide group/aminocyclitols); ofloxacin 96%, temafloxacin 96%, levofloxacin 96% (fluoroquinolones); erythromycin 98%, clarithromycin 98%, josamycin 30% (macrolides); vancomycin 0% (glycopeptide); tetracycline 94%, minocycline 94% (tetracyclines); fosfomycin 100%; mikamycin B 30%, nosiheptide 0% (peptide); rifampicin 2% (ansamycin); streptomycin 2% (basic oligosaccharide group); chloramphenicol 2% . Arbekacin resistance was observed in one case: the cross resistance was complete among the aminocyclitol antibiotics tested in this study and streptomycin, probably due to the ribosomal alteration.

Jpn J Antibiot, 1992 Dec, 45(12), 1684 - 99
{Clinical studies on cefprozil granules in pediatric skin soft tissues infections}; Motohiro T et al.; Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections . MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients . An inoculum size of 10(6) CFU/ml was used in the MIC-determinations . CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1) . To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d . and 14 cases of q.i.d.) was administered for an average of 6 days . The results obtained are summarized as follows . 1 . With regard to the 53 isolates of S . aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml . 45 strains (84.9%) were inhibited at 0.78 micrograms/ml . MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S . aureus (MRSA) was 100 micrograms/ml . The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively . The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively . CFPZ showed the second highest activity after MCIPC against S . aureus . 2 . CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses . 3 . For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively . The efficacy rates on these days were 90.4, 100 and 100%, respectively . The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater . Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days . 4 . Bacteriological effects of CFPZ were determined against 60 strains of S . aureus.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1992 Dec, 45(12), 1622 - 34
{Clinical evaluation of cefprozil in children}; Mochizuki Y et al.; Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin, was evaluated for its efficacy and safety in 42 children with bacterial infections (Table 1), and the following results were obtained . 1 . CFPZ was administered in 3 or 4 divided doses at daily dosages ranging from 15.3 to 60.0 mg/kg to 42 patients (19 cases of acute tonsillitis and/or laryngitis, pharyngitis, 13 cases of pneumonia, 2 cases each of suppurative cervical lymphadenitis and UTI, and 1 case each of scarlet fever, acute otitis media, suppurative parotitis, impetigo contagiosa, furuncle and acute enteritis) and the following clinical results were obtained: excellent; 24 cases, good; 14 cases, fair; 4 cases . The overall efficacy rate was 90.5% (Table 3) . 2 . MICs of CFPZ against 50 strains of isolated organisms are shown in Table 4 . In 19 cases out of 28 cases examined, causative organisms were successfully eradicated and strain of Staphylococcus aureus was decreased in 1 case . 3 . Diarrhea was observed in 2 cases (cases 8, 11) . In case 8, the symptom disappeared spontaneously . Case 11 improved immediately after the administration of the drug was stopped . Among 39 children who went through laboratory tests, eosinophilia which seemed to be related to the administration of this drug was observed in 2 cases (cases 29, 38) . Slight elevations of S-GOT and S-GPT were found in 1 case (case 22) (Table 7) . 4 . These data suggest that CFPZ is a safe and useful new antibiotic in the treatment of children with susceptible bacterial infections.

Infect Control Hosp Epidemiol, 1992 Dec, 13(12), 711 - 8
Methicillin-resistant Staphylococcus aureus: a questionnaire survey of 75 long-term care facilities in western New York; Mylotte JM et al.; OBJECTIVES: To determine the frequency of recognition of methicillin-resistant Staphylococcus aureus (MRSA) as an infection control problem and its prevalence among long-term care facilities, and to evaluate whether certain long-term care facility characteristics such as bed size, ownership, level of infection control activity, and frequency of resident transfers to acute care hospitals are related to the recognition or prevalence of MRSA in this setting . DESIGN: Questionnaire survey . SETTING: Seventy-five long-term care facilities in the 8 counties of western New York . RESULTS: Seventy-five of 81 (92.6%) long-term care facilities returned a completed questionnaire . Seventy-nine percent were considered to have a "limited" level of infection control activity (part-time infection control practitioner who spent less than 10 hours a week on infection control activities) . The larger the long-term care facility, the more time was spent on infection control activities (p = .01) . Seventy-two percent of the long-term care facilities screened new admissions for MRSA by reviewing culture reports; 69% of the long-term care facilities had a specific infection control policy for MRSA . Sixteen of the 75 (21%) facilities felt they had an infection control problem with MRSA . By univariate analysis, the only characteristic significantly associated with this recognition was use of nurse practitioners or physician assistants by a facility (p < .05) . Eighty-one percent of the 75 long-term care facilities had identified one or more patients with MRSA in the year prior to the survey . By univariate analysis, the only characteristics that were significantly associated with the number of residents with MRSA were the monthly average number of residents transferred to acute care facilities (p = .034) and facility bed size (p = .022); there was also a trend toward increasing intensity of infection control activities (p = .085) . However, facility bed size and the average number of resident transfers per month to acute care facilities were strongly associated (p = .0002) . By stepwise logistic regression analysis, only bed size was an independent predictor of the number of residents with MRSA . Many long-term care facilities had tried to eradicate MRSA; ciprofloxacin was most commonly used to eradicate MRSA . CONCLUSIONS: The vast majority of the 75 long-term care facilities in the 8 counties of western New York have identified patients with MRSA, although only a minority (21%) of them actually believed that an infection control problem existed . Facility size (a surrogate for the monthly average number of resident transfers to acute care facilities) seems to be an important factor in determining the number of residents with MRSA in long-term care facilities in our geographic region . The major longitudinal studies of MRSA in such facilities have so far been done only in Veterans Affairs facilities . Further studies are needed in freestanding long-term care facilities, the largest group of long-term care facilities in the United States, to determine the epidemiology of MRSA in this setting and to develop practical and valid infection control methods for residents with MRSA.

J Antimicrob Chemother, 1992 Dec, 30(6), 821 - 6
Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus; Wadsworth SJ et al.; The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited . To investigate the changing patterns of in-vitro susceptibility of S . aureus to 16 antibiotics, 190 clinical isolates from two different years were studied . The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989 . For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin . These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%) . The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated . MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%) . It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S . aureus . A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.

Acta Paediatr Jpn, 1992 Dec, 34(6), 579 - 83
The inhibition of lymphocyte blastogenesis by asparaginase: critical role of glutamine in both T and B lymphocyte transformation; Kitoh T et al.; L-Asparaginase has long been used in the treatment of acute lymphoblastic leukemia or malignant lymphoma in childhood . To determine cell type specific sensitivity to this drug, the L-asparaginase-mediated inhibition of blastogenesis of human peripheral T or B lymphocytes was compared . The rate of incorporation of {3H}-thymidine into the DNA of either T lymphocytes due to phytohemagglutinin (PHA) or B lymphocytes due to Staphylococcus aureus Cowan I (SAC) was measured by the addition of Escherichia coli L-asparaginase in the medium . The blastogenic response of either T or B lymphocytes was also determined in medium depleted of exogenous asparagine and/or glutamine, both of which are hydrolyzed by this enzyme . The in vitro blastogenesis of either human T lymphocytes due to PHA or B lymphocytes due to SAC was inhibited by the inclusion of asparaginase in the medium . The deprivation of exogenous asparagine did not have any inhibitory effect on the blastogenic response of both T and B lymphocytes to each mitogen . On the other hand, the glutamine concentration in the culture medium provided a critical influence on the proliferative response of T and B lymphocytes . The rate of incorporation of {3H}-thymidine into DNA was increased markedly as the concentration of glutamine was increased from 2(-7)-2 mmol/l . It is concluded that the mechanism of inhibition of PHA- or SAC-stimulated lymphocyte blastogenesis by L-asparaginase is not asparagine deprivation but glutamine deprivation . Glutamine, which is the most abundant amino acid, is thought to have an important role in the immune response of lymphocytes.

J Rheumatol, 1992 Dec, 19(12), 1859 - 67
Abnormal glycosylation of hemopexin in arthritic rats can be blocked by bindarit; Saso L et al.; Induction of arthritis in rats with Freund's complete adjuvant was accompanied by a distinctive alteration of concanavalin A (Con-A) reactivity in their serum proteins in which the concentrations of selected Con-A reactive proteins were significantly higher when compared to healthy rats . To assess if the observed increase in Con-A reactivity of specific serum proteins reflects an increase in carbohydrate moieties in these proteins in addition to an increase in their protein concentrations, a heme binding serum glycoprotein, hemopexin, also an acute phase reactant, was selected as a marker protein . Hemopexin was purified to apparent homogeneity from pools of serum samples derived from rats with yeast induced inflammation, a monospecific polyclonal antibody was prepared and was used for immunoblot analysis . It was noted that the concentration of hemopexin increased in rats with adjuvant induced arthritis; however, its concentration fell to normal levels after administration with a newly synthesized drug, bindarit, (2-{(1-benzyl-indazol-3-yl)methoxy}-2-methyl propionic acid, C19H20N2O3 . Hemopexin was micropurified individually from healthy rats, adjuvant induced arthritic rats, and adjuvant arthritic rats treated with bindarit, cleaved with a Glu-C endopeptidase, Staphylococcus aureus protease V8, and the resultant peptide fragments resolved by SDS-PAGE and examined by silver staining, Coomassie blue staining, and lectin blots using Con-A . It was subsequently noted that hemopexin isolated from adjuvant induced arthritic rats showed a significant increase in Con-A reactivity in selected peptide fragments and that such an increase in glycosylation could be reversed to a pattern similar to healthy rats following treatment with bindarit.(ABSTRACT TRUNCATED AT 250 WORDS)

Indian J Med Res, 1992 Dec, 96, 344 - 9
A simple radioassay for detection of antithyroglobulin autoantibodies; Kumar A et al.; Radioassay technique for detection of anti-thyroglobulin autoantibodies (ATA) in serum samples using protein-A rich Staphylococcus aureus as an immune complex separating agent was comparable (r = 0.99; n = 42; P < 0.001) to that evaluated with anti-human gammaglobulin (AHGG) . The inter- and intra-assay coefficient of variations were lower (7.4 and 2.2% respectively) using Staph . aureus as compared to that observed with AHGG (10.4 and 4.7% respectively) . A highly significant correlation was observed (r = 0.53; n = 71; P < 0.001) between per cent bound radiolabel thyroglobulin in radioassay and log reciprocal titre of ATA by haemagglutination method . Radioassay scored more number of positive sera as compared to haemagglutination method for normal controls (6 vs 1; n = 46) and patients of thyroid diseases (151 vs 70; n = 238) . Due to the relatively poor stability of tracer on storage larger inter-assay coefficient of variations were observed with the radiolabelled preparations older than 10-12 days . The radioassay method evaluated is sensitive, reproducible and useful in detecting presence of anti-thyroglobulin autoantibodies.

Am J Pathol, 1992 Dec, 141(6), 1299 - 307
Development and characterization of an experimental model of brain abscess in the rat; Flaris NA et al.; Brain abscesses were produced in the rat by direct intracerebral injection of agarose beads laden with Staphylococcus aureus . The method proved to be easy, reproducible, effective and was associated with a low mortality rate . The histopathologic features of the experimental abscess are similar to other animal models and to human abscesses . The encapsulation of the lesion, macrophage/microglial response, astrocytic activation, and changes in the surrounding brain parenchyma were studied by immunohistochemistry . Edema, diffuse microglial activation and diffuse astrocytosis characterized the early reaction of the injected cerebral hemisphere . After day 10, edema subsided, and the microglial and astrocytic responses became restricted to the area around the lesion . Fibronectin deposition in the capsule preceded the appearance of myofibroblasts, which was concurrent with the beginning of collagen deposition on day 9 . Hypervascularity of the capsule appeared as early as day 6 and persisted through day 28 . This study suggests that brain abscess formation can be separated into three components: an initial period of edema and glial activation; an intermediate phase of neovascularization and fibronectin deposition; and a final phase of collagen deposition and progressive fibrosis . This new model offers an excellent paradigm for the analysis of neural tissue reaction and de novo fibrous tissue deposition.

Transplantation, 1992 Dec, 54(6), 1025 - 30
The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes; Morikawa K et al.; We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro . FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner . Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest . In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506 . Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71) . Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system . Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line . These results indicate that FK506 has discrete effects on the different stages of the B cell maturation.

Nucleic Acids Res, 1992 Nov 11, 20(21), 5549 - 54
DNA conformational change induced by the bacteriophage phi 29 connector; Valpuesta JM et al.; Translocation of viral DNA inwards and outwards of the capsid of double-stranded DNA bacteriophages occurs through the connector, a key viral structure that is known to interact with DNA . It is shown here that phage phi 29 connector binds both linear and circular double-stranded DNA . However, DNA-mediated protection of phi 29 connectors against Staphylococcus aureus endoprotease V8 digestion suggests that binding to linear DNA is more stable than to circular DNA . Endoprotease V8-protection assays also suggest that the length of the linear DNA required to produce a stable phi 29 connector-DNA interaction is, at least, twice longer than the phi 29 connector channel . This result is confirmed by experiments of phi 29 connector-protection of DNA against DNase I digestion . Furthermore, DNA circularization assays indicate that phi 29 connectors restrain negative supercoiling when bound to linear DNA . This DNA conformational change is not observed upon binding to circular DNA and it could reflect the existence of some left-handed DNA coiling or DNA untwisting inside of the phi 29 connector channel.

Biochim Biophys Acta, 1992 Nov 9, 1111(2), 211 - 20
Influence of staphylococcal delta-toxin on the phosphatidylcholine headgroup as observed using 2H-NMR; Rydall JR et al.; The interaction of the 8-toxin peptide isolated from Staphylococcus aureus with the headgroup region of lipid bilayer membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was investigated using deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy . At relatively low peptide/lipid ratios (P/L < 0.10), all 2H- and 31P-NMR spectral lineshapes at 25 degrees C were indicative of a single population of liquid-crystalline lipids in a bilayer arrangement . At these P/L ratios, delta-toxin had only marginal effects on the size of the quadrupole splitting measured from POPC labelled at either the alpha-methylene (POPC-alpha-d2) or the beta-methylene segment (POPC-beta-d2) of the choline headgroup and, similarly small effects on the magnitude of the chemical shift anisotropy (CSA) of the 31P-NMR spectrum . With increasing amounts of delta-toxin (0.10 < P/L < 0.15) the size of the 2H quadrupole splitting from POPC-alpha-d2, as well as the magnitude of the 31P-CSA, decreased progressively and rapidly . The quadrupole splitting from POPC-beta-d2, however, remained relatively unaffected . At yet higher levels of delta-toxin (P/L > 0.15), all 2H- and 31P-NMR spectra indicated the presence of multiple lipid populations experiencing varying degrees of increased conformational disordering . The spectral lineshapes of these apparently nonbilayer spectral components reverted to bilayer-type lineshapes upon lowering the measuring temperature to 5 degrees C . At the utmost highest level of delta-toxin measured here (P/L = 0.20), all 2H- and 31P-NMR spectra consisted of a single, broad, apparently nonbilayer-type component, indicative of hindered but virtual isotropic motional averaging of the POPC headgroups . In this case no reversion to bilayer-type spectra could be obtained by decreasing the temperature . We could obtain no evidence that the conformation of the choline headgroup of POPC was responding to any specific influence of delta-toxin on bilayer surface electrostatics.

Health Prog, 1992 Dec, 73(10), 35 - 7, 56
Improving utilization and patient care . A rural hospital reduces length of stay through policy revisions and education; Cwiek MA et al.; In 1990 Saint Vincent Memorial Hospital, Taylorville, IL, intensified efforts to improve resource utilization . A program of daily case review and medical staff education has helped the hospital reduce average length of stay from between 7 and 8 days to between 5 and 6.8 days . Steps taken to achieve this include: Hiring an outside medical adviser to oversee collection and analysis of data related to length of stay and conduct case reviews Appointing a medical review officer and a physician-specific case manager Establishing a Utilization Management Task Force, which has reformed the policy concerning patients with methicillin-resistant Staphylococcus aureus to ensure discharge in a timely manner; implemented a nonacute-day reporting system; and completed a transitional care study to identify the benefits of transferring medically stable Medicare patients to the Skilled Nursing Facility.

J Antimicrob Chemother, 1992 Nov, 30(5), 587 - 96
Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus; Farmer TH et al.; Twenty one strains of Staphylococcus aureus, of varying resistance to mupirocin, were examined in order to determine the mechanism of resistance to this antibiotic; six of these strains were mupirocin sensitive (MIC 0.12-1.0 mg/L) nine moderately resistant strains (MIC 8-256 mg/L) and six highly resistant strains (MIC > 2048 mg/L) . Mupirocin showed a time-dependent inhibition of the target enzyme, isoleucyl-tRNA synthetase (IRS); incubation of the antibiotic with this enzyme before adding the substrates markedly increased inhibition in sensitive strains . The IRS I50 values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain (P < 0.01) . The mean I50 value for sensitive strains was 3.3 x 10(-2) mg/L, in moderately resistant strains it was 1.3 x 10(-1) mg/L and in highly resistant strains it was 7.5 mg/L . No degradation of mupirocin could be detected during extended incubation of the antibiotic with cell free extracts from four resistant S . aureus strains . We conclude that the production of a modified IRS enzyme is the major cause of mupirocin resistance in the strains studied.

J Rheumatol, 1992 Nov, 19(11), 1817 - 9
Klebsiella pneumoniae septic arthritis of a lumbar facet joint; Chevalier X et al.; Only 3 cases of isolated septic arthritis of a lumbar facet joint have been reported, all due to Staphylococcus aureus . We describe a case of Klebsiella pneumoniae septic arthritis of a lumbar facet joint in an HLA-B27 positive patient.

Antimicrob Agents Chemother, 1992 Nov, 36(11), 2506 - 11
Transport of pefloxacin across the bacterial cytoplasmic membrane in quinolone-susceptible Staphylococcus aureus; Furet YX et al.; Binding to phospholipids, uptake by simple diffusion, and an energy-dependent, carrier-mediated efflux are thought to characterize interactions between fluoroquinolones and bacterial cytoplasmic membranes . Here, we have found that an endogenous active efflux is unlikely in quinolone-susceptible Staphylococcus aureus . The protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), increased pefloxacin uptake in different membrane systems under conditions which excluded carrier-mediated transport, i.e., in bacterial cells at 4 degrees C and in protein-free phosphatidylglycerol liposomes . When plotted as a function of outer pH, the CCCP effect, both in S . aureus cells and in phosphatidylglycerol liposomes, correlated with pefloxacin labeling of everted S . aureus membrane vesicles, with all three profiles showing maximal effect at an acidic pH . So the CCCP effect may result not from inhibition of the proton motive force, as previously thought, but rather from acidification of the intramembrane space by the protonophore, leading to enhanced binding of the positive pefloxacin species to the inner leaflet of the bilayer . Moreover, antistaphylococcal potency and uptake profiles of pefloxacin in S . aureus and phosphatidylglycerol liposomes, assayed as a function of outer pH, peaked at a neutral pH . These observations suggest that zwitterionic and positive quinolone species are responsible for diffusion through and binding to the cytoplasmic membrane, respectively.

Eur Respir J, 1992 Nov, 5(10), 1249 - 53
Nosocomial pneumonia in critically ill comatose patients: need for a differential therapeutic approach; Rello J et al.; The purpose of this prospective clinical study was to determine the incidence, bacteriology and outcome of lower respiratory tract infections developed among 208 consecutive, critically ill comatose patients, hospitalized in a university hospital, medical-surgical intensive care unit, over a three year period . Nosocomial pneumonia developed in 53 (25%) patients after a mean of 8.1 days (range 3-31 days) . Furthermore, there were five superinfections, raising the mean incidence to 28% . One patient developed secondary bacteraemia, and another two had septic shock . Fifteen (28%) patients from the pneumonia group died, and six of these deaths were considered to be directly related to nosocomial pneumonia . Identification of the causative agent, using the protected specimen brush technique, was possible in 42 episodes; in 10 (24%) of these cases more than one microorganism was isolated . Gram-positive cocci represented 53% of isolates, and Staphylococcus aureus accounted for 78% of all Gram-positive cocci, being the most frequent microorganism in this population . In conclusion, nosocomial pneumonia is a common complication of critically ill comatose patients . Its characteristic aetiological spectrum in this population should affect antibiotic prescription . Consequently, we suggest including antimicrobial drugs which are active against S . aureus in the empirical regimen until aetiological diagnosis is established.

Nippon Saikingaku Zasshi, 1992 Nov, 47(6), 767 - 75
{Proposal for the nosocomial infection control of methicillin-resistant Staphylococcus aureus (MRSA)}; Taguchi F et al.; To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospital environments, quantitative isolation of MRSA from environmental and human specimens was performed . It was found that as many as 6 x 10(4) colony forming units (CFU)/100cm2 of MRSA and also methicillin-resistant coagulase-negative Staphylococcus (MRCNS) were isolated from 1) 25-100% of the bed-mattresses tested in 10 out of 11 (90%) hospitals, and also 2) bed sheets for patients, floors of patient wards, laundry, bath-room, toilet and laundry storage-room . And seven and eight palms of 20 patients were contaminated with MRCNS and MRSA, respectively, and MRCNS contamination was revealed in six of medical staffs . These results indicate that hospital environments, especially the mattresses and hospital floors are highly contaminated with MRCNS and MRSA, and sanitation and cleanliness of mattresses and floors are necessary to prevent the dissemination of both MRCNS and MRSA in hospital.

Curr Eye Res, 1992 Nov, 11(11), 1111 - 9
Methicillin-resistant Staphylococcus aureus keratitis in the rabbit: therapy with ciprofloxacin, vancomycin and cefazolin; Callegan MC et al.; To determine the efficacy of a fluoroquinolone antibiotic in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) keratitis, topical administration of 0.3% ciprofloxacin was compared with topical 5.0% vancomycin or 5.0% cefazolin in experimental infections in the rabbit eye . The infections were established by intrastromal injection of 100 colony forming units (CFU) of MRSA, which resulted in greater than 10(6) CFU per cornea by 12 hr postinfection . Chemotherapy (one drop every 15 min) was given from 4-9, 10-15, or 10-20 hr postinfection . Early therapy (4-9 hr postinfection) with ciprofloxacin rendered all eyes free of bacteria; ciprofloxacin was significantly more effective than vancomycin or cefazolin . When treatment was initiated 6 hr later (10-15 hr postinfection), no corneas became free of bacteria, but ciprofloxacin was again more effective than vancomycin or cefazolin . Bacterial killing by ciprofloxacin after treatment from 10-20 hr postinfection was also significantly greater than that of vancomycin . Overall, the results show that ciprofloxacin is effective in killing methicillin-resistant staphylococcus aureus, and is most effective when applied during the very early stages of infection.

Can J Microbiol, 1992 Nov, 38(11), 1097 - 101
Detection of enterotoxigenicity of Staphylococcus aureus strains: a comparative use of the modified Ouchterlony precipitation test, reversed passive latex agglutination test, and avidin-biotin ELISA; Adesiyun AA et al.; The avidin-biotin enzyme-linked immunosorbent assay (ELISA), reversed passive latex agglutination (RPLA) test, and the modified Ouchterlony precipitation test (MOPT) were compared in detecting enterotoxin production by Staphylococcus aureus strains . A total of 1015 strains isolated from human beings, animals, and foods were tested for staphylococcal enterotoxins A (SEA), B (SEB), and C (SEC) . Of these, 495 (48.8%), 467 (46.0%), and 204 (20.1%) were classified as enterotoxigenic by the ELISA, RPLA test, and MOPT, respectively . The difference in the number of strains classified as enterotoxigenic by the ELISA and RPLA test was not significant (P > or = 0.05; chi 2), but both tests detected significantly (P < 0.001; chi 2) more enterotoxigenic strains than the MOPT . The combined use of the three assay systems classified 258 (25.4%), 278 (27.4%), and 263 (25.9%) of 1015 strains tested as positive for SEA, SEB, and SEC, respectively . However, the three systems were all positive in only 29.1% of SEA-producing strains, 32.0% of SEB-producing strains, and 25.1% of SEC-producing strains . The MOPT was negative when the corresponding ELISA and RPLA test were positive (46.9% for SEA, 43.5% for SEB, and 40% for SEC); the RPLA test was negative when the corresponding ELISA was positive (10.5% for SEA, 15.5% for SEB, and 25.5% for SEC); and the ELISA was negative when the RPLA test was positive (13.6% for SEA, 9.0% for SEB, and 9.5% for SEC) . All factors considered, the RPLA test appears most suitable for quantitatively screening large numbers of strains for staphylococcal enterotoxins.

Res Vet Sci, 1992 Nov, 53(3), 346 - 53
Vaccination against experimental staphylococcal mastitis in dairy heifers; Watson DL; Vaccination-challenge experiments were carried out with dairy heifers using new, killed cell-toxoid-adjuvant Staphylococcus aureus vaccines . The organisms in the vaccines were cultured under conditions which simulated in vivo growth and induced expression of a pseudocapsule . Dextran sulphate which promotes synthesis of IgG2 antibody was included in the vaccines as the primary adjuvant . Vaccinated heifers developed very high levels of both IgG1 and IgG2 anti-pseudocapsule antibody in serum, however, titres of neutralising antibody against toxoided haemolysins were generally low . Vaccinated and unvaccinated control heifers were challenged by intramammary infusion of three virulent strains of S aureus in four experiments . Vaccinated heifers were more resistant to clinical mastitis following challenge than were controls, and the vaccinates had significantly greater milk production than controls following challenge . The most promising vaccine had dextran sulphate combined with mineral oil as the adjuvant injected intramuscularly.

J Dairy Sci, 1992 Nov, 75(11), 3185 - 90
Evaluation of a nisin-based germicidal formulation on teat skin of live cows; Sears PM et al.; A purified preparation of the nontoxic antimicrobial peptide, nisin (AMBICIN N), was used in the formulation of a germicidal sanitizer suitable for use on cow teats . The germicidal activity of the formulation against mastitis pathogens was measured on teat skin of live cows . The nisin-based formulation gave a mean log reduction of 3.90 against Staphylococcus aureus and 4.22 log reduction against Escherichia coli after exposure for 1 min to the germicide . This activity was comparable with that exhibited by a 1% iodophor teat dip but was significantly greater than that exhibited by the .1 and .5% iodophors and by the .5% chlorhexidine digluconate teat dips . The nisin-based formulation showed little or no potential for skin irritation after multiple application to skin, but iodophor and chlorhexidine digluconate teat dips showed significant potential for skin irritation in comparable studies.

J Appl Bacteriol, 1992 Nov, 73(5), 395 - 400
Evaluation of antimicrobial interactions between chlorhexidine, quaternary ammonium compounds, preservatives and excipients; Pons JL et al.; The antimicrobial interactions of 49 combinations of chlorhexidine, quaternary ammonium compounds, preservatives and excipients were evaluated by the method of Berenbaum and the checkerboard titration method, with Staphylococcus aureus CIP 53154 and Escherichia coli CIP 54127 as test strains . MIC determinations were carried out as a preliminary step, and relative growth intensity was used to describe the bacteriostatic activity of surface-active agents (Amonyl 380 BA, Amonyl 671 SB) . In the study of combinations, results were interpreted with Fractional Inhibitory Concentration indexes and represented by isobolograms . A fair correlation was shown between the method of Berenbaum and the checkerboard titration method . Combinations between chlorhexidine, cetrimonium bromide and benzalkonium chloride were synergistic or additive; combinations of antiseptics and preservatives were generally not antagonistic . The methods were also well adapted to the study of interactions involving surface-active agents, a critical problem in the formulation of topical antimicrobial agents.

J Appl Bacteriol, 1992 Nov, 73(5), 388 - 94
A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey; Willix DJ et al.; Both honey and sugar are used with good effect as dressings for wounds and ulcers . The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources . Manuka honey is known to have a high level of the latter . Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide . Honeys with activity in the middle of the normal range were used . A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species . The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h . The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).

Am Rev Respir Dis, 1992 Nov, 146(5 Pt 1), 1279 - 86
The effect of aerosolized recombinant human granulocyte macrophage colony-stimulating factor on lung leukocytes in nonhuman primates; Rose RM et al.; The number and function of myeloid cells in the lungs are critical determinants of health and disease . To examine whether these cells can be modulated in vivo by a colony-stimulating factor (CSF), recombinant human granulocyte macrophage-CSF (GM-CSF) was given to cynomolgus monkeys by either continuous intravenous infusion (7,200 U/kg/day) for 2 wk or by aerosol exposure to 10(7) U on 1 or 2 consecutive days . At intervals after the initiation of GM-CSF administration, animals underwent bronchoalveolar lavage (BAL) and had peripheral blood sampled to characterize changes in lung and circulating phagocytic cells . Compared with animals exposed to bovine serum albumin, there was an increase in the total number of BAL cells retrieved . This increase was greatest in animals receiving aerosolized GM-CSF, and it was the result of more macrophages and neutrophils . Both lung macrophages and blood neutrophils from animals exposed to aerosolized GM-CSF exhibited an augmented respiratory burst in response to phorbol myristate acetate . Lung macrophages from GM-CSF-exposed animals exhibited increased capacity to bind and/or ingest opsonized and unopsonized Staphylococcus aureus . Despite functional activation of lung phagocytic cells, biochemical analyses of BAL fluid for markers of lung injury revealed an increase in only some parameters in the GM-CSF group . Intravenous administration of GM-CSF had the expected effect on augmenting the number of myeloid cells in the bloodstream . Aerosolized GM-CSF produced a transient effect on circulating myeloid cell number between 3 and 5 days after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Poult Sci, 1992 Nov, 71(11), 1873 - 8
Differential resistance to Staphylococcus aureus challenge in major histocompatibility (B) complex congenic lines; Cotter PF et al.; Ten inbred B-congenic Leghorn lines were challenged with two isolates of Staphylococcus aureus at 3 days and 6 wk of age . Significant differences in mortality were observed among such lines when challenged at 3 days with either S . aureus Isolate P4L (moderately pathogenic) or S . aureus Isolate 3727 (highly pathogenic) . Line 331 (B2/B2 genotype) had lower mortality than either Line 004 (B17/B17, chi 2 = 4.13, P < .05) or Line 253 (B18/B18, chi 2 = 4.23, P < .05) challenged with Isolate P4L . The use of a susceptibility index allowed for the detection of additional differences among the various lines challenged by Isolate 3727 . Line 336 (BQ/BQ) was more resistant than either Line 335 (B19/B19, P < .01) or Line 330 (B21/B21, P < .01) . No significant differences were found among the lines challenged at 6 wk by either isolate . The results provide additional evidence for the importance of the B complex in genetically determined disease resistance, and further demonstrate the usefulness of congenic lines in such investigations.

J Clin Invest, 1992 Nov, 90(5), 1978 - 83
Alterations in the protein composition of maturing phagosomes; Pitt A et al.; We investigated the protein composition of J774-E clone macrophage phagosomes isolated at different stages of phagolysosome biogenesis . Phagosomes formed by internalizing antibody-coated Staphylococcus aureus for 3 min followed by chase for 0, 4, 9, or 15 min were isolated by density gradient centrifugation . Enrichment and purity of the phagosome preparations were quantitated by radiolabeled ligand recovery, enzyme markers, and electron microscopy . One-dimensional SDS-PAGE analyses of the isolated phagosomes revealed virtually identical protein compositions . However, Western blot analyses with antibodies directed against selected proteins of known itineraries along the endocytic pathway demonstrated distinct differences in phagosome protein compositions . Accumulating within the maturing phagosome were the 31-kD subunit of the vacuolar proton pump, cathepsin D,beta-glucuronidase, the cation dependent mannose 6-phosphate receptor, and LAMP-1 . Decreasing within the maturing phagosome were the FcII receptor, the mannose receptor, and alpha-adaptin . These results indicate that although the macrophage phagosome's total protein composition changes little during phagolysosome formation, the maturing phagosome both receives and eliminates, possibly by protein recycling, specific membrane and sequestered proteins.

Clin Geriatr Med, 1992 Nov, 8(4), 853 - 68
Methicillin-resistant Staphylococcus aureus infection; Bradley SF; Elderly patients with chronic illnesses are at increased risk of becoming colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA) . Therapeutic choices for the treatment of MRSA have been limited by the ever-expanding resistance of organisms and drug toxicity . In hospitals, the MRSA carrier state has been associated with increased risk of infection and possible dissemination of the organism to other patients . The epidemiology of MRSA and its significance in long-term care have been less well defined . Isolation procedures and steps to contain or eradicate MRSA should be accommodated to the individual needs of the facility and its resources.

J Infect Dis, 1992 Nov, 166(5), 1066 - 72
Characterization of Staphylococcus aureus isolates with decreased susceptibility to vancomycin and teicoplanin: isolation and purification of a constitutively produced protein associated with decreased susceptibility; Daum RS et al.; "Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin . A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives . This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution . Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media . Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity . The mechanism of decreased susceptibility to glycopeptide antibiotics among S . aureus derivative isolates is uncertain . The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

J Bacteriol, 1992 Nov, 174(21), 7044 - 7
Regulation of the Staphylococcus aureus plasmid pI258 mercury resistance operon; Chu L et al.; Experiments involving fusion between the Staphylococcus aureus plasmid pI258-encoded mer operon and the reporter gene beta-lactamase, mutational analysis, and trans-complementation studies have shown that the merR gene of pI258, which shows DNA sequence similarity with known merR genes from other bacteria, regulates the expression of the mer operon in vivo . The merR gene product is a trans-acting protein that activates mer operon transcription in the presence of the inducers Hg2+ and Cd2+ . A glutathione-S-transferase-MerR fusion protein specifically bound and protected a 27-nucleotide operator sequence from DNase I digestion . This operator sequence is highly homologous with mer operator sequences of other known systems.

Eur J Immunol, 1992 Nov, 22(11), 2831 - 9
Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens; Defrance T et al.; The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors . In man, on average, 30% of the tonsillar B cell pool expresses this antigen . In the present report, a detailed comparison of the CD5+ and CD5- B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken . CD5+ B cells were positively selected by panning or by sorting from tonsils . Two-color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells . CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti-IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13-acetate (PMA) . The growth-response of small dense CD5- B cells to these T cell-independent mitogens was comparable to that of CD5+ B cells, whereas the low-density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig-cross-linking agents and PMA . Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)-2 and IL-4 . When used in co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects . CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co-cultured with SAC or cross-linked anti-CD40 antibodies and IL-2 . However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5- B cells.

Appl Microbiol Biotechnol, 1992 Nov, 38(2), 220 - 5
Continuous production of restriction endonucleases: continuous two-stage cultivation with E . coli JM103; continuous cell disintegration and purification by affinity chromatography; Beer HD et al.; The optimization of the production of recombinant DNA-derived proteins in Escherichia coli was investigated . We chose restriction endonucleases EcoRI and EcoRV from E . coli as model proteins, despite the observation that overproduction can result in a toxic effect to the cells . The enzymes were expressed as fusion proteins consisting of protein A from Staphylococcus aureus and the desired enzyme in order to facilitate purification . The expression of the fusion protein was induced by a temperature shift using the pR promoter of phage lambda regulated by the repressor plasmid pRK248cI . Data from batch fermentations provided the basis for planning a continuous two-stage fermentation . The EcoRI enzyme activity was investigated as a function of the induction time after cell disintegration and allowed an estimation of yield of the continuous culture . Plasmid instability, which was only observed under continuous conditions, could be prevented by adding tetracycline (resistance of the repressor plasmid) to the medium . We established a continuous cell disintegration system and purified the fusion protein semicontinuously by affinity chromatography . The biological activity of the fusion protein was the same as the native endonuclease so there was no need for cleavage of the fusion protein and the product could be used without further processing.

J Hosp Infect, 1992 Nov, 22 Suppl A, 43 - 50
Postoperative complications due to methicillin-resistant Staphylococcus aureus (MRSA) in an elderly patient: management and control of MRSA; Emmerson AM et al.; An elderly lady was admitted to hospital for elective resection of an adenocarcinoma of the colon . Following an anastomotic leak she developed intra-abdominal sepsis and underwent abdominal drainage of pus . During recovery from her second operation, she developed pneumonia and a bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) . She was treated with vancomycin and co-trimoxazole and survived without further sequelae . Details of the development and treatment of this case are discussed . Procedures for the control and eradication of MRSA infections in hospitals are reviewed.

J Hosp Infect, 1992 Nov, 22(3), 207 - 15
Long-term carriage, and transmission of methicillin-resistant Staphylococcus aureus after discharge from hospital; Frenay HM et al.; The purpose of this study was to determine whether patients who become carriers of methicillin-resistant Staphylococcus aureus (MRSA) during their stay in hospital, remain colonized after discharge . Thirty-six patients colonized with MRSA during one of three outbreaks at Utrecht University Hospital (1986-89) were screened 2 or 3 years after they had become carriers . Patients were also interviewed to determine factors contributing to persistent carriage, such as antibiotics, re-admissions to the hospital, presence of skin lesions and chronic diseases . At the same time transmission of MRSA to family members was determined . The epidemic MRSA strain was still found in three patients (8%) . One was a cystic fibrosis patient who had had frequent re-admissions to the hospital and had received several course of antibiotic treatment . Both of the other patients had skin lesions: a fistula and a colostomy respectively . None of the 44 family members of the patients was colonized or infected with MRSA . We conclude that long-term MRSA carriage occurs with low frequency and is comparable to persistent carriage of methicillin-sensitive Staphylococcus aureus (MSSA) . Transmission of MRSA to healthy individuals in an antibiotic-free environment is a rare event.

J Hosp Infect, 1992 Nov, 22(3), 197 - 205
Multiresistant Klebsiella pneumoniae in a neonatal nursery: the importance of maintenance of infection control policies and procedures in the prevention of outbreaks; Coovadia YM et al.; During a 3-week period, nine babies in the neonatal unit of a large teaching hospital in Durban were infected or colonized with Klebsiella pneumoniae resistant to a range of antimicrobial agents including amikacin and cefotaxime . Resistance to cefotaxime was reduced by clavulanic acid in vitro suggesting production of extended-spectrum beta-lactamase activity . All the isolates had the same antibiotic resistance profile, belonged to the same serotype (K17), were non-typable with bacteriophages, and had identical plasmid profiles indicating that they belonged to the same strain . During a 1-day microbiological survey of the ward, the outbreak strain was isolated from the nose and hands of a doctor based in the nursery and from the hands of a nurse and the mother of an infected baby . The strain was also isolated from nine of 67 environmental samples . Investigation revealed that infection control practices which had been instituted following a previous outbreak in the nursery with multi-resistant methicillin-resistant Staphylococcus aureus (MRSA) were not being adhered to . The re-introduction and strict enforcement of these procedures under the supervision of an Infection Control Nurse resulted in the abrupt end of the outbreak.

J Exp Med, 1992 Nov 1, 176(5), 1387 - 98
Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells; D'Andrea A et al.; Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35 . NKSF/IL-12 has multiple effects on T and NK cells and was originally identified and purified from the supernatant fluid of Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cell lines . We have produced a panel of monoclonal antibodies against both chains of NKSF/IL-12 . Some of these antibodies have neutralizing activity, and several combinations of them have been used to establish sensitive radioimmunoassays detecting the free p40 chain, the free p35 chain, or the p70 heterodimer . Using these reagents, we have determined that most EBV-transformed human B lymphoblastoid cell lines constitutively produce low levels of the p70 heterodimer and an excess of the free p40 chain, whereas Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived cell lines produce neither . Production of both p40 and p70 is increased several-fold upon stimulation of the EBV-transformed cell lines with phorbol diesters . The ability of supernatant fluids from unstimulated and phorbol diester-stimulated cell lines to induce interferon gamma (IFN-gamma) production from T and NK cells, one of the effects of NKSF/IL-12, parallels the levels of production of the p70 heterodimer, known to be the biologically active form of NKSF/IL-12 . Staphylococcus aureus Cowan I strain (SAC) and other stimuli induce accumulation of p40 mRNA and production of both p40 and p70 by peripheral blood mononuclear cells (PBMC) . The producer cells appear to include both adherent cells and nonadherent lymphocytes, possibly B cells . The supernatant fluids from SAC-stimulated PBMC mediate the typical functions of NKSF/IL-12 (i.e., IFN-gamma induction, mitogenic effects on T/NK blasts, enhancement of NK cell cytotoxicity) at concentrations of p70 similar to those at which recombinant NKSF/IL-12 mediates the same functions . Moreover, these activities are significantly inhibited by anti-NKSF/IL-12 antibodies . The neutralizing anti-NKSF/IL-12 antibodies also inhibit 85% of the IFN-gamma production in response to SAC, an NKSF/IL-12 inducer, and approximately 50% of the IFN-gamma production in response to non-NKSF/IL-12-inducers such as IL-2, phytohemagglutinin, and anti-CD3 antibodies . These results indicate that induced or constitutively produced NKSF/IL-12 has a major role in facilitating IFN-gamma production by peripheral blood lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Arq Bras Cardiol, 1992 Nov, 59(5), 379 - 83
{Meningitis and other neurological complications in infectious endocarditis}; Jorge Sdo C et al.; PURPOSE--To study the localization, etiological agents and the respective prognosis in patients with infective endocarditis with or without neurological complications, with emphasis on the association of endocarditis and meningitis . METHODS--222 patients with clinical, echocardiographic and laboratory diagnosis of infective endocarditis were treated at Instituto Dante Pazzanese de Cardiologia from 1985 to 1990 . They were classified in two groups: group A-116 patients without neurological complications, ages 4 months-76 (mean 30) years old and 66.3% males . group B-56 patients with neurological complication, ages 1-71 (mean 31) years old and 46.4% males . A third group, group C, comprised 17 patients, ages 8-51 (mean 23.7) years old and 9 patients (52.9%) male, assisted at Hospital Emilio Ribas, which is specialized at infectious diseases, which presented meningitis as the unique manifestation of neurological complication associated to the diagnosis of infective endocarditis (IE) . In all patients the diagnosis of IE was based on the presence of at least two of three essential findings: echocardiogram with vegetations or valvar dysfunctions, positive hemocultures and the compatible clinical picture . For the comparative analysis among the groups was employed through the chi-square test corrected according to Yates . RESULTS--No differences of sex and age of the patients were found among the three groups . Predominated the Staphylococcus aureus as etiological agent . The localization of cardiac lesions was similar in the three groups, except for the tricuspid valve affected in 16.3% of patients of group A and 2.3% of group B . There was a greater association of the structures on the left side of the heart with IE of group B (p < 0.05) . Group B and C showed a general mortality rate greater than group A (p < 0.001) . CONCLUSION--Meningitis and other neurological complications showed interrelationship between the presence of "Staphylococcus aureus" as etiological agent of endocarditis and the association with infection of the left heart side.

Rev Hosp Clin Fac Med Sao Paulo, 1992 Nov-Dec, 47(6), 285 - 9
{Toxic shock syndrome after reduction mammaplasty: a case report}; de Almeida OM et al.; The clinical features of the toxic shock syndrome are well established . It is rapidly developing disease and may be lethal if not recognized and treated in time . Once the syndrome was associated with the use of tampon by menstruating women . Recently this syndrome has been reported as due to Staphylococcus aureus infection . A severe case of toxic shock syndrome in a 18-years-old patient after reduction mammoplasty is reported, and the importance of an early diagnosis is emphasized.

J Periodontol, 1992 Nov, 63(11), 908 - 13
Refractory periodontitis associated with abnormal polymorphonuclear leukocyte phagocytosis and cigarette smoking; MacFarlane GD et al.; To learn if refractory periodontitis may be associated with defects in peripheral blood polymorphonuclear leukocyte (PMN) function, phagocytosis and chemotaxis were analyzed in 31 otherwise healthy patients and 12 unaffected controls . When compared to controls, no chemotactic defects to 10 nM f-Met-Leu-Phe (fMLP) were detected . In contrast, phagocytosis was significantly impaired (P < 0.001) . The mean rates of adhesion and ingestion of opsonized Staphylococcus aureus by PMNs were 7.1 +/- 1.7 (+/- SD) and 1.4 +/- 0.5 bacteria/100 PMNs/minute respectively for patients, and 11.0 +/- 2.4 and 3.1 +/- 0.6 for unaffected, healthy controls . While the quality of oral hygiene and access to dental care were high, a retrospective search for associated environmental variables showed that 90% (28 of 31) of the refractory patients were smokers . The frequency of smokers is particularly striking, since only 21% of adults in Minnesota use tobacco regularly . These data suggest that there is a strong association between a peripheral blood PMN defect and refractory periodontitis . Furthermore, these studies suggest that tobacco use may contribute to this association.

Am J Physiol, 1992 Nov, 263(5 Pt 2), H1430 - 6
Expression of Na(+)-K(+)-ATPase alpha 1- and alpha 3-isoforms in adult and neonatal ferret hearts; Ng YC et al.; We have demonstrated previously that in adult ferret heart two alpha-subunit isoforms of the Na(+)-K(+)-ATPase, alpha(+) and alpha, are expressed . The alpha(+)-isoform may comprise either alpha 2-, or alpha 3-, or both isoforms . The present studies further characterize the alpha(+)-isoform . The alpha(+)-isoform of ferret heart did not react with an alpha 2-specific monoclonal antibody, but rather with two different alpha 3-specific polyclonal antibodies . Electrophoretic mobility of the alpha(+)-isoform in sodium dodecyl sulfate polyacrylamide gel electrophoresis is slower than that of the alpha 2-isoform, but similar to that of the alpha 3-isoform . Limited proteolytic peptide mapping was performed using Staphylococcus aureus V8 . Proteolytic fragments were then immunostained with an alpha 3-specific antibody . The peptide maps of ferret heart alpha(+)-isoform and rat brain alpha 3-isoform were identical, as were those of ferret heart alpha(+)-isoform and ferret brain alpha 3-isoform . These results indicate that the alpha(+)-isoform of ferret heart is an alpha 3-isoform . During postnatal development, the same isoforms expressed in the adult ferret heart (alpha 1 and alpha 3), were also expressed in neonatal heart . In adult or neonatal heart alpha 2-isoform was not detectable . Relative abundances of the isoforms in ventricular and atrial tissues differed . Compared with ventricular tissue, left and right atrial tissues expressed much less alpha 3 than alpha 1 . It is concluded that, unlike rat heart, alpha 1- and alpha 3-isoforms are expressed in adult ferret heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Infection, 1992 Nov-Dec, 20(6), 332 - 5
Carriage of methicillin-resistant Staphylococcus aureus by non-hospitalized subjects in Israel; Dan M et al.; The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the anterior nares and axilla was studied in 920 non-hospitalized subjects: 350 drug addicts, 350 individuals presenting at a hospital emergency room for various reasons, and 220 hospital health care workers . S . aureus was isolated from 105 (11.4%) subjects, in six (6.3%) of whom the isolates were methicillin-resistant . The isolation rate of the organism and the prevalence of resistant strains in the different subgroups were, respectively: drug-addicts, n = 32 (9.1%), n = 2 (6.9%); emergency room patients, n = 36 (10.2%), n = 1 (3.2%); and hospital health care workers, n = 37 (16.8%), n = 3 (8.5%) . Our findings suggest that MRSA remains uncommon in the community, while the prevalence of S . aureus carriage (including methicillin-resistant strains) in hospital personnel is quite similar in divergent geographical areas.

Cytokine, 1992 Nov, 4(6), 513 - 9
Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines; Bjork L et al.; The effects of Staphylococcus aureus enterotoxin A (SEA) and lipopolysaccharide (LPS) in cytokine production were assessed at the single cell level in cells obtained from healthy blood donors . Cytokine production was studied with UV-microscopy of fixed and permeabilized cells stained with cytokine specific monoclonal antibodies . The cytokines evaluated included tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-2, IL-4, interferon (IFN)-gamma and TNF-beta . LPS exhibited marked production of IL-1 alpha, IL-1 beta, TNF-alpha, IL-6 and IL-8 . After LPS stimulation IL-1 alpha, IL-1 beta, TNF-alpha and IL-8 were the dominating products, all peaking at or before 4 hours after cell stimulation . In addition, IL-10 production was evident after 12 hours of cell stimulation . The T-lymphocyte-derived cytokines TNF-beta, IL-2, IFN-gamma and IL-4 were never detected in the cultures . All cytokine production, except IL-8, was downregulated at 96 hours . In contrast, peak production of IL-1 alpha, IL-1 beta and IL-8, which were the dominant products, occurred after 12 hours in the SEA-stimulated cultures . Further, a significant T-lymphocyte production of TNF-beta, TNF-alpha, IFN-gamma and IL-2 was found with peak production 12-48 hours after initiation . Only low amounts of IL-6 were evident . The two types of cytokine pattern and kinetics found may correspond to the different clinical conditions after invasive Gram-negative Escherichia coli vs Gram-positive Staphylococcus aureus infections in humans, with a much more rapid onset of disease after E . coli infections.(ABSTRACT TRUNCATED AT 250 WORDS)

J Indian Med Assoc, 1992 Nov, 90(11), 290 - 2
Septic cavernous sinus thrombophlebitis: a review of 35 cases; Thatai D et al.; Thirty-five cases of septic cavernous sinus thrombophlebitis seen over the past 5 years are reviewed . Of these 80% were secondary to infection of the medial 1/3rd of the face . In more than 2/3rds of the cases the infecting organism was Staphylococcus aureus . Even with appropriate antibiotic therapy the overall mortality was 34.3%.

J Biol Chem, 1992 Oct 25, 267(30), 21782 - 6
Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin examined by truncation mutagenesis; Walker B et al.; The alpha-hemolysin (alpha HL) from Staphylococcus aureus causes the lysis of susceptible cells such as rabbit erythrocytes (rRBCs) . Lysis is associated with the formation of a hexameric pore in the plasma membrane . Here we show that truncation mutants of alpha HL missing 2 to 22 N-terminal amino acids form oligomers on the surfaces of rRBCs but fail to lyse the cells . By contrast, mutants missing 3 or 5 amino acids at the C terminus are very inefficient at oligomerization but do lyse rRBCs, albeit extremely slowly . The C-terminal truncation mutants, retarded as monomers on the cell surface, undergo a conformational change in which the protease-sensitive loop located near the midpoint of the polypeptide chain becomes occluded . Judged by this criterion, polypeptides truncated at the N terminus, frozen as nonlytic oligomers, are in a similar conformation . A second proteolytic site near the N terminus of the polypeptide becomes inaccessible in the lytic pore formed by the wild-type polypeptide, supporting the idea that a second conformational change occurs upon pore formation . These findings suggest a pathway for assembly of the lytic pore in which alpha HL first binds to target cells as a monomer, which is converted to a nonlytic oligomeric intermediate before formation of the pore . In keeping with this model, an N-terminal truncation mutant blocks the slow lysis induced by a C-terminal truncation mutant, presumably by diverting the weakly lytic subunits into inactive oligomers.

J Biol Chem, 1992 Oct 25, 267(30), 21678 - 84
Purification and initial characterization of the proteasome from the higher plant Spinacia oleracea; Ozaki M et al.; The proteasome (multicatalytic protease complex), a high molecular weight protein complex, has been purified from spinach leaves by successive chromatography on DEAE-cellulose, Bio-Gel A-1.5m, DEAE-TOYOPEARL 650C, and DEAE-5PW . The molecular mass was estimated to be 850 kDa by gel filtration . Polyacrylamide gel electrophoresis of the proteasome gave a single protein band under nondenaturing conditions and at least 10 bands in the range of 21-32 kDa in the presence of sodium dodecyl sulfate . By electron microscopy after negative staining with uranyl acetate, the proteasome from spinach appeared as symmetrical ring-shaped particles . The substrate specificity of proteasomes indicates that they contain at least three types of activity, namely, chymotrypsin-like, Staphylococcus aureus V8 protease-like, and trypsin-like activities . The former two activities were enhanced by poly-L-lysine or sodium dodecyl sulfate . Moreover, we examined the immunological reactivities of proteasomes from various eukaryotes . As a result, cross-immunoreactivities of some subunits were observed . These properties of the proteasome are similar to those of proteasomes isolated from various other eukaryotic sources.

FEMS Microbiol Lett, 1992 Oct 15, 76(3), 243 - 8
Conjugative trimethoprim resistance in Staphylococcus aureus; Udo EE et al.; A multiply resistant Staphylococcus aureus isolate, WBG7410, harbours plasmids of 38, 26, 2.8, 2.4 and 1.9 kb and transfers trimethoprim and kanamycin resistance at high frequencies by conjugation . The transconjugants contained the 38-kb plasmid, pWBG707, and the 2.8-kb plasmid . Plasmid pWBG707 was shown to encode trimethoprim resistance, was conjugative and mobilised at high frequencies the 2.8-kb plasmid which presumably encodes kanamycin resistance . Plasmid pWBG707 was isolated mostly in the open circular form and analysis with EcoRI restriction endonuclease suggests that pWBG707 is a new conjugative plasmid distinct from the other conjugative plasmids reported in S . aureus.

FEMS Microbiol Lett, 1992 Oct 15, 76(3), 221 - 6
Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains; Najioullah F et al.; The effects of fosfomycin on penicillin-binding proteins (PBPs) were studied on the methicillin-resistant Staphylococcus aureus strain CIP (Collection de l'Institut Pasteur, Paris, France) 65-25 and on a methicillin-susceptible S . aureus strain CIP 65-6 . The combinations of fosfomycin and oxacillin were synergistic, additive or antagonistic, depending on antibiotic concentrations . Fosfomycin induced modifications of the PBP profile of the two strains studied . In particular, it increased the expression of PBP2 . This suggested that this protein is inducible; the only PBP not affected by fosfomycin was PBP3.

Proc Natl Acad Sci U S A, 1992 Oct 15, 89(20), 9474 - 8
Reduction of arsenate to arsenite by the ArsC protein of the arsenic resistance operon of Staphylococcus aureus plasmid pI258; Ji G et al.; The arsenic resistance operon of Staphylococcus aureus plasmid pI258 consists of three genes, arsR (encoding the repressor regulatory protein), arsB (the determinant of the membrane efflux protein that confers resistance by pumping arsenic from the cells), and arsC (the small gene whose protein product is required for arsenate resistance only, not for arsenite resistance) . ArsC has now been shown to be an arsenate reductase, converting intracellular arsenate {As(V)} to arsenite {As(III)}, which is then exported from the cells by an energy-dependent efflux process . The arsenate reductase activity was found in the soluble cytoplasmic fraction in Escherichia coli (and not associated with the periplasmic fraction or the sedimentable cell envelope) . Purified ArsC protein coupled in vitro with thioredoxin plus dithiothreitol (but not 2-mercaptoethanol or reduced glutathione) to reduce arsenate to arsenite.

J Immunol, 1992 Oct 15, 149(8), 2742 - 8
Regulation of paf-acether receptor expression in human B cells; Nguer CM et al.; Paf-acether (paf) is a phospholipid cytokine alloted with potent inflammatory and immunoregulatory properties . Recent reports indicated that in human B cell lines, paf modulated both early and late activation events . In our study, we showed that four of six human B cell lines specifically bound {3H}paf irrespective of the stage of differentiation, the presence of EBV genome or cell surface phenotype . Binding was saturated and fit a one receptor model with a dissociation constant ranging from 1 to 6 nM and a number of sites per cell ranging from approximately equal to 4000 in Rjc13 to approximately equal to 30,000 in Raji or IM9 . In addition, our data indicate that 1) maximal expression occurred during the log phase growth; 2) paf itself (10-100 nM) or rIL-4 (100 U/ml) up-regulated by two- to threefold the number of paf binding sites without affecting the affinity . Finally, we found that activated normal B lymphocytes exhibited a higher capacity than resting B cells to incorporate and metabolize {3H}paf at 37 degrees C . Resting B lymphocytes lacked specific binding capacity for paf, yet specific paf receptors were induced upon stimulation via Staphylococcus aureus Cowan I or phorbol 12,13 dibutyrate plus ionomycin . These results suggest that B cell activation is a critical event for paf receptor expression and modulation.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2233 - 8
Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate; Jaresko GS et al.; Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections . Their activities have been compared in vitro but not in vivo . In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects . Concentrations of the antimicrobial agents in serum and suction-induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively . The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis . Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations . Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding . The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5 . Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid . The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S . aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K . pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin.

J Trauma, 1992 Oct, 33(4), 568 - 73
Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody; Hinshaw LB et al.; A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved . The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF) . The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S . aureus, 4 x 10(10) colony forming units/kilogram . The baboons infused with S . aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time . Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6 . Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.

J Infect Dis, 1992 Oct, 166(4), 911 - 5
Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylococcus aureus isolates; Lee VT et al.; The association between staphylococcal enterotoxin (SE) B and toxic shock syndrome (TSS) toxin 1 (TSST-1) in menstrual and nonmenstrual TSS was examined . Production of SEB and TSST-1 in the culture supernatants from 344 Staphylococcus aureus isolates was quantitated by noncompetitive ELISA (lower detection limit, 0.5 ng/mL for both assays) . In the ELISA for SEB, cross-reactive antibodies to SEC were removed by absorption in a biotin-streptavidin-agarose column (SEC1 at concentrations to 100,000 ng/mL could not be detected) . Among TSST-1-negative isolates, SEB production in nonmenstrual TSS isolates (8/13, 62%) was more prevalent than that in either menstrual TSS isolates (1/4; P = .3), non-TSS infections (15/103, 15%; P less than .001), or asymptomatic carriers (14/105, 13%; P less than .001) . Expression of SEB and TSST-1 was usually mutually exclusive (only 1.5% of 344 isolates produced both SEB and TSST-1) . Multilocus enzyme electrophoretic typing (ET) suggested a clonal origin for both SEB-(55% of ET-5) and TSST-1 (76% of ET-19)-producing isolates . Thus, SEB may be an important cause in TSS where TSST-1 is not elaborated, especially in nonmenstrual TSS isolates.

Ann Intern Med, 1992 Oct 1, 117(7), 560 - 6
Right-sided endocarditis in intravenous drug users . Prognostic features in 102 episodes; Hecht SR et al.; OBJECTIVE: To describe the clinical, laboratory, and echocardiographic findings in a large group of patients with right-sided endocarditis and to determine whether any of these findings is predictive of prognosis . DESIGN: Retrospective survey of medical records to evaluate the course of hospitalization with follow-up on 6-month survival . Review of two-dimensional echocardiograms by an observer blinded to clinical information . SETTING: Large, metropolitan, voluntary hospital . PATIENTS: One hundred twenty-one intravenous drug users with clinical and bacteriologic evidence of 132 episodes of endocarditis . The presence of a right-sided valvular vegetation detected by two-dimensional echocardiography was required for entry into the study . MEASUREMENTS AND RESULTS: Staphylococcus aureus was the most common infecting organism (82%, 108 of 132) . Vegetations involved the tricuspid valve in 127 episodes, the pulmonic in 4, and both in 1; they ranged in size from 0.4 to 4.3 cm (mean, 1.5 +/- 0.7 cm) . Vegetations greater than 1.0 cm were present in 106 cases (80%) . Among patients with isolated native right-sided endocarditis who reached a definite end point in treatment, mortality was 7% (7 of 98) . Vegetations greater than 2.0 cm were associated with a significantly higher mortality compared with vegetations of 2.0 cm or less (33% compared with 1.3%, P less than 0.001) . CONCLUSIONS: Overall, right-sided endocarditis has a favorable prognosis . Although complications and prolonged fever are common, most cases respond to medical therapy . Our findings suggest that vegetation size may be an important predictor of outcome and that vegetations greater than 2.0 cm are associated with increased mortality.

J Biochem Biophys Methods, 1992 Oct, 25(2-3), 83 - 94
A fluorimetric assay for the effects of cytolytic toxins on the transport properties of resealed erythrocyte ghosts; Dalla Serra M et al.; We prepared resealed erythrocyte ghosts loaded with SPQ and chloride . We demonstrated that these membranes were still functional, as they were capable of exchanging anions, most probably through the band-3 protein . When cytolytic toxins (Escherichia coli hemolysin and Staphylococcus aureus alpha-toxin) were offered to the resealed ghosts, the internal SPQ was released . This could be attributed to the formation of toxin-induced ion channels into the ghost membrane that were so large that SPQ could escape through them . This release was actually independent of the anion-exchanging protein, since DIDS had no inhibitory effect on it . Due to their simplicity, and because they do not lyse, erythrocyte ghosts may serve as useful models to study the action of cytolytic pore-forming toxins . To assess the validity of these model membranes we compared results obtained using RBC and resealed erythrocyte ghosts as targets for the toxin, finding complete consistency . Pre-assembled toxin channels could also be studied on the ghosts . Applying different proteolytic enzymes to the external compartment after channel formation, we found that performed E . coli hemolysin pores were at least partially destroyed by enzymatic digestion.

J Biochem (Tokyo), 1992 Oct, 112(4), 557 - 61
Identification of the disulfide bonds in human plasma protein SP-40,40 (apolipoprotein-J); Choi-Miura NH et al.; SP-40,40, a human plasma protein, is a modulator of the membrane attack complex formation of the complement system as well as a subcomponent of high-density lipoproteins . In the present study, the positions of the disulfide bonds in SP-40,40 were determined . SP-40,40 was purified from human seminal plasma by affinity chromatography using an anti-SP-40,40 monoclonal antibody and reversed-phase, high-performance liquid chromatography (HPLC) . The protein was digested with trypsin and the fragments were separated by reversed-phase HPLC . The peptides containing disulfide bonds were fluorophotometrically detected with 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F) . The peptides containing more than two disulfide bonds were further digested with Staphylococcus aureus V8 protease and lysylendopeptidase, and the fragments were isolated by HPLC . The amino acid compositions and the amino acid sequences of the peptides containing only a disulfide bond were determined . Disulfide bonds thus determined were between Cys58(alpha)-Cys107(beta), Cys68(alpha)-Cys99(beta), Cys75(alpha)-Cys94(beta), and Cys86(alpha)-Cys80(beta) . Since there was no free sulfhydryl groups in the SP-40,40 molecule, Cys78(alpha) and Cys91(beta) should also be linked by a disulfide bond . It is notable that all of the disulfide bonds in SP-40,40 are not only formed by inter-chain pairing, but also appear to form an antiparallel ladder-like structure between the two chains . The unique structure could be related to the functions of SP-40,40.

J Antimicrob Chemother, 1992 Oct, 30(4), 489 - 96
Frequencies of subpopulations of aminoglycoside- and vancomycin-resistant variants in Staphylococcus aureus and Staphylococcus epidermidis; Radberg G et al.; Selection and regrowth of resistant variants, which are present in low frequencies in the initial inoculum, were seen when large inocula of five strains of Staphylococcus aureus and four strains of Staphylococcus epidermidis were incubated in broth with amikacin, gentamicin, netilmicin and tobramycin . Statistical analysis showed no significant difference between the aminoglycosides in the selective growth of resistant variants (P > 0.5) . Vancomycin differed significantly from the aminoglycosides in both the frequency of, and selection of resistant variants (P < 0.001) . No bacteria resistant to > 1 x MIC was seen in the vancomycin-exposed cultures of S . aureus and S . epidermidis, while in most aminoglycoside-exposed cultures, bacteria resistant to 4-16 x MIC were seen.

Zentralbl Bakteriol, 1992 Oct, 277(3), 309 - 19
Characterization of methicillin-susceptible and methicillin-resistant Staphylococcus aureus isolates by molecular typing methods; Kaufhold A et al.; Two groups of clinical Staphylococcus aureus isolates were examined by molecular typing methods . Detailed protocols for the technical procedures are described . By means of plasmid DNA profiles, plasmid DNA restriction enzyme digestion, as well as whole-cell DNA endonuclease digestions subjected to conventional agarose gel electrophoresis and pulsed-field gel electrophoresis, eight methicillin-susceptible S . aureus strains from three patients segregated into three different groups . Consecutive isolates from the same patient revealed identical fingerprints . Generally, good agreement between different molecular typing methods also was achieved in the investigation of 28 methicillin-resistant isolates . However, compared to whole-cell DNA restriction endonuclease analysis, plasmid DNA profiling (all but one strain had detectable plasmid DNA) showed a somewhat greater discriminatory ability . The techniques evaluated were reproducible and relatively easy to perform and provided valuable tools for studying the epidemiology of S . aureus in hospitals.

Jpn J Antibiot, 1992 Oct, 45(10), 1319 - 31
{Experimental study on intramaxillary injection of fosfomycin . Effects of fosfomycin on experimental acute sinusitis in rabbits}; Kobayashi T et al.; We studied effects of intramaxillary injection of fosfomycin (FOM) on experimental sinusitis in rabbits . The experimental sinusitis was induced by intramaxillary injection of Staphylococcus aureus to rabbits for 3 successive days . 1 . 0.5, 1, 3 or 5% FOM with saline as a control was instilled into the maxillary sinus and the maxillary sinus mucosa were examined macroscopically and light and electron microscopically . 3% and 5% FOM suppressed the damage of mucosa macroscopically and scanning electron microscopically . 2 . After administration of 3% FOM and saline twice a week, the maxillary sinus mucosa was examined macroscopically and light and electron microscopically . The maxillary sinus injected with 3% FOM showed almost normal mucosa after 2 weeks while that injected with saline showed severe mucosal damage . S . aureus were decreased by 3% FOM injection and not found in the maxillary sinus in a week . The results indicate that intramaxillary injection of FOM is very effective in the treatment of sinusitis.

Jpn J Antibiot, 1992 Oct, 45(10), 1312 - 8
{Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus . IV . Combined effects of arbekacin with cefmetazole or flomoxef}; Deguchi K et al.; Antibacterial effects of combination use of arbekacin (ABK) with cefmetazole (CMZ) or flomoxef (FMOX) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained . 1 . Antibacterial effects of combinations of ABK with CMZ and with FMOX were equally potent against MRSA at clinically expected 1 MIC of ABK in blood . However, at a sub MIC of ABK different effects were observed between the 2 combinations . The former combination was slightly less effective than the latter . 2 . In either combination the potency of the antibacterial activity was less dependent on the concentration of CMZ or FMOX, but was strongly dependent on ABK concentrations . These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs . 3 . It appears that the antibacterial activity of the combination of the sub MIC of ABK with a beta-lactam is an important point in considering the effectiveness of a combination therapy.

Jpn J Antibiot, 1992 Oct, 45(10), 1305 - 11
{Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus . III . Combined effects of arbekacin with cefotiam or cefuzonam}; Deguchi K et al.; Antibacterial effects of combination use of arbekacin (ABK) with cefotiam (CTM) or cefuzonam (CZON) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained . 1 . Antibacterial effects of combinations of ABK with CTM and with CZON were equally potent against MRSA at clinically expected 1 MIC of ABK in blood . However, at a sub MIC of ABK the different effects were observed between the 2 combinations . The antibacterial effect of the former was strong and that of the latter was a little weak . 2 . In either combination the potency of the antibacterial activity was less dependent on the concentration of CTM or CZON, but was strongly dependent on ABK concentrations . These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs . 3 . The combination use of ABK with CTM appears to be useful in cases of infection by MRSA alone while the combination use of ABK with CZON appears to be useful in cases of double infection with MRSA and Gram-negative bacterium.

Can J Vet Res, 1992 Oct, 56(4), 275 - 80
A cohort study of coagulase negative staphylococcal mastitis in selected dairy herds in Prince Edward Island; Davidson TJ et al.; The epidemiology and importance of coagulase negative staphylococcal (CNS) mastitis in Prince Edward Island had not been documented . To investigate this, a cohort of 84 cows at seven farms were quarter sampled eight times over a lactation, commencing with samples taken prior to drying off in the previous lactation . Thirteen species of CNS were isolated . The quarter prevalence of CNS mastitis varied from 4.8% to 6.4% in the first five months of lactation and increased to 14.2 to 16.6% in the last four months of lactation . The geometric mean somatic cell counts (SCC) for quarters infected with CNS and uninfected quarters were 90 x 10(3) and 64 x 10(3) respectively (difference significant at p > 0.005) . The two month new infection risk of CNS was 9.0% while the two month elimination risk was 74.4% . Infection with CNS did not alter the risk of subsequent infection with Staphylococcus aureus . The results from this project support the classification of CNS as a minor pathogen in mastitis control programs.

Infect Control Hosp Epidemiol, 1992 Oct, 13(10), 587 - 93
A comparison of clinical virulence of nosocomially acquired methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections in a university hospital; Hershow RC et al.; OBJECTIVES: To compare the clinical virulence of nosocomially acquired methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S aureus (MSSA) infections in 1989 . DESIGN: A retrospective comparison of host factors, in-hospital exposures, sites of infections, and outcomes of patients with nosocomial MRSA and MSSA infections . SETTING: University of Illinois Hospital, Chicago, Illinois . PARTICIPANTS: Forty-four adult patients with nosocomial S aureus infections . RESULTS: The 22 MRSA-infected and 22 MSSA-infected persons were similar regarding mean age, gender, underlying diseases, and exposure to surgery . Before developing infection, MRSA-infected persons were more likely to have received antibiotics (73% compared with 27%, odds ratio = 7.1, 95% confidence interval {CI95} = 2.0-25.8 p = .003) and to have stayed in the hospital > 2 weeks (64% compared with 18%, odds ratio = 7.9, CI95 = 2.0-31.6, p = .002) . Bacteremia was the most common presentation in the MRSA and MSSA groups (55% and 59%, respectively) . Infectious complications and death were infrequent in both groups . CONCLUSIONS: MRSA and MSSA strains infect patients with similar demographic features and underlying diseases, but MRSA infections are significantly more common among patients with previous antibiotic therapy and a prolonged preinfection hospital stay . Clinical presentations and outcomes did not differ significantly between the 2 groups . Thus, similar to studies in the early 1980s, our findings do not suggest greater intrinsic virulence of MRSA.

Infect Control Hosp Epidemiol, 1992 Oct, 13(10), 582 - 6
Methicillin-resistant Staphylococcus aureus in U.S . hospitals, 1975-1991; Panlilio AL et al.; OBJECTIVES: Analyze changes that have occurred among U.S . hospitals over a 17-year period, 1975 through 1991, in the percentage of Staphylococcus aureus resistant to beta-lactam antibiotics and associated with nosocomial infections . DESIGN: Retrospective review . The percentage of methicillin-resistant S aureus (MRSA) was defined as the number of S aureus isolates resistant to either methicillin, oxacillin, or nafcillin divided by the total number of S aureus isolates for which methicillin, oxacillin, or nafcillin susceptibility test results were reported to the National Nosocomial Infections Surveillance (NNIS) System . SETTING: NNIS System hospitals . RESULTS: Of the 66,132 S aureus isolates that were tested for susceptibility to methicillin, oxacillin, or nafcillin during 1975 through 1991, 6,986 (11%) were resistant to methicillin, oxacillin, or nafcillin . The percentage MRSA among all hospitals rose from 2.4% in 1975 to 29% in 1991, but the rate of increase differed significantly among 3 bed-size categories: < 200 beds, 200 to 499 beds, and > or = 500 beds . In 1991, for hospitals with < 200 beds, 14.9% of S aureus isolates were MRSA; for hospitals with 200 to 499 beds, 20.3% were MRSA; and for hospitals with > or = 500 beds, 38.3% were MRSA . The percentage MRSA in each of the bed-size categories rose above 5% at different times: in 1983, for hospitals with > or = 500 beds; in 1985, for hospitals with 200 to 499 beds; and in 1987, for hospitals with < 200 beds . CONCLUSIONS: This study suggests that hospitals of all sizes are facing the problem of MRSA, the problem appears to be increasing regardless of hospital size, and control measures advocated for MRSA appear to require re-evaluation . Further study of MRSA in hospitals would benefit our understanding of this costly pathogen.

Res Rep Health Eff Inst, 1992 Oct, (53), 1 - 39, discussion 41-9
Use of physical chemistry and in vivo exposure to investigate the toxicity of formaldehyde bound to carbonaceous particles in the murine lung; Jakab GJ et al.; Knowledge about the health effects of exposure to formaldehyde associated with automotive emissions is of pivotal importance in the risk assessment of this agent . Mobile sources emit many combustion-derived pollutants, including formaldehyde, in association with respirable carbon particles . Because it is hydrophilic, most of the inhaled formaldehyde is absorbed in the upper respiratory tract . However, if the organic vapor is adsorbed on respirable particles, formaldehyde may be deposited in the deep lung with the inhaled particles and may be available to interact adversely with cells along the lung parenchyma . On the respiratory surface, the alveolar macrophage phagocytic system plays the pivotal role in defending the lung against infectious agents . Susceptibility to respiratory infections is a relevant and sensitive indicator of the adverse effects of air pollution because acute and chronic exposures to a variety of air pollutants have been shown to decrease pulmonary antibacterial defenses . The goal of this research was to investigate whether exposure to formaldehyde decreases resistance to respiratory infections through dysfunctions of the alveolar macrophage phagocytic system . The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles . A carbon black, Regal GR, was used in these studies as a surrogate for the carbonaceous core of Diesel particulate matter . This material was selected to represent the worst-case scenario because the carbon black was expected to adsorb formaldehyde strongly . To accomplish this goal, mice were exposed to formaldehyde and to carbon black and formaldehyde combinations; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependent intrapulmonary killing of Staphylococcus aureus after an inhalation challenge with the bacterium . The salient findings of the bactericidal studies are as follows: Fifteen parts per million (ppm)* formaldehyde impaired the intrapulmonary killing of S . aureus when exposure followed the bacterial challenge . One ppm formaldehyde impaired the intrapulmonary killing of S . aureus when exposure preceded and was continued after the bacterial challenge . Coexposures to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde, or 10 mg/m3 carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect on the intrapulmonary killing of S . aureus . Preexposure for four hours per day for four days to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde had no effect on the intrapulmonary killing of S . aureus when the assay was performed one day after the cessation of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Zentralbl Veterinarmed A, 1992 Oct, 39(8), 593 - 9
Influence of medicinal herbs on phagocytosis by bovine neutrophils; Hu S et al.; Twenty-six herbal preparations made from 24 medicinal herbs, categorized as antipyretics in Chinese materia medica, were tested in vitro to determine their effects upon phagocytosis of 32P-labelled Staphylococcus aureus by neutrophils isolated from bovine blood and milk . The percentage of phagocytosis was determined after incubating (1 hour at 37 degrees C) 1.25 x 10(7) neutrophils, 1 x 10(8) 32P-labelled S . aureus and 10% skimmed milk with herbal solutions . Concentrations of herbal preparations tested were 100%, 10% and 1% (v/v) . When compared with PBSS (0.01 M phosphate buffered saline solution) controls, most of the herbs at high concentrations inhibited phagocytosis while at lower concentrations phagocytosis was increased . All 26 herbal preparations significantly increased blood neutrophil activity at their proper concentrations . The most active herbs in promoting blood neutrophil phagocytosis were observed for Herba verbenae, Flos chrysanthemi, Flos lonicerae, Radix sophorae flavescentis, Herba houttuyniae, Radix isatidis, Herba patriniae, Berberini sulfatis at the lowest concentration and for Folium hibisci at the high concentration with the increased percentage of more than 40.0% in comparison with PBSS control . Of the 19 herbal preparations tested with milk neutrophils, 18 herbs greatly increased phagocytosis at suitable concentrations . The most active preparations in stimulating milk neutrophil functions included Folium hibisci, Flos chrysanthemi, Radix bupleuri, Radix stellariae, Herba houttuyniae, Herba senecionis scandentis, Caulis lonicerae and Flos lonicerae which increased phagocytosis by over 35.0%.

Bol Med Hosp Infant Mex, 1992 Oct, 49(10), 666 - 70
{Nosocomial infection in the neonatal period at a third level care center}; Barroso-Aguirre J et al.; Results are presented on epidemiologic surveillance of nosocomial infection of all neonates attended at the Instituto Nacional de Perinatologia throughout 1988-1990, reporting rates of 2.1, 2.9 and 5.5 per 100 discharge for each of the years studied . Data are presented in full by service, showing rates of 4.7, 9.5 and 23.0 per 100 discharge in Neonatal Intensive Care Unit (NICU) and 1.5, 3.2 and 6.7 per 100 discharge for Neonatal Intermediate Care (NIC) for the same three years . With respect to type of infection, septicemia, pneumonia and conjunctivitis come as the most frequent causes of infection and Staphylococcus sp coagulase negative (30%), Staphylococcus aureus (27%) and Escherichia coli (7%) as the prevailing microorganisms in nosocomial infection.

Am J Infect Control, 1992 Oct, 20(5), 248 - 55
Emergence and control of methicillin-resistant Staphylococcus aureus in a children's hospital and pediatric long-term care facility; Stover BH et al.; BACKGROUND: After a 6-year quiescence, methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 30 patients in a children's hospital and a pediatric long-term care facility from November 1987 through April 1989 . After six nosocomial cases had occurred at the children's hospital, increased infection control measures directed at MRSA were initiated in August 1988 . Because MRSA had been identified in three patients in the pediatric long-term care facility within 24 hours of their admission to the children's hospital, other patients transferred from the pediatric long-term care facility to the children's hospital were isolated and screened for MRSA . METHODS: We reviewed the medical records of these patients and evaluated their response to therapy with rifampin alone or in combination with trimethoprim-sulfamethoxazole . RESULTS: In the 8-month period after initiation of infection control measures, MRSA was identified in 10 residents of the pediatric long-term care facility; there was also one nosocomial children's hospital case . Phage typing showed that one MRSA strain predominated in patients at the pediatric long-term care facility but did not implicate this strain as the source for MRSA introduction into the children's hospital . Of 16 patients with MRSA who completed therapy and were available for follow-up, 13 (81%) had elimination of colonization . CONCLUSION: Prompt institution of MRSA surveillance, barrier isolation, and therapy to eliminate colonization should be considered in hospitals with a new introduction of MRSA.

Am J Surg, 1992 Oct, 164(4A Suppl), 24S - 27S
A reassessment of the activity of the third-generation cephalosporins against anaerobes and Staphylococcus aureus; Canawati HN; The in vitro activity of cefotaxime (CTX) alone and in combination with its metabolite desacetylcefotaxime (dCTX) was evaluated against 106 isolates of Bacteroides species . and 32 strains of Staphylococcus aureus . All strains were recovered from infected tissues of diabetic patients . Addition of dCTX to the parent compound markedly increased the inhibitory activity against Bacteroides species in general and Bacteroides fragilis and Bacteroides vulgatus in particular . No effect of the combination of both agents on Bacteroides thetaiotaomicron or Bacteroides ovatus was observed; 50% of B . fragilis infections were susceptible to CTX alone and 81% became susceptible to CTX plus dCTX . In addition, a partial synergistic interaction against 20 strains of B . fragilis resulted in a four- to nine-fold reduction in the minimal inhibitory concentration (MIC) after dCTX was added to CTX . Interestingly, 10 of 20 strains that exhibited an MIC of 64-128 micrograms/mL with CTX alone became very susceptible after the combination of parent and metabolite . This favorable positive interaction of both agents was also observed with S . aureus; a two- to four-fold reduction in MIC values was observed when dCTX was added.

Kyobu Geka, 1992 Oct, 45(11), 985 - 90
{Treatment of postoperative mediastinitis using an omental pedicle flap}; Matsuyoshi T et al.; Four patients with postoperative mediastinitis who were treated by omentopexy at the Fukuoka University Hospital between 1989 and 1990 . Three of the 4 patients healed successfully, another one died of multiple organ failure 83 days after surgery . All patients were received coronary artery bypass surgery harvesting a left internal thoracic artery for ischemic heart disease . Three patients had diabetes mellitus, one patient had renal failure preoperatively . Recognition of mediastinitis was made by sternal wound purulent discharge and sternal dehiscence . Culture of the discharge fluid yielded methicillin-resistant Staphylococcus aureus in three, and Enterococcus cloacae in one . Irrigation with popidone-iodine or blonopol were ineffective . Thus, the wound was treated with debridement and omentopexy with an omental pedicle flap, respectively . Postoperative course after omentopexy were excellent, had no complications . We conclude that the omentopexy is useful in the treatment of postoperative refractory anterior mediastinitis.

An Med Interna, 1992 Oct, 9(10), 473 - 7
{Infectious endocarditis in parenteral drug addicts: study of 57 cases}; Gabriel Botella F et al.; We present 57 cases of infectious endocarditis (IE) in 51 parenterally drug addicts (PDA) admitted at the Internal Medicine Service of the Hospital Clinico of Valencia between January ist, 1988 and January 15th, 1992 . The disease affected young patients, 84% of them being HIV-1+ and 86% presenting CD4+ lymphocytes lower than 200 cells/mm3 . Fever was the most constant symptom, with radiological disorders and presence of vegetations by echocardiogram in 65% and 53% of episodes, respectively, and affectation of the tricuspid valve in 59% of patients . The diagnosis of endocarditis was definitive in 51% of cases, possible in 15% and probable in 22%, being cardiac failure the most severe complication, present in 23% of episodes . The detection of significant valve regurgitation in patients with IE and without developing cardiac failure is not predictive of future complications, nor its absence identifies patients with a favourable prognosis . Staphylococcus aureus was the most frequently isolated germ (48%), being methicillin-resistant in 15% of cases and with a slower response to the treatment with vancomycin than the methicillin-sensitive . Five patients died, all of them with CD4+ lower than 50 cells/mm3, which may have a predictive value in the follow-up of these patients.

Clin Infect Dis, 1992 Oct, 15(4), 668 - 77
Pyomyositis in North America: case reports and review; Christin L et al.; We report two cases and review the characteristics of pyomyositis . The courses of patients who presented with pyomyositis at the Maricopa Medical Center (Phoenix) are detailed . Ninety-eight reported cases over the last 20 years in North America, found through a MEDLINE search, are summarized . Infection with the human immunodeficiency virus (HIV) may predispose the patient to pyomyositis . The onset is usually insidious with progression to large purulent collections and significant morbidity . The diagnosis is frequently suggested by findings of imaging studies . Staphylococcus aureus is responsible for most cases in tropical areas but is less frequently associated with cases in North America . Since infection with HIV predisposes patients to bacterial infections, pyomyositis will occur more frequently in this patient population . Increased awareness of the disease will improve management . Following aspiration or surgical drainage, therapy with broad-spectrum empirical antibiotics may be considered initially in the treatment of pyomyositis.

Clin Infect Dis, 1992 Oct, 15(4), 636 - 8
Acute pubic osteomyelitis in athletes; Ukwu HN et al.; Three cases of pubic osteomyelitis in athletes are reported . The clinical presentation in each case was acute groin, hip, or perineal pain; fever; chills; inability to bear weight; and pubic symphysis tenderness . Since radiographic changes in the pubic bone can be delayed, a high index of suspicion is required by the clinician . Although Staphylococcus aureus is the dominant pathogen in pubic osteomyelitis, it is recommended that the diagnosis be established by culture of blood or pubic bone aspirate so that specific therapy can be instituted quickly.

Arch Intern Med, 1992 Oct, 152(10), 2109 - 12
A prospective study of Staphylococcus aureus nasal colonization and intravenous therapy-related phlebitis; Lipsky BA et al.; BACKGROUND--Intravenous (IV) therapy-associated phlebitis is common, but its causes are ill defined . Some cases may be related to bacterial colonization of the skin surrounding the IV catheter, especially by Staphylococcus aureus . This prospective study examined the association of phlebitis with anterior nares S aureus carriage, as well as with other potential risk factors . METHODS--Selected demographic and clinical data and a nares culture were collected from patients on designated wards by us and from the IV therapy team at the time of initial IV catheter placement . Patients were followed up for signs and symptoms of phlebitis for the duration of the initial catheter's use and for up to two additional IV placements . Potential risk factors were compared for patients who developed phlebitis and those who did not by the Cox multivariate proportional hazards model . RESULTS--During 10 weeks, 273 men with a total of 416 catheter placements had fully evaluable data . Phlebitis occurred during 13.7% of the catheter placements . Nasal cultures yielded S aureus from 14.3% of the patients, but none of the IV team nurses . Surprisingly, S aureus nasal colonization was related (at borderline statistical significance) to a reduction in phlebitis risk . Location of the patient on a surgical ward, the presence of infection at any site, and a larger-gauge catheter were each significant independent risk factors for phlebitis . The highest risk of phlebitis appeared to have been within 12 to 24 hours of catheter placement . CONCLUSIONS--The primary finding of this study was that nasal colonization with S aureus did not increase the risk of developing IV catheter-associated phlebitis . Our rate of IV catheter-associated phlebitis was similar to that in other studies, but the factors predisposing to phlebitis differed somewhat from those in previous studies.

Todays OR Nurse, 1992 Oct, 14(10), 15 - 21
The facts about methicillin-resistant Staphylococcus aureus; Jackson MM; 1 . Staphylococcus aureus is a gram-positive organism that can be cultured from the anterior nares of 30% to 40% of the general population . S aureus causes about 10% of all nosocomial infections, and is the leading cause of surgical wound infections . 2 . Several factors can influence the recovery of MRSA from specimens, including mixed cultures in the person, a person who is an intermittent carrier, and a culture that is taken or transported incorrectly . 3 . Two approaches can be used to reduce the risk of cross-transmission of organisms among patients and health-care workers: a generic infection precautions strategy for all patients, and identifying patients infected or colonized with MRSA and treating them differently than other patients.

Proc Natl Acad Sci U S A, 1992 Oct 1, 89(19), 8938 - 42
Emr, an Escherichia coli locus for multidrug resistance; Lomovskaya O et al.; An Escherichia coli chromosomal DNA fragment cloned on a multicopy plasmid conferred resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds . The sequence of the cloned emr locus located at minute 57.5 of the chromosome revealed two open reading frames, emrA and emrB . emrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential alpha-helices to span the inner membrane . The peptide is homologous to QacA, a multidrug-resistant pump from Staphylococcus aureus, and belongs to a gene family that includes tetracycline-resistant pumps of Gram-positive bacteria and the galactose/H+ symporter of E . coli . emrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain . An active pho-fusion to the C domain suggested that EmrA is a membrane protein . Disruption of emrB significantly increased sensitivity of cells to uncouplers . The cellular content of uncoupler increased in the order: overexpressed emrB cells greater than wild type greater than emrB-.

Proc Natl Acad Sci U S A, 1992 Oct 1, 89(19), 8903 - 7
Bacterial ADP-ribosyltransferase with a substrate specificity of the rho protein disassembles the Golgi apparatus in Vero cells and mimics the action of brefeldin A; Sugai M et al.; Epidermal-cell differentiation inhibitor (EDIN) is an exoenzyme produced by Staphylococcus aureus that catalyzes the ADP-ribosylation of rho proteins, members of the small GTP-binding protein family . In this study we demonstrate that EDIN induces a rapid morphological change in the Golgi structure of monkey kidney Vero cells that is similar to the changes elicited by brefeldin A (BFA) . Treatment of Vero cells with EDIN resulted in a rapid disappearance of N-7-(4-nitrobenzo-2-oxa-1,3-diazole)-6-aminocaproylsphingosine, a 110-kDa protein (beta-COP, coat protein), and mannosidase II from the Golgi structure . Lower doses of EDIN and BFA had a synergistic effect on the redistribution of the Golgi markers . The similarities in the effects of EDIN and BFA in Vero cells also include the EDIN- or BFA-mediated protection of Vero cells from ricin cytotoxicity and prevention of the effects of EDIN or BFA on the distribution of Golgi markers by the pretreatment of Vero cells with guanosine 5'-{gamma-thio}triphosphate or forskolin . Incubation of a Vero-cell homogenate with {32P}NAD+ and EDIN in vitro resulted in the appearance of a labeled band with an apparent molecular mass of 22 kDa . The morphological change of the Golgi structure induced by EDIN was inhibited by nicotinamide, an inhibitor of EDIN-catalyzed ADP-ribosylation . Thus these data suggest that a rho protein is involved in the membrane trafficking between the Golgi and the endoplasmic reticulum of Vero cells and that this rho protein may be a target shared by EDIN and BFA.

Kidney Int Suppl, 1992 Oct, 38, S91 - 5
Polymorphonuclear cell function and infection in dialysis; Vanholder R et al.; End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality . In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species . Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production . This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample . Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia . Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients.

J Med Microbiol, 1992 Oct, 37(4), 238 - 44
The production of a bactericidal monoglyceride in staphylococcal abscesses; Engler HD et al.; The treatment of abscess homogenates with calcium ionophores stimulated the production of a bactericidal lipid with properties indistinguishable from those of a previously unidentified bactericidal lipid that had been detected in staphylococcal abscesses . The lipid was identified as a monoglyceride by thin layer chromatography . It resembled the unidentified lipid in that it had a high specific activity, exhibited differential activity, was inhibited by Staphylococcus aureus delta toxin, lecithin and Ca++, and its activity was reduced by oxidation . Stimulation of monoglyceride production by calcium ionophore requires the joint presence of components from the sedimented and supernatant fractions of abscess homogenates, and was not produced if boiled homogenate was used . The addition of verapamil interfered with the production of monoglyceride in homogenates treated with calcium ionophore . Monoglyceride was produced only in abscess homogenates and not in homogenates of other normal tissues or tissues taken from mice infected with S . aureus . Calcium ionophore could be replaced by inositol triphosphate, suggesting that monoglyceride production involved the release of calcium from intracellular stores . The 2-monoglyceride was the form originally produced in abscess homogenates, but this spontaneously isomerized to the 1-monoglyceride . The fatty-acid moiety of the monoglyceride consisted primarily of 16:0 and 16:1 fatty acids.

J Med Microbiol, 1992 Oct, 37(4), 235 - 7
The esterification of fatty acids by Staphylococcus aureus fatty acid modifying enzyme (FAME) and its inhibition by glycerides; Kapral FA et al.; Fifty-five randomly selected Staphylococcus aureus strains were examined for fatty acid modifying enzyme (FAME) production . Of these, 20.4% did not elaborate the enzyme . Amongst the remaining strains, the lowest level produced in culture was 0.1 unit/10(9) cocci and the maximum was 2.01 U/10(9) cocci; the median level was 0.4 U/10(9) cocci . In a series of straight-chain saturated fatty acids with 11-24 carbons, all could be esterified by FAME . However, those with 15-19 carbons were generally better substrates than the others . For a particular chain length, the unsaturated forms were better substrates than the saturated form . Triglycerides with unsaturated fatty acid side chains were potent inhibitors of FAME . Diglycerides were almost as active as triglycerides, but monoglycerides were much less inhibitory . FAME was purified by gel filtration followed by hydrophobic interaction chromatography on hexyl agarose . FAME and lipase may have a role in determining the survival of S . aureus in lesions.

J Med Microbiol, 1992 Oct, 37(4), 227 - 31
Extracellular proteins as a potential marker of active Staphylococcus aureus infection in bone; Krikler SJ et al.; The potential of extracellular protein antigens of Staphylococcus aureus as markers of infection of bone was investigated by immunoblotting . Serum from patients with S . aureus bone infection showed levels of IgG antibodies to a preparation of soluble extracellular proteins of 17-81 kDa which were significantly higher than those found in serum from normal controls . By contrast, immunoblots of various whole cell or cell wall-derived antigens gave complex patterns of response which were unsuitable for positive diagnosis of S . aureus bone infection.

J Clin Microbiol, 1992 Oct, 30(10), 2583 - 8
Latex agglutination-negative methicillin-resistant Staphylococcus aureus recovered from neonates: epidemiologic features and comparison of typing methods; Wanger AR et al.; An unusual strain of methicillin-resistant Staphylococcus aureus (MRSA) was repeatedly isolated from infants in a newborn special care unit (NBSC) and a newborn intensive care unit . Between January 1989 and March 1990, approximately 100 isolates from infected or colonized infants were recovered . Surveillance cultures taken during this time revealed a 20% colonization rate, which was defined as recovery of MRSA from the nares, umbilicus, or groin . Isolates were identified as S . aureus by tube coagulase reactivity and heat-stable nuclease production but were unreactive in a latex agglutination assay . Representative isolates that were collected during the outbreak and that were found to share the latex agglutination assay-negative phenotype were compared by antibiogram (12 isolates), bacteriophage typing (20 isolates), capsular polysaccharide typing (30 isolates), and plasmid as well as chromosomal DNA analyses (20 isolates) . All isolates known to be associated with the outbreak had nearly identical antibiograms and were notably susceptible to clindamycin . Staphylococcal bacteriophage typing was not useful in determining the relatedness of the isolates, since the majority were nontypeable . Plasmid pattern analysis revealed one large plasmid (approximately 100 kb) of equivalent size among the isolates . Capsular polysaccharide typing revealed that 14 of 30 isolates tested were type 5 . Isolates identified in children at two other hospitals in the city which were also unreactive by the latex agglutination assay and clindamycin susceptible had plasmid and antibiogram patterns identical to those of isolates from the NBSC . Pulsed-field gel electrophoresis of restriction enzyme-digested genomic DNAs from the outbreak isolates demonstrated identical patterns which could be clearly differentiated from those of other unrelated MRSA . The strain from the NBSC is, therefore, unique and underscores the need for caution in interpreting the latex agglutination reactivities of MRSA isolates.

Invest Ophthalmol Vis Sci, 1992 Oct, 33(11), 3017 - 23
Topical antibiotic therapy for the treatment of experimental Staphylococcus aureus keratitis; Callegan MC et al.; A rabbit model of Staphylococcus aureus keratitis was developed to study the chemotherapeutic efficacy of ciprofloxacin, vancomycin, and cefazolin . Intrastromal injection of 100 colony forming units of log phase S . aureus ATCC strain 25923 resulted in rapid growth in the cornea, peaking at 10(7) cfu/cornea by 12 hr post-infection . Slit-lamp examination revealed that infected eyes reached 30% of maximum inflammation by 10 hr and 60% by 22 hr post-infection . Antibiotic therapy (one drop every 15 min for 5 hr) was initiated at 4 hr post-infection (experiment 1) or 10 hr post-infection (experiment 2) . Another group was initiated at 10 hr post-infection and treated for 10 hr (experiment 3) . In experiment 1, treatment from 4-9 hr post-infection with 0.3% ciprofloxacin drops decreased the cfu per cornea 6.1 logs, compared to placebo-treated controls (P = 0.0001), and rendered 50% of inoculated eyes sterile . Vancomycin (5.0%) and cefazolin (5.0%) each lowered the cfu per cornea 4.6 logs (P = 0.0187) but did not sterilize any eyes . In experiment 2, therapy from 10-15 hr post-infection with 0.3% ciprofloxacin reduced the cfu per cornea 0.9 logs (P = 0.0001) . Vancomycin (5.0%) and cefazolin (5.0%) decreased the cfu per cornea 0.2 logs (P = 0.3973) and 0.3 logs (P = 0.1307), respectively . In experiment 3, therapy from 10-20 hr post-infection with 0.3% ciprofloxacin reduced the cfu per cornea 3.9 logs (P < 0.0001) . In this keratitis model, ciprofloxacin was more effective than vancomycin or cefazolin in killing S . aureus.

Eur Heart J, 1992 Oct, 13(10), 1441 - 3
Infective right atrial thrombus: a rare complication of total parenteral nutrition in an adult; Badano L et al.; We describe a case of an infective right atrial thrombus, following total parenteral nutrition, in a 21-year-old woman undergoing a surgical procedure for long-standing chronic ulcerative colitis . She presented with high temperature and the illness did not respond to antibiotic therapy . A 2-dimensional echocardiogram showed a mobile right atrial mass that at surgery was identified as a thrombus . Thrombus cultures grew coagulase-negative Staphylococcus aureus.

Diabet Med, 1992 Oct, 9(8), 749 - 52
Foot infections in diabetes are rarely due to a single microorganism; Hunt JA; The purpose of this study was to investigate the frequency with which multiple organisms can be isolated from severe foot infections in diabetic patients with carefully planned techniques of collection and processing of specimens . One hundred and seventy-seven organisms were isolated from 52 patient admissions (mean 3.4 per infection) at a district hospital . This was compared to a mean of 2.1 organisms per lesion at a local university hospital and 2.3 at a smaller community hospital . Staphylococcus aureus was isolated in about half of all lesions at the three hospitals, while anaerobic organisms were isolated from 30 at the district hospital, 10 at the university hospital, and 4 at the community hospital . This study concludes that, firstly, proper techniques for collection, transportation and examination of culture specimens are important in the isolation of multiple organisms from foot infections in diabetes, and secondly, Staphylococcus aureus is often absent while anaerobic organisms are common.

Clin Cardiol, 1992 Oct, 15(10), 777 - 80
Delayed presentation of a mitral annular perforation complicating Staphylococcus aureus infective endocarditis; Quigley RL et al.; This report describes a patient who presented with congestive heart failure secondary to a mitral annular-left atrial fistula . There was a remote history of Staphylococcus aureus endocarditis involving the mitral valve which was treated medically 30 years previously . The sterile fistula was managed surgically with an annuloplasty.

Clin Exp Immunol, 1992 Oct, 90(1), 135 - 40
Human immunoglobulin production in immunodeficient mice: enhancement by immunosuppression of host and in vitro activation of human mononuclear cells; Cavacini LA et al.; The affect of host and donor related factors on successful engraftment of human cells into mice was examined to minimize the variability that has been observed in successful development of human-mouse chimera for the study of human disease and immune physiology and regulation . Human immunoglobulin production in severe combined immunodeficiency (SCID) mice engrafted with human peripheral blood mononuclear cells (PBMC) was augmented by immunosuppressing recipient mice and activating donor PBMC . Immunosuppression of recipient mice with 3 Gy of gamma-irradiation induced a 10-fold increase in human IgG in the sera of engrafted SCID mice . Variation in production of human IgG in recipient mice correlated with preinjection phenotype and activation status of injected PBMC . Mice injected with PBMC with a low CD4/CD8 ratio (less than 0.5) produced no detectable circulating human immunoglobulin . When the CD4/CD8 ratio was greater than 1.5, human IgG was detected in sera of PBMC-recipient SCID mice . Serum IgG increased 10-fold following in vitro activation of donor PBMC with anti-CD3, IL-2 and Staphylococcus aureus . Successful engraftment and serum IgG production was evidenced by an increase in the recovery of activated human IgG+ cells in the spleens of mice with maximal IgG production . Optimization of functional engraftment required modification of both the host (SCID mice) and the donor cells.

Int J Syst Bacteriol, 1992 Oct, 42(4), 642 - 4
Identity of V factor in culture medium used for prior growth of two strains of Staphylococcus aureus; Niven DF et al.; Staphylococcus aureus ATCC 12598 and ATCC 25923 were starved of pyridine nucleotides and precursors and then grown in a semidefined medium containing {carbonyl-14C}nicotinamide . Samples of medium from late-exponential-phase and stationary-phase cultures were analyzed for 14C-metabolites . In all cases, V factor was present primarily as NAD.

J Formos Med Assoc, 1992 Oct, 91(10), 945 - 50
Epidemiologic investigation of nosocomial outbreak of methicillin-resistant Staphylococcus aureus by plasmid pattern analysis; Chang SC et al.; Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become an important problem with increasing frequency . In order to learn if plasmid pattern analysis can be used in epidemiologic investigations of MRSA infections, the authors did plasmid extractions of 70 MRSA stock isolates using a rapid lysostaphin lysis method . All isolates carried at least one plasmid . Most of the isolates had one large plasmid of 24-28 megadaltons (Md) . Many also carried one or two small plasmids . Accordingly, 12 different patterns were identified . From these background results, we applied this method to the investigation of two small nosocomial outbreaks of MRSA infection . It was found that the analysis of plasmid pattern and restriction endonuclease analysis are more discriminative than antibiograms . Strains with the same antibiograms can be different by plasmid analysis . It is concluded that the plasmid pattern with a restriction endonuclease analysis study is a reliable method for epidemiologic study of MRSA infections.

J Bacteriol, 1992 Oct, 174(19), 6303 - 6
Analysis of a peptidoglycan hydrolase gene from Staphylococcus aureus NCTC 8325; Wang X et al.; We have investigated the expression of the peptidoglycan hydrolase gene (lytA) of Staphylococcus aureus NCTC 8325 . Results from in vitro transcription-translation analysis, maxicell experiments, and Northern (RNA) blot analysis suggest that the lytA gene encodes a polypeptide of M(r) approximately 50,000 . Physical mapping data indicate that the lytA gene originated from prophage 11 in the NCTC 8325 strain.

J Virol, 1992 Oct, 66(10), 5924 - 8
Staphylococcal exotoxin superantigens induce human immunodeficiency virus type 1 expression in naturally infected CD4+ T cells; Brinchmann JE et al.; A high proportion of Staphylococcus aureus strains of human origin produce one or more exotoxins . In vivo, these toxins may give rise to a variety of clinical syndromes . In vitro, staphylococcal exotoxins have been shown to bind both to human leukocyte antigen (HLA) class II molecules on antigen-presenting cells and to the T-cell receptors on large fractions of T cells . The result of this interaction may be proliferation of the T cells, T-cell anergy, or apoptosis, depending on several factors, including the state of the responding cells and the presence of accessory molecules . Using naturally infected peripheral blood mononuclear cells depleted of CD8+ T cells, we have shown that staphylococcal exotoxins are powerful inducers of human immunodeficiency virus type 1 expression and that they induce expression at low concentrations and with greater efficiency than other T-cell mitogens . Human immunodeficiency virus type 1 was produced entirely by CD4+ T cells in this model; monocytes were expendable both as a source of virus and as a source of HLA class II molecules as long as other cells expressing HLA class II molecules were present . The results suggest that infection by S . aureus may be a cofactor in the immunopathogenesis of AIDS.

J Immunol, 1992 Oct 1, 149(7), 2459 - 65
Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages; Manthey CL et al.; Taxol, a microtubule stabilizing agent, exhibits promise in the treatment of breast and ovarian tumors . Recently, this novel drug has been shown to activate murine macrophages to express TNF-alpha and to down-regulate TNF-alpha receptors, activities shared by bacterial LPS . Our study sought to determine if taxol could regulate gene expression in murine macrophages and to examine further the ability of taxol to generate an LPS-like signal . Toward this end, the ability of taxol to induce TNF-alpha mRNA and five other genes (IL-1 beta, IP-10, D3, D7, and D8) associated with LPS-activation of macrophages was examined by Northern blot analysis . Taxol alone (1-30 microM) induced murine C3H/OuJ macrophages to secrete bioactive TNF-alpha and express increased levels of each of the six genes under investigation . The magnitude and the kinetics of induction of each gene closely resembled that seen with Escherichia coli K235 LPS . Macrophages from LPS-hyporesponsive C3H/HeJ mice, however, failed to induce detectably any of the genes in response to taxol, despite being sensitive to the microtubule stabilizing effects of taxol as determined by immunofluorescence microscopy . The gene induction activity of taxol was in marked contrast to an alternative macrophage activator, heat killed Staphylococcus aureus, which induced a distinct gene profile in C3H/OuJ macrophages and which was equally active in C3H/OuJ and C3H/HeJ macrophages . These data are consistent with an ability of taxol to generate an LPS-like signal, possibly through a common signaling intermediate . As a first step toward identifying signal responses shared by taxol and LPS, we have shown that taxol, as shown previously for LPS, rapidly induces the tyrosine phosphorylation of a 41- and 42-kDa protein.

J Vasc Surg, 1992 Oct, 16(4), 651 - 8; discussion 658-60
Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic graft infections; Colburn MD et al.; We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system . The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass . Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta . This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation . One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts . Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily) . All grafts were sterilely removed between 3 and 4 weeks after implantation . There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Mem Inst Oswaldo Cruz, 1992 Oct-Dec, 87(4), 575 - 81
Delayed phagocytosis and bacterial killing in Chediak-Higashi syndrome neutrophils detected by a fluorochrome assay . Ultrastructural aspects; Bellinati-Pires R et al.; The few studies already published about phagocyte functions in Chediak-Higashi syndrome (CHS) has stated that neutrophils present slow rate of bacterial killing but normally ingest microorganisms . In the present study, both phagocytosis and killing of Staphylococcus aureus were verified to be delayed in neutrophils from two patients with CHS when these functions were simultaneously evaluated by a fluorochrome phagocytosis assay . Electron microscopic examination showed morphologic differences among neutrophils from CHS patients and normal neutrophils regarding the cytoplasmic structures and the aspects of the phagolysosomes . It was noteworthy the presence of giant phagolysosomes enclosing bacteria in active proliferation commonly observed in CHS neutrophils after 45 min of phagocytosis, which corresponded with the impaired bactericidal activity of these leukocytes . The present results suggest that phagocytosis may also be defective in CHS, and point out to the sensitivity of the fluorochrome phagocytosis assay and its application in clinical laboratories.

J Antimicrob Chemother, 1992 Oct, 30(4), 509 - 23
Investigation of the in-vitro uptake, intraphagocytic biological activity and effects on neutrophil superoxide generation of dirithromycin compared with erythromycin; Joone GK et al.; The cellular uptake by human neutrophils and the intraphagocytic biological activity of the new macrolide antimicrobial agent dirithromycin (0.01-2 mg/L) compared with erythromycin was investigated in vitro . Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila were used as the test intracellular microbial pathogens . After coincubation (45 min at 37 degrees C) of neutrophils with a fixed concentration of 2 mg/L of each antibiotic the respective intracellular/extracellular ratios for erythromycin and dirithromycin were 6.1 +/- 2.5 and 10.6 +/- 2 respectively (P < 0.005) . Using a combination of techniques (colony counting, radiometry and fluorescence microscopy) both erythromycin and dirithromycin at concentrations of 0.01 and 0.5 mg/L and higher, respectively, were found to possess dose-related intraphagocytic bacteristatic activity for each of the test microbial pathogens . The effects of dirithromycin and erythromycin (1-20 mg/L) on neutrophil chemotaxis and generation of reactive oxidants by these cells were also investigated in vitro . Both antimicrobial agents caused a dose-related stimulation of neutrophil migration which was associated with inhibition of leucoattractant-activated generation of superoxide and activity of the myeloperoxidase/H2O2/halide system . However, superoxide generation by neutrophils activited with opsonized zymosan or phorbol myristate acetate was unaffected by the macrolides . These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis.

Lymphokine Cytokine Res, 1992 Oct, 11(5), 201 - 7
Secretion of thioredoxin after in vitro activation of human B cells; Ericson ML et al.; The redox-active enzyme thioredoxin (Trx) is secreted by various virus-transformed cell lines of B- and T-cell origin and has been considered to play an autoregulatory role as a cofactor during cellular growth processes . We show in this paper that exposure of B lymphocytes from normal, healthy donors and B cells from B-type chronic lymphocytic leukemia (B-CLL) to Staphylococcus aureus Cowan I (SAC) induced expression of Trx mRNA . By combining SAC, or the phorbol ester TPA, with IL-2 and the conditioned medium of a T-cell hybridoma (BSF-MP6), we could strongly enhance the Trx expression . After {35S}methionine labeling of stimulated B-CLL cells in vitro, Trx was immunoprecipitated both from cell extracts and from the medium with antibodies against human placenta Trx . Secretion of newly synthesized Trx was also confirmed by a quantitative radioimmunoassay for human Trx . During 24 h cultivation experiments, treatment with SAC induced a 5-fold increase of the Trx content of normal B lymphocytes as well as in B-CLL cells . Approximately two-thirds of the total amount of the enzyme was released into the medium.

J Protein Chem, 1992 Oct, 11(5), 517 - 25
Recombinant human glucagon: large-scale purification and biochemical characterization; Yoshikawa K et al.; Recombinant glucagon was expressed in Escherichia coli as a fusion protein including the glucagon sequence therein as previously reported {Ishizaki et al . (1992) . Appl . Microbiol . Biotechnol . 36, 483-486} . We developed a large-scale method for the isolation and purification of recombinant glucagon . After cell disruption, the resultant pellets were solubilized with 2 M guanidine-HCl, to which Staphylococcus aureus V8 protease had been added, and were digested into intermediates composed of 53- and 60-residue peptides containing the glucagon moiety . After the digestion came to an end, the solution was desalted, and the remaining V8 protease was allowed to resume digestion of the intermediates into glucagon, followed by partial purification by S-Sepharose and Sephacryl S-100 chromatographies . The glucagon obtained was found to be not less than 99.5% pure by analytical HPLC . One liter of culture produced about 180 mg of pure glucagon . The amino acid composition and the sequence agreed well with the theoretical values . Radioreceptor assay gave an affinity constant similar to that of pancreatic glucagon, and similar activities in cAMP production and glycogenolysis were also observed . Thus, the recombinant glucagon was confirmed to be biochemically identical with pancreatic glucagon.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2334 - 7
Investigation of the early killing of Staphylococcus aureus by daptomycin by using an in vitro pharmacodynamic model; Vance-Bryan K et al.; The purpose of this study was to develop a pharmacodynamic model to describe the dependency of the rate of Staphylococcus aureus killing upon the concentration of daptomycin . A range of free (unbound) daptomycin concentrations ranging from 0.12 to 27 times the MIC were simulated in the peripheral compartment of a two-compartment pharmacokinetic model . Log-linear regression of free daptomycin concentrations versus growth or kill rate constants showed a significant correlation (r = -0.90; P less than 0.001) . A Lineweaver-Burk plot of the reciprocal transformation of these data yielded a poor fit (r = -0.38; P greater than 0.05) . When a Lineweaver-Burk-type regression analysis was performed on the reciprocal of the change in the rate constant rather than the rate constant itself, the result demonstrated good correlation (r = 0.90; P less than 0.0001) . The observations were also well described by a sigmoidal maximum plateau pharmacologic effect model, in which the pharmacologic effect of daptomycin is a reduction in the bacterial exponential growth rate constant from the baseline in the absence of antibiotic to a lower (positive) growth or (negative) death rate constant observed in the presence of antibiotic . These data confirm that daptomycin exhibits concentration-dependent killing over a wide range of free daptomycin concentrations relative to the MIC and suggest that this is a saturable process similar to the Michaelis-Menten pharmacokinetic elimination of certain drugs.

J Clin Microbiol, 1992 Oct, 30(10), 2599 - 605
Epidemiologic typing and delineation of genetic relatedness of methicillin-resistant Staphylococcus aureus by macrorestriction analysis of genomic DNA by using pulsed-field gel electrophoresis; Struelens MJ et al.; To evaluate the usefulness of phenotypic and genotypic analyses for the epidemiologic typing of methicillin-resistant Staphylococcus aureus (MRSA), we characterized 64 epidemic MRSA isolates and 10 sporadic methicillin-susceptible S . aureus isolates from a university hospital and 18 MRSA isolates from hospitals in different geographical areas . Chromosomal DNA macrorestriction analysis with SstII was resolved by pulsed-field gel electrophoresis and compared with antibiotype analysis, phage type analysis, and standard genomic DNA restriction analysis with BglII . Indices of the discriminatory ability of these methods were 0.982, 0.959, 0.947, and 0.959, respectively . Macrorestriction patterns of 94% of MRSA isolates from patients, personnel, and the environment associated with a nosocomial outbreak were closely related (similarity coefficient, 85 to 100%) . In contrast, methicillin-susceptible S . aureus isolates showed a marked diversity of macrorestriction patterns (median similarity, 41%) . MRSA isolates from other geographical areas showed diverse macrorestriction patterns, with the exception of four isolates displaying identical or closely related patterns; these isolates were associated with concurrent outbreaks in four other Belgian hospitals . A concordance of genomic DNA macrorestriction typing with phenotypic methods was observed for 60 to 65% of MRSA isolates, and a concordance with standard DNA restriction analysis was found for 79 to 98% of these isolates . In conclusion, genomic DNA macrorestriction analysis was a useful complement to phenotypic methods for delineating epidemic isolates of MRSA, for identifying their nosocomial reservoirs, and for tracing their intra- and interhospital spread . The genetic relatedness of MRSA isolates, as estimated by this technique, appeared to correlate with their space-time clustering.

Kansenshogaku Zasshi, 1992 Oct, 66(10), 1436 - 43
Staphylococcus aureus bacteremia in patients with hematologic disorders; Funada H et al.; During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit . MRSA replaced methicillin-sensitive strains (MSSA) in the last four years . The skin and upper respiratory tract were the two most common primary foci . Most episodes occurred during neutropenia . Pharyngeal colonization often preceded the development of bacteremia . Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures . Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin . The survival rate did not differ materially between MRSA and MSSA bacteremias . Secondary foci, chiefly located in the lung, were found in 30% of all patients with S . aureus bacteremia . Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.

Biull Eksp Biol Med, 1992 Oct, 114(10), 383 - 5
{The prophylactic administration of interleukin-2 increases the survival of mice with an acute intra-abdominal infection caused by Staphylococcus aureus}; Shadrin OV et al.; The effect of RIL-2 on the survival of mice with acute Staphylococcus aureus strain 5/2 intra-abdominal {correction of intraperitoneal} infection was studied . RIL-2 was ineffective when administered simultaneously with the LD100 dose of bacteria . Antibiotics (gentamycin or combination of penicillin and streptomycin) administered in the same fashion cured 100% of animals . However, RIL-2 proved to be effective when administered simultaneously with LD70 dose of bacteria . The prophylactic course of RIL-2 consisting of repeated injections on days 3, 2 and 1 before the challenge with LD100 dose of bacteria also resulted in the marked increase of the survival of mice . The hypothetical mechanisms of action and the prospects of RIL-2 application are discussed.

J R Coll Surg Edinb, 1992 Oct, 37(5), 305 - 8
Median sternotomy wound dehiscence: a retrospective case control study of risk factors and outcome; Bryan AJ et al.; Over a 5-year period from 1985 to 1989, 2760 patients underwent open heart surgery at the University Hospital of Wales . Of these, 44 (1.6%, 35 men, mean age 61 years) developed median sternotomy dehiscence 2-40 (median 9) days after surgery . Infection was an associated factor in 18 patients (41%) and Staphylococcus aureus the predominant isolate in seven of those . Thirty-seven patients underwent rewiring of the sternotomy wound and seven patients underwent debridement, removal of wires and delayed closure . In those undergoing rewiring, sternal stability was maintained in 34 patients (92%) . There were seven deaths (16%), of which two were considered to be wound-related . Median hospital stay of survivors was 34 (range 16-84) days . Comparison with 88 matched controls by univariate analysis showed preoperative chronic obstructive airways disease, reduced FEV1/FVC ratio (both P < 0.001) and smoking (P < 0.05) were all more common in the dehiscence group . In addition, reoperation for bleeding (P < 0.05), prolonged bypass time, postoperative ventilation period and length of stay in the intensive care unit (all P < 0.001) were more common in the study group.

J Med Chem, 1992 Sep 18, 35(19), 3469 - 73
Synthesis and antibacterial activity of 1-(substituted pyrrolyl)-7-(substituted amino)-6-fluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylic acids; Liu JH et al.; Seventeen quinolone compounds characterized by having a fluorine atom at the 6-position, a substituted amino at the 7-position, and a substituted pyrrolyl at the 1-position were synthesized for the first time . The in vitro antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were tested . Among these agents obtained, compound 24 showed significantly enhanced activity against S . aureus . The results indicate that there is much room for modifications at the N-1 position.

J Virol, 1992 Sep, 66(9), 5384 - 92
Sites of in vivo phosphorylation of vesicular stomatitis virus matrix protein; Kaptur PE et al.; We mapped the in vivo phosphorylation sites for the matrix (M) protein of the Orsay and San Juan strains of vesicular stomatitis virus, Indiana serotype, using limited proteolysis and phosphoamino acid analysis . M protein was solubilized from 32P-labeled virions by using detergent and high-salt conditions, then treated with either trypsin or Staphylococcus aureus V8 protease, and analyzed by polyacrylamide gel electrophoresis and autoradiography to determine which fragments contained phosphate residues . The M protein fragment extending from amino acid 20 to the carboxy terminus contained approximately 70% of the control 32P label, while the fragment extending from amino acid 35 to the carboxy terminus had only trace amounts of label . These data indicate that the major phosphorylation site was between amino acids 20 and 34 in the Orsay strain M protein . Phosphoamino acid analysis of M protein by thin-layer electrophoresis showed the presence of phosphothreonine and phosphoserine and that phosphothreonine continued to be released after prolonged vapor-phase acid hydrolysis . These data identify Thr-31 as the primary in vivo phosphate acceptor for M protein of the Orsay strain of vesicular stomatitis virus . The San Juan strain M protein has serine at position 32, which may also be an important phosphate acceptor . In addition, phosphorylation at Ser-2, -3, or -17 occurs to a greater extent in the San Juan strain M protein than in the Orsay strain M protein . The subcellular distribution of phosphorylated M protein was investigated to determine a probable intracellular site(s) of phosphorylation . Phosphorylated M protein was associated primarily with cellular membranes, suggesting phosphorylation by a membrane-associated kinase . Virion M protein was phosphorylated to a greater extent than membrane-bound M protein, indicating that M protein phosphorylation occurs at a late stage in virus assembly . Phosphorylation of wild-type and temperature-sensitive mutant M protein was studied in vivo at the nonpermissive temperature . The data show that phosphorylated M protein was detected only in wild-type virus-infected cells and virions, suggesting that association with nucleocapsids may be required for M protein phosphorylation or that misfolding of mutant M protein at the nonpermissive temperature prevents phosphorylation.

FEBS Lett, 1992 Sep 7, 309(2), 115 - 8
The complete primary structure of abrin-a B chain; Chen YL et al.; The complete 267 amino acid sequence of abrin-a B chain was determined by analysis of peptides obtained by digestion with trypsin, chymotrypsin, lysyl endopeptidase, Staphylococcus aureus V8 protease and thermolysin . The sequence is not identical with that predicted previously by nucleotide sequencing, indicating the presence of isoforms of abrin . Comparison of the amino acid sequence of abrin-a B chain with that of ricin-D B chain reveals a high degree of sequence identity (59%) . Abrin-a B chain appears to consist of two domains, each domain with subdomains (alpha, beta, gamma) of about 40 amino acid residues.

Pol Tyg Lek, 1992 Sep 7-14, 47(36-37), 799 - 801
{Effect of ethylenediaminetetraacetic acid disodium salt and doxycycline on drug resistant bacteria}; Rudy M et al.; Effect of Na2EDTA and doxycycline applied alone and in combination in the treatment of experimentally induced dermatitis in rabbits with Staphylococcus aureus resistant to tetracyclines was studied . The rabbits were divided into three groups . The animals of group I were treated locally with the ointment containing 1% doxycycline or 1% Na2EDTA . In group II topical treatment was applied by means of injections of Na2EDTA solution in doses of 12.5 and 6.25 mg Na2EDTA per 1 kg/body weight . Group III was also treated locally with Na2EDTA solution like in group II, but additionally doxycycline in a dose of 50 micrograms per 1 kg/body weight was given i.v . Favourable therapeutic results were observed in the case of local, simultaneous application of Na2EDTA and doxycycline, or local application of Na2EDTA, and intravenous administration of doxycycline . However, the best therapeutic effect was seen in the case of local, simultaneous application of the ointment containing Na2EDTA and doxycycline.

J Spinal Disord, 1992 Sep, 5(3), 277 - 85
Postoperative wound infections complicating adult spine surgery; Stambough JL et al.; A review of 19 consecutive patients treated for deep wound infections after spinal surgery was performed . Patients were analyzed for preoperative risk factors, original diagnosis requiring surgery, onset of infection, presentation, treatment, and outcome . These patients (10 men, nine women), with a mean age of 44 years (range 18-74) were treated for 13 deep and six subcutaneous infections: 16 spine infections and nine graft site infections (six with both) . All 19 presented with draining wounds on an average of 17 days after surgery (range 4-86) . Staphylococcus aureus was cultured in 14 . Patients were treated with i.v . antibiotics for an average of 3 weeks (range 0-14) followed by oral antibiotics for an average of 6 weeks (range 2-12) . Surgical treatment included an average of 1.8 debridements (range 0-5), primary closure in two, delayed primary closure in seven, and healing by secondary intent in 10 . All but three patients were noted to be malnourished at the onset of their infection, with a total lymphocyte count of less than 2,000 . Three patients required removal of their hardware . Eighteen of 19 healed or their infections were stabilized, 17 of 18 arthrodeses fused, and no patient had neurological deterioration secondary to the infection . The treatment outlined produced satisfactory results in all but one patient . We conclude that postoperative spine infections are frequently associated with poor nutrition . Although definitive diagnosis is determined by the culture, clinical exam is helpful in establishing a presumptive diagnosis and, thus, earlier institution of surgical and antibiotic treatment.

J Med Microbiol, 1992 Sep, 37(3), 192 - 4
Carotenoid pigment levels in Staphylococcus aureus and sensitivity to oleic acid; Xiong Z et al.; Staphylococcus aureus mutants lacking pigment, or expressing only low levels of pigment, were more sensitive to oleic acid than were the parent strain and mutants making more pigment than the parent . One class of mutants (colour index 5), although possessing significant levels of pigment, were nevertheless quite sensitive to oleic acid . This suggested that only certain carotenoids in the biosynthetic pathway were capable of imparting resistance to fatty acids . The phenotypic expression of pigment also affected the sensitivity of a strain to oleic acid . The parent S . aureus strain 18Z, when grown to express its maximal pigment potential, was more resistant to oleic acid than when it was grown to express minimal levels of pigment.

J Pediatr Orthop, 1992 Sep-Oct, 12(5), 663 - 6
Acute pyogenic psoas abscess in children; Parbhoo A et al.; In a retrospective study, 24 patients treated at King Edward VIII Hospital from 1985 to 1988 for acute pyogenic psoas abscess were reviewed . The main initial complaints were a painful hip and difficulty in walking . Twenty-two patients had a fixed flexion deformity of the ipsilateral hip . Ultrasonography used as a screening method elucidated the clinical diagnosis in 19 patients . Twenty-two children required incision and drainage, and Staphylococcus aureus was isolated in 20 patients either on blood culture or pus swab . Although the condition is common in the tropics, an acute pyogenic psoas abscess should always be considered in the differential diagnosis of pain in the hip region.

J Pediatr Orthop, 1992 Sep-Oct, 12(5), 658 - 62
Toxic shock syndrome in patients with external fixators; Turker R et al.; Toxic shock syndrome (TSS), first described by Todd et al . in 1978, can be a life-threatening entity . Familiarity with the pathogenesis and clinical presentation of TSS may help achieve early diagnosis and prompt appropriate intervention . TSS is not a septicemia, but a toxemia . The most extensively described pathogenesis involves a focus of specific Staphylococcus aureus strains capable of producing an exotoxin (TSST-1) . We report two patients who developed TSS while in external fixators and describe their initial symptoms, management, and subsequent problems . This report will serve to alert pediatric orthopaedic surgeons to this entity and enable them to recognize its rather precipitous presentation and initiate appropriate treatment.

J Immunol, 1992 Sep 1, 149(5), 1771 - 8
Human low molecular weight B cell growth factor induces surface IgM+/A- B cells to express and secrete IgA; Bertolini JN et al.; The regulation of Ig class expression has been a controversial area of research . It is well established that T cells, and/or their products, influence which Ig isotype is produced during an immune response . In this study the regulation of Ig secretion of activated human IgM+/A- B cells was examined . Human T cell supernatants induced PWM-activated IgM+/A- B cells to switch to IgA secretion . Purification of the lymphokine mediating this effect involved hydroxylapatite, ion exchange, and gel filtration chromatography . The purified lymphokine could induce switch of IgM+/A- B cells, and it was also capable of inducing proliferation of Staphylococcus aureus Cowan 1 strain (SAC)-activated IgM+/A- B cells . SDS-PAGE and isoelectric focusing indicated the protein mediating this activity had a molecular mass of approximately 14 kDa and a pI of 6.8 . These results suggested that the observed activity might be due to low m.w . B cell growth factor (LMW-BCGF), a lymphokine which is capable of inducing proliferation of SAC-activated B cells and has a molecular weight and pI value in the range of the purified protein . Indeed, rLMW-BCGF was able to switch IgM+/A- B-cells to IgA expression and secretion as well as induce the proliferation of SAC-activated IgM+/A- B cells . These results demonstrate that LMW-BCGF is capable of inducing PWM-activated IgM+/A- B-cells to switch to IgA possibly by providing a proliferation signal which induces clonal expansion of IgM+/A- B cells, the progeny of which express a range of isotypes including IgA . This study also demonstrates that lymphokine induced isotype switching involves an intermediate stage of B cell development where human B cells coexpress IgM and a downstream isotype on their surface.

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