Infect Immun, 1999 Apr, 67(4), 1894 - 900 Mapping of staphylococcal enterotoxin A functional binding sites and presentation by monoclonal antibodies and fusion proteins; Mahana W; Staphylococal enterotoxins (SE) bind with high affinity to major histocompatibility complex (MHC) class II proteins and stimulate large number of T cells via the Vbeta region of the T-cell receptor (TCR) . To map the epitopes of SE type A (SEA) involved in MHC binding and cell proliferation, 20 specific anti-SEA monoclonal antibodies (MAbs) and two large glutathione S-transferase fusion proteins corresponding to the amino and carboxy termini, respectively, of SEA were used . The functionality of these antibodies was tested, by MHC binding inhibition, interleukin-2 production, and T-cell proliferation assays . Moreover, I studied the ability of the MAbs to present SEA in vitro to human and murine cells and their reactivity with the two fusion proteins . This study showed that all of the MAbs have a defined effect on one or both immunological properties of SEA and were able to present SEA to human and murine cells . However, one MAb (4H8) recognized SEA but without any interference with its biological activities . When the MAbs were tested to react with the two fusion proteins representing the SEA molecule, all of the MAbs were negative except for two . These results confirmed the presence of two functionally different binding sites of SEA with MHC class II molecules and the importance of the disulfide loop for the mitogenic activity of SEA . I further demonstrated that MAbs can present SEA to immune cells independent of the site recognized by the antibody and that the integrity of the SEA molecule is very important for its functions. Eur Heart J, 1999 Feb, 20(3), 232 - 41 Perivalvular abscesses associated with endocarditis; clinical features and prognostic factors of overall survival in a series of 233 cases . Perivalvular Abscesses French Multicentre Study; Choussat R et al.; AIMS: The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis . METHODS AND RESULTS: During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study . Of the patients, 213 received medical surgical therapy and 20 medical therapy alone . No causative microorganism could be identified in 31% of cases . Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography . Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%) . The 1 month operative mortality was 16% . Actuarial rates for overall survival at 3 and 27 months in operated patients were 75 +/- 10% and 59 +/- 11%, respectively . Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality . Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality . CONCLUSION: The data determined prognostic factors of abscesses associated with infective endocarditis. Int Ophthalmol Clin, 1998 Fall, 38(4), 1 - 13 Corneal surface disease topology; Marsh PB et al.; The specific morphology and distribution of corneal surface lesions may point toward a specific diagnosis and pathogenesis in individual cases (see Fig 1) . Staining lesions may be fine (e.g., staphylococcal) or punctate (e.g., keratitis sicca) . The size and appearance of staining and nonstaining lesions of the epithelium and subepithelial cornea may be characteristic for a particular disease process (e.g., HSV, EKC) . Finally, the location of lesions is important . Inferior staining (staphylococcal disease, lagophthalmos) will be incited by a different cause as compared to superior (molluscum, trachoma, vernal keratoconjunctivitis) and peripheral (contact lens-induced, collagen vascular disease) staining patterns . Central lesions are more likely to indicate tear deficiency, superficial corneal dystrophies, viral infections, or metabolic conditions . Knowledge of these patterns of disease can allow accurate diagnosis and more expedient and successful treatment of corneal surface disease. Aust N Z J Ophthalmol, 1999 Feb, 27(1), 45 - 8 Late infection of hydroxyapatite orbital implants; Sloan BH et al.; BACKGROUND: Exposure and minor complications of hydroxyapatite orbital implants are common . Infection appears to be rare and fibrovascular ingrowth into hydroxyapatite implants may make infection and extrusion less likely than with other types of orbital implant . METHODS: We describe three cases of chronic low-grade infection of hydroxyapatite implants, occurring late after apparently uncomplicated surgery, with tiny or inapparent areas of conjunctival loss or exposure . RESULTS: Two of the three cases grew Staphylococcus oureus on culture . All three implants ultimately needed to be removed . A characteristic histological pattern was seen, with abrupt transition between vascularized and abscessed implant . CONCLUSIONS: Chronic infection of hydroxyapatite implants can occur late, in the absence of large conjunctival defects, or other obvious risk factors.While exposure of the implant to pathogens through a breach in the conjunctiva may have been a factor, it appeared that the infection may have arisen in an avascular portion of the implant prior to the conjunctival breakdown in one or more of these cases. Can J Cardiol, 1999 Feb, 15(2), 217 - 22 Mycotic aneurysm complicating staphylococcal endocarditis; Shaikholeslami R et al.; OBJECTIVE: To emphasize the role of noninvasive diagnostic investigative methods and their importance in early detection of mycotic aneurysm related to staphylococcal endocarditis, and of monitoring therapy or identifying complications . PATIENTS AND METHODS: Two patients with mycotic aneurysm that developed as complications of staphylococcal endocarditis are presented . The first patient had mesenteric artery mycotic aneurysm and presented with sudden rupture one month after initial diagnosis of mitral valve infective endocarditis and completion of a full course of antimicrobial therapy . The second patient had multiple cerebral mycotic microaneurysms and presented with hemorrhagic cerebral embolization from aortic valve infective endocarditis . RESULTS: The first patient died because of ischemic cerebral edema 48 h after rupture of the mesenteric artery mycotic aneurysm and massive hemoperitoneum, which was treated surgically with distal ileal resection and ileostomy . The second patient was alive two years after prolonged antimicrobial therapy and aortic replacement to treat moderate aortic regurgitation and progressive left ventricular enlargement . CONCLUSIONS: Mycotic aneurysm is a rare complication of infective endocarditis but has a high mortality rate because of its early or late potential catastrophic rupture . Diagnosis by noninvasive diagnostic imaging techniques of mycotic aneurysm before rupture would be beneficial for its treatment. Int J Cancer, 1999 Mar 31, 81(1), 156 - 63 Long-term survival and complete cures of B16 melanoma-carrying animals after therapy with tumor-targeted IL-2 and SEA; Rosendahl A et al.; The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo . To engineer SAg for cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215 tumor-reactive antibody . Strong reduction of lung metastasis was seen in mice carrying established lung metastases of the poorly immunogenic B16-C215 melanoma after Fab-SEA therapy . However, important anti-tumor effector functions, such as IFN-gamma secretion and CTL activity, gradually declined during therapy . In this study, we show that Fab-SEA immunotherapy is strongly potentiated by Fab-IL-2 co-administration . Combined Fab-IL-2 and Fab-SEA therapy prolongs the immune response in vivo, limits the development of immunological unresponsiveness and promotes maximal anti-tumor effects . Significantly prolonged survival was noted in tumor-carrying animals treated with Fab-SEA/Fab-IL-2 as compared with Fab-SEA or Fab-IL-2 alone . Combination therapy resulted in complete cure in 90% of tumor-bearing animals, whereas only 10% long-term survival was seen in Fab-SEA or Fab-IL-2-treated animals . Single Fab-SEA therapy induced a hyporesponsive state after 2 cycles of treatment . In contrast, the immune response after combination therapy was characterized by substantially augmented IFN-gamma and TNF-alpha production and strong CTL activity . Our data demonstrate that combined Fab-SEA and Fab-IL-2 therapy prolongs the immune response in vivo and induced long-term survival of more than 90% of the animals carrying the highly aggressive B16 melanoma. J Exp Med, 1999 Mar 15, 189(6), 907 - 18 An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization; Mehlin C et al.; Staphylococcus epidermidis releases factors that activate the HIV-1 long terminal repeat, induce cytokine release, and activate nuclear factor B in cells of macrophage lineage . The active material had a mass of 34,500 daltons, was inactivated by proteases and partitioned into the phenol layer on hot aqueous phenol extraction, and thus was termed phenol-soluble modulin (PSM) . High performance liquid chromatography (HPLC) of crude PSM yielded two peaks of activity designated PSM peak 1 and peak 2 . MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectroscopy indicated the presence of two components in peak 1, which were designated PSM and PSM . Peak 2 contained a single component, designated PSM . Separation of PSM and PSM in peak 1 could be achieved by a second HPLC procedure . The structure of each component was determined by amino acid sequence analysis and identification and sequencing of their genes . PSM, PSM, and PSM were 22-, 44-, and 25-amino acid, respectively, strongly hydrophobic polypeptides . PSM was identified as Staphylococcus epidermidis delta toxin, whereas PSM and PSM exhibited more distant homology to previously described staphylococcal toxins . They appeared to exist as a complex or aggregate with activity greater than the component parts . The properties of the S . epidermidis PSMs suggest that they may contribute to the systemic manifestations of Gram-positive sepsis. J Bone Joint Surg Am, 1999 Feb, 81(2), 177 - 90 The functional outcome of operative treatment of ununited fractures of the humeral diaphysis in older patients; Ring D et al.; Twenty-two elderly patients (average age, seventy-two years) who had an atrophic, unstable, ununited fracture of the humeral diaphysis were managed with plate-and-screw fixation and application of an autogenous bone graft from the iliac crest . Fifteen of the patients had had at least one previous operation in an attempt to obtain union of the fracture . One patient had an active infection and two had a quiescent infection, all with Staphylococcus epidermidis . The average duration of nonunion before the patients were first seen by us was two years and four months (range, five months to sixteen years) . Fifteen of the nonunions were synovial . In each patient, at least one modification of the standard technique of plate-and-screw fixation was needed as a result of osteopenia . In order to enhance fixation, the standard protocol incorporated the use of a long plate (with an average of eleven holes and an average length that was 76 percent of that of the bone), a plate with a blade (used in thirteen patients), and replacement of loose, 4.5-millimeter cortical-bone screws with 6.5-millimeter cancellous-bone screws (twelve patients) . Spiked nuts (Schuhli nut; Synthes, Paoli, Pennsylvania) that lock the screws to the plate, creating a solid point of fixation analogous to a blade, were incorporated into the protocol when they became available (used in six patients) . In five limbs, the nonunion was associated with an osseous defect that could not be addressed by shortening of the bone alone . Three of these limbs were stabilized with a bridge plate that had been contoured to stand away from the bone at the site of nonunion (so-called wave-plate osteosynthesis), and the remaining two limbs were stabilized with a combination of intramedullary and extramedullary plates . In one of these two limbs, the extramedullary plate was contoured (that is, a wave plate) . The fracture united in twenty (91 percent) of the patients . There was no progressive loosening or breakage of a fixation device, even in two patients who had radiographs that were suggestive of an incomplete union . Five of the patients were followed for a limited duration (average, one year and six months) as a result of death or illness . They had two excellent results, two good results, and one poor result according to a modification of the rating system of Constant and Murley . The remaining seventeen patients, including the two who had a persistent nonunion, were followed for an average of three years and one month (range, two years to five years and ten months) . They had significant improvements in all of the functional scores at the most recent follow-up evaluation: the average score according to the modified system of Constant and Murley increased from 9 to 72 points (p < 0.001), the average score according to the Enforced Social Dependency Scale decreased from 39 to 9 points (p < 0.001), and the average score based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire decreased from 77 to 24 points (p < 0.001) . According to the scores based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire, nine of the seventeen patients who had been followed for more than two years had an excellent result, four had a good result, two had a fair result, and the two who had a persistent nonunion had a poor result . Complications included postoperative delirium, a stitch abscess, transient radial nerve palsy, a fracture distal to the plate, and the need for a blood transfusion, in one patient each . Two patients had a fibrous union . There were no major medical complications . An unstable, united fracture of the humeral diaphysis can be extremely disabling and may threaten the ability of an elderly patient to function independently . Operative treatment can be very successful when the techniques of plate-and-screw fixation are modified to address osteopenia and relative or absolute loss of bone . Healing of the fracture substantially improves function and the degree of independence Life Sci, 1999, 64(6-7), 443 - 8 Role of M2 muscarinic receptors in airway smooth muscle contraction; Hirshman CA et al.; Airway smooth muscle expresses both M2 and M3 muscarinic receptors with the majority of the receptors of the M2 subtype . Activation of M3 receptors, which couple to Gq, initiates contraction of airway smooth muscle while activation of M2 receptors, which couple to Gi, inhibits beta-adrenergic mediated relaxation . Increased sensitivity to intracellular Ca2+ is an important mechanism for agonist-induced contraction of airway smooth muscle but the signal transduction pathways involved are uncertain . We studied Ca2+ sensitization by acetylcholine (ACh) and endothelin-1 (ET-1) in porcine tracheal smooth muscle by measuring contractions at constant {Ca2+} in strips permeabilized with Staphylococcal alpha-toxin . Both ACh and ET-1 contracted airway smooth muscle at constant {Ca2+} . Pretreatment with pertussis toxin for 18-20 hours reduced ACh contractions, but had no effect on those of ET-1 or GTPgammaS . We conclude that the M2 muscarinic receptor contributes to airway smooth muscle contraction at constant {Ca2+} via the heterotrimeric G-protein Gi. Cell Immunol . 1999 Feb 25;192(1):86. Papers to appear in forthcoming issues {New quinolone versus vancomycin/tobramycin for intestinal sterilization in patients who undergo allogeneic bone marrow transplantation} Hosen N, Teshima H, Karasuno T, Ujiie H, Nakao T, Yagi T, Hatanaka K, Kawamoto S, Hiraoka A, Nakamura H, Masaoka T. Fifth Department of Internal Medicine, Center for Cancer and Cardiovascular Diseases, OsakaThe frequency of infection in recipients of allogeneic bone marrow transplants (BMT) who received oral new quinolones (NQ) was compared with that in BMT recipients who were given oral vancomycin/tobramycin (V/T) . Between 1984 and 1997, our hospital treated 79 patients with V/T and 90 patients with NQ . Number of febrile days, duration of intravenous antibiotics administration, and frequency of documented infections were statistically the same for both groups . However, the frequency of grampositive bacterial infections, especially staphylococcal infections, was slightly higher in patients receiving NQ than in patients receiving V/T (p = 0.12) . Of the patients who received NQ, those who underwent unrelated donor BMT procedures were generally febrile for slightly longer periods than those who underwent related donor BMT procedures (p = 0.10) . These results suggest that oral NQ is as effective as oral V/T for the prevention of serious gramnegative bacterial infections in patients who undergo BMTs. Biochem Biophys Res Commun, 1999 Mar 5, 256(1), 223 - 30 SEA-scFv as a bifunctional antibody: construction of a bacterial expression system and its functional analysis; Sakurai N et al.; A SEA-antibody single chain Fv (SEA-scFv) fusion protein was produced by bacterial expression system in this study . SEA-scFv has both staphylococcal enterotoxin A (SEA) effects and antibody activity directed at the epithelial mucin core protein MUC1, a cancer associated antigen . It was expressed mostly in the cytoplasm as an insoluble form . The gene product was solubilized by guanidine hydrochloride, refolded by conventional dilution method, and purified using metal-chelating chromatography . The resulting SEA-scFv fusion protein preparation was found to react with MUC1 and MHC class II antigens and had the ability to enhance cytotoxicity of lymphokine activated killer cells with a T cell phenotype against a human bile duct carcinoma cell line, TFK-1, expressing MUC1 . This genetically engineered SEA-scFv fusion protein promises to be an important reagent for cancer immunotherapy . Childs Nerv Syst, 1999 Jan, 15(1), 38 - 43; discussion 43-4 Cerebrospinal fluid shunt infection in children: efficiency of management protocol, rate of persistent shunt colonization, and significance of 'off-antibiotics' trial; Wang KC et al.; To evaluate the efficiency of our management protocol, 33 pediatric cases of bacteria-infected cerebrospinal fluid shunt were reviewed . The causative organism was staphylococcus in 23 patients . In 23 patients, shunt infection was managed according to the protocol . The complexity of the shunt system did not prolong hospitalization . Unchanged but externalized tubings showed persistent colonization despite adequate antibiotics in 10 of 21 patients . Staphylococcal infection was oxacillin-resistant in 7 of 19 . The efficiency of an 'off-antibiotics' trial was minimal . Further modification of the protocol is expected to enhance efficiency of the management. Eur J Immunol, 1999 Feb, 29(2), 437 - 45 Anti-Vbeta8 antibodies induce and maintain staphylococcal enterotoxin B-triggered Vbeta8+ T cell anergy; Aroeira LS et al.; The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy is poorly understood . We demonstrated earlier that B cells play an important role in the maintenance of SEB-induced T cell anergy in vivo and in vitro . Here, we demonstrate that B cells are not essential in SEB-induced T cell activation, but are important for the maintenance of T cell memory phenotype and anergy in vivo . Studying the activated B cell repertoire, we observe that SEB treatment increases serum anti-Vbeta8 antibody titer as detected by enzyme-linked immunosorbent assay using soluble Vbeta8 chains as antigens, and by staining of a Vbeta8-expressing thymoma . These antibodies disappear gradually after immunization with SEB, whereas the capacity of the T cells to respond to SEB in vitro is restored . Anti-Vbeta8 monoclonal antibody treatment causes Vbeta8+ T cell unresponsiveness to SEB in vitro (anergy), without affecting CD4Vbeta8+ T cell frequency . Together, these results suggest a new mechanism to explain the maintenance of SEB-induced T cell anergy, which is dependent on B cells and on anti-Vbeta8 antibody that specifically interacts with Vbeta8+ T cells. Infect Control Hosp Epidemiol, 1999 Feb, 20(2), 128 - 31 Investigation of suspected nosocomial clusters of Staphylococcus haemolyticus infections; Perl TM et al.; OBJECTIVE: To determine whether typing methods can discriminate among Staphylococcus haemolyticus isolates . DESIGN: Molecular epidemiological evaluation of S . haemolyticus isolates obtained from patients hospitalized on a hematology service and in a surgical intensive-care unit (SICU) . SETTING: A large Midwestern teaching hospital . INTERVENTIONS: None . RESULTS: Over 22 days, S . haemolyticus was isolated from five patients on the hematology service . Isolates from four patients had the same unusual antibiogram and biotype . Ribotyping, restriction endonuclease digestion of plasmid DNA (REAP), and whole chromosomal DNA analysis by pulsed-field gel electrophoresis (PFGE) confirmed that these isolates were identical and different from the fifth patient's isolate and from 6 control isolates . In a second cluster, 11 S . haemolyticus isolates obtained from eight patients in the SICU had similar antibiograms and biotypes . By REAP and ribotype analysis, isolates from four patients were identical . However, PFGE indicated that only two of these patients shared a common strain . CONCLUSIONS: Antibiograms or biotyping may discriminate among isolates of S . haemolyticus if the results of these tests are unusual . Many clinical isolates can be differentiated by REAP analysis, ribotyping, or PFGE . However, some isolates are identical by all of these methods, suggesting that they may have been transmitted nosocomially. J Appl Microbiol, 1999 Feb, 86(2), 194 - 202 Use of a modified Robbins device to directly compare the adhesion of Staphylococcus epidermidis RP62A to surfaces; Linton CJ et al.; Staphylococcus epidermidis is a frequent cause of infection associated with the use of biomedical devices . Flow cell studies of the interaction between bacteria and surfaces do not generally allow direct comparison of different materials using the same bacterial suspension . The use of a modified Robbins Device (MRD) to compare the adhesion to different surfaces of Staph . epidermidis RP62A grown in continuous culture was investigated . Adhesion to glass was compared with siliconized glass, plasma-conditioned glass, titanium, stainless steel and Teflon . Attachment to siliconized glass was also compared with glass under differing ionic strength, and divalent cation concentrations . Both the differences in numbers adhering and changes in adhesion (slope) through the MRD were compared . There was a trend towards higher numbers adhering to the discs at the in-flow end of the MRD than at the outflow end, probably reflecting depletion of adherent bacteria in the interacting stream . Adhesion of Staph . epidermidis RP62A to siliconized glass and Teflon was reduced when compared to glass with increasing flow rates . Adhesion to stainless steel was not affected by flow rate and titanium gave a different slope of adhesion through the MRD when compared with glass, suggesting an interaction with different sub-populations within the interacting stream . Differences between siliconized glass and glass at flow rates of 300 ml h-1 were abolished by the addition of calcium or EDTA and reduced by the addition of magnesium . Increasing ionic strength reduced the statistical significance of the differences between glass and siliconized glass . Pre-conditioning of glass with pooled human plasma reduced adhesion compared with untreated glass and again gave a different slope to glass . The MRD linked to a chemostat can be used to compare directly bacterial adhesion to potential biomaterials . Variable depletion of the interacting stream should be taken into account in the interpretation of results . Divalent cation concentration, substrate properties and flow rate were important determinants of the comparative adhesion of Staph . epidermidis RP62A to surfaces. J Magn Reson, 1999 Mar, 137(1), 39 - 45 Computer assisted assignment of 13C or 15N edited 3D-NOESY-HSQC spectra using back calculated and experimental spectra; Gorler A et al.; A new tool, for the simulation of 15N or 13C edited 3D-NOESY-HSQC spectra using the complete relaxation matrix approach, has been developed and integrated in the program AURELIA . This tool should be particularly useful for the fast and reliable computer assisted assignment of 3D-NOESY-HSQC spectra by comparing back-calculated and experimental spectra in an iterative process . Folded spectra are sometimes used to enhance the digital resolution in the indirect dimensions of multidimensional spectra . However, these spectra are usually difficult to analyze . To simplify this assignment process we have incorporated the simulation and automated annotation of folded peaks into the program . It is hereby possible to simulate multiple folding in all three dimensions of 3D 15N- or 13C-NOESY-HSQC spectra . By comparing experimental 3D-NOESY-HSQC spectra with spectra back calculated from a single trial structure or a set of trial structures, a user can easily check if the final structures explain all experimental NOEs . The new feature has been successfully tested with the histidine-containing phosphocarrier protein HPr from Staphylococcus carnosus . Proc Natl Acad Sci U S A, 1999 Mar 2, 96(5), 2025 - 30 Energy-based de novo protein folding by conformational space annealing and an off-lattice united-residue force field: application to the 10-55 fragment of staphylococcal protein A and to apo calbindin D9K; Lee J et al.; The conformational space annealing (CSA) method for global optimization has been applied to the 10-55 fragment of the B-domain of staphylococcal protein A (protein A) and to a 75-residue protein, apo calbindin D9K (PDB ID code), by using the UNRES off-lattice united-residue force field . Although the potential was not calibrated with these two proteins, the native-like structures were found among the low-energy conformations, without the use of threading or secondary-structure predictions . This is because the CSA method can find many distinct families of low-energy conformations . Starting from random conformations, the CSA method found that there are two families of low-energy conformations for each of the two proteins, the native-like fold and its mirror image . The CSA method converged to the same low-energy folds in all cases studied, as opposed to other optimization methods . It appears that the CSA method with the UNRES force field, which is based on the thermodynamic hypothesis, can be used in prediction of protein structures in real time. Nat Struct Biol, 1999 Feb, 6(2), 134 - 40 Crystal structure of staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel; Olson R et al.; Staphylococcal LukF, LukS, HgammaII, and alpha-hemolysin are self-assembling, channel-forming proteins related in sequence and function . In the alpha-hemolysin heptamer, the channel-forming beta-strands and the amino latch make long excursions from the protomer core . Here we report the crystal structure of the water soluble form of LukF . In the LukF structure the channel-forming region folds into an amphipathic, three-strand beta-sheet and the amino latch forms a beta-strand extending a central beta-sheet . The LukF structure illustrates how a channel-forming toxin masks protein-protein and protein-membrane interfaces prior to cell binding and assembly, and together with the alpha-hemolysin heptamer structure, they define the end points on the pathway of toxin assembly. J Bacteriol, 1999 Mar, 181(5), 1481 - 8 Molecular characterization of the nitrite-reducing system of Staphylococcus carnosus; Neubauer H et al.; Characterization of a nitrite reductase-negative Staphylococcus carnosus Tn917 mutant led to the identification of the nir operon, which encodes NirBD, the dissimilatory NADH-dependent nitrite reductase; SirA, the putative oxidase and chelatase, and SirB, the uroporphyrinogen III methylase, both of which are necessary for biosynthesis of the siroheme prosthetic group; and NirR, which revealed no convincing similarity to proteins with known functions . We suggest that NirR is essential for nir promoter activity . In the absence of NirR, a weak promoter upstream of sirA seems to drive transcription of sirA, nirB, nirD, and sirB in the stationary-growth phase . In primer extension experiments one predominant and several weaker transcription start sites were identified in the nir promoter region . Northern blot analyses indicated that anaerobiosis and nitrite are induction factors of the nir operon: cells grown aerobically with nitrite revealed small amounts of full-length transcript whereas cells grown anaerobically with or without nitrite showed large amounts of full-length transcript . Although a transcript is detectable, no nitrite reduction occurs in cells grown aerobically with nitrite, indicating an additional oxygen-controlled step at the level of translation, enzyme folding, assembly, or insertion of prosthetic groups . The nitrite-reducing activity expressed during anaerobiosis is switched off reversibly when the oxygen tension increases, most likely due to competition for electrons with the aerobic respiratory chain . Another gene, nirC, is located upstream of the nir operon . nirC encodes a putative integral membrane-spanning protein of unknown function . A nirC mutant showed no distinct phenotype. Nephrol Dial Transplant, 1999, 14 Suppl 1, 14 - 6 T cell subsets in experimental lupus nephritis: modulation by bacterial superantigen; De Heer E et al.; Chronic graft-vs-host disease (GvH), induced by injection of DBA/2 lymphocytes into (C57BL/6 x DBA/2)F1 hybrids, is a murine model for lupus nephritis, associated with a Th2-dependent polyclonal B cell activation . The development of glomerulosclerosis in this model is preceded by a glomerular influx of LFA-1+ T cells . We investigated whether exposure to bacterial superantigen would modulate the course of this autoimmune syndrome . Injection of the bacterial superantigen staphylococcal enterotoxin B (SEB) in mice has been shown to induce the activation of TcRVbeta8+ T cells . Within 2 weeks after GvH induction, mice were injected twice with 20 microg of SEB and the following parameters were examined: cytokine and Ig profile, proteinuria and renal pathology . The second SEB injection induced in GvH mice an increased release of both interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) as compared with control F1 mice . No differences were observed in IL-2 production . SEB-treated GvH mice demonstrated a delayed onset of proteinuria . Histological analysis of the kidney showed that SEB-challenged GvH mice displayed significantly more interstitial inflammation and mesangial proliferation together with more IgG2a deposits in glomeruli than non-injected GvH mice . From these results, we conclude that GvH mice are more responsive to SEB in terms of cytokine production and that bacterial infection can modulate the course of this renal disease from a membranous to a more proliferative type of nephropathy. Biomaterials, 1999 Feb, 20(4), 323 - 7 Hydroxyapatite-coated orthopaedic screws as infection resistant materials: in vitro study; Arciola CR et al.; The authors evaluated in vitro the adherence of a Staphylococcus epidermidis strain to hydroxyapatite-coated stainless-steel screws-used in orthopaedic surgery for external fracture fixation-in comparison with the adherence to uncoated screws . Evaluations were also performed on analogous groups of screws immersed for 72 and 168 h in a solution at 37 degrees C, in order to simulate the interstitial fluid in a simplified way . Adherence values on coated prostheses resulted significantly lower compared with those observed on metal prostheses, both in basal conditions and after immersion in saline solution . Moreover, both on coated and on uncoated screws a significant reduction in bacterial adherence was noted related to the duration of the prosthesis permanence in saline solution. Jpn J Thorac Cardiovasc Surg, 1998 Dec, 46(12), 1349 - 53 {A case of coronary arterial fistula originating from both coronary artery and draining to the right atrium}; Obana M et al.; We encountered a case with bilateral fistulas of coronary arteries into the right atrium, a rare cardiac anomaly . The case was a 17-year-old woman, who visited our hospital at the age of 11 because of fever . At that time, the patient was diagnosed as having a left coronary artery-right atrial fistula through cardiac catheterization (CAG) . When the patient developed staphylococcus infected endocarditis at the age of 16, a thick fistula of the coronary artery, directly running from the deformed left coronary arterial sinus, a fistula of the left circumflex branch, and also a fistula of the right coronary artery into the right atrium were detected by CAG . The outlets of these fistulas were closed from the inside of the right atrium under artificial cardiopulmonary circulation and cardiac arrest, and each fistula was ligated at the outside of cardiac chambers . At that time, we took particular care that any branch of the sinuatrial node was not injured . Although all fistulas were confirmed to be closed by postoperative CAG, and no evidence of ischemia was detected by myocardial scintigraphy, deformity of the left coronary arterial sinus remained, requiring further follow up. Bone Marrow Transplant, 1999 Jan, 23(1), 27 - 33 Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation; Salazar R et al.; The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC . They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery . Febrile patients received i.v . imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively . Amphotericin B lipid complex was further given on day 7 or 8 of fever . Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days . Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred . Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis . Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one . The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia. J Appl Microbiol, 1999 Jan, 86(1), 22 - 8 The effect of diet on aerobic bacterial flora associated with intestine of Arctic charr (Salvelinus alpinus L.); Ringo E et al.; In order to extend the knowledge on the possible effect of diet on the gastrointestinal microbial community of fish, Arctic charr (Salvelinus alpinus L.) were fed diets containing high (23.7%) and low (6.4%) levels of carbohydrate . The number of viable aerobic and facultative aerobic bacteria associated with the digestive tract were not influenced by dietary regimen . A wide range of bacterial species was isolated, and the predominant bacterial species of both rearing groups were identified as Staphylococcus . There were, however, some differences in bacterial composition between the rearing groups, as well as inter-individual variations . For example, atypical Aeromonas salmonicida were isolated from the small and large intestine of two fish fed low dietary carbohydrate, while Aer . caviae-like isolates were found in the small intestine of four fish fed high carbohydrate . Non-motile Aeromonas spp . were found in the rearing group fed high dietary carbohydrate, but at low frequencies . Dietary manipulation seemed to influence the species composition of carnobacteria, Gram-positive rods, oxidase and catalase-negative and fermentative metabolism . Carnobacterium piscicola-like bacteria were only found in the small intestine, while C . mobile-like and Carnobacterium spp . were isolated from the large intestine of fish fed high carbohydrate . On the contrary, C . divergens-like isolates were found associated with the small and large intestine of fish fed low dietary carbohydrate. Vet Clin North Am Small Anim Pract, 1999 Jan, 29(1), 73 - 111, xi Medical dissolution and prevention of canine struvite urolithiasis . Twenty years of experience; Osborne CA et al.; Two types of canine struvite uroliths have been recognized: infection-induced struvite is the most common type; sterile struvite is uncommonly recognized . Infection-induced struvite is most commonly associated with urease-producing staphylococcal UTI . For dogs that qualify, medical dissolution is an effective method of treatment . Medical dissolution protocols encompass: (1) eradication or control of UTI; (2) use of calculolytic diets; and (3) administration of urease inhibitors to patients with persistent UTI caused by urease-producing microbes. Hum Immunol, 1999 Feb, 60(2), 127 - 39 Analysis of the cord blood T lymphocyte response to superantigen; Macardle PJ et al.; We have characterized the T lymphocyte population of the human neonate in respect of the expression of phenotypic profiles for naive, memory and differentiated populations . We have examined the response of the neonate T cell to the superantigen Staphylococcus enterotoxin B (SEB) and compared the response to T cells from healthy adults . We found that the primary response to SEB is equivalent in neonates and adults but that the secondary response demonstrates hyporesponsiveness in the neonate that is more profound than in adults . This response was associated with increased expression of CD25; the alpha chain of the IL-2 receptor, equivalent to that seen in responding cells from adults . A modest increased expression of CD122 and CD132, the beta and gamma chains of the IL-2 receptor, was also observed . There was no increase in the IL-4 receptor (CD124) . The hyporesponsive neonate T cells proliferated in response to exogenous IL-2 but the response was less than none SEB treated cells . The neonate cells did not respond to IL-4 . We also examined the expression of MHC class II molecules on SEB stimulated cells and found that both neonate and adult T cells upregulate MHC class II to a similar degree . The difference in the hyporesponsive cells appears to result in part from a lower production of IL-2 and in part from a lower ability of cord cells to respond to IL-2 . Since the stimulated cord cells expressed IL-2 receptor at the same levels as similarly treated adult cells; there may be differences in down stream signaling pathways. Exp Lung Res, 1999 Jan-Feb, 25(1), 41 - 54 Neutrophil influx and migration in rabbit airways in response to staphylococcal enterotoxin-A; Peterson BT et al.; Single-cycle lavages performed on the lungs of rabbits 7 hours after they received intravenous staphylococcal enterotoxin-A (SEA) showed that most of the neutrophils were found in the second of 5 fractions of fluid removed from the lungs . To determine whether this finding reflected an accumulation of neutrophils in the airways versus the alveolar regions of the lungs, we counted the neutrophils in histologic sections (20 microns) and estimated the concentration of neutrophils in the epithelial lining fluid of the airways versus the alveoli . Comparisons of the morphometric measurements and the lavage data showed a strong correlation between the 2 methods (r = .90, P < .001), but the lavage technique underestimated the morphometric value by a factor of 7 . The histologic examination confirmed that the concentration of neutrophils in the airways was 3-4 times higher than in the alveoli . There were no differences between the alveoli and the airways with respect to the concentration of endogenous proteins and the chemoattractant, interleukin (IL)-8 . Lavages performed in additional rabbits 4 and 18 hours after injection of SEA showed that neutrophils most likely entered the alveolar region in response to SEA and migrated into the airways . The single-cycle technique provides a reliable measure of the relative concentration of neutrophils in the airways versus the alveoli. Biochemistry, 1999 Feb 16, 38(7), 2213 - 23 Effects of proline mutations on the folding of staphylococcal nuclease; Maki K et al.; Effects of proline isomerizations on the equilibrium unfolding and kinetic refolding of staphylococcal nuclease were studied by circular dichroism in the peptide region (225 nm) and fluorescence spectra of a tryptophan residue . For this purpose, four single mutants (P11A, P31A, P42A, and P56A) and four multiple mutants (P11A/P47T/P117G, P11A/P31A/P47T/P117G, P11A/P31A/P42A/P47T/P117G, and P11A/P31A/P42A/P47T/P56A/P117G) were constructed . These mutants, together with the single and double mutants for Pro47 and Pro117 constructed in our previous study, cover all six proline sites of the nuclease . The P11A, P31A, and P42A mutations did not change the stability of the protein remarkably, while the P56A mutation increased protein stability to a small extent by 0.5 kcal/mol . The refolding kinetics of the protein were, however, affected remarkably by three of the mutations, namely, P11A, P31A, and P56A . Most notably, the amplitude of the slow phase of the triphasic refolding kinetics of the nuclease observed by stopped-flow circular dichroism decreased by increasing the number of the proline mutations; the slow phase disappeared completely in the proline-free mutant (P11A/P31A/P42A/P47T/P56A/P117G) . The kinetic refolding reactions of the wild-type protein assessed in the presence of Escherichia coli cyclophilin A showed that the slow phase was accelerated by cyclophilin, indicating that the slow phase was rate-limited by cis-trans isomerization of the proline residues . Although the fast and middle phases of the refolding kinetics were not affected by cyclophilin, the amplitude of the middle phase decreased when the number of the proline mutations increased; the percent amplitudes for the wild-type protein and the proline-free mutants were 43 and 13%, respectively . In addition to these three phases detected with stopped-flow circular dichroism, a very fast phase of refolding was observed with stopped-flow fluorescence, which had a shorter dead time (3.6 ms) than the stopped-flow circular dichroism . The following conclusions were drawn . (1) The effects of the P11A, P31A, and P56A mutations on the refolding kinetics indicate that the isomerizations of the three proline residues are rate-limiting, suggesting that the structures around these residues (Pro11, Pro31, and Pro56) may be organized at an early stage of refolding . (2) The fast phase corresponds to the refolding of the native proline isomer, and the middle phase whose amplitude has decreased when the number of proline mutations was increased may correspond to the slow refolding of non-native proline isomers . The occurrence of the fast- and slow-refolding reactions together with the slow phase rate-limited by the proline isomerization suggests that there are parallel folding pathways for the native and non-native proline isomers . (3) The middle phase did not completely disappear in the proline-free mutant . This suggests that the slow-folding isomer is produced not only by the proline isomerizations but also by another conformational event that is not related to the prolines . (4) The very fast phase detected with the fluorescent measurements suggests that there is an intermediate at a very early stage of kinetic refolding. Infect Immun, 1999 Mar, 67(3), 1521 - 5 Correlation of temperature and toxicity in murine studies of staphylococcal enterotoxins and toxic shock syndrome toxin 1; Stiles BG et al.; This study describes a quick (<12 h) assay for detecting temperature decreases in BALB/c and C57BL/6 mice injected intraperitoneally (i.p . ) with staphylococcal enterotoxin A (SEA), SEB, or SEC3 or toxic shock syndrome toxin 1 and a potentiating dose of lipopolysaccharide (LPS) . Toxin-specific antisera effectively neutralized the temperature fluctuations in this model . Orally administered SEA or SEB (50 microg/animal), with or without LPS, did not have an effect on temperature or lethality . Versus wild-type mice, transgenic knockout mice lacking the p55 receptor for tumor necrosis factor (TNF) or gamma interferon were protected against an i.p . challenge of SEA plus LPS . The p75 receptor for TNF and intercellular adhesion molecule 1 have a negligible role in this toxic shock model. Arthroscopy, 1999 Jan-Feb, 15(1), 35 - 40 Septic arthritis following arthroscopic meniscus repair: a cluster of three cases; Blevins FT et al.; Three cases of Staphylococcus epidermidis septic arthritis following inside-out arthroscopic meniscus repair within a 4-day period at the same facility are described . All three patients responded to surgical debridement and 4 to 6 weeks of intravenous antibiotics . In each instance, the meniscus and repair sutures were left intact; 12- to 38-month follow-up revealed no evidence of infection or meniscal symptoms . Epidemiological investigation implicated the meniscus repair cannulas as one of the few factors common to all three cases . Molecular typing of bacterial DNA revealed that two of the three isolated organisms showed identical pulsed-field gel electrophoretic patterns, implying a common source of inoculation . Experimental contamination of the cannulas revealed that only sterilization involving ultrasonification, lumen washing by water jet, and steam sterilization resulted in clean and sterile cannulas. Br J Dermatol, 1998 Dec, 139 Suppl 53, 1 - 3 Bacteria and the skin: clinical practice and therapy update; Thestrup-Pedersen K; Any doctor using antibiotics should be aware of the increasing worldwide problem with multiresistant bacteria, with the majority of hospital-based infections in some countries being caused by these bacteria . Proper use of antibiotics is therefore mandatory for any physician, including for dermatologists, who treat bacterial infections of the skin . Detailed knowledge is needed of when to use topical versus systemic antibiotics, and for how long such treatments should be given . Besides the clinical symptoms of bacterial infections and treatment guidelines, an increased awareness has focused on the possible importance of bacterial toxins, including superantigens, and their contribution to skin inflammation . Rare syndromes such as Kawasaki's syndrome, toxic epidermal necrolysis or staphylococcal scalded skin syndrome, are well-known diseases elicited by specific bacterial toxins . But many observations give indirect support to the notion that bacteriae can augment the immune inflammation seen in common and important diseases such as psoriasis and atopic dermatitis . This supplement provides up-to-date information about skin bacteriology, information on the possible importance of superantigens for chronic skin diseases, and practical guidelines for the use of both topical and systemic antibiotic therapy, together with a review of the dangers following improper use . This information is important for all doctors, including dermatologists. J Biochem (Tokyo), 1999 Feb, 125(2), 375 - 82 Isolation and amino acid sequence of a phospholipase A2 inhibitor from the blood plasma of the sea krait, Laticauda semifasciata; Ohkura N et al.; A phospholipase A2 (PLA2) inhibitor was purified from the blood plasma of a sea krait, Laticauda semifasciata, by sequential chromatography on Sephadex G-200, Mono Q, and Phenyl Sepharose columns . The purified inhibitor was found to be the same type as the PLA2 inhibitors, named PLIgamma, that had been purified from the blood plasma of the Thai cobra Naja naja kaouthia {Ohkura et al . (1994) Biochem . Biophys . Res . Commun . 200, 784-788} and Chinese mamushi Agkistrodon blomhoffii siniticus {Ohkura et al . (1997) Biochem . J . 325, 527-531} . Like other PLIgammas, the L . semifasciata inhibitor (LsPLIgamma) inhibited equally all of the PLA2s investigated including Elapid venom PLA2s (group I), Crotalid and Viperid venom PLA2s (group II), and honeybee PLA2 (group III) . The LsPLIgamma was a 100-kDa glycoprotein composed of two distinct subunits, LsPLIgamma-A and LsPLIgamma-B, with an approximate molar ratio of 2:1 . The amino acid sequences of the two subunits were determined by alignment of the peptides obtained by lysyl endopeptidase, endoproteinase Asp-N, and staphylococcal V8 protease digestions . LsPLIgamma-A and LsPLIgamma-B were composed of 182 and 181 amino acid residues, respectively; and the former subunit was a glycoprotein containing one asparagine-linked sugar chain at the position 157 . The sequences of LsPLIgamma-A and LsPLIgamma-B showed 65 and 74% homology, respectively, to those of the corresponding subunits of N . naja kaouthia PLIgamma, and had two tandem patterns of cysteine residues, characteristic of the urokinase-type plasminogen activator receptor (uPAR) and members of the Ly-6 superfamily. J Invest Dermatol, 1999 Feb, 112(2), 171 - 6 Staphylococcal toxins augment specific IgE responses by atopic patients exposed to allergen; Hofer MF et al.; Microbial agents are known to play a significant role in aggravating allergic diseases . Recently described viral and bacterial superantigens represent one important strategy by which infectious agents can stimulate the immune response . In previous work, we reported that the staphylococcal toxin toxic shock toxin-1 (TSST-1), a prototypic superantigen, induces in vitro total IgE synthesis after cross-linking T and B cells . This study was carried out to establish a potential link between superantigens and the enhanced IgE response to specific allergens in allergic patients . Peripheral blood mononuclear cells from atopic patients were isolated during and outside the pollen allergen season and stimulated with TSST-1, a prototypic superantigen . Total IgE and interferon-gamma production were measured in supernatants of these cultures . Outside the pollen season, TSST-1 significantly increased total IgE production only in the presence of exogenous interleukin-4, whereas during the pollen season IgE production was significantly enhanced without the need of exogenous interleukin-4 . This increase in the absence of exogenous interleukin-4 was associated with significantly lower interferon-gamma production by peripheral blood mononuclear cells stimulated by TSST-1 during the pollen season . Moreover, TSST-1 stimulation of peripheral blood mononuclear cells from inhalant allergic patients was followed by an increased production of allergen-specific IgE that was restricted to the allergen to which the patient was allergic and recently exposed . In addition, TSST-1 induced on B cells the expression of B7.2, a molecule that has recently been demonstrated to enhance T helper 2 responses and to be involved in IgE regulation . This study, by demonstrating that superantigens can augment allergen-specific IgE synthesis and B7.2 expression, provides a mechanism by which microbial superantigens may modulate allergic responses. Pediatr Neurosurg, 1998 Dec, 29(6), 297 - 9 Pediatric intracranial epidural abscess secondary to an infected scalp vein catheter; Lefkowitz MA et al.; The authors present a case of a 5-week-old infant developing a retrotorcular epidural abscess as a result of an infected scalp vein catheter . The abscess developed in the absence of sinusitis, otitis, trauma, or prior surgery . The diagnosis of epidural abscess was made on the basis of magnetic resonance imaging and ultrasound-guided aspiration of the fluid collection . An identified strain of Staphylococcus epidermidis was cultured from both the intravenous catheter and the abscess . The patient underwent a suboccipital craniectomy with drainage of the abscess and a 6-week total course of intravenous antibiotics . Magnetic resonance imaging 4 months after the procedure and 2.5-year pediatric clinic follow-up have demonstrated no evidence of neurologic deficit or recurrence . When present, a scalp vein catheter must be considered as an etiologic agent for an intracranial epidural abscess in this age-group. J Immunol, 1999 Feb 15, 162(4), 2299 - 307 Bacterial superantigens induce down-modulation of CC chemokine responsiveness in human monocytes via an alternative chemokine ligand-independent mechanism; Rahimpour R et al.; Staphylococcal superantigens (SAgs) are very potent T cell mitogens, but they can also activate monocytes by binding directly to MHC class II molecules in a manner independent of TCR coengagement . Induction of proinflammatory cytokines and chemokine expression in monocytes by superantigens has recently been reported . Here we report that superantigen stimulation of human peripheral blood monocytes results in a rapid, dose-dependent, and specific down-regulation of chemokine (macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemotactic protein-1 and MIP-1beta) binding sites (e.g., CCR1, CCR2, and CCR5), which correlates with a concomitant hyporesponsiveness of human monocytes to these CC chemokine ligands . This down-regulation occurs 15-30 min following superantigen stimulation and is specific to chemokine receptors, in that binding and responsiveness of monocytes to the chemoattractant formyl-tripeptide FMLP are not affected . We further demonstrate that SAg-induced down-modulation of chemokine binding and monocyte hyporesponsiveness to the chemokines MIP-1alpha, monocyte chemotactic protein-1, and MIP-1beta is mediated through cellular protein tyrosine kinases, and the down-modulation can be mimicked by an MHC class II-specific mAb . Additionally, our observations indicate that SAg-induced loss of chemokine binding and monocyte responsiveness is probably mediated by secreted serine proteinases . Bacterial SAg-induced down-modulation of chemokine responsiveness represents a previously unrecognized strategy by some bacteria to subvert immune responses by affecting the intricate balance between chemokine and chemokine receptor expression and function. J Immunol, 1999 Feb 15, 162(4), 2235 - 42 Mitogenic activity of purified capsular polysaccharide A from Bacteroides fragilis: differential stimulatory effect on mouse and rat lymphocytes in vitro; Brubaker JO et al.; Bacteroides fragilis, a Gram-negative colonic bacterium, induces the formation of abscesses associated with intra-abdominal sepsis in humans . The singular ability of this organism to modulate abscess formation in experimental rodent models resides in the structurally distinct and ionically charged capsular polysaccharides A (PS A) and B (PS B) . The regulation of abscess formation in animals is dependent on T lymphocytes . However, the manner in which PS A interacts with T cells remains unknown . We therefore tested the T cell stimulatory capacity of purified PS A on mouse and rat lymphocytes in cellular proliferation assays and found that the PS A molecule possesses mitogenic characteristics distinguishable from those of the polyclonal B cell activator LPS, the T cell mitogen Con A, and staphylococcal enterotoxin A superantigen . Further, PS A stimulated proliferation of normal mouse and rat lymphocytes differentially . Mouse B cells responded to PS A in a fashion that did not require exogenous APC function, while rat T lymphocyte responses to PS A required APC function derived from autologous or xenogenic feeder cells . Cellular depletion experiments showed that the CD4+ subset of rat spleen cells was the primary responder cell type to PS A in vitro . The differential stimulatory effects of PS A on mouse and rat lymphocytes may reflect its ability to stimulate different lymphocyte subsets in vivo through the activities of receptor/counter-receptor pairs present on responder lymphocytes and cognate APC. Ann Pharmacother, 1999 Jan, 33(1), 27 - 31 Pill-induced esophagitis caused by oral rifampin; Smith SJ et al.; OBJECTIVE: To report a case of pill-induced esophagitis caused by oral rifampin . DATA SOURCES: English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles . DATA SYNTHESIS: A large number of oral medications have been reported to cause pill-induced esophagitis . This case represents the second report attributed to rifampin . A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy . The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx . A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow . Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth . Sixteen days after first reporting dysphagia, he was placed on a full liquid diet . Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture . CONCLUSIONS: Oral rifampin may cause esophagitis . Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients . Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications. Biosci Biotechnol Biochem, 1998 Nov, 62(11), 2217 - 22 A novel ELISA format for the rapid and sensitive detection of staphylococcal enterotoxin A; Giletto A et al.; Staphylococcal food poisoning is one of the leading causes of bacterial food poisoning each year . Detection kits for staphylococcal enterotoxins are commercially available and the assays can require from one and a half to twenty-four hours to complete with detection limits ranging from 0.5 to 2 ng enterotoxin per gram of food . We have successfully demonstrated a microsphere-packed capillary (MPC) ELISA for the detection of staphylococcal enterotoxin A (SEA) and have compared it to two commercially available kits . The MPC assay detected a lower amount of SEA in ham, chicken, cheese, and bean sprouts than either of the two commercially available kits . In addition, the novel MPC assay was completed in less than ten minutes, as compared to three and twenty-four hours for the two commercially available kits . This research also demonstrated that the MPC ELISA can contain integrated positive and negative controls and has the potential to simultaneously detect and identify multiple enterotoxins. Radiol Med (Torino), 1998 Oct, 96(4), 369 - 74 {Insertion and management of long-term central venous devices: role of radiologic imaging techniques}; Capaccioli L et al.; INTRODUCTION: Anticancer chemotherapy causes irreversible damage to the endothelial wall of small vessels . This is the reason why long-term (more than 3 months) central venous devices are essential to administer chemotherapy drugs to cancer patients and antibiotics for chronic or severe infections and in patients requiring long-term parenteral nutrition . We report our experience with the percutaneous implantation of central venous devices in a radiology department . MATERIAL AND METHODS: March, 1993, to August, 1997, eighty-seven consecutive patients (26 men and 61 women, mean age: 55 years) were examined . The indications for central venous catheter placement included anticancer chemotherapy in 82 cancer patients, repeated blood transfusion in one patient with bone marrow aplasia and nutritional support in four cancer patients . Eighty-four central venous devices (75 totally subcutaneous systems--Port-a-cath Dome--, and 9 partially tunneled catheters--Groshong) were inserted . The average follow-up was 6.5 months (range: 1-18) . All procedures were performed in the radiology department and venous access was achieved with fluoroscopy using the Seldinger technique . Chest radiography with the patient standing was routinely performed after the procedure and repeated the day after to assess the catheter position and the presence of pneumothorax . The venous catheters were placed in the subclavian vein in 68 cases (12 in the right side and 56 in the left side), internal jugular vein in 12 cases (9 in the right side and 3 in the left side) and right femoral vein in 4 cases . We prefer the subclavian vein (80.9%) for better cosmetic results, wider catheter angulation and easier fixation to the deep plane . RESULTS: The first access failed in 6 cases (6.8%) . A pneumothorax occurred in 4 patients (4.7%) and late complications were seen in 15 patients (17.8%) after a mean of 15.7 weeks (range: 2-48) . Catheter-related infections developed in 6 patients (7.1%) after a mean of 20 weeks (range: 5-48) . The microorganisms cultured from these catheters was the Staphylococcus epidermidis . After two weeks' specific antibiotic therapy, all the devices were removed . Deep venous thrombosis occurred only in one patient after 10 months and was successfully treated with direct thrombolytic infusion . The catheter was displaced in the right atrium in two patients after 11 and 12 weeks, respectively: both catheters were removed by transfemoral catheterization . CONCLUSIONS: The percutaneous implantation of--long-term central venous devices is a safe and tolerable procedure . In our experience, the radiology-assisted placement of these devices offers many advantages over surgical implantation . In particular, fluoroscopy allows direct visualization of the catheter position while insertion and positioning are essentially "blind" at surgery, which complicates venous access and increases the risk of catheter malpositioning . Radiologic follow-up is also useful to depict and correct complications. An Esp Pediatr, 1998 Nov, 49(5), 481 - 6 {Septic osteoarthritis in children}; Ramos Amador JT et al.; OBJECTIVE: Our objectives were to assess the clinical and microbiological aspects of septic osteoarthritis in children admitted to our center from 1987 until July 1997 and to determine the sensitivity of ultrasound in this age group . PATIENTS AND METHODS: The medical records of 36 children diagnosed as having septic osteoarthritis of the hip were reviewed retrospectively . The diagnosis had been based on clinical criteria, along with synovectomy and drainage of purulent material from the affected joint . An X-ray and/or ultrasound had been performed when the diagnosis was suspected . RESULTS: Nineteen children were diagnosed during the neonatal period, 8 between the ages of 1 and 12 months and 9 older than one year of age . Mean age at diagnosis was 16.8 +/- 6.2 months (median 29 days, range 6 days to 13 years) . The hip was involved in 32 children, the ankle in 3 and the elbow in 1 . A microbiological diagnosis was achieved in 22 cases (61%) by culture from blood, CSF, and/or synovial fluid . The most common isolates were Gram positive cocci (S . aureus in 9 cases and coagulase negative Staphylococcus in 3) . The diagnostic value of the X-rays was very low (18%) . The ultrasound was initially considered abnormal in 64.5% of the patients, with a lower sensitivity in the neonatal period . After a mean follow-up period of 36 months, the outcome was good in 86% of the cases, although three children continue with sequelae . Two preterm infants died due to sepsis associated with the osteoarthritis . CONCLUSIONS: At the time of diagnosis of septic arthritis of the hip, the ultrasound is frequently normal . Due to the poor outcome when there is a delay in surgery, we suggest immediate synovectomy and drainage when there is clinical suspicion of septic arthritis despite an apparently normal ultrasound. Eur J Immunol, 1999 Jan, 29(1), 23 - 9 Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes; Bertone S et al.; Different HLA class I-specific killer inhibitory receptors (KIR) are expressed in vivo by a fraction of activated T cells, predominantly CD8+, in which they may inhibit TCR-mediated cell functions . In an attempt to identify mechanisms leading to KIR expression in T cells, we analyzed the effect of transforming growth factor-beta (TGF-beta) in T cells responding to bacterial superantigens in vitro . We show that TGF-beta induces the expression of CD94/NKG2A in cells responding to toxic shock syndrome toxin 1 or to other staphylococcal superantigens . Remarkably, maximal CD94 expression occurred at (low) TGF-beta concentrations which have no substantial effect on lymphocyte proliferation . Maximal CD94 expression occurred when TGF-beta was added shortly after the cells were placed in culture . No expression could be induced in CD94/NKG2A-negative T cell clones . Although both CD4+ and CD8+ expressed CD94, the simultaneous expression of NKG2A was mostly confined to CD8+ cells . Monoclonal antibody-mediated cross-linking of CD94/NKG2A led to an impairment of T cell triggering via CD3, as determined in a redirected killing assay using the Fcgamma receptor-positive P815 murine target cells. Clin Exp Immunol, 1999 Jan, 115(1), 136 - 43 Administration of intravenous immunoglobulin (IVIG) in vivo--down-regulatory effects on the IL-1 system; Aukrust P et al.; Modulation of the cytokine network may be of importance for the beneficial effects of therapy with IVIG seen in a wide range of immune-mediated disorders . In the present study we investigate the effect of IVIG administration in vivo on the IL-1 system in 12 patients with primary hypogammaglobulinaemia . Before IVIG infusion these patients had significantly elevated levels of IL-1alpha and IL-1beta both in plasma and in supernatants from peripheral blood mononuclear cells (PBMC) compared with healthy controls . After one bolus infusion with IVIG (0.4 g/kg) we found a significant change in the profile of the components of the IL-1 system: a marked increase in levels of IL-1 receptor antagonist (IL-1Ra) and neutralizing antibodies against IL-1alpha, a moderate decrease in levels of IL-1alpha, IL-1beta and soluble (s) IL-1 receptor type I and a significant increase in sIL-1 receptor type II levels . These changes were found both in plasma and in PBMC isolated after IVIG administration . Furthermore, pooled serum obtained after IVIG infusion suppressed lipopolysaccharide- and staphylococcal enterotoxin B-stimulated, but not phorbol myristate acetate-stimulated, release of IL-1alpha and IL-1beta from PBMC isolated from healthy controls . Finally, these changes in circulating levels of various IL-1 modulators after IVIG infusion appeared to cause a significantly impaired ability of IL-1 to stimulate PBMC for tumour necrosis factor-alpha release . Our findings suggest that IVIG administration may not only down-regulate the activity in the IL-1 system, but also hamper IL-1 stimulation of PBMC. Acta Orthop Scand, 1998 Dec, 69(6), 559 - 65 Bone bank service in Finland . Experience of bacteriologic, serologic and clinical results of the Turku Bone Bank 1972-1995; Aho AJ et al.; 560 bones were harvested by The Turku Bone Bank between 1972-1995 . It was started with massive allografts for bone tumor surgery, but today most are femoral heads for hip revision surgery . The increase in harvested bones nearly trebled from 1984-1989 to 1990-1995 . Only 1 positive hepatitis C test was found . There were no hepatitis B or HIV positive donors . The incidence of discarding after screening was 24%, with positive bacterial growth (8%, usually Staphylococcus epidermidis) as the commonest reason . 2 massive grafts with negative cultures when harvesting were positive after thawing and resulted in deep infection . 369 allografts were transplanted . The infection rate of massive allografts for bone tumor surgery was 5/63 in 1973-1995, and 2/52 in 1985-1995 . The infection rate for hip revision surgery was 3.4% . The clinical functional results correspond to those reported in larger international series. Proc Natl Acad Sci U S A, 1999 Feb 2, 96(3), 893 - 8 Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism; Ha T et al.; Fluorescence resonance energy transfer and fluorescence polarization anisotropy are used to investigate single molecules of the enzyme staphylococcal nuclease . Intramolecular fluorescence resonance energy transfer and fluorescence polarization anisotropy measurements of fluorescently labeled staphylococcal nuclease molecules reveal distinct patterns of fluctuations that may be attributed to protein conformational dynamics on the millisecond time scale . Intermolecular fluorescence resonance energy transfer measurements provide information about the dynamic interactions of staphylococcal nuclease with single substrate molecules . The experimental methods demonstrated here should prove generally useful in studies of protein folding and enzyme catalysis at single-molecule resolution. Appl Environ Microbiol, 1999 Feb, 65(2), 591 - 8 Molecular analysis of expression of the lantibiotic pep5 immunity phenotype; Pag U et al.; The lantibiotic Pep5 is produced by Staphylococcus epidermidis 5 . Within its biosynthetic gene cluster, the immunity gene pepI, providing producer self-protection, is localized upstream of the structural gene pepA . Pep5 production and the immunity phenotype have been found to be tightly coupled (M . Reis, M . Eschbach-Bludau, M . I . Iglesias-Wind, T . Kupke, and H.-G . Sahl, Appl . Environ . Microbiol . 60:2876-2883, 1994) . To study this phenomenon, we analyzed pepA and pepI transcription and translation and constructed a number of strains containing various fragments of the gene cluster and expressing different levels of immunity . Complementation of a pepA-expressing strain with pepI in trans did not result in phenotypic immunity or production of PepI . On the other hand, neither pepA nor its product was found to be involved in immunity, since suppression of the translation of the pepA mRNA by mutation of the ATG start codon did not reduce the level of immunity . Moreover, homologous and heterologous expression of pepI from a xylose-inducible promoter resulted in significant Pep5 insensitivity . Most important for expression of the immunity phenotype was the stability of pepI transcripts, which in the wild-type strain, is achieved by an inverted repeat with a free energy of -56.9 kJ/mol, localized downstream of pepA . We performed site-directed mutagenesis to study the functional role of PepI and constructed F13D PepI, I17R PepI, and PepI 1-65; all mutants showed reduced levels of immunity . Western blot analysis indicated that F13D PepI and PepI 1-65 were not produced correctly or were partially degraded, while I17R PepI apparently was less efficient in providing self-protection than the wild-type PepI. Ann Rheum Dis, 1998 Nov, 57(11), 687 - 90 Treatment of staphylococcal septic arthritis in rabbits by systemic antibiotics and intra-articular corticosteroids; Wysenbeek AJ et al.; OBJECTIVE: To assess the effect of intra-articular corticosteroids added to systemic antibiotics in experimental septic arthritis . METHODS: Rabbits were injected intra-articularly by Staphylococcus epidermidis . Rabbits received no additional treatment and served as control (group 1), were treated with systemic antibiotics (group 2), or treated with systemic antibiotics and intra-articular corticosteroids (group 3) . After 15 days animals were killed and joint histopathological-histochemical parameters were assessed . RESULTS: All rabbits survived the experiment . The treated groups (2-3) had lower histological-histochemical scores in comparison with the untreated group (1) . Group 3 had significantly lower scores in joint sections in comparison with group 2: (mean (SD) 6.5 (1.4) v 4.0 (1.0), p = 0.001 and 7.4 (2.6) v 4.2 (2.2), p = 0.01), because of lower damage expressed in clustering of chondrocytes, pannus formation, proteoglycan depletion, and synovitis . CONCLUSION: Addition of local corticosteroids to systemic antibiotics in septic arthritis seems to be harmless, and improves joint histological-histochemical parameters in this experimental setting. Curr Microbiol, 1999 Mar, 38(3), 194 - 6 The effects of low-frequency ultrasound on Staphylococcus epidermidis; Singer AJ et al.; Low frequency ultrasound (LFUS) significantly enhances skin permeability to a variety of drugs; however, its bacterial effects have not been well studied . Staphylococcus epidermidis organisms were grown and standardized to 10(5) cfu/ml 24 h prior to investigation and suspended in normal saline . LFUS was applied with two probes immersed in the bacterial suspensions over a range of suspension volumes, intensities, and exposure times . The suspension temperature was measured, and a sample was removed, streaked onto blood agar plates, and incubated at 37 degrees C for 24 h . Quantitative bacterial counts were then obtained . LFUS resulted in significant reductions in bacterial counts that correlated with fluid temperature . Probe size and ultrasound intensity appeared to affect bacterial counts, but were also correlated with temperature . Bacterial growth was minimal with temperatures exceeding 45 degrees C . While LFUS can reduce bacterial counts, these conditions have the potential to cause burns in humans. Ann Dermatol Venereol, 1998 Dec, 125(12), 885 - 7 {The resistance of Propionibacterium acnes and Staphylococcus epidermidis to cyclines . The Research and Study Group on Acne}; Noyon V et al.; BACKGROUND: A rising percentage of tetracycline-resistant Propionibacterium acnes strains has been reported in the English literature . PATIENTS AND METHODS: We studied a population of 16 patients with acne who had been treated with oral tetracyclines during the preceding year . A bacteriological examination of a skin biopsy was obtained in all patients to determine aerobic and anaerobic flora as wells as resistance to tetracycline and minocycline . RESULTS: Staphylococcus epidermidis strains were frequently resistant to tetracycline (87.5%) as well as minocycline (30%) . Tetracycline-resistant Propionibacterium acnes were also observed (7%) . Inversely, we were unable to evidence any minocycline-resistant Propionibacterium acnes strains . CONCLUSION: These findings emphasize the importance of determining whether therapeutic response is related or not to the presence of resistant strains. Biochemistry, 1998 Dec 22, 37(51), 18010 - 7 Monitoring the sizes of denatured ensembles of staphylococcal nuclease proteins: implications regarding m values, intermediates, and thermodynamics; Baskakov IV et al.; Fluorescence and size-exclusion chromatography (SEC) are used to monitor urea denaturation of wild-type staphylococcal nuclease (SN) as well as the m+ and m- mutants A69T and V66W, respectively . It is found that the SEC partition coefficient, 1/Kd, is directly proportional to the Stokes radii of proteins . From the Stokes radii, the denatured ensembles of the three proteins are found to be highly compact in the limit of low urea concentration and expand significantly with increasing urea concentration . The m values from fluorescence-detected denaturation of the SN proteins are generally considered to reflect the relative sizes of denatured ensembles . However, the rank order of m values of the SN proteins studied do not correspond to the rank order of denatured ensemble sizes detected by 1/Kd, suggesting that m values reflect more than just surface area increases on denaturation . SEC provides two complementary ways to demonstrate the existence of intermediates in urea denaturation and illustrates that V66W undergoes a three-state transition . Fluorescence-detected urea denaturations of A69T and wt SN do not correspond with 1/Kd-detected denaturation profiles, a result that would ordinarily mean that the transitions are non-two-state . However, this interpretation fails to recognize the rapidly changing size and thermodynamic character of the denatured ensembles of these proteins both within and outside of the transition zone . The implications of the changing sizes and thermodynamic character of the denatured ensembles for SN proteins are manifold, requiring a reconsideration of the thermodynamics of proteins whose denatured ensembles behave as those of SN proteins. Eur J Dermatol, 1999 Jan-Feb, 9(1), 48 - 50 Contiguous inflammation of the skin; Helmbold P et al.; Contiguous inflammation of the skin (CIS) is a condition comprising localized inflammatory skin reactions which are secondary to a source of infection originating in deeper anatomical structures (bacterial or sterile abscesses, neoplasm-associated inflammations, foreign bodies, osteomyelitis, sinusitis, etc.) . The main clinical symptom of contiguous inflammation of the skin is an asymmetrical, localized and painful erythema in combination with different case-specific symptoms . Four patients are presented below, who developed CIS caused by an ethmoidal carcinoma with superinfection, a postoperative mediastinal abscess, an odontogenic staphylococcal abscess and a purulent sinusitis maxillaris . The purpose of this paper is to bring attention to this condition and to offer guidelines for a rapid diagnosis of its underlying, potentially life-threatening, causal inflammatory focus. Biochem Biophys Res Commun, 1999 Jan 27, 254(3), 605 - 13 An homologue of the human 100-kDa protein (p100) is differentially expressed by Histoplasma capsulatum during infection of murine macrophages; Porta A et al.; Using differential display reverse transcription-PCR (DDRT-PCR) we have identified several sequences that are specifically expressed by Histoplasma capsulatum during infection of murine macrophages (MPhi) . Here, we report the characterization of a clone, pHc12, identified as a differentially expressed gene 1 hour after infection of MPhi . Screening of a cDNA library of H . capsulatum allowed us to isolate a clone, pHc12-E, that contains the complete coding sequence . We show that after infection the level of transcription of this gene increases about 5 fold . Analysis of its sequence revealed the presence of an open reading frame of 890 aa (ORF890) that shares respectively 30 and 33% identity with human and Caenorhabditis elegans p100 kD and rat p105 kD co-activator proteins . Using the two-dimensional Hydrophobic Cluster Analysis (HCA) method, we showed that H . capsulatum ORF890 and p100 kD co-activator proteins are clearly related . The H . capsulatum protein consists of a four-fold repeated module (domains I to IV) like the p100 kD co-activator proteins, whose three-dimensional (3D) structure is related to staphylococcal thermonuclease, followed by a modified fifth "hybrid" domain which partially resembles the structure of the tudor domain found in multiple copies in the Drosophila melanogaster tudor protein . These data strongly suggest that ORF890 is homologous to human p100 kD and that this protein, named Hcp100, may play an essential role during infection by co-activating the expression of specific genes . J Immunol, 1999 Jan 15, 162(2), 659 - 68 T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes; Schafer PH et al.; p38 mitogen-activated protein kinase (MAPK) (p38) is involved in various cellular responses, including LPS stimulation of monocytes, resulting in production of proinflammatory cytokines such as TNF-alpha . However, the function of p38 during antigenic stimulation of T cells is largely unknown . Stimulation of the human Th cell clone HA-1.70 with either the superantigen staphylococcal enterotoxin B (SEB) or with a specific antigenic peptide resulted in p38 activation and the release of TNF-alpha . MAPK-activated protein kinase-2 (MAPKAPK-2), an in vivo substrate for p38, was also activated by T cell signaling . SB 203580, a selective inhibitor of p38, blocked p38 and MAPKAPK-2 activation in the T cell clone but did not completely inhibit TNF-alpha release . PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-alpha production by the clone . In human peripheral T cells, p38 was not activated by SEB, but rather by CD28 cross-linking, whereas in the human leukemic T cell line Jurkat, p38 was activated by CD3 and CD28 cross-linking in an additive fashion . TNF-alpha production by peripheral T cells in response to SEB and anti-CD28 mAb correlated more closely with ERK activity than with p38 activity . Therefore, various forms of T cell stimulation can activate the p38 pathway depending on the cells examined . Furthermore, unlike LPS-stimulated monocytes, TNF-alpha production by T cells is only partially p38-dependent. J Immunol Methods, 1998 Dec 1, 221(1-2), 151 - 7 Novel peptides binding to the Fc-portion of immunoglobulins obtained from a combinatorial phage display peptide library; Krook M et al.; Peptides interacting with the Fc portion of human IgG (IgG Fc) were selected from a phage display decapeptide library . The library was selected five times and interacting phage peptides were eluted either with Staphylococcal protein A or at low pH . Individual peptide phage clones were found to interact more strongly with IgG Fc than did either the original library or the wild-type phage . Increasing concentrations of protein A could competitively reduce the interaction of a peptide phage clone (FARLVSSIRY) eluted with protein A to the same level as the original library . Furthermore, when immunoglobulins from chicken, donkey, human, mouse, swine, rabbit, and sheep were included, peptide phage clones FGRLVSSIRY and TWKTSRISIF interacted strongly with human IgG Fc and porcine IgG and weakly with the immunoglobulins obtained from the other species. Tissue Antigens, 1998 Dec, 52(6), 530 - 8 Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines; Nielsen MB et al.; Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris . Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC class II . Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells . We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris . Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites of SEA . Mutations in only one of the two MHC class II binding sites of SEA has different effects on T-cell activation . Thus, SEA molecules with a mutation in the MHC class II beta-binding site induce protein tyrosine phosphorylation, but not IFN-gamma production or co-stimulation of cytokine-mediated proliferation . In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile . Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation . This suggests that both MHC class II binding sites are involved in the autopresentation of SEA by psoriatic T cells . In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris. Immunology, 1998 Dec, 95(4), 512 - 21 Distinct functions of interferon-gamma for chemokine expression in models of acute lung inflammation; Neumann B et al.; Challenge of the immune system with bacterial superantigens or endotoxin induces the systemic release of cytokines followed by lethal septic shock . The lung is particularly susceptible to systemic toxin exposure resulting in acute leucocyte infiltration and vascular damage . In the present study, the functions of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) for chemokine regulation during acute lung inflammation were examined . Following administration of the superantigen, staphylococcal enterotoxin B (SEB), lung mRNA levels of the chemokines cytokine-induced neutrophil chemo-attractant (KC), lipopolysaccharide-induced CXC chemokine (LIX), macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha and MIP-2 were increased to a similar extent both in controls and in mice deficient for the IFN-gamma or 55 000 MW TNF receptors . In contrast, interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig) mRNA expression was markedly reduced in mice deficient for IFN-gamma or IFN-gamma receptor, but not in 55 000 MW TNF receptor knockout mice . In situ hybridization experiments demonstrated that IP-10 was highly expressed in lung interstitial macrophages of C57BL/6, but not of IFN-gamma receptor-deficient mice . In contrast to SEB administration, treatment with lipopolysaccharide resulted in a strong induction of IP-10 and Mig in IFN-gamma receptor-deficient mice . Together, these results establish a critical function of IFN-gamma for chemokine induction in acute lung inflammation that is dependent on the nature of the inflammatory stimulus. Br J Dermatol, 1998 Nov, 139(5), 784 - 90 Effects of recombinant human soluble interleukin-4 receptor on interleukin-4/staphylococcal enterotoxin B-stimulated peripheral mononuclear cells from patients with atopic eczema; Sperhake K et al.; In atopic eczema both in local inflammatory reactions and in peripheral blood high interleukin (IL) 4: interferon-gamma (IFN-gamma) production ratios have been demonstrated, indicating predominance of TH2 cell subsets resulting in increased IL-4 production and high serum IgE . The in vitro immunomodulatory effects of recombinant human soluble IL-4 receptor (rsIL-4R) on IL-4-stimulated lymphocyte proliferation, IgE and IFN-gamma production were studied in peripheral blood mononuclear cells from 10 patients with atopic eczema and seven healthy donors . In addition to control cultures (without any stimulus) and cultures with simultaneous application of rsIL-4R and IL-4, time-kinetic experiments were performed . We further investigated the influence of rsIL-4R on IL-4 production in staphylococcal enterotoxin B (SEB) stimulated peripheral blood mononuclear cells . Early addition of rsIL-4R to IL-4-stimulated peripheral blood mononuclear cells resulted in an increase in IFN-gamma production and in suppression of IL-4 induced proliferation and IgE secretion . Unexpectedly, rsIL-4R in combination with SEB exhibited an IL-4 protective effect with a significant increase in detectable IL-4 in the culture supernatants . The present data support the assumption that rsIL-4R might be a promising new immunomodulatory substance in the treatment of atopic eczema. J Cardiovasc Nurs, 1999 Jan, 13(2), 82 - 96 Prosthetic valve endocarditis leading to valve replacement: a case study; Hubner C; Infective endocarditis (IE) is a pathologic condition of native or prosthetic heart valves or endocardium, which may result in valve destruction and congestive heart failure . It occurs more frequently in men than in women, and there is an increased trend in the elderly . The following conditions predispose patients to IE: congenital and rheumatic heart disease, calcification or stenosis of a valve, prosthetic valve surgery, a previous episode of endocarditis, poor dentition, parenteral drug abuse, and placement of intravascular lines or devices . Effective treatment frequently involves a combination of intense antibiotic therapy and surgical repair . Risk of death from IE is related to age over 60, diagnosis of staphylococcal infection, involvement of an aortic or prosthetic valve, and the presence of any of the following sequelae of endocarditis: congestive heart failure, embolic phenomenon, and neurologic deficit . Clinicians should suspect endocarditis in patients presenting with fever of unknown origin and who are at risk for endocarditis . Timely evaluation with transthoracic or transesophageal echocardiography may identify patients in the early stages of endocarditis and direct the patient to definitive therapy . Early treatment of native and prosthetic valve endocarditis may decrease its overall morbidity and mortality . This case study illustrates some of the challenges in effectively managing prosthetic valve endocarditis. Diagn Microbiol Infect Dis, 1998 Nov, 32(3), 177 - 83 Molecular characterization of epidemic multiresistant Staphylococcus haemolyticus isolates; Tabe Y et al.; Fifty-five Staphylococcus haemolyticus specimens isolated from patients and neonatal intensive care unit staff were tested for susceptibility to 12 antimicrobial agents . There were 34 multidrug-resistant isolates which were resistant to oxacillin, ampicillin, cefazolin, cefmetazole, imipenem, and gentamicin . These isolates had a higher frequency of resistance to tobramicin and ofloxacin, and relatively high MICs (2 to 4 micrograms/mL) for vancomycin, although none of the isolates were vancomycin resistant . To investigate hospital-acquired colonization and infection by multiresistant S . haemolyticus, we examined all isolates by pulsed-field gel electrophoresis (PFGE) after SmaI and SstII digestion, and detected an endemic PFGE pattern in multiresistant isolates . The results suggested that local spread of multiresistant S . haemolyticus was hospital acquired, and that the hospital staffs functioned as a reservoir. Immunity, 1998 Dec, 9(6), 807 - 16 Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B; Li H et al.; Superantigens (SAGs) are a class of immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the V beta domain of the T cell antigen receptor (TCR) . The three-dimensional structure of the complex between a TCR beta chain (mouse V beta8.2) and the SAG staphylococcal enterotoxin B (SEB) at 2.4 A resolution reveals why SEB recognizes only certain V beta families, as well as why only certain SAGs bind mouse V beta8.2 . Models of the TCR-SEB-peptide/MHC class II complex indicate that V alpha interacts with the MHC beta chain in the TCR-SAG-MHC complex . The extent of the interaction is variable and is largely determined by the geometry of V alpha/V beta domain association . This variability can account for the preferential expression of certain V alpha regions among T cells reactive with SEB. Eur J Pharmacol, 1998 Dec 18, 363(2-3), 189 - 95 Neutrophil migration induced by staphylococcal enterotoxin type A in mice: a pharmacological analysis; Desouza IA et al.; Staphylococcal enterotoxin type A induced marked neutrophil migration into the mouse peritoneal cavity and was dependent on the number of resident macrophages . This migratory response was dose- (16-64 microg of staphylococcal enterotoxin type A/cavity) and time-dependent, peaking at 12 h and disappearing after 72 h . Dexamethasone (0.5 mg/kg) inhibited the neutrophil migration induced by staphylococcal enterotoxin type A (32 microg; 42% inhibition) . A similar response was observed with the platelet-activating factor-acether receptor antagonist, BN 52021 (ginkgolide B, 3-(1,1-dimethylethyl)-hexahydro-1,4-7b-trihydroxy-8-methyl-9H-1,7alph a (epoxymethano-1H,6alphaH-cyclopenta (c) furo (2,3-b) furo (3', 2': 3,4) cyclopenta (1,2-d) furan-5, 9, 12 (4H)-trione); 10 mg/kg; 57% inhibition), the histamine H2 receptor antagonist, cimetidine (2 mg/kg; 31% inhibition), the lipoxygenase inhibitor, BWA4C (N-(3-phenoxycinnamyl) acetohydroxamic acid); 10 mg/kg; 73% inhibition), and capsaicin (trans-8-methyl-N-vanillyl-6-nonamide), a sensory C-fiber neuropeptide depletor . In contrast, indomethacin (5 mg/kg) had no effect on staphylococcal enterotoxin type A-induced chemotaxis . We conclude that the peritonitis induced by staphylococcal enterotoxin type A in mice is macrophage-dependent . The mechanism whereby staphylococcal enterotoxin type A stimulates macrophages to induce neutrophil recruitment remains to be elucidated. J Arthroplasty, 1998 Dec, 13(8), 854 - 9 The suppression of heterotopic ossifications: radiation versus NSAID therapy--a prospective study; Sell S et al.; This prospective, randomized study compares the effect of postoperative irradiation and nonsteroidal anti-inflammatory drug (NSAID) therapy on the prevention of heterotopic ossifications after the implantation of a total hip endoprosthesis . A total of 154 operations were performed; one group of patients underwent radiation treatment of 3 x 3.3 Gy, and the other group took 3 x 50 mg of diclofenac per day over a period of 3 weeks . Average age, sex, preoperative diagnosis, and risk factors were similar in both groups . Postoperative radiation began on average 2.9 days after operation, and the radiation therapy was finished on average within 3.8 days . NSAID prophylaxis was begun on the first postoperative day . Heterotopic ossifications occurred in two of the patients who had undergone postoperative prophylaxis by radiation . In both cases, the ossification was Brooker I, and there was no functional impairment . There were no ossifications of Brooker II-IV in this group . One patient had a Staphylococcus epidermidis infection, and fistula revision had to be carried out; the prosthesis could be left in place . In the group treated with NSAID, 16 heterotopic ossifications stage Brooker I and 2 stage Brooker II could be detected . Eleven patients stopped the treatment because of gastrointestinal problems . Both postoperative radiation and NSAID therapy have proved to be effective prophylactic methods . In direct comparison, radiation prophylaxis by 3 x 3.3 Gy proved to be slightly more successful than NSAID prophylaxis. Chemotherapy, 1999 Jan-Feb, 45(1), 56 - 60 Reduction of mucoid Staphylococcus epidermidis adherence to intraocular lenses by selected antimicrobial agents; Kadry AA et al.; The effect of low concentrations of various antimicrobial agents on the adherence of mucoid Staphylococcus epidermidis to intraocular lenses was investigated . Adherent growth of S . epidermidis on to polymethylmethacrylate lenses was greatly diminished by ciprofloxacin and clindamycin (>75%), followed by ceftazidime ( approximately 50%) and less affected by gentamicin and vancomycin (<25%) compared to the adherent growth of control untreated cells . The reduction in adherence growth was concentration-dependent and found to be due to the inhibition of slime production since no growth inhibition was observed at the concentrations used . Cell surface hydrophobicity was markedly reduced in parallel to the inhibition of adherence as compared to the control cells . The differential effect of antibiotics on adherence, regardless of their antimicrobial activity, may have a clinical significance in reducing the incidence of postoperative endophthalmitis and intraocular inflammation due to the reduction of cell adherence. EMBO J, 1999 Jan 4, 18(1), 156 - 66 Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor; Izquierdo M et al.; Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection) . Cysteine proteases (caspases) belonging to the CPP32 family are activated during this process . We have produced transgenic mice expressing baculovirus p35, a broad-range caspase inhibitor . Thymocytes from p35 transgenic mice were resistant in vitro to several apoptosis-inducing agents; this resistance correlated with the inhibition of CPP32-like activity . Negative selection in vivo of thymocytes triggered by two exogenous antigens, staphylococcal enterotoxin B superantigen and an antigenic peptide in the F5 T-cell receptor transgenic model, was specifically inhibited in p35 transgenic mice . Our results provide direct evidence for caspase involvement in negative selection during thymocyte development. J Laryngol Otol, 1998 Sep, 112(9), 845 - 8 Bacteriology of the maxillary and ethmoid sinuses in chronic sinusitis; Jiang RS et al.; The bacteriology of chronic sinusitis was studied by using swab and mucosal specimens from both the maxillary and ethmoid sinuses . The specimens of the maxillary sinus were taken through translabial antroscopy . The specimens of the ethmoid sinus were taken after removing the ethmoid bulla during functional endoscopic sinus surgery (FESS) . Eighty-six samples of each type of specimen were collected . Among the maxillary sinus samples, the culture rate was 60.5 per cent from the swab specimens and 36 per cent from the mucosal specimens . Among the ethmoid sinus samples, the culture rate was 58.1 per cent from the swab specimens and 75.6 per cent from the mucosal . The p-value by the Chi-Square test is higher than 0.01 (p = 0.015) . As there were more isolates of Staphylococcus epidermidis from the mucosal specimens, they are not a better choice of specimen for sampling the ethmoid sinus than a swab specimen. Ann Thorac Surg, 1998 Nov, 66(5), 1782 - 6 Outcome of primary empyema thoracis: therapeutic and microbiologic aspects; Mandal AK et al.; BACKGROUND: This study was undertaken to determine whether all adult patients with primary empyema thoracis need decortication . METHODS: A management algorithm was developed and analyzed in a prospective, longitudinal, nonblinded study of 179 consecutive adult patients . The treatment options included thoracentesis, closed (tube) thoracostomy, image-guided catheter drainage, and decortication . We reviewed the outcomes of these procedures as they related to the pleural fluid cultures isolated and the antibiotic regimens used . RESULTS: Of the 179 patients, 20 had thoracentesis as the primary procedure, and 18 (90%) were cured . Ninety patients underwent closed thoracostomy as the primary procedure with a cure rate of 62% (56 patients) and a mortality rate of 11% (10 patients), and 24 patients required a secondary procedure . Seventy-six patients underwent decortication as either the primary or the secondary procedure with a cure rate of 88% (67 patients) and a mortality rate of 1.3% (1 patient); 8 patients required conversion to open thoracostomy . Hospital stay for decortication was 14+/-1 days and for closed thoracostomy, 17+/-1 days (p < 0.05) . Decortication was necessary in 55% of patients with anaerobic infections and in 50% with aerobic infections . Clindamycin in combination with gentamicin sulfate was the most efficacious regimen with a success rate of 82% (51 of 62 patients); only 33% (17 of 52) were cured with penicillin . The overall mortality rate in this study was 6.7% (12 of 179 patients) . CONCLUSIONS: Forty-two percent of patients with primary empyema thoracis ultimately require decortication . Decortication is more frequently necessary for anaerobic, tuberculous, staphylococcal, and pneumococcal infections . Although the overall mortality in this study was low, mortality remains high in elderly patients and patients with comorbid disease. Virology, 1998 Dec 5, 252(1), 235 - 57 Binding of the human cytomegalovirus 80-kDa immediate-early protein (IE2) to minor groove A/T-rich sequences bounded by CG dinucleotides is regulated by protein oligomerization and phosphorylation; Waheed I et al.; The 80-kDa immediate-early regulatory protein IE2 of human cytomegalovirus (HCMV) functions as an essential positive transactivator of downstream viral promoters, but it also specifically down-regulates transcription from the major immediate-early promoter through a 14-bp DNA target motif known as the cis-repression signal (CRS) located at the transcription start site . The IE2 protein purified from bacteria as a fusion product of either staphylococcal Protein A/IE2(290-579) or glutathione-S-transferase (GST)/IE2(346-579) bound specifically to a {32P}-labeled CRS oligonucleotide probe in an in vitro electrophoretic mobility shift assay (EMSA) . In contrast, no direct interaction with the CRS probes could be detected with IE2 wild-type protein in extracts from infected or transfected mammalian cells or when synthesized by in vitro translation . However, in vitro phosphorylation of GST/IE2(346-579) by incubation with either the catalytic subunit of protein kinase A (PKA) or a HeLa cell nuclear extract strongly inhibited its DNA-binding activity . This process required ATP hydrolysis and could be reversed by subsequent incubation with bacterial alkaline phosphatase . Importantly, dephosphorylation of the constitutively expressed native IE2 protein present in a nuclear extract from the U373(A45) cell line unmasked a specific CRS DNA-binding activity that could be supershifted with anti-IE2 monoclonal antibody (mAb) . A series of high-molecular-weight hetero-oligomeric DNA-bound structures of intermediate mobility were formed in EMSA assays when a mixture of staphylococcal Protein A/IE2 and GST/IE2 was coincubated with the CRS probe . Coincubation with a DNA-binding negative but dimerization-competent GST/IE2 deletion mutant competitively inhibited DNA-binding by staphylococcal Protein A/IE2, whereas coincubation with a GST/IE2 deletion mutant that lacked the ability to both dimerize and bind to DNA failed to influence the mobility of the DNA-bound staphylococcal Protein A/IE2 protein . Therefore, IE2 appears to bind to DNA as a higher-order oligomer in which the presence of subunits with mutant DNA-binding domains interferes with the overall DNA-binding function . A series of point mutations introduced into each of nine conserved motifs throughout the DNA-binding and dimerization domain, all of which abolish the ability of the transfected intact IE2 protein to autoregulate the MIE promoter, also all lacked the ability to bind to CRS sequences as GST/IE2(346-379) fusion proteins . Detailed analysis of point mutations in the 14-bp CRS target DNA binding motif revealed that IE2 binds in a relatively sequence-independent manner to 10-bp-long A/T-rich DNA elements bounded on each side by CG dinucleotides . Moreover, the A/T-rich minor groove binding agent distamycin, but not the G/C-rich minor groove binding agent chromomycin-A3, actively competed with IE2 for binding to the CRS motif in a dose-dependent fashion . In conclusion, IE2 binds preferentially as multimerized dimers to A/T-rich sequences in the minor groove that are flanked on both sides by appropriately spaced CG dinucleotides, and inhibition of the DNA-binding or oligomerization activity by PKA phosphorylation probably accounts for the inactivity of the mammalian and in vitro translated forms of the protein. Eur J Biochem, 1998 Dec 1, 258(2), 890 - 6 Protein LA, a novel hybrid protein with unique single-chain Fv antibody- and Fab-binding properties; Svensson HG et al.; Existing Ig-binding proteins all suffer from limitations in their binding spectrum . In the pursuit of the ultimate, non-restricted, Ig-binding protein, we have constructed the hybrid protein LA, by fusing four of the Ig kappa light-chain-binding domains of peptostreptococcal protein L with four of the IgGFc- and Fab-binding regions of staphylococcal protein A . Ligand-blot experiments demonstrated that the L and the A components were both functional in the hybrid, as the protein was shown to bind purified kappa light chains and IgGFc . Protein LA bound human Ig of different classes and IgG from a wide range of mammalian species . IgG, IgM and IgA were purified from human serum and saliva by affinity chromatography on protein LA agarose . Similarly, single-chain Fv (scFv) antibodies carrying the kappa light-chain variable domain or expressing the V(H)III (variable domain of the heavy chain of Ig) determinant, were efficiently purified on immobilized protein LA . As judged by surface plasmon resonance (SPR), protein LA showed enhanced affinity for all tested ligands, including several scFv antibodies, compared with proteins L and A alone . SPR analysis also demonstrated that binding of a ligand to one of the components in protein LA did not affect the ability of the hybrid protein to interact simultaneously with a ligand for the other component . The antigen-binding capacity of a kappa-expressing scFv antibody was unaffected by the interaction with protein LA, whereas the binding of a V(H)III-expressing scFv antibody to its antigen was, unexpectedly, blocked by protein A and protein LA . Together, these data demonstrate that protein LA represents a highly versatile Ig-binding molecule. Front Biosci, 1999 Jan 01, 4, D1 - 8 Aminoglycoside resistance mediated by the bifunctional enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase; Culebras E et al.; The expression of the bifunctional aminoglycoside inactivating enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase is the most important mechanism of high-level aminoglycoside resistance in Staphylococcus and Enterococcus . The enzyme is unique because it presents two different aminoglycoside-modifying activities located in different regions of the molecule . The gene aac(6')-aph(2") which encodes the synthesis of the enzyme is present in Tn4100-like transposons which are inserted both in R plasmids and the chromosomes of aminoglycoside-resistant isolates . The genetic structure of aac(6')-aph(2")-containing isolates indicates that their origin is not clonal, but plasmid conjugation together with multiple insertion events are in the basis of the rapid spread of aminoglycoside resistance among Gram-positive bacteria . There is not any prevalent genetic linkage of aac(6')-aph(2") with other antibiotic-resistance determinant . However, most methicillin resistant Staphylococcus strains present also high-level aminoglycoside resistance as the consequence of constant antibiotic pressure . This situation could change in the next future with the reported reemergence of gentamicin-susceptible MRSA isolates . Recent data show that inhibitors of eukaryotic protein kinases inhibit as well the aminoglycoside phosphotransferase activity . This effect indicates a common structure for these two families of proteins and opens the possibility for a meaningful survey of inhibitors of 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase useful in clinical practice. Mayo Clin Proc, 1998 Dec, 73(12), 1161 - 6 Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus; Walikonis JE et al.; OBJECTIVE: To establish and validate a double-antibody radioimmunoassay (RIA) for detecting serum auto-antibodies against glutamic acid decarboxylase (GAD65) . This enzyme catalyzes synthesis of the neurotransmitter gamma-aminobutyric acid in neurons and pancreatic islet cells . MATERIAL AND METHODS: We compared the frequency of GAD65 and other "thyrogastric" autoantibodies in adult patients with stiff-man (Moersch-Woltman) syndrome, type 1 diabetes, or polyendocrine disorders and in healthy subjects . The frequency of pancreatic islet cell antibody (ICA) detection was also assessed . The GAD65 RIA was validated by testing blinded samples, by confirming the specificity of low-titered positive results by "cold" antigen inhibition, and by comparing the RIA results with results of a kit assay incorporating staphylococcal protein A as immunoprecipitant . Recombinant GAD65 protein labeled with 125I was used as antigen, and a combination of anti-human IgG and IgM was used as immunoprecipitant . Seropositivity was determined for ICA and gastric parietal cell antibodies by indirect immunofluorescence assays and for thyroid peroxidase (microsome) and thyroglobulin antibodies by agglutination assays . RESULTS: We detected GAD65-specific antibodies in all but 1 of 46 local patients with stiff-man syndrome (98%); 16 had evidence of diabetes . Positive values exceeded 20 nmol/L in 96%, and 89% were ICA-positive; 76% had additional thyrogastric antibodies . Of 41 patients with type 1 diabetes (17 local and 24 workshop serum specimens), 33 were GAD65 antibody-positive (80%); 85% of these positive values were 20 nmol/L or lower . Only 18% of sera from patients with type 1 diabetes were ICA-positive, but 59% had other thyrogastric autoantibodies . Of 20 patients with autoimmune endocrinopathies without diabetes or stiff-man syndrome, 35% were GAD65 antibody-positive, 5% were ICA-positive, and 90% were thyrogastric antibody-positive . Of 117 healthy control subjects, 8% were GAD65 antibody-positive, and a third of those had other thyrogastric antibodies (14% overall); none was ICA-positive . CONCLUSION: Seropositivity in the double-antibody RIA for GAD65 autoantibody is a sensitive and specific marker of predisposition to type 1 diabetes and related organ-specific autoimmune disorders . As such, this RIA is complemented by assays for thyroid and gastric parietal cell autoantibodies. J Refract Surg, 1998 Nov-Dec, 14(6), 631 - 5 Microbiological examination of bandage soft contact lenses used in laser refractive surgery; Detorakis ET et al.; BACKGROUND: Disposable soft contact lenses are known to be colonized by bacteria and play a key role in bacterial keratitis pathogenesis . Such lenses, commonly used after laser refractive surgery procedures in which postoperative corneal infiltrations are sometimes observed, are potentially a substrate for bacterial inoculation . This study evaluates the extent of such a contamination . METHODS: Sixty disposable lenses collected from 60 eyes of patients who underwent photorefractive keratectomy (PRK), photoastigmatic refractive keratectomy (PARK), or laser in situ keratomileusis (LASIK) for the treatment of myopia or hyperopia were collected under sterile conditions over 4 months and cultured in various media . Results were statistically analyzed and the correlation with clinical and epidemiological data was examined . RESULTS: Eleven (18.3%) of the examined lenses were contaminated with Staphylococcus epidermidis . No other bacteria or fungi were found . Contamination was significantly more common among female patients (P = .036) . Correlation with the other clinical or operative parameters examined was statistically insignificant . CONCLUSIONS: Contamination was independent of the surgical procedure and females who were frequent users of eyelid cosmetics displayed higher contamination frequencies, suggesting that bacteria possibly originate from eyelid flora . The isolation of Staphylococcus epidermidis requires close postoperative surveillance, since it is a known cause of keratitis . Prophylactic postoperative treatment with tobramycin, gentamycin, or sulphonamides could be indicated. J Pharmacol Exp Ther, 1998 Dec, 287(3), 1098 - 104 Ebselen protects mice against T cell-dependent, TNF-mediated apoptotic liver injury; Tiegs G et al.; The seleno-organic drug ebselen (2-phenyl-1, 2-benzoisoselenazol-3(2H)-one) has glutathione peroxidase-like activity, and inhibits lipoxygenases, oxidative burst of leukocytes, nitric oxide synthases, protein kinases and leukocyte migration . This study elaborates in vivo in mice hitherto unknown immunopharmacological properties of ebselen . The compound was comparatively investigated in two different T cell-dependent hepatic hyperinflammation models and in two alternative models of receptor-activated liver apoptosis . Mice orally pretreated with ebselen were dose-dependently protected from concanavalin A (ConA)-induced liver injury . In livers from ebselen-pretreated mice exposed to ConA, the nuclear antiapoptotic transcription factor NFkappaB was upregulated . The release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF) was downregulated, while the ciculating amount of the anti-inflammatory cytokine interleukin-10 (IL-10) was increased . Ebselen protected also from liver injury induced by the superantigen staphylococcal enterotoxin B in galactosamine (GalN)-sensitized mice . Furthermore, ebselen protected the liver and enhanced circulating IL-10 in GalN-sensitized mice treated with recombinant TNF, i.e., the common distal mediator of ConA and SEB-induced hepatotoxicity . The activation of apoptosis-executing proteases, i.e., caspases, was blocked in livers of ebselen-treated mice following TNF receptor, but not following CD95 receptor activation . We propose a novel mechanism for the immunomodulatory properties of the drug and suggest that it might be useful in the therapy of T cell-mediated inflammatory disorders. Infect Immun, 1999 Jan, 67(1), 244 - 52 Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)-glucan; Soltys J et al.; Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock . In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, beta-(1,6)-branched beta-(1,3)-glucan (soluble beta-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice . In vitro stimulation of lymphocytes isolated from soluble beta-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppre