Staphylococcus

Clin Exp Immunol, 1993 Jun, 92(3), 437 - 41
T cell receptor V beta repertoire in HIV-infection individuals: lack of evidence for selective V beta deletion; Boyer V et al.; The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS . The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific V beta genes . To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 HIV+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V beta gene expression . In contrast to a recent study, the results presented here fail to provide evidence that selective loss of V beta-bearing T cells occurs in HIV+ individuals . Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing V beta subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen . Collectively, these data suggest that CD4 loss in HIV patients does not occur in a V beta-selective, superantigen-mediated fashion.

J Neuroimmunol, 1993 Jun, 45(1-2), 83 - 8
Effects of staphylococcal enterotoxin B on T cell receptor V beta utilization and clinical manifestations of experimental allergic encephalomyelitis; Kalman B et al.; Staphylococcal enterotoxin B (SEB) is a superantigen (SA) that up-regulates and then subsequently down-regulates and deletes T cells expressing V beta 8 T cell receptor (TcR) chains (Marrack and Kappler, 1990; Johnson et al., 1991) . We have investigated the effect of SEB on experimental allergic encephalomyelitis (EAE) in PL/J mice, where the predominant encephalitogenic T cells are V beta 8+ (Acha Orbea et al., 1988; Zamvil et al., 1988) . SEB did not enhance induction of EAE when administered prior to or after immunization for EAE . PL/J mice pretreated with SEB developed anergy and deletion of V beta 8 bearing cells and concomitant reduction in the incidence of EAE . Following SEB pretreatment, a redistribution in the TcR utilization of MBP-specific lymphocytes occurred . As a result, there was a low frequency of V beta 8 and expansion of other, normally less frequent, myelin basic protein (MBP)-specific clones . These observations indicate that systemic exposure to superantigen can influence organ-specific autoimmune diseases . We observed V beta-specific elimination, rather than activation, of autoimmune clones, a finding of potential therapeutic value . Modification of the TcR repertoire by systemic exposure to this SA indicates plasticity of immune reactivity and demonstrates a mechanism by which an environmental exposure (SEB) can influence a genetically determined, T cell mediated autoimmune disease.

Transfusion, 1993 Jun, 33(6), 450 - 7
The use of a chemiluminescence-linked universal bacterial ribosomal RNA gene probe and blood gas analysis for the rapid detection of bacterial contamination in white cell-reduced and nonreduced platelets; Brecher ME et al.; Because of the rising incidence of bacterial growth and septic platelet transfusions in aging units, platelet storage is currently limited in the United States to 5 days . This approved shelf life of platelets might be altered if methods were devised to rapidly detect infected units and/or to decrease the incidence of bacterially contaminated platelets . An investigation was conducted on the effect of a prototype blood collection system with an in-line filter for the production of white cell-reduced platelet-rich plasma on the growth of bacteria in platelets prepared from whole blood that had been inoculated with Staphylococcus epidermidis . Additional studies were conducted with a chemiluminescence-linked ribosomal RNA (rRNA) gene probe and with blood gas analysis to identify possible methods for the rapid detection of bacterial contamination . All units were followed for 9 days of storage . The filtration of the platelet-rich plasma resulted in an approximate 2 log10 reduction in white cells with an average loss of 6.7 percent of platelets . Filtration did not appear to alter bacterial growth . In all platelet units that supported growth, pO2 dropped to negligible values and pCO2 rose relative to culture-negative units . The changes were most sensitive and specific beyond 5 days of storage . The universal bacterial rRNA probe assay was able to detect S . epidermidis in concentrations as low as 1 x 10(3) colony-forming units per mL in some cases and reliably detected all units contaminated at a concentration of 1 x 10(4) colony-forming units per mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Cancer, 1993 May 28, 54(3), 482 - 8
Superantigen-induced cytokines suppress growth of human colon-carcinoma cells; Dohlsten M et al.; We have recently demonstrated that the superantigen staphylococcal enterotoxin A (SEA) conjugated to colon-carcinoma-reactive monoclonal antibodies (MAbs) directs T cells to lyse human colon-carcinoma cells, representing a potential novel tumor therapy . To further analyze the mechanism of antitumor effects of superantigen-activated T cells, we compared the activity of free and MAb-conjugated SEA in a long term in vitro co-culture assay of human peripheral-blood mononuclear cells (PBMC) and colon-carcinoma cell lines . Activation of resting T lymphocytes with SEA conjugated to the colon-carcinoma-reactive MAb C215 or free SEA resulted in strong inhibition of the growth of all studied colon-carcinoma cell lines . The growth of WiDr colon-carcinoma cells was unaffected by the presence of unactivated mononuclear cells, whereas addition of pM concentrations of SEA or C215-SEA conjugate completely suppressed tumor-cell growth . The suppressive effect was mediated by both CD4+ and CD8+ T cells and required the presence of MHC-Class II+ monocytes . The inhibition of tumor-cell growth was to a large extent mediated by soluble factors present in supernatants from SEA- or C215-SEA-activated mononuclear cells . Quantitation of cytokine mRNA in SEA-activated mononuclear cells by the reverse transcriptase-polymerase chain reaction (RT-PCR) revealed strong induction of mRNA encoding the cytokines IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha, TNF-beta and IFN-gamma . The use of cytokine-specific MAb demonstrated that IFN-gamma was of major importance for the tumor-growth-inhibitory activity in supernatants of SEA-activated lymphocytes . Addition of recombinant cytokines to WiDr colon-carcinoma cells showed that TNF-alpha was able to act synergistically with IFN-gamma to suppress tumor-cell growth . The local production of tumor-suppressive cytokines induced by MAb-targeted superantigens is likely to be of particular relevance for inhibition of the growth of tumor cells not expressing the targeted tumor-associated antigen.

Biochemistry, 1993 May 18, 32(19), 5222 - 32
Effects of amino acid substitutions on the pressure denaturation of staphylococcal nuclease as monitored by fluorescence and nuclear magnetic resonance spectroscopy; Royer CA et al.; In the present study we have used high hydrostatic pressure coupled with either time-resolved and steady-state fluorescence or NMR spectroscopy in order to investigate the effects of amino acid substitutions on the high-pressure denaturation properties of staphylococcal nuclease . This protein has been shown previously to be structurally heterogeneous in its native state . On the NMR time scale, four distinct interconverting conformational forms arise from the population of both cis and trans Xaa-Pro peptide bonds (His46-Pro47 and Lys116-Pro117) {Evans et al . (1989) Biochemistry 28, 362; Loh et al . (1991) in Techniques in Protein Chemistry II, pp 275-282, Academic Press, New York} . Mutations in the protein sequence have been shown to change the distribution among the various forms {Alexandrescu et al . (1989) Biochemistry 28, 204; Alexandrescu et al . (1990) Biochemistry 29, 4516} . Time-resolved fluorescence on a series of mutants with altered equilibria for cis/trans isomerism about the 116-117 peptide bond did not reveal any simple relationship between the position of the cis/trans equilibrium in the folded state and the heterogeneity of the fluorescence decay . However, the specific dynamic properties of each mutant, as revealed by time-resolved fluorescence, do appear to be correlated with their partial molar volume changes of denaturation . A striking finding is that mutation of either (or both) of the prolines that exhibits structural heterogeneity to glycine greatly alters the stability of the protein to pressure . These mutations also result in decreased chain mobility as assessed by time-resolved fluorescence . It appears that packing defects, which allow for peptide bond cis/trans heterogeneity in the wild-type protein, are removed by the Pro-->Gly substitutions.

J Immunol, 1993 May 15, 150(10), 4331 - 7
Role of CD8 in staphylococcal enterotoxin B-mediated lysis by cytotoxic T lymphocytes; Hoo WS et al.; Recent evidence has suggested that recognition of superantigens such as the staphylococcal enterotoxins by CTL occurs independently of the accessory molecule CD8 . These conclusions are based on the observation that antibodies to CD8 do not appear to be effective inhibitors of T cell lysis that is mediated by enterotoxin . This is in contrast to the well-known inhibitory effects of anti-CD8 antibodies on T cell activation by most peptide/class I complexes . In this study, we show that lysis of staphylococcus enterotoxin B (SEB)-bearing target cells by the mouse alloreactive CTL clone 2C is inhibited by anti-CD8 antibodies . SEB-mediated lysis by a polyclonal population of mouse CTL was also inhibited by anti-CD8 antibodies, but only under conditions where the SEB concentration is low . Inhibition occurs even when class I negative Daudi cells are used as targets . Thus, the observed inhibition does not appear to be due to the prevention of intercellular interactions between CD8 and class I molecules but is probably a consequence of preventing the intracellular association of CD8 and TCR . At the high ligand densities used in most previous studies, very few of the CD8/TCR complexes may be required for activation . Under these conditions, lysis may appear to be CD8 "independent" because 1) there are a sufficient number of preexisting CD8/TCR complexes for activation; or 2) prohibitively high concentrations of antibody would be needed to saturate unassociated CD8.

J Immunol, 1993 May 15, 150(10), 4284 - 91
Superantigen-induced peripheral tolerance inhibits T cell responses to immunogenic peptides in TCR (beta-chain) transgenic mice; Perkins DL et al.; TCR (beta-chain) transgenic mice were tolerized with the superantigen staphylococcal enterotoxin B (SEB) . Three to 28 days after tolerization with SEB, flow cytometry of peripheral T cells showed the persistence of SEB-unresponsive T cells that did not express reduced levels of the TCR (beta-chain) transgene . Stimulation of the tolerized T cells with a panel of superantigens (SEC1), mitogens (Con A, PHA, and pertussis toxin) and mAb (anti-CD3 epsilon) did not induce T cell proliferation . In contrast to other models, exogenous rIL-2 did not reverse unresponsiveness and induce proliferation . In addition, lymphokines rIL-4 and rIL-6 also did not induce proliferation . However, the unresponsive T cells did respond to the combination of PMA plus ionomycin, but not to PMA or ionomycin alone . Thus, the block in signal transduction in the anergic state occurs between the stimulation of cell surface receptors and the activation of protein kinase C and the increase in intracellular calcium . In addition, these results show that mature T cells tolerized with the superantigen SEB are unresponsive to a wide array of T cell stimuli, indicating a block in a common signal transduction pathway.

J Chromatogr, 1993 May 7, 637(1), 55 - 62
Glycosidase digestion, electrophoresis and chromatographic analysis of recombinant human granulocyte colony-stimulating factor glycoforms produced in Chinese hamster ovary cells; Clogston CL et al.; Recombinant human granulocyte colony stimulating factor (G-CSF) produced in Chinese hamster ovary cells is glycosylated . The carbohydrate compositional analysis indicated that G-CSF molecule contains sialic acid, galactose and galactosamine . By isolation and characterization of the purified glycopeptides obtained from cleavages by Staphylococcal aureus V-8 protease and cyanogen bromide, the O-linked glycosylation site was confirmed to be a Thr residue at position 133 . Neuraminidase and O-glycanase digestion followed by sodium dodecyl sulfate polyacrylamide and isoelectric focusing gel electrophoreses distinguished two possible carbohydrate structures attached at Thr-133: structure A, NeuNAc-Gal-beta(1,3)-GalNAc-O-Thr; and structure B, NeuNAc-Gal-beta(1,3)-{NeuNAc}-GalNAc-O-Thr . Different glycoforms, undigested or after glycosidase digestion, can also be separated by ion-exchange or reversed-phase high-performance liquid chromatography . The approach described in this report provides a simple and valuable procedure to characterize glycoprotein structures containing simple carbohydrate moieties.

Protein Sci, 1993 May, 2(5), 851 - 8
NMR analysis of staphylococcal nuclease thermal quench refolding kinetics; Kautz RA et al.; Thermally unfolded staphylococcal nuclease has been rapidly quenched to temperatures near 0 degree C and the refolding behavior examined using an NMR kinetic experiment . Unfolded protein, exhibiting random coil chemical shifts, persists following the quench and refolds in two distinct kinetic phases . A protein folding intermediate with a trans Lys 116-Pro 117 peptide bond is transiently overpopulated and relaxes to the predominantly cis native cis-trans equilibrium . The rate of trans-->cis isomerization in the native-like nuclease intermediate is approximately 100-fold faster than that observed in a Lys-Pro model peptide . The activation enthalpy of 20 kcal/mol observed for the nuclease Lys 116-Pro 117 peptide bond is comparable to that observed for other X-Pro isomerizations.

Protein Sci, 1993 May, 2(5), 838 - 50
Stress and strain in staphylococcal nuclease; Hodel A et al.; Protein molecules generally adopt a tertiary structure in which all backbone and side chain conformations are arranged in local energy minima; however, in several well-refined protein structures examples of locally strained geometries, such as cis peptide bonds, have been observed . Staphylococcal nuclease A contains a single cis peptide bond between residues Lys 116 and Pro 117 within a type VIa beta-turn . Alternative native folded forms of nuclease A have been detected by NMR spectroscopy and attributed to a mixture of cis and trans isomers at the Lys 116-Pro 117 peptide bond . Analyses of nuclease variants K116G and K116A by NMR spectroscopy and X-ray crystallography are reported herein . The structure of K116A is indistinguishable from that of nuclease A, including a cis 116-117 peptide bond (92% populated in solution) . The overall fold of K116G is also indistinguishable from nuclease A except in the region of the substitution (residues 112-117), which contains a predominantly trans Gly 116-Pro 117 peptide bond (80% populated in solution) . Both Lys and Ala would be prohibited from adopting the backbone conformation of Gly 116 due to steric clashes between the beta-carbon and the surrounding residues . One explanation for these results is that the position of the ends of the residue 112-117 loop only allow trans conformations where the local backbone interactions associated with the phi and psi torsion angles are strained . When the 116-117 peptide bond is cis, less strained backbone conformations are available . Thus the relaxation of the backbone strain intrinsic to the trans conformation compensates for the energetically unfavorable cis X-Pro peptide bond . With the removal of the side chain from residue 116 (K116G), the backbone strain of the trans conformation is reduced to the point that the conformation associated with the cis peptide bond is no longer favorable.

J Med Microbiol, 1993 May, 38(5), 354 - 9
Clearance and tissue distribution of staphylococcal enterotoxin A in the rat and potential use of adsorbents for removal from plasma; Nagaki M et al.; Many of the profound effects of staphylococcal septicaemia are thought to be the result of entry of enterotoxins into the systemic circulation . The aim of this study was to investigate the disposition of staphylococcal enterotoxin A (SEA) in the rat and its possible removal from blood . SEA labelled with 125I was administered intravenously (250 micrograms/kg) to rats . The blood clearance of SEA showed a biphasic pattern; an initial fast disappearance (half-life c . 3 min) was followed by a slower one (half-life c . 2 h) . Thirty minutes after injection of 125I-labelled SEA, most of the radioactivity was concentrated in the kidneys, indicating that renal excretion was the main route of elimination of SEA . The adsorption capacities of polymer-coated activated charcoal (DHP-1 and Adsorba 150C), uncharged resin (Amberlite XAD-7), anion exchange resin (Dowex-1) and polymyxin B matrix were assessed by measurement of the equilibrium adsorption isotherms for SEA . DHP-1 charcoal, Amberlite XAD-7 resin and Dowex-1 resin adsorbed similar amounts of SEA in human plasma . Plasma perfusion experiments were performed in vitro with small columns containing either charcoal or resin adsorbents . Over 4 h perfusion, DHP-1 charcoal removed 50% of the initial amount of 125I-SEA, Adsorba 150C charcoal 8.1% of SEA and Amberlite XAD-7 resin 32.5% of SEA . These results suggest that it may be feasible to develop the adsorbent columns for direct removal of SEA from the plasma of patients with staphylococcal septicaemia.

Proc Natl Acad Sci U S A, 1993 May 1, 90(9), 3811 - 4
Atomic force microscopy of biochemically tagged DNA; Murray MN et al.; Small fragments of DNA of known length were made with the polymerase chain reaction . These fragments had biotin molecules covalently attached at their ends . They were subsequently labeled with a chimeric protein fusion between streptavidin and two immunoglobulin G-binding domains of staphylococcal protein A . This tetrameric species was expected to bind up to four DNA molecules via their attached biotin moieties . The DNA-protein complex was deposited on mica and imaged with an atomic force microscope . The images revealed the protein chimera at the expected location at the ends of the strands of DNA as well as the expected dimers, trimers, and tetramers of DNA bound to a single protein.

J Exp Med, 1993 May 1, 177(5), 1481 - 5
Bacterial superantigens mediate T cell deletions in the mouse severe combined immunodeficiency-human liver/thymus model; Baccala R et al.; The ability to analyze T cell receptor (TCR) thymic repertoire shaping in humans by self and foreign ligands is hampered by the lack of suitable models . We recently documented that the mouse severe combined immunodeficiency (SCID)-human fetal liver/thymus model recapitulates the TCR V beta gene repertoire of human thymocytes . Here, we show that an exogenous superantigen, staphylococcal enterotoxin B, administered to such mice induces clonal deletions in both CD4+8- and CD8+4- cells involving the same human V beta clones that are selected in vitro by this toxin . This model, therefore, may allow comprehensive studies into the effects of microbial and other agents on human T cell thymic selection processes in a biologically relevant setting.

Infect Immun, 1993 May, 61(5), 1743 - 9
Effect of growth conditions on expression and antigenicity of Staphylococcus epidermidis RP62A cell envelope proteins; McDermid KP et al.; Staphylococcus epidermidis RP62A (ATCC 35984) was grown in tryptic soy broth (TSB), iron-depleted TSB (TSB-Fe), iron-reconstituted TSB-Fe (TSB+Fe), a chemically defined medium, and fetal calf serum (FCS) and on silastic disks in chambers that were sutured to the pig peritoneal wall . Bacterial cell wall proteins were extracted by digestion with recombinant lysostaphin, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and detected by silver staining . Cell wall proteins from TSB-, chemically defined medium-, or FCS-grown cells had a complex profile of greater than 25 protein bands spanning the full molecular mass range . By contrast, a digest obtained from in vivo-grown cells had only five major proteins of 40 kDa or greater . Proteins of 130 and 106 kDa were present in the cell envelopes of TSB-Fe- and in vivo-grown cells but not in those grown in TSB or TSB+Fe . A 43-kDa protein expressed by in vitro-grown cells and 52- and 96-kDa proteins expressed by in vivo-grown cells reacted with antisera from pigs with the chamber implants and from catheterized, paracatheter-inoculated pigs but not with hyperimmune sera from pigs immunized with TSB-grown cells . The data indicate that S . epidermidis, growing under in vivo conditions, expresses antigens distinct from those that are grown in vitro.

Eur J Immunol, 1993 May, 23(5), 1197 - 200
Clonal deletion as direct consequence of an in vivo T cell response to bacterial superantigen; Wahl C et al.; To date clonal deletion of peripheral mature T cells is restricted to in vivo model systems characterized by prolonged exposure of mice to antigens and clonal T cell expansion preceding clonal deletion . Here we describe that upon challenge of mice with the superantigen staphylococcal enterotoxin B two immediate events become imposed on ligand-reactive V beta 8+ T cells in lymph node cells draining the local site of injection . First, and within hours V beta selective clonal deletion is initiated via an apoptotic process . Second, the remaining V beta 8+ T cells first develop a profound state of ligand-specific unresponsiveness and subsequently initiate clonal in vivo growth . It is suggested that the dichotomy of events observed reflects a direct consequence of T cell receptor occupancy in the context of inappropriate signalling.

J Immunol, 1993 May 1, 150(9), 3785 - 92
Profound deletion of mature T cells in vivo by chronic exposure to exogenous superantigen; McCormack JE et al.; It has been noted previously that superantigens can under different circumstances stimulate activation, expansion, anergy, and/or deletion of reactive T cells in vivo and in vitro . Here, we present a detailed examination of the expansion and deletion of T cells in vivo in response to the superantigens staphylococcal enterotoxin A (SEA) in the B10.BR mouse . Mice were either acutely or chronically exposed to varying doses of SEA, and the relative level of T cells bearing SEA-reactive V beta elements was followed over time in lymphocytes purified from peripheral blood, lymph nodes, mesenteric lymph nodes, and spleen . In most cases, an initial sharp rise in the proportion of reactive T cells was followed by a dramatic decline . Cells of the CD4+ and CD8+ lineages displayed subtle differences in their kinetics of activation and deletion, as well as their sensitivity to different doses of SEA . Furthermore, cells bearing either of two V beta elements previously characterized as SEA-reactive showed some differences in their responses to SEA treatment . Acute exposure usually caused the disappearance of only 50% to 70% of reactive T cells; however, chronic exposure to SEA caused almost complete deletion of target T cells . Deletion was evident even in animals treated with very low doses of SEA, doses that were too small to cause any apparent T cell proliferation . Thus, proliferation does not appear to be a prerequisite for peripheral deletion of T cells.

J Immunol, 1993 May 1, 150(9), 3776 - 84
Acquired resistance to superantigen-induced T cell shock . V beta selective T cell unresponsiveness unfolds directly from a transient state of hyperreactivity; Miethke T et al.; TCR V beta selective T cell activation and systemic release of T cell-derived lymphokines causing lethal shock in D-galactosamine (D-Gal)-sensitized mice depicts only one facet of in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB) . An immediate second major aspect represents the induction of peripheral unresponsiveness in SEB-reactive V beta 8+ T cells . SEB causes in vivo within 4 h resistance to an otherwise lethal challenge with SEB plus D-Gal, as well as to a challenge with the heterologous ligand toxic shock syndrome toxin 1 plus D-Gal . Contrary to the first challenge, no serum-borne IL-2 and TNF are discernible during the second challenge . On the other hand, kinetic analyses in vitro of LN cells draining the site of the first in vivo challenge indicate that SEB-reactive T cells develop via a transient state of hyperreactivity into a profound state of ligand-specific unresponsiveness . Yet unresponsive V beta 8+ T cells express IL-2R and are responsive to the growth-promoting effect of IL-2 . Cyclosporin A does not impair sequential induction of hyperreactivity and unresponsiveness with concomitant IL-2R expression, but effectively blocks systemic IL-2 and TNF release during the initial hyperreactive phase . Taken together, the in vitro data imply that ligand-specific hyperreactivity followed immediately by ligand-specific unresponsiveness represents a hallmark of in vivo challenge with the superantigen SEB . The in vivo data suggest the existence of additional suppressive elements masking the ligand specificity of the state of unresponsiveness induced by SEB.

Pathol Biol (Paris), 1993 May, 41(5), 500 - 8
{Infectious complications of venous catheters}; Rey D; Infection is the most frequent complication of venous catheters . The various types of infection are defined, followed by a review of the modalities of contamination of a catheter . The microorganism most frequently involved is Staphylococcus . The bacteriological diagnosis of a venous catheter infection is essentially based on semiquantitative culture according to Maki's technique or a quantitative method (Cleri or Brun-Buisson) . Bacteriological diagnostic methods are also being developed to allow maintenance of the catheter . Treatment is primarily preventive, while, in addition to systemic antibiotics, curative treatment may also consist of attempts to maintain the infected catheter in place and the so-called "antibiotic lock" technique.

Z Naturforsch {C}, 1993 May-Jun, 48(5-6), 488 - 94
Differential effect of Hg(II) on {d(A)n.d(T)n} and {d(A-T)n.d(A-T)n} sequences: circular dichroism (CD) measurements and endonuclease digestion studies using poly{d(A).d(T)} and poly{d(A-T).d(A-T)} as substrates; Ok SR et al.; The long-wavelength positive CD bands of poly{d(A).d(T)} and poly{d(A-T).d(A-T)} become inverted upon the addition of Hg(ClO4)2 . Poly{d(A).d(T)} requires higher levels of mercury to undergo inversion than poly{d(A-T).d(A-T)} . Mercurated poly{d(A).d(T)} is digested more rapidly than the control by DNase I or staphylococcal nuclease at low levels of Hg(ClO4)2 . Let r identical to {Hg(ClO4)2}added/{DNA-P} . A 4- to 5-fold rate increase occurs with DNase I at r = 0.25; a 2-fold increase with staphylococcal nuclease at r = 0.2 . By contrast, digestion of poly{d(A-T).d(A-T)} decreases immediately with increasing r . The noted rate increases appear to be due to a modification of poly{d(A).d(T)} helix structure prior to the chiroptical conversion . The modification is interpreted as a widening of the minor groove, permitting, thus, a better binding of DNase I to its substrate . The overall changes in CD as well as enzymatic digestion rates are taken to signal mercury-induced alterations in helix screwness from right-to-left . They are totally reversible subsequent to the removal of mercury.

J Exp Med, 1993 May 1, 177(5), 1451 - 9
The selective ablation of interleukin 2-producing cells isolated from transgenic mice; Minasi LE et al.; To better understand the requirement for interleukin 2 (IL-2) in specific immune responses, we have established the use of cell ablation to selectively eliminate T cells that produce IL-2 . To accomplish this we have generated transgenic mice that express the herpes simplex virus 1-thymidine kinase (HSV-TK) gene under the transcriptional control of the murine IL-2 promoter that renders IL-2-producing cells sensitive to the cytotoxic effects of the antiviral drug ganciclovir (GANC) . HSV-TK activity was specifically expressed in activated T cells from transgenic mice . When CD4 T cells from transgenic mice were stimulated with the superantigen staphylococcal enterotoxin A (SEA) in the presence of GANC, proliferation and IL-2 production were almost completely inhibited and the activated CD4+V beta 3+ T cell population, eliminated . Proliferation was not restored by adding IL-2, showing that most proliferating cells are not bystander cells . In contrast, the proliferative response to concanavalin A (Con A) was only partially inhibited by treatment of CD4 T cells with GANC, although the efficiency of eliminating IL-2-producing cells was shown to be comparable with that achieved using SEA . This suggests that a portion of the proliferative response to Con A occurs via an alternative pathway not requiring IL-2 synthesis and release.

J Biomol NMR, 1993 May, 3(3), 297 - 306
Measurement of two- and three-bond 13C-1H J couplings to the C delta carbons of leucine residues in staphylococcal nuclease; Vuister GW et al.; A new 1H-detected 3D NMR experiment is described that permits quantitative measurement of two- and three-bond 13C-1H couplings in proteins with selectively 13C-enriched methyl sites . The method is demonstrated for staphylococcal nuclease selectively {5,5 13C}-labeled in all 11 leucine positions and ligated with thymidine 3',5'-biphosphate and Ca2+ . Two- and three-bond 13C methyl-proton couplings are reported and, together with the measured three-bond JC alpha C delta in uniformly 13C-enriched staphylococcal nuclease, the chi 2-angles and the stereospecific assignments of the C delta methyl group with respect to the prochiral beta-protons were determined . The same residues that were previously found to have high degrees of internal mobility on the basis of 13C relaxation times have measured coupling constants that are indicative of motional averaging.

Zentralbl Veterinarmed B, 1993 May, 40(3), 206 - 14
Staphylococcus intermedius: current knowledge on a pathogen of veterinary importance; Greene RT et al.; It has been 16 years since the identification of S . intermedius as a new species . Numerous investigations using cell wall and DNA analytic methods have now clearly demonstrated significant differences to warrant the creation of this new species . However, studies investigating virulence factors associated with S . intermedius have not uncovered evidence that differentiates virulent from non-virulent isolates . Therefore, at the present time, it is difficult for veterinary clinicians and microbiologists to determine the clinical significance of many S . intermedius isolates . Host-bacterial interactions and the hosts' immune status appear to be the factors most crucial in determining the outcome of infections, not the virulence of the organism . Continued research in the virulence factor field will hopefully lead to a better understanding on how we can differentiate virulent from nonvirulent isolates of S . intermedius.

J Antimicrob Chemother, 1993 May, 31 Suppl D, 103 - 11
Experimental foreign body infection in mice; Espersen F et al.; A number of experimental foreign body infections have been described . We present here an easy, reproducible staphylococcal foreign body infection model in mice . The failure of treatment with methicillin and gentamicin is demonstrated, while the usefulness of antibiotic prophylaxis is documented . The usual correlations between pharmacokinetic parameters and the effect of antibiotics in vivo seem not to hold when a foreign body is present . The model may be applicable to large-scale evaluation of different antibiotic regimens.

Aust N Z J Ophthalmol, 1993 May, 21(2), 99 - 103
Fusidic acid prophylaxis before cataract surgery: patient self-administration; Gray TB et al.; In a placebo-controlled, randomised, double-blind clinical trial, the authors evaluated the efficacy of patient-administered 1% fusidic acid viscous eye drops in clearing the commonest organisms causing pseudophakic endophthalmitis (Staphylococcus epidermidis and aureus) from the lids and conjunctivae of 79 patients before cataract surgery . The treatment group self-administered fusidic acid viscous eye drops four times daily for seven days before surgery; the placebo group received inert ophthalmic drops . Fellow eyes of both groups remained untreated as a natural control . Lower fornix and lid margin cultures were taken from both eyes before and after treatment . Before treatment, there was no statistical difference in organism counts between the groups . After treatment, eyes receiving fusidic acid were more likely to be free of clinically relevant Staphylococcus spp . than all pre-treatment eyes (for lids, P << 0.001; conjunctivae, P = 0.02) . A highly significant (P < 0.001) number of lid margins were rendered 'clinically clean' (i.e., 0-49 organisms/swab) by fusidic acid when compared with untreated eyes . Treatment also effectively (P < 0.05) reduced the numbers of bacteria isolated from conjunctivae . This study indicates that there is a highly significant reduction of Staphylococcus spp . (P << 0.001), non-Staphylococcus spp . (P << 0.001) and attainment of sterile eyes (P << 0.001) at operation gained by patient self-administration of 1% fusidic acid four times daily for seven days before surgery.

Thorax, 1993 May, 48(5), 578 - 80
Pneumatoceles and pneumothoraces complicating staphylococcal pneumonia: treatment by synchronous independent lung ventilation; Lohse AW et al.; A 54 year old man with a staphylococcal sepsis developed staphylococcal pneumonia complicated by multiple pneumatoceles and bilateral tension pneumothoraces caused by bronchopleural fistulae . Excessive enlargement of the right sided pneumatoceles and a tension pneumothorax not improved by drainage led to mediastinal shift and compression of the right lung . Reversal of the mediastinal shift and closure of the bronchopleural fistulae was achieved by assisted independent lung ventilation.

AIDS Res Hum Retroviruses, 1993 May, 9(5), 455 - 64
Regulation of HIV production by blood mononuclear cells from HIV-infected donors: I . Lack of correlation between HIV-1 production and T cell activation; Moran PA et al.; The relationship between production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from HIV-1-infected donors and the level of T cell activation by various stimuli was examined . Stimulation of PBMCs with soluble anti-CD3 antibody or staphylococcal enterotoxin/superantigen (SAg) was found to be 100-1000 times more effective at inducing production of HIV-1 than was stimulation with immobilized anti-CD3 or various other T cell activating agents . However, proliferation of CD4+ T cells and lymphokine production following stimulation with soluble anti-CD3 were less than with immobilized anti-CD3 . To determine whether immobilized anti-CD3 stimulated cells may produce a factor(s) that suppresses HIV production, dual-chamber coculture experiments were performed in which soluble and immobilized anti-CD3-stimulated CD8-depleted PBMCs were separated by porous membranes . Stimulation of cells by immobilized anti-CD3 suppressed HIV-1 production by soluble anti-CD3-stimulated cells in the inner chamber, suggesting that diffusible factor(s) are involved in suppressing HIV-1 production . Experiments in which exogenous cytokines were added to cells stimulated with soluble anti-CD3 did not reveal the suppressive factor(s) produced; however, IL-7 was found to markedly increase HIV-1 production . Both T cells and monocytes were found to be required for soluble anti-CD3 to induce high levels of HIV-1 production, suggesting a role for adhesion molecules . Our results thus show that (1) soluble anti-CD3 is a powerful stimulus for HIV production, (2) there is not an absolute correlation between the level of HIV-1 production and T cell activation following stimulation of PBMCs with T cell activating agents, (3) immobilized anti-CD3 stimulation produces a factor that decreases HIV replication, and (4) T cell monocyte interactions are important for production of HIV-1 following stimulation with soluble anti-CD3.

Nippon Jibiinkoka Gakkai Kaiho, 1993 May, 96(5), 810 - 7
{Gamma delta T cells in the palatine tonsil--immunohistological and functional study}; Kawaguchi T; In the present study, the gamma delta T cell content of the tonsillar T cell population has been evaluated for the first time . Flow cytometric analysis showed that 1.56% of T cells in palatine tonsils obtained from patients with recurrent tonsillitis (n = 17) expressed the gamma delta T cell receptor . Next, the tissue distribution of these cells in palatine tonsil was examined immunohistologically . Gamma delta T cell receptor positive cells and CD3 positive cells were counted in the crypt epithelium, tonsillar epithelium on the free surface and in the interfollicular space (n = 29) . The gamma delta T cell content of the whole T cell population in each of these regions was calculated and compared . It was demonstrated that T cells in the crypt epithelium contained more gamma delta T cell receptor bearing cells than did T cells infiltrating the tonsillar epithelium on the free surface . T cells in the interfollicular space included even fewer gamma delta T cells . The gamma delta T cell content of tonsillar T cells showed a gradual decrease with age in each region . Then, infiltration of gamma delta T cells in the crypt epithelium was compared among recurrent tonsillitis, hypertrophic tonsil and focus tonsil (PPP) specimens . Recurrent tonsillitis showed the highest gamma delta T cell content in T cells infiltrating the crypt epithelium . There was no remarkable infiltration of these cells in the crypt epithelium of focus tonsil . Furthermore, the gamma delta T cell population was isolated from tonsillar lymphocytes and stimulated with staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1).(ABSTRACT TRUNCATED AT 250 WORDS)

J Hosp Infect, 1993 May, 24(1), 47 - 61
Daily scrub with chlorhexidine reduces skin colonization by antibiotic-resistant Staphylococcus epidermidis; Hedin G et al.; The aim of this study was to establish whether long-term use of chlorhexidine would prevent skin colonization by antibiotic-resistant Staphylococcus epidermidis . Ten nurses, working on a ward for haematological disorders, volunteered to participate in the test . They washed one arm every morning for three weeks with chlorhexidine gluconate, ('Hibiscrub' ICI Pharmaceuticals) . The other arm served as a negative control . Samples from the antecubital fossa of both arms were taken two to three times a week during the wash period and two weeks thereafter, giving a total of 216 samples . The appearance of resistant S . epidermidis with different antibiograms was analysed . During the wash period the total bacterial counts and the counts of the resistant S . epidermidis strains on the test arm were both about one-tenth of those on the control arm, a significant difference (P < 0.05) . Moreover, there were significantly fewer resistant S . epidermidis on the test arm, 1.3 per sample, than on the control arm, 2.5 per sample (P < 0.01) . Most of the resistant S . epidermidis were only found once or a few times on the same site, after which they disappeared, though a few persisted on the skin even during 'Hibiscrub' washing . In an agar dilution test, chlorhexidine minimum inhibitory concentrations (MICs) of persisting strains were the same as for strains disappearing from the skin following 'Hibiscrub' washing, 1.0 or 2.0 mg l-1, but somewhat higher than MICs of strains isolated from healthy carriers outside the hospital whose MICs were 0.5 mg l-1 . The relative contribution to the skin counts by those S . epidermidis strains found only occasionally were compared with those found repeatedly but no difference in reduction was found between these categories during 'Hibiscrub' washing.

AIDS Res Hum Retroviruses, 1993 May, 9(5), 465 - 73
Regulation of HIV production by blood mononuclear cells from HIV-infected donors: II . HIV-1 production depends on T cell-monocyte interaction; Diegel ML et al.; Cell-cell interactions induced between T cells and monocytes by certain soluble anti-CD3 monoclonal antibodies (MAbs) were previously shown to be required for high-level production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from infected donors . Staphylococcal enterotoxin or superantigen (SAg) is another mitogen inducing monocytes-T cell interactions that exhibit potent induction of HIV-1 production . Antibodies to several adhesion molecules were used to test the requirements for T cell- and monocyte-associated adhesion molecules in HIV-1 production following activation with anti-CD3 or SAg . Blocking of either CD2-LFA-3, or CD18-ICAM-1, inhibited anti-CD3- or SAg-induced HIV-1 production by more than 90% without inhibiting CD4+ T cell proliferation . Inhibition of HIV production was observed when either the T cell or monocyte coreceptor was bound by MAbs to these adhesion molecules . Blocking of CD28-B7 interactions by soluble CTLA-4 fusion protein, a CD28 homolog, inhibited both HIV-1 production and CD4+ T cell proliferation . Fc binding was not required for HIV-1 inhibition by MAbs to CD2 and CD18, because Fab or F(ab')2 fragments of these MAbs inhibited HIV-1 production by more than 80% . A chimeric single-chain MAb to CD2 was produced, containing heavy and light chain variable regions from MAb 35.1 to CD2 linked to the constant regions of human IgG1 (CD2 SFv-Ig) . This humanized CD2 SFv-Ig inhibited HIV-1 production by 30% to > 98% . These results thus indicate that simultaneous engagement of multiple adhesion pathways between T cells and monocytes are required for HIV production by patients PBMCs and may have implications for therapy of HIV infections.

J Immunol, 1993 May 1, 150(9), 3873 - 81
Study of activation of murine T cells with bacterial superantigens . In vitro induction of enhanced responses in CD4+ T cells and of anergy in CD8+ T cells; Yan XJ et al.; Primary and secondary responses of murine CD4+ T cells and CD8+ T cells upon stimulation with staphylococcal enterotoxin E (SEE) bearing superantigenic properties were examined . Both isolated C57BL/6 splenic CD4+ T cells and CD8+ T cells proliferated and produced IL-2 and IFN-gamma upon stimulation with SEE in substantial levels . The amounts of IL-2 were greater in CD4+ T cells and those of IFN-gamma were somewhat greater in CD8+ T cells . SEE-induced CD4+ T lymphoblasts, larger parts of which bore the V beta 11 element in their TCR, proliferated, produced IL-2 and IFN-gamma, and showed toxin-dependent cytotoxicity in substantial levels upon restimulation with SEE . By contrast, SEE-induced CD8+ T lymphoblasts, the larger part of which bore the V beta 11 element, did not show the first two of the three responses at all upon restimulation with SEE, whereas these cells showed greater cytotoxicity . The CD8+ T lymphoblasts did not suppress the reactivity of the CD4+ T lymphoblasts . Both SEE-induced CD4+ T lymphoblasts and CD8+ T lymphoblasts proliferated and produced IL-2 and IFN-gamma in comparable levels upon stimulation with rIL-2 or mAb to CD3 or V beta 11.

Biull Eksp Biol Med, 1993 May, 115(5), 475 - 6
{Correlation of protein content in salivary gland tissue, oral mucosa and saliva in experimental staphylococcal sialoadenitis}; Mikhailov VV et al.; The dependence between the total content and excretion of protein (P) in salivary gland tissue (SGT), oral mucosa (OM) and saliva has been investigated . The difference between P contents in intact gland and during staphylococcus sialoadenitis has been shown . After 2 hours of staphylococcus toxin injection in non-stimulated SGT P contents are not changed, and in saliva--are increased . After 24 hours in non-stimulated SGT P contents are decreased, in OM P contents are increased . By stimulation of SGT, P contents increases, in OM--decreases.

Biochim Biophys Acta, 1993 Apr 21, 1163(1), 81 - 8
Molecular dynamics study of the stability of staphylococcal nuclease mutants: component analysis of the free energy difference of denaturation; Yamaotsu N et al.; The stability of two mutants G88V (Gly-88-->Val) and A69T (Ala-69-->Thr) of staphylococcal nuclease was analyzed by molecular dynamics simulations . The calculated free energy differences of denaturation for G88V and A69T were -1.1 and -2.8 kcal/mol, respectively . These values are in good agreement with the experimental values . The free energy differences divided into electrostatic and van der Waals components were analyzed . These two mutants are mainly destabilized due to van der Waals interactions . There is little difference between the electrostatic contribution to the free energy change in the native state and that in the denatured state . In each mutant structure, a small cavity appears in the vicinity of the perturbed residue . It is suggested that intramolecular van der Waals interactions of the mutants are weaker than those of the wild-type . Furthermore, analyses of the contributions of each residue near the perturbed residue and of water to the free energy difference of denaturation suggest that the interaction between water and the perturbed residue plays a very important role in the stability of staphylococcal nuclease, and that a small hydrophobic core consisting of the three aromatic rings (Tyr-27, Phe-34, Phe-76) and the side chain of Met-32 is also important for the stability.

Proc Natl Acad Sci U S A, 1993 Apr 15, 90(8), 3275 - 9
The alpha aneurism: a structural motif revealed in an insertion mutant of staphylococcal nuclease; Keefe LJ et al.; The x-ray crystal structure of a mutant of staphylococcal nuclease that contains a single glycine residue inserted in the C-terminal alpha-helix has been solved to 1.67 A resolution and refined to a crystallographic R value of 0.170 . This inserted glycine residue is accommodated in the alpha-helix by formation of a previously uncharacterized bulge, which we term the alpha aneurism . A conformational search of known protein structures has identified the alpha aneurism in a number of protein families, including the histocompatibility antigens and hemoglobins.

Vet Rec, 1993 Apr 3, 132(14), 351 - 3
A comparison of lincomycin hydrochloride and clindamycin hydrochloride in the treatment of superficial pyoderma in dogs; Harvey RG et al.; Thirty dogs with superficial pyoderma were randomly allocated to treatments with either lincomycin hydrochloride (22 mg/kg twice daily) or clindamycin hydrochloride (11 mg/kg once daily), initially for three weeks . Samples were taken from pustules, from adjacent apparently uninvolved skin, and from the nares . These were submitted for bacterial culture and sensitivity testing . The dogs were re-examined after three weeks treatment and samples for bacteriology were taken from the nares, from any pustules that were present or from skin in the area that was previously affected; the treatment was extended if necessary . Seventy-one per cent of the dogs given lincomycin hydrochloride responded within three weeks compared with 81 per cent of the dogs treated with clindamycin hydrochloride . The overall response rates, including those given longer courses of treatment were 93 per cent for those treated with lincomycin hydrochloride and 94 per cent for those treated with clindamycin hydrochloride, and there was no statistically significant difference between the groups either after three weeks treatment or after extended treatment . The microbiological results demonstrated that Staphylococcus intermedius was present on the skin adjacent to pustules and suggested that the nasal carriage of S intermedius was a result of cutaneous colonisation.

Protein Sci, 1993 Apr, 2(4), 567 - 76
Thermal unfolding of staphylococcal nuclease and several mutant forms thereof studied by differential scanning calorimetry; Tanaka A et al.; The effects of eight mutations on the thermodynamics of the reversible thermal unfolding of staphylococcal nuclease have been determined over a range of pH and protein concentration by means of differential scanning calorimetry . Variation of the protein concentration was included in our study because we found a significant dependence of the thermodynamics of protein unfolding on concentration . Values for the change in the standard free energy of unfolding, delta delta G0d, produced by the mutations in the pH range 5.0-7.0 varied from 1.9 kcal mol-1 (apparent stabilization) for H124L to -2.8 kcal mol-1 (apparent destabilization) for L25A . As has been observed in numerous other cases, there is no correlation in magnitude or sign between delta delta G0d and the corresponding values for delta delta Hd and T delta delta S0d, the latter quantities being in most cases much larger in magnitude than delta delta G0d . This fact emphasizes the difficulty in attempting to correlate the thermodynamic changes with structural changes observed by X-ray crystallography.

Vet Microbiol, 1993 Apr, 34(4), 363 - 72
Antibiotic-resistance and plasmids in Staphylococcus hyicus isolated from pigs with exudative epidermitis and from healthy pigs; Wegener HC et al.; A total of 100 S . hyicus strains isolated from healthy piglets and piglets with exudative epidermitis originating from 100 different herds was examined for drug-resistance and prevalence of plasmids . Resistance to macrolide/linosamide antibiotics could be related to plasmids in 55 (93%) of the 59 resistant strains: A plasmid of 2.4 kb mediating resistance to macrolides and lincosamides was observed in 25 strains, and a plasmid of 11.5 kb mediating resistance to both macrolides/lincosamides and tetracycline was observed in 30 strains . A plasmid with a molecular weight of 4.5 kb was shown by curing experiments to be associated with resistance to tetracycline in 12 strains . All together, 47 strains were resistant to tetracycline . In 42 (89%) of these strains tetracycline-resistance was found to be encoded by plasmids . Fifty six strains were resistant to streptomycin, and resistance was associated with the presence of a 4.4 kb plasmid in 17 strains studied . Resistance to penicillin, observed in 44 strains, and resistance to kanamycin, observed in 15 strains, could not be related to plasmids in any of these strains . The 11.5 kb plasmid was observed in 39% of the strains isolated from piglets with EE, and in 7% of the strains isolated from healthy piglets . Despite its higher prevalence in strains from piglets with EE, the 11.5 kb plasmid could not be shown to encode production of capsule or exfoliative substances: factors which might play a role in the development of exudative epidermitis in piglets.

J Antibiot (Tokyo), 1993 Apr, 46(4), 661 - 7
Octapeptide derivatives of teicoplanin antibiotics; Malbarba A et al.; A series of octapeptide derivatives of teicoplanin-A2 component 2 (CTA/2), its aglycone (TD), and the L-lysyl derivatives of an amide of CTA/2 and TD, were prepared by condensation of the terminal amino group with N-hydroxysuccinimidyl esters of tert-butyloxycarbonyl (BOC) L- and D-amino acids, followed by acidic (TFA) removal of the BOC protecting function . The antimicrobial properties of these compounds were compared with those of the corresponding unmodified antibiotics and their N15-acetyl derivatives . The most active derivatives were the octapeptides with N-terminal glycine or lysine whose in vitro activity was comparable to that of the parent teicoplanins . The glycinyl and lysyl derivatives of CTA/2 showed better activity than CTA/2 against clinical isolates of Staphylococcus epidermidis and S . haemolyticus for which teicoplanin MICs were relatively high . No significant difference in their antibacterial activity was observed between octapeptides containing L- or D-lysine.

Can J Vet Res, 1993 Apr, 57(2), 119 - 25
Staphylococcus hyicus virulence in relation to exudative epidermitis in pigs; Wegener HC et al.; Staphylococcus hyicus strains with different phage types, plasmid profiles, and antibiotic resistance patterns were isolated from piglets with exudative epidermitis . The strains could be divided into virulent strains, producing exudative epidermitis, and avirulent strains, producing no dermal changes when injected in experimental piglets . The results showed that both virulent and avirulent strains were present simultaneously on diseased piglets . This constitutes a diagnostic problem . Concentrated culture supernatants from nine virulent strains injected in the skin of healthy piglets produced a crusting reaction in all piglets . Acanthosis was observed in the histopathological examination of the crustaceous skin . Concentrated culture supernatants from nine avirulent strains produced no macroscopic or microscopic skin changes . Protein profiles from all virulent strains and seven out of nine avirulent strains showed a high degree of protein band homology . An approximately 30 kDa protein present in all concentrated culture supernatants capable of producing skin changes, could not be detected in samples that did not produce skin changes . No other protein showed a similar association . It is concluded that crusting reaction of piglet skin is a suitable indicator of virulence in S . hyicus in relation to exudative epidermitis, and that virulent strains produce a 30 kDa protein, absent in concentrated culture supernatants from avirulent strains . This 30 kDa protein might be an exfoliative toxin.

J Appl Bacteriol, 1993 Apr, 74(4), 411 - 6
Fibronectin and proteolytic fragments of fibronectin interfere with the adhesion of Staphylococcus epidermidis to plastic; Dunne WM et al.; The adhesion of five strains of slime-positive Staphylococcus epidermidis to plastic microwells was significantly diminished (P < 0.005) in a concentration-dependent fashion when wells were previously coated with increasing concentrations (1.6-13.1 micrograms cm-2) of human fibronectin (FN) . The adhesion of four of five strains was significantly reduced when wells were coated with 3.2 micrograms cm-2 of FN and at concentrations > or = 6.5 micrograms cm-2 the adhesion of all slime-positive strains was significantly reduced . The coating of microwells with chymotryptic fragments of FN containing the heparin-binding, gelatin-binding, or cell-binding domains also reduced bacterial adhesion but none of the fragments exceeded the anti-adhesive activity of intact FN . A comparison of FN-coated or albumin-coated microwells showed that both proteins caused a significant reduction in the adhesion of test strains to plastic but that the anti-adhesive activity of FN was greater than albumin at all concentrations tested . The adhesion of the slime-negative phase variant of one of the test strains to plastic was neither enhanced nor reduced by FN coating indicating that the production of an exopolysaccharide by Staph . epidermidis influences interactions with protein-coated surfaces . These results support the contention that FN does not mediate the adhesion of all strains of Staph . epidermidis to plastic surfaces.

J Pediatr Surg, 1993 Apr, 28(4), 627 - 9
Persistent catheter-related bacteremia: clearance with antibiotics and urokinase; Ascher DP et al.; A patient with terminal osteogenic sarcoma and catheter-related coagulase-negative staphylococcal bacteremia was treated with vancomycin and blood cultures were positive for 4 days documented with quantitative colony counts . Urokinase therapy was initiated and was associated with a transient bacteremia with markedly increased colony counts of coagulase-negative Staphylococcus prior to eradication of the catheter-related infection . We feel that the combination of urokinase and appropriate antibiotics may be an effective method to eradicate line-associated coagulase-negative staphylococcal infection in selected patients.

Clin Podiatr Med Surg, 1993 Apr, 10(2), 249 - 69
Infection and the older patient; Abramson C; An increasing number of elderly patients are in and out of doctors' offices, hospitals, nursing homes, and so forth, under continual medical care . Numerous invasive procedures allow for casual transfer of infectious diseases by fellow patients as well as health care workers . Dramatic increases in infectious diseases such as foot infections, pneumonia, staphylococcal infections and, because of necessary invasive and blood transfusion procedures, AIDS can be expected in the future . The elderly patient is often a debilitated, compromised, immunodeficient host who is highly susceptible to any number of infections . With this in mind as the population grows older, clinicians must begin to apply Universal Precautions in their practices if they have not already done so, and not underestimate any disease or symptom in any patient, regardless of their age or their condition.

Cutis, 1993 Apr, 51(4), 276 - 8
Transfer of bacteria associated with cryotherapy; Wolf R et al.; The aim of this study was to determine whether living bacteria can be transmitted by cryosurgery with carbon dioxide . Cultures were taken from the outer layer of the ice before starting treatment, and again at the end of the working day during ten consecutive working days . Each of ten dry ice blocks was sterile prior to use . Staphylococcus epidermidis was isolated from six of the latter following use . This finding indicates that the dry ice was contaminated during the procedure and that bacteria were transmitted from the patient's skin to the dry ice and to culture media . The medical implications of this finding require serious consideration regarding the risk of infection to both patient and clinical personnel from this procedure.

Transplantation, 1993 Apr, 55(4), 785 - 9
Renal transplantation following immunoadsorption in highly sensitized recipients; Ross CN et al.; Five highly sensitized patients, with panel reactivity greater than 80% for 1.75-5 years, were treated by extracorporeal staphylococcal protein-A immunoadsorption, prednisolone, and cyclophosphamide . The five patients underwent treatment of 18-40 (mean 31) liters of plasma, respectively in 4-7 (mean 5.6) sessions . This reduced the titer of cytotoxic antibodies to sensitizing antigens to < 1/8 in all cases and abolished reactivity to crossreacting antigens . Two patients required retreatment following resynthesis of cytotoxic antibodies . All five patients have been transplanted, and four of these now have stable serum creatinines of 168 mumol/L at 34 months, 208 mumol/L at 29 months, 96 mumol/L at 5 months, and 125 mumol/L at 3 months posttransplantation . One patient had primary graft dysfunction due to acute tubular necrosis; the kidney was removed after eight weeks and showed cortical necrosis without evidence of acute rejection.

Am J Kidney Dis, 1993 Apr, 21(4), 411 - 8
Biocompatibility of a glucose-polymer-containing peritoneal dialysis fluid; de Fijter CW et al.; The currently available glucose-containing peritoneal dialysis fluids (PDF), which are all hyperosmolar, are toxic to the cells present in the peritoneal cavity . However, glucose-polymer solutions, being isosmolar, may have improved biocompatibility in this respect . We therefore compared in vitro the effects of PDF containing glucose-polymers with that of glucose solutions on the function of donor granulocytes and monocytes (MN), and on the viability of mesothelial cells . In addition, the function of peritoneal macrophages (PMO) of eight patients was studied in a randomized cross-over setting following intraperitoneal exposure to glucose-polymer-versus glucose-monomer-containing fluid of comparable ultrafiltration capacity . Donor granulocytes, as well as MN, showed significantly better phagocytosis of both Staphylococcus epidermidis and Escherichia coli after incubation in the glucose-polymer solution as compared with the 3.86% glucose-containing fluid . Their oxidative metabolism, as measured by chemiluminescence, also showed that the glucose-polymer solution was less inhibitory than fluids containing 2.27 or 3.86% glucose . Patient-derived PMO showed a significantly better phagocytic capacity for S epidermidis and E coli, a significantly higher killing of E coli, and a significantly higher chemiluminescence response after intraperitoneal exposure to the glucose-polymer solution as compared with the glucose-monomer-based fluid . Increasing the osmolality of the glucose-polymer solution to that of the respective glucose solutions blunted the favorable effect on phagocyte function, suggesting the beneficial effect to be osmolality-mediated . However, no major difference was observed between the glucose-polymer solution and the glucose-based fluid in their effects on mesothelial viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Rheumatol, 1993 Apr, 32(4), 339 - 41
Vertebral osteomyelitis due to Staphylococcus epidermidis; De Wit D et al.; Vertebral osteomyelitis due to Staphylococcus epidermidis is extremely rare and usually occurs in the context of immunosuppression in association with an adequate portal of entry for infection . This paper reports a case of vertebral osteomyelitis due to S . epidermidis in a man with no evidence of immunosuppression or obvious portal of entry . The patient presented with severe back pain but there were no clinical signs of infection . Radiographs and computerized tomographs showed destruction of thoracic vertebral bodies and an adjacent soft tissue mass . S . epidermidis was grown from multiple blood cultures . All isolates had identical antibiograms and biochemical profiles . There was evidence of healing of the vertebral bodies and resolution of the soft tissue mass after appropriate antistaphylococcal treatment.

Eur J Immunol, 1993 Apr, 23(4), 815 - 9
Clonal deletion of thymic mature T cells induced by staphylococcal enterotoxin B in murine fetal thymus organ culture; Aiba Y et al.; The present study aims at investigating the intrathymic maturational stage of T cells at which clonal deletion can be induced . Staphylococcal enterotoxin B (SEB) was added to organ cultures of murine fetal thymus lobes at various time points of culture, and V beta 8-expressing cells were assayed on day 14 . V beta 8 low-expressing (V beta 8lo) cells were reduced to 40-60% of the control receiving no SEB, though the reduction was ambiguous when SEB was given on day 13 . In marked contrast, V beta 8 high-expressing (V beta 8hi) cells were virtually completely deleted in all groups including the group given SEB on day 13 . Most of the V beta 8hi cells that were deleted by 24 h of treatment with SEB were shown to be of the CD4+8- mature phenotype, though CD4-8+V beta 8hi cells were also deleted . It was further shown that the thymic V beta 8hi CD4+8- cells recovered from organs cultured for 14 days without SEB responded to immobilized anti-V beta 8 monoclonal antibody, indicating that V beta 8hi cells, which were highly sensitive to clonal deletion, were functionally competent mature T cells . These results strongly suggest that the thymus is capable of eliminating all T cells recognizing antigen present in the thymus regardless of the maturational stage of T cells.

Eur J Immunol, 1993 Apr, 23(4), 809 - 14
Effects of intrathymic injection of organ-specific autoantigens, parietal cells, at the neonatal stage on autoreactive effector and suppressor T cell precursors; Murakami K et al.; Thymectomy on day 3 after birth (3d-Tx) induces autoimmune gastritis (AIG) in 81%, and oophoritis (AIO) in 25% of BALB/c mice at the age of 2 to 3 months . Intrathymic, but not intraperitoneal injection of syngeneic parietal cells into sex-matched BALB/c mice within 24 h of birth resulted in almost complete prevention of the development of AIG in these mice in which 3d-Tx was performed . The prevention induced was parietal cell specific, since the development of AIO was not inhibited in female mice . Moreover, the injection of BALB/c liver cells, Mls-matched (BALB/c) and -disparate (DBA/2) B blasts which resulted in V beta 6 T cell deletion, as well as the injection of staphylococcal enterotoxin B failed to prevent the diseases . These findings suggested that recognition of an autoantigen in the thymus is necessary for the induction of tolerance, and that involvement of Mls-1 antigens in the pathogenesis of AIG, as has been suggested previously (Schwartz, R . H., Cell 1989 . 57: 1073), was unlikely . T cells that suppress the development of organ-specific autoimmune diseases in 3d-Tx mice seem to maintain the unresponsiveness of autoreactive T cells at the periphery in normal mice . In agreement with our previous observations, we found that intraperitoneal (i.p.) injection of spleen cells from 3-month-old normal mice into 3d-Tx mice on day 10 after birth prevented the development of AIG, whereas spleen cells from age-matched AIG+ (mice with AIG) or AIG- (mice without AIG) 3d-Tx mice failed to do this . This implies that the suppressor cells probably affect the differentiation of effector-precursor to effector . In fact, these suppressor cells did not inhibit the adoptive transfer of AIG to nu/nu BALB/c mice by spleen cells from 3d-Tx mice manifesting AIG . By negative selection using monoclonal antibody and complement, it was confirmed that the phenotype of the suppressor cell was CD4 . In contrast to 3d-Tx, 10d-Tx did not induce AIG, indicating the peripheralization of the suppressor cell by that time . On the other hand, intrathymic injection of parietal cells immediately after birth did not affect suppressor cell generation, implying that some T cells, including suppressor cells, escape thymus selection . We postulate that these cells correspond to the precursors of the autoreactive effector T cells and suppressor T cells that are present in normal mice.

J Neurosurg, 1993 Apr, 78(4), 630 - 7
T-cell receptor V-gene usage in neoplasms of the central nervous system . A comparative analysis in cultured tumor infiltrating and peripheral blood T cells; Merlo A et al.; The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization . Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells . Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells . Autologous peripheral blood mononuclear cells from the same patients were similarly cultured . After 4 to 5 weeks of culture, 97.3% +/- 2.6% (mean +/- standard deviation) of the resulting cell populations were CD3-positive lymphocytes . The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-alpha 2, V-beta 5, 6, 8, and 12, V-gamma 4 and 9 families, and from two subfamilies of V-delta 2 . Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1% . In contrast, a different expression of individual V-gene products, concerning both alpha/beta and gamma/delta T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients . In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-beta T-cell receptors . Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

J Appl Physiol, 1993 Apr, 74(4), 1972 - 80
Staphylococcal alpha-toxin induced ventilation-perfusion mismatch in isolated blood-free perfused rabbit lungs; Walmrath D et al.; Gas exchange conditions in blood-free perfused isolated rabbit lungs were assessed by the use of the multiple inert gas elimination technique . Under baseline conditions, unimodal narrow distribution of perfusion and ventilation to midrange-ventilation-perfusion (VA/Q) areas was noted . Intravascular challenge with staphylococcal alpha-toxin caused a rapid increase in pulmonary arterial pressure (to > 40 mmHg within approximately 15 min) and delayed-onset (> 10-15 min) lung edema formation, with unaltered ventilation pressures . The vasoconstrictor response was paralleled by a progressive, severe leftward shift of perfusion to areas with low-VA/Q ratios, accompanied by a minor fraction of shunt flow . At pulmonary arterial pressures > 40 mmHg, extreme VA/Q mismatch with near absence of perfusate flow to midrange-VA/Q areas was registered . Vasoconstrictor response and VA/Q mismatch, but not the progressive edema formation, were virtually completely suppressed in lungs pretreated with acetylsalicylic acid or the thromboxane receptor antagonist BM 13505 . Moreover, "rescue" application of BM 13505 after onset of alpha-toxin-induced pressor response and gas exchange abnormalities completely reversed pressure elevation and loss of VA/Q matching . We conclude that the marked vasoconstrictor response to staphylococcal alpha-toxin is paralleled by severe VA/Q mismatch with predominant perfusion of low-VA/Q areas independent of lung edema formation . Pressor response and VA/Q mismatch, but not vascular leakage, are suppressed by thromboxane inhibition.

Am J Physiol, 1993 Apr, 264(4 Pt 1), G708 - 17
Beta-adrenergic inhibition of electrical and mechanical activity in canine colon: role of cAMP; Smith TK et al.; The effects of beta-adrenergic receptor stimulation on the electrical and mechanical activity of canine colonic circular muscles were compared with forskolin (Fsk), a known stimulator of adenylate cyclase . The actions of isoproterenol (Iso) were mediated by beta 2-receptors . Iso and Fsk increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in both the presence and absence of acetylcholine (ACh), whereas ACh (0.3 microM) alone reduced cAMP levels . These agents caused inhibition of spontaneous and ACh-induced contractions . Inhibition was associated with a reduction in the amplitude and duration of electrical slow waves recorded near the submucosal border . Near the myenteric border, Iso and Fsk hyperpolarized the membrane by up to 30 mV and changed the pattern of electrical rhythmicity . These effects were mimicked by 8-bromo-cAMP (1-3 mM) . Contractile inhibition with Fsk and Iso was associated with a decrease in the amplitude and duration of Ca2+ transients measured with fura-2 fluorescence . cAMP (10-300 microM) reduced the Ca2+ sensitivity of the contractile apparatus in muscles permeabilized with staphylococcal alpha-toxin . The actions of Iso appear linked to cAMP . We hypothesize that cAMP produces relaxation both by modulation of membrane ionic channels with a consequent decline in the entry of Ca2+ as well as through a decrease in the sensitivity of the contractile apparatus to Ca2+.

Avian Dis, 1993 Apr-Jun, 37(2), 536 - 41
Staphylococcosis of turkeys . 6 . Development of penicillin resistance in an interfering strain of Staphylococcus epidermidis; Whitehead SS et al.; Staphylococcus epidermidis strain 115, used as an interfering agent to help reduce the incidence of staphylococcosis in turkeys, was converted into a penicillin- and chloramphenicol-resistant strain designated 115R . This was accomplished by introducing a plasmid carrying the beta-lactamase (penicillinase) and chloramphenicol-resistance genes into S . epidermidis 115 by electroporation . The resultant strain, 115R, was an efficient producer of beta-lactamase and had marked increased resistance to penicillin and chloramphenicol . A beta-lactamase DNA probe was used to confirm the presence of the beta-lactamase gene in strain 115R . S . epidermidis strain 115R retained the characteristics of tissue adherence, bacteriocin production, and non-virulence that were present in the original non-transformed strain 115, and in addition should theoretically remain colonized in poults following treatment with penicillin.

Hum Immunol, 1993 Apr, 36(4), 259 - 67
Signal transduction mechanisms of HLA-DR-mediated interleukin-1 beta production in human monocytes . Role of protein kinase C and tyrosine kinase activation; Palkama T et al.; The signal transduction pathways leading to the expression of IL-1 beta in human monocytes via HLA-DR stimulation were investigated . SEB, a staphylococcal enterotoxin that binds to HLA-DR molecules, induced IL-1 beta expression in human monocytes . Protein synthesis inhibition by cycloheximide did not inhibit SEB-mediated IL-1 beta signal, indicating that protein synthesis is not required for the MHC class-II-mediated IL-1 beta expression . The effect of PKC, PKA, and tyrosine kinase inhibitors on HLA-DR-mediated IL-1 beta mRNA expression was then determined . H7, a preferential PKC inhibitor, completely inhibited IL-1 beta signal induced by SEB . The role of PKC on HLA-DR-mediated IL-1 beta induction was further confirmed by the ability of SEB to activate PKC on monocytes directly when measured with labeled phorbol ester ({3H}Pbt2)-binding capacity of whole cells . HA 1004, a preferential PKA inhibitor, and isobutyl-methyl-xanthine (IBMX), which inhibits the degradation of cAMP, had no effect on SEB-induced IL-1 beta signal, excluding the role of cAMP on HLA-DR-mediated IL-1 beta expression . Two tyrosine kinase inhibitors, genistein and dihydroxycinnamate, both inhibited SEB-induced IL-1 beta mRNA in monocytes . SEB also induced enhanced tyrosine phosphorylation of several proteins in human monocytes when determined with antiphosphotyrosine immunoblotting . Our results demonstrate that both PKC and protein tyrosine kinases are involved in HLA-DR-induced IL-1 beta expression in human monocytes.

Minerva Anestesiol, 1993 Apr, 59(4), 187 - 92
{Pneumonia in severe head injury . A prospective study}; Mergoni M et al.; Impairment of the state of consciousness is an important contributing factor in the onset of respiratory tract infections; in this study the data were collected prospectively to investigate the incidence and clinical implications of pneumonia in a population of head injured patients . The study was conducted on all patients treated at our centre throughout 1990 . The incidence of pneumonia in the head injured was 10.8% versus 7.3% in the rest of the patients . Mortality in the group with pneumonia was not significantly different from the group without pneumonia . The average time of onset was on the fifth day from admission . The lung injury score (LIS) on the sixth day, the time on artificial ventilation and the length of stay in intensive care were significantly greater in those with pneumonia (1.18, 14.6 days and 21.9 days versus 0.8, 4.2 days and 12.9 days respectively) . Staphylococcus was the single most frequently isolated germ . Our study concludes that pneumonia represents a relatively frequent and early complication in patients with head injury, and it is associated with prolonged artificial ventilation and longer staying in ICU.

Ginekol Pol, 1993 Apr, 64(4), 193 - 6
{Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils in neonates}; Orzeszko-Spaczynska A et al.; Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils (PMN) obtained from umbilical venous blood was estimated in 30 neonates and their mothers by the use of fluorochrome microassay of Pantazis and Kniker . Phagocytosis of Staphylococcus was similar in both groups and controls, while intracellular bacteria killing was significantly impaired in PMN obtained from the neonates . These results may indicate that increased susceptibility to infection observed in neonates may be partly caused by PMN function impairment.

Wiad Lek, 1993 Apr, 46(7-8), 308 - 10
{Diagnostic and therapeutic difficulties in staphylococcal sepsis}; Adrych K et al.; A case is described of a 38-year-old man treated for three years for diabetes mellitus admitted to an internal department for elucidation of the cause of protracted fever . Staphylococcal sepsis was diagnosed with pneumonia and retroperitoneal abscess . Surgical treatment was given and targeted antibiotic-therapy was administered . The patient was discharged from the hospital after 38 days as cured . An observation of 18 months failed to show the recurrence of the infection.

Int J Syst Bacteriol, 1993 Apr, 43(2), 237 - 44
Staphylococcus pasteuri sp . nov., isolated from human, animal, and food specimens; Chesneau O et al.; A new novobiocin-susceptible species of the genus Staphylococcus, Staphylococcus pasteuri, is described on the basis of the results of a study of seven strains isolated from human, animal, and food specimens . DNA relatedness experiments (S1 nuclease method) showed that these strains form a homogeneous genomic species related at DNA homology levels of 2 to 13% to 27 type strains representing known Staphylococcus species . The use of a method based on rRNA gene restriction site polymorphism provides clear-cut distinction between this new species and Staphylococcus warneri, which is the most similar species phenotypically . The type strain of the new species is strain BM9357 (= ATCC 51129).

Cardiovasc Surg, 1993 Apr, 1(2), 113 - 7
Sartorius myoplasty in the treatment of exposed arterial grafts; Sladen JG et al.; The long-term success of sartorius myoplasty in 14 of 16 patients who presented with an exposed vascular graft in an infected groin is described . The presenting complications were wound dehiscence (ten patients), hemorrhage (two), skin erosion (two), late bilateral fistulas (one) and false aneurysm (one) . Ten grafts were prosthetic and six autogenous . Positive cultures were obtained from 15 wounds; four grew Staphylococcus epidermidis, the remainder mixed or Gram-negative bacteria . Each groin was radically debrided, including the surface of the arterial graft, and, if possible, closed immediately with a sartorius myoplasty applied directly to the graft . Twist, fan and loop myoplasties were equally effective . Grossly infected wounds were debrided initially and obviously infected grafts were replaced in situ before myoplasty . Sartorius myoplasty is recommended as an elegant solution for the infected groin in which there is an exposed arterial graft.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 33 - 7
{Antibacterial therapy of acute pyo-destructive lesions in the lungs}; Mustafin DG; Clinical analysis of the efficacy of modern antibacterial therapy in 721 patients with acute infectious destructive process in the lungs was performed . The peculiarities of the program of the antibacterial therapy and its intensity in 367 patients with lung abscesses, 282 patients with mainly staphylococcal destructive processes in the lungs and 72 patients with septic metastatic destructive processes in the lungs were revealed . The target-aimed treatment of the patients in complex with bronchial sanation, correction of the immune deficiency, detoxication and quantum hemotherapy provided good results in 96 per cent of the cases.

Gen Physiol Biophys, 1993 Apr, 12(2), 95 - 111
Relation between ionic channel conductance and conductivity of media containing different nonelectrolytes . A novel method of pore size determination; Sabirov RZ et al.; The effects of nonelectrolytes on conductivity and viscosity of KCl solutions as well as on ion channel conductance were studied . Mobility of ions in solutions were found to solely depend on percent concentration (w/w) of the nonelectrolytes added and to be effectively independent on their chemical nature (sugars or polyglycols) and molecular size . Proportional changes in both the ion channel conductance and the conductivity of bulk solution induced by low m . w . nonelectrolytes may be used as a criterion of diffusion mechanism of ion transport through channels . The slope of the dependence of ion channel conductance on conductivity of bulk solution containing different concentrations of nonelectrolytes is a good measure of channel permeability for nonelectrolyte . A new method of pore size determination is introduced . Results of practical application of this simple method to three types of ion channels (formed by alpha-latrotoxin, staphylococcal alpha-toxin and its N-terminal fragment) are shown . The advantages and disadvantages of the method are discussed.

Arch Fr Pediatr, 1993 Apr, 50(4), 331 - 3
{Treatment of neutropenia in Shwachman's syndrome with granulocyte growth factor (G-CSF)}; Grill J et al.; BACKGROUND . Patients with Shwachman syndrome have neutropenia and depressed neutrophil chemotaxis and are therefore susceptible to recurrent infections . The diversity of causative microbial agents makes prevention of infection difficult . Some may be life-threatening, despite antibiotic therapy and even leukocyte transfusion . PATIENT . A 15 day-old boy presented with a staphylococcal cutaneous abscess . Neutropenia was detected when he was 45 day-old and Shwachman syndrome was diagnosed at the age of 8 months . He was then suffering from pneumonia plus pancreatic insufficiency, metaphysical chondroplasia and short stature . Frequent infections continued through childhood, but became less frequent from the age of 11 years . At 17 years, he still had neutropenia (polymorphonuclear leukocytes less than 300/mm3) and profound depressed chemotaxis . He was given subcutaneous injections of recombinant human granulocytes colony stimulating factor (rhG-CSF), 1 microgram/kg/day, for 15 days . The polymorphonuclear count increased above 1000/mm3 during the second week of treatment, and this effect was seen again during a second course of rhG-CSF . The benefit was not sustained when treatment was discontinued . CONCLUSION . These results confirm earlier reports of the effect of 5 micrograms/kg/day of rhG-CSF but the responses were greater and earlier . While more precise information concerning the treatment of this disease is required, rhG-CSF can be useful in patients with severe infections.

J Immunol, 1993 Apr 1, 150(7), 3062 - 9
SEB induced anergy: modulation of immune response to T cell determinants of myoglobin and myelin basic protein; Gaur A et al.; Superantigens have the ability to stimulate a subset of T cells based upon their expressed TCR beta-chain . It has been demonstrated that the administration of staphylococcal enterotoxin B (SEB) in mice leads to unresponsiveness in V beta 8+ T cells in vivo which are the same T cells that could be stimulated in vitro by this enterotoxin . We present here data on the effect of SEB administration in DBA/2 and (PL/J x SJL)F1 mice on their T cell response to two different T cell determinants, the responses against which are dominated by the use of V beta 8+ T cells . Treatment of mice with SEB not only diminished their primary T cell proliferative response to these determinants, but also was able to effectively reduce the memory T cell response . SEB treatment, however, showed only a modest effect in preventing Ac 1-11-induced experimental autoimmune encephalomyelitis in H-2u mice.

Biochem Biophys Res Commun, 1993 Mar 31, 191(3), 1211 - 7
Identification of binding domains on the superantigen, toxic shock syndrome-1, for class II MHC molecules; Soos JM et al.; Toxic shock syndrome toxin-1 (TSST-1) is a member of the staphylococcal enterotoxin superantigen family . In order to determine the regions on the TSST-1 molecule involved in binding to class II MHC, seven overlapping peptides of the entire TSST-1 molecule were synthesized and tested for their ability to compete with 125I-TSST-1 for binding to class II MHC on murine A20 cells and HLA on Raji cells . Peptides corresponding to N-terminal amino acid residues 39 through 68 and C-terminal residues 155 through 194 competed with 125I-TSST-1 for binding to class II MHC . Also, binding studies with class II MHC beta-chain peptides indicate that regions encompassed by I-A beta b(30-60) and I-A beta b(60-90) are binding regions for TSST-1 . Thus, we have identified binding domains on the TSST-1 molecule for class II MHC molecule receptors on antigen presenting cells.

Biochemistry, 1993 Mar 16, 32(10), 2534 - 41
Effect of proline mutations on the stability and kinetics of folding of staphylococcal nuclease; Nakano T et al.; The role of proline in the stability and kinetics of folding of wild-type staphylococcal nuclease and its P117G, P117T, and P31A mutants was examined as a function of guanidinium thiocyanate (Gdn-SCN) concentration . Replacement of Pro-117 with Gly or Thr caused small increases in stability, whereas substitution of Pro-31 by Ala led to a small decrease in stability . The slopes of the plots of delta G against denaturant concentration (m) for the mutant proteins are significantly smaller than for the wild-type, suggesting a decrease in the solvent-accessible surface area of the denatured state relative to that of the wild-type . The rates of unfolding and refolding were monitored using tryptophan fluorescence . The kinetic traces for refolding in the presence of Gdn-SCN were triphasic for the wild-type protein and P31A but biphasic for P117G and P117T mutants . The slower phases were typically 10% of the total amplitude except in the transition region . The rates of the fastest and medium phases of the wild-type were essentially unaffected by the mutations . Double-jump experiments in which the protein was unfolded in a high concentration of denaturant for a short time period and then refolded to final Gdn-SCN concentrations near the Cm revealed a fast increase in fluorescence emission corresponding to formation of the native state, followed by a slower decrease with an amplitude that varied with the guanidine concentration and time of unfolding.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood, 1993 Mar 15, 81(6), 1521 - 6
Acute infectious mononucleosis stimulates the selective expression/expansion of V beta 6.1-3 and V beta 7 T cells; Smith TJ et al.; Acute infectious mononucleosis (AIM) is caused by the Epstein-Barr virus (EBV) and is characterized by a proliferation of atypical lymphocytes, predominantly CD8+ T cells . Various diseases associated with T-cell activation have been shown to stimulate the selective expansion of certain V beta (variable region of the T-cell receptor beta chain) expressing T-cell populations . The purpose of this investigation was to determine if the proliferation of T cells accompanying AIM is associated with selective expression/expansion of distinct populations of V beta T cells . We determined V beta expression in eight patients with clinical and laboratory evidence of AIM, including an atypical lymphocytosis . Gel electrophoresis and quantitative analysis were performed on cDNA amplified by the polymerase chain reaction (PCR) using different V beta region primers . Gel electrophoresis analysis showed prominent V beta 6.1-3 and V beta 7 bands in all eight patients with AIM but not in the controls . Quantitative PCR analysis showed that the V beta 6.1-3 and V beta 7 mean PCR ratios increased, respectively, from 163.0 +/- 22.5 and 142.3 +/- 5.5 in controls to 339.9 +/- 38.8 (P < .03) and 396.1 +/- 45.6 (P < .01) in the eight patients with AIM . Two of the eight patients who had increased V beta 6.1-3 and V beta 7 expression were retested after clinical resolution of AIM and no longer had evidence of increased V beta 6.1-3 and V beta 7 T-cell expression . AIM is associated with a selective increased expression of V beta 6.1-3 and V beta 7 T cells present at the time of initial clinical symptoms and atypical lymphocytosis . This increased expression resolves following recovery from AIM . This V beta-specific selective expression resembles the super-antigen response seen after staphylococcal toxin stimulation and may be caused by EBV triggering of selective expansion of V beta 6.1-3 and V beta 7 T-cell subsets.

J Immunol Methods, 1993 Mar 15, 160(1), 97 - 105
Assessment of the suitability of commercially available SpA affinity solid phases for the purification of murine monoclonal antibodies at process scale; Godfrey MA et al.; Eight commercially available staphylococcal protein A (SpA) affinity chromatography solid phases were evaluated in order to establish their potential for the large-scale purification of a murine monoclonal antibody (MAb, mIgG1) . The antibody was produced in-house, serum-free, in a hollow fibre bioreactor . Solid phases were tested for the effects of salt concentration, pH, and the presence of MAb on ligand leakage and flow rate . These effects were compared using the solid phases in stirred-tank (roller-mixing) and flow-through (packed-bed) modes of operation . Ligand leakage in the absence of MAb was generally at its lowest when the solid phases were used in a flow-through mode . In this mode of operation increasing the inorganic salt concentration and pH of the washing/adsorption buffer from 150 mM at pH 8.6, to 3 M at pH 8.9, typically produced a 10% increase in MAb capacity of the solid phases (20% for Sepharose CL-4B) . However, contamination of the purified antibodies was also greatly increased due to an elevated level of background ligand leakage from the matrices . Residual contaminating levels of SpA in affinity purified MAbs were lowest with a low salt (NaCl, 150 mM) glycine (1 M) adsorption/washing buffer . Maximal antibody capacity was achieved for all matrices on frontal analysis (breakthrough curves), as opposed to a pulse mode of use . The largest capacity was found for Prosep A 'high capacity' (12-15 mg/ml column volume), where capacity approached its experimentally determined theoretical capacity (C/Co = 0.5) regardless of its mode of use . The relatively high MAb capacity of Prosep A 'high capacity' was further reflected in a superior dynamic isotherm . Frontal analysis, however, generally resulted in a greater SpA contamination of the purified MAbs . Under these conditions the lowest levels of SpA contamination were found for the Prosep A 'high capacity', and Repligen solid phases (12 ppm) on purifying 12.8 and 4.3 mg of MAb respectively . For the large scale downstream processing of a MAb for therapeutic applications, Prosep A 'high capacity', would appear to be the most appropriate of the solid phases tested.

J Immunol, 1993 Mar 15, 150(6), 2148 - 59
Accessory cell function of keratinocytes for superantigens . Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction; Nickoloff BJ et al.; A growing body of evidence points to a role for epidermal keratinocytes as active participants in immunologic reactions . Inasmuch as certain T cell-mediated skin diseases, such as psoriasis and atopic dermatitis, are triggered by microbial infection, we asked whether multipassaged human keratinocytes could provide the costimulatory signals necessary to induce autologous T cell proliferation in response to bacterial-derived super-antigens . On exposure to IFN-gamma, keratinocytes are induced to express HLA-DR and HLA-DQ class II MHC Ag, and the lymphocyte function-associated Ag-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1) . This change in keratinocyte phenotype is accompanied by the ability of these cells to support T cell proliferation induced by two different bacterial-derived superantigens, staphylococcal enterotoxins A and B . Superantigen-driven proliferation in the presence of IFN-gamma-treated keratinocytes was significantly inhibited (70-90% reduction) by mAb against the LFA-1 alpha- or beta-chain or ICAM-1 . Proliferation was not inhibited by mAb against the CD28 ligands BB-1 or B7, even though these keratinocytes express BB-1 . In addition to previous defined roles for class II MHC Ag, stimulation of LFA-1 on the T cells by ICAM-1 on the keratinocytes also plays an important costimulatory role in this superantigen-mediated response . The accessory cell capability of keratinocytes was not unique to superantigen driven responses as PHA, as well as anti-CD3 mAb also induced vigorous T cell proliferation when IFN-gamma-treated keratinocytes were added . However, IFN-gamma-treated keratinocytes consistently failed to provoke an allogeneic response . These data demonstrate that 1) keratinocytes can serve as accessory cells for T cell proliferation using a variety of different stimuli, 2) the LFA-1/ICAM-1 interaction plays a major role in keratinocyte-mediated costimulation, and 3) previous reports in which IFN-gamma-treated keratinocytes failed to support T cell proliferation to nominal or alloantigens, may reflect impaired Ag presentation via class II MHC molecules, rather than lack of necessary costimulatory signals . These findings highlighting the accessory cell function of keratinocytes may have implications for our understanding of the pathogenesis of immunologic disorders of the skin.

J Biol Chem, 1993 Mar 5, 268(7), 5285 - 92
Functional complementation of staphylococcal alpha-hemolysin fragments . Overlaps, nicks, and gaps in the glycine-rich loop; Walker B et al.; The final steps in assembly of the lytic pore formed by staphylococcal alpha-hemolysin (alpha HL) involve the formation of a nonlytic oligomeric pore precursor, followed by the formation of a transmembrane channel . In this study, truncation mutants of alpha HL encompassing the NH2-terminal or COOH-terminal half of the polypeptide chain and all, part, or none of the central glycine-rich loop were obtained by in vitro, coupled transcription and translation of mutant plasmid DNAs . These polypeptides were unable to oligomerize upon or cause lysis of rabbit erythrocytes (rRBCs) . Twenty-one pairs of the same truncation mutants constituting discontinuous alpha HL chains with overlaps, nicks, and gaps in the central loop were obtained by cotranslation . When incubated with rRBCs, many of the pairs were able to form hetero-oligomers with wild-type alpha-hemolysin (s-alpha HL) and most of these formed homo-oligomers in the absence of s-alpha HL . However, only members of a subset of these pairs were able to lyse the cells . The lytic combinations contained overlaps, nicks, or gaps, but only two pairs, with nicks between amino acid residues 128 and 129 and between 131 and 132 had hemolytic activities approaching that of the wild-type polypeptide . Active combinations could also be obtained by separately translating NH2- and COOH-terminal truncation mutants and then combining them . These findings suggest that the integrity of the central loop is of little significance for oligomer formation but that it is more important for the final step in pore assembly or alternatively for determining the correct structure of the conductive channel . Our findings disagree with previous reports of NH2- and COOH-terminal fragments with hemolytic activity and of the prevention of hemolysis by proteolytic cleavage in the central loop . This discord is attributed to experimental and interpretative ambiguities in the earlier protein chemistry . For example, we show that loss of hemolytic activity after treatment with trypsin is not due to cleavage after Lys-131, as previously proposed, but to the removal of a small NH2-terminal peptide through cleavage after Lys-8.

J Perinatol, 1993 Mar-Apr, 13(2), 153 - 8
Central venous catheters in low birth weight infants: incidence of related complications; Schiff DE et al.; To test the hypothesis that the incidence of central venous catheter-related complications is increased in very low (< 1000 gm) and low (1001 to 1500 gm) birth weight infants compared with larger infants, we retrospectively analyzed the charts of 51 infants with gestational ages 24 to 42 weeks, weighing 0.43 to 12.2 kg at catheter insertion, who had 69 catheters placed at 1 week to 11 months of age between January 1986 and June 1989 at our hospitals . The incidence of infectious and mechanical complications and the frequency of total and infection-related complications were significantly greater for infants weighing < 1000 gm at catheter insertion (p < 0.05) . Oxacillin-resistant coagulase-negative Staphylococcus organisms accounted for 14 of the 17 episodes of catheter-related septicemia (82%) . Six of these episodes were initially treated with antibiotics but without catheter removal; none resolved with catheter salvage . Central venous catheters in very low and low birth weight infants had an 85% and 64% incidence of associated complications, respectively, and should be used with caution in these patients.

Acta Paediatr, 1993 Mar, 82(3), 324 - 6
Successful trimethoprim-sulfamethoxazole therapy in a patient with hyperimmunoglobulin E syndrome; Hattori K et al.; A male patient with hyperimmunoglobulin E syndrome is described . Recurrent lymphadenitis and cutaneous staphylococcal abscesses were resistant to various antibiotics, and chemotaxis and hydrogen peroxide production of polymorphonuclear leukocytes were impaired . Following trimethoprim-sulfamethoxazole therapy, he was free from the above infections, and impaired polymorphonuclear leukocyte functions recovered and serum IgE decreased to approximately one-fifth of its initial level . Subsequent irregular medications, however, resulted in impairment of polymorphonuclear leukocyte functions and an increased serum IgE concentration, which recovered after regular resumption of trimethoprim-sulfamethoxazole treatment . From these results, the beneficial effects of trimethoprim-sulfamethoxazole in hyperimmunoglobulin E syndrome are clinically apparent, but in vitro studies failed to demonstrate the positive effect of trimethoprim-sulfamethoxazole on polymorphonuclear leukocytes and their mechanism still remains to be elucidated.

Optom Vis Sci, 1993 Mar, 70(3), 185 - 91
Microbial contamination of hydrophilic contact lenses: quantitation and identification of microorganisms associated with contact lenses while on the eye; Hart DE et al.; Previous studies have demonstrated the presence of microorganisms on hydrogel contact lenses under various usage conditions . We conducted this study to quantify and identify viable bacteria and fungi associated with hydrogel contact lenses while on the eye . We removed the lenses from patients' eyes using aseptic techniques and cultured them to identify loosely adherent, as well as lens bound, microorganisms . Lenses were vortexed in a transfer medium (thereafter called the lens extract) and the lenses were then incubated in an agar sandwich separately from the transfer medium . We cultured 108 lenses (82 daily wear and 26 extended wear) from 49 patients . Bacteria were cultured from 38% (41) of the lenses; for 31 of these 41 lenses bacteria were isolated only from the lens extracts (made by vortexing lenses in a transfer medium), suggesting a transient association with the lenses . No fungi were isolated . Counts of less than 10 colony forming units (CFU)/lens were observed on 89% of the lenses . Staphylococcus epidermidis were the most frequently isolated bacteria . A statistically significant relation was observed between increased CFU/lens and increased lens age for extended wear lenses (p = 0.028).

Natl Med J India, 1993 Mar-Apr, 6(2), 67 - 70
Antibiotics in febrile neutropenia: a randomized prospective comparison of two combinations; Madiajagane R et al.; BACKGROUND . Problems of initial empirical antibiotic therapy in febrile neutropenia are further complicated by other factors such as cost and the pattern of infective organisms in a particular institution . We, therefore, conducted a randomized study comparing the efficacy of two sets of antibiotics which differed in their spectrum of action, availability and price . METHODS . Sixty episodes of febrile neutropenia in 40 patients who were not on any prophylactic antibiotics were randomized into one of two arms--cefotaxime and gentamicin or ciprofloxacin and gentamicin . Depending upon the response by 72 hours, they were crossed over to the other arm or continued with the same combination . Empirical antifungal therapy was added in those who did not become afebrile . RESULTS . Infection was documented either clinically, bacteriologically or radiologically in 42% of the febrile episodes . The commonest organism isolated was Klebsiella and the commonest organism producing bacteraemia was the Staphylococcus . The temperature was reduced to normal without cross-over in 53% of the febrile episodes with cefotaxime and gentamicin and in 60% with ciprofloxacin and gentamicin (p > 0.05) . After cross-over the temperature came down in 30% of the episodes with cefotaxime and gentamicin (initial combination) and 40% with ciprofloxacin and gentamicin (initial combination; p > 0.05) . The overall response rate without empirical antifungal therapy was 83% in the patients on cefotaxime and gentamicin (initial combination; p > 0.05) . While both the arms of the study had a 100% response rate, there was no significant difference between the efficacy of the antibiotic combinations . The ciprofloxacin-gentamicin combination is one-third as expensive as cefotaxime-gentamicin and is more readily available . CONCLUSION . We recommend the use of ciprofloxacin and gentamicin as the initial drug combination and cefotaxime and gentamicin only when the former is not effective.

Z Kardiol, 1993 Mar, 82(3), 172 - 4
{Detection of pacemaker electrode infection using intravascular ultrasound}; Kerber S et al.; The case of a 60-year-old man who developed fever 14 months after last implantation of a DDD pacemaker system is reported . Though staphylococcus epidermidis could be identified in several blood cultures, transthoracic and transesophageal echocardiograms and scintigraphy with antibodies to human leucocytes could not identify any focus of infection . The percutaneous intravascular and intracavitary ultrasound examination clearly demonstrated a vegetation within the subclavian vein, being attached to the ventricular lead; within that segment of the vein the atrial lead showed a small hyperdense structure . Further vegetations along the leads within the right atrium and ventricle could be ruled out . Subsequent removal of the pacemaker system caused resolution of the signs of inflammation.

AIDS Res Hum Retroviruses, 1993 Mar, 9(3), 241 - 6
T cell response to staphylococcal superantigens by asymptomatic HIV-infected individuals exhibits selective changes in T cell receptor V beta-chain usage; Bisset LR et al.; Recognition that the murine mammary tumor C-type retrovirus and the replication-defective murine leukemia virus have "superantigen" properties raises the specter that human immunodeficiency virus might also generate T cell impairment and destruction as a result of inherent superantigen properties . The observation that individuals with AIDS lack the expression of several T cell receptor V beta-chain genes lends support to this hypothesis . Staphylococcal exotoxins represent another class of superantigen with a similar ability to stimulate large numbers of T cells bearing specific T cell receptor V beta-chain types . To examine the hypothesis that T cells from HIV-infected individuals may be exposed to a superantigen during the infection process, we have compared the ability of T cells from asymptomatic HIV-infected donors and healthy donors to respond to stimulation with several known staphylococcal exotoxin superantigens . Following in vitro stimulation with staphylococcal enterotoxin D and staphylococcal enterotoxin E, asymptomatic HIV-infected individuals responded with a significantly different T cell receptor V beta-chain usage to that observed for healthy individuals . This skewed V beta-chain usage is likely to reflect preferential conditioning of T cells bearing specific V beta-chains as a result of HIV infection, supporting the hypothesis of superantigen involvement early in the course of infection.

Oral Surg Oral Med Oral Pathol, 1993 Mar, 75(3), 391 - 6
Postextraction osteomyelitis in a bone marrow transplant recipient; Barasch A et al.; This report describes a case of mandibular osteomyelitis after a dental extraction in a patient who subsequently underwent bone marrow transplantation (BMT) for lymphoblastic lymphoma . Surgical guidelines consistent with National Cancer Institute recommendations were followed for the extraction, which was performed before initiation of the myelosuppressive conditioning regimen . However, moderate tenderness developed at the extraction site beginning 10 days after marrow infusion . On day 26 the patient became febrile and blood culture-positive for Staphylococcus epidermidis . Radiographs exposed on day 28 demonstrated changes consistent with low-grade osteomyelitis, including diffuse loss of lamina dura and an irregular osseous rarefaction extending 1 cm posterior to the extraction site . Although the indwelling Hickman catheter was the presumed source for bacteremia, clinical and radiographic data led to consideration of mandibular osteomyelitis as an alternative cause . Characteristics of this infection in BMT recipients are reviewed . Recommendations for dental extractions and prophylactic antibiotic regimens for catheterized BMT recipients are also discussed . Although mandibular osteomyelitic lesions are not common in profoundly immunosuppressed BMT recipients, prompt recognition and treatment are essential when the disease occurs.

J Clin Microbiol, 1993 Mar, 31(3), 490 - 3
Numerical approach to reference identification of Staphylococcus, Stomatococcus, and Micrococcus spp; Rhoden DL et al.; A numerical-code system for the reference identification of Staphylococcus species, Stomatococcus mucilaginosus, and Micrococcus species was established by using a selected panel of conventional biochemicals . Results from 824 cultures (289 eye isolate cultures, 147 reference strains, and 388 known control strains) were used to generate a list of 354 identification code numbers . Each six-digit code number was based on results from 18 conventional biochemical reactions . Seven milliliters of purple agar base with 1% sterile carbohydrate solution added was poured into 60-mm-diameter agar plates . All biochemical tests were inoculated with 1 drop of a heavy broth suspension, incubated at 35 degrees C, and read daily for 3 days . All reactions were read and interpreted by the method of Kloos et al . (G . A . Hebert, C . G . Crowder, G . A . Hancock, W . R . Jarvis, and C . Thornsberry, J . Clin . Microbiol . 26:1939-1949, 1988; W . E . Kloos and D . W . Lambe, Jr., P . 222-237, in A . Balows, W . J . Hansler, Jr., K . L . Herrmann, H . D . Isenberg, and H . J . Shadomy, ed., Manual of Clinical Microbiology, 5th ed., 1991) . This modified reference identification method was 96 to 98% accurate and could have value in reference and public health laboratory settings.

EMBO J, 1993 Mar, 12(3), 861 - 7
OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences; Murzin AG; A novel folding motif has been observed in four different proteins which bind oligonucleotides or oligosaccharides: staphylococcal nuclease, anticodon binding domain of asp-tRNA synthetase and B-subunits of heat-labile enterotoxin and verotoxin-1 . The common fold of the four proteins, which we call the OB-fold, has a five-stranded beta-sheet coiled to form a closed beta-barrel . This barrel is capped by an alpha-helix located between the third and fourth strands . The barrel-helix frameworks can be superimposed with r.m.s . deviations of 1.4-2.2 A, but no similarities can be observed in the corresponding alignment of the four sequences . The nucleotide or sugar binding sites, known for three of the four proteins, are located in nearly the same position in each protein: on the side surface of the beta-barrel, where three loops come together . Here we describe the determinants of the OB-fold, based on an analysis of all four structures . These proposed determinants explain how very different sequences adopt the OB-fold . They also suggest a reinterpretation of the controversial structure of gene 5 ssDNA binding protein, which exhibits some topological and functional similarities with the OB-fold proteins.

Proteins, 1993 Mar, 15(3), 312 - 21
Binding interactions of kistrin with platelet glycoprotein IIb-IIIa: analysis by site-directed mutagenesis; Dennis MS et al.; The binding interactions between platelet fibrinogen receptor, glycoprotein (GP) IIb-IIIa, and kistrin, a snake venom disintegrin protein that contains the adhesion site recognition sequence Arg-Gly-Asp (RGD) and potently inhibits platelet aggregation, have been investigated by site-directed mutagenesis of a synthetic kistrin gene . Kistrin was expressed as a fusion protein in Escherichia coli under control of the alkaline phosphatase promoter . This construction included the stII signal sequence to direct secretion to the periplasmic space and one synthetic (Z) domain of Staphylococcal protein A to allow affinity purification using IgG Sepharose . Kistrin was cleaved from the Z-domain by site-specific proteolysis using a mutant subtilisin BPN' and purified by reverse-phase HPLC . This approach facilitated the rapid purification of a set of 43 alanine replacement mutants whose relative affinity for GP IIb-IIIa was measured by competition with immobilized kistrin and by inhibition of platelet aggregation in human platelet-rich plasma . Alanine replacements at R49, G50, and D51 led to weaker inhibitors of platelet aggregation by 90-fold, 2-fold, and > 200-fold, respectively . The conservative D51E mutant was still > 100-fold less potent whereas R49K had a minor effect (1.8-fold), implying the critical nature of the aspartate for high affinity binding . However, mutations outside of the RGD region led to proteins indistinguishable from kistrin, suggesting no substantial secondary binding interactions . Furthermore, reduced kistrin is not active . We therefore propose that a favorable conformation of the RGD region alone is responsible for the high affinity binding of kistrin to GP IIb-IIIa.

Clin Infect Dis, 1993 Mar, 16(3), 435 - 8
Staphylococcal meningitis can present as an abscess of a single lateral ventricle; Robinson EN Jr; Ventricular obstruction and hydrocephalus are recognized complications of neurosurgical procedures and meningitis that has been previously treated . The confinement of bacterial meningitis solely to a lateral ventricle in an otherwise healthy individual, however, is rare . I describe a case in which a ventricular abscess occurred as the presenting manifestation of staphylococcal meningitis in a man who had no history of head trauma or neurosurgery.

Transfusion, 1993 Mar, 33(3), 234 - 42
Treatment of refractoriness to platelet transfusion by protein A column therapy; Christie DJ et al.; Ten thrombocytopenic patients (platelets < 10-24 x 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy . Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response . All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500 . Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens . Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient . Patients received from 1 to 14 treatments . A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500 . Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/- 11 x 10(9) per L as compared with counts of 16 +/- 7 x 10(9) per L (p < 0.0005) before treatment . Posttransfusion CCI values determined in four of these patients averaged 2480 +/- 810 and 10,010 +/- 3540 (p < 0.005) before and after treatment, respectively . In contrast, among the four unresponsive patients, platelet counts averaged 10 +/- 9 and 13 +/- 10 x 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/- 1410 and 1520 +/- 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

J Neurosurg Sci, 1993 Mar, 37(1), 19 - 23
Efficacy of ampicillin/sulbactam combination in experimental shunt infections caused by Staphylococcus epidermidis . A light and scanning electron microscope study; Gedikoglu Y et al.; In this study, the efficacy of ampicillin/sulbactam combination in reactions of periventricular tissue of the lateral ventricle induced by the presence of infected (Staphylococcus epidermidis) silicone rubber shunt tubing was examined by using light and scanning electron microscopy . It was demonstrated that reactive changes to implants had occurred in periventricular tissue in the control group . In infected shunt tubing without given prophylactic antibiotic group, generalized meningitis and ventriculitis, loss of integrity of ependymal cells, numerous inflammatory cells, bacterial colonies, exuda and even pus were seen . It was also shown that rarely inflammatory reactions, minimal disintegration of ependymal cells, no bacterial colonies, and phagocytes were present in the group which was given prophylactic ampicillin/sulbactam combination per and postoperatively . We think that ampicillin/sulbactam combination is very effective in prevention and treatment of shunt infections.

Am J Crit Care, 1993 Mar, 2(2), 145 - 54; quiz 155-6
Common infections in heart transplant patients; Vaska PL; Infection is the primary cause of morbidity and mortality following cardiac transplantation because of the strict immunosuppressive regimens patients follow . In the immediate postoperative phase, patients are more susceptible to infection because of interruption of their external barriers to infection . Cardiac transplant recipients are most likely to succumb to infections caused by cytomegalovirus, Epstein-Barr virus and bacterial organisms, especially staphylococcus . Fungal, protozoal and herpes simplex infections are also frequently troublesome to the transplant recipient . Critical care clinicians can control the incidence of infection in the cardiac transplant population by initiating measures to maintain external barriers, monitoring the patient for early signs of infection, and instituting appropriate isolation techniques.

Clin Exp Rheumatol, 1993 Mar-Apr, 11 Suppl 8, S17 - 21
Superantigens as immunogens and tolerogens; Lobo-Yeo A et al.; Superantigens are a family of proteins that are receiving a great deal of attention as a group of potent immunomodulatory molecules . They combine with MHC class II molecules to form the ligands that stimulate T cells via the V beta element of the T cell receptor . Two groups of superantigens have been described: those expressed endogenously such as the mouse mammary tumour virus (MMTV) and the exogenously derived products such as the Staphylococcal enterotoxins . Here we review the interactions between the superantigens and MHC class II molecules, the mechanisms of T cell activation, the role of superantigens in the induction of tolerance and their involvement in autoimmune diseases.

Hum Immunol, 1993 Mar, 36(3), 142 - 8
Inhibition of allostimulated HLA-DQ and DP-specific T cells by staphylococcal enterotoxin A; Masewicz S et al.; Bacterial superantigens have two immunologically important features . They bind MHC class II molecules and stimulate T cells bearing certain V beta TCR phenotypes . Superantigens such as SEA, SEB, and TSST bind to each of the three HLA class II isotypes (DR, DQ, and DP) . Allotypic variation seems to play an important role in superantigen binding to class II molecules, but the functional implications of these differences remain largely unknown . In the present investigation, we studied the effects of SEA, SEB, and TSST on allostimulation of HLA-DR-, DQ-, and DP-allospecific T-cell clones . To avoid direct stimulation of T-cell responses by the superantigens, SEA and/or SEB nonresponsive T-cell clones were selected . We show that SEA strongly inhibited DQ- and DP-specific T-cell responses . In contrast, SEB and TSST had only weak inhibitory effects . DR-specific T-cell responses were unaffected or only weakly inhibited by the superantigens tested . The inhibition appeared not to be due to induction of cytotoxicity or suppression of either T cells or EBV-LCLs by SEA . In conclusion, the bacterial superantigen SEA can block alloantigen-specific stimulation of T clones in vitro . These results suggest that SEA binds to certain MHC class II molecules in a way that prevents MHC-TCR interactions.

Eur Cytokine Netw, 1993 Mar-Apr, 4(2), 89 - 98
Cytokine down-regulation in endotoxin tolerance; Mengozzi M et al.; Cytokine production is down-regulated in LPS tolerance . 1) This down-regulation has been reported in various animal species and cell types, and can be induced both in vivo and in vitro (indicating a desensitization of the cytokine-producing cells) . 2) It can also be induced in humans in vivo and in vitro . 3) It is reversible, since the refractory state can be bypassed by administering LPS along with IFN-gamma or PMA . 4) Under certain conditions, it is specific since cytokines will still be induced in response to non-LPS stimuli (Staphylococcus, zymosan, MDP), meaning a real LPS-desensitization is involved rather than an aspecific blockade of cytokine synthesis . 5) in vivo, due to the complexity of the system, other factors than a simple desensitization of cytokine-producing cells contribute to LPS tolerance (aspecific blockade of cytokine synthesis, corticosteroid-dependent feedback, increased clearance by RES and changes in macrophage populations, inhibitory cytokines.

Res Microbiol, 1993 Mar-Apr, 144(3), 237 - 44
Development of a phage typing system for Staphylococcus hyicus; Wegener HC; Bacteriophages were released by 98% of 100 Staphylococcus hyicus strains studied after treatment with mitomycin C . Twenty-three phages with different lytic spectra were included in a phage typing system and used for typing S . hyicus . On a test-set of 100 epidemiologically unrelated S . hyicus strains isolated from Danish pig herds, the phages were able to type 92% of the strains, producing 16 different phage types . Reproducibility of the phage typing system after subculture of the strains and using fresh phage stock was 96% . Typability ranged from 52 to 80% when typing porcine strains originating from other countries . Although phages were isolated from porcine skin strains exclusively, the system produced phage types in S . hyicus strains of bovine origin . Ten strains of S . aureus and S . chromogens were not typable by these phages . Strains belonging to one phage type (A/B/C/W) were isolated significantly more often from piglets with exudative epidermidis than from healthy piglets . The phage typing system described appears to be a valuable tool in diagnosis of exudative epidermidis in pigs, and furthermore, might be of value in epidemiological studies of S . hyicus.

Cell Immunol, 1993 Mar, 147(1), 12 - 24
Regulation of lymphocyte aggregation and proliferation through adhesion molecule CD54 (ICAM-1); Gronberg A et al.; The effect of two mouse mAb (LB-2 and G1B2) against human CD54 (intercellular adhesion molecule-1, ICAM-1) in lymphocyte aggregation and proliferation systems was investigated . The LB-2 mAb, but not G1B2, inhibited phorbol ester-induced aggregation of B lymphoblastoid cells . In addition, LB-2, but not G1B2, induced aggregation and proliferation of peripheral blood mononuclear cells (PBMC) in cultures containing FCS . The Fab fragment of LB-2 always (10/10 donors) induced proliferation while the intact mAb was active in 3/11 donors . When cultures contained human serum (HS), LB-2 and its Fab fragment induced proliferation in 1/9 and 1/4 donors, respectively . Addition of HS to FCS cultures inhibited proliferation induced by LB-2 Fab, indicating the presence of an inhibitory factor in human serum . Addition of anti-CD18 mAb to cultures stimulated by LB-2 Fab caused partial inhibition of proliferation but did not prevent aggregate formation . A combination of anti-CD18 and anti-CD29 mAb resulted in a nearly complete inhibition of proliferation but did not inhibit aggregate formation . In these experiments it was found that the anti-CD29 mAb 4B4 in itself induced cell aggregation of PBMC and enhanced aggregation induced by the anti-CD3 mAb OKT3 . Both LB-2 and G1B2 showed significant inhibition (> 60%) of proliferation when human PBMC were stimulated by the antigen PPD in the presence of HS, but not when stimulated by staphylococcal enterotoxin A (SEA) or IL-2 . This study describes two mAb against separate epitopes on CD54 which are differentially involved in cell aggregation or induction of proliferation but are of similar importance in antigen-specific responses . Furthermore, the new finding that the LB-2 mAb or its Fab fragment can induce cell aggregation and proliferation defines a signaling function of CD54 which may work independent of crosslinking or costimulation.

J Neuroimmunol, 1993 Mar, 43(1-2), 39 - 43
Treatment of PL/J mice with the superantigen, staphylococcal enterotoxin B, prevents development of experimental allergic encephalomyelitis; Soos JM et al.; Experimental allergic encephalomyelitis (EAE), an antigen induced autoimmune disease, is mediated by V beta 8+ CD4+ T cells in PL/J mice after injection with the autoantigen, myelin basic protein (MBP) . Recently the superantigen, staphylococcal enterotoxin B (SEB), has been shown to peripherally anergize and delete T cells in a V beta specific manner . By treatment of PL/J mice with SEB, we have been able to protect PL/J mice from the development of EAE . Two-color FACS analysis of the spleens of SEB treated mice showed depletion of V beta 8+ CD4+ T cells . Consistent with this observation, spleen cells of SEB treated mice that did not show signs of EAE could not be stimulated in vitro with SEB but did respond to SEA . Thus, V beta specific superantigens may prove to be a preventative therapy for autoimmune diseases mediated by V beta specific T lymphocytes.

Eur J Immunol, 1993 Mar, 23(3), 747 - 53
Thymic and peripheral apoptosis of antigen-specific T cells might cooperate in establishing self tolerance; D'Adamio L et al.; Aside from CD4+CD8+ double-positive (DP) thymocytes, the subpopulations of T lineage cells affected by negative selection are unknown . To address whether this process occurs in more mature cell types, we have compared the responses of purified single-positive (SP) murine thymocytes and peripheral T cells to the superantigen staphylococcal enterotoxin B (SEB) utilizing as antigen-presenting cells (APC) a fibroblast cell line expressing transfected I-Ek class II molecules . Whereas approximately 70% of SEB-reactive SP thymocytes, either CD4+ or CD8+, undergo programmed cell death (apoptosis) and, therefore, negative selection, CD4+ and CD8+ antigen-specific peripheral T cells are predominantly activated and proliferate to APC+SEB . Thus, mature thymocytes and peripheral T cells, with identical patterns and levels of expression of CD4, CD8 and T cell receptor (TCR), are programmed to elicit different responses following TCR stimulation . Unexpectedly, however activation of peripheral T cells was preceded by deletion of a large fraction of V beta 8+ T lymphocytes (SEB specific) . This surprising phenomenon was also observed in in vivo studies: in fact, administration of SEB to adult mice resulted in depletion of the majority of antigen-specific T cells from the peripheral lymphoid tissues analyzed (lymph nodes and spleen) . This depletion is the consequence of deletion as indicated by program cell death of V beta 8+ T cells and is followed by proliferation of the remaining SEB-reactive T cells . Clonal elimination of peripheral T cells may represent a mechanism by which tolerance to self antigens never expressed in and/or exported to the thymus is achieved.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Mar-Apr, (2), 99 - 101
{An experimental validation of immunotherapy with purified staphylococcal anatoxin}; Semenova IB et al.; Inbred mice have proved to be a promising model for the evaluation of antigen-specific and antigen-nonspecific immunomodulating activity of purified staphylococcal toxoid in humans . This toxoid induces the formation of pronounced humoral response to homologous and heterologous infections in humans and mice . In animal experiments purified staphylococcal toxoid has shown its capacity for the correction of secondary immune deficiency of different origin; when introduced into humans having secondary immunodeficiency associated with bacterial infections of different etiology, the preparation reproduces this effect.

Biull Eksp Biol Med, 1993 Mar, 115(3), 278 - 80
{Analysis of the immunomodulating action of SK in mice of various strains}; Zlishcheva EI et al.; Peculiarities of immunomodulative action of different mice breeds' SK have been determined by changes of activity level of 5'-nucleotidase in macrophages from peritoneal exudate (MPE) and by changes of animals' sensitivity to staphylococcus infection . It has been established that the character of SK influence on activity level of 5'-nucleotidase in MPE and resistance depends on dose, type of administration and the mice breed . Revealed by hypodermic injection, dependence between the activity of 5'-nucleotidase in MPE and sensitivity to staphylococcus infection, whose character was determined by animals' genotype, had straight character in C57Bl/6 mice, and reverse character in CBA mice.

Rev Sanid Hig Publica (Madr), 1993 Mar-Apr, 67(2), 153 - 63
{Nosocomial infection and its impact on the stay in a neonatal intensive care unit (1988-1991)}; Herruzo Cabrera R et al.; BACKGROUND: Neonatal intensive care units show one of the highest frequencies of nosocomial infections (NI), specially in teaching hospitals . METHODS: The cumulative incidence and distribution of NI in a neonatal intensive care unit of a teaching hospital during three years and three months (536 children) is studied, evaluating the relation between NI and its risk factors with X2 and variance analysis and, finally, estimating the excess stays with a multiple linear regression . RESULTS: The global cumulative incidence of NI was 11% (or an incidence density of 30.7 per 100 children/month); the prevailing etiological agents were negative coagulase Staphylococcus and fungi of Candida Sp . When analyzing, according to the kind of infection, sepsis associated to catheter, stands out . The relation between the different intrinsic or extrinsic risk factors and the NI was studied as well, and it stood out that infected children suffer manipulations as: Central catheter, assisted respiration, parenteral feeding et cetera, with a greater frequency (twice as much) that of non infected children . CONCLUSIONS: The cumulative incidence of NI is moderate-low; but is is necessary to continue insisting and increasing the current control measures and on the other hand, is is necessary to calculate the excess stays, due to NI, with multivariate methods because the direct estimation produces an overestimation of that one.

Srp Arh Celok Lek, 1993 Mar-Jul, 121(3-7), 78 - 80
{Occurrence of bacterial infection and sensitivity of their causative agents to antibiotic drugs in patients with acute leukemias}; Mijovic A et al.; The paper summarizes the results of the study of bacterial infections, occurring in neutropenic patients with acute leukaemia treated at the Radivoje Berovic Intensive care unit of the Institute of Haematology, University Clinical Centre, Belgrade . The majority of infectious episodes, as well as most bacteriaemias, were caused by Gram-positive bacteria keeping rapid increase of Gram-positive bacteriaemias in neutropenic patients . Our results suggest that in studied hospital conditions, amikacin should replace gentamicin as empiric antibiotic therapy (in addition to a beta-lactam antibiotic) . In non-responding patients addition of an anti-staphylococcal agent should be considered.

FEMS Microbiol Lett, 1993 Feb 15, 107(1), 77 - 82
A method for the enumeration of bacterial adhesion to epithelial cells using image analysis; Evans-Hurrell JA et al.; Computerised image analysis was utilised to enumerate the attachment of Staphylococcus epidermidis to HEp2 cell monolayers . A differential staining technique was employed such that individual staphylococcal cells stood out in sharp contrast against the uneven cell surface and granular contents of the epithelial cells . The primary image analysis operation involved subtracting an out-of-focus image from an in-focus image of the bacteria on the monolayer, thereby accentuating the bacterial image . Enumeration, using a particle counting routine, was rapid and reproducible, facilitating counting in excess of 700 bacteria per field at x 500 magnification . The computerised programme compared favourably with manual counting and would provide a rapid, objective and morphologically discriminatory method for evaluating bacterial attachment to various tissues.

Biomaterials, 1993 Feb, 14(3), 184 - 8
In vitro assessment of bacterial adhesion to Hydromer-coated cerebrospinal fluid shunts; Bridgett MJ et al.; The adherence of five strains of Staphylococcus epidermidis and one strain of S . aureus to both untreated and Hydromer-coated silicone rubber cerebrospinal fluid shunts was studied in vitro using epifluorescent image analysis . All five strains of S . epidermidis showed similar levels of adherence to untreated shunts, whilst S . aureus adhered slightly better . The Hydromer coating, a hydrogel material which creates a hydrophilic layer on the shunt surface, was found to reduce bacterial adhesion levels by approximately 90% in the six strains of bacteria tested . Unfortunately, uniform coverage of the shunt surfaces (particularly internally) with Hydromer coating was not achieved during sample preparation . Bacterial adhesion levels in such areas were identical to untreated controls . This may pose problems in the in vivo use of Hydromer-coated shunts.

Protein Eng, 1993 Feb, 6(2), 221 - 7
Overexpression and purification of avian ovomucoid third domains in Escherichia coli; Hinck AP et al.; Genetic engineering studies of ovomucoid domains have been hindered by the lack of an efficient procedure for overproducing this protein . The novel scheme presented here has led to the isolation of chicken ovomucoid third domain (OMCHI3) at a level of 22 mg pure protein/l Escherichia coli culture medium . The gene coding for OMCHI3 was fused to the 3' end of the gene encoding staphylococcal nuclease (SNase) . Expression of the chimeric gene was placed under control of the strong transcription and translation signals of the phage T7 promoter . Upon isopropyl-beta-D-galactopyranoside induction, the cells harboring the target plasmid efficiently overproduced the protein (30% of the total soluble protein) . The 56-residue fragment corresponding to OMCHI3 was then liberated by cyanogen bromide (CNBr) cleavage at a genetically engineered methionine residue located at the nuclease--OMCHI3 junction (OMCHI3 lacks an internal methionine) . SDS--PAGE, enzyme inhibition studies and NMR spectroscopy all indicated that the recombinant OMCHI3 has properties identical to those of OMCHI3 isolated from its natural source . The expression system was easily adapted for the production of {98% U 15N} OMCHI3 . The expression vector was mutated for overexpression of turkey ovomucoid third domain (OMTKY3), which differs from OMCHI3 by three amino acid substitutions . Since many other avian ovomucoid domains also lack methionine residues, this approach should be suitable for large-scale production and isotope labeling of homologous proteinase inhibitors with a variety of inhibitory specificities.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Feb, 41(2), 282 - 7
{Prosthetic valve endocarditis after double valve replacement}; Yamaguchi A et al.; This is a report of a patient who underwent re-AVR due to prosthetic valve endocarditis after double valve replacement (MVR, AVR) . A 54-year-old female was admitted to other hospital on April 14, 1990, because of high fever, progressive anemia, and cardiomegaly . The patient was hospitalized to our department urgently with the diagnosis of prosthetic valve endocarditis . Arterial blood culture grew methicillin-resistant Staphylococcus epidermidis . Echocardiography showed a vegetation at the disc of the mechanical valve in the mitral position, but we could not find any vegetation or thrombus there at the reoperation, and the aortic mechanical valve seemed to be intact . Signs of inflammation continued to be positive after reoperation . On the 33rd hospital day, a diastolic murmur was heard, and emergency cardiac catheterization was done . Detachment of the prosthetic aortic valve and rupture of the sinus of Valsalva due to mycotic aneurysm, and the dissection of the aorta had occurred . We performed re-AVR and replacement of the ascending aorta . The patient died of multiple organ failure following drug-induced hepatic failure . It is suggestive that we missed the prosthetic aortic valve endocarditis during the reoperation . Our thoughts and introspections on the echocardiographic diagnosis of the prosthetic valve endocarditis after double valve replacement were discussed.

Diagn Microbiol Infect Dis, 1993 Feb, 16(2), 123 - 9
Comparison of oral cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections; Stevens DL et al.; This multicenter, randomized, double-blind study was designed to compare the safety and efficacy of cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections . Patients were aged > or = 12 years with acute (< or = 7 days duration), single-site skin or skin-structure infections . The 7- to 10-day treatment regimens were cefpodoxime proxetil (400 mg cefpodoxime) orally with food twice a day with cefaclor-matched placebo (orally, fasting, three times a day); or cefaclor (Ceclor; 500 mg anhydrous equivalent) orally, fasting, three times a day, with cefpodoxime-matched placebo (orally with food twice a day) . Clinical progress and cultures were evaluated upon admission to the study; on study days 7-10 and 15-18; and 2-3 weeks after treatment . Cefpodoxime had lower minimum inhibitory concentrations against the majority of Staphylococcus species than did cefaclor . Both treatments were highly effective (99% pathogen eradication and 86% cure rate) . These high eradication rates were not unexpected in this study of minor infections in which patients with resistant pathogens were excluded . Cefaclor had a higher failure rate {2 (4%) of 57}, than did cefpodoxime {2 (1%) of 139; p not significant} . Most patients in both groups completed treatment as planned: 185 (74%) of 249 cefpodoxime-treated patients and 91 (75%) of 122 cefaclor-treated patients . Both treatments were well tolerated and considered safe and effective in the treatment of skin and skin structure infections . However, the twice-a-day dosing regimen for cefpodoxime proxetil compared with the three-times-a-day regimen for cefaclor may result in better patient compliance.

Semin Immunol, 1993 Feb, 5(1), 47 - 55
Staphylococcal superantigens as inducers of signal transduction in MHC class II-positive cells; Mourad W et al.; Staphylococcal superantigens (SEs and TSST-1) interact with and potentially activate two of the main subsets of the immune system: T lymphocytes and MHC class II-positive cells . Since the interaction of SEs and TSST-1 with MHC class II molecules is the first step in triggering immune cells activation, a detailed understanding of the nature of this interaction is essential for understanding its effect on the immune system and for designing therapeutic strategies for SEs and TSST-1-mediated injury . A series of events is induced in MHC class II-positive cells (B cells, activated T cells, monocytes, and synoviocytes) upon engagement with superantigens . Some of these events require monomeric forms of superantigens, whereas others are critically dependent on cross-linking of toxin-bound MHC class II molecules by a biochemical agent (biotin-avidin) or a natural physiological one such as the TCR . The ability of superantigens to induce polyclonal activation of MHC class II-positive cells may confer to the superantigen its capacity to trigger autoimmune diseases.

Semin Immunol, 1993 Feb, 5(1), 41 - 6
Gamma delta T cell reactivity towards bacterial superantigens; Rust CJ et al.; Human TCR gamma delta positive T cells can proliferate in response to stimulation with staphylococcal enterotoxins (SEs) or mediate lysis of SE pulsed target cells . In the small number of studies reported, the proliferative response of gamma delta T cells was limited to V gamma 9 negative cells and, in vitro, such responses do not require the presence of MHC class II molecules for antigen presentation . Proliferative responses have been found after stimulation with SEA, SEB and TSST . The cytolytic activity of gamma delta T cells can be mediated by two different mechanisms: either gamma delta T cells specifically interact with SEA pulsed target cells--this is most likely TCR mediated recognition--or gamma delta T cells mediate antibody dependent cellular cytotoxicity (ADCC) . This latter reactivity depends on Fc-receptor expression by the gamma delta T cell clones and the presence of SE specific antibodies during the assay . So far cytotoxic gamma delta T cell reactivity has only been found against the highly homologous enterotoxins SEA and SEE . Finally, HLA-class II positive gamma delta T cell clones can present SE to other SE reactive T cells but appear to be relatively resistant to T cell mediated lysis . Taken together, TCR gamma delta positive T cells are able to respond to a number of bacterial superantigens and may therefore be involved in local immune responses to such antigens . This may be especially relevant for those gamma delta T cell subpopulations that are preferentially found in the (intestinal) epithelia where exposure to bacterial superantigens is likely to occur.

Semin Immunol, 1993 Feb, 5(1), 33 - 9
The CD8 T cell response to staphylococcal enterotoxins; Herrmann T et al.; Staphylococcal enterotoxins (SE) are superantigens that bind to MHC class II molecules and activate T lymphocytes via the T cell receptor (TCR) V beta domain . By analogy with T cell responses to conventional peptide antigens, it might be predicted that CD4 (MHC class II restricted) cells would respond better to SE than CD8 (MHC class I restricted) cells . Here we summarize evidence that in fact CD8 cells respond as well as CD4 cells to SE both in vitro and in vivo . These findings emphasize the unique character of TCR-superantigen interactions.

Semin Immunol, 1993 Feb, 5(1), 3 - 11
Superantigens of microbial origin; Micusan VV et al.; Food poisoning associated staphylococcal enterotoxins and other bacterial products of diverse origin are now the focus of immunological research . These substances have special properties which determine their designation as superantigens . They influence T cell functions by controlling their repertoire, their cytokines production and their modulation of the immune response . As a consequence, superantigens might be at the origin of bacterial and autoimmune diseases . In this review we describe mainly the staphylococcal enterotoxins as representative members of the superantigen family.

Semin Immunol, 1993 Feb, 5(1), 23 - 32
Interactions between staphylococcal superantigens and MHC class II molecules; Labrecque N et al.; Superantigen binding to MHC class II molecules is a prerequisite for T cell stimulation . While the presentation of superantigens is not MHC restricted, allelic and isotypic variations in the ability of class II molecules to interact and present these superantigens exist . SEs bind to MHC class II molecules outside of the peptide binding groove, differences in binding affinities of the toxins for class II alleles and isotypes have been shown . In addition, a direct interaction between T cell receptor and MHC class II molecules could be responsible for these differences . In this review we provide a molecular analysis of the interactions of SEs with class II molecules.

Int J Sports Med, 1993 Feb, 14(2), 86 - 92
The effect of chronic and acute exercise on immunity in rats; Lin YS et al.; The effects of exercise training and acute exercise on the immune system were investigated in rats . For chronic exercise training, the rats ran on a drum exerciser at the intensity of about 60-70% of maximal oxygen consumption (VO2max) for 30 min and then extended up to 60 min per day, 5 days per week for 10 weeks . The rats were at rest for 3 days before sacrifice . The mitogenic activity of spleen lymphocytes to concanavalin A (Con A) and staphylococcal enterotoxin B (SEB) decreased as compared to the sedentary control, while proliferative response to lipopolysaccharide (LPS) increased . The interleukin-2 (IL-2) production in the training group was reduced . The immunomodulatory effect after acute exercise has also been investigated and it showed profound enhancement of cell proliferation to Con A, SEB and LPS in mild (50% VO2max for 10 min) and moderate (70% VO2max for 10 min) exercise groups . The enhancing activity was less prominent after severe exercise (> 75%) VO2max until exhaustion) . The IL2 production increased in all of these acute exercise groups . Nevertheless, there was no significant variation between exercise and control groups in the cell number per spleen and the percentages of various lymphocyte populations, i.e., total T, CD4+, CD8+ and IL-2R+ T cells as well as B cells . In summary, this study indicates that chronic exercise training may cause the reduction of T cell activity while acute exercise manifests an enhancing effect . However, B cell proliferation was elevated in both chronic and acute exercise groups.

Zentralbl Veterinarmed B, 1993 Feb, 40(1), 13 - 20
Diagnostic value of phage typing, antibiogram typing, and plasmid profiling of Staphylococcus hyicus from piglets with exudative epidermitis; Wegener HC; A total of 989 isolates of S . hyicus were recovered from the skin of 103 piglets (9.6 isolates per piglet) with exudative epidermitis (EE), and phage typed . Phage patterns of 806 typable isolates (81%) could be divided into 44 distinct phage types . From 1 to 6 different phage types were found on individual piglets, with an average of 1.9 phage type per piglet . Antibiogram patterns of 384 isolates from 40 randomly selected piglets with EE showed a mean of 2.3 different antibiograms per investigated piglet, ranging from 1 to 6 antibiograms per piglet . Plasmid profiles of 248 S . hyicus isolates from 25 randomly selected piglets showed an average of 2.8 different plasmid profiles per piglet . Seven EE outbreaks in pig herds vaccinated with autogenous vaccine were investigated . In all these herds, strains recovered from the present outbreak differed by two or more type markers to the strains from the previous outbreak used for production of the autogenous vaccine . This finding suggest, that lack of protection might be due to the presence of other virulent types in the investigated herd than those used for production of autogenous vaccine.

Ann Ophthalmol, 1993 Feb, 25(2), 77 - 8
Endophthalmitis in intravenous drug abuse; Schlossberg D et al.; Endophthalmitis usually results from surgical trauma, and it rarely complicates intravenous drug abuse . A case is reported of an intravenous drug abuser who had staphylococcal endophthalmitis.

Am J Infect Control, 1993 Feb, 21(1), 16 - 20
A cluster of coagulase-negative staphylococcal bacteremias associated with peripheral vascular catheter colonization in a neonatal intensive care unit; Gellert GA et al.; BACKGROUND: A cluster of six neonatal cases of coagulase-negative staphylococcal bacteremias occurred in a Los Angeles County neonatal intensive care unit in March 1989 . METHODS: A retrospective cohort study assessed the impact of host-and delivery-related variables, length of hospitalization, duration of antibiotic treatment, performance or duration of invasive procedures, and staffing variables on risk of coagulase-negative staphylococcal bacteremia . RESULTS: Unstratified analyses yielded eight risk factors with risk ratios greater than 2 . After stratification by gestational age (less than 29 weeks) and low birth weight (less than 1500 gm), frequency of blood transfusions, duration of respiratory therapy, heparin lock and central vascular line placement, and hyperalimentation remained associated with elevated risk . Two species were identified, arguing against a common source of infection . Of four cohort months with more than 15 very low birth weight infants in the neonatal intensive care unit, an elevation of coagulase-negative staphylococcus-positive blood cultures and diagnosed bacteremias occurred in only two . CONCLUSIONS: This cluster of coagulase-negative staphylococcal bacteremia was probably caused by frequent manipulation of catheters in neonates who were at heightened risk because of low birth weight and prematurity.

Ann Pharmacother, 1993 Feb, 27(2), 170 - 3
Suspected nafcillin-induced interstitial nephritis; Guharoy SR et al.; OBJECTIVE: To present a case of nafcillin-induced interstitial nephritis . METHODOLOGY: Case report and literature review . SETTING: Hospital . RESULTS: Three days following initiation of nafcillin therapy for staphylococcal pneumonia, an 80-year-old woman developed allergic manifestations and progressive renal impairment suggestive of acute allergic interstitial nephritis . These manifestations were completely reversed within 96 hours of cessation of nafcillin therapy . CONCLUSIONS: In the clinical setting of acute renal failure in a patient on nafcillin therapy, acute interstitial nephritis should be considered . Prompt cessation of nafcillin therapy has generally been associated with reversal of symptoms and an improvement in renal function.

Kyobu Geka, 1993 Feb, 46(2), 124 - 8
{Suppurative mediastinitis after open heart surgery: in comparison between infants-children and adults}; Fukasawa M et al.; Among 361 consecutive patients who underwent open surgery from Jan . 1987 to Sept . 1991, risk factors and clinical courses were analyzed retrospectively in comparison between infants-children and adults . Seven mediastinitis (4.0%) occurred in 173 adult patients (20 to 75 y/o, mean: 54.4 y/o) and were not associated with age, sex, type of disease, and duration of operation or cardiopulmonary bypass . Postoperative mediastinitis significantly increased in the patients with low output syndrome (LOS) determined as use of IABP and/or assistant circulations (p < 0.001) and reexploration for bleeding or tamponase was associated with an increased risk for mediastinitis (p < 0.01) . Five mediastinitis (2.7%) occurred in 188 infants and children (0 to 17 y/o, mean: 4.2 y/o) . All patients involved with mediastinitis were less than 12 month old (2.6 +/- 3.3 month) . None of the other factors was associated with an increased risk for this complication . Bacterial cultures of exudate were positive in 11 of 12 patients, and identified as MRSA in 10 and Staphylococcus epidermidis in one . In the seven of adult patients, two developed sepsis and four died with other organic failures or mediastinal bleeding . All five of infants healed after postoperative 33 to 145 days . The immature state of immune response might associate with postoperative mediastinitis in infants, whether LOS may be important in the immune suppression by surgical stress in adults, and the prognosis of mediastinitis might be effected by prolonged depression of postoperative cardiac function in adult patients.

J Gen Microbiol, 1993 Feb, 139 ( Pt 2), 267 - 77
Molecular analysis and expression of the lipase of Staphylococcus epidermidis; Farrell AM et al.; Lipase of Staphylococcus epidermidis 9 was purified from culture supernatant fluid . Two polypeptides (51 and 43 kDa) were detected by SDS-PAGE, of which the 43 kDa polypeptide reacted with anti-lipase serum . The S . epidermidis 9 lipase gene (gehC) was cloned in Escherichia coli and localized to a 2.1 kb sequence by subcloning and transposon mutagenesis . The nucleotide sequence of gehC (2064 nucleotides) was determined and the predicted amino acid sequence of the encoded lipase (77 kDa) identified . A 97 kDa lipase was detected in extracts of E . coli harbouring gehC and in post-exponential-phase culture supernatant fluids of S . epidermidis 9 . Data presented indicate that the lipase behaves anomalously during SDS-PAGE and that a pro-lipase is proteolytically processed in cultures of S . epidermidis 9 during growth.

Eur J Immunol, 1993 Feb, 23(2), 398 - 402
Human interleukin-5 induces staphylococcal A Cowan 1 strain-activated human B cells to secrete IgM; Bertolini JN et al.; Studies on the role of human interleukin (IL)-5 in B cell growth and differentiation have yielded conflicting results . To clarify this issue, we studied the role of purified recombinant IL-5 on activated human B cells which were depleted of T cells and adherent cells . Human IL-5 augments IgM secretion, but not IgG or IgA secretion of purified human B cells activated with staphylococcal A Cowan 1 strain (SAC) . However, the period of B cell activation with SAC is critical for the B cell to respond to IL-5 . After 24 h of SAC activation, human B cells are responsive to the IL-5 signal, but with longer periods of activation, IL-5 responsiveness diminishes . This may explain some of the previous conflicting results . The IgM enhancement was not seen when B cells were activated with pokeweed mitogen . In addition, human recombinant IL-4 synergized with IL-5 in augmenting IgM secretion by SAC-activated B cells, while IL-5 synergized with IL-2 to augment IgM, IgG and IgA secretion by SAC-activated B cells . As the purified IL-5 was derived from a COS-1 cell supernatant, and COS-1 cells secrete IL-6, we examined whether a polyclonal IL-6 antibody blocked the IgM-enhancing activity of IL-5 . IL-6 antibody did not block the IL-5 enhancement of IgM secretion, but a monoclonal antibody to IL-5 inhibited the human IL-5 activity on human B cells . These results demonstrate that human IL-5 augments IgM secretion of SAC-activated human B-cells . In addition, this lymphokine synergizes with IL-4 and IL-2 in supporting Ig secretion.

Burns, 1993 Feb, 19(1), 22 - 5
Early diagnosis of staphylococcal toxaemia in burned children; McAllister RM et al.; The features of toxic shock syndrome in burned children have been described in a review of seven patients (J . D . Frame et al., Burns 1985; 11, 234) . These include a 'prodromal' 24-48 h period with diarrhoea, vomiting, general malaise, pyrexia, tachycardia and tachypnoea . The white cell count and haemoglobin concentration fall prior to the 'shock' phase, which occurs 3-4 days postburn . Once 'shock' has occurred the mortality of the condition is approximately 50 per cent; in the absence of 'shock' it is much reduced . We have undertaken a retrospective review of six burned children who were admitted in a 2-year period to the Mount Vernon NHS Trust Burns Unit with a clinical diagnosis of toxic shock syndrome . The evidence from our patients suggests that reliable early diagnostic signs are a rapidly developing severe pyrexia of 39.5 degrees C or above, and a simultaneously increasing tachycardia and tachypnoea to high levels . There is a sudden profound fall in the white cell count and haemoglobin concentration over a period of hours between 1 and 3 days from injury . Specific treatment should be instituted before the onset of 'shock' . The name staphylococcal toxaemia might promote earlier diagnosis and treatment of this condition and so reduce its mortality.

Scand J Immunol, 1993 Feb, 37(2), 257 - 64
The alternative binding site for protein A in the Fab fragment of immunoglobulins; Ibrahim S et al.; Twenty-six new human or murine monoclonal immunoglobulins (IgM, IgA, murine IgG1 or human IgG3) with a known V-region sequence were tested for alternative (non-Fc) binding to Staphylococcal protein A . Seven of them did not bind at all . Four immunoglobulins (all mouse IgG1) were bound but easily eluted (at pH 6) . They were probably bound via the Fc part . All eleven were classified as negative for alternative binding . Fifteen immunoglobulins were found to bind more firmly; they came off the protein A column at pH 4-3 (alternative binders) . Amino acid sequences of immunoglobulins that have been typed in the present work or earlier (25 binders and 26 non-binders) were compared . The light chain, the C region of the heavy chain and the D and JH segments look irrelevant for alternative binding . The N-terminal portion (amino acids 1-94) of the H chain probably forms the ligand of protein A . A peptide making the ligand cannot be reliably localized within this stretch but binder proteins had a high homology in residues 6-29 . All mouse immunoglobulins expressing VH genes of families J606 or S107 were alternative binders; those expressing other families were non-binders.

J Clin Invest, 1993 Feb, 91(2), 602 - 7
Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens {see comment}; Takei S et al.; Superantigens are products of bacteria with dual affinity for HLA-DR and the variable region of the beta chain of the T cell receptor, leading to the stimulation of large numbers of T cells . Because there is evidence for the involvement of superantigens in various disease conditions in which intravenous IgG (IVIgG) is used as therapy, the purpose of the present study was to determine if IVIgG contains antibodies inhibitory to T cell stimulation by the superantigens . ELISA and Western assays revealed high concentrations of antibodies in the pooled IgG against eight different staphylococcal toxin (Staph-toxin) superantigens . The IVIgG inhibited in vitro stimulation of human peripheral blood T cells by the Staph-toxins, but did not inhibit responses elicited by phytohemagglutinin or anti-CD3 . Inhibition was mediated by Staph-toxin-specific antibodies as shown by affinity adsorption depletion studies . The antibodies functioned by inhibiting the binding and/or presentation of Staph-toxins by DR+ accessory cells . In conclusion, this report is the first to show that normal pooled IgG contains antibodies against a major group of the superantigens, the Staph-toxins, and that the antibodies can inhibit Staph-toxin-elicited T cell activation, suggesting a possible immunoregulatory role for the antibodies in vivo.

J Clin Microbiol, 1993 Feb, 31(2), 426 - 7
Cervical adenitis caused by Staphylococcus epidermidis; Ryan-Poirier K et al.; Staphylococcus epidermidis, a human commensal, is a common cause of bacteremia in immunocompromised patients with indwelling medical devices . We report a case of isolated cervical adenitis caused by S . epidermidis in an immunocompetent patient and comment on the presumed pathogenesis.

J Med Microbiol, 1993 Feb, 38(2), 96 - 102
Serum and tissue protein binding and cell surface properties of Staphylococcus lugdunensis; Paulsson M et al.; Eleven strains of Staphylococcus lugdunensis from different clinical sources were investigated for their ability to bind 125I-labelled collagen (Cn) type I and IV, fibronectin (Fn), vitronectin (Vn), laminin (Lm), fibrinogen (Fg), thrombospondin, plasminogen (glu- and lys-form) and human IgG . All the strains bound these proteins, although a higher degree of binding was obtained for Cn types I and IV and IgG with mean values of 36%, 32% and 26% binding, respectively . In tests with proteins immobilised on latex beads in a particle agglutination assay, eight of the 11 strains bound Cn type I and seven bound Fg, whereas no strain bound immobilised IgG . Binding to immobilised Cn-I, Fg, Lm and Vn was abolished when the bacterial cells were treated with proteases or heat, indicating cell-surface receptors with protein characteristics . Cell-surface extracts of S . lugdunensis 2342 were able to totally inhibit binding of the homologous strain and S . aureus Cowan 1 to latex-immobilised proteins Cn-I, Lm, Vn, Fn and Fg . The binding of 125I-labelled Cn IV by S . lugdunensis 2342, was heat sensitive, whereas the binding to S . aureus Cowan 1 was heat resistant . The strains gave negative results in tests for the presence of protein A with a S . aureus protein A gene probe and with sensitised red blood cells . No production of heat-stable nuclease (TNase) could be detected by monoclonal antibodies against TNase or by the polymerase chain reaction with an oligonucleotide sequence from S . aureus TNase as primer.(ABSTRACT TRUNCATED AT 250 WORDS)

J Gen Virol, 1993 Feb, 74 ( Pt 2), 175 - 82
Processing of the dengue virus type 2 proteins prM and C-prM; Murray JM et al.; A glycoprotein C-prM of 35,000 M(r) was immuno-precipitated from lysates of Aedes albopictus cells infected with dengue virus type 2 (DEN-2) using antisera directed against the C protein or an amino-terminal fragment of the prM glycoprotein . C-prM was not detected in infected Vero cells . The prM glycoprotein synthesized in infected A . albopictus and Vero cells was cleaved to produce the membrane-associated virion protein (M) and the non-M fragment (pr) immediately preceding or occurring simultaneously with the release of viral particles from cells . The cleavage was less efficient in mosquito cells . The pr fragment was found only in the medium and was not rapidly degraded . To obtain pr-specific and M-specific antisera for these studies, proteins containing fragments of DEN-2 prM fused with staphylococcal Protein A were synthesized in Escherichia coli using the expression vector pRIT2T . The fusion proteins were stable and were used to raise antisera in rabbits for immunoprecipitation of radiolabelled cell extracts and culture medium . This is the first report of the detection of a C-prM protein in flavivirus-infected cells and the identification of the pr component of prM.

Oral Surg Oral Med Oral Pathol, 1993 Feb, 75(2), 220 - 4
Oral Crohn's disease and pyostomatitis vegetans . An unusual association; Ficarra G et al.; Oral features of Crohn's disease include ulcers, lip fissuring, cobblestone plaques, angular cheilitis, polypoid lesions, and perioral erythema . Pyostomatitis vegetans is a rare eruption of the oral mucosa characterized by tiny yellow pustules . It is considered a marker for inflammatory bowel disease . We describe a 45-year-old woman with a 6-month history of painful sores in her mouth, diarrhea, weight loss, and cutaneous lesions . Oral examination revealed cobblestone plaques and indentation on the tongue and friable vegetating pustules on the labial commissures . Staphylococcus simulans was isolated from the pustules . Laboratory studies revealed leucocytosis, eosinophilia, and low hemoglobin and zinc levels . Histologic study of the labial lesions revealed hyperplastic epithelium with intraepithelial clefts that contain eosinophils and neutrophils . Tongue lesions showed chronic inflammation with noncaseating granulomas . Later, colonoscopy and biopsy demonstrated Crohn's disease of the anorectal region . Pyostomatitis vegetans lesions regressed after oral zinc supplementation . Prednisone treatment resulted in healing of the tongue lesions . In our patient, pyostomatitis vegetans appeared to be related to zinc deficiency that may have been caused by malabsorption . The pathogenetic interrelationship between pyostomatitis vegetans and Crohn's disease is discussed.

J Immunol, 1993 Feb 1, 150(3), 763 - 70
The fate of anergic T cells in vivo; Migita K et al.; The kinetics of Staphylococcal enterotoxin B-(SEB) induced peripheral tolerance has been investigated . Ten days after SEB injection, thymectomized BALB/cByJ mice showed suppressed spleen cell proliferative responses to SEB . After 2 mo the SEB-specific response was partly recovered . Four months later the response of spleen cells of SEB-primed mice was comparable to those of control mice . The proportion of CD4+, V beta 8+ T cells was diminished in the tolerized mice and was not restored even after the response was recovered . Purified CD4+, V beta 8+ T cells from SEB-primed mice after 4 mo responded similarly to SEB as control CD4+, V beta 8+ T cells . These expressed a similar profile of surface markers compared with that of unprimed control cells, except a homing receptor was slightly lower . An experiment that addressed the possibility that non-anergic T cells expand over time and are in fact responsible for the recovery of the proliferative response showed that such events unlikely occur in vivo . Therefore, the data indicate that T cell anergy is reversible in vivo . It is also suggested that the challenge with superantigen results in neither clonal expansion nor specific CD4+, V beta 8+ T cell memory.

J Bacteriol, 1993 Feb, 175(3), 851 - 7
Characterization of a sucrase gene from Staphylococcus xylosus; Bruckner R et al.; The Staphylococcus xylosus gene scrB, encoding a sucrase, has been isolated from a genomic library of S . xylosus constructed in Escherichia coli . The gene was detected by its ability to confer utilization of the glucose and fructose residues of raffinose in an E . coli strain that is not able to metabolize galactose . It was found to reside within a 1.8-kb DNA fragment, the nucleotide sequence of which was determined . One large open reading frame, which is preceded by a ribosome binding site, is encoded on the fragment . Its deduced amino acid sequence yields a protein with a molecular mass of 57.377 kDa which shows significant homology with bacterial sucrose-6-phosphate hydrolases and sucrases . Overexpression of scrB in E . coli by the bacteriophage T7 polymerase promoter system resulted in the production of a protein with an apparent molecular mass of 58 kDa . Disruption of the scrB gene in the S . xylosus genome rendered S . xylosus unable to utilize sucrose . Thus, the ScrB sucrase is essential for sucrose metabolism in S . xylosus.

Infect Immun, 1993 Feb, 61(2), 391 - 8
Immunity and responses of circulating leukocytes and lymphocytes in monkeys to aerosolized staphylococcal enterotoxin B; Tseng J et al.; Rhesus monkeys immunized intramuscularly or orally with staphylococcal enterotoxin B (SEB) toxoid or SEB toxoid incorporated in microspheres made of poly(DL-lactide-co-glycolide) were challenged with a lethal dose of aerosolized SEB to study their immunity and cellular responses in the circulation . It was found that circulating antibodies play a critical role in preventing SEB from triggering toxicosis . Monkeys with high levels of antibodies survived, while those with low levels underwent 2 to 3 days of toxicosis and died . Intramuscular immunization induced high levels and oral immunization induced low levels of antibodies . The circulating antibodies in surviving monkeys decreased dramatically within 20 min and started to rebound at 90 min after SEB challenge . At 90 min, the dying monkeys showed in the circulation a dramatic increase of polymorphonuclear leukocytes and decreases of NK cells and monocytes (CD16 and CD56 markers) as well as of lymphocytes with HLA-DR, CD2, CD8, and IL2R alpha (CD25) markers . The number of polymorphonuclear leukocytes showed an inverse correlation with the numbers of monocytes and various lymphocyte subpopulations which, except for IL-2R, CD16, and CD56(+) cells, showed a direct correlation with one another . The changes in the populations of leukocytes, monocytes, NK cells, and lymphocytes seem to be an indication of initial toxicosis; however, the roles of these cells in toxicosis and death remain to be defined.

J Infect Dis, 1993 Feb, 167(2), 329 - 36
Staphylococcus epidermidis adhesion to hydrophobic biomedical polymer is mediated by platelets; Wang IW et al.; A quantitative investigation on the effects of plasma proteins and platelets on the adhesion of Staphylococcus epidermidis RP62A to a hydrophobic biomedical polymer (National Heart, Lung, and Blood Institute reference polyethylene) was carried out under well-defined shear conditions approximating human blood circulation by using a rotating disk system . The results showed that contact-activated platelets mediated S . epidermidis adhesion to the polymer surface . In the range of physiologic shear conditions, the adhesive coefficient (ratio of bacteria per unit area to the product of bacterial flux and the duration of the experiment) to platelets was significantly greater than to the protein-adsorbed polyethylene surface by at least one order of magnitude (P < or = .01) . The presence of absorbed plasma proteins on polyethylene reduced the adhesion of S . epidermidis compared with that seen with the bare polymer surface . These studies show that S . epidermidis adhesion to polyethylene is mediated by contact-activated platelets, not absorbed plasma proteins.

J Pharmacol Exp Ther, 1993 Feb, 264(2), 977 - 83
Ethanol-induced desensitization of adenylate cyclase: role of the adenosine receptor and GTP-binding proteins; Rabin RA; Chronic exposure to ethanol decreases receptor stimulation of cyclic AMP production . In PC 12 cells, chronic treatment with ethanol decreased the maximal stimulation of cyclic AMP accumulation by 2-chloroadenosine without altering the concentration of drug required for half-maximal stimulation . This desensitization was shown to occur after a 7-day exposure to 25 mM ethanol, which is comparable to the legal limit for intoxication in most states . When adenylate cyclase activity was measured directly in PC 12 cells permeabilized with Staphylococcal alpha-toxin, chronic ethanol treatment also decreased enzyme activity . After chronic ethanol exposure, cholera toxin-dependent {32P}ADP ribosylation of both the 44,000 and 52,000 dalton isoforms of the alpha-subunit of the stimulatory GTP-binding regulatory protein of adenylate cyclase (Gs alpha) was reduced . Similarly, an ethanol-induced decrease in the amounts of both isoforms of Gs alpha was found by immunoblot analysis . This decrease in Gs alpha levels was not observed after chronic ethanol exposure of A126-1B2-1 cells, which are functionally deficient in protein kinase A . Immunoblot analysis using an antiserum that recognizes both the alpha-subunit of the inhibitory GTP-binding regulatory protein of adenylate cyclase (Gi alpha)1 and Gi alpha 2 indicated that chronic ethanol treatment did not alter membrane levels of these GTP-binding proteins . Chronic ethanol exposure of PC 12 cells did not alter the affinity of the adenosine A2 receptor for the radioligand {3H}CGS 21680, nor was there a change in the density of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Ind Med, 1993 Feb, 50(2), 183 - 4
Lymphocyte B and T cell subsets in peripheral blood from patients with asbestosis; Peng L et al.; Peripheral blood lymphocytes were analysed by indirect staphylococcus protein A (SPA) rosette assay using monoclonal antibodies that identify B cells, total T cells (OKT3+), helper-inducer T cells (OKT4+), and suppressor-cytotoxic T cells (OKT8+) . The purpose of this investigation was to determine the characteristics of lymphocyte B and T subsets in peripheral blood, and the relation of the changes to radiographic abnormalities in workers exposed to asbestos.

Mol Pharmacol, 1993 Feb, 43(2), 217 - 25
Identification of the benzomorphan opiate binding site on the catalytic subunit of acetylcholinesterase; Coleman BA et al.; The interaction of a benzomorphan opiate with the active site of the catalytic subunit of acetylcholinesterase was studied using photoaffinity labeling . UV irradiation of (-)-N-{3H}allylnormetazocine bound to Torpedo acetylcholinesterase resulted in covalent incorporation of 60-70% of the bound ligand . The labeled catalytic subunit was subjected to chemical cleavage with cyanogen bromide and proteolytic degradation with trypsin, chymotrypsin, and staphylococcal V8 protease . The resulting peptide fragments were purified by high performance liquid chromatography and sequenced in the gas phase . The label was not stable under the conditions of the sequencing, but a peptide fragment consisting of Gln74 to Glu82 was reproducibly labeled . These amino acids are located at the rim of a gorge leading to the active site of the enzyme . Molecular modeling studies then demonstrated that these residues can be placed within van der Waals contact of the (-)-N-{3H}allylnormetazocine molecule while it is bound to the active site of the enzyme.

Infect Immun, 1993 Feb, 61(2), 551 - 8
Isolation and characterization of transposon mutants of Staphylococcus epidermidis deficient in capsular polysaccharide/adhesin and slime; Muller E et al.; We used transposon (Tn) mutagenesis to study the role of capsular polysaccharide/adhesin (PS/A) and slime in adherence of Staphylococcus epidermidis to catheters . pLTV1, containing Tn917-LTV1, was transformed into S . epidermidis M187 by protoplast fusion with S . aureus RN4220(pLTV1), creating M187(pLTV1) . Tn mutants were isolated following growth at 42 degrees C; mutants deficient in PS/A and slime production were selected . PS/A- and slime-deficient Tn mutants had a 10-fold decrease in vitro in the initial phase of adherence to catheters, comparable to levels of strains that do not produce PS/A . Introduction of Tn917-LTV1-interrupted DNA from PS/A-deficient mutant M187sn3 into the parental strain via transformation of protoplasts yielded recipients with inserts identical to those of the Tn mutant that were PS/A and slime deficient . Chromosomal DNA flanking the Tn in mutant M187sn3 was cloned into Escherichia coli . The cloned DNA was found to hybridize to approximately 5-kb EcoRI fragments from the parental strain and from control Tn mutants that express parental levels of PS/A and to either approximately 9- or approximately 14-kb EcoRI fragments from other highly adherent, PS/A-producing strains . Mapping studies demonstrated that in the eight PS/A-deficient mutants that have been isolated, the Tn insertions all occur within a region of approximately 11.6 kb that is defined by three EcoRI sites . These results support previous findings indicating that in S . epidermidis PS/A is involved with in vitro adherence to plastic biomaterials and elaboration of PS/A is closely associated with slime production.

Antibiot Khimioter, 1993 Feb-Mar, 38(2-3), 40 - 2
{Ciprofloxacin in the treatment of staphylococcal endocarditis}; Demin AA et al.; Ciprofloxacin was used in treatment of 5 patients with infectious endocarditis and bacterial vegetations on the values by the findings of the echocardiography . The hemocultures produced the growth of Staphylococcus epidermidis and S . aureus in 3 and 2 patients respectively . The degree of endocarditis was high in 3 patients and intermediate in 2 patients . The drug was administered intravenously in a dose of 200 mg 2 times a day for 4 weeks . The efficacy of the treatment was estimated by following-up the disease time course: the patients were examined prior to the treatment, every week during the treatment and after the treatment completion . The complex clinico-laboratory investigations showed that ciprofloxacin (Ciprinol, KRKA, Slavonia) is a highly efficient chemotherapeutic drug of the group of fluoroquinolones for the treatment of infectious (staphylococcal) endocarditis due to the sensitive microbes . The intravenous drug is useful in treatment of severe forms of infectious endocarditis . The drug is not toxic and well tolerated by the patients after its intravenous administration.

Cell Immunol, 1993 Feb, 146(2), 249 - 60
Function of dipeptidyl peptidase IV (CD26, Tp103) in transfected human T cells; Hegen M et al.; CD26 (Tp103) is a proteolytic enzyme (dipeptidyl peptidase IV) expressed on the T cell surface that defines an alternative activation signal for human T lymphocytes . It is absent from or present in only low amounts on resting T cells but it is expressed strongly after activation . Crosslinking of CD26/Tp103 via the monoclonal antibody CB.1 triggers functional activities in preactivated T cells . To study the molecular requirements for T cell activation via CD26 we transfected a cDNA encoding CD26 into several CD26-negative cells . In Jurkat T cell leukemia cells that normally do not express the CD26 antigen, the transfected CD26 molecule is functional because the monoclonal antibody CB.1 induces an increase of cytosolic Ca2+ concentration and IL-2 production . For this stimulatory effect a crosslinking of the monoclonal antibody CB.1 is necessary . After modulation of the TCR/CD3 complex the transfected Jurkat cells were insensitive to triggering via CD26 . Moreover, a CD26-transfected TCR-negative variant of Jurkat cells did not respond to CD26 triggering despite high levels of expression of the molecule on their surface . These data demonstrate that the function of CD26/Tp103 is dependent on the expression of the T cell receptor complex . In search of a physiological function of CD26 we found a costimulatory effect of mAb CB.1 in combination with the nonstimulatory anti-CD3 antibody BMA030 and an additive effect in the response to the superantigen staphylococcal enterotoxin E . Transfected Jurkat cells, however, did not show a reproducibly enhanced responsiveness to the superantigen compared to that of untransfected cells.

Acta Virol, 1993 Feb, 37(1), 54 - 60
Interferon system in patients with rheumatoid arthritis and sclerodermia systematica; Scheglovitova ON et al.; In the blood of patients with rheumatoid arthritis and/or sclerodermia systematica usually acid-labile interferon-alpha (IFN-alpha) was found . Blood leukocytes cannot be considered the source of its production as they spontaneously produce IFN-gamma identified with specific antiserum . Blood leukocytes of tested patients generated in vitro a reduced amount of staphylococcus enterotoxin A-induced IFN-gamma and virus-induced acid-labile IFN-alpha . This findings support the assumption of impaired functioning of T- and B-blood cells in autoimmune diseases . The production of Newcastle diseases virus-induced IFN-alpha and influenza virus-induced acid-stable IFN-alpha by patients' leukocytes has not been altered . Acid-labile IFN-alpha obtained from the blood of tested patients, IFN-gamma spontaneously generated by leukocytes in vitro and acid-labile IFN-alpha produced by leukocytes in vitro following induction with influenza virus show similar sensitivity to pH 2.0 and time patterns of the antiviral state development in human diploid fibroblast culture.

Eur J Immunol, 1993 Feb, 23(2), 578 - 81
Peripheral clonal deletion of superantigen-reactive T cells is enhanced by cortisone; Lussow AR et al.; The T cell receptor (TcR) V beta-specific expansion, deletion and induction of nonresponsiveness among murine T cells responding to superantigens in the periphery has been well characterized . Here we demonstrate that clonal deletion of staphylococcal enterotoxin (SE) B-reactive V beta 8.2+ cells can be significantly increased when mice are injected with hydrocortisone (HC) following superantigen stimulation in vivo . The induced sensitivity to HC persists for at least 30 days after SEB injection, making it unlikely that proliferating cells were uniquely responsible for the enhanced deletion . Superantigen-induced HC sensitivity was a general phenomenon and could also be observed among V beta 11+ cells after the injection of SEA . Experiments conducted on thymectomized mice indicated that HC-sensitive, SEB-responsive cells could not be accounted for by rapidly produced, immature lymphocytes recently exported from the thymus . Further, V beta 8.1+ peripheral lymphocytes from TcR transgenic mice expressing the Mls-1a superantigen were sensitive to HC . These results imply that the majority of cells remaining after superantigen-induced clonal expansion and deletion in vivo have indeed reacted with the superantigen . Implications for differential superantigen recognition by T cells expressing the same TcR V beta domain, perhaps due to a significant V alpha contribution to the interaction in vivo, are discussed.

Eur J Immunol, 1993 Feb, 23(2), 523 - 9
Manipulation of the superantigen-induced lymphokine response . Selective induction of interleukin-10 or interferon-gamma synthesis in small resting CD4+ T cells; Cardell S et al.; The production of several lymphokines by freshly isolated CD4+ T cells has been analyzed at the single-cell level, after stimulation with staphylococcal enterotoxin B (SEB) . High frequencies of cells producing interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were induced, but very low frequencies of CD4+ T cells produced IL-4, IL-5 or IL-10 in response to SEB . Exogenously added IL-4 markedly altered the lymphokine profile induced during primary SEB stimulation . IFN-gamma production was reduced, while a high fraction of cells contained IL-10 and IL-4 after activation in the presence of IL-4 . We further demonstrate that IL-4 and IL-10 or IFN-gamma production was selectively induced in resting, high-density CD4+ T cells during primary stimulation, by SEB + IL-4 or SEB . Under conditions where both IL-10 and IFN-gamma were produced, most cells contained only one of the two lymphokines.

J Exp Med, 1993 Feb 1, 177(2), 283 - 93
Localization of a site on bacterial superantigens that determines T cell receptor beta chain specificity; Mollick JA et al.; A defining characteristic of superantigens is their ability to stimulate T cells based predominantly on the type of variable segment of the T cell receptor (TCR) beta chain (V beta) . The V beta specificity of these toxins most likely results from direct contact between the toxin and the TCR, although the low affinity nature of this binding has prevented direct assessment of this interaction . To identify important functional sites on the toxin, we created chimeric enterotoxin genes between staphylococcal enterotoxins A and E (SEA and SEE) and tested the V beta specificity of the chimeric toxins . This approach allowed us to identify three amino acid residues in the extreme COOH terminus of these toxins that are largely responsible for their ability to stimulate either human V beta 5- or V beta 8-bearing T cells, or mouse V beta 3 or V beta 11 . We also found that residues in the NH2 terminus were required for wild-type levels of V beta-specific T cell activation, suggesting that the NH2 and COOH ends of these superantigens may come together to form the full TCR V beta contact site . SEA and SEE also differ with respect to their class II binding characteristics . Using the same chimeric molecules, we demonstrate that the first third of the molecule controls the class II binding phenotype . These data lead us to propose that for SEA and SEE, and perhaps for all bacterial-derived superantigens, the COOH and NH2 termini together form the contact sites for the TCR and therefore largely determine the V beta specificity of the toxin, while the NH2 terminus alone binds major histocompatibility complex class II molecules . The predominant role of the COOH terminus of bacterial superantigens in determining V beta specificity resembles current models being proposed for virally encoded superantigens, suggesting that these molecules may demonstrate some structural relationship not seen at the amino acid level.

J Immunol, 1993 Feb 1, 150(3), 726 - 35
Proliferation of human T lymphocytes induced with superantigens is not dependent on costimulation by the CD28 counter-receptor B7; Damle NK et al.; Staphylococcal enterotoxins, also known as superantigens (SAg), bind class II MHC molecules on APC and upon direct cell-to-cell contact stimulate proliferation of T cells expressing appropriate V beta gene products . The T cell surface molecule CD28 binds its costimulatory counter-receptor, B7 expressed on APC, and augments IL-2 production and T cell growth . Although the role of B7 costimulation during Ag-specific responses of T cells is established, its involvement during the activation of T cells with SAg has not been examined . Using a soluble Ig C gamma 1 chimera of CTLA-4, a second receptor for B7 and a homologue of CD28, this study examines the role of B7 expressed on APC during the induction of proliferation of CD4+ T cells upon stimulation with SAg (SAg/staphylococcal enterotoxins) . CTLA-4lg, which has a higher avidity for B7 than CD28, had no effect on the synthesis of IL-2 as well as proliferative responses of CD4+ T cells induced by SAg presented on allogeneic EBV-transformed B cells, and IFN-gamma-activated endothelial cells . In contrast, T cell proliferation induced by alloAg presentation by the same APC was significantly inhibited by CTLA-4lg . mAb directed at the CD11a/CD18 molecule inhibited both SAg-induced and alloAg-induced proliferation of T cells . AlloAg-primed CD4+ T cells, which expressed both class II MHC and intercellular adhesion molecule-1 but not B7, presented SAg to and induced proliferation of both resting and SAg-primed T cells . These responses were inhibited by mAb directed at CD11a/CD18 but not by CTLA-4 Rg . These results suggest that SAg-induced responses differ from those induced by alloAg in that they are not obligatorily dependent on the costimulation by B7 . In contrast, adhesive interaction between CD11a/CD18 on T cells and its counter-receptor on SAg-presenting cells is necessary and probably sufficient to support SAg-induced proliferation of T cells.

Eur J Biochem, 1993 Jan 15, 211(1-2), 105 - 10
Purification and characterization of an aminopeptidase A from Staphylococcus chromogenes and its use for the synthesis of amino-acid derivatives and dipeptides; Yoshpe-Besancon I et al.; An aminopeptidase with original specificity was purified 3800-fold to homogeneity from a cellular extract of Staphylococcus chromogenes . The enzyme was specific for acidic amino acids (Asp and Glu) at the N-terminus of peptides and thus can be classified as an aminopeptidase A . However, its specificity was not restricted to acidic amino acids: alpha-hydroxy acids such as L-malic and L-lactic acids were also accepted in position P1 . The enzyme had a broad specificity for the residue at position P' 1, accepting all types of amino acids, including Pro, in this position . The optimal conditions for the hydrolysis of Asp-Phe-NH2 were pH 9.5 and 60 degrees C . The enzyme was inhibited by chelating agents and serine-protease inhibitors . The activity lost by treatment with chelating agents could be restored by Mn2+ or Zn2+ which also stimulated the native enzyme . This suggests that it is a metalloprotease with a serine residue essential for the activity . The native enzyme had an apparent molecular mass of 430 kDa on gradient-gel electrophoresis and subunits of 43 kDa as determined by SDS/PAGE . The enzyme catalyzed the synthesis of peptide and amino acid derivatives such as Asp-Phe-OMe (Aspartame) and malyl-Tyr-OEt from L-Asp and L-malic acid as acyl donors and L-Phe-OMe and L-Tyr-OEt as nucleophiles, respectively . The use of the enzyme as a reagent in protease-catalyzed peptide synthesis, N-terminal protection and subsequent deprotection, is described.

Biochem Biophys Res Commun, 1993 Jan 15, 190(1), 20 - 6
The disulfide bond arrangement of leukemia inhibitory factor: homology to oncostatin M and structural implications; Nicola NA et al.; Murine leukemia inhibitory factor (LIF) (the fully active recombinant form produced in E . coli) was digested in the unreduced state with trypsin and Staphylococcal V8 protease in 0.05% sodium dodecyl sulfate . Disulfide-bonded peptides were identified by altered mobility on reverse-phase high-performance liquid chromatography in the presence or absence of dithiothreitol and subjected to amino acid sequencing . Peptides containing more than one disulfide bond were subjected to further proteolysis and disulfide-bonded subfragments identified and sequenced . The three disulfide bonds are CYS13-CYS135, CYS19-CYS132 and CYS61-164 and the first and third of these are clearly homologous to the two disulfide bonds in oncostatin M . The spatial organization of the cysteine residues in the predicted four alpha-helical bundle structure of LIF (Bazan, Neuron 7,197;1991) is compatible with these disulfide assignments.

J Immunol, 1993 Jan 15, 150(2), 664 - 72
Studies of T cell deletion and T cell anergy following in vivo administration of SEB to normal and lupus-prone mice; Scott DE et al.; This study examines the responses of lupus-prone NZB, (NZB x NZW) F1, BXSB, MRL-lpr/lpr and control mice (H-2 and Mls matched) to in vivo administration of the superantigen staphylococcal enterotoxin B (SEB) . Two weeks after i.v . administration of 500 micrograms SEB, CD4+V beta 8+ lymph node T cells were deleted equivalently by lupus-prone and control mice . However, IE+ strains deleted a greater proportion (47% to 77%) of their CD4+V beta 8+ cells than did IE- strains (24% to 27%) . CD8+V beta 8+ cells were deleted less than CD4+V beta 8+ cells by injection of 500 micrograms SEB . IE- strains failed to delete CD8+V beta 8+ cells, whereas six of seven IE+ strains deleted > 25% of their CD8+V beta 8+ cells . IE+ MRL-lpr/lpr mice showed some impairment in deletion: they failed to delete CD8+V beta 8+ cells at all doses of SEB and had reduced deletion of CD4+V beta 8+ cells at low doses of in vivo SEB (10 and 50 micrograms) . Peripheral expansion of the intrathymically deleted V beta 7 TCR family was not observed in lupus-prone mice 2 wk after 500 micrograms in vivo SEB . In vitro restimulation with SEB of mice previously injected with 500 micrograms SEB demonstrated anergy in T cells from all strains, including the IE- and MRL-lpr/lpr . This result contrasts with previous reports of tolerance defects in lupus-prone strains using B cell read-out assays as measures of tolerance . The present study demonstrates that there is no global defect in peripheral T cell deletion or anergy in lupus-prone mice to the superantigen SEB . Although additional Ag would need to be studied, these experiments raise the possibility that some reported tolerance defects in lupus-prone strains may reflect excessive B cell responses to relatively normal T cell signals.

Blood, 1993 Jan 15, 81(2), 446 - 53
Expression and function of a receptor for hyaluronan-mediated motility on normal and malignant B lymphocytes; Turley EA et al.; Migration through extracellular matrix is fundamental to malignant invasion . A receptor for hyaluronan-mediated motility (RHAMM) has previously been shown to play a fundamental role in locomotion of ras-transformed cells as well as functioning in signal transduction . Expression of RHAMM was characterized on B lymphocytes from normal and malignant lymphoid tissues using multiparameter phenotypic immunofluorescence analysis as well as functional analysis of its role in locomotion of malignant hairy cell leukemia B cells . RHAMM is not detectable on most normal B cells located in blood, spleen, or lymph node, but it is detectable on bone marrow and thymic B cells . Among B-cell malignancies, it is expressed on most terminally differentiated B cells from multiple myeloma bone marrows, is present on a subset of non-Hodgkin's lymphomas, and is absent on B chronic lymphocytic leukemia . Activation of peripheral blood B cells by Staphylococcus A cowan (SAC), but not by pokeweed mitogen, induced transient expression of RHAMM at day 3 of culture, suggesting RHAMM may be used by antigen-activated normal B cells . For malignant cells, expression of RHAMM increased on long-term culture of bone marrow plasma cells from multiple myeloma patients, indicating prolonged expression in contrast to the transient expression on SAC-activated normal B cells . Intriguingly, RHAMM was expressed on hairy leukemia cells located in spleen but absent from those in peripheral blood of the same patient . RHAMM, as expressed on splenic hairy cells, was a 58-Kd molecule that binds hyaluronan, is encoded by a 5.2-kb messenger RNA, and participates in locomotion by these cells . Hairy cells locomoted in response to hyaluronan at 4 mu per minute . Monoclonal antibody to RHAMM inhibited this locomotion almost completely as detected using video time-lapse cinemicrography . These observations are consistent with a role for RHAMM in malignant invasion and metastatic growth.

Abdom Imaging, 1993, 18(3), 225 - 6
Staphylococcal esophagitis causing giant ulcers; Miller JT Jr et al.; A 29-year-old woman with Hodgkin disease developed odynophagia while receiving chemotherapy . Large esophageal ulcers due to staphylococcal infection of the mucosa were visualized by endoscopy and radiography . This unusual bacterial esophagitis represents another potential cause of giant esophageal ulcerations.

Biosens Bioelectron, 1993, 8(1), 39 - 48
Study of immunoglobulin G thin layers obtained by the Langmuir-Blodgett method: application to immunosensors; Barraud A et al.; Nowadays, immunosensors play a leading part in the field of bioanalytical chemistry research . As with any biosensor, they need appropriate transducers and a suitable technique to immobilize the active biocomponents . In this study, two transduction modes were chosen: mass effects (quartz microbalance measurements) and geometric and dielectric effects (capacitance measurements) . The Langmuir-Blodgett (LB) method appears to be quite suitable for generating biospecific surfaces . This work has focused on the detection of staphylococcal enterotoxin B, the corresponding antibody being immobilized at the surface of fatty acids by a variant of the LB method . The composition of the film and the nature of antibody-fatty acid interactions were studied by means of the two transducers mentioned above . FTIR (Fourier transform infra-red) spectroscopy and protein diagnostic assay . Influence of several parameters (pH, ionic strength, transfer pressure, antibody concentration in the subphase) was investigated . The immobilization rate reached its maximum when experimental conditions allowed optimal electrostatic interactions . In this case, the quartz crystal microbalance response, in air, reached 55 Hz per monolayer of immobilized immunoglobulin G and the equivalent capacitance variation, measured in liquid media, was around 300 pF cm-2 . Activity of the biospecific LB films, when binding enterotoxin, was checked by the classical ELISA (enzyme immuno-linked assay) technique.

J Fr Ophtalmol, 1993, 16(1), 10 - 3
{Bacterial contamination of the anterior chamber and cataract surgery}; Pospisil A et al.; The authors report the results of bacteriologic cultures of the anterior chamber aspirate after cataract surgery . The results were positive for 15 cases (24%) . Nine cultures were positive for 27 eyes operated by phacoemulsification and 6 cultures were positive for 35 eyes operated by extracapsular cataract extraction . The origin of these organisms is the normal bacterial flora of the conjunctiva and the inoculum size is very small . The most commonly identified organisms are coagulase-negative staphylococcus and propionibacterium acnes.

Pediatr Pathol, 1993 Jan-Feb, 13(1), 1 - 8
Idiopathic hydropericardium as a cause of death of a preterm neonate; Stanek J et al.; We report a case of a very premature infant who died on day 17 of life because of clinically unsuspected cardiac tamponade due to a pericardial effusion with no gross or microscopic features of myocardial inflammation or perforation . The pericardial effusion probably accumulated for 8 days prior to his death, as evidenced by chest X-ray films . The only relevant microscopic finding was a prominent pericardial and myocardial interstitial edema . Although Staphylococcus epidermidis line sepsis, central venous catheter trauma, hypoalbuminemia, anemia, and heart failure could be possible contributory factors, no definitive cause of the pericardial effusion was found and the etiology of this condition remains obscure.

J Biochem (Tokyo), 1993 Jan, 113(1), 29 - 35
Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin; Maeda T et al.; Fibronectin contains at least two distinct oligopeptide sequences serving as signals for the interaction with cell surface adhesion receptors termed integrins . One of these sequences, Arg-Gly-Asp-Ser (RGDS) tetrapeptide, was shown to be transferred to a truncated form of Staphylococcal IgG-binding protein (hereafter referred to as tSPA) with retention of its cell-adhesive activity {Maeda, T . et al . (1989) J . Biol . Chem . 264, 15165-15168} . We have extended the observation to another cell-adhesive sequence, Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (referred to as "CS1" sequence), to demonstrate that: i) the tSPA grafted with the sequence mediated adhesion of human lymphoma and rhabdomyosarcoma cells, mouse melanoma cells, but not of hamster fibroblasts; ii) antibodies against integrin alpha 4 and beta 1 subunits specifically inhibited cell adhesion mediated by the CS1-grafted tSPA; iii) a heterodivalent tSPA grafted with both RGDS and CS1 sequences at different sites was more potent in promoting cell adhesion than the monovalent tSPAs grafted with either sequence alone . These results indicate that not only the RGDS but also the CS1 sequence can be transferred to tSPA with retention of its cell-adhesive activity as well as its cell-type specificity, and that the grafted CS1 sequence is recognized by the same integrin isotype as the authentic sequence within intact fibronectin.

J Biomol NMR, 1993 Jan, 3(1), 67 - 80
The use of 1JC alpha H alpha coupling constants as a probe for protein backbone conformation; Vuister GW et al.; Simple pseudo-3D modifications to the constant-time HSQC and HCACO experiments are described that allow accurate (+/- 0.5 Hz) measurement of one bond JC alpha H alpha coupling constants in proteins that are uniformly enriched with 13C . An empirical phi,psi-surface is calculated which describes the deviation of 1JC alpha H alpha from its random coil value, using 203 1JC alpha H alpha values measured for residues in the proteins calmodulin, staphylococcal nuclease, and basic pancreatic trypsin inhibitor, for which phi and psi are known with good precision from previous X-ray crystallographic studies . Residues in alpha-helical conformation exhibit positive deviations of 4-5 Hz, whereas deviations in beta-sheet are small and, on average, slightly negative . Data indicate that 1JC alpha H alpha depends primarily on psi, and that 1JC alpha H alpha may be useful as a qualitative probe for secondary structure . Comparison of 1JC alpha H alpha coupling constants measured in free calmodulin and in its complex with a 26-amino-acid peptide fragment of myosin light-chain kinase confirm that the calmodulin secondary structure is retained upon complexation but that disruption of the middle part of the 'central helix' is even more extensive than in free calmodulin.

Clin Infect Dis, 1993 Jan, 16(1), 100 - 6
Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses; Kain KC et al.; To further characterize the clinical spectrum of nonmenstrual toxic shock syndrome (NMTSS), we constrasted and compared the clinical and laboratory features of 24 patients with NMTSS with those of 21 patients with menstrual TSS (MTSS), using univariate and stepwise discriminant analyses . In contrast to patients with MTSS, those with NMTSS comprised a heterogeneous group with varying host factors and clinical presentations . The NMTSS group differed from the MTSS group in terms of the frequency of prior antimicrobial treatment (46% vs . 16%; P = .05), the rate of nosocomial acquisition (65% vs . 0; P = .0001), and the time of onset of fever and rash in relation to the initial symptoms (P = .005 and .03, respectively, with earlier onset in the NMTSS group) . In addition, NMTSS patients experienced more frequent renal and CNS complications and less frequent musculoskeletal involvement (P = .07 in all three cases) . Stepwise discriminant analysis identified four variables (delayed onset of TSS symptoms after precipitating injury or event, more frequent CNS manifestations, less frequent musculoskeletal involvement, and higher degree of anemia) differentiating NMTSS patients from MTSS produced TSS toxin 1 (TSST-1) with comparable frequency (62% vs . 84%; P = .2), but production of staphylococcal enterotoxin A (SEA) was less common in NMTSS than in MTSS (33% vs . 74%; P = .01) . Furthermore, MTSS-associated isolates more commonly coexpressed TSST-1 and SEA than did NMTSS-associated isolates (68% vs . 28%; P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1993 Jan, 31(1), 129 - 38
The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits; Chavanet P et al.; This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE) . MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L . In rabbits treated with a single-dose i.v . regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001) . Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug . From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S . epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S . epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.

Nutr Hosp, 1993 Jan, 8(1), 53 - 9
{Sepsis due to multiple-lumen catheters in bone marrow transplantation with total parenteral nutrition . The effect of the type of isolation}; Oloriz MR et al.; The use of catheters for total parenteral nutrition frequently leads to infectious complications which are more common and virulent in patients with marrow aplasia . The main purpose of this paper was to evaluate the influence in the development of catheter-induced sepsis of the place where it was introduced (in the theatre or hospitalization unit), the type of isolation (laminar flux unit or conventional room), and its relation to the period of isolation and of the total parenteral nutrition . Forty-one bone-marrow transplant patients were studied, 18 of them autologous and 23 allogenic, who were administered total parenteral nutrition with a two-way central venous polyurethane catheter . Of the 41 catheters applied, 16 were introduced in the operating theater and 25 in the hospitalization unit: of these, 7 and 11 respectively were infected . Isolation was as follows: 21 in standard rooms and 20 in a laminar flux unit, with 11 and 7 infections respectively . We believe that the lower level of infections in laminar flux isolation was not significant, this being a reduced number of case studies . The duration of the catheter and total parenteral nutrition for the 18 patients with sepsis was 36.5 +/- 15.1 and 23.7 +/- 8.4 days respectively: this was greater--albeit possibly not significantly so because of the special characteristics of these patients--than the 29.1 +/- 12.9 and 19.5 +/- 10.9 days for non-septic cases . This reveals a catheter sepsis rate of 43.9%, in 88% of cases caused by skin flora micro-organisms (66.6% coagulase-negative staphylococcus).(ABSTRACT TRUNCATED AT 250 WORDS)

Int Immunol, 1993 Jan, 5(1), 55 - 61
Skewed T cell receptor V alpha repertoire among superantigen reactive murine T cells; Waanders GA et al.; Reactivity of murine T cells with viral or bacterial superantigens is clearly correlated with the expression of TCR V beta domains . Thus, T cells responding to the minor lymphocyte stimulatory locus (Mls-1a) or staphylococcal enterotoxin B (SEB) express predominantly TCR V beta 6 or V beta 8.2 respectively . We have investigated the involvement of the other major variable element of the TCR, the V alpha domain, in these superantigen responses . Using a panel of anti-TCR V alpha mAbs, it is demonstrated that the TCR V alpha repertoire among superantigen stimulated V beta 6+ or V beta 8.2+ blasts (responding to Mls-1a or SEB respectively in vitro) is altered in comparison with anti-CD3 stimulated cells expressing the same V beta domains . Furthermore, the TCR V alpha repertoire is strongly skewed in TCR V beta 8.2 transgenic mice that have undergone extensive peripheral clonal deletion after SEB injection . These data imply that the V alpha domain influences superantigen recognition by the TCR.

Cancer Immunol Immunother, 1993, 36(4), 223 - 8
T cell killing of human colon carcinomas by monoclonal-antibody-targeted superantigens; Lando PA et al.; The bacterial superantigen staphylococcal enterotoxin A (SEA) induces T cell activation as well as directing activated T cells to kill major-histocompatibility-complex-class-II-expressing tumours such as freshly prepared leukemia cells . We now report that conjugates of SEA and the colon-carcinoma-reactive mAb C215 mediate T-cell-dependent killing of freshly isolated cells obtained from surgical specimens of human colon carcinomas . Cytotoxicity was observed at nanomolar concentrations of conjugate while no or very low effects were seen with the mAb C215 or SEA alone . Tumour-infiltrating lymphocytes (TIL) did not exert any cytotoxicity against conjugate-treated tumour cells immediately after isolation . In vitro culture of TIL with interleukin-2 and SEA resulted in SEA-mAb-conjugate-dependent killing of freshly isolated tumour cells . This suggests that mAb-SEA conjugates may be of potential use to target T lymphocytes, including TIL, against colon carcinoma cells in vivo.

Appl Environ Microbiol, 1993 Jan, 59(1), 285 - 9
Microbial degradation of dibenzofuran, fluorene, and dibenzo-p-dioxin by Staphylococcus auriculans DBF63; Monna L et al.; Staphylococcus auriculans DBF63, which can grow on dibenzofuran (DBF) or fluorene (FN) as the sole source of carbon and energy, was isolated . Salicylic acid and gentisic acid accumulated in the culture broth of this strain when DBF was supplied as a growth substrate . Also, the formation of 9-fluorenol, 9-fluorenone, 4-hydroxy-9-fluorenone, and 1-hydroxy-9-fluorenone was demonstrated, and accumulation of 1,1a-dihydroxy-1-hydro-9-fluorenone was observed when this strain grew on FN . On the basis of these results, the degradation pathways of DBF and FN were proposed . The analogous oxidation products of dibenzo-p-dioxin were obtained by incubation with DBF-grown S . auriculans DBF63 cells.

Lab Anim, 1993 Jan, 27(1), 73 - 6
Grass pollen specific antibody in the plasma of normal dogs; Wheeler AW; An investigation carried out with healthy beagle dogs showed that their plasmas contained detectable levels of grass pollen specific IgG antibody, as measured by a radiometric assay involving the binding of IgG to radio-iodinated staphylococcal protein A . These samples did not, however, contain detectable homocytotropic-type antibodies specific for grass pollen extract.

J Pediatr Surg, 1993 Jan, 28(1), 26 - 30
Wound infection in pediatric surgery: a study in 1,094 neonates; Davenport M et al.; In an analysis of 1,433 wounds created in 1,094 neonates admitted to a regional neonatal surgical unit during the period April 1975 to December 1987, the mean incidence of infection was 16.6% . During this time there was an increase in the incidence of infection from 12.5% in the first 6 years to 18.8% in the last 7 years (P < .01) . Contaminated wounds had an infection rate of 20.7%, whereas the rate in clean wounds was 11.1% (P < .001) . Gestational age and birth weight had no influence on the incidence of wound infection . Increasing wound length (P < .001), increasing duration of operation (P < .001), and contamination at operation (P < .001) were all associated with a higher incidence of infection . Staphylococcal species were the most frequently isolated organisms from all categories of infected wounds (clean, potential, and actual contamination).

Dermatology, 1993, 186(2), 153 - 4
Staphylococcal scaled skin syndrome in an adult: possible influence of non-steroidal anti-inflammatory drugs; Khuong MA et al.; A 89-year-old woman presented with typical staphylococcal scaled skin syndrome (SSSS) . An abscess of the left buttock related to non-steroidal anti-inflammatory drug (NSAID) injections was evacuated . We discuss the influence of NSAID administration on SSSS risk factors, i.e . renal insufficiency and immunosuppression.

Cancer Immunol Immunother, 1993, 36(2), 89 - 93
Superantigen-based tumor therapy: in vivo activation of cytotoxic T cells; Hedlund G et al.; We have recently demonstrated that the superantigen staphylococcal enterotoxin A (SEA) targets in vitro activated cytotoxic T lymphocytes against tumor cells expressing major histocompatibility complex (MHC) class II antigens . In this report we analyze the use of SEA as an immunoactivator in vivo . Treatment of mice with SEA activated a fraction of CD3+ T cells apparently as a function of their T cell receptor V beta expression . SEA induced interleukin-2 receptor expression and proliferation in both CD4+ and CD8+ T cells . This proliferative response was dose-dependent (0.1-100 micrograms/mouse), peaked during day 1 after treatment and declined to background levels within 4 days . The cytotoxic response, measured as cytotoxicity to SEA-coated MHC class II+ target cells (staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity, SDCC), was maximal at a dosage of 1 microgram SEA/mouse . The SDCC was confined to the CD8+ T cell compartment, peaked 2 days after treatment and declined to background levels within 4 days . A second injection of SEA on day 5 after the first SEA treatment resulted in SDCC function with kinetics and magnitude identical to that seen after one injection . These results pave the way for the use of SEA in the treatment of MHC class II+ tumors.

Eur J Immunol, 1993 Jan, 23(1), 90 - 5
H-2 I-E molecules isolated from Mls1a stimulatory cells do not activate Mls1a-responsive T cells but do present exogenous staphylococcal enterotoxins; Macphail S et al.; The T cell response to allogeneic murine Mls determinants is not H-2 restricted but is dependent on H-2 class II molecules on the Mls-expressing stimulator cells . We have tested planar membranes containing H-2 class II I-E molecules alone or with I-A molecules for their ability to activate a panel of Mls1a-specific T hybrids . Despite the ability of the planar membranes to activate an alloreactive T hybrid and to present staphylococcal enterotoxins or an antigenic peptide to appropriately responsive T hybrids, they failed to stimulate the Mls1a-specific T hybrids . These findings, in the light of the various controls demonstrating sufficiency of the I-E molecules in the planar membranes, indicate that Mls1a determinants are not covalently bound to I-E molecules; the two molecular species are thus either not physically associated or are linked by a relatively weak interaction . In addition, our experiments show that isolated I-E molecules but not I-A molecules present staphylococcal enterotoxins A and B to two independently derived T hybrids expressing T cell receptor V beta 1, V beta 2 and V beta 6 elements.

Arch Surg, 1993 Jan, 128(1), 68 - 71; discussion 72
Polymorphonuclear cell-mediated vascular injury in anergic surgical patients; Stergiopoulos SA et al.; We examined the responses of primed polymorphonuclear neutrophils (PMNs) adhered to vascular endothelium, which can lead to endothelial cell damage as a mechanism of the capillary leak syndrome, the main cause of death in anergic patients . We tested PMNs from (1) preoperative reactive patients, (2) preoperative anergic patients, (3) anergic patients in the surgical intensive care unit, and (4) healthy controls for in vitro adherence and cytotoxicity on cultured human vein endothelial cells . Adherence of PMNs was 12.9% +/- 3.9% in preoperative anergic patients and 13.1% +/- 3.2% in anergic patients in the surgical intensive care unit compared with 9.0% +/- 2.1% in preoperative reactive patients (P < .05) . Cytotoxicity was 6.0% +/- 2.8% in preoperative reactive patients, 13.7% +/- 4.1% in preoperative anergic patients, and 14.3% +/- 4.6% in anergic patients in the surgical intensive care unit . The PMNs from preoperative anergic patients were more cytotoxic against human vein endothelial cells when stimulated by Staphylococcus epidermidis or formyl-methionyleucylphenylalanine . We conclude that PMNs from anergic surgical patients adhere more to endothelial cells and can produce increased cytotoxicity that may lead to detrimental results.

J Exp Med, 1993 Jan 1, 177(1), 175 - 84
Two adjacent residues in staphylococcal enterotoxins A and E determine T cell receptor V beta specificity; Hudson KR et al.; The T cell receptor (TCR) V beta-determining region of two bacterial superantigens, staphylococcal enterotoxin A (SEA) and SEE, has been mapped to the COOH-terminal region of SEA and SEE using a panel of recombinant SEA/SEE hybrids . Total TCR V beta mRNA enrichment in human peripheral blood T cell cultures was determined by a novel single-tube amplification technique using a redundant V beta-specific primer . SEA routinely enriched mRNA coding for hV beta 1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hV beta 5.1, 6.3, 6.4, 6.9, and 8.1 mRNA . Exchanging residues 206 and 207 was sufficient to convert in toto the TCR V beta response of human peripheral T lymphocytes . In addition, an SEA-reactive murine T cell line, SO3 (mV beta 17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hV beta 8.1), unresponsive to SEA was stimulated strongly by SEA-P206D207 . Exchanging all other regions of SEA and SEE except residues 206 and 207 did little to change the V beta response . Thus, the V beta binding region appears to be a stable, discrete domain localized within the COOH-terminal region that is largely unaffected by the considerable amino acid variability between SEA and SEE . This region may interact directly with TCR V beta.

J Immunol, 1993 Jan 1, 150(1), 59 - 66
Fresh and cultured Langerhans cells display differential capacities to activate hapten-specific T cells; Dai R et al.; Langerhans cells (LC) that have been cultured for 3 days acquire potent T cell-activating properties when compared to freshly prepared, uncultured LC . By contrast, fresh LC are superior to cultured LC in the ability to process native protein Ag . To define further the disparate functional properties of these epidermally derived APC, freshly isolated and cultured epidermal cells (EC) enriched for LC were prepared from BALB/c mice . Highly purified T cells from naive mice, and from mice sensitized epicutaneously with dinitrofluorobenzene, have been examined for their capacity to respond to fresh and cultured EC; 1) in the presence of staphylococcal enterotoxin B; and 2) after the EC had been derivatized with dinitrofluorobenzene . Both fresh and cultured EC activated syngeneic T cells in the presence of staphylococcal enterotoxin B, and fresh and cultured DNP-derivatized EC induced proliferation among DNP-specific T cells . Only cultured, hapten-derivatized EC were able to activate unprimed syngeneic T cells in vitro, and these cells responded as though "primed" when re-exposed to DNP-derivatized spleen cells in secondary cultures . In addition, naive lymphocytes that were activated by cultured DNP-EC were able to evoke local contact hypersensitivity reactions when injected into the pinnae of naive mice that were then painted with dinitrofluorobenzene . By contrast, naive syngeneic T cells exposed to fresh DNP-EC neither proliferated nor differentiated into effector cells . We conclude that fresh LC can constitutively activate primed, but not unprimed, hapten-specific T cells, whereas cultured LC readily both primed and unprimed T cells . The capacity of hapten-derivatized cultured EC to convert naive, hapten-specific T cells into cells that mediate contact hypersensitivity supports the proposal that cultured LC are the functional equivalents of epidermal LC that have migrated to draining lymph nodes . The ability of hapten-derivatized fresh LC to activate primed, hapten-specific T cells is consistent with the view that fresh LC are functionally equivalent to LC within the epidermis.

J Cell Biol, 1993 Jan, 120(1), 103 - 15
Identification of intermediates in the pathway of protein import into chloroplasts and their localization to envelope contact sites; Schnell DJ et al.; We have used a hybrid precursor protein to study the pathway of protein import into chloroplasts . This hybrid (pS/protA) consists of the precursor to the small subunit of Rubisco (pS) fused to the IgG binding domains of staphylococcal protein A . The pS/protA is efficiently imported into isolated chloroplasts and is processed to its mature form (S/protA) . In addition to the mature stromal form, two intermediates in the pathway of pS/protA import were identified at early time points in the import reaction . The first intermediate represents unprocessed pS/protA bound to the outer surface of the chloroplast envelope and is analogous to a previously characterized form of pS that is specifically bound to the chloroplast surface and can be subsequently translocated in the stroma (Cline, K., M . Werner-Washburne, T . H . Lubben, and K . Keegstra . 1985 . J . Biol . Chem . 260:3691-3696.) The second intermediate represents a partially translocated form of the precursor that remains associated with the envelope membrane . This form is processed to mature S/protA, but remains susceptible to exogenously added protease in intact chloroplasts . We conclude that the envelope associated S/protA is spanning both the outer and inner chloroplast membranes en route to the stroma . Biochemical and immunochemical localization of the two translocation intermediates indicates that both forms are exposed at the surface of the outer membrane at sites where the outer and inner membrane are closely apposed . These contact zones appear to be organized in a reticular network on the outer envelope . We propose a model for protein import into chloroplasts that has as its central features two distinct protein conducting channels in the outer and inner envelope membranes, each gated open by a distinct subdomain of the pS signal sequence.

Adv Exp Med Biol, 1993, 329, 41 - 6
Dendritic cells are potent antigen-presenting cells for microbial superantigen; Iqball S et al.; Dendritic cells (DC) were found to be more efficient than macrophages (MO) in activating T cell responses to Staphylococcal enterotoxin B (SEB) using the hanging drop techniques and DC as antigen presenting cells (APC) . When superantigen was presented via DC, the activation of T cells was not dependent on antigen processing and MHC class II molecules IA and IE were involved.

Nephron, 1993, 64(3), 382 - 7
Effect of peritoneal dialysis effluent on superoxide anion production by polymorphonuclear neutrophils; Daniels I et al.; Peritoneal dialysis effluent (PDE) contains at least 2 factors capable of affecting superoxide generation by polymorphonuclear neutrophils (PMN) in response to both particulate and soluble stimuli . A low molecular weight fraction (< 1.2 kD) enhanced the response to the chemotactic peptide fMLP and to preopsonised Staphylococcus epidermidis and Candida guilliermondii . A higher molecular weight fraction (> 1.2 kD) inhibited superoxide production in response to phorbol myristate acetate (PMA) . The effects of PDE were dose dependent over the range of 10-70% (v/v) and simply augmented and reduced the dose-response curve to fMLP and PMA, respectively . There was no alteration in the concentration of stimulus required to give maximal superoxide production in either case . These data suggest that factors capable of affecting superoxide production by PMN accumulate in uraemia and are removed from the circulation into dialysis fluid.

Perit Dial Int, 1993, 13(2), 104 - 11
Cell function and viability in glucose polymer peritoneal dialysis fluids; Liberek T et al.; OBJECTIVE: To investigate the biocompatibility profile of a new peritoneal dialysis fluid containing glucose polymer (GPF) . DESIGN: Viability and function of peripheral neutrophils (PMN) from healthy donors and cultured human peritoneal mesothelial cells were assessed in vitro after exposure to dialysis fluids . Phagocytosis, leukotriene B4 synthesis, and respiratory burst activation were measured following stimulation with serum-treated zymosan (STZ) or opsonized Staphylococcus epidermidis (S . epidermidis) . Bacterial growth in the fluids was also investigated . In vivo pH equilibration of GPF and subsequent respiratory burst activation following incubation in spent dialysate were studied . RESULTS: For all the host defense parameters measured, commercial dialysis fluids (Dianeal; 1.36% and 3.86% glucose) and GPF (pH 5.2) were significantly more inhibitory than the control buffer (pH 7.3) . Mesothelial cell viability was reduced by all the fluids tested irrespective of pH . Glucose polymer fluid was significantly more inhibitory than Dianeal 1.36% for STZ phagocytosis and respiratory burst activation . In contrast, it was less suppressive than Dianeal 3.86% for LTB4 synthesis . For all parameters tested, except LTB4 generation, there was a marked effect of pH, with GPF being significantly more inhibitory at pH 5.2 than at pH 7.3 . None of the fluids tested supported the growth of S . epidermidis, although the viable counts in GFP were significantly higher than in Dianeal . Fluid inhibition of PMN respiratory burst activation and cytotoxicity were reduced in a time-dependent manner following increasing dwell time in vivo . CONCLUSIONS: GPF does not appear to be significantly different from Dianeal as far as host defense parameters are concerned . However, the cell viability and bacterial survival data suggest some possibly negative aspects of this fluid formation.

J Immunol, 1993 Jan 1, 150(1), 190 - 6
Herpes simplex virus interferes with monocyte accessory cell function; Hayward AR et al.; HSV is a successful human pathogen that causes severe infections in immunocompromised adults and newborn humans . The possibility that HSV might evade host immune responses by interfering with accessory cell function was investigated in vitro using newborns' monocytes adhered to plastic . These cells lost their ability to present staphylococcal enterotoxin B to resting T cells in a stimulatory form after overnight culture with HSV . The interference with T cell proliferation required live virus and was abolished by heat- or UV inactivation . The T cell proliferative response was restored by the addition of IL-2 . Furthermore, HSV-precultured monocytes had a reduced production of IL-1 alpha and TNF-beta after phorbol-ionomycin stimulation . Wild-type HSV and a HSV mutant lacking the primary virion host shutoff protein both interfered with IL-1 synthesis and presentation of staphylococcal enterotoxin B for T cell proliferation . These results suggest that HSV can interfere with the provision by human monocytes of costimulator factors that are essential for T cell stimulation . This effect of HSV may be due to secondary shutoff mechanisms that decrease host protein synthesis or secretion after HSV infection.

J Immunol, 1993 Jan 1, 150(1), 185 - 9
LP-BM5 murine retrovirus-induced immunodeficiency disease in allogeneic SCID chimeric mice . Inability to recognize a putative viral superantigen does not prevent induction of disease; Gilmore GL et al.; T cell recognition of viral superantigens has been postulated to contribute to the pathogenesis of the immunodeficiency disease induced in mice by infection with the LP-BM5 murine leukemia virus complex . A candidate superantigen has been identified in the B cell lymphoma line B6-1710 derived from an LP-BM5-infected C57BL/6 (H-2b) mouse . We have asked whether the stimulatory activity expressed by B6-1710 behaves as a superantigen by assessing the ability of T cells from fully allogeneic H-2b-->H-2d SCID chimeric mice to respond to the line . T cells from allochimeric mice failed to respond to B6-1710, whereas they responded normally to Staphylococcus enterotoxin B, a well characterized superantigen . Despite this finding, allochimeric mice were fully susceptible to the immune deficiency disease induced by LP-BM5 virus infection . These findings show that the role of superantigen expression in retrovirus-induced immune deficiency disease remains to be defined.

Acta Neurochir (Wien), 1993, 122(3-4), 266 - 70
Reaction of rabbit lateral periventricular tissue to non-infected and infected (Staphylococcus epidermidis) shunt tubing implants . A light and transmission electron microscope study; Gedikoglu Y et al.; The reactions of periventricular tissue of the lateral ventricle to non-infected and infected (Staphylococcus Epidermidis) silicone shunt tubing were examined by light and transmission electron microscopy . It was shown that reactive changes occurred in periventricular tissue in response to the implant of sterile shunt tubing . On the other hand in infected implanted silicone shunt tubing, proliferation of inflammatory cells within the ventricle and periventricular tissue, loss of integrity of the ependyma, glial cell proliferation, and excessive extracellular oedema were demonstrated . Proliferation of ependymal cells combined with inflammatory responses may be a factor in the pathogenesis of infected shunt obstruction.

Folia Microbiol (Praha), 1993, 38(3), 245 - 52
Modified simplified method for isolation of lysostaphin from the culture filtrate of Staphylococcus staphylolyticus; Marova I et al.; The present paper reports a modified method for isolation of lysostaphin--a bacteriolytic agent with specific affinity for staphylococcal cell wall . The proposed purification scheme includes three steps . The first procedure is ultrafiltration through a membrane filter giving a yield of 75.6% . The result of ultrafiltration is a concentrated, 10-times purified preparation of lysostaphin with specific activity 0.62 U/mg which can be used for digestion of S . aureus cells . Further step, performed by ion-exchange chromatography on DEAE-cellulose, yields a 60-times purified preparation containing a mixture of enzyme components of lysostaphin . The yield of this step is 47.2%, the preparation contains 3.54 U/mg protein . Using gel filtration on Sephadex G-50 a component with hexosaminidase activity was separated from the endopeptidase component on the basis of molar mass difference . A 270-times purified preparation of lysostaphin-endopeptidase with minimum of contaminating substances was obtained in this step . The yield of gel filtration was 22.1%, specific activity increased up to 16.3 U/mg protein.

Eur J Haematol Suppl, 1993, 54, 6 - 9
Teicoplanin in gram-positive infection: microbiological aspects; Spencer RC; The widespread use of indwelling catheters and successful antibiotic treatment of Gram-negative infections has led to an increase of Gram-positive infections in severely neutropenic patients; Staphylococcus epidermidis is predominant in these infections . The problems associated with the use of vancomycin in treating such infections can be overcome by the glycopeptide antibiotic teicoplanin . It is as effective as vancomycin, but does not cause "red man" syndrome, is uncommonly nephrotoxic, can be given as a rapid bolus once daily, and routine serum monitoring is not required . Other approaches to reducing catheter-related infections include improved training of personnel in catheter insertion and the development of new materials and methods in cannula production.

Ann Otolaryngol Chir Cervicofac, 1993, 110(2), 81 - 6
{Bacterial epidemiology of chronic otitis . Prophylactic and therapeutic deductions}; Julien N et al.; Antimicrobial sampling was performed in the external auditory canal and in the mastoid cavity when possible in 80 middle ears operated on during the last 15 months . These samplings concerned 20 cholesteatomas . 25 suppurative chronic otitis, 25 non suppurative chronic otitis and 6 miscellaneous . In 20 out of 80 cases (25%), one or several microbial agents were identified: cholesteatomas (35%), suppurative chronic otitis (38%), non suppurative ones (4%) and miscellaneous (16%) . In most cases a staphylococcus or a negative gram agent was sensitive to amoxycillin-clavulanique acid . When sampling was performed in the mastoid cavity, the agent was not sensitive to this antibiotic (80% of cases) . This study demonstrates that a prophylactic therapy against aerobic and anaerobic agents is necessary in non suppurative chronic otitis whereas the antimicrobial therapy must be adapted in other pathologies.

Acta Chir Orthop Traumatol Cech, 1993, 60(2), 100 - 3
{Basic indicators of cellular immunity in patients with chronic staphylococcal osteomyelitis}; Pudil R et al.; The objective of the presented work is to compare the state of the immune system in patients with chronic osteomyelitis with a group of the healthy population . The authors followed up on a long-term basis a group of 24 patients with chronic osteomyelitis of staphylococcal origin; they completed immunological examinations comprising cellular and humoral immunity (in particular assessment of T-lymphocytes and their sub-populations by means of monoclonal antibodies, examination of phagocytic capacities of blood elements, assessment of selected plasma protein and immunoglobulin levels) . Comparison of results of these examinations in patients with chronic osteomyelitis and the healthy population proved statistically very significant differences in particular in the number of T-lymphocytes (reduction of T-lymphocytes CD 4+, i.e . helpers, immunity stimulating cells and reduction of the ratio of immunity promoting lymphocytes and immunity inhibiting lymphocytes) . The authors found also significant differences in the levels of plasma proteins and immunoglobulins.

Lung, 1993, 171(4), 225 - 33
Studies of phagocytic and killing activities of alveolar macrophages in patients with sarcoidosis; Orosi P et al.; Phagocytosis and killing activities of alveolar macrophages were compared in 17 patients with stage 1 sarcoidosis and 6 healthy controls . The average total cell count of bronchoalveolar lavage fluid from patients with sarcoidosis was 7.8 +/- 7.5 x 10(6) cells; 70.4 +/- 15% of these cells were alveolar macrophages and 25.9 +/- 16.2% lymphocytes . Average total cell count from controls was 8.33 +/- 8.6 x 10(6) cells, with 92.7 +/- 5.9% alveolar macrophages and 6.6 +/- 4.4% lymphocytes . Purified alveolar macrophages were tested in in vitro antibacterial assays using S . aureus as a test microbe . Moderate decreases in the kinetics of staphylococcal ingestion were detected in the sarcoidosis group . The intracellular killing activity of macrophages was much lower in the patients with sarcoid than in control subjects . In a pilot study, intracellular killing activity of macrophages from 1 patient with sarcoidosis was greatly enhanced by 24 hr treatment with transfer factor . In summary, alveolar macrophages from patients with radiographic stage 1 sarcoidosis have decreased bacterial ingestion and intracellular killing activities . These results suggest that macrophages undergo complex functional changes in sarcoidosis that may influence both disease development and host defenses.

Doc Ophthalmol, 1993, 83(1), 33 - 41
Infectious scleritis: report of four cases; Sainz de la Maza M et al.; While systemic autoimmune diseases are the main possibilities in the differential diagnosis of scleritis, other less common etiologies such as infections must also be considered . The authors report four cases of infectious scleritis to review predisposing factors, clinical characteristics, methods of diagnostic approach, and response to therapy . Two patients had primary scleritis and two patients had secondary scleritis following extension of primary corneal infection (corneoscleritis) . Diagnoses included three local infections (one each with Staphylococcus . Acanthamoeba, and herpes simplex) and one systemic infection (Lyme disease) . Stains, cultures, or immunologic studies from scleral, conjunctival, and/or corneal tissues, and serologic tests were used to make the diagnosis . Medical therapy, including antimicrobial agents, was instituted in all patients, and surgical procedures were additionally required in two patients (scleral grafting in one and two penetrating keratoplasties in another); the patient who required two penetrating keratoplasties had corneoscleritis and underwent eventual enucleation . Infectious agents should be considered in the differential diagnosis of scleritis.

Med Dosw Mikrobiol, 1993, 45(2), 263 - 5
{Effect of treatment with autologous staphylococcal vaccine on the course of the immunologic process}; Tulecka T et al.; In 18 patients with furunculosis and in 9 with chronic inflammation of upper respiratory tract, some cellular immunity parameters were tested . These were: phagocytosis index and bactericidal activity against leukocytes . Humoral immunity was also investigated by measurement of serum gammaglobulins . All test were performed before treatment and 30 days after application of the last dose of autologous vaccine . In 12 patients with furunculosis, improvement of the clinical status (disappearance of furunculosis) was appearing together with an increase of phagocytosis index and bactericidal activity of leukocytes without changes in gamma-globulin levels . No such changes were found in remaining patients in whom no clinical improvement was found . The authors suggest that cellular immunity factors studied in this investigation permit for evaluation of the immunity status in patients receiving autologous staphylococcal vaccine.

Clin Oncol (R Coll Radiol), 1993, 5(5), 317 - 8
Lung abscesses mimicking multiple pulmonary metastases; Runciman DM et al.; Five patients receiving chemotherapy for cancer through Hickman central venous catheters had lung lesions detected by plain chest radiography or computed tomography . In each case these were initially misdiagnosed as metastases, although they ultimately proved to be staphylococcal abscesses . Because of the grave implications of an erroneous diagnosis of metastatic malignant disease, clinicians are urged to consider abscesses in the differential diagnosis of radiological chest abnormalities in such patients.

Scand J Infect Dis Suppl, 1993, 90, 1 - 59
Staphylococcus epidermidis--hospital epidemiology and the detection of methicillin resistance; Hedin G; Infections in immunocompromised patients and in patients with indwelling prosthetic devices are often caused by hospital strains of Staphylococcus epidermidis resistant to methicillin . Tests for the detection of methicillin resistance, indicating resistance to all beta-lactam antibiotics, were evaluated in order to define a suitable screening test . A broth tube breakpoint test with a large inoculum, 10(7) colony forming units (cfu), gave the highest recovery of resistant strains . False resistance due to hyperproduction of beta-lactamase was excluded . The results correlated completely with the detection of the resistance gene, mecA, by the polymerase chain reaction . In 2/3 of the resistant strains tested the expression of the methicillin resistance was heterogeneous, only one cell in 10(2) to 10(4) expressed the resistance within 72 h in both . In broth screening tests an inoculum of at least 10(6) cfu therefore was required to detect all resistant strains within 24 h . Using agar dilution, 48 h incubation must be considered . In disc diffusion tests reliable results were obtained after only 16 h of incubation when discs containing cephradine 5 and 30 micrograms, oxacillin 1 microgram or cephalexin 30 micrograms were used, and the first disc is recommended for routine work . The epidemiology of S . epidermidis strains resistant to ciprofloxacin and/or gentamicin was studied in an isolation unit for patients undergoing bone marrow transplantation . Antibiograms and plasmids were used for typing and 31 such strains were found . Of 54 staff members 10 were colonized in the nares only, two in the nares and perineum and one in the nares and stool . In ambient air and on the clothes of staff a few of the strains predominated quantitatively . These strains colonized the skin of some of the patients who seemed to be the main dispersers . Possible routes of cross-infection were indirect contact transfer via the hands and clothes of staff (82% of the clothes were contaminated), and direct as well as indirect airborne transmission . To study the effects of chlorhexidine on skin bacteria, ten nurses washed one arm with chlorhexidine-detergent every morning for 3 weeks; the other arm served as control . The depression of the normal skin flora did not lead to a colonization with more antibiotic-resistant hospital strains . During the wash period the counts of antibiotic-resistant S . epidermidis on the treated arms were significantly reduced compared with the control arms, as also were the number of different strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Agents Actions, 1993, 39 Spec No, C86 - 8
Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470; Berger AE et al.; The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit collagen-induced arthritis in rats . To determine if the anti-arthritic effects of AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell responses in vitro . Responses of human cells to tetanus toxoid (TT), and those of murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls difference were inhibited by AGM-1470 . Responses of human cells to SE, OKT3 and PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were augmented on d6-8 . The amount of IL-2 in SEA cultures was augmented on d4 and d5 . There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA, CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases in CD25 and CD45RO in TT cultures . These results indicated that the angiogenesis inhibitor AGM-1470 also modulates human and murine lymphocyte function.

Med Oncol Tumor Pharmacother, 1993, 10(1-2), 37 - 47
Monoclonal antibodies and superantigens: a novel therapeutic approach; Kalland T et al.; We have developed a monoclonal antibody (mAb) based therapy intended for the treatment of solid tumors utilizing both main arms of the immune system by incorporating the colon carcinoma recognizing mAb C215 and the T cell activating bacterial staphylococcal enterotoxin A (SEA) in a single hybrid molecule . The recombinant tumor specific superantigen C215-SEA retained excellent antigen binding properties while the binding to MHC class II was markedly reduced and should allow targeting of a large fraction of T cells to tumors in vivo . C215-SEA mediated T cell killing of C215 expressing tumor cells irrespective of their expression of MHC class II antigens and induced levels of IFN-gamma and TNF in mononuclear cells sufficient to completely suppress the growth of colon carcinoma cells in vitro . In initial studies of anti-tumor effects, C215Fab-SEA was found to markedly inhibit the growth of colon carcinoma cells transplanted to Scid mice adoptively transferred with human mononuclear cells.

Rev Mal Respir, 1993, 10(5), 471 - 2
{Fistulous pulmonary abscess in the bronchi detected by staphylococcal spondylodiscitis, with the presence of bony sequestra in the bronchial secretions}; Montane J et al.; The authors report the case of a man aged 70 who was admitted to hospital for staphylococcal pulmonary suppuration which occurred during the long-term follow-up for an osteosynthesis for a fractured humerus . The diagnosis of a pulmonary abscess in contiguity with a staphylococcal spondylodiscitis was only established by computed tomographic examination and the aspiration from a vertebral body . The outcome was fatal, despite appropriate antibiotic treatment, on account of the past medical history of the patient . The diagnosis might have been made by the presence of osseous sequestra in the bronchial secretions, the bronchial fistulae in contiguity with the vertebral column was confirmed at autopsy.

Urol Int, 1993, 51(3), 129 - 32
Antimicrobial treatment for chronic prostatitis as a means of defining the role of Ureaplasma urealyticum; Ohkawa M et al.; A study was conducted to assess the clinical and microbiological effects of antimicrobial treatment for chronic prostatitis as a means of defining the role of Ureaplasma urealyticum . Significant U . urealyticum cells were considered to be isolated from the prostates of 18 of 143 prostatitis patients . These patients with ureaplasma-associated prostatitis were randomly treated with either ofloxacin or minocycline for 2 weeks; 4 patients were excluded due to voluntary withdrawal . U . urealyticum was eradicated in all the patients . Symptoms were resolved in 10 patients, and leukocytes in expressed prostatic secretion were cleared in 4 patients; both drug treatments revealed similar results . Even if we exclude 3 patients with significant coexistent Staphylococcus epidermidis cells before treatment, 3 of 11 patients evaluated showed complete resolution of symptoms and clearance of leukocytes in expressed prostatic fluid . These results suggest that U . urealyticum is a causative organism in some patients with chronic prostatitis.

Microbios, 1993, 75(304), 185 - 95
Studies on mutational cross-resistance between ciprofloxacin, novobiocin and coumermycin in Escherichia coli and Staphylococcus warneri; Howard BM et al.; Nalidixic acid resistant mutants of Escherichia coli KL16 were tested against ciprofloxacin, coumermycin and novobiocin . The mutants gyrA, nalB and nal-24 were more resistant than KL16 to ciprofloxacin, whereas the nal-31 strain was hypersensitive . Only the nalB mutant was more resistant to novobiocin than KL16, but gyrA, nal-31 and nal-24 mutants were more sensitive to coumermycin than KL16 . Newly-isolated novobiocin-resistant mutants of KL16 were not cross-resistant to coumermycin or ciprofloxacin . Some coumermycin-resistant mutants were cross-resistant to novobiocin but not ciprofloxacin, whereas mutants resistant to novobiocin and ciprofloxacin were isolated at higher coumermycin concentrations . Two types of Staphylococcus warneri mutant were isolated on media containing novobiocin or coumermycin . Each was resistant to both coumarins, but one was highly resistant to novobiocin and the other to coumermycin . High level resistance to both coumarins was unstable . E . coli mutants differed in susceptibility to bactericidal concentrations of ciprofloxacin, and S . warneri mutants behaved similarly . These results suggest the modes of action of the coumarins are not identical.

Microbiol Immunol, 1993, 37(7), 573 - 82
Induction of acute arthritis in mice by peptidoglycan derived from gram-positive bacteria and its possible role in cytokine production; Onta T et al.; The activities of a water-soluble peptidoglycan fragment derived from Staphylococcus epidermidis (SEPS) were examined as to their role in proliferation of spleen mononuclear cells (SMNC) from various strains of mice, the production of cytokines in vitro, and the induction of an inflammatory reaction in vivo . The proliferation of SMNC from C3H/HeN, C57BL/6, AKR, DBA/2, and ddY mice in reaction to SEPS in vitro showed a peak on day 3 and was greater than that of SMNC from BALB/c mice . The cells of SMNC from C3H/HeN mice responsive to SEPS were indicated to be mainly macrophages . A time kinetics experiment showed a coincidence in the proliferation of SMNC in reaction to SEPS and the detection of colony-stimulating factor (CSF) activity . Interleukin 2 (IL-2) activity was not detected during the incubation periods . When SEPS was administered to mice, much stronger mRNA transcripts of granulocyte-macrophage (GM)-CSF were detected in the lungs of C3H/HeN mice than in BALB/c mice . On the other hand, the amounts of IL-1 and PGE2 produced by SMNC of BALB/c mice stimulated by SEPS were greater than those produced in C3H/HeN mice . SEPS was confirmed to induce arthritis in BALB/c mice, but not in C3H/HeN mice . Our findings suggest that the production of GM-CSF is involved in the in vitro proliferation of SMNC in reaction to SEPS and that along with IL-1 and PGE2 production, contributes to the inflammation by SEPS in vivo.

Microbiol Immunol, 1993, 37(7), 537 - 41
Changes in the susceptibility of 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated HL-60 cells to staphylococcal leukocidin; Morinaga N et al.; Susceptibility of human promyelocytic leukemia HL-60 cells to staphylococcal leukocidin following treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) was examined . TPA treatment for 6 hr rendered the cells very resistant transiently to leukocidin . There was no change in binding of leukocidin to the cells, but leukocidin-induced 45CaCl2 influx, phospholipase A2 and C activities were inhibited . Further incubation with TPA rendered the cells sensitive again and then more sensitive than original HL-60 cells following increase of the binding, and leukocidin-induced activities described above appeared again . Those cells treated with TPA for more than 18 hr started to differentiate to macrophages morphologically and functionally . These data suggest that the differentiated cells were more sensitive than original HL-60 cells because of increased binding of leukocidin and that treatment of TPA for 6 hr may transiently impair the signal transduction system of leukocidin after binding of leukocidin to the specific receptor of the cell membrane . Using these TPA-treated cells, it was shown in this report that calcium influx, phospholipase A2 and C activities were important to induce cytotoxic action of leukocidin after binding of leukocidin to specific receptors on the cells.

Intensive Care Med, 1993, 19(6), 347 - 50
Pharmacokinetics of vancomycin during continuous hemodiafiltration; Santre C et al.; OBJECTIVE: To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD) . DESIGN: Prospective exploratory, open-labelled study . SETTING: Critical Care Unit in a University Medical Centre . PATIENTS: 3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study . INTERVENTION: Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection . Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion . MEASUREMENTS AND RESULTS: Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23) . The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion . The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5) . The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively . Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min . The mean volume of distribution was 47.4 +/- 6.4 l . CONCLUSION: CVVHD is effective for vancomycin elimination . In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.

J Clin Apheresis, 1993, 8(2), 72 - 7
Successful management of paraprotein-associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A; Weinstein R et al.; Two patients with paraprotein-associated peripheral polyneuropathy were treated successfully using immunoadsorption of patient's plasma with staphylococcal protein A . Both had previously been treated with immunosuppressive agents or plasma exchange, and were rapidly relapsing at the time of their protein A immunoadsorption therapy . One patient was treated "on-line" with a blood cell separator, and one was treated "off-line." Both responded well to therapy with minimal toxicity . Serum levels of circulating immune complexes were elevated in one patient and remained so during and after therapy . Immunoadsorption with protein A should be investigated as a therapeutic option for patients with paraprotein-associated peripheral polyneuropathy . The therapy is relatively easy to administer, particularly "off-line," and was well tolerated by our patients . More experience, including formal clinical trials, will be required to properly define the indications for, and mechanism of response to, this therapy.

Eur J Cardiothorac Surg, 1993, 7(9), 501 - 2
Primary sternal osteomyelitis; Skoutelis AT et al.; Primary sternal osteomyelitis is a rare condition . Only few cases have been reported in the English literature . We describe the case of a young woman presenting with persistent fever and chest pain . Radionuclide bone scan and computed tomography of the chest were consistent with metastatic neoplasm . Surgical intervention, however, revealed primary staphylococcal osteomyelitis and the patient was successfully treated with combined extensive surgical debridement and intravenous antibiotics.

Acta Microbiol Hung, 1993, 40(2), 151 - 7
Follow-up of the effect of BCG vaccine treatment in bladder tumour patients; Kulcsar G et al.; The effect of intravesical BCG vaccine treatment in 38 patients with superficial bladder tumour after TUR (Transurethral Resection) was followed by the lymphocyte transformation test (LTT) and the staphylococcus phagocytosis test of in vitro washed leukocytes . The results have confirmed the immunostimulating and hence anti-tumour effect of intravesical BCG vaccine . Monitoring of the cellular immune response is suitable for the continuous follow-up of the BCG effect . Comparing the tolerable side-effects with their favourable therapeutic results, BCG vaccine is considered to be effective for the prevention of recurrences in treating superficial bladder tumours.

Nat Toxins, 1993, 1(4), 250 - 4
Purification of staphylococcal enterotoxin E; Brehm RD et al.; Staphylococcal enterotoxin E has been purified by a combination of Red-A ligand chromatography and Mono-S (cation-exchange) chromatography . Commencing with 30 litres of fermenter-grown culture the method has been used to purify 17 mg of toxin, giving a purification yield of around 40% . The purity of the toxin was over 98% when analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, but demonstrated three isoelectric forms by isoelectric focusing, with pl values of 7.6, 7.4, and 7.0 . This method adds to the versatility of the Red-A matrix system which can also be used for the purification of staphylococcal enterotoxins A, B, and C2.

Immunodeficiency, 1993, 4(1-4), 15 - 6
Activation of CVID patients' T cells with conventional antigens and superantigens; Fischer MB et al.; Defects in T cell function are known to be present in a subset of patients with CVID, but the true nature of these defects still has to be revealed . In prior studies we described that T cells from these patients show an impaired proliferative response following activation with recall antigens (E . coli, Tet . Tox., TBE and PPD) . Gene expression of IL2 and IFN-gamma in patients' T cells following antigenic stimulation was significantly reduced compared to controls, while IL-2R transcripts were normal . To further characterize the defect we examined T cell responses to bacterial enterotoxins, collectively termed superantigens . Following stimulation with optimal (10 ng/ml p < 0.05) as well as suboptimal (1 ng/ml p < 0.0025) concentrations of staphylococcal enterotoxin A (SEA), proliferative response and cytokine release (IL-2 and IFNg) were significantly decreased in patients' T cells as compared to controls' . When patients' T cells were stimulated with staph . enterotox . C3 (SEC3) an even more pronounced difference between patients' and controls' T cells could be observed (10 ng/ml p < 0.002, 1 ng/ml p < 0.0005) . Our data indicate that, in addition to the defect in antigen-induced T cell activation, T cells of CVID patients express a broader impairment in the interaction between the antigen presenting cell and the TCR.

Immunodeficiency, 1993, 4(1-4), 137 - 9
Characterization of anergy to the superantigen Staphylococcus enterotoxin B; Dannecker G et al.; In vivo administration of superantigens leads to activation and subsequent depletion or anergy of T cells expressing defined V beta-T cell receptors (TCR) . Superantigens have therefore become intensively studied tools for examining parameters of immunoregulation and they may represent model antigens for pathogenic agents . An HIV-encoded superantigen has for example been implicated in the dramatic loss of helper T cells in AIDS . We investigated the response of V beta 8+ T cells in mice after primary and secondary exposure to the superantigen Staphylococcus Enterotoxin B (SEB).

Ann Dermatol Venereol, 1993, 120(9), 589 - 97
{Cutaneous manifestations of Kawasaki disease . Apropos of 30 cases}; Ducos MH et al.; A series of 30 cases of Kawasaki disease has been studied retrospectively over a period of 11 years . The aim was to reassess the diagnostic value of the dermatological manifestations . A modification of the extremities was observed in 28 patients (23 had early inflammatory lesions, 25 had late desquamation) . Exanthema was constant, polymorphous and most often urticaria-like . Vesicles, pustules or purpura were noted during the course of the eruption in 7 patients . A perineal eruption was observed in 17 cases and was found of good diagnostic value even though not pathognomonic . Cheilitis was the most frequent of buccopharyngeal modifications (93 p . 100) . Conjunctival hyperemia was noted in 26 patients . Eight children had cardiovascular complications . Among these cases, the modification of the extremities seemed to be more pronounced and stomatitis and arthritis were apparently more frequent . Most of all, the inflammatory syndrome was significantly more severe as concerns CRP and polymorphonuclear leukocytes counts . Dermatological examination often rules out other diagnoses, such as measles, scarlet fever and staphylococcal toxic shock syndrome . However, a complete etiological workup remains mandatory.

Doc Ophthalmol, 1993, 84(4), 387 - 93
Intracapsular and extracapsular pseudophakic endophthalmitis: a comparison; Verbraeken HE; A hundred and four cases of post cataract endophthalmitis with positive vitreous cultures are discussed . Functional results depend largely on the infecting agent but even after Staphylococcus epidermidis infections some eyes may be lost . Although post lens surgery endophthalmitis carries the best prognosis in the endophthalmitis group, 40% of the eyes are lost, sometimes caused by a delayed vitrectomy decision . Comparing intracapsular and extracapsular lens surgery two big differences were noted: (1) the bacteriology, and (2) the functional results . The bacteriological spectrum of the ICCE was composed of 1/3 of S . epidermidis, 70% of Gram + cocci and 80% of Gram+organisms . After extracapsular lens extraction the majority of cases (60%) were caused by S . epidermidis (statistical significance 0.01) . The difference in functional result is explained by the difference in bacteriology: if only the S . epidermidis cases are compared, functional results between both categories are nearly equal . ECCE seems to make the eye more vulnerable to infection by a low virulent agent.

Klin Med (Mosk), 1993, 71(6), 27 - 30
{Current approaches to conservative therapy of acute infectious lung destruction}; Mustafin DG et al.; Differential programs of conservative treatment (antibacterial in combination with sanatorium) including correction of immune deficiency, detoxication, quantum hemotherapy resulted in appreciable responses in 84.8% out of 894 patients with acute destruction of the lungs . Radical surgery was performed in 67 (7.5%) patients . Specific features of the treatment according to intensive conservative schemes are presented for 484 patients with acute pulmonary abscess, 282 with staphylococcal pulmonary destruction, 106 with septic pulmonary destruction and 22 with pulmonary gangrene . Total lethality reached 7.7%.

Retina, 1993, 13(4), 331 - 4
Intravenous cefazolin in penetrating eye injuries . Treatment of experimental posttraumatic endophthalmitis; Alfaro DV et al.; The use of intravenous antibiotics as prophylaxis in penetrating eye injuries is strictly empiric and not based on scientific data supporting their use . To determine the efficacy of prophylactic intravenous cefazolin in penetrating eye injuries, a rabbit model of posttraumatic endophthalmitis was developed . Forty rabbits received penetrating eye injuries followed immediately by an intravitreal inoculum of live Staphylococcus epidermidis . The rabbits then were randomly divided into four groups: group 1 received three doses of intravenous cefazolin; group 2 received six doses, and group 3 received nine doses; group 4 received no treatment and served as controls . All control rabbits developed 4+ vitreitis; rabbits receiving three doses of the antibiotic developed 2+ vitreitis, and those receiving six or nine doses of cefazolin showed no vitreous inflammation (P < or = 0.0001) . Histologic examination of control eyes showed an exuberant reaction with formation of retrolental membranes, vitreous abscess, and retinal detachment . Eyes treated with nine doses of cefazolin were devoid of inflammatory cells . These findings suggest that intravenous cefazolin is effective in preventing the development of posttraumatic endophthalmitis in a rabbit model.

Ter Arkh, 1993, 65(11), 64 - 6
{The clinico-bacteriological and pharmacokinetic evaluation of vancomycin in clinical practice}; Orlov VA et al.; Clinical application of vancomycin in 24 patients produced a response in 83.3% of the patients . The drug was active against pneumococcal pneumonia, bronchitis, staphylococcal endocarditis and mastitis . Positive pharmacokinetic parameters of the drug allows introduction of the antibiotic 1-2 times daily.

Adv Perit Dial, 1993, 9, 211 - 4
Treatment of peritonitis in CAPD with ciprofloxacin: long-term experience; Perez Fontan M et al.; We present the long-term results of a protocol of empirical monotherapy of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis with ciprofloxacin . One hundred and fifteen episodes of peritonitis were studied . The treatment protocol included 5 days of intraperitoneal (IP) administration of the drug, followed by 10 days of oral therapy . A good clinical response was obtained in 83% of the cases, while treatment failure was observed in 4% and relapse in 7% . A decrease in the sensitivity to ciprofloxacin of the peritonitis agents was observed in the study, with Staphylococcus spp . in particular . Three episodes of peritonitis due to bacteria resistant in vitro to ciprofloxacin responded to the treatment protocol . Ciprofloxacin attained good plasma levels both after oral and IP administration . However, dialysate levels were poor after oral administration . The most frequent side effect was gastric intolerance to oral ciprofloxacin . Two patients experienced severe adverse reactions to the drug . Ciprofloxacin may be a good choice for empirical monotherapy of CAPD-related peritonitis . However, the emergence of bacterial resistances must be carefully monitored . The drug should be administered intraperitoneally, at least to induce remission of the infection . Side effects are not frequent, but ciprofloxacin should not be considered an innocuous drug.

J Hosp Infect, 1993 Jan, 23(1), 51 - 4
Effect of surgical mask position on bacterial contamination of the operative field; Berger SA et al.; The influence of surgical mask usage on bacterial contamination of the operative field was studied during 30 cardiac catheterization procedures . Mask position was varied during each procedure according to a predesigned random table . The number of bacterial colonies recoverable when no mask was worn was significantly higher than that detected when a full mask was worn (P < 0.002) . Shedding of Staphylococcus epidermidis was greater when no mask was worn (mean 5.2 colonies 10 min-1) than shedding with full mask (mean 2.7 colonies 10 min-1; P < 0.004) . Although mask placement below the nose was associated with higher mean colony counts than that above the nose, these differences were not statistically significant.

J Clin Immunol, 1993 Jan, 13(1), 30 - 40
Lymphocyte phenotype and function in the chronic fatigue syndrome; Straus SE et al.; Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function . Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry . Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced . The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58) . CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B . Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities . These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions . This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

Infect Immun, 1993 Jan, 61(1), 64 - 70
Purification of a factor which provides a costimulatory signal for gamma interferon production; Nakamura K et al.; A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock . The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose . It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis . It induced IFN-gamma production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate- and nylon wool-adherent cells . Anti-CD3 MAb induced the highest level of production of the three . The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-gamma in these cells . The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA . However, the factor failed to stimulate IFN-gamma production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed . Treatment with pronase or heat abolished these activities . These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-gamma production in resting T or natural killer cells . It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).

Zh Mikrobiol Epidemiol Immunobiol, 1993 Jan-Feb, (1), 65 - 8
{The modulation of cellular immunity in vivo and in vitro under the action of purified staphylococcal anatoxin}; Semenova IB et al.; Purified staphylococcal toxoid modulates (mainly suppresses) cell-mediated immune response to heterogeneous antigens of animal origin (to sheep red blood cells as shown by the delayed hypersensitivity reaction) or bacterial origin (to BCG as shown by the splenocyte migration test) . The direction and manifestation of modulation depend on the strain of mice, dose of the toxoid, dose and nature of the test antigen and the immunization schedule (intervals between the injections of the antigen).

Pediatrie, 1993, 48(10), 687 - 91
{S . aureus neuromeningeal infection in 3 children with ventricular shunts without cytochemical changes in the lumbar cerebrospinal fluid}; Jourdan C et al.; The authors report on three cases of staphylococcal cerebrospinal fluid (CSF) infection with normal white blood cell count and normal CSF glucose level in repeated lumbar CSF examination . All three children (2 months, 17 months and 4 years old) have been operated for neonatal hydrocephalus with setting of a ventriculo-peritoneal shunt one to two months before . Infection was suspected because of fever without evocative clinical signs . In two cases plasma C reactive protein level was increased, and in all three cases a leucocytosis was present . The diagnosis was made by bacteriological examination of the ventricular CSF . Both surgical and medical management were required and the bacteriological outcome was favourable . Since neurological sequellae may occur if the treatment is delayed such atypical infection needs to be promptly assessed.

Cell Biophys, 1993 Jan-Jun, 22(1-3), 147 - 64
Targeting of superantigens; Kalland T et al.; The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on MHC class II antigens . In order to induce T lymphocytes to reject a tumor, we substituted the specificity of SEA for MHC class II molecules with specificity for tumor cells by combining SEA with a MAb recognizing colon carcinomas . Chemical conjugates or recombinant fusion proteins of the MAb C215 and SEA retained excellent antigen binding properties whereas the binding to MHC class II was markedly reduced . The hybrid proteins directed SEA responsive T cells to tumors with specificity determined by the specificity of the MAb . Significant tumor cell killing was obtained at picomolar concentrations of the hybrid proteins and was the result of direct cell mediated by cytotoxicity as well as production of tumoricidal cytokines by T cells . Targeting of superantigens represents a novel approach to specific immunomodulation and deserves further study as a potential therapy for malignant disease.

Eur Biophys J, 1993, 22(4), 269 - 77
Hydrophilic surface maps of channel-forming peptides: analysis of amphipathic helices; Kerr ID et al.; Ion channels may be formed by bundles of amphipathic alpha-helices aligned parallel to one another and spanning a lipid bilayer membrane, with the hydrophilic faces of the helices lining a central pore . In order to provide insight into the packing of such helices in bundles, a method has been developed to evaluate hydrophilic surface maps of amphipathic alpha-helices and to display these surfaces in a readily interpretable form . The procedure is based upon empirical energy calculations of interactions of a water molecule with an amphipathic alpha-helix . The method has been applied to three channel-forming peptides: Staphylococcal delta-toxin; alamethicin; and a synthetic leucine- and serine-containing peptide . Particular emphasis is placed upon the effects of sidechain conformational flexibility on hydrophilic surface maps . A family of models of the delta-toxin helix is generated by a simulated annealing procedure . The results of hydrophilic surface map analyses provide more exact definition of the centre of the hydrophilic face of amphipathic helices, and of the variation of the position of the centre in response to changes in sidechain conformation . This information is used to define families of preliminary models for a given ion channel, as is illustrated for delta-toxin.

J Biol Chem, 1992 Dec 25, 267(36), 26121 - 7
Sphingomyelinase and cell-permeable ceramide analogs stimulate cellular proliferation in quiescent Swiss 3T3 fibroblasts; Olivera A et al.; Sphingomyelin or the products derived from its metabolism may constitute a signaling system involved in a variety of cellular processes . The activation of a plasma membrane neutral sphingomyelinase, which catalyzes the first step in sphingomyelin turnover, has been suggested to play an important role in cellular differentiation . We have studied the effect of exogenous staphylococcal sphingomyelinase on DNA synthesis and on the composition of membrane sphingolipids in quiescent Swiss 3T3 fibroblasts . Sphingomyelinase stimulated proliferation of Swiss 3T3 cells and potentiated the mitogenic action of other growth factors, such as insulin, epidermal growth factor, and bombesin . Treatment with sphingomyelinase produced a significant decrease in sphingomyelin accompanied by a corresponding increase in ceramide levels . No significant increases were detected in the levels of products derived from ceramide, i.e . ceramide 1-phosphate, sphingosine, or sphingosine 1-phosphate . To further investigate the role of ceramide in cellular proliferation, we studied the effect of cell-permeable analogs of ceramide on DNA synthesis in quiescent Swiss 3T3 cells . Both N-hexanoylsphingosine and N-acetylsphingosine at low concentrations stimulated {3H}thymidine incorporation and acted synergistically with a wide variety of growth factors known to induce proliferation of quiescent Swiss 3T3 fibroblasts . Similar effects were observed with bovine brain ceramides . These results suggest that ceramide may be involved in the regulation of cellular proliferation.

FEMS Microbiol Lett, 1992 Dec 15, 79(1-3), 249 - 54
Lipase of Staphylococcus hyicus: analysis of the catalytic triad by site-directed mutagenesis; Jager S et al.; In this study the putative catalytic triad Ser-His-Asp of the Staphylococcus hyicus ssp . hyicus lipase was investigated . Putative catalytic sites determined by homology comparisons of three staphylococcal and other non-staphylococcal lipases were altered by site-directed mutagenesis . Since the mutations did not influence the secretion of the lipase, the decrease in lipase activity of the mutants strongly supports the proposed involvement of Ser369 and His600 in catalysis . Asp559 is postulated to be the third amino acid of the triad.

Blood, 1992 Dec 15, 80(12), 3144 - 56
Human T-cell development in SCID-hu mice: staphylococcal enterotoxins induce specific clonal deletions, proliferation, and anergy; Waller EK et al.; SCID-hu mice provide an in vivo model for studying the events of normal intrathymic human T-cell development and differentiation . We injected SCID-hu mice with staphylococcal enterotoxins (SE) and determined their effects on the development and responsiveness of human T-cell populations defined by their expression of CD4 and CD8, and the type of V beta molecule in their T-cell receptors . After single intraperitoneal injections of SEB or SEE, we observed specific effects on thymic T cells expressing a cognate V beta T-cell receptor (TCR) (V beta 12.1 in the case of SEB-treated SCID-hu mice and V beta 8.1 in the case of SEE-treated mice) using both immunohistochemical staining of thymic frozen sections and flow cytometric analyses . An injection of SEB resulted in a 32% decrease in the total percentages of V beta 12.1+ cells in thymic sections after 2 days, with the greatest effect seen in the medulla, without a demonstrable effect on V beta 5.2/5.3+ or V beta 8.1+ cells . Fluorescence-activated cell sorter analysis demonstrated that TCRhi thymocytes expressing a cognate V beta TCR declined transiently by 35% to 45% 1 to 2 days after the injection of SE . Analysis of thymic subpopulations showed decreases in the TCRhi CD4+8- and CD4-8+ cells and an increase in TCRlo CD4-8+ cells . Multiple injections of SE resulted in 50% to 60% decreases in cognate V beta TCR+ CD4+8- populations . Thymocytes prepared from SE-treated SCID-hu mice demonstrated specific anergy to the SE to which they had previously been exposed in vivo, but had a normal proliferative response to other superantigens in an in vitro assay . In contrast to the effects on thymic T cells, single injections of SE resulted in a twofold increase in the total numbers of circulating CD4+8- and CD4-8+ human T cells and a fourfold to eightfold increase in T cells expressing a cognate V beta TCR . Using SE as superantigens in SCID-hu mice, we have been able to induce antigen-specific clonal deletions, anergy, and proliferation of human T cells.

Biochemistry, 1992 Dec 15, 31(49), 12369 - 75
Kinetic evidence of microscopic states in protein folding; Chen HM et al.; Staphylococcal nuclease unfolds at acidic pHs and refolds at neutral pH . Previous kinetic analysis based on both the direct pH jump and the sequential pH jump, from a native condition (pH 7.0) to pHs beyond unfolding transition zones (pH 3.0 and pH 12), and vice versa, supports the mechanism, D3<-->D2<-->D1<-->N0, in which N0 is the native state and D's are the three substates of the denatured form {Chen, H.M., You, J.L., Markin, V.S., & Tsong, T.Y . (1990) J . Mol . Biol . 220, 771-778; Chen, H.M., Markin, V.S., & Tsong, T.Y . (1992) Biochemistry 31, 1483-1491} . Here we show that both the single- and the double-pH jump kinetics of folding and unfolding to the intermediate pHs (3.4-5.0, i.e., in the transition zone), in which both the native and the denatured states coexist, are not compatible with this simple sequential model . At 25 degrees C, log tau 1(-1) (for the D1<-->N0 step) and log tau 2(-1) (for the D2<-->D1 step) vs pH show a square root of-shaped dependence on the final pH, with minimal values (tau 1(-1) of 0.56 s-1 and tau 2(-1) of around pH 3.9 . The third relaxation tau 3 (for the D3<-->D2 step, 35 s) was independent of pH in the range 3.4-8.5 . The square root of-shaped dependence on pH of log tau 1(-1) and log tau 2(-1) cannot be reproduced by the above but can be accounted for if each of N0, D1, and D2 is composed of many microscopic states in rapid equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood, 1992 Dec 15, 80(12), 3227 - 34
Influenza A virus binding to human neutrophils and cross-linking requirements for activation; Daigneault DE et al.; Although neutrophils are not viewed as a principal defense against influenza A virus (IAV) infection, their interactions are both complex and clinically relevant . Activation of the neutrophil is distinctive from that described for chemoattractants . To more fully characterize the pathway by which IAV stimulates the human neutrophil, we have examined its binding characteristics . First, inhibition studies with various sialic acid-containing and sialic-free sugars showed that IAV binds to sialic acid residues and activates receptors distinct from those used by Concanavalin-A (Con-A) and formyl-methionyl-leucyl-phenylalanine (FMLP) and that overlap those bound by wheat germ agglutinin (WGA) . That viral hemagglutinin (HA) mediates viral binding and activation was shown by preincubating neutrophils with purified monovalent bromelain-released HA (BHA) and showing that IAV-induced membrane depolarization and hydrogen peroxide (H2O2) production were inhibited approximately 95% . However, binding inhibition required significantly higher concentrations of purified HA, suggesting that binding and cell activation have different interactive requirements . Desialation of the neutrophil surface membrane by neuraminidase treatment resulted in a 90.6% +/- 4.4% and 53.1% +/- 8.7% inhibition of IAV activation of neutrophils and viral binding, respectively . Resialation with ganglioside GT1b totally restored viral binding, but did not reverse the inhibition of activation . Thus, although HA was shown to mediate binding and neutrophil activation, viral binding per se was insufficient to stimulate the cell . Having demonstrated the functional role of HA, we sought to establish the mechanism of stimulation . HA in three different forms (BHA, HA-rosettes, and HA-liposomes) failed to activate the cell, although H2O2 production evoked by IAV stimulation was reduced in competitive inhibition studies with each preparation . Upon cross-linking with a monoclonal antibody to HA, activation comparable to that of intact virus was observed . The requirement for cross-linking of functional receptors, as opposed to activation through the neutrophil Fc receptor, was confirmed in experiments using staphylococcal A protein . These studies have shown the chemical specificity of IAV binding to the human neutrophil, the character of the receptor(s) stimulated to activate the IAV-evoked response, and the activation requirement for cross-linking those receptors responsible for stimulating functional responses.

J Chromatogr, 1992 Dec 11, 584(1), 109 - 13
Adsorption behaviour of lipase from Staphylococcus carnosus on a hydrophobic adsorbent; Kerzel P et al.; The adsorption of proteins on a solid surface with a subsequent desorption is a well known final purification step in downstream processing . Here the adsorption behaviour of a microbial lipase on the hydrophobic Fractogel TSK butyl 650 in a crude fermentation supernatant is investigated . The measured equilibrium curves differ from fermentation to fermentation by up to +/- 65% . The adsorption capacity increases with decreasing particle diameter of the adsorbent and is influenced by the method of contacting the supernatant with the adsorbent . The rate of desorption depends largely on the adsorption conditions, which is an indication of different orientations of the adsorbed enzyme.

Immunol Lett, 1992 Dec, 34(3), 229 - 36
Locally superantigen-activated peritoneal cytolytic T lymphocytes belong to the CD8+ CD45RC- subset and lyse MHC class II+ tumor cells; Hansson J et al.; Bacterial encoded superantigens (SA) are capable of activating and targeting cytolytic human and mouse T lymphocytes (CTL) to lyse major histocompatibility complex class II positive (MHC class II+) target cells . In this study both in vitro and in vivo activated rat CTL were directed against MHC II+ tumor targets by bacterial encoded SA . Polyclonal in vitro activation of rat peripheral blood T lymphocytes generated CTL capable of killing MHC class II+ human BSM cells coated by staphylococcal enterotoxin (SE) -A, -E, -D, and TSST-1 but not by SEB or SEC1-3 . Allo selective peritoneal CTL generated by intraperitoneal stimulation with allogeneic spleen cells were directed against BSM cells by SEA, -D, and -E but not by SEB, SEC1-3 or TSST-1 . Based on the above observations, and in order to locally activate CTL, SEA was chosen for in vivo priming of rats by intraperitoneal inoculation of the toxin . SEA injection generated highly cytolytic CTL, and maximum cytolytic responses were seen at 50-250 micrograms SEA per animal with a peak in response 48-72 hours after injection of the toxin . The cytolytic activity of peritoneal SEA reactive effector cells was confined to the TCR alpha beta+ CD4- CD8+ CD45RC- cell population . MHC class II- colon carcinoma cells were insensitive to lysis by SEA reactive CTL but colon carcinoma cells induced to express MHC class II by interferon-gamma (IFN-gamma) treatment were efficiently lysed in the presence of SEA . Comparison of rat and human MHC II+ colon carcinomas revealed a peak in sensitivity to lysis at 10-100 ng SEA/ml for both tumor targets . These findings suggest that superantigens can be used in local immunotherapy of peritoneal tumors such as ovarian and colorectal carcinomatosis, with inducible or constitutive expression of MHC class II.

Br J Surg, 1992 Dec, 79(12), 1262 - 7
Prosthetic vascular graft infection; O'Brien T et al.; The aetiology, diagnosis and management of prosthetic vascular graft infection are reviewed . The importance of contamination at the time of surgery as the crucial aetiological factor is highlighted . Staphylococcus epidermidis is the causative organism in over 50 per cent of cases and the reasons for this are explored . Sound surgical technique, use of prophylactic antibiotics and the avoidance of a groin incision are emphasized as the most important factors in prevention of graft infection . Difficulties of diagnosis are highlighted and the diagnostic role of various imaging methods is assessed . Graft excision with extra-anatomic revascularization is presented as the conventional surgical solution, while the roles of less radical surgical solutions and non-operative management are discussed.

Ann Pharmacother, 1992 Dec, 26(12), 1523 - 4
Dobutamine-induced fever; Robison-Strane SR et al.; OBJECTIVE: To report a case of dobutamine-induced fever . PATIENT: A 71-year-old woman with congestive heart failure who developed a fever after receiving dobutamine during two separate hospital admissions . RESULTS: Other possible causes of the fever during the first admission included relapse of staphylococcal sepsis and drug fever from vancomycin or metoclopramide . However, rechallenge with dobutamine on a subsequent admission demonstrated a highly probable relationship between dobutamine and fever . CONCLUSIONS: A strong temporal relationship between dobutamine and fever was noted during the patient's second admission and the case was not complicated by other new medications . No underlying infectious or noninfectious cause of the fever was found . Therefore, when patients receiving dobutamine become febrile, dobutamine should be considered as a possible cause.

Diabet Med, 1992 Dec, 9(10), 947 - 9
Staphylococcal septicaemia complicating intracavernosal autoinjection therapy for impotence in a man with diabetes; Parfitt VJ et al.; Intracavernosal injection of vasoactive drugs is a safe, effective, and commonly used treatment for impotence in diabetic men . In prospective studies infection has rarely occurred . We report a case of life-threatening Staphylococcal septicaemia complicating this treatment in a 61-year-old man with Type 2 diabetes, probably due to a combination of an unsterile technique and drug-induced priapism . Infection is a potential risk in diabetic men using intracavernosal injection therapy and those offered it should be informed of the importance of a scrupulous sterile technique and the need to seek urgent medical help for decompression if an erection persists for more than 4-6 h.

Appl Environ Microbiol, 1992 Dec, 58(12), 4083 - 5
Applicability of an immunoblot technique combined with a semiautomated electrophoresis system for detection of staphylococcal enterotoxins in food extracts; Orden JA et al.; We studied the usefulness of an immunoblot technique for the detection of staphylococcal enterotoxins (SEs) in strains and food extracts . Food samples (milk, yogurt, hot dog sausage, cheese, and mayonnaise) were artificially contaminated with SEA through SEE . Protein A did not interfere with the results; it appeared on electrophoresis gels as bands with molecular weights higher than those of the SEs . Other food proteins were not revealed by the technique . The immunoblot technique proved to be fast, specific, and sensitive for the detection of SEs in foods.

Am J Vet Res, 1992 Dec, 53(12), 2333 - 6
Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations; Budsberg SC et al.; Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes . The disposition curve for IV administration was best represented as a 2-compartment open model . Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration . Bioavailability after IM administration was 87% . Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval . Intramuscular administration induced signs of pain and cannot be recommended.

Eur J Pediatr, 1992 Dec, 151(12), 876 - 84
A comparison of ceftazidime and aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn . European Society for Paediatric Infectious Diseases--Neonatal Sepsis Study Group; de Louvois J et al.; We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn . In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ + AMP) was compared to an amino-glycoside/ampicillin combination (AG + AMP) . In all cases treatment was based on "an intention to treat" . Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients . The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis . A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant . The cure rate for evaluable patients with proven infection who were treated with CAZ + AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG + AMP (66%, 26/39), (P < 0.002) . The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG + AMP (86%, 32/37) was not significant . Treatment failed in 28/150 (18.7%) evaluable patients . There were significantly fewer failures (P < 0.001) with CAZ + AMP than with AG + AMP therapy . There were 55 staphylococcal infections . Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ + AMP and in 16/29 evaluable patients treated with AG + AMP . None of the study centres encountered problems with ceftazidime resistant bacteria . The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Dig Dis Sci, 1992 Dec, 37(12), 1915 - 7
Fibrin ring granulomas in hepatitis A; Ruel M et al.; Fibrin ring granuloma is characterized by a fibrinous ring surrounding a central fat vacuole . It has been found in the liver and bone marrow of patients with Q fever, and occasionally with visceral leishmaniasis, cytomegalovirus, Epstein-Barr virus, Staphylococcus epidermidis infections, Hodgkin's lymphoma, and hypersensitivity to allopurinol . We describe a case of serologically confirmed viral hepatitis A with this lesion in the liver biopsy . A false positive anti-hepatitis A virus IgM result has been excluded . This is, to our knowledge, the second reported case of type A hepatitis with hepatic fibrin ring granulomas . It confirms that hepatitis A should be included in the differential diagnosis of this lesion.

Acta Orthop Scand, 1992 Dec, 63(6), 661 - 4
Increased resistance of bacteria after adherence to polymethyl methacrylate . An in vitro study; Arizono T et al.; The pathobiology of total joint prosthesis infection was investigated in vitro . Discs of polymethylmethacrylate (PMMA) were exposed to a suspension containing cells of 10(8) per mL Staphylococcus epidermidis E-46 . After 12 hours, exposed discs were rinsed with phosphate-buffered saline and placed in brain heart infusion broth containing antibiotics (2.5 mg per mL of Cephaloridine) . After gentle shaking for 24 hours at 37 degrees C, the bacteria on the PMMA surface were detached and washed with phosphate-buffered saline to remove the antibiotics . Compared with the free bacteria which were detached from the PMMA by sonication immediately after exposure to the antibiotic solution, those allowed to remain adhered to the PMMA surface were more resistant to antibiotics . Scanning electron microscopy showed accumulation of bacteria surrounded by slime on PMMA discs exposed for 12 hours . Our results indicate that resistance of bacteria to antibiotics is increased after adherence to the biomaterial and formation of a slime layer.

Epidemiol Infect, 1992 Dec, 109(3), 433 - 44
A longitudinal study of Staphylococcus hyicus colonization of vagina of gilts and transmission to piglets; Wegener HC et al.; High Staphylococcus hyicus colonization rates were found in vaginal samples of healthy breeding sows and in skin samples of their offspring . Twenty-two different phage types were identified among the 720 isolates of S . hyicus examined . Two to 13 different phage types were isolated per herd . Phage typing, as well as characterization of about 10% of the isolates by plasmid profiles and antibiogram patterns, showed that, several different clones of S . hyicus could be present simultaneously in vagina of gilts and also on skin of piglets . Generally isolates from the vagina of one animal were identical as regards to phage types, plasmid profiles, and antibiogram patterns during the entire investigation period . Isolates from the skin of piglets were of the same type as their mothers, indicating that vertical transmission had taken place . S . hyicus strains isolated from the skin of piglets within 24 h after birth were identical to strains isolated 3 weeks after birth from the same litter, indicating that the vaginal strains became part of a stable skin flora.

Epidemiol Infect, 1992 Dec, 109(3), 423 - 32
A study of phenotypic variation of Staphylococcus epidermidis using Congo red agar; Deighton MA et al.; This study examines a series of phenotypic variants of Staphylococcus epidermidis that were generated from a pair of parent variants, isolated from valvular tissue of a patient with prosthetic valve endocarditis . The variants were initially classified by examining their colonial morphology on Congo red agar . In addition to differences in Congo red binding and colonial morphology, they differed in the expression of several surface components and enzymes . Despite these phenotypic differences, all variants had the same restriction endonuclease profile of plasmid DNA . Examination of a collection of clinical isolates demonstrated that phenotypic variation is a common property of S . epidermidis . The ability to express different combinations of surface components and enzymes could contribute to the virulence of S . epidermidis strains by enabling these organisms to colonize a range of diverse environments.

J Paediatr Child Health, 1992 Dec, 28(6), 447 - 50
Primary staphylococcal pneumonia in childhood: a review of 69 cases; Knight GJ et al.; Primary staphylococcal pneumonia is a rapidly progressive illness with well-described clinical and radiological features and a significant mortality rate . This retrospective study of cases diagnosed over a 20 year period at a tertiary paediatric hospital was undertaken to document the epidemiology and assess the management and mortality of the disease . The survey demonstrated that far fewer patients are being seen than formerly and confirmed that this is a disease primarily affecting infants and Aboriginal children . The initial radiological features were not diagnostic in the majority of cases but typical changes appeared in most at some time during the illness . The use of surgical drainage was not associated with a decrease in the duration of fever or length of hospital stay . The mortality rate has improved but remains significant.

Curr Opin Immunol, 1992 Dec, 4(6), 728 - 32
T-cell subsets in autoimmunity; Mason D et al.; The demonstration that functionally different T-cell subsets can be defined by the isoforms of the leukocyte-common antigen, CD45, that they express, has prompted studies on the roles of these subsets in autoimmunity . The results have led to the identification of a particular subset of CD4+ T cells that have the ability to inhibit autoimmune disease . Further, it has been shown that diabetes in the B-B rat can be transferred by in vitro activation of T cells by Staphylococcal enterotoxin suggesting that superantigens may play a role in the pathogenesis of this disease . However, in this system too, it appears that a subset of T cells can inhibit the induction of autoaggressive cells . In other experimental autoimmune diseases there is evidence that CD8+ T cells can be protective and that these cells may mediate this protection by the synthesis of transforming growth factor-beta.

J Med Microbiol, 1992 Dec, 37(6), 368 - 75
Comparison of cell-wall teichoic acid with high-molecular-weight extracellular slime material from Staphylococcus epidermidis; Hussain M et al.; Extracellular high-mol.-wt material was separated from liquid cultures of Staphylococcus epidermidis . This material contained protein c . 20% w/w and polysaccharide c . 80% w/w . The polysaccharide was isolated by gel and ion-exchange chromatography and contained glycerol phosphate, glucose, N-acetylglucosamine, and D-alanine . Cell-wall teichoic acid was isolated from strain RP-62A and had a similar composition.

J Exp Med, 1992 Dec 1, 176(6), 1779 - 84
Identification of HLA-DR alpha chain residues critical for binding of the toxic shock syndrome toxin superantigen; Panina-Bordignon P et al.; Staphylococcal toxic shock syndrome toxin 1 (TSST-1) binds to major histocompatibility complex class II molecules, and the toxin-class II complexes induce proliferation of T cells expressing V beta 2 sequences . To define the residues involved in TSST-1 binding, a set of transfectants expressing 21 HLA-DR alpha chain mutants were analyzed for their abilities to bind and present TSST-1 and to present an antigenic peptide . Mutations at DR alpha positions 36 and 39 markedly decreased the ability of the DR7 molecule to bind and present TSST-1 but did not affect the ability to present an antigenic peptide . These data indicate that DR alpha residues 36 and 39, predicted to be located on an outer loop, are important in the formation of the TSST-1 binding site on DR molecules.

J Clin Oncol, 1992 Dec, 10(12), 1907 - 13
Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome; Foss FM et al.; PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin {DCF}) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sezary syndrome (SS) . PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26 . Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment . RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%) . No responses were observed in the seven patients with visceral involvement . The median progression-free survival of patients who responded was 13.1 months . IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two . Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia . CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

J Clin Microbiol, 1992 Dec, 30(12), 3270 - 3
Capsular polysaccharide serotyping scheme for Staphylococcus epidermidis; Fattom A et al.; A scheme for the capsular typing of Staphylococcus epidermidis that is based on direct slide agglutination between proteinase-treated bacterial cells and specific antisera is described . Antisera were prepared from serum from rabbits immunized with two selected strains of encapsulated S . epidermidis isolated from bacteremic patients . Antisera were shown to be type specific and designated type 1 and type 2 . Blood isolates of S . epidermidis from hospitals in different locations within the United States and Europe were serotyped, and it was found that over 90% of all strains were of type 1 or type 2 . Type-specific antibodies mediated type-specific opsonophagocytosis and killing of S . epidermidis . The specificity was shown to be due to two distinct capsular polysaccharides . The data presented in this report may open a new window on the pathogenesis of S . epidermidis which could lead to the development of new vaccines and therapies.

Infect Immun, 1992 Dec, 60(12), 5190 - 6
Dual roles for class II major histocompatibility complex molecules in staphylococcal enterotoxin-induced cytokine production and in vivo toxicity; Grossman D et al.; The staphylococcal enterotoxins (SE) specifically bind to class II major histocompatibility complex (MHC) proteins, resulting in activation of monocytes and T cells . The SE cause weight loss in mice, which is dependent on T-cell stimulation and tumor necrosis factor alpha (TNF-alpha) production . Here we use a mutant of staphylococcal enterotoxin A that binds class II MHC molecules and activates monocytes but not T cells to evaluate the relative contributions of monocyte- and T-cell-stimulatory activities to in vivo toxicity . The mutant toxin did not cause weight loss in B10 . BR mice but did stimulate monocyte TNF-alpha production in vitro, as did the wild-type toxin . Addition of a supernatant from toxin-activated T cells enhanced monocyte-stimulatory activity of both mutant and wild-type toxins fivefold . The effect of the supernatant could be mimicked by recombinant gamma interferon (IFN-gamma) and was inhibited by antibody to IFN-gamma . These results suggest that toxin-induced monocyte TNF-alpha production is upregulated by IFN-gamma, which likely represents the T-cell requirement in SE-mediated weight loss . Our studies thus implicate two distinct class II MHC-dependent signaling pathways for SE, the first involving direct signal transduction through class II MHC molecules mediated by either mutant or wild-type toxin and the second requiring T-cell stimulation by toxin-class II MHC complexes with consequent production of IFN-gamma . We suggest that both pathways are required for optimal monocyte TNF-alpha production in vitro and SE-induced toxicity in vivo.

Blood, 1992 Dec 1, 80(11), 2797 - 804
Interleukin-11 promotes accessory cell-dependent B-cell differentiation in humans; Anderson KC et al.; Interleukin-11 (IL-11) is a recently described stromal-derived cytokine that supports the growth of an IL-6-dependent murine plasmacytoma line in the presence of antibody to IL-6 and appears to act in a manner similar to IL-6 on hematopoietic stem cells . Because IL-6 is known to promote differentiation of normal human B cells, the role of IL-11 on B-cell differentiation in vitro was characterized . IL-11 does not result in significantly increased DNA synthesis or Ig secretion by purified B cells alone or B cells cultured with Staphylococcus Cowan I, a T-cell-independent B-cell mitogen . In contrast, purified B cells cultured in the presence of pokeweed mitogen (PWM), irradiated T cells, and monocytes show increased DNA synthesis at day 3 and increased IgG and IgM secretion at day 7 of culture; addition of IL-11 further augments Ig secretion without change in DNA synthesis, an effect that can only be partially blocked by monoclonal antibody to IL-6 . Similar experiments confirmed that increased IgG secretion was demonstrable when either IL-11 or IL-6 was added to B cells + CD4+/45RA- T cells + monocytes + PWM; in contrast, Ig secretion was low and equivalent when CD4+/45RA+ T cells were cultured with B cells+monocytes+PWM with or without IL-6 or IL-11 . Neither IL-6 nor IL-11 could significantly increase phytohemagglutinin (PHA)-induced DNA synthesis by CD4+/45RA- or CD4+/45RA+ T cells . Although PWM or IL-11 induced IL-6 mRNA expression in both CD4+/45RA- T cells and monocytes, in neither cell did IL-11 increase IL-6 mRNA expression over that noted to PWM alone . These observations support the view that IL-11 promotes differentiation of human B lymphocytes only in the presence of accessory T cells and monocytes and that a minor component of this effect may be through stimulation of IL-6 production by CD4+/45RA- T cells and monocytes.

J Urol, 1992 Dec, 148(6), 1905 - 6
Prosthetic penile infection: "rescue procedure" with rifamycin; Teloken C et al.; Penile prosthetic implantation is a successful procedure for the management of male erectile impotence . However, infection remains the most serious complication requiring removal of the device . Later reinsertion can be difficult due to fibrosis and a shortened penis . We present 3 cases of penile infection with Staphylococcus epidermidis in which a new penile prosthesis was placed after 72 hours of continuous irrigation of the corpora cavernosa with rifamycin . The procedure requires judicious selection of patients and a stable clinical status.

Int Immunol, 1992 Dec, 4(12), 1381 - 8
Life and death of a superantigen-reactive human CD4+ T cell clone: staphylococcal enterotoxins induce death by apoptosis but simultaneously trigger a proliferative response in the presence of HLA-DR+ antigen-presenting cells; Kabelitz D et al.; We report that a human CD4+ T cell clone with specificity for staphylococcal enterotoxin (SE) superantigens A, D, and E can respond to SEs in two seemingly opposite ways . In the absence of antigen presenting cells (APC), SEA, D, and E (but not SEB or C1) strongly inhibited in a dose-dependent manner the responsiveness of clone D894/25 to exogenous IL-2 . Growth inhibition was due to SE-induced programmed cell death (apoptosis) as shown by propidium iodide staining and the appearance of the characteristic ladder pattern of DNA fragmentation . Apoptotic cell death was accompanied by significant cell lysis after 4 and 8 h as measured in a 51Cr release assay . In contrast (but as expected), a proliferative response of clone D894/25 was triggered by SEA, D, and E in the absence of exogenous IL-2 but presence of HLA class II-positive lymphoblastoid cell line (LCL) as APC . Moreover, the addition of LCL feeder cells partially prevented the suppression of IL-2 responsiveness by SEs . Surprisingly, however, the latter two culture conditions (i.e . presence of LCL feeder cells with or without exogenous IL-2) were associated with similar levels of induced cell death as in the absence of LCL . At the clonal level, these data demonstrate that SE superantigens induce programmed cell death in a fraction (40-50%) of responsive mature T cells, irrespective of the presence or absence of MHC class II-positive APC . We conclude that the proliferative response of clone D894/25 which is triggered by SEs in the presence of APC and absence of IL-2 must originate from the fraction (50-60%) of clone T cells surviving SE-induced cell death.

Int Immunol, 1992 Dec, 4(12), 1351 - 60
A co-stimulatory role for CD28 in the activation of CD4+ T lymphocytes by staphylococcal enterotoxin B; Goldbach-Mansky R et al.; In this study we investigated the differential effect of the co-stimulatory receptor ligand molecules CD2/LFA-3, LFA-1/ICAM-1, and CD28/B7 on microbial superantigen mediated activation of CD4+ T cells . Highly purified CD4+ T cells, depleted of antigen presenting cells (APCs), do not proliferate in response to the superantigen, staphylococcal enterotoxin B (SEB) . However, CD4+ T cells do respond to SEB in the presence of the LFA-3, ICAM-1, and B7 positive erythroleukemic cell line K562, murine L cells, human B7 transfected L cells or CD28 mAb . The K562 plus SEB induced response can be inhibited by combinations of mAbs to CD2 and LFA-1, and to LFA-3, ICAM-1, and B7 . Addition of CD28 mAb to the CD2 and LFA-1 inhibited cultures could restore the response . Furthermore, soluble CD28 mAb alone is able to synergize with SEB to induce a proliferative CD4+ T cell response . CD4+ T cells depleted of APCs could also be activated by a pool of four mAbs directed to the V beta 5, V beta 6, V beta 8, and V beta 12 region of the TCR when a co-stimulatory signal was provided by the CD28 mAb, while the V beta mAbs alone or in combination are unable to activate CD4+ T cells in the absence of APCs . In contrast, addition of soluble mAbs to CD2 and LFA-1 molecules failed to co-stimulate SEB activated CD4+ T lymphocytes . The kinetics of the different modes of activation are distinct . SEB induced proliferation is most efficient in the presence of autologous APCs with maximal proliferation at a log4 lower SEB concentration than when CD28 mAbs were used . SEB plus K562 activation peaks on day 7, while SEB plus CD28 mAb induced proliferative responses do not peak until day 9 . Thus, superantigen mediated activation of CD4+ T cells requires co-stimulatory signals, among which CD28 has distinct and unique effects.

J Immunol, 1992 Dec 1, 149(11), 3550 - 3
Negative selection of thymocytes . A novel polymerase chain reaction-based molecular analysis detects requirements for macromolecular synthesis; D'Adamio L et al.; Self-tolerance is mainly established through clonal deletion of autoreactive T cells during thymic differentiation . The mechanisms by which deletion is achieved are poorly understood . Here we use a specific polymerase chain reaction-based system to characterize DNA fragmentation and show that after in vivo treatment of neonatal mice with staphylococcus enterotoxin B, selective apoptosis of V beta 8+ thymocytes occurs . This process precedes detectable deletion of V beta 8+ cells as determined by phenotypic analysis . Moreover, in vivo administration of cycloheximide and, to a lesser extent, actinomycin D, inhibits apoptosis of staphylococcus enterotoxin B specific thymocytes . Thus, macromolecular synthesis is a requirement for negative selection.

J Antimicrob Chemother, 1992 Dec, 30(6), 753 - 68
Novel membrane proteins present in teicoplanin-resistant, vancomycin-sensitive, coagulase-negative Staphylococcus spp; O'Hare MD et al.; Clinical isolates of Staphylococcus epidermidis and Staphylococcus haemolyticus resistant to teicoplanin (MIC 64 mg/L) and sensitive to vancomycin (MIC 2 mg/L), were compared with vancomycin- and teicoplanin-sensitive isolates (MICs 1 mg/L) of the same species . No apparent differences between the sensitive and resistant strains of either pair were found with respect to binding of teicoplanin to the bacteria, or to the amino acid content or degree of cross-linkage of purified peptidoglycan . The resistant strains did not inactivate teicoplanin in the surrounding medium . Analysis of the membrane proteins of the resistant S . epidermidis strain grown in the presence or absence of sub-inhibitory levels of teicoplanin (4 mg/L), showed the presence of a 39 kDa protein which was either absent, or present in considerably reduced amounts, in the sensitive strain . Fractionation of cell components after lysis of protoplasts showed that the 39 kDa protein was present predominantly in the membrane fraction but also in small amounts in the wall fraction . Similar investigations with S . haemolyticus revealed the presence of a 35 kDa protein in membranes of the resistant strain: the amount was increased substantially by growth in sub-inhibitory levels of teicoplanin . Membranes prepared by mechanical disintegration of bacteria or by osmotic lysis of protoplasts showed large apparent differences in the amounts of the 39 kDa protein.

Isr J Med Sci, 1992 Dec, 28(12), 864 - 8
Confusion as the presenting manifestation of vertebral osteomyelitis: a case report; Shuper A et al.; A 44-year-old patient presented with increasing confusion . He was first diagnosed as having intermittent pressure hydrocephalus but a further evaluation showed CSF pleocytosis and hypoglycorrhachia . Five weeks later, his physical examination was unrevealing . Nuclear imaging techniques were conflicting, with negative gallium- and indium-labelled white blood cells scans but a Tc scan pointing towards a vertebral infection . A well-demarcated lesion in the T9 vertebral body, demonstrated by CT scan, confirmed the diagnosis of vertebral osteomyelitis . Although we were unable to recover the causative organism, antibiotic treatment for presumed staphylococcal osteomyelitis resulted in full recovery . This case indicates that vertebral osteomyelitis may cause significant meningeal inflammation even in the absence of epidural or subdural abscess . We recommend that in patients with meningitis without a clear etiology vertebral osteomyelitis should be considered and pursued with CT scannings of the vertebrae, a procedure that can yield positive findings even when other scanning modalities are negative.

Int Immunol, 1992 Dec, 4(12), 1399 - 406
Identification of single amino acid substitutions in the staphylococcal nuclease protein that enhance and diminish T cell clone recognition of naturally processed peptides; Finnegan A et al.; It has been inferred that residue changes that affect T cell recognition of synthetic peptides will have a similar effect in the intact protein . However, since small peptides do not require antigen processing it is possible that residue changes in synthetic peptides will not have an equivalent effect in the intact protein . Mutant proteins of staphylococcal nuclease (Nase) and 15mer synthetic peptides with corresponding substitutions were compared to determine if residue changes within an immunodominant epitope have an effect on the generation of naturally processed peptides . Five different substitutions in the synthetic peptide resulted in loss of reactivity of individual Nase-specific clones . When the same single amino acid changes were made in the intact protein, the naturally-processed peptides were also unable to stimulate the Nase-specific clones . However, two other substitutions in the synthetic peptide were stimulatory for a T cell clone even though the same changes in the intact protein were non-stimulatory . These results suggest that certain residue changes affect recognition of the naturally processed peptide but not the synthetic peptide with the same amino acid change . In addition, these results demonstrate that the effects of amino acid substitutions in synthetic peptides on T cell recognition may not always reflect the effects of these substitutions in the intact protein . Substitutions located outside Nase-specific T cell epitopes were also examined . Thirty different mutant proteins were all stimulatory . Moreover, a number of these mutants proteins were 50- to 100-fold more efficient in their stimulatory capacity than the native Nase protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1992 Nov 24, 31(46), 11390 - 6
A kinetic study of the folding of staphylococcal nuclease using size-exclusion chromatography; Shalongo W et al.; The kinetics of the hydrodynamic volume change accompanying the reversible unfolding of staphylococcal nuclease have been observed by size-exclusion chromatography at 4 degrees C and pH 7.0 using the denaturant guanidine hydrochloride . The observed chromatographic profiles have been simulated by a six-component unfolding/refolding mechanism using a consistent set of equilibrium and kinetic parameters . The native protein is an equilibrium mixture of the cis and trans isomers of the peptide bond preceding proline-117 . The native conformation containing the cis isomer dominates the equilibrium mixture, is more stable, and unfolds more slowly at its transition midpoint . The denatured protein is an equilibrium mixture of at least four components, the cis/trans isomers of proline-117 and one of the five remaining prolines . The dominant refolding pathway is initiated from the denatured component containing the trans isomer of proline-117 . The six-component mechanism is consistent with tryptophan fluorescence kinetic measurements of the wild-type protein and with chromatographic measurements of a mutant P117G protein.

J Mol Biol, 1992 Nov 20, 228(2), 338 - 42
A peptide model for proline isomerism in the unfolded state of staphylococcal nuclease; Raleigh DP et al.; Nuclear magnetic resonance spectroscopy has been used to investigate a synthetic peptide (YVYKPNNTHE) corresponding to residues 113 to 122 of staphylococcal nuclease . In the major folded state of the protein this region forms a type VIa beta-turn containing a cis Lys116-Pro117 peptide bond . There is, however, no evidence for any significant population of such a turn in the peptide in aqueous solution and the X-Pro bond is predominantly in the trans configuration . The peptide exhibits several well-resolved minor resonances due to the presence of a small fraction (4 +/- 2%) of the cis-proline isomer . The ratio of cis to trans isomer populations was found to be independent of temperature between 5 degrees C and 70 degrees C, indicating that delta H for the isomerism is close to zero . Using magnetization transfer techniques the rate of trans to cis interconversion was found to be 0.025(+/- 0.013) s-1 at 50 degrees C . The thermodynamics and kinetics of isomerism in the peptide are very similar to those estimated for the Lys116-Pro117 peptide bond in unfolded nuclease, suggesting that the cis-trans equilibrium in the unfolded protein is largely determined by the residues adjacent to Pro117 in the sequence . These results are consistent with previous suggestions that the cis-proline bond is stabilized late in the folding process and that the predominance of the cis form in folded nuclease is due to stabilizing interactions within the protein that give rise to a favorable enthalpy term.

FEMS Microbiol Lett, 1992 Nov 15, 78(1), 59 - 63
Cadmium-resistance plasmid in Staphylococcus lugdunensis; Poitevin-Later F et al.; Plasmids that confer resistance to cadmium (MIC > or = 125 microM), were found in 18 out of 30 independent Staphylococcus lugdunensis strains from clinical specimens . Variants that were cured of their plasmid were cadmium sensitive . Restriction endonuclease sites of a 3.2-kb cadmium-resistance plasmid of S . lugdunensis, designated pLUG10, were similar to those of pOX6, a S . aureus cadmium-resistance plasmid containing the cadB gene . Southern-blot hybridisation was performed with a probe intragenic to cadB . Hybridisation was found with the cadB probe in the cadmium-resistant S . lugdunensis isolates to the 2.9-, 3.2- and 3.7-kb plasmids . These findings suggest that cadmium-resistance in some S . lugdunensis strains is due to a gene sharing homology with the cadB gene of S . aureus.

Toxicon, 1992 Nov, 30(11), 1427 - 40
Role of Tyr and Trp in membrane responses of Pyrularia thionin determined by optical and NMR spectra following Tyr iodination and Trp modification; Fracki WS et al.; Pyrularia thionin is a strongly basic and bioactive 47 amino acid peptide which contains two Tyr residues at positions 13 and 45 and one Trp at position 8 . Limited iodination does not have a significant effect, but prolonged iodination of the peptide leads to progressive inactivation for all known cellular responses (Evans, J . et al . (1989) Proc . natn . Acad . Sci . U.S.A . 86, 5849-5853) . 1H NMR spectra of the native Pyrularia thionin show four Tyr bands, two arising from each Tyr residue . One resonance band for the epsilon hydrogens of Tyr 45 disappears early during limited iodination and the band from the delta hydrogens shifts to low field . The two bands corresponding to Tyr 13 remain during limited iodination, but both decrease in intensity during prolonged iodination, with the epsilon hydrogen band decreasing somewhat more . The resonance bands arising from Trp disappear during prolonged iodination . This sequence of reactions is verified by the optical absorbance properties of two small peptide fragments obtained by Staphylococcal V8 protease hydrolysis of thionin which had been iodinated to varying degrees . Limited iodination did not significantly inhibit the thionin's biological activity, yet the fragment from the -COOH terminus showed the conversion of Tyr 45 to diiodoTyr . This treatment did not significantly modify the Tyr 13 or Trp 8 located in the -NH2 terminal fragment . More extensive iodination resulted in a disappearance of Trp 8 absorbance with an accompanying conversion of Tyr 13 to the monoiodo form . Extensive iodination yielded two atoms of iodine in the Tyr 45-containing fragment, and only one atom in the Tyr 13 fragment . The data indicate that Tyr 45 of the native thionin is more readily iodinated, proceeding to the diiodo form without significant loss of activity . Prolonged iodination does not lead to the formation of any diiodoTyr 13, but does lead to modification of Trp 8 and probably formation of monoiodoTyr 13 . Modification of Trp 8 with N-bromosuccinimide inhibits the hemolytic activity of the thionin, showing that Trp 8 is necessary for Pyrularia thionin activity . It is most likely Trp 8 modification during prolonged iodination which results in the loss of biological activity.

Paraplegia, 1992 Nov, 30(11), 788 - 90
Vertebral osteomyelitis following manipulation of spondylitic necks--a possible risk; Lewis M et al.; Neurological complications of neck manipulation are well recognised but are usually due to acute vascular incidents . However, we describe two patients with cervical spondylosis, who developed staphylococcal osteomyelitis of the cervical spine with progressive tetraplegia, apparently following manipulation of the neck by a chiropractor . Although it is possible that the manipulation resulted in cervical spine trauma sufficient to cause local haemorrhage, the area becoming a nidus for infection, it is also conceivable that the patients underwent neck manipulation in an attempt to relieve pain due to an already existing osteomyelitis of the cervical spine, and the manipulation may have hastened the onset of spinal cord paralysis . Clearly, this could have occurred, as the average time between the onset of symptoms and diagnosis of vertebral osteomyelitis in most published series is about 2 months . Approximately 80% of cases of osteomyelitis occur in the 50-70 age group, a group in which cervical spondylosis is extremely common . It would seem that neck manipulation is particularly contraindicated in older patients with cervical spondylosis.

Immunopharmacology, 1992 Nov-Dec, 24(3), 203 - 17
Methylxanthine-induced inhibition of the antigen- and superantigen-specific activation of T and B lymphocytes; Rosenthal LA et al.; Methylxanthines have been shown to have a variety of effects on hematopoietic cell activation and function . These compounds inhibit cAMP-specific phosphodiesterase activity resulting in increased levels of intracellular cAMP . In the present study, we examined the effects of two methylxanthines, pentoxifylline (PTX) and caffeine, on the responses of both mouse and human lymphocytes to stimulation with polyclonal T- and B-cell mitogens, antigens, and the microbial superantigen, staphylococcal enterotoxin B (SEB) . Both PTX and caffeine significantly inhibited mitogen- and SEB-induced proliferation by murine spleen cells, SEB- and antigen-induced proliferation and lymphokine secretion by murine Th1 and Th2 clones, and the generation of antigen-specific antibody producing murine spleen cells . These compounds also inhibited the proliferative responses of human lymphocytes to phytohemagglutinin, SEB, and tetanus toxoid . Efforts to determine whether these methylxanthine compounds mediated their inhibitory effects through a specific protein kinase pathway revealed a role for cAMP-dependent protein kinase A in methylxanthine-induced immunomodulation . However, it is possible that a protein kinase A-independent pathway may also be involved . These data demonstrate that the methylxanthines, PTX and caffeine, have profound effects on cells of the immune system and may have a potential use as immunotherapeutic agents in the treatment of various inflammatory conditions and autoimmune diseases.

Int Immunol, 1992 Nov, 4(11), 1293 - 302
B cell differentiation: I . Development and functional analysis of murine B cells immortalized by a recombinant retrovirus; Chen YW et al.; B lymphoblast cells were immortalized by infection with a v-myc and v-raf/mil containing recombinant retrovirus . The immortalized B cells do not require exogenous growth factors or mitogens for growth . These cells express characteristic mature B cell phenotypic markers including IgM and IgD . Northern blot analysis detected mu and delta mRNA, and Southern blot analysis revealed rearrangements of Ig genes but not TCR genes in these cells . The immortalized B cells were found to respond to B cell mitogens by proliferation and IgM secretion, and to respond to IL-4 by an increase in la expression . Furthermore, they were found to differentiate to secrete IgM and to switch to IgG1 production following interaction with Staphylococcal enterotoxin B- activated Th2 cells . These cell lines are thus valuable tools for analyzing the molecular events involved in B lymphocyte growth and differentiation.

Eur J Pediatr, 1992 Nov, 151(11), 806 - 10
Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor; Hobbs JR et al.; A boy whose chronic granulomatous disease (CGD) manifested in infancy, and whose elder brother had died at 7 years of age, had phagocytes with complete lack of functional cytochrome B-245 and which could not be induced by interferon gamma to achieve adequate staphylococcal killing . He underwent an elective displacement bone marrow transplant from a volunteer unrelated donor at the age of 8 months . This has achieved 100% replacement of the CGD granulocytes by those of the normal volunteer and the boy has since had a normal childhood for 3 years . Six previous transplants for CGD are briefly reviewed and illustrate that the host abnormal marrow must be completely displaced using an adequate dose of busulphan to ensure 100% stable engraftment of the donor's marrow and that this is best done under elective conditions before septic foci and irreversible organ damage have occurred . Criteria need to be developed to identify early those patients likely to have severe morbidity.

Eur J Biochem, 1992 Nov 1, 209(3), 823 - 8
Identification of functionally active fragments of staphylococcal enterotoxin B; Alakhov VYu et al.; It has been found that staphylococcal enterotoxin B contains a proteolysis-sensitive sequence in the cysteine loop formed by two half-cystines located in the middle of the toxin polypeptide chain . Fragments of the enterotoxin formed as a result of its digestion in this region have been isolated, their N-terminal sequences have been determined and sites of proteolysis have been identified . It has been demonstrated that the N-terminal fragment of staphylococcal enterotoxin B is capable of activating T cell proliferation in the culture of human mononuclear cells practically to the same degree as the intact enterotoxin . The toxin's C-terminal fragment possesses an ability to activate calmodulin-dependent enzymes and is probably the toxicogenic part of the enterotoxin.

Cell Immunol, 1992 Nov, 145(1), 78 - 90
Relative resistance of intermediate TCR cells to anti-CD3 mAb in mice in vivo and their partial functional characterization; Tsuchida M et al.; In addition to T cells differentiated in the thymus, T cells, possibly of extrathymic origin, were recently demonstrated in the liver of mice . These T cells are characterized by the expression of intermediate TCR and contain double-negative CD4-8- cells . A further characterization of intermediate TCR cells was carried out . When mice were injected ip with anti-CD3 mAb, bright TCR cells (i.e., regular T cells) and intermediate TCR cells were reduced on Day 3, depending on the amount of mAb . Because of the resistance of intermediate TCR cells to treatment, injection of an appropriate dose of antibody (i.e., 100 micrograms/mouse) eliminated most bright TCR cells, but not intermediate TCR cells . This dose revealed that a significant proportion of intermediate TCR cells also reside in the periphery . Hepatic and splenic mononuclear cells (MNC), in which intermediate TCR cells became abundant after treatment, showed a unique response to T cell mitogens and IL-2 . Thus, the intermediate TCR cell-enriched population could not respond to a T cell mitogen, Con A, but responded well to a super antigen, staphylococcal enterotoxin B, and IL-2 . MNC obtained from athymic nude mice, which comprise only intermediate TCR cells, responded in the same manner . These findings revealed that intermediate TCR cells are present not only in the liver but also in the periphery, and that they have a unique function distinct from regular T cells.

Infect Immun, 1992 Nov, 60(11), 4957 - 60
Role of the adhesion molecule lymphocyte function associated antigen 1 in toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta secretion by human monocytes; See RH et al.; We previously demonstrated that the induction by staphylococcal toxic shock syndrome toxin 1 (TSST-1) of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion by human monocytes requires direct T cell-monocyte contact . In the present study, a role for the adhesion molecule lymphocyte function associated antigen 1 (LFA-1) in TSST-1-induced cytokine secretion by human monocytes among 12 normal healthy donors was investigated . Monoclonal antibodies to the alpha chain (anti-CD11a) and to the beta chain (anti-CD18) of LFA-1 significantly inhibited TSST-1-induced TNF-alpha and IL-1 beta secretion (P < 0.025; Wilcoxon signed-rank test, two tailed), while a control monoclonal antibody directed against the monocyte CD14 antigen had no effect . These results suggest that LFA-1 may play an important role in the secretion of TNF-alpha and IL-1 beta by TSST-1-stimulated human monocytes, likely by promoting cell-cell adhesion between monocytes and lymphocytes.

Infect Immun, 1992 Nov, 60(11), 4832 - 7
Feedback suppression of staphylococcal enterotoxin-stimulated T-lymphocyte proliferation by macrophages through inductive nitric oxide synthesis; Isobe K et al.; Staphylococcal enterotoxin A (SEA)- or SEB-stimulated T-lymphocyte proliferation was suppressed by the addition of high numbers of murine peritoneal macrophages or rat peritoneal or alveolar macrophages, whereas lower numbers of murine peritoneal macrophages enhanced the T-lymphocyte response . Suppression was associated with the increase of accumulation of nitrite, a product of nitric oxide, in the culture supernatants . This macrophage-mediated suppression was totally reversed by the addition of NG-monomethyl-L-arginine, a homolog of L-arginine, indicating that macrophage-mediated suppression of T-lymphocyte proliferation was mediated through the nitric oxide-synthesizing pathway activity . Macrophages in large numbers spontaneously produced nitric oxide in culture supernatant fluids . By the addition of autologous or allogeneic spleen cells but not thymocytes to SEA- or SEB-stimulated macrophage culture, nitric oxide production was greatly increased . When T lymphocytes in spleen cells were killed by antibody before addition to macrophage culture, nitric oxide production was diminished to the basal level . These results suggest that in addition to the action to support the process of T-lymphocyte activation by SEA or SEB, macrophages display a feedback regulatory action on the SEA- or SEB-stimulated T-cell proliferative response by releasing nitric oxide through interaction between macrophages and activated T lymphocytes.

Eur J Immunol, 1992 Nov, 22(11), 2789 - 93
The viral superantigen Mls-1a induces interferon-gamma secretion by specifically primed CD8+ cells but fails to trigger cytotoxicity; Herrmann T et al.; Superantigens can be operationally defined by their ability to stimulate CD4+ and CD8+ T cells via the T cell receptor beta chain variable domain (TcR V beta) . We show here that effector functions of CD8+ T cells specific for superantigens differ depending upon the nature of the superantigen involved . Hence, activated CD8+ T cells bearing TcR V beta specific for the superantigen Mls-1a {encoded in the open reading frame of the 3' long terminal repeat of endogenous mouse mammary tumor virus (MMTV)} are unable to lyse Mls-1a-bearing target cells despite the fact that they release interferon-gamma (IFN-gamma) upon Mls-1a stimulation . In contrast CD8+ T cells specific for the exogenous superantigen staphylococcal enterotoxin B (SEB) readily mediate both lysis and IFN-gamma secretion when exposed to SEB-bearing target cells . This dissociation between lysis and IFN-gamma production by Mls-1a-specific CD8+ T cells is independent of the initial stimulus used for activation and appears not to be simply explained by a low Mls-1a determinant density . We suggest that this phenomenon reflects differing TcR affinity thresholds for lymphokine secretion and cytolysis . Such differences may be exploited by retroviruses such as MMTV in order to escape immunosurveillance.

Cell Immunol, 1992 Nov, 145(1), 11 - 20
CD28 and staphylococcal enterotoxins synergize to induce MHC-independent T-cell proliferation; Green JM et al.; The bacterial exotoxins staphylococcal enterotoxin A and B (SEA and SEB) mediate disease through their effects on T lymphocytes . In this manuscript we have demonstrated that both SEA and SEB can directly activate purified T cells in the absence of accessory cells as determined by a transition from G0 to G1 and induction of IL-2 receptor expression . However, neither SEA nor SEB alone was sufficient to result in T-cell proliferation . The induction of T-cell proliferation by SEB or SEA required the addition of a second costimulatory signal . This could be provided by either accessory cells or monoclonal antibody stimulation of CD28 . As previously reported, T-cell proliferation induced by enterotoxin in the presence of accessory cells was partially inhibited by a blocking antibody against class II MHC . In contrast, in purified T cells when costimulation was provided through CD28, proliferation was not inhibited by class II antibody, and HLA-DR expression was not detectable . In addition, costimulation through CD28 was partially resistant to the effects of cyclosporin A . These results demonstrate that CD28 costimulation is sufficient to induce proliferation of enterotoxin-activated T cells, and that this effect is independent of class II MHC expression.

East Afr Med J, 1992 Nov, 69(11), 616 - 8
Management of hand infection in Khartoum; Ezeldeen K et al.; One hundred and fifty patients with hand infection seen during 6 months period at Khartoum Teaching Hospital were studied . The disease is more common among young males manual and industrial workers (M:F = 2:1) . Common types of hand infections were paronychia in (41%) of patients, volar infections in (30.6%) and subcutaneous infections in (30%) of patients . 30% of patients needed hospital admission including all diabetics (n = 15) . Two patients had serious complications that resulted in above elbow amputation . The first was a diabetic with spreading cellulitis and the second was a mentally retarded with gas gangrene . Initial empirical antibiotic therapy was prescribed in 89% of patients and later was modified according to sensitivity results . 90% of patients needed surgical drainage . Bacteriological examination showed Staph . aureus in 51% of cultures and the staphylococcus was resistant to penicillin in 77% of cultures . Apart from two deaths, the rest of the patients had satisfactory outcome.

Kansenshogaku Zasshi, 1992 Nov, 66(11), 1532 - 7
{Relationship between hand-washing activity of disinfectants and in vitro bactericidal activity in the presence of peptone}; Motai S et al.; A study was made on the relation between in vitro bactericidal activity against Staphylococcus epidermidis which is the main bacterial flora of skin and the disinfecting activity of hand-washing with povidone-iodine, sodium hydrochloride, chloramin-T, chlorhexidine gluconate and benzalkonium-chloride . Although the bactericidal activity of povidone-iodine and sodium hydrochloride was significantly high as compared with those of the other three disinfectants, both povidone-iodine and sodium hydrochloride showed no or a little hand-washing effects . In vitro the bactericidal activity of both povidone-iodine and sodium chloride were significantly retarded by the addition of peptone in the reaction mixture . On the other hand, chloramin-T, chlorhexidine gluconate and benzalkonium chloride showed a high disinfecting activity in hand washing in spite of low in vitro bactericidal activity . Moreover, the bactericidal activity of these three disinfectants were not suppressed by the addition of peptone in the reaction mixture . These results strongly suggested that hand washing effect of disinfectant is affected by the protein on the hand and that hand-washing activity of disinfectant should be determined by in vitro bactericidal activity in the presence of peptone.

Cytokine, 1992 Nov, 4(6), 576 - 80
Influence of surgery on in-vitro cytokine production by human monocytes; Cabie A et al.; Surgery leads to significant modulation of the immune system, in which cytokines play a major role . Circulating interleukin 6 (IL-6) and IL-1 have been reported following surgery whereas tumor necrosis factor alpha (TNF-alpha) is only found in gut ischemia-associated surgery . We have investigated the consequences of surgery on in-vitro cytokine production by human monocytes stimulated by lipopolysaccharide (LPS) and staphylococcal toxic shock syndrome toxin-1 (TSST-1) . Comparisons were made between the responsiveness of cells obtained the day before (D-1), during (D0) and after (D1, D2, D3) surgery . Patients undergoing abdominal aortic surgery (N = 9), carotid surgery (N = 4) and spinal surgery (N = 4) have been studied . A significant decrease of TNF-alpha, IL-1 beta and IL-1 alpha production by monocytes prepared from blood samples taken during the surgery was noticed, whereas IL-6 production was not significantly modified . On D2 a significant increase of monocyte responsiveness was observed and levels of cytokine productions rose back to initial values by the end of the follow up . The diminished in-vitro cytokine production observed during surgery might be the consequence of the effects of anaesthetic drugs, whereas the enhancement observed on D2 might reflect the surgical stress, leading to in-vivo priming of circulating monocytes.

Nature, 1992 Oct 29, 359(6398), 841 - 3
Enterotoxin residues determining T-cell receptor V beta binding specificity; Irwin MJ et al.; Superantigens such as the staphylococcal enterotoxins bind to major histocompatibility complex (MHC) class II molecules and activate T cells through a specific interaction between the V beta region of the T-cell antigen receptor (TCR) and the toxin . The TCR beta-chain alone is sufficient to produce the interaction with the enterotoxin-class II complex . Identification of the regions of enterotoxins that interact with TCR has so far proved equivocal because of difficulties in distinguishing between direct effects on T-cell recognition and indirect effects resulting from alteration of binding to class II . For example, amino-terminal truncations of SEB abrogated T-cell stimulation whereas carboxy-terminal truncation of SEA stopped its mitogenic activity . The most comprehensive study to date, accounting for both enterotoxin binding to class II and enterotoxin interactions with the TCR, identified two functionally important regions for SEB binding to TCR . Although the amino-acid sequences of staphylococcal enterotoxins A and E are 82% identical, they activate T cells bearing different V beta elements . We have assayed the binding of cells coated with these enterotoxins to soluble secreted TCR beta-chain protein and find that V beta 3 binds enterotoxin A but not E, whereas V beta 11 binds enterotoxin but not A . To map the amino-acid residues responsible for these different binding specificities, we prepared a series of hybrids between the two staphylococcal enterotoxins . We report that just two amino-acid residues near the carboxy terminus of the enterotoxins are responsible for the discrimination between these molecules by V beta 3 and V beta 11.(ABSTRACT TRUNCATED AT 250 WORDS)

Nature, 1992 Oct 29, 359(6398), 801 - 6
Crystal structure of staphylococcal enterotoxin B, a superantigen; Swaminathan S et al.; The three-dimensional structure of staphylococcal enterotoxin B, which is both a toxin and a super-antigen, has been determined to a resolution of 2.5 A . The unusual main-chain fold containing two domains may represent a general motif adopted by all staphylococcal enterotoxins . The T-cell receptor binding site encompasses a shallow cavity formed by both domains . The MHCII molecule binds to an adjacent site . Another cavity with possible biological activity was also identified.

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