Clin Microbiol Infect, 2001 Jul, 7(7), 388 - 91 Polyclonal Staphylococcus epidermidis intravascular catheter-related infections; Rijnders BJ et al.; During a 4-month period we prospectively investigated the frequency of polyclonal catheter infections with Staphylococcus epidermidis . Of each catheter with pure growth of S . epidermidis, six colonies were genotypically analyzed with pulsed-field gel electrophoresis . Two out of 12 patients with catheter infection had a polyclonal infection . Both clones of each catheter had a clearly different antibiotic susceptibility . This study shows that polyclonal catheter infections are not exceptional . Further studies are needed to define the clinical consequences of polyclonal catheter infection. Br J Dermatol, 2001 Sep, 145(3), 415 - 21 Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in alopecia areata patients with a poor response to topical immunotherapy; Yoshino T et al.; BACKGROUND: Topical immunotherapy with a contact allergen is effective in alopecia areata (AA) . However, the mechanism of the effect is still unknown, and pretreatment prediction of the outcome of therapy in each patient remains difficult . OBJECTIVES: To predict the clinical effect of this therapy in AA patients, we investigated the relationship between clinical responses to topical immunotherapy and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to T-cell stimulants . METHODS: PBMC were taken from 67 AA patients before or during diphenylcyclopropenone immunotherapy and from 14 healthy controls, and proliferative responses to phytohaemagglutinin and staphylococcal enterotoxin B were evaluated by measuring {3H}-thymidine incorporation . RESULTS: PBMC from the AA patients with a good clinical response to immunotherapy showed a normal level of proliferation, whereas PBMC from the poor responders showed a markedly suppressed proliferative response and interleukin (IL)-2 production, but increased IL-4 production compared with the controls . CONCLUSIONS: The proliferative response of PBMC to T-cell stimulants may be one of the indicators of the clinical effect of topical immunotherapy for AA. Acta Obstet Gynecol Scand, 2001 Sep, 80(9), 813 - 7 The significance of asymptomatic bacteremia for the newborn; Petanovic M et al.; BACKGROUND: So far, there has been no systematic detection of asymptomatic bacteremia in pregnant women . Consequently, its possible effects on newborn infants have not been discussed . The aim of this study was to determine the incidence of asymptomatic bacteremia in pregnant and parturient women and neonates as well as to assess its influence on the health condition of newborn infants during the first three months of life . METHODS: A total of 626 blood cultures were taken from 353 pregnant women (with single-fetus pregnancy)and their newborns: 156 during pregnancy, and immediately after delivery from 235 mothers and their 235 newborns . Blood culture results were clinically and statistically analyzed along with data on the development of the newborns . RESULTS: Positive blood culture was found in 12% of pregnant women, in 19% of parturient women and 25% of the newborns . The most often isolated bacteria were: Staphylococcus epidermidis in 36 cases (18%), Escherichia coli in 35 cases (17.5%) and Enterococcus in 20 cases (10%) . Asymptomatic bacteremia was found to be in a statistically significant correlation with signs and symptoms of life-threatening conditions (p<0.01), early-onset and late-onset infections and other disorders occurring in newborn infants (p<0.05), mostly of the female sex . CONCLUSION: It seems that asymptomatic bacteremia cannot be considered harmless but appears to influence the health of newborns. Biol Chem, 2001 Jul, 382(7), 1095 - 9 Isolation and characterization of a highly specific serine endopeptidase from an oral strain of Staphylococcus epidermidis; Moon JL et al.; Infection by Staphylococcus epidermidis, an opportunistic pathogen, has become a major problem due to the increased use of implanted medical devices and the growing number of patients who are therapeutically or infectiously immunosuppressed . These infections appear to proceed via modulation of the coagulation and complement systems . In this communication we describe the purification and characterization of a novel extracellular proteinase from an oral strain of S . epidermidis that can degrade fibrinogen, complement protein C5, and several other proteins . This proteinase has a strong preference for cleavage after glutamic acid residues, but not after aspartic acid . The S . epidermidis enzyme may be a multifunctional protein which not only provides this organism with both the ability to evade the complement defense system and to dysregulate the coagulation cascade, but also supplies nutrients for its growth through the degradation of Glu-rich proteins. Ann Fr Anesth Reanim, 2001 Aug, 20(7), 600 - 3 {Evaluation of antibacterial filters for peridural obstetrical anesthesia}; Morris W et al.; OBJECTIVES: To assess the antibacterial efficiency of filters used in obstetrics when epidural top-ups are performed . STUDY DESIGN: Observational prospective study . PATIENTS AND METHODS: We aseptically collected 201 antibacterial filters that had been used for top-ups with ropivacaine +/- sufentanil for epidural analgesia during labour . We flushed them first with 2 mL of saline and then with 2 mL of a solution containing 1.5 x 10(6) Staphylococcus epidermidis/mL . The filtrates were incubated at 37 degrees C for 72 h . Number of top-ups and duration of epidural analgesia are expressed as median (extremes) . RESULTS: 3 (1-10) top-ups were performed for labour analgesia over a period of 6.5 h (1.8-18) . After filtering, all the solutions were found to be sterile . Especially, when using Staphylococcus epidermidis solutions, bacteria were not found beyond any filter . These results suggest the integrity of the filter membrane after several boluses . No infection related to epidural analgesia was reported . CONCLUSION: Antibacterial filters provide a good protection against a potentially contaminated procedure during epidural top-ups. J Soc Biol, 2001, 195(1), 65 - 8 {T-cell-depleted HLA non-identical bone marrow transplantation in the child: prevention of graft-versus-host reaction by administration of donor T lymphocytes alloreactive against the recipient}; Cavazzana-Calvo M et al.; The success of HSCT from HLA partially disparate donors depends on the development of new strategies able to efficiently prevent GVHD and to protect patients from infections and relapse . Using an immunotoxin (IT) directed against the alpha-chain (p55) of the human IL-2r (RFT5-SMPT-dgA), we have previously shown that it is possible to kill mature T cells activated towards a specific HLA complex by a one-way MLR . We designed a clinical trial assessing the effect of infusing increasing doses of T lymphocytes in the setting of children recipients of non HLA genetically identical HSCT . Thirteen patients have been enrolled from September 1998 to April 2000 and fourteen HSCT have been realized in 13 patients (pts) . Donors were MUD in 3 cases and familial HLA partially disparate in the remaining cases . Allodepleted donor T cells were injected between day +14 and day +30 provided that ATG was undetectable in the serum and blood PMN counts was > 500/microliter . The mean age of these patients was 17 months (range 1 to 42) . Diagnosis included immune deficient and malignant hemopathies . Three patients received 1 x 10(5) allodepleted T cell/kg, 7 patients received 4 x 10(5)/kg and 4 patients received 6 x 10(5)/kg allodepleted T cells . Full inhibition of MLR was achieved in 12 out of 14 cases . In two cases, a residual T cell reactivity to the recipient was observed (4 to 5%) and patients developed grade II aGVHD . aGVHD occurred in 4 out of 11 grafted patients (all grade II) . No chronic GVHD has developed, so far . Three patients died from severe VOD or PHT at day +34, day 51 and day +166, while one infected patient by VZV, CMV and EBV before HSCT died 6 months after transplantation from meningoencephalitis and another patient died from relapse at day +291 . The patient for which there was no engraftment died at day +48 from staphylococcus infection . Overall survival is 54%, with a median follow up of 8 months; the mean time to reach a blood lymphocyte count > 500 was 41 days, to reach a CD3 count > 300 microliters 63 days (20-111), CD4 > 200 microliters 97 days and positive mitogen-induced proliferation 90 days . In three patients, a tetanus-toxoid positive proliferation was detected before immunization . From this intermediate analysis, we conclude that 1) specific allodepletion is an effective approach to prevent aGVHD in a haploincompatible setting, 2) data on immunological reconstitution suggest that infused T cells do survive and expand . A higher number of patients must be enrolled to determine the optimal number of T cells to infuse. Acta Crystallogr D Biol Crystallogr, 2001 Sep, 57(Pt 9), 1270 - 5 Epub 2001 Aug 23. Structure of staphylococcal enterotoxin C2 at various pH levels; Kumaran D et al.; The three-dimensional structure of staphylococcal enterotoxin C2 (SEC2), a toxin as well as a superantigen, has been determined at various pH levels from two different crystal forms, tetragonal (pH 5.0, 5.5, 6.0 and 6.5) and monoclinic (pH 8.0) at 100 and 293 K, respectively, by the molecular-replacement method . Tetragonal crystals belong to space group P4(3)2(1)2, with unit-cell parameters a = b = 42.68, c = 289.15 A (at pH 5.0), and monoclinic crystals to space group P2(1), with unit-cell parameters a = 43.3, b = 70.6, c = 42.2 A, beta = 90.3 degrees . SEC2 contains a zinc-binding motif, D+HExxH, and accordingly a Zn atom has been identified . The coordination of the zinc ion suggests that it may be catalytic zinc rather than structural, but there is so far no biological evidence that it possesses catalytic activity . However, superantigen staphylococcal exfoliative toxins A and B have been shown to have enzymatic activity after their fold was identified to be similar to that of serine protease . The structure and its conformation are similar to the previously reported structures of SEC2 . Though it was expected that the zinc ion may be leached out, as the histidines coordinating the zinc ion are expected to be protonated below pH 6.0, zinc is present at all pH values . The coordination distances to zinc increase with decreasing pH, with the distances being the least at pH 8.0 . The results of automated model building using the ARP/wARP program for different data sets collected at various pH values are discussed. Appl Environ Microbiol, 2001 Sep, 67(9), 4096 - 104 Characterization of the single superoxide dismutase of Staphylococcus xylosus; Barriere C et al.; Staphylococcus xylosus is a facultative anaerobic bacterium used as a starter culture for fermented meat products . In an attempt to analyze the antioxidant capacities of this organism, the superoxide dismutase (SOD) was characterized . S . xylosus contains a single cytoplasmic SOD, which was not inhibited by H2O2 . The SOD activity in crude extracts was completely lost upon metal depletion, but it could be recovered by manganese and very weakly by iron . It is therefore suggested that the S . xylosus SOD is a manganese-preferring enzyme . The corresponding gene, sod, was isolated from a genomic library of S . xylosus DNA and complemented the growth defect of an Escherichia coli SOD-deficient mutant . As deduced from the nucleotide sequence, sod encodes a protein of 199 amino acids with a molecular mass of 22.5 kDa . Two transcriptional start sites 25 and 120 bp upstream of the sod start codon were identified . A terminator-like structure downstream of the gene suggested a monocistronic sod mRNA . Regulation of sod expression was studied using fusions of the sod promoters to a genomic promoterless beta-galactosidase gene . The sod expression was not affected by manganese and increased slightly with paraquat . It was induced during stationary phase in a complex medium but not in a chemically defined medium . To investigate the physiological role of SOD, a mutant devoid of SOD activity was constructed . Growth experiments showed that sod is not essential for aerobic growth in complex medium . However, in chemically defined medium without leucine, isoleucine, and valine, the sod mutant hardly grew, in contrast to the wild-type strain . In addition, the mutant was sensitive to hyperbaric oxygen and to paraquat . Therefore, sod plays an important role in the protection of S . xylosus from oxidative stress. Ann Vasc Surg, 2001 Jul, 15(4), 421 - 9 Experimental treatment of vascular graft infection due to Staphylococcus epidermidis by in situ replacement with a rifampin-bonded polyester graft; Coggia M et al.; In situ prosthetic graft replacement (ISPGR) of an infected prosthesis raises the risk of recurrent infection in the new graft, especially in cases involving drug-resistant microorganisms . The purpose of this animal study was to evaluate in situ replacement of a vascular graft infected by a highly rifampin-resistant strain of Staphylococcus epidermidis with the use of a rifampin-bonded polyester graft . Antibiotic bonding was obtained by soaking grafts in a high dose of rifampin solution (60 mg/mL) . The infrarenal abdominal aorta of 20 dogs was replaced using a polyester prosthesis infected with a highly rifampin-resistant strain of Staphylococcus epidermidis . One week later, the 18 surviving animals were randomized into three groups . Group I (n = 6) did not undergo reoperation . Group II (n = 6) underwent ISPGR using a rifampin-bonded prosthesis . Group III (n = 6) underwent ISPGR using an untreated prosthesis . All surviving animals were killed 28 days after the first procedure . Infectious signs were noted and bacteriological study was carried out on explanted prostheses and various tissue samples . The findings of this experimental study show that soaking a polyester prosthesis in a high-dose rifampin solution can prevent reinfection after in situ replacement of a prosthesis infected by a highly rifampin-resistant Staphylococcus epidermidis. J Cataract Refract Surg, 2001 Aug, 27(8), 1298 - 302 In vitro adherence of Staphylococcus epidermidis to silicone punctual plugs and collagen implants; John T et al.; PURPOSE: To evaluate in vitro adherence of Staphylococcus epidermidis to silicone punctal plugs and collagen implants . SETTING: Loyola University Medical Center, Maywood, Illinois, USA . METHODS: Silicone punctal plugs and collagen implants were exposed to S epidermidis (3 x 10(8) colony forming units/mL) for 0, 5, 30, and 60 minutes, rinsed in sterile saline, and processed for light, scanning (SEM), and transmission (TEM) electron microscopy . Scanning electron microscopy (x2000) was used to quantify bacteria/mm2 adhering to the devices . RESULTS: The mean S epidermidis/mm2 +/- (SD) adhering to each device were as follows: baseline, silicone punctal plug, 1593 +/- 899, and collagen implant, 7168 +/- 2895 (P =.000, paired Student t test); 5 minutes, silicone punctal plug, 3833 +/- 537, and collagen implant, 6571 +/- 2240 (P =.008); 30 minutes, silicone punctal plug, 13 988 +/- 9076, and collagen implant, 10 404 +/- 1731 (P =.2616); and 60 minutes, silicone punctal plug, 12 644 +/- 10 402, and collagen implant, 11 748 +/- 2685 (P =.8056) . CONCLUSIONS: Staphylococcus epidermidis adhered significantly more to collagen implants than to silicone punctal plugs at 0 and 5 minutes . No significant difference in bacterial adherence was seen at 30 and 60 minutes . For both devices, bacterial adherence increased with increasing exposure. J Investig Med, 2001 Sep, 49(5), 442 - 9 Tacrolimus and cyclosporine A inhibit allostimulatory capacity and cytokine production of human myeloid dendritic cells; Szabo G et al.; Myeloid dendritic cells (DCs) are pivotal in the recognition of alloantigens and, therefore, in the induction of allograft rejection . Induction of alloreactive T cell proliferation by myeloid DCs depends on the maturation of DCs, the expression of costimulatory molecules, and the cytokine environment . This study investigated the effects of tacrolimus and cyclosporine A (CsA) on DC maturation and allostimulatory capacity . Myeloid DCs were propagated from normal blood monocytes with interleukin (IL) 4 and GM-CSF for 7 days in the presence or absence of tacrolimus (FK506; 10 nM) or CsA (1 microg/mL) . Exposure of DCs during maturation to tacrolimus or CsA resulted in no significant change in the expression of DC phenotypic markers, including CD80, CD86, and HLA Class I and II antigens determined by flow cytometry . T cell proliferation in one-way, mixed-leukocyte reaction experiments revealed a decreased allostimulatory capacity of DCs that matured in the presence of tacrolimus or CsA compared with untreated controls (P<0.02) . Production of inflammatory cytokines, tumor necrosis factor alpha (P<0.04) and IL-12 (P<0.04) in response to lipopolysaccharide (1 microg/mL) or staphylococcal enterotoxin B (1 microg/mL) induction was significantly reduced in DCs exposed to tacrolimus or CsA during maturation . In contrast, production of the immuninhibitory cytokine IL-10 was not decreased in tacrolimus- or CsA-treated DCs . These results suggest that tacrolimus and CsA inhibit the allostimulatory capacity of in vitro-generated myeloid DCs without significant effects on DC phenotypic maturation . Decreased production of IL-12 and tumor necrosis factor alpha, but not of IL-10, is likely to contribute to the impaired accessory-cell function of tacrolimus- and CsA-treated DCs . Thus, tacrolimus and CsA can inhibit recognition of alloantigens by decreasing the accessory-cell capacity of monocyte-derived myeloid DCs. Nephrol Dial Transplant, 2001 Sep, 16(9), 1845 - 9 Long-term experience with the Thomas shunt, the forgotten permanent vascular access for haemodialysis; Coronel F et al.; BACKGROUND: Vascular access complications are the main cause of hospitalization in dialysis patients . The difficulty in creating and maintaining vascular access after several years on haemodialysis (HD) remains the primary problem in these patients . The femoro-femoral Thomas shunt is a permanent vascular access that was used in the 1970s and is all but forgotten at present . We analysed our experience with the Thomas shunt since 1979 in patients with no other possibility of regular vascular access . METHODS: We retrospectively studied 27 Thomas shunts implanted in 10 patients, aged 27-75 years at the time of first shunt implantation . Prior to implantation of the Thomas shunt, these patients had experienced 80 failed vascular accesses (plus four patients on CAPD), with an average of 8.6 accesses per patient . All Thomas shunts were implanted in femoral vessels . Clinical data were extracted from hospital and dialysis unit records and were analysed for efficacy, complications, and duration of patency . RESULTS: Total follow-up was 1176 months, with an average shunt duration of 43.7 months (range 3-151 months) . One-, 2-, 3- and 6-year survival rates were 85, 57, 49 and 25% respectively . Five patients spent more than 10 years on HD using the Thomas shunt, and one patient had the same unit for 12.5 years . A high blood flow (450 ml/min) was obtained, without recirculation, due to the characteristics of this shunt . Efficacy, measured as percentage urea reduction (PRU), was high (on average 77.8+/-1.5%) . The infection incidence was one episode every 37.5 patient-months, Staphylococcus species being the most commonly isolated . There were no shunt removals because of infection . The most important cause of shunt withdrawal was thrombosis, with an incidence of one episode every 7 patient-months . Percutaneous angioplasty was successful in the majority of stenosis episodes . CONCLUSIONS: This study indicates that the Thomas shunt provides a good permanent vascular access for HD patients who have no other possibility of a regular vascular access . This shunt offers high dialysis efficacy without recirculation and an access duration comparable to AV fistulae . For these reasons the Thomas shunt should continue to be used as a vascular access in HD. Clin Nephrol, 2001 Aug, 56(2), 124 - 31 Etiology of bacterial septicemia in chronic dialysis patients in the United States; Abbott KC et al.; AIMS: Previous studies have identified risk factors for and mortality associated with hospitalized septicemia (septicemia) in patients with end-stage renal disease (ESRD) . However, the etiologies of septicemia in this population have not been determined . METHODS: 327,993 patients in the United States Renal Data System initiated on ESRD therapy between January 1, 1992, and June 30, 1997, who never received renal transplants were analyzed in a retrospective registry study of hospitalized cases of septicemia (ICD9 038.x) . RESULTS: Of the study population, 43,441 (13.2%) had septicemia . In logistic regression analysis, septicemia was associated with female gender, African American race, ESRD due to diabetes and obstruction/chronic pyelonephritis, increased age, and hemodialysis (vs . peritoneal dialysis) . Polycystic kidney disease and glomerulonephritis were associated with decreased risk of septicemia . At initiation of dialysis, higher hemoglobin, and lower weight, creatinine, and albumin were associated with septicemia . Among patients with septicemia, the leading specified etiologies were Staphylococcus (34%) and miscellaneous Gram-negative rods (21.7%) . Etiologies of septicemia were significantly associated with hemodialysis (Gram-positives and Pneumococcus), female gender (Gram-negatives except Pseudomonas), African American race (Staphylococcus), and diabetes (global) . Hemodialysis (vs . peritoneal dialysis) and Staphylococcus as an etiology of septicemia were associated with repeated hospitalizations for septicemia . Septicemia was independently associated with patient mortality, and African Americans and females with septicemia were at disproportionately greater risk of mortality . CONCLUSIONS: This study identifies significant associations between septicemia and female gender, African American race, hemodialysis, and higher hemoglobin . Significant associations between etiologies of septicemia and patient subgroups are also identified. Mt Sinai J Med, 2001 Sep-Oct, 68(4-5), 298 - 308 Evaluation and treatment of itching in HIV-infected patients; Gelfand JM et al.; Itching is a common complaint among patients infected with HIV and may cause significant morbidity and embarrassment . Although idiopathic HIV-pruritus has been described, it is probably less common than was previously thought . In most patients, a careful history and physical examination will show that a dermatosis accounts for their pruritus . Dry skin, seborrheic dermatitis, eczema, psoriasis, pruritic papular eruption, staphylococcal folliculitis and prurigo nodularis are frequently encountered in these patients . These common dermatoses, drug eruptions, several rarer conditions and systemic causes of itching should be excluded before diagnosing idiopathic HIV-pruritus . Treatment should be directed to the underlying skin problem and may be supplemented with sedating antihistamines . Phototherapy is a safe and effective therapeutic modality for many pruritic dermatoses as well as for idiopathic pruritus. Biochim Biophys Acta, 2001 Aug 13, 1548(2), 203 - 12 Conformational adjustments of SNase R and its N-terminal fragments probed by monoclonal antibodies; Qin ZJ et al.; Two monoclonal antibodies specific for staphylococcal nuclease R (SNase R) (McAb2C9 and McAb1B8) were prepared and used to probe protein folding during peptide elongation, by measuring antibody binding to seven N-terminal fragments (SNR141, SNR135, SNR121, SNR110, SNR102, SNR79 and SNR52) of SNase R . Comparative studies of the conformations of the N-terminal fragments have shown that all seven fragments of SNase R have a certain amount of residual structure, indicating that folding may occur during elongation of the nascent peptide chain . We show that the binding abilities of the intact enzyme and its seven fragments to the monoclonal antibodies are not simply proportional to the length of the peptide chain, suggesting that there may be continuous conformational adjustment in the nascent peptide chain as new C-terminal amino acids are added . A folding intermediate close in structure to the native state but with structural features in common with SNR121 is highly populated in 0.6 M GuHCl, and is also formed transiently during folding. Am Surg, 2001 Aug, 67(8), 745 - 7 Postoperative staphylococcal toxic shock syndrome due to pre-existing staphylococcal infection: case report and review of the literature; Odom SR et al.; Staphylococcal postoperative toxic shock syndrome (PTSS) has been associated with a variety of surgical procedures . It is generally believed that the source of infection is acquired at or near the time of surgery . PTSS has been specifically associated with nasal packing, insertion of hardware, surgical drains, retained foreign materials, and breaks in sterile technique . Although PTSS has been associated with postoperative abscesses, development of PTSS after surgery of a pre-existing source of infection has not been described . We report a case of PTSS that developed after vertebral abscess drainage, and we review the literature to determine the incidence of PTSS due to preexisting staphylococcal infection. Adv Perit Dial, 2001, 17, 98 - 100 Bag exchange in continuous ambulatory peritoneal dialysis without use of a face mask: experience of five years; Figueiredo AE et al.; This article describes our five-year experience of continuous ambulatory peritoneal dialysis (CAPD) with bag exchanges performed without use of a face mask . The study took place in the renal unit at a university hospital . All patients admitted to the CAPD program from February 1995 to March 2000 were trained to perform bag exchanges without use of a face mask . Occurrence of peritonitis episodes was the outcome of interest . We evaluated 94 patients (52 women, 42 men) with a mean age of 48 +/- 21 years and a total follow-up of 50,502 patient-days . During that time, 79 episodes of peritonitis occurred in 46 patients, for a peritonitis rate of 0.57 episodes/year . The most frequently isolated micro-organisms were Staphylococcus epidermidis in 20 patients (25.3%) and S . aureus in 11 patients (13.9%) . Renal transplantation was the major cause of drop-out {23 patients (43.4%)}, followed by peritonitis {14 patients (26.4%)}, death due to cardiovascular complications {9 patients (17.0%)}, loss of ultrafiltration {2 patients (3.8%)}, and other causes {5 patients (9.4%)} . The probability of being free of peritonitis at 12 months was 0.60, and at 60 months, 0.37 . Peritonitis rates during the study period were not different from those reported by other centers, supporting the hypothesis that routine use of a face mask during CAPD bag exchange may be unnecessary. J Interferon Cytokine Res, 2001 Jul, 21(7), 507 - 14 Cytokines and cell surface receptors as target end points of immunosuppression with cyclosporine A; Sindhi R et al.; Targets of cyclosporine (CsA) were identified from an array of stimulated lymphocyte responses (sLR) comprising 34 stimulation conditions in whole blood from 3 normal human volunteers (NHV) containing clinically relevant CsA concentrations (0-1200 ng/ml) in vitro . In whole blood from 5 additional NHV, selected targets (intracellular interleukin-2 {IL-2}, tumor-necrosis factor-alpha {TNF-alpha}, and interferon-gamma {IFN-gamma}) were measured in phorbol myristate acetate (PMA)-ionomycin-stimulated T lymphocytes . Effect:concentration relationships were analyzed with E(max) pharmacodynamic (PD) equations and expressed as the concentration associated with one-half maximal inhibitory effect (EC(50)) . CsA demonstrated a rich matrix of inhibitory effects on T cells (CD3(+)), B cells (CD19(+)), dendritic cells (DC) (CD11c(+)), and basophils (CD123(+)) but not on monocytes (CD14(+)) (n = 3) . PD analyses suggested that the EC(50) of CsA (1) for IL-2 in CD3(+) cells in NHV (n = 8) was similar to the EC(50) demonstrated by us previously in CD4(+) cells from transplanted patients (n = 13) (EC(50) = 260 ng/ml vs . 249 ng/ml), (2) for each cytokine was different under identical stimulation conditions (TNF-alpha, 324 ng/ml; IFN-gamma, 504 ng/ml), and (3) was relatively constant for a given cytokine under different stimulation conditions (e.g., PMA-ionomycin or the staphylococcal enterotoxin B {SEB} superantigen) . In conclusion, inhibition of cytokine targets by CsA is concentration dependent . Further, a given CsA concentration may produce similar inhibitory effects across different stimulation conditions . Measurement of cytokine target expression may, therefore, allow effect-controlled administration of CsA during clinical transplantation. Proc Natl Acad Sci U S A, 2001 Aug 28, 98(18), 10137 - 41 Epub 2001 Aug 14. Partitioning of a polymer into a nanoscopic protein pore obeys a simple scaling law; Movileanu L et al.; The dependence of the rate on polymer mass was examined for the reaction of four sulfhydryl-directed poly(ethylene glycol) reagents with cysteine residues located in the lumen of the staphylococcal alpha-hemolysin pore . The logarithms of the apparent rate constants for a particular site in the lumen were proportional to N, the number of repeat units in a polymer chain . The proportionality constant was -(a/D)(5/3), where a is the persistence length of the polymer ( approximately 3.5A) and D is the diameter of the pore . Despite some incongruencies with the assumptions of the derivation, the result suggests that the polymers partition into the lumen of the pore according to the simple scaling law of Daoud and de Gennes, c(pore)/c(solution) = exp(-N(a/D)(5/3)) . Therefore, the measured reaction rates yield an estimate of the diameter of the pore and might be applied to determine the approximate dimensions of cavities within other similar proteins. J Perinatol, 2001 Apr-May, 21(3), 186 - 92 Nosocomial coagulase negative staphylococcal (CoNS) catheter-related sepsis in preterm infants: definition, diagnosis, prophylaxis, and prevention; Craft A et al.; Nosocomial infections with coagulase negative staphylococcus (CoNS) are a frequent and significant cause of morbidity in the preterm infant . Infections diagnosed after the first 72 hours of life are arbitrarily deemed to be "nosocomial." There are many difficulties encountered in efforts to evaluate and compare nosocomial sepsis in the NICU . An issue of primary concern is the lack of uniformity in the definition of sepsis in the NICU . Based on the frequency of positive blood cultures in infants less than 1000 g, it appears reasonable to evaluate methods for the prevention of nosocomial sepsis . These include prophylactic antibiotic administration, antiseptic impregnated catheters, and the use of an antibiotic lock technique. Transplantation, 2001 Aug 15, 72(3), 422 - 7 Measurement of mycophenolate mofetil effect in transplant recipients; Ogawa N et al.; BACKGROUND: Immunosuppression involves the nature of the immunosuppressive agents and individual differences in patient factors . We investigated whether the effect of mycophenolate mofetil (MMF) is measurable using an in vitro measure of immunocompetence and related its effects to cyclosporine (CsA) in vitro . METHODS: Liver or kidney transplant recipients receiving prednisone; CsA or tacrolimus; and MMF, azathioprine (AZA), or neither, were studied . Immunocompetence was assessed by one-way mixed lymphocyte culture using patients' peripheral blood leukocytes (PBL) and three validated stimulators . The effect of immunosuppressive agents added in vitro on normal PBL stimulation by Staphylococcus enterotoxin B was determined by the carboxyfluorescein diacetate succinimidyl ester measurement of division . RESULTS: Patients receiving MMF had an average immunocompetence level of 12+/-23, compared with 39.7+/-65 and 25.5+/-42 for those receiving AZA or neither AZA nor MMF, respectively . Thus, there was an approximately 80% suppression of the response in the MMF group . Assessment of normal cell division revealed that CsA allowed multiple cell generations but suppressed the numbers of cells in each, whereas MMF blocked proliferation into subsequent generations . Addition of clinically relevant levels of mycophenolic acid, the active agent for MMF, added to more moderate levels of CsA, was required to achieve greater than 80% suppression, consistent with the degree of immunocompetence depression measured in patients . CONCLUSIONS: These data provide the novel finding that the effect of MMF treatment on patients is measurable in their PBL as decreased immunocompetence in vitro . The effect of MMF on normal PBL approximates the 80% inhibition that we found in patients . Moreover, the effect of MMF on cell division provides a rationale for the superior effectiveness of regimens including MMF. Antimicrob Agents Chemother, 2001 Sep, 45(9), 2460 - 7 Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study; Wysocki M et al.; A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections . A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%) . Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared . Microbiological and clinical outcomes and safety were similar . CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001) . The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) {P = 0.026} and 414 versus 818 g(2) {P = 0.057}, respectively) . The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001) . In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV. Infect Immun, 2001 Sep, 69(9), 5949 - 52 Role of endogenous interleukin-12 in immune response to staphylococcal enterotoxin B in mice; Lauw FN et al.; In the present study, the roles of interleukin 12 (IL-12) and IL-18 and their possible interaction during superantigen-induced responses were studied by injection of staphylococcal enterotoxin B (SEB) into mice . These data suggest that the role of IL-12 in SEB-induced responses is limited to sustaining gamma interferon release by an IL-18-independent mechanism. J Pediatr Ophthalmol Strabismus, 2001 Jul-Aug, 38(4), 207 - 12 Diagnosis and management of chronic blepharokeratoconjunctivitis in children; Farpour B et al.; PURPOSE: To describe the history, symptoms, and clinical signs and discuss the treatment of blepharokeratoconjunctivitis . METHODS: Eight children (five girls and three boys), ranging in age from 3.5-13 years, were clinically diagnosed with blepharokeratoconjunctivitis . Microbiology studies were performed in four of the eight children . Treatment consisted of lid hygiene, oral erythromycin suspension, and preservative-free steroids . Duration of therapy was directed by clinical improvement . RESULTS: Average age at onset was 3.2 years (range: 0.5-8 years) . Lid disease, conjunctival redness, and inferior superficial corneal vascularization were consistent features (100%) . Other signs were punctate corneal epithelial staining, inferior subepithelial vascularization and infiltrate, conjunctival phlyctenules, corneal phlyctenules, and circumferential pannus . Microbiology testing demonstrated coagulase-negative staphylococcus and Propionibacterium acnes . Average follow-up was 8.3 months (range: 2-23 months) . All patients had relief of symptoms within 2-3 weeks . Clinical signs took more time to regress but all had progressive improvement of the ocular surface by 2 months . Blepharokeratoconjunctivitis reactivated in all patients during follow-up, and repeat therapy was administered . CONCLUSION: Blepharokeratoconjunctivitis in childhood is a chronic inflammatory process that can have different presentations . It can be successfully treated with oral erythromycin and topical steroids. J Long Term Eff Med Implants, 2001, 11(1-2), 1 - 12 Infections related to breast implants reported to the Food and Drug Administration, 1977-1997; Brown SL et al.; The FDA has a surveillance system for monitoring adverse events related to medical devices . Infection reports submitted to the FDA by breast implant manufacturers between 1977 and 1997 are characterized . Two cases of death caused by toxic shock syndrome after mammoplasty reported to the FDA are presented . Overall, 1,971 reports with a principal adverse event of infection were reported in this time frame . There was a large increase in the number of reports on infections related to breast implants between 1992 and 1995 due to the publicity and litigation surrounding breast implants . When an organism was identified in the report, the most common organism reported was Staphylococcus sp . Information on the time between the implantation and the onset of the infection or the explantation of the implant was not always reported . However, in reports that did contain this information, there were differences between the length of time to infection onset reported for saline breast implants (earlier) compared to silicone gel breast implants (later) . More than half of the reports (56.6%) asserted only that there was an infection and that breast implants were explanted as a result; the remaining reports asserted that infection and other signs, symptoms, or diagnoses had afflicted the patient. Vnitr Lek, 2001 Jun, 47(6), 375 - 80 {Pitfalls in the diagnosis of infectious endocarditis}; Schildberger J et al.; A group of 63 patients with infectious endocarditis (IE) (1991-1998) was subjected to a detailed retrospective analysis . The authors investigated the age of the patients, site of IE, type of infectious agent, incidence of coinciding diseases or interventions in the close premorbid period of IE, size of vegetation, incidence of embilizations, heart failure, indications for vital early cardiosurgery, number of deaths . From the clinical analysis it may be concluded: 1 . There is a new group of patients with IE, who before development of the disease have no manifest cardiac disease who however frequently suffer from another coinciding disease; 2 . There is a significant increase of dextrolateral IE (frequently "pacemaker" IE); 3 . The ratio of staphylococcal strains in the etiopathogenesis of IE is rising; 4 . The mean age of the affected patients is rising (as well as the age scatter); 5 . IE is unfortunately frequently diagnosed only after embolization of the vegetation (mostly cerebrovascular attacks) in obscure febrile conditions. Int J Syst Evol Microbiol, 2001 Jul, 51(Pt 4), 1343 - 7 Comparative ribotyping of Staphylococcus intermedius isolated from members of the Canoidea gives possible evidence for host-specificity and co-evolution of bacteria and hosts; Aarestrup FM; A total of 41 Staphylococcus intermedius isolates were isolated from skin of healthy members of six phylogenetic groups within the Canoidea (the dog family, skunk subfamily, weasel subfamily, racoon family, red panda and bear family) of different geographical origin and compared by EcoRI ribotyping and cluster analysis . The S . intermedius isolates from the different families and subfamilies clustered together in separate groups, almost completely following the phylogenetic relationship of the animal hosts . These ribotype data indicate host-specificity of different types of S . intermedius and suggest co-evolution between the animal hosts within the Canoidea and S . intermedius. Eur J Biochem, 2001 Aug, 268(15), 4269 - 77 Recombinant human factor VIII-specific affinity ligands selected from phage-displayed combinatorial libraries of protein A; Nord K et al.; Factor VIII-specific affibodies were selected from phage displayed libraries constructed by combinatorial mutagenesis of an alpha helical bacterial receptor domain derived from staphylococcal protein A . Bead-immobilized recombinant human factor VIII (rVIII) (80 and 90 kDa chains) protein was used during competitive biopannings in the presence of free 80-kDa chain protein, resulting in the selection of several binders that showed dissociation constants (Kd) in the range 100-200 nM as determined by biosensor analyses . One variant (Z{rVIII:3}, 90-kDa chain specific) was further characterized in small-scale affinity chromatography experiments, and showed efficient and selective recovery of biologically active rVIII from Chinese hamster ovary cell supernatant-derived feed stocks . The purity of the enriched rVIII was comparable with rVIII material purified by immunoaffinity chromatography using a 90-kDa chain-specific monoclonal antibody . Interestingly, epitope mapping showed that the monoclonal antibody and the affibody ligand competed for the same or at least overlapping epitopes on rVIII . In addition, the Z{rVIII:3} variant was produced by peptide synthesis with a C-terminal cysteine to enable directed coupling to solid supports . This 59-residue protein was analyzed by circular dichroism and showed a secondary structure content similar to that of the parental Z domain used as scaffold . In biosensor studies, the synthetic affibody was immobilized recruiting the C-terminal cysteine residue, and demonstrated to bind both recombinantly produced and plasma-derived factor VIII . From a secondary library, constructed by re-randomization of relevant positions identified after alignment of the first-generation variants, a panel of affinity-improved second-generation affibodies were selected of which one clone showed a dissociation constant (Kd) for rVIII of 5 nM . Several of these variants also showed higher apparent binding efficiencies towards rVIII when analyzed as immobilized ligands in biosensor experiments . Taken together, the results suggest that affibody ligands produced by bacterial or synthetic routes could be of interest as an alternative to monoclonal antibodies in purification processes or as diagnostic or monitoring tools. Eur J Biochem, 2001 Aug, 268(15), 4227 - 32 Probing the conformational state of a truncated staphylococcal nuclease R using time of flight mass spectrometry with limited proteolysis; Yang F et al.; The conformational state of C-terminally truncated staphylococcal nuclease R (SNR135), with and without bound ligands, has been studied by performing limited proteolysis with a specific endoproteinase Glu-C followed by electrophoresis and mass spectrometry . Comparison of the accessibility of the cleavage sites shows that the C-terminal truncation of 14 amino-acid residues causes significant unfolding of the C-terminal part of alpha helix 1 and the center of alpha helix 2, but there is little effect on other regions of the nuclease, in particular the N-terminal subdomain, which includes the active site of the nuclease . The truncation also makes the overall conformation of the nuclease more loose and flexible . Binding of ligands makes helices 1 and 2 more resistant to protease Glu-C attack and converts the partially unfolded state to a native-like state, although the conformational stability of the SNR135 complex is still much lower than that of the full-length enzyme . The results suggest that the amino-acid residues around the active site in the truncated nuclease are arranged in a similar topology to those in the full-length nuclease . The study shows that there is a clear-cut correlation between protease susceptibility and conformational stability of the protein, and the initial proteolytic events are the most critical for evaluating the conformational features of the protein . This study demonstrates how mass spectrometry can be combined with limited proteolysis to observe conformational changes induced by ligand binding. J Ethnopharmacol, 2001 Sep, 77(1), 85 - 90 Immunomodulatory effect of concentrated lime juice extract on activated human mononuclear cells; Gharagozloo M et al.; In this study, the in vitro immunomodulatory effect of concentrated juice of Citrus aurantifolia cv . swingle (Lime) was investigated . Clarified fresh lime juice was concentrated by freeze-drying . After dialysis against phosphate buffered saline and sterilization by a Millipore filter, it was used for further experiments . Immunogenic property of the CLJ extract was documented by production of specific polyclonal antibodies in rabbits . The immunomodulatory effect of the extract was tested in mitogen activated cultured mononuclear cells . The culture results indicated that proliferation of phytohemagglutinin (PHA) activated mononuclear cells were significantly inhibited by 250 and 500 microg/ml of CLJ extract, whereas only 500 microg/ml of the extract could inhibit proliferation of staphylococcal protein A (SPA) activated mononuclear cells (P<0.05) . The abrogation of this inhibitory effect of the CLJ extract was noted by adding anti-CLJ antibody to the lymphocyte culture . Considering these data, it can be concluded that the CLJ extract possesses immunomodulatory principles, which may mainly be due to the protein components of the extract. Protein Expr Purif, 2001 Aug, 22(3), 467 - 71 Cloning, expression, and purification of the Staphylococcus simulans lysostaphin using the intein-chitin-binding domain (CBD) system; Szweda P et al.; The Staphylococcus simulans gene encoding lysostaphin has been PCR amplified from pRG5 recombinant plasmid (ATCC 67076) and cloned into Escherichia coli expression pTYB12 vector (IMPACT-CN System, New England BioLabs) which allows the overexpression of a target protein as a fusion to a self-cleavable affinity tag . The self-cleavage activity of the intein allows the release of the lysostaphin enzyme from the chitin-bound intein tag, resulting in a single-column purification of the target protein . This abundant overproduction allows purifying milligram amounts of the enzyme . Eur J Immunol, 2001 Aug, 31(8), 2302 - 12 Superantigen overcomes resistance of IL-6-deficient mice towards MOG-induced EAE by a TNFR1 controlled pathway; Eugster HP et al.; Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein peptide 35-55 (MOG) leads to a chronic form of disease characterized by demyelination, inflammation and gliosis in the central nervous system (CNS) . Recently IL-6 and LT alpha were found to be required for induction of the disease . The main features associated with EAE resistance of IL-6(-/-) and LT alpha(-/-) mice were reduced T cell proliferation and endothelial activation . As shown here treatment of MOG-immunized IL-6(-/-) mice with staphylococcal enterotoxin B (SEB)reversed their resistance to MOG-induced EAE . SEB failed to restore susceptibility to EAE in LT alpha(-/-) mice . The effect of SEB to induce EAE in IL-6(-/-) mice depends on TNF receptor type 1 (TNFR1) signaling because IL-6/TNF/LT alpha(-/-) and IL-6/TNFR1(-/-) are refractory to SEB . TNFR1 is involved in SEB induced trafficking of T cells into the CNS as evidenced by the failure to up-regulate VCAM-1 on CNS endothelium and lack of accumulation of V beta 8(+) T cells in the CNS of IL-6/TNFR1(-/-) mice upon immunization with MOG and treatment with SEB . The course of SEB triggered EAE in MOG immunized IL-6(-/-) mice was characterized by reduced severity and duration of clinical manifestations, which were associated with a significant drop of CNS infiltrating neutrophils and MIP-2 expression after peak disease . Taken collectively the effect of SEB to overcome EAE resistance points to a transient IL-6 independent but TNFR1 dependent proinflamatory pathway in EAE pathogenesis and suggests a crucial function for IL-6 in disease perpetuation. Anal Biochem, 2001 Aug 1, 295(1), 22 - 30 Dual labeling of a binding protein allows for specific fluorescence detection of native protein; Karlstrom A et al.; Fluorescence resonance energy transfer has been investigated in the context of specific detection of unlabeled proteins . A model system based on the staphylococcal protein A (SPA)-IgG interaction was designed, in which a single domain was engineered to facilitate site-specific incorporation of fluorophores . An Asn23Cys mutant of the B domain from SPA was expressed in Escherichia coli and subsequently labeled at the introduced unique thiol and at an amino group, using N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-IAEDANS) and succinimidyl 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoate (NBD-X, SE), respectively . Biosensor analysis of purified doubly labeled protein showed that high-affinity binding to the Fc region of IgG was retained . The fluorescence emission spectrum of the doubly labeled protein showed a shift in the relative emission of the two fluorophores in the presence of Fc3(1) fragments, which bind specifically to the B domain . In addition, the fluorescence emission ratio 480/525 nm was shown to increase with increasing concentration of Fc3(1), whereas the presence of a control protein did not affect the emission ratio over the same concentration range . Ophthalmic Surg Lasers, 2001 Jul-Aug, 32(4), 322 - 4 Acute bilateral postoperative endophthalmitis in a HLA-DQ5-positive patient: possible susceptibility to infections; Nicoli CL et al.; An unusual case of bilateral acute endophthalmitis in association with the HLA-DQ5 histocompatibility antigen is reported . A 35-year-old woman with high myopia and cataracts in both eyes underwent phacoemulsification procedures performed in separate sessions using different viscoelastic substances and following the same strict prophylactic measures . After each surgical procedure, she developed S . epidermidis acute endophthalmitis in the right eye and Propionibacterium acnes acute endophthalmitis in the left eye; both were successfully treated with capsular bag irrigation and intracameral vancomycin (1 mg/0.1 mL) . She tested positive for the HLA-DQ5 (DQ1), DQ2 antigen . The question is raised as to whether the HLA-DQ5 histocompatibility antigen may be a predisposing factor for both staphylococcal and P . Acnes acute endophthalmitis . A multicenter prospective study is proposed to identify this HLA antigen in all patients scheduled for cataract surgery who have a history of postoperative endophthalmitis in the fellow eye. Tidsskr Nor Laegeforen, 2000 Aug 30, 120(20), 2403 - 6 {Intraspinal infections in patients treated with epidural analgesia}; Lovstad RZ et al.; BACKGROUND: Intraspinal infections (meningitis, epidural abscess) may occur spontaneously or present as a complication of epidural analgesia . MATERIAL AND METHODS: All cases during the 1991-99 period of clinically significant intraspinal infections in patients treated with epidural analgesia were analysed from clinical records in our institution . RESULTS: One patient with uncertain, three patients with well documented meningitis, and one patient with epidural abscess were identified . The treatment time varied from 12 to 49 days in patients with documented infections; the number of catheters varied from one to six . Skin bacteria were isolated from one patient (Staphylococcus sp), opportunistic bacteria (Pseudomonas, Enterococcus, Micrococcus sp) were isolated from three others . Two of the patients were at risk because of probable immunosuppression and chronic infections . Diagnosis and surgery of the patient who developed epidural abscess were significantly delayed because of three negative MRs with and without gadolinium enhancement . INTERPRETATION: Because of the danger of infection related to epidural analgesia, all patients have to be properly monitored as long as they have epidural catheters and also after the removal of catheters . Some epidural abscesses spread longitudinally and may present as a diffuse process on MR without mechanical compression of the medulla, and may be interpreted as negative findings . Myelography with CT scan is an alternative method of investigation in such cases . Early neurosurgical diagnosis and intervention may prevent serious complications. Acta Anaesthesiol Scand, 2001 Aug, 45(7), 853 - 7 Determinants of ICU mortality in necrotizing pancreatitis: the influence of Staphylococcus epidermidis; Ala-Kokko TI et al.; BACKGROUND: The severity of acute necrotizing pancreatitis ranges from self-limited to rapidly progressive illness leading to multiple organ failure . Several scoring systems and clinical parameters have been used to predict the course of the disease . The aim of this study was to evaluate the clinical and microbiological determinants of poor outcome in necrotizing acute pancreatitis . METHODS: Medical records of 67 consecutive patients admitted to the intensive care unit (ICU) of Oulu University Hospital due to acute necrotizing pancreatitis were retrospectively analyzed . All patients received standard surgical intensive care . RESULTS: Patients who died (n=14) had significantly higher APACHE II, SAPS II and Ranson scores at admission to the ICU and maximum SOFA score achieved during ICU stay than did the survivors . The non-survivors were hospitalized later from the time the symptoms were first manifest (5.3 vs . 2.4 days, P=0.051) . Mechanical ventilation (P=0.002), surgical management (P=0.028), open packing surgical management (P=0.03), renal replacement therapy (P<0.001), use of inotropic drugs (P=0.012) and Staphylococcus epidermidis growth (P=0.029) in infected pancreatic tissue were all associated with mortality . CONCLUSIONS: In this study the time to hospitalization, severity of illness, intensity of care, and surgical management were associated with poor outcome . In addition, Staphylococcus epidermidis in pancreatic necrosis was associated with increased mortality. FEMS Microbiol Lett, 2001 Jul 24, 201(2), 181 - 5 Roles of superoxide dismutase and catalase of Staphylococcus xylosus in the inhibition of linoleic acid oxidation; Barriere C et al.; Staphylococcus xylosus used as starter culture in sausages decreases the level of volatile organic compounds arising from lipid oxidation and so contributes to the aroma by avoiding rancidity . The aim of this study was to characterize the roles of catalase and superoxide dismutase (SOD) in the inhibition of free fatty acid oxidation by comparing antioxidant capacity of the S . xylosus wild-type strain with those of the katA mutant and the sod mutant . Antioxidant capacity was determined by measuring the volatile organic compounds and the conjugated diene hydroperoxides arising from linoleic acid oxidation . The three strains inhibited the oxidation of linoleic acid . However, the katA mutant, and especially the sod mutant, had less antioxidant capacity than the S . xylosus wild-type strain . Thus both catalase and SOD of S . xylosus contributed to the inhibition of lipid oxidation. J Immunol, 2001 Aug 1, 167(3), 1371 - 8 H2-O inhibits presentation of bacterial superantigens, but not endogenous self antigens; Qi L et al.; H2-O/HLA-DO are MHC class II accessory molecules that modulate exogenous Ag presentation . Most class II accessory molecules are expressed in all professional APC; however, H2-O is only expressed in B cells and medullary thymic epithelial cells . Because B cells present exogenous Ags and superantigens (SAgs), and medullary thymic epithelial cells are specialized APC for self Ags during negative selection in the thymus, we have hypothesized that H2-O might play a role in MHC class II-restricted SAg and self Ag presentation . In this study, we demonstrate that H2-O expression inhibits presentation of the bacterial SAgs staphylococcal enterotoxins A and B to four SAg-reactive T hybridoma cells . In contrast, H2-O has no effect on presentation of endogenous self Ags, as measured by tumorigenicity in vivo and Ag presentation to three self Ag-specific T hybridoma cells . Additional experiments suggest that H2-O inhibits presentation of exogenous Ags by both newly synthesized and recycling MHC class II molecules . These data suggest H2-O may have a physiological role in tolerance induction and SAg-mediated toxic shock. Skin Pharmacol Appl Skin Physiol, 2001 Jul-Aug, 14(4), 234 - 42 Immunomodulation induced by Avène spring water on Th1- and Th2-dependent cytokine production in healthy subjects and atopic dermatitis patients; Portales P et al.; Avene spring water (ASW) is commonly used in France for treating atopic dermatitis and psoriasis . Previous works demonstrated modulation of cell membrane fluidity by ASW . The aims of the present study were (a) to investigate a possible in vitro effect of ASW on Th1- and Th2-dependent cytokine production using peripheral blood mononuclear cells from healthy individuals and (b) to investigate both the in vitro effect of ASW on AD patients' cells and the in vivo cellular and clinical modifications induced by a 3-week Avene Medical Spa water cure (AMSWC) . The effect of ASW was tested on lymphocyte cultures, which were stimulated in vitro by various mitogens and a superantigen of staphylococcal origin . The lymphocyte proliferation and the production of the cytokines IL-2, IL-4 and IFN-gamma were tested . The results showed that ASW-containing medium enhanced the lymphoproliferative response to some mitogens . IL-2 and IFN-gamma production were also increased in stimulated culture supernatants . Conversely, ASW-containing medium induced a decrease in IL-4 production by normal peripheral blood lymphocytes . Furthermore, AMSWC was able to amend the clinical features as well as the immunological Th2 profile of atopic dermatitis . Science, 2001 Jul 20, 293(5529), 487 - 9 Persistence of native-like topology in a denatured protein in 8 M urea; Shortle D et al.; Experimental methods have demonstrated that when a protein unfolds, not all of its structure is lost . Here we report measurement of residual dipolar couplings in denatured forms of the small protein staphylococcal nuclease oriented in strained polyacrylamide gels . A highly significant correlation among the dipolar couplings for individual residues suggests that a native-like spatial positioning and orientation of chain segments (topology) persists to concentrations of at least 8 molar urea . These data demonstrate that long-range ordering can occur well before a folding protein attains a compact conformation, a conclusion not anticipated by any of the standard models of protein folding. Int J Antimicrob Agents, 2001 Jul, 18(1), 55 - 9 Elucidation of antibiotic effectiveness against Staphylococcus epidermidis during intraocular lens implantation; Kadry AA et al.; The effect of various antimicrobial agents commonly used in irrigating solutions on the hydrophobicity and adherence of Staphylococcus epidermidis ATCC 14990 was investigated . The longest post-antibiotic effect (PAE=3.2 h) was obtained with gentamicin followed by ciprofloxacin (2.7 h), clindamycin (2.2 h), ceftazidime (1.8 h) and vancomycin (1.6 h) . The post-antibiotic effect on surface hydrophobicity of cells previously treated with gentamicin, ciprofloxacin, or clindamycin for 120 min resulted in a substantial decrease in affinities to hexadecane (31.4, 28.5 and 27%, respectively) compared with control untreated cells . Less effect was noted with cells previously treated with ceftazidime or vancomycin (20.5 and 15.8%, respectively) . Similar but less marked results were obtained when the cells were exposed to antibiotics for 30 or 60 min . The post-antibiotic effect on adherence of cells to both intraocular lenses and to epithelial cells showed that adherence to lenses decreased as the time of exposure to antimicrobial agents increased . Adherence was greatly diminished with cells treated with gentamicin or ciprofloxacin compared with control untreated cells . Adherence was less affected by clindamycin, ceftazidime and vancomycin . The data supported the use of antimicrobial agents in irrigating solution during intraocular surgery, since, reduced adherence (colonization) and might result in a lower incidence of endophthalmitis. Immunology, 2001 Jul, 103(3), 270 - 80 Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an activated phenotype of CD8+ T cells; Sullivan YB et al.; Aside from an intermediate stage in thymic T-cell development, the expression of CD4 and CD8 is generally thought to be mutually exclusive, associated with helper or cytotoxic T-cell functions, respectively . Stimulation of CD8+ T cells, however, induces the de novo expression of CD4 . We demonstrate that while superantigen (staphylococcal enterotoxin B, SEB) and anti-CD3/CD28 costimulation of purified CD8+ T cells induced the expression of CD4 on CD8+ T cells by 30 and 17%, respectively, phytohaemagglutinin (PHA) stimulation did not induce CD4 expression on purified CD8+ T cells but significantly induced the expression of both CD4 on CD8 (CD4dimCD8bright) and CD8 on CD4 (CD4brightCD8dim) T cells in unfractionated peripheral blood mononuclear cells (PBMC) . The level of the PHA-mediated induction of CD4dimCD8bright and CD4brightCD8dim was at 27 and 17%, respectively . Depletion of CD4+ T cells from PBMC abrogated this PHA-mediated effect . Autologous CD4+ and CD8+ T-cell co-cultures in the presence of PHA induced this CD4dimCD8bright T-cell expression by 33%, demonstrating a role for CD4 cells in the PHA-mediated induction of the double positive cells . The induction of CD4dimCD8bright was independent of a soluble factor(s) . Phenotypic analysis of CD4dimCD8bright T cells indicated significantly higher levels of CD95, CD25, CD38, CD69, CD28, and CD45RO expression than their CD8+CD4- counterparts . CD4dimCD8bright T cells were also negative for CD1a expression and were predominantly T-cell receptor (TCR) alphabeta cells . Our data demonstrate that CD4dimCD8bright T cells are an activated phenotype of CD8+ T cells and suggest that CD4 upregulation on CD8+ T cells may function as an additional marker to identify activated CD8+ T cells. Biochim Biophys Acta, 1971 Dec 28, 251(3), 345 - 56 Guanidination and nitroguanidination of staphylococcal enterotoxin B; Spero L et al.; Guanidination of the free amino groups of staphylococcal enterotoxin B with 3,5-dimethyl-1-guanylpyrazole converted 31-32 of 33 epsilon-amino groups and 30% of the N-terminal residue . This product, although markedly reduced in solubility, suffered no gross change in conformation and retained full biological activity . A derivative prepared by reaction with O-methylisourea with only one lysyl residue unaltered lost most of its emetic activity . Nitroguanidination with 3,5-dimethyl-1-nitroguanylpyrazole converted up to 28 of the epsilon-amino groups and essentially all of the N-terminus . This material was greatly reduced in ability to produce emesis and like the O-methylisourea prepared guanidinated enterotoxin, gave only a line of partial identity in double diffusion . The loss of activity is attributed to unfolding and it is concluded that the free amino groups of enterotoxin B do not critically participate in either its antigenic determinants or its active center for emesis. Scand J Infect Dis, 2001, 33(6), 408 - 12 Interaction of Staphylococcus epidermidis from infected hip prostheses with neutrophil granulocytes; Augustinsson A et al.; This study focuses on the interaction of Staphylococcus epidermidis isolated from granulation tissue covering infected hip prostheses and neutrophil granulocytes . Bacterial strains isolated from normal flora were used as controls . The bacteria were well characterized with routine methods and further characterized with random amplified polymorphic DNA analyses and slime tests . Phagocytosis and chemiluminescence (CL) assays were used in the neutrophil interaction studies . The prostheses strains were ingested to a lesser extent than strains from normal flora (p < or = 0.001) . There was no significant difference between the prostheses strains and the normal flora strains in terms of total CL response . However, the extracellular CL response from the neutrophils was lower in comparison with the normal flora when interacting with the prostheses strains . The results of this study support the notion that S . epidermidis strains isolated from infected hip prostheses have an enhanced capacity to resist phagocytosis and that most of these strains elicit a reduced inflammatory response, measured as the production of extracellular oxidative metabolites from the neutrophils, compared to normal flora. J Am Anim Hosp Assoc, 2001 Jul-Aug, 37(4), 356 - 63 Immunomodulation therapy for feline leukemia virus infection; McCaw DL et al.; Clinically ill feline leukemia virus (FeLV)-infected cats, treated with Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were compared with cats treated with saline (SAL) . Nine cats received SPA/SAL, nine received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL . Twelve cats survived and completed the 100-week therapy . Significantly more owners of cats treated with SPA/SAL thought their cat's health improved during treatment compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison) or SPA/IFN (P=0.05, pair-wise comparison) . No significant differences in body weight, temperature, hematocrit, red blood cell counts, mean corpuscular hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status, survival time, activity, or appetite scores were observed . No significant differences in the owners' subjective assessment of their cat's health following treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen . Therapy with SPA as a single agent results in the owners' subjective impression of improved health of their FeLV-infected cats. Neurol India, 2001 Jun, 49(2), 210 - 2 Posterior fossa dermoid in association with Klippel-Feil syndrome--a short report; Sharma MS et al.; A posterior fossa dermoid cyst in association with the Klippel-Feil syndrome, in a 4 year old child is reported . Early diagnosis to prevent complications like neural compression, cyst rupture and staphylococcal meningitis justifies investigation for posterior fossa dermoids in cases of Klippel-Feil syndrome . Their embryological basis is discussed. Trop Doct, 2001 Jul, 31(3), 154 - 5 Pyomyositis in adults: a 12 year review; Yusufu LM et al.; From January 1988 to December 1999, 43 adults with pyomyositis were managed at Ahmadu Bello UniversityTeaching Hospital, Zaria, Nigeria . Staphylococcus aureuswas the most commonly cultured organism (92.5%) . All the 41 patients responded well to incision and adequate drainage, antibiotics and partial thickness skin grafting in 10 patients (23.2%).Two patients (4.65%) died from septicaemia, while being resuscitated. Toxicol Pathol, 2001 May-Jun, 29(3), 369 - 78 Cellular and cytokine responses in the circulation and tissue reactions in the lung of rhesus monkeys (Macaca mulatta) pretreated with cyclosporin A and challenged with staphylococcal enterotoxin B; Komisar JL et al.; Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice against staphylococcal enterotoxin B (SEB) intoxication . To determine whether CsA treatment would work in a species closer to humans . 4 rhesus monkeys were given 50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of SEB . The CsA was not protective: one of the monkeys died and the other three had to be euthanised when they became moribund . All monkeys made IL-2, TNF, and IFN-gamma in response to SEB . In addition, there was about a 10-fold increase in ACTH levels 2 hr after SEB challenge . CsA significantly suppressed in vitro proliferation of lymphocytes from treated monkeys . Both CsA-treated monkeys and monkeys that had been challenged in a previous experiment with a lethal dose of SEB but had received no cyclosporin had pathologic changes in several organs . The most prominent changes were marked edema and leukocytic infiltration of the bronchial and bronchiolar mucosa . The CsA treatment appeared to reduce the intensity of lung inflammation, but this effect was not sufficient to protect the monkeys . The results suggest that CsA alone may not be an effective therapeutic agent for humans suffering from SEB intoxication or gram-positive septic shock. J Immunol, 2001 Jul 15, 167(2), 987 - 94 Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling; Bulut Y et al.; Toll-like receptor 2 (TLR2) and TLR4 play important roles in innate immune responses to various microbial agents . We have previously shown that human dermal endothelial cells (HMEC) express TLR4, but very little TLR2, and respond to LPS, but not to Mycobacterium tuberculosis 19-kDa lipoprotein, unless transfected with TLR2 . Here we report that HMEC are unresponsive to several additional biologically relevant TLR2 ligands, including, phenol-soluble modulin (PSM), a complex of three small secreted polypeptides from the skin commensal Staphylococcus epidermidis, soluble tuberculosis factor (STF), and Borrelia burgdorferi outer surface protein A lipoprotein (OspA-L) . Expression of TLR2 renders HMEC responsive to all these ligands . We further characterized the signaling pathway in response to STF, OspA-L, and PSM in TLR2-transfected HMEC . The TLR2 signaling pathway for NF-kappaB trans-activation shares the IL-1R signaling molecules . Dominant negative constructs of TLR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC, supporting the concept of functional cooperation between TLR2 and TLR6 for all these TLR2 ligands . Moreover, we show that Toll-interacting protein (Tollip) coimmunoprecipitates with TLR2 and TLR4 using HEK 293 cells, and overexpression of Tollip inhibits NF-kappaB activation in response to TLR2 and TLR4 signaling . Collectively, these findings suggest that there is functional interaction between TLR2 and TLR6 in the cellular response to STF and OspA-L in addition to S . epidermidis (PSM) Ags, and that engagement of TLR2 triggers a signaling cascade, which shares the IL-1R signaling molecules, similar to the TLR4-LPS signaling cascade . Our data also suggest that Tollip may be an important constituent of both the TLR2 and TLR4 signaling pathways. Enferm Infecc Microbiol Clin, 2001 Jun-Jul, 19(6), 257 - 60 {Abscess of the psoas muscle . Description of a series of 23 cases}; Penado S et al.; BACKGROUND: Abscess of the psoas muscle (PA) is an infrequent disease of difficult diagnosis . During the last decade, the number of cases has increased because of the raising use of radiology tecniques: ecography, computerized tomography and magnetic resonance nuclear . METHODS: The presentation and management of psoas abscess was studied retrospectively in 23 patients from 1992 2000 . RESULTS: Sixteen of 23 abscesses were regarded as secundary: spondylodiscitis and pyelonefritis were most frequent pathologic processes . Homolateral pain in the flank area and hip were the usual manifestations . The duration of symptoms prior to the diagnosis was superior than 7 days.Staphylococcus aureus was the most common pathogen, followed by Escherichia coli and Mycobacterium tuberculosis.All abscesses were diagnosed by computerized tomography images . Seven patients underwent percutaneous drainage, while nine received surgical debridement.Four of the patients with psoas abscess died and only three relapsed . CONCLUSIONS: Not specific symptoms and signs and subacute presentation difficult diagnosis of AP . High range antibiotics and drainage (percutaneous or surgical) should be considered as the election treatment. Comp Immunol Microbiol Infect Dis, 2001 Jul, 24(3), 165 - 85 Chronic Fatigue Syndrome (CFS) in 15 dogs and cats with specific biochemical and microbiological anomalies; Tarello W; A great deal of controversy and speculation surrounds the etiology of Chronic Fatigue Syndrome (CFS) in human patients and the existence of a similar illness in animals . To evaluate the association with a presumptive staphylococcal infection and bacteremia, seven dogs and eight cats diagnosed with CFS (two meeting the CDC working case definition) were submitted to rapid blood cultures and fresh blood smears investigations . Nine out of 15 blood cultures proved Staph-positive and four isolates were specified as S . xilosus (3) and S . intermedius (1) . The presence of micrococci-like organisms in the blood was of common observation among these subjects, in association with fatigue/pain-related symptoms and biochemical abnormalities suggestive of a myopathy . Following treatment with a low dosage arsenical drug (thiacetarsamide sodium, Caparsolate, i.v., 0.1 ml/kg/day) all patients experienced complete remission . Micrococci disappeared from the blood at post-treatment controls made 10-30 days later . The outcomes were compared with those of five healthy controls and five 'sick with other illness' patients showing significant difference. Protein Eng, 2001 May, 14(5), 343 - 7 Comparing the effect on protein stability of methionine oxidation versus mutagenesis: steps toward engineering oxidative resistance in proteins; Kim YH et al.; The biological activity of some proteins is known to be sensitive to oxidative damage caused by a variety of oxidants . The model protein staphylococcal nuclease was used to explore the effect on protein structural stability of oxidizing methionine to the sulfoxide form . These effects were compared with the effects of substituting methionines with isoleucine and leucine, a potential strategy for stabilizing proteins against oxidative damage . Wild-type nuclease and various mutants were oxidized with hydrogen peroxide . Stabilities of both oxidized and unoxidized proteins were determined by guanidine hydrochloride denaturation . Oxidation destabilized the wild-type protein by over 4 kcal/mol . This large loss of stability supports the idea that in some cases loss of biological activity is linked to disruption of the protein native state . Comparison of mutant protein's stability losses upon oxidation showed that methionines 65 and 98 had a much greater destabilizing effect when oxidized than methionines 26 or 32 . While substitution of methionine 98 carried as great an energetic penalty as oxidation, substitution at position 65 was less disruptive than oxidation . Thus a simple substitution mutagenesis strategy to protect a protein against oxidative destabilization is practical for some methionine residues. Med Trop (Mars), 2000, 60(4), 375 - 7 {The new poor expatriates in the third world}; Perret JL et al.; This report describes four cases involving French expatriates who developed serious health problems while living destitute in Senegal . A 37-year-old man presented with embolism-like symptoms in relation with lung involvement due to spreading of untreated staphylococcal skin infection . A 64-year-old man was admitted for high output cardiac failure secondary to severe anemia caused by malnutrition . A 50-year-old man presented recurrent fever with loss of consciousness after successful treatment of neuromalaria and finally attributed to delirium tremens . A 25-year-old man was hospitalized with presumed meningoencephalitis that had been ongoing for two weeks . All four patients had been in Senegal for several months and had cut all ties to mainland France . Being jobless and homeless, they had been unable to obtain proper nutrition or medications . With minimal entry requirements and low-cost air travel, Senegal has been come a common sight-seeing destination and has developed a small but apparently growing population of destitute travelers . Alienation from the home community and resulting seclusion enhance clinical consequences and delay intervention by foreign service officials. J Virol, 2001 Aug, 75(15), 7030 - 41 Therapeutic effect of a Gag-nuclease fusion protein against retroviral infection in vivo; Schumann G et al.; Recently, remarkable progress has been made in developing effective combination drug therapies that can control but not cure retroviral replication . Even when effective, these drug regimens are toxic, they require demanding administration schedules, and resistant viruses can emerge . Thus the need for new gene-based therapies continues . In one such approach, capsid-targeted viral inactivation (CTVI), nucleases fused to viral coat proteins are expressed in infected cells and become incorporated during virion assembly . CTVI can eliminate infectious murine retrovirus titer in tissue culture . Here we describe transgenic mice expressing fusions of the Moloney murine leukemia virus (Mo-MuLV) Gag protein to staphylococcal nuclease . This work tests the protective effect and demonstrates in vivo proof-of-principle of CTVI in transgenic mice expressing endogenous proviral copies of Mo-MuLV . The antiviral protein-expressing mice are phenotypically normal, attesting to the lack of toxicity of the fusion protein . The Mo-MuLV infection was much less virulent in transgenic littermates than in nontransgenic littermates . Gag-nuclease expression reduced infectious titers in blood up to 10-fold, decreased splenomegaly and leukemic infiltration, and increased life spans up to 2.5-fold in transgenic relative to nontransgenic infected animals . These results suggest that gene therapies based on similar fusion proteins, designed to attack human immunodeficiency virus or other retroviruses, could provide substantial therapeutic benefits. J Leukoc Biol, 2001 Jul, 70(1), 80 - 6 Induction of interleukin-8 in human neutrophils after MHC class II cross-linking with superantigens; Lei L et al.; Neutrophils have been shown to express major histocompatibility complex class II (MHC II) after stimulation . However, reports concerning the functional effect of MCH II expression are still lacking . In our hands, granulocyte-monocyte colony-stimulating factor (GM-CSF) alone and in combination with interferon (IFN)-gamma, but not IFN-gamma or interleukin (IL)-3, induced a significant level of expression of human leukocyte antigen DR on neutrophils . The addition of staphylococcal enterotoxin E to neutrophils resulted in a significant increase in IL-8 production only after prestimulation with GM-CSF alone or in combination with IFN-gamma but had no effect on neutrophils preincubated with IFN-gamma alone or IL-3 . Staphylococcal enterotoxin A, another bivalent superantigen, also stimulated production of IL-8 by preincubated polymorphonuclear neutrophils, whereas staphylococcal enterotoxin A mutants that are not able to cross-link MHC II molecules failed to induce IL-8 production . Taken together, our results clearly demonstrate that after induction of MHC II, neutrophils are able to respond to MHC II-specific stimulation . These findings support the ideas that the induced MHC II complex is completely functional and that neutrophils may be able to present antigens. FEBS Lett, 2001 Jun 29, 500(1-2), 52 - 5 The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines; Krakauer T et al.; Excessive release of proinflammatory cytokines mediates the toxic effect of superantigenic staphylococcal exotoxins (SE) . Baicalin, a flavone isolated from the Chinese herb Scutellaria baicalensis Georgi and used in China to treat infectious diseases, inhibited SE-stimulated T-cell proliferation (by 98%) and production of interleukin 1beta, interleukin 6, tumor necrosis factor, interferon gamma, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta mRNA and protein by human peripheral blood mononuclear cells . These data suggest that baicalin may be therapeutically useful for mitigating the pathogenic effects of SE by inhibiting the signaling pathways activated by superantigens. Clin Pharmacokinet, 2001, 40(5), 327 - 41 Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials; Burman WJ et al.; The rifamycin antibacterials, rifampicin (rifampin), rifabutin and rifapentine, are uniquely potent in the treatment of patients with tuberculosis and chronic staphylococcal infections . Absorption is variably affected by food; the maximal concentration of rifampicin is decreased by food, whereas rifapentine absorption is increased in the presence of food . The rifamycins are well-known inducers of enzyme systems involved in the metabolism of many drugs, most notably those metabolised by cytochrome P450 (CYP) 3A . The relative potency of the rifamycins as CYP3A inducers is rifampin > rifapentine > rifabutin; rifabutin is also a CYP3A substrate . The antituberculosis activity of rifampicin is decreased by a modest dose reduction from 600 to 450mg . This somewhat surprising finding may be due to the binding of rifampicin to serum proteins, limiting free, active concentrations of the drug . However, increasing the administration interval (after the first 2 to 8 weeks of therapy) has little effect on the sterilising activity of rifampicin, suggesting that relatively brief exposures to a critical concentration of rifampicin are sufficient to kill intermittently metabolising mycobacterial populations . The high protein binding of rifapentine (97%) may explain the suboptimal efficacy of the currently recommended dose of this drug . The toxicity of rifampicin is related to dose and administration interval, with increasing rates of presumed hypersensitivity with higher doses combined with administration frequency of once weekly or less . Rifabutin toxicity is related to dose and concomitant use of CYP3A inhibitors . The rifamycins illustrate the complexity of predicting the pharmacodynamics of treatment of an intracellular pathogen with the capacity for dormancy. Int J Impot Res, 2000 Oct, 12(5), 285 - 8 The role of intraoperative antibiotic irrigation and postoperative antibiotic therapy for contaminated implantable prosthesis: in a rat model in vivo; Acar O et al.; The aim of this study was to determine the usefulness of intraoperative antibiotic irrigation solution and long-term effective antibiotic therapy for the infected prostheses . Forty-five male Wistar albino rats were divided into three equal groups and a small piece of silicone prosthesis contaminated with Staphylococcus epidermidis was implanted into the scrotum . In the first group, the silicone pieces were irrigated with an antibiotic solution intraoperatively and antibiotic therapy was applied for 20 days postoperatively . The second group underwent only antibiotic therapy . In the third group (control) neither intraoperative irrigation nor postoperative antibiotic therapy was applied . Postoperative clinical infection was determined as follow-up . All implants were extracted 20 days after the implantation and cultured to observe the bacterial growth . In the first group, in 13 rats the cultures were negative and in two rats, the cultures revealed positive bacterial growth . In the second group, in four rats the cultures were negative, in five rats the cultures were positive and six rats revealed infectious findings . In the third group, 13 rats revealed infectious findings, and in the remaining two rats the cultures were positive . The differences between three groups are statistically significant (P < 0.05) . We conclude that intraoperative antibiotic irrigation and postoperative antibiotic therapy are highly beneficial in the infected prosthesis surgery. Kansenshogaku Zasshi, 2001 May, 75(5), 390 - 7 {A questionnaire survey on the theory of postoperative infection prophylaxis in gynecology}; Shinagawa N et al.; A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among gynecologists in Japan in the period from April to July 2000 . Fifty-six of the 83 gynecologists replied, and the following consensus was obtained . An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli and Bacteroides fragilis group . Use an AMP agent that archives a bactericidal concentrations in both the serum and operating site . Use an AMP agent that has little unfavourable side effects . The newer agents should be considered as a therapeutics for postoperative infections . The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed . The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and cefmetazole (CMZ) . The most commonly used agent for clean-contaminated operations where low grade level of bacterial invasion expected is CTM, followed by CEZ and CMZ, where as operations where mild grade level of bacterial invasion expected is flomxef (FMOX), followed by CTM and other cephalosporins. Vet Microbiol, 2001 Sep 20, 82(2), 177 - 85 Staphylococcus sciuri as a part of skin, nasal and oral flora in healthy dogs; Stepanovic S et al.; The coagulase-negative species Staphylococcus sciuri is widespread in nature and is associated with a variety of domestic and wild animals . However, the occurrence of S . sciuri in dogs has received little attention so far . In the present study, we established the prevalence of S . sciuri in a large population of healthy dogs, and characterized isolated strains . Samples from two mucous membrane sites (anterior nares and mouth), and two hair-coated sites (head and withers) were taken from 122 dogs and inoculated into STS agar, a novel selective medium that was introduced and tested in the study . In total, 116 isolates of S . sciuri were obtained from 488 specimens . S . sciuri was isolated from 56 out of 122 (46%) dogs . The occurrence of S . sciuri in the anterior nares and mouth were significantly higher than those in withers and head . No significant association of S . sciuri occurrence in dogs and factors such as sex, age, and living environment (indoor/outdoor) was found . Out of 56 dogs, which tested positive for S . sciuri, 30 (54%) would have it as a resident flora . Thus, we showed that S . sciuri was frequently present as a part of skin, nasal and oral flora in healthy dogs both as a resident and transient carriage. Kidney Int, 2001 Jul, 60(1), 1 - 13 Infectious complications of the hemodialysis access; Nassar GM et al.; Infectious complications of the vascular access are a major source of morbidity and mortality among hemodialysis (HD) patients . Numerous reports implicate the vascular access in up to 48 to 73% of all bacteremias in HD patients . The incidence of vascular access-related infection is highest when central venous dialysis catheters are employed . Native arteriovenous fistulas carry the lowest risk of infection . Unfortunately, prosthetic arteriovenous grafts, which represent the most common type of HD access in the United States, have been repeatedly shown to be a risk factor for bacteremic and nonbacteremic infections . Silent infection in old nonfunctional clotted prosthetic arteriovenous grafts has recently been recognized as a frequent cause of bacteremia and morbidity among HD patients . High proportions of infections related to the vascular access are caused by staphylococcal organisms, which carry high rates of mortality, recurrence, and metastatic complications . Management of vascular access-related infection has two aspects: The first relates to the choice, duration, and mode of administration of antibiotic therapy . Empiric antibiotic therapy, guided by demographic data and severity of illness, should be employed when the causative organisms are unknown . Prolonged administration of specific parenteral antibiotics is crucial in decreasing complications of infection, especially in cases of staphylococcal bacteremia . The second aspect relates to management of the vascular access . Efforts directed toward bacteriological cure should be concurrent with efforts to preserve native venous access sites whenever possible . Efforts to prevent vascular access-related infection should focus on increasing placement of arteriovenous fistulas and minimizing insertion of central venous dialysis catheters . Careful inspection and monitoring of the vascular access is of paramount importance in early detection of vascular access site-related infections . Several new approaches aimed at preventing catheter and prosthetic graft-related infection are being explored. J Surg Res, 2001 Jul, 99(1), 70 - 4 Affinity of Staphylococcus epidermidis to various prosthetic graft materials; Demirer S et al.; BACKGROUND: Abdominal wall hernias have always been a major problem for general surgeons . The techniques of repairing primary, recurrent, and incisional hernias have evolved throughout the years at an accelerating trend, especially after production of prosthetic graft materials . Although looked upon with suspicion due to infection, fistula formation, and foreign body reaction, prosthetic graft materials are used deliberately in primary and recurrent hernias . The present study was designed to evaluate bacterial adherence to frequently used prosthetic graft materials . MATERIALS AND METHODS: The study was carried out in five different groups with each group consisting of 10 identical samples of the same kind of prosthetic graft material . The prosthetic graft materials used in the study were polypropylene, polyglactin 910, polyester fibers, steel, and polytetrafluoroethylene (PTFE) . These prosthetic graft materials were incubated in vitro with a Staphylococcus epidermidis strain which was ++++ adhesion positive . The degree of adhesion of S . epidermidis to prosthetic graft materials was assessed by the ELISA method . RESULTS: Vicryl grafts showed significantly minimal bacterial adhesion whereas PTFE grafts tended to have more adhesion but this did not reach a statistical significance . Other graft materials did not show any difference for bacterial adhesion (Table 3) . CONCLUSION: These results suggest that in vitro S . epidermidis adhesion to Vicryl grafts is less than other types of prosthetic graft materials (P < 0.05 for all comparisons) . Further in vitro and in vivo studies are required to confirm these results and to understand the complex interactions among bacteria, graft material, microenvironment, and surgical technique . Vet Dermatol, 2001 Jun, 12(3), 171 - 5 Antimicrobial activity of enrofloxacin against Staphylococcus intermedius strains isolated from canine pyodermas; Ganiere JP et al.; This study examined and compared the minimal inhibition concentrations (MICs) of enrofloxacin against 393 Staphylococcus intermedius strains isolated in France from canine pyodermas during three different years, 1995 (174 isolates), 1997 (101 isolates) and 1999 (118 isolates) . The MICs of enrofloxacin against these strains ranged from 0.063 to 64 mg L-1, with MIC50 and MIC90 equal to 0.125 and 0.25 mg L-1, respectively . Two resistant strains were found, but only among isolates collected in 1999 . The data show that resistance to enrofloxacin among S . intermedius strains is still rare in dogs, but the selection in vitro of variants in which the MICs were increased 4-16-fold after 10 serial passages in subinhibitory concentrations of enrofloxacin suggests that inappropriate use might favour the development of resistant strains in vivo. Vet Dermatol, 2001 Jun, 12(3), 163 - 9 Evaluation of the clinical efficacy of marbofloxacin (Zeniquin) tablets for the treatment of canine pyoderma: an open clinical trial; Paradis M et al.; The efficacy and field safety of marbofloxacin (Zeniquin) for the treatment of superficial and deep bacterial pyoderma were evaluated . Seventy-two dogs were treated with 2.75 mg kg-1 of marbofloxacin orally once daily for 21 or 28 days . Sixty-two dogs (86%) had superficial pyoderma and 10 (14%) had deep pyoderma . A history of prior pyoderma was reported in 39/72 dogs . Pretreatment aerobic bacteriologic cultures of skin lesions were performed in 47 cases and the predominant pathogen isolated was Staphylococcus intermedius . Treatment was successful in 62/72 (86.1%) dogs, improvement was noted in 6/72 (8.3%) dogs and treatment failed in 4/72 (5.6%) dogs . Adverse effects associated with treatment included listlessness, anorexia, vomiting, soft stool, flatulence and polydipsia; these adverse effects were seen in only 6/81 dogs . Marbofloxacin was safe and effective for the treatment of superficial and deep pyoderma in dogs at the dosage used in this study. J Immunol, 2001 Jul 1, 167(1), 181 - 7 Functional heterogeneity of cytokines and cytolytic effector molecules in human CD8+ T lymphocytes; Sandberg JK et al.; CD8(+) T cells use a number of effector mechanisms to protect the host against infection . We have studied human CD8(+) T cells specific for CMV pp65(495-503) epitope, or for staphylococcal enterotoxin B, for the expression patterns of five cytokines and cytolytic effector molecules before and after antigenic stimulation . Ex vivo, the cytolytic molecule granzyme B was detected in a majority of circulating CMV-specific CD8(+) T cells, whereas perforin was rarely expressed . Both were highly expressed after Ag-specific activation accompanied by CD45RO up-regulation . TNF-alpha, IFN gamma, and IL-2 were sequentially acquired on recognition of Ag, but surprisingly, only around half of the CMV-specific CD8(+) T cells responded to antigenic stimuli with production of any cytokine measured . A dominant population coexpressed TNF-alpha and IFN-gamma, and cells expressing TNF-alpha only, IFN-gamma only, or all three cytokines together also occurred at lower but clearly detectable frequencies . Interestingly, perforin expression and production of IFN-gamma and TNF-alpha in CD8(+) T cells responding to staphylococcal enterotoxin B appeared to be largely segregated, and no IL-2 was detected in perforin-positive cells . Together, these data indicate that human CD8(+) T cells can be functionally segregated in vivo and have implications for the understanding of human CD8(+) T cell differentiation and specialization and regulation of effector mechanisms. Ter Arkh, 2001, 73(3), 45 - 8 {Characteristics of expression of active oxygen forms by blood cells in patients with chronic bronchitis}; Abdrakhmanova LM et al.; AIM: To study generation of active oxygen forms in the whole blood of patients with chronic bronchitis and correction of the detected disorders . MATERIAL AND METHODS: By means of registration of spontaneous and staphylococcus-induced luminol-dependent chemiluminescence (LDCL) of the whole blood, generation of active oxygen forms in 73 patients with chronic bronchitis (CB) has been studied . RESULTS: By the intensity of luminescence, all the examinees were divided into two groups . In group 1 LDCL was high, in group 2 LDCL was under the control level . Combined treatment of group 1 patients included inhalations of ceruloplasmin antioxidant . Patients of group 2 were administered sodium hypochlorite that possesses prooxidation properties . Compared to conventional treatment, the above two treatments produced marked positive changes in the studied indices and clinical symptoms . CONCLUSION: The method of chemiluminescence registration of the whole blood allows validation of pathogenetic therapy of patients with CB and improves outcomes of the treatment. Clin Immunol, 2001 Jul, 100(1), 49 - 56 Cytokine and chemokine dysregulation in hyper-IgE syndrome; Chehimi J et al.; Hyper-IgE syndrome is characterized by severe recurrent staphylococcal infections, eczema, bone abnormalities, and markedly elevated levels of immunoglobulin E (IgE) . The genetic basis is not known and the central immunologic defect is largely undefined . Reduced neutrophil chemotaxis is often described, and variable T cell defects have been demonstrated in some patients . It has been hypothesized that hyper-IgE is associated with a Th1/Th2 imbalance . We wished to characterize cytokine and chemokine imbalances that might reflect the underlying disease process or reflect ongoing pathologic processes . Nine patients with hyper-IgE syndrome and six controls were studied . Radioimmunoassays, flow cytometry, and gene array analyses were performed to characterize cytokine and chemokine production . Hyper-IgE patients express more IL-12, while ENA-78, MCP-3, and eotaxin are markedly underexpressed . Underexpression of a set of chemokines could explain a number of features of hyper-IgE syndrome and may offer a new paradigm for the understanding of this disorder . Eur Biophys J, 2001, 30(2), 147 - 61 Dynamics and orientation of amphipathic peptides in solution and bound to membranes: a steady-state and time-resolved fluorescence study of staphylococcal delta-toxin and its synthetic analogues; Talbot JC et al.; The environment of both the hydrophilic and hydrophobic sides of alpha-helical delta-toxin are probed by tryptophanyl (Trp) fluorescence, when self-association occurs in solution and on binding to membranes . The fluorescence parameters of staphylococcal delta-toxin (Trp15 on the polar side of the amphipathic helix) and synthetic analogues with single Trp at position 5 or 16 (on the apolar side) were studied . The time-resolved fluorescence decays of the peptides in solution show that the local environment of their single Trp is always heterogeneous . Although the self-association degree increases with concentration, as shown by fluorescence anisotropy decays, the lifetimes (and their statistical weight) of Trp16 do not change, contrary to what is observed for Trp15 . The first step of self-association is then driven by hydrophobic interactions between apolar sides of alpha-helices, whilst further oligomerization involves their polar side (Trp15) via electrostatic interactions . This is supported by dissociation induced by salt . For all self-associated peptides, the polarity of the Trp microenvironment was not significantly modified upon binding to phospholipid vesicles, as indicated by the small shifts of the fluorescence emission spectra and lifetime values . However, the relative populations of the lifetime classes vary with bound-peptide density similar to the rates of their global motions in bilayers or smaller particles . Quenching experiments by water or lipid-soluble compounds show changes of the orientation of membrane-inserted peptides, from probably dimers lying flat at the interface at low peptide density, to oligomers spanning the membrane and inducing membrane fragmentation at high peptide density. Ann Pharmacother, 2001 Jun, 35(6), 765 - 9 Adjunctive rifampin therapy for central nervous system staphylococcal infections; Brackbill ML et al.; OBJECTIVE: To review the published clinical data assessing the role of adjunctive rifampin therapy for the treatment of staphylococcal central nervous system (CNS) infections . DATA SOURCES: A MEDLINE search (January 1966-March 2000) of English-language literature pertaining to CNS staphylococcal infections and rifampin was performed; tertiary sources were also used . DATA EXTRACTION: Human data and case reports were included, as no clinical trials have been published . DATA SYNTHESIS: Retrospective reviews of rifampin used in combination with other antibiotics for serious bacterial infections show conflicting results . Few case reports have described clinical successes with adjunctive rifampin therapy for CNS infections . CONCLUSIONS: The routine use of adjunctive rifampin for CNS infections cannot be justified. J Microbiol Methods, 2001 Jul 30, 46(1), 63 - 7 Separation of Listeria from cheese and enrichment media using antibody-coated microbeads and centrifugation; Kaclikova E et al.; An immunoseparation system for the separation of Listeria from enriched cheese samples was developed . The system utilizes polystyrene microbeads (3.8 microm in diameter) coated with covalently bound anti-Listeria genus-specific antibody . The beads were incubated with cheese enriched in half-Fraser broth and the bead-bacterial complex was separated by centrifugation at 110 g then spread on selective agar plates . Although cross-reactivity with certain Gram-positive bacteria (Staphylococcus saprophyticus and Arthrobacter sp.) was determined, this had no negative effect on capture effectiveness of the beads to Listeria spp . The minimum density of Listeria cells positively detected by immunoseparation with subsequent plating was 10(0) cfu/ml . The application of the separation method facilitates a reduction in the time of Listeria detection in cheese by 2 days without affecting the sensitivity. Med Clin (Barc), 2001 May 5, 116(16), 610 - 1 {Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996)}; Figuera A et al.; BACKGROUND: We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia . PATIENTS AND METHOD: Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study . A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h . Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started.The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h . Differences between percentages were analyzed using the *2test . RESULTS: 137 patients were evaluated.The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%) . The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached . The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed . The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%) . There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7% . The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001) . CONCLUSIONS: PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia. J Nat Toxins, 2001 May, 10(2), 111 - 8 Characterization of coagulase from Staphylococcus intermedius; Komori Y et al.; A protein coagulase was isolated from Staphylococcus intermedius 6131 using bovine prothrombin-Sepharose 4B and Bio-gel P-4 column chromatographies . Homogeneity was demonstrated by the formation of a single band in polyacrylamide gel electrophoresis and isoelectric focusing . The purified preparation possesses a molecular weight of 64,500, an isoelectric point of 4.1, consists of 615 total amino acid residues and demonstrates coagulase activity for human and rabbit fibrinogen, but does not show the activity for rat or guinea pig fibrinogens . This purified protein contains galactose and fucose, and the amino-terminal amino acid sequence was determined . The coagulase activity is inhibited by N-bromosuccinimide (NBS), suggesting that tryptophan is involved in this activity . The coagulase was heat stable to 80 degrees C and stable to pH over the range of 7-9 . This is the first report of coagulase from Staphylococcus intermedius. Curr Microbiol, 2001 May, 42(5), 361 - 7 Characterization of vitronectin-binding proteins of Staphylococcus epidermidis; Li DQ et al.; Staphylococcus epidermidis is the most common microorganism that is isolated from the cerebrospinal fluid (CSF) shunt infection patients . Vitronectin adsorbed on the surface of implants may mediate bacterial adhesion and colonization . To characterize vitronectin-binding properties, we analyzed S . epidermidis BD5703 isolated from a CSF shunt infection . Expression of vitronectin-binding protein(s) depended on culture media . Two proteins (60 and 52 kDa) were purified from vitronectin affinity chromatography . Two other vitronectin-binding proteins (21 and 16 kDa) were purified from an ion-exchange column . All purified proteins blocked bacterial binding of immobilized vitronectin significantly except the 16-kDa protein . The N-terminal sequences of the 21- and 16-kDa proteins did not show any appreciable amino acid sequence homology . The 52-kDa protein was sequenced by mass spectrometry and identified as an autolysin . This report demonstrates that interaction of vitronectin with multiple recognition sites on BD5703 surface may contribute to bacterial colonization. Transfusion, 2001 Jun, 41(6), 815 - 8 Determination of the degree of bacterial contamination of whole-blood collections using an automated microbe-detection system; de Korte D et al.; BACKGROUND: The prevalence of bacterial contamination in whole-blood collections, either with immediate sampling or sampling after overnight storage as whole blood at 20 degrees C, is determined . STUDY DESIGN AND METHODS: Whole blood was collected under blood bank conditions in special five-bag systems, allowing sampling in a closed system for culture bottles . Samples were taken within 2 hours after collection (Group 1) or after overnight storage of the whole blood at 20 degrees C (Group 2) . Culture bottles were incubated for 7 days, and positive samples were entered on agar plates for confirmation and determination . RESULTS: In Group 1, 9219 units were tested; 27 units were positive with positive subculture, that is, 0.29 percent with a 95% CI of 0.19 to 0.42 percent . In Group 2, 9038 units were tested; 36 units were positive with positive subculture, that is, 0.39 percent with a 95% CI of 0.28 to 0.55 percent . No significant difference could be found between the two test groups . The majority of bacteria were either Staphylococcus (all coagulase-negative) or Propionibacterium species . CONCLUSION: For a total of 18,257 units, 0.34 percent (CI, 0.25-0.44) of whole-blood collections appeared to have bacterial contamination (mainly skin-derived) . Overnight storage of whole blood at 20 degrees C did not have a significant effect on the prevalence of bacterial contamination. Eur Cytokine Netw, 2001 Apr-Jun, 12(2), 210 - 22 Regulation of helper T cell responses to staphylococcal superantigens; Cameron SB et al.; Staphylococcal superantigens (sAgs) including toxic shock syndrome toxin-1 (TSST-1) and related enterotoxins are exoproteins with unique immunobiological properties . They bind to major histocompatibility complex (MHC) class II molecules of antigen-presenting cells outside the peptide groove, and induce massive proliferation of T cells bearing specific V beta determinants . This tri-molecular interaction leads to uncontrolled release of various proinflammatory cytokines especially interferon-gamma (IFN-gamma) and tumor necrosis factor-a (TNF-alpha), the key cytokines causing sAg-mediated shock . The effector T cells involved in this hyper-immune response are predominantly of the T helper-1 (Th1) phenotype . There is also some evidence that polarization to a Th2 response with the production of classical anti-inflammatory cytokines (such as interleukins IL-4 and IL-6) also occurs . Moreover, the emergence of a novel regulatory T cell (Tr1) subset, producing mainly IL-10 but little or no IL-2 and IL-4, has recently been described following repeated sAg stimulation . In this review, the current knowledge regarding the regulation of T helper cell subsets in response to staphylococcal sAgs is critically evaluated, and the role of various cytokines which directly influence T cell differentiation and polarization is summarized . Particular emphasis is directed towards pro-inflammatory as well as anti-inflammatory and regulatory effector functions during toxic shock . Based on this review, we propose that a delayed production of IL-10 by Tr1 cells may be the most prominent driving force in the down-regulation of the Th1 hyper-immune response, and the critical determinant for the eventual recovery of the host. J Mol Biol, 2001 Jun 22, 309(5), 1165 - 75 The origin of pH-dependent changes in m-values for the denaturant-induced unfolding of proteins; Whitten ST et al.; Denaturant-induced unfolding is one of the most prevalent means of evaluating the structural stability of proteins and of determining the energetic consequences of mutations or changes in solution conditions . In spite of the widespread use of this approach, controversies and inconsistencies still persist with regard to the interpretation of the results of such studies . For example, most proteins show either a significant increase or a decrease (as much as 100 %) in the denaturant-dependence of the free energy of unfolding (i.e . the m-value) under increasingly acidic conditions . The pH dependence of the m-value is given different interpretations depending on whether the m-values increase or decrease with decreasing pH . In cases where m-values decrease, the decrease is attributed to the presence of an intermediate that becomes transiently stabilized during the unfolding transition at low pH . Cases where m-values increase as pH is lowered are usually interpreted in terms of an increase in the amount of surface area exposed by the denatured state at low pH . We have developed a general thermodynamic model that accounts for both types of behavior in terms of an intermediate that is populated throughout the unfolding transition . The model provides a unified framework for explaining both types of observed behavior, and the validity of the model was tested through the analysis of the pH dependence of m-values of staphylococcal nuclease . According to the model, the observed increase in m-values with decreasing pH is consistent with the existence of an intermediate that is populated during urea and guanidine unfolding . The intermediate becomes less populated during the unfolding transition at lower pH values giving rise to the apparent increase in m-values . These results argue that the prevailing interpretation need not apply to all proteins . J Infect Dis, 2001 Jul 1, 184(1), 52 - 5 Epub 2001 May 22. Functional study of antibodies against a fibrogenin-binding protein in Staphylococcus epidermidis adherence to polyethylene catheters; Pei L et al.; Staphylococcus epidermidis is an important pathogen in foreign body-associated infections . In a previous study, we showed that a surface-located fibrinogen-binding protein, termed Fbe, from S . epidermidis mediated the bacterial adherence to fibrinogen-coated surfaces in vitro . In the present study, we demonstrate that antibodies against Fbe can block adherence of S . epidermidis to fibrinogen-coated catheters, subcutaneously implanted catheters from rats, and peripheral venous catheters from human patients. J Biol Chem, 2001 Sep 7, 276(36), 33452 - 7 Epub 2001 Jun 07. Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens; Andersen PS et al.; Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR) . It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling . To test this, we generated variants of Staphylococcus enterotoxin C3 (SEC3) with up to a 150-fold increase in TCR affinity . By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells . Thus, the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands . Comparable studies using anti-TCR antibodies of known affinity confirmed these observations . By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength. J Med Primatol, 2001 Feb, 30(1), 26 - 35 Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon; Poaty-Mavoungou V et al.; Six different species of nonhuman primates housed at the CIRMF Primate Center, cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta), mandrills (Mandrillus sphinx), vervets (Cercopithecus aethiops pygerythrus), chimpanzees (Pan troglodyte) and baboons (Papio hamadryas), were evaluated for their natural killer cell activity and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin and staphylococcal enterotoxin A) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens . Basic information on normal immune fu