J Exp Med, 1996 May 1, 183(5), 2329 - 36 Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice; Bullard DC et al.; During the initial phase of the inflammatory response, leukocytes marginate and roll along the endothelial surface, a process mediated largely by the selectins and their ligands . Mice with mutations in individual selectins show no spontaneous disease and have mild or negligible deficiencies of inflammatory responses . In contrast, we find that mice with null mutations in both endothelial selectins (P and E) develop a phenotype of leukocyte adhesion deficiency characterized by mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe deficiencies of leukocyte rolling in cremaster venules with or without addition of TNF-alpha, and an absence of neutrophil emigration at 4 h in response to intraperitoneal Streptococcus pneumoniae peritonitis . These mice provide strong evidence for the functional importance of selectins in vivo. J Med Microbiol, 1996 May, 44(5), 381 - 9 Purification and properties of a novel glycosaminoglycan depolymerase from Streptococcus intermedius strain UNS 35; Shain H et al.; A glycosaminoglycan (GAG) depolymerase that acts on chondroitin sulphate A (CS-A), chondroitin sulphate C (CS-C) and hyaluronic acid (HA) was purified to apparent homogeneity from a culture of Streptococcus intermedius, strain UNS 35, grown in minimal medium supplemented with CS-A as the sole carbon source . The enzyme was purified by ammonium sulphate precipitation followed by serial chromatography on DEAE Trisacryl M, CM Trisacryl M and heparin-agarose . SDS-PAGE analysis of the purified enzyme yielded a single band with a mol.wt of c . 83000 . The purified GAG depolymerase was unusual in its substrate specificity . The enzyme was initially regarded as a CS depolymerase because of its induction by CS-A . However, the GAG depolymerase exhibited greatest activity against HA, whereas the degradation rates of CS-A and CS-C were c . 8% and 2%, respectively, of the rate with HA . On this basis the enzyme could be classified as a hyaluronidase rather than a CS depolymerase . The pH optimum was around neutrality and the enzyme was unusual in having a high pI of approximately 9.3. J Bacteriol, 1996 May, 178(10), 2971 - 4 Demonstration of UDP-glucose dehydrogenase activity in cell extracts of Escherichia coli expressing the pneumococcal cap3A gene required for the synthesis of type 3 capsular polysaccharide; Arrecubieta C et al.; The gene cluster of Streptococcus pneumoniae coding for the type 3 capsular polysaccharide contains four genes (cap3ABCD) . A DNA fragment containing the cap3A gene was amplified by PCR and cloned under the control of a T7 RNA polymerase-dependent promoter . Overexpression of this gene in Escherichia coli resulted both in a 47-kDa protein in the cytoplasm of isopropyl-beta-D-thiogalactopyranoside-induced bacteria and in high levels of UDP-glucose dehydrogenase activity . These data demonstrate, in a direct experimental way, that cap3A encodes the UDP-glucose dehydrogenase of pneumococcus type 3. Am J Respir Crit Care Med, 1996 May, 153(5), 1567 - 70 Lung hyaluronan decreases during group B streptococcal pneumonia in neonatal piglets; Juul SE et al.; Neonatal Group B streptococcus (GBS) sepsis and pneumonia result in lung injury and remain a major cause of morbidity and mortality in the newborn . Increased lung hyaluronan (HA) content is an important component of the lung's early response to damage in diseases such as adult respiratory distress syndrome (ARDS), infant respiratory distress syndrome (IRDS), and bleomycin-induced fibrosis . It is known, however, that GBS virulence factors include specific secretory enzymes such as hyaluronidase, an enzyme which breaks down HA . We therefore hypothesized that in lobar GBS pneumonia, lung HA would be decreased compared with normal values, and that in lobar pneumonia with atelectasis, lung HA would be further decreased because of increased substrate availability . The right lower lobes (RLL) and left lower lobes (LLL) of anesthetized piglets 16 +/- 2 d old were each selectively inoculated with 1 x 10(9) colony-forming units (CFU) GBS via an endobronchial catheter (n = 7) . The LLL was subsequently collapsed by endobronchial occlusion following 10 min of 100% O2 . Control animals (n = 6) was anesthetized, instrumented, and ventilated without exposure to GBS . At 4 h, lungs were removed and HA extracted and assayed using a competitive inhibition assay . HA extracted from areas of lobar pneumonia was significantly decreased (27 +/- 6.6 micrograms/g wet lung, p < 0.005) when compared with control values of control piglets (51 +/- 19.6 micrograms/g wet lung) . Atelectasis plus lobar pneumonia further decreased lung HA to 10 +/- 13.3 micrograms/g wet lung, p < 0.0001 . We conclude that lobar GBS decreases lung HA and that this process is augmented by collapsed lung regions, and speculate that this departure from the usual early lung response to injury contributes to GBS invasion of lung parenchyma. J Infect Dis, 1996 May, 173(5), 1077 - 84 Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection; de Moraes-Pinto MI et al.; Transplacental transfer of specific IgG antibodies was studied in 46 pairs of human immunodeficiency virus type 1 (HIV-1)-seropositive women and their neonates and in 53 pairs of healthy HIV-seronegative mothers and their newborns . Neonatal and maternal sera were assessed by nephelometry for total levels of serum IgG and by ELISA for IgG antibodies to herpes simplex virus (HSV), varicella-zoster virus (VZV), measles virus, tetanus toxoid, streptolysin O, and Streptococcus pneumoniae capsular antigens . Placental transfer of IgG antibodies to VZV, tetanus toxoid, measles, streptolysin O, and S . pneumoniae was decreased by maternal HIV infection . Maternal levels of total IgG had an independent effect on transfer of antibodies to HSV, VZV, measles, and S . pneumoniae . Neonatal antibody levels to tetanus toxoid, measles, and S . pneumoniae were significantly lower in the HIV group . Both maternal hypergammaglobulinemia and maternal HIV infection may contribute to these low antibody levels at birth and thus lead to early infection in this high-risk population. Infect Immun, 1996 May, 64(5), 1846 - 9 Streptococcus mitis cell walls and lipopolysaccharide induce lethality in D-galactosamine-sensitized mice by a tumor necrosis factor-dependent pathway; Le Roy D et al.; Purified cells walls of Streptococcus mitis induced tumor necrosis factor in vitro in whole blood of both lipopolysaccharide (LPS)-sensitive OF1 and LPS-resistant C3H/HeJ mice . They were as effective as heat-killed bacteria in inducing death in both strains of mice sensitized with D-galactosamine . Lethality was suppressed by anti-tumor necrosis factor antibodies . The histopathophysiological findings in mice after challenge with LPS or gram-positive cell walls were indistinguishable. Infect Immun, 1996 May, 64(5), 1672 - 8 An Eikenella corrodens toxin detected by plaque toxin-neutralizing monoclonal antibodies; Levine M et al.; Bacterial plaque from the gingival region of teeth contains cytotoxic agents which lyse undifferentiated human HL60 cells . A small panel of monoclonal antibodies (MAbs) was found to abrogate much of this activity and to detect antigens in certain strains of Streptococcus mitis and Eikenella corrodens . The aim of this study was to determine whether these bacterial antigens might be involved in HL60 cells cytolysis . Saline extracts were obtained by homogenizing washed, stationary-phase cells in 65 mM NaCl with a tight-fitting Potter-Elvehjem homogenizer . The extracts of E . corrodens were toxic to HL60 cells, whereas similar extracts of S . mitis were nontoxic . Adding plaque toxin-neutralizing MAb 3hE5 blocked the toxic effect of E . corrodens extract S . mitis extracts contained a single, strongly reactive antigen of 140 kDa (s140K antigen) detected on Western blots (immunoblots) by three MAbs from the panel . Rabbit antibodies raised to this antigen excised from the gel (anti-s140K serum) detected larger antigens in addition to s140K . E . corrodens extracts contained a number of antigens detected by the MAbs . Immunoglobulin G (IgG) was purified from anti-s140K serum by passage through DE52 cellulose . A 100-fold excess (by weight) of the purified IgG to E . corrodens protein specifically cross-precipitated an 80-kDa antigen plus a nonantigenic 16-kDa protein, presumably attached noncovalently . The remaining supernatant fraction had no toxic activity . A similar ratio of control IgG (from nonimmunized rabbits) did not precipitate these proteins, and the supernatant fraction had the same activity as the extract not treated with IgG . The proteins of 80 and 16 kDa were also detected in the anti-s140K immunoprecipitate by rabbit IgG antibodies to E . corrodens whole cells . The 80-kDa antigen, alone or complexed with the 16-kDa protein, may be involved in mediating the toxic activity in E . corrodens and plaque extracts. Transplantation, 1996 Apr 27, 61(8), 1156 - 61 Discriminant quantitation of posttransplant hepatic reticuloendothelial function . The impact of ischemic preservation; Klein AS et al.; This study focuses upon two discrete components of posttransplant hepatic reticuloendothelial system (RES) function-phagocytosis and killing of bacteria-under various conditions of ischemic preservation . We had previously reported that, following intravenous injection of rats with 51Cr and 125I double-labeled Escherichia coli, hepatic 51Cr levels can be used to reliably quantify hepatic phagocytic clearance of the bacteria from the blood (HPC), while the subsequent release of 125I from the liver accurately parallels hepatic bacterial killing . Here, Wistar rats were transplanted with syngeneic livers perfused with either normal saline (NS) or University of Wisconsin solution (UW) and stored at 4 degrees C for 1, 2, or 3 hr prior to implantation . Control rats underwent laparotomy and hepatic artery ligation . Using the double-labeled E coli assay, HPC was decreased in all transplanted animals when compared with controls, reaching a nadir on the third postoperative day (P < 0.05) . In rats transplanted with livers preserved in NS, the fraction of phagocytosed organisms that were subsequently killed (hepatic killing efficiency=HKE) was increased to 142%, 129%, or 112% of normal following 1, 2, or 3 hr of cold ischemia, respectively; P < 0.05) . Conversely, preservation of donor allografts in UW was associated with marked depression of HKE . Moreover, rats receiving NS- or UW-preserved livers tolerated an intravenous challenge with Streptococcus pneumoniae poorly (50% mortality) compared with hepatic artery ligated controls (12% mortality) at 7 days . Ischemic preservation of rat livers in NS resulted in a dose (of ischemia)-dependent reduction of hepatic phagocytosis coupled with a potentiation of HKE . Preservation in UW, however, produced a striking suppression of both components of hepatic RES function . Following a septic challenge survival was reduced in both groups of transplanted rats. FEMS Microbiol Lett, 1996 Apr 15, 138(1), 89 - 95 Prevotella intermedia and Prevotella nigrescens serotypes, ribotypes and binding characteristics; Dahlen GG et al.; Type strains and 62 clinical isolates of Prevotella intermedia and Prevotella nigrescens were typed with the use of genomic DNA fingerprints and rRNA gene probes . The strains were further serotyped with monoclonal antibodies and characterized with SDS-PAGE, enzymatic activities, hemolysis and hemagglutination and coaggregation with Streptococcus and Actinomyces spp . P . intermedia and P . nigrescens were found to have distinct ribotype patterns which correspond to previously defined serotyupes I and II/III, respectively . No clear phenotypic difference related to hemolysis, hemagglutination and coaggregation with streptococcus and actinomyces species, or expression of aminopeptides and lipase was found between P . intermedia and P . migrescens. J Biol Chem, 1996 Apr 12, 271(15), 8786 - 90 Structural and immunochemical characterization of the type VIII group B Streptococcus capsular polysaccharide; Kogan G et al.; The type VIII capsular polysaccharide has been isolated and purified from a newly described strain of group B Streptococcus which is a leading cause of sepsis and neonatal meningitis in Japan . The polysaccharide contains D-glucose, D-galactose, L-rhamnose, and sialic acid in the molar ratio 1:1:1:1 . By means of high resolution 1H nuclear magnetic resonance (1H NMR), 13C NMR, and homo- and heterocorrelated NMR, the repeating unit structure of the type VIII polysaccharide was delineated as the following, {formula: see text} Enzymatic studies established this polysaccharide as the first from which sialic acid, linked to a branched beta-D-galactopyranosyl residue, is known to be removed by bacterial neuraminidase. Oral Microbiol Immunol, 1996 Apr, 11(2), 121 - 8 Identification of a repeated epitope recognized by human serum antibodies in a surface protein antigen of Streptococcus mutans; Senpuku H et al.; This study determined the antigen determinants of a 190-kDa protein antigen of Streptococcus mutans that is involved in the initial attachment to the tooth surface . In 5 subjects, the reactivities of serum antibodies to 7 overlapping surface protein antigen fragments covering the entire antigen molecule and 19 sequential overlapping synthetic 19-mer peptides covering the entire A-region of the surface protein antigen were examined with enzyme-linked immunosorbent assay (ELISA) . The study showed that the A-region of the antigen is strongly immunogenic in humans and contains several widely distributed epitopes . In addition, an amino acid sequence of the one of dominant epitopes in a certain subject was identified as LTAENTAI with ELISA inhibition assays using the relevant truncated peptides . This epitope was located both at the positions from L-346 to I-364 and L-430 to E-437 of the antigen molecule, and serum antibodies against the epitope were found in 3 of the 5 subjects. Oral Microbiol Immunol, 1996 Apr, 11(2), 115 - 20 Purification and properties of extracellular glucosyltransferase from Streptococcus bovis; Uezono Y et al.; Eight Streptococcus bovis strains were classified into 3 types on the basis of isoelectric point (pI) and molecular mass (M(r)) of extracellular glucosyltransferase . Strains ATCC 9809, 35034 and 43143 produced glucosyltransferase of pI 3.7 and M(r) 165 kDa; strains ATCC 15351, 27960 and 33317 produced glucosyltransferase of pI 4.1 and M(r) 140 kDa; strains ATCC 43085 and 43144 did not produce any glucosyltransferase . The glucosyltransferase form S . bovis 9809 was purified by Bio-Gel hydroxyapatite chromatography and DEAE-Toyopearl chromatography . The S . bovis 9809 glucosyltransferase was immunologically identical with the other 5 S . bovis glucosyltransferases and not related to mutants streptococcal glucosyltransferases . The specific activity, the optimum pH and the Km value for sucrose were 17.9 U/mg protein, 6.0 and 5.0 mM, respectively . The first 11 N-terminal amino acid residues of the glucosyltransferases were DETSAVTLTRE, and the region was hydrophilic . The glucosyltransferases from S . bovis 9809 and 3317 synthesized from sucrose 1, 6-alpha-D-glucan with 9 and 2 mol%, 1, 3, 6-alpha-branched glucose, respectively. Microbiology, 1996 Apr, 142 ( Pt 4), 837 - 43 Surface location of HPr, a phosphocarrier of the phosphoenolpyruvate: sugar phosphotransferase system in Streptococcus suis; Dubreuil JD et al.; HPr is a low-molecular-mass phosphocarrier protein of the bacterial phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS) found in the cytoplasm or associated with the inner surface of the cytoplasmic membrane . Treatment of Streptococcus suis cells with a Sorvall Omnimixer, a technique used to extract cell surface components, resulted in the extraction of a major protein with a molecular mass of 9 kDa . Several lines of evidence suggested that this protein was HPr: (i) the S . suis protein showed homology over the first 35 N-terminal amino acid residues with the HPrs of Streptococcus salivarius and Streptococcus mutans, including the signature sequence for the site of PEP-dependent phosphorylation; (ii) it cross-reacted with the S . salivarius anti-HPr antibody preparation; (iii) it could be phosphorylated by enzyme I at the expense of PEP, and by a membrane-associated kinase at the expense of ATP; and (iv) it possessed phosphocarrier activity when used as a source of HPr in an in vitro PTS assay . The data suggested that a portion of the cellular HPr is associated with the external cell surface in S . suis, a result that was confirmed by immunogold electron microscopy . The cellular HPr of S . suis consisted of two forms that could be distinguished by the presence or the absence of the N-terminal methionine . Amino acid sequence analysis indicated that the cell-surface-associated HPr of S . suis lacked the N-terminal methionine residue. Acupunct Electrother Res, 1996 Apr-Jun, 21(2), 133 - 60 Significant mercury deposits in internal organs following the removal of dental amalgam, & development of pre-cancer on the gingiva and the sides of the tongue and their represented organs as a result of inadvertent exposure to strong curing light (used to solidify synthetic dental filling material) & effective treatment: a clinical case report, along with organ representation areas for each tooth; Omura Y et al.; Because of the reduced effectiveness of antibiotics against bacteria (e.g . Chlamydia trachomatis, alpha-Streptococcus, Borrelia burgdorferi, etc.) and viruses (e.g . Herpes Family Viruses) in the presence of mercury, as well as the fact that the 1st author has found that mercury exists in cancer and pre-cancer cell nuclei, the presence of dental amalgam (which contains about 50% mercury) in the human mouth is considered to be a potential hazard for the individual's health . In order to solve this problem, 3 amalgam fillings were removed from the teeth of the subject of this case study . In order to fill the newly created empty spaces in the teeth where the amalgams had formerly existed, a synthetic dental-filling substance was introduced and to solidify the synthetic substance, curing light (wavelength range reportedly between 400-520 nm) was radiated onto the substance in order to accelerate the solidifying process by photo-polymerization . In spite of considerable care not to inhale mercury vapor or swallow minute particles of dental amalgam during the process of removing it by drilling, mercury entered the body of the subject . Precautions such as the use of a rubber dam and strong air suction, as well as frequent water suctioning and washing of the mouth were insufficient . Significant deposits of mercury, previously non-existent, were found in the lungs, kidneys, endocrine organs, liver, and heart with abnormal low-voltage ECGs (similar to those recorded 1-3 weeks after i.v . injection of radioisotope Thallium-201 for Cardiac SPECT) in all the limb leads and V1 (but almost normal ECGs in the precordial leads V2-V6) the day after the procedures were performed . Enhanced mercury evaporation by increased temperature and microscopic amalgam particles created by drilling may have contributed to mercury entering the lungs and G.I . system and then the blood circulation, creating abnormal deposits of mercury in the organs named above . Such mercury contamination may then contribute to intractable infections or pre-cancer . However, these mercury deposits, which commonly occur in such cases, were successfully eliminated by the oral intake of 100 mg tablet of Chinese parsley (Cilantro) 4 times a day (for average weight adults) with a number of drug-uptake enhancement methods developed by the 1st author, including different stimulation methods on the accurate organ representation areas of the hands (which have been mapped using the Bi-Digital O-Ring Test), without injections of chelating agents . Ingestion of Chinese parsley, accompanied by drug-uptake enhancement methods, was initiated before the amalgam removal procedure and continued for about 2 to 3 weeks afterwards, and ECGs became almost normal . During the use of strong bluish curing light to create a photo-polymerization reaction to solidify the synthetic filling material, the adjacent gingiva and the side of the tongue were inadvertently exposed . This exposure to the strong bluish light was found to produce pre-cancerous conditions in the gingiva, the exposed areas of the tongue, as well as in the corresponding organs represented on those areas of the tongue, and abnormally increased enzyme levels in the liver . These abnormalities were also successfully reversed by the oral intake of a mixture of EPA with DHA and Chinese parsley, augmented by one of the non-invasive drug-uptake enhancement methods previously described by the 1st author, repeated 4 times each day for 2 weeks. Curr Microbiol, 1996 Apr, 32(4), 221 - 4 Inducer expulsion is not a determinant of diauxic growth in Streptococcus bovis; Kearns DB et al.; When Streptococcus bovis JB1 was repeatedly transferred in a medium that contained the non-metabolizable glucose analog, 2-deoxyglucose, it lost its phosphotransferase system (PTS) for glucose but was still able to take up glucose via a facilitated diffusion mechanism . The wild type (JB1) had an inducible enzyme II lactose, but the mutant (JB1(2DG)) had a constitutive lactose PTS . JB1(2DG) was no longer able to exclude lactose when it was provided with glucose, but it retained its ability to expel a non-metabolizable lactose analog . Because JB1(2DG) could utilize glucose and lactose simultaneously and grow in a non-diauxic fashion, it appeared that inducer expulsion was not an important catabolite regulatory mechanism . Based on these results, inducer expulsion may be an artifact of non-metabolizable sugars. West Afr J Med, 1996 Apr-Jun, 15(2), 111 - 6 An open evaluation of the efficacy and safety of the new macrolide roxithromycin in the treatment of lower respiratory tract infections and pneumonia in Nigerian patients; Isah AO et al.; Roxithromycin, a new introduction into the macrolide class of antibiotics possesses favourable pharmacokinetic properties enabling a once daily dosing . This study evaluates its efficacy, safety and tolerability, previously demonstrated in Europe and North America, in Nigeria patients suffering from lower respiratory tract infections . 32 patients, aged 18-65 years with acute bronchitis/acute exacerbation of chronic bronchitis and pneumonia were administered roxithromycin 300 mg once daily . 25 patients (12 males, 13 females: aged 39.2 +/- 2.7 years) were evaluable for clinical efficacy at the end of the study . The mean duration of treatment was 6.9 +/- 0.5 days . 22 patients (88.0%) responded to therapy . Sputum culture was positive in 5 patients (20.0%): Streptococcus pneumonia and resistant Klebsiella pneumonia . Therapy was discontinued in 3 patients due to non-response . The two patients in whom Klebsiella were isolated did not show any significant clinical improvement . The third non responding patient developed empyema . Gram negative bacilli were identified in the pleural aspirate but no patients with resistant Streptococcus pneumonia improved clinically . Adverse effects were mild, transient and included nausea (4) and diarrhoea (1) . The study suggests that roxithromycin is an effective and well tolerated antibacterial in the treatment of lower respiratory tract infection. Antimicrob Agents Chemother, 1996 Apr, 40(4), 941 - 6 Amoxicillin dose-effect relationship with Streptococcus pneumoniae in a mouse pneumonia model and roles of in vitro penicillin susceptibilities, autolysis, and tolerance properties of the strains; Azoulay-Dupuis E et al.; We used a mouse model of pneumococcal pneumonia to assess the bactericidal effect of increasing doses of amoxicillin (AMX) against clinical strains with various susceptibilities to penicillin . Twelve strains that exhibited similar virulence in mice were selected . Three were penicillin susceptible (PS) (penicillin and AMX MICs = 0.01 to 0.03 microgram/ml), three were intermediately resistant (PIR) (penicillin and AMX MICs = 0.5 to 1 microgram/ml), and six were penicillin resistant (PR) (penicillin and AMX MICs = 1 to 8 micrograms/ml) . Leukopenic Swiss mice were infected intratracheally with 10(7) CFU of each strain . Treatment was initiated 3 h after infection and consisted of a single subcutaneous injection of AMX at doses ranging from 2.5 to 10 mg/kg (PS strains), 5 to 100 (PIR strains), and 25 to 3,000 (PR strains) . Bacterial killing kinetics were recorded in the lungs over 9 h . The maximal log CFU reduction (Emax) was observed 3 h postinjection . The relation between Emax and log10(dose/MIC) showed two populations . With seven strains (the three PS, the three PIR, and one of the six PR {MICs, penicillin/AMX = 4/1}) a good correlation was observed between Emax and log10(dose/MIC) (r = 0.772; P < 0.02) . A bactericidal effect equal to 3.5 log10 CFU was observed at a log10(dose/MIC) = 2 . At this ratio, with the five other PR strains, Emax varied from 0.4 to 1.6 log10 CFU . In brain heart infusion medium containing AMX at 50 times the relevant MIC, these five PR strains were tolerant in vitro . Treatment failure with AMX was found in vivo, with tolerant, highly resistant strains. Antimicrob Agents Chemother, 1996 Apr, 40(4), 895 - 8 Relationship of MICs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections; Jacobs RF et al.; In June 1993, the National Committee for Clinical Laboratory Standards (NCCLS) recommended stringent new interpretive guidelines for antibiotics indicated for Streptococcus pneumoniae meningitis . To assess the predictive values of the recommended breakpoints, retrospective data were collected from patients who had S . pneumoniae infections and were treated with cefotaxime monotherapy . Susceptibilities based on the NCCLS interpretative categories were compared with clinical and bacteriologic outcomes . In 76 evaluable patients, the most common infections were bacteremia-septicemia (n = 49), meningitis (n = 37), and lower respiratory tract infection (n = 14) . Under the NCCLS breakpoints proposed in 1993, 55 isolates would have been classed as susceptible to cefotaxime (MIC, < or = 0.25 microgram/ml), 18 would have been classed as intermediate (MIC, 0.5 to 1.0 microgram/ml), and 2 would have been classed as resistant (MIC, > or = 2 micrograms/ml) . Of 75 cefotaxime-treated patients for whom cefotaxime MICs were recorded, 73 were clinically cured or improved (37 of 37 with meningitis and 36 of 38 with other infections) . One case of bacteremia and one case of bone-and-joint infection were scored as therapeutic failures because initial monotherapy had to be modified because of an adverse drug reaction . Excluding these patients, there were 18 patients infected with S . pneumoniae that would have been classed as not fully susceptible (i.e., MICs > or = 0.5 microgram/ml); all of these patients were cured or improved . The results of this analysis demonstrate that successful treatment with cefotaxime did not correlate well with the guidelines for the susceptibility of pneumococcal isolates to either penicillin or cefotaxime established by the 1993 NCCLS breakpoint recommendations . Because of this study and other similar findings, the NCCLS adopted more clinically relevant guidelines in 1994. Antimicrob Agents Chemother, 1996 Apr, 40(4), 829 - 34 Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics; Grebe T et al.; High-level resistance to beta-lactam antibiotics in Streptococcus pneumoniae is mediated by successive alterations in essential penicillin-binding proteins (PBPs) . In the present work, single amino acid changes in S . pneumoniae PBP 2x and PBP 2b that result in reduced affinity for the antibiotic and that confer first-level beta-lactam resistance are defined . Point mutations in the PBP genes were generated by PCR-derived mutagenesis . Those conferring maximal resistance to either cefotaxime (pbp2x) or piperacillin (pbp2b) were obtained after transformation of the susceptible laboratory strain R6 with the PCR-amplified PBP genes and selection on agar with various concentrations of the antibiotic . In the case of PBP 2x, transformants for which the cefotaxime MIC was 0.16 microgram/ml contained the substitution of a Thr for an Ala at position 550 (Thr550-->Ala), close to the PBP homology box Lys547SerGly, a mutation frequently observed in laboratory mutants and in a high-level cefotaxime-resistant clinical isolate as well . After further selection, transformants resisting 0.3 microgram of cefotaxime per ml were obtained; they contained the substitution Gly550 as the result of two mutations in the same codon . In PBP 2b, Thr446-->Ala, adjacent to another homology box Ser443SerAsn, was the mutation selected with piperacillin . This substitution has been described in all clinical isolates with a low-affinity PBP 2b but was distinct from point mutations found in laboratory mutants . Both pbp2b with the single mutation and a mosaic pbp2b of a clinical isolate conferred a twofold increase in piperacillin resistance . Attempts to select PBP 2b variants at higher piperacillin concentrations were unsuccessful . The mutated PBP 2b also markedly reduced the lytic response to piperacillin, suggesting that such a mutation is an important step in resistance development in clinical isolates. Antimicrob Agents Chemother, 1996 Apr, 40(4), 1039 - 40 In vitro activities of oxazolidinones U-100592 and U-100766 against penicillin-resistant and cephalosporin-resistant strains of Streptococcus pneumoniae; Mason EO Jr et al.; Two oxazolidinones and ceftriaxone, imipenem, rifampin, and vancomycin were tested against 162 penicillin-intermediate and 68 penicillin-resistant strains of pneumococci . U-100592 is two- to fourfold more active than U-100766 against penicillin-resistant pneumococci . The MICs of U-100592 at which 90% of the isolates were inhibited were 0.25 and 0.5 microgram/ml for penicillin-intermediate and -resistant strains, respectively, and 0.5 microgram/ml for ceftriaxone-susceptible, -intermediate, and -resistant strains . U-100592 MICs for 7 of 230 strains (2 from blood, 3 from middle-ear fluid, and 2 from the upper respiratory tract) were 1 microgram/ml. Antimicrob Agents Chemother, 1996 Apr, 40(4), 1005 - 8 Comparative efficacy and safety of 3-day azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children; Pacifico L et al.; The efficacy and safety of a 3-day course of azithromycin oral suspension (10 mg/kg of body weight once daily) were compared with those of penicillin V (50,000 U/kg/day in two divided doses) in children aged 3 to 12 years for the treatment of symptomatic pharyngitis caused by the group A beta-hemolytic streptococcus (GABHS) . For the 154 evaluable patients, the original infecting strain of GABHS was eliminated at the end of follow-up (34 to 36 days after treatment started) from 67 (85.8%) of 78 penicillin-treated patients and 41 (53.9%) of 76 azithromycin-treated patients (P < 0.0001) . Overall clinical success was achieved in 71 (91.0%) of 78 penicillin V-treated patients and 57 (75.0%) of 76 azithromycin-treated patients (P < 0.05) . Potential drug-related adverse events were reported for 5.5 and 8.6% of the penicillin V- and azithromycin-treated patients, respectively (P = 0.6) . In the present study, a once-daily (10 mg/kg), 3-day oral regimen of azithromycin was as safe as a 10-day course of penicillin but did not represent an effective alternative to penicillin for the treatment of GABHS pharyngitis, even for those children with azithromycin-susceptible strains. Protein Sci, 1996 Apr, 5(4), 693 - 704 The domain organization of streptokinase: nuclear magnetic resonance, circular dichroism, and functional characterization of proteolytic fragments; Parrado J et al.; Streptococcus equisimilis streptokinase (SK) is a bacterial protein of unknown tertiary structure and domain organization that is used extensively to treat acute myocardial infarction following coronary thrombosis . Six fragments of SK were generated by limited proteolysis with chymotrypsin and purified . NMR and CD experiments have shown that the secondary and tertiary structure present in the native molecule is preserved within all fragments, except the N-terminal fragment SK7 . NMR spectra demonstrate the presence in SK of three structurally autonomous domains and a less structured C-terminal "tail." Cleavage within the N-terminal domain generates an N-terminal fragment, SK7, which remains noncovalently associated with the remainder of the molecule; in isolation, SK7 adopts an unfolded conformation . The abilities of these fragments to induce active site formation within human plasminogen upon formation of their heterodimeric complex were assayed . The lowest mass SK fragment exhibiting Plg-dependent activator activity was shown to be SK27 (mass 27,000, residues 147-380), which contains both central and C-terminal domains, although this activity was reduced approximately 6,000-fold relative to that of full-length SK . The activity of a 36,000 mass fragment, SK36 (residues 64-380), which differs from SK27 in possessing a portion of the N-terminal domain, was reduced to 0.1-1.0% of that of SK . Other fragments (masses 7,000, 11,000, 16,000, 17,000, 25,000, and 26,000), representing either single domains or single domains extended by portions of other domains, were inactive . However, SK7 (residues 1-63), at a 100-fold molar excess concentration, greatly potentiated the activities of SK27 and SK36, by up to 50- and > 130-fold, respectively . These findings demonstrate that all of SK's three domains are essential for native-like SK activity . The central and C-terminal domains mediate plasminogen-binding and active site-generating functions, whereas the N-terminal domain mediates an activity-potentiating function. J Korean Med Sci, 1996 Apr, 11(2), 133 - 6 Comparison of M-serotypes of Streptococcus pyogenes isolated from healthy elementary school children in two rural areas; Kim SJ et al.; Serotypings have been used as markers for epidemiological surveys of Streptococcus pyogenes infections . Seventy-seven strains of S . pyogenes isolated from the throats of elementary school children in Kangwon Province in Korea in March and April 1992 were serotyped with M and/or opacity factor (OF) antisera . Sixty-eight strains of S . pyogenes from healthy school children in Chungnam Province in March 1993 were also serotyped and the distribution of serotype was compared with the isolates from those living in Kangwon Province . The distributions of M types were quite different between the two areas . M-78 (46.8%) and M-28 (22.1%) were most frequently encountered in Kangwon Province, while M-5 (20.6%), M-12 (16.2%), M-3 (13.2%), M-1 (11.8%) and M-62 (11.8%) were frequently isolated in Chungnam Province . Eighty-seven percent of strains in Kangwon produced OF while 33.2% of those in Chungnam produced OF (P < 0.0001) . The difference in the distribution of serotypes and of OF production in the isolates from the children in the two provinces may be responsible for differences in the epidemiology of group A streptococcal infections and their sequelae. Can J Physiol Pharmacol, 1996 Apr, 74(4), 368 - 75 Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis; Modanlou HD et al.; The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets . Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery . The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion . Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively . Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling . ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits . The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01) . In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations . In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1) . Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group . There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group . In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002) . The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations . Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis. J Clin Microbiol, 1996 Apr, 34(4), 853 - 9 Genetic relatedness within and between serotypes of Streptococcus pneumoniae from the United Kingdom: analysis of multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and antimicrobial resistance patterns; Hall LM et al.; A collection of 54 isolates of invasive Streptococcus pneumoniae of serotypes 3 and 14 and serogroups 6, 9, 19, and 23 was investigated . Multilocus enzyme electrophoresis and pulsed-field gel electrophoresis suggested that two clones were represented in the collection, one of serotype 14 isolates, most of which were resistant to erythromycin, and one of serotype 9V isolates, in which resistance to penicillin (MIC, 1 microgram/ml), cefotaxime, and co-trimoxazole was common . Among other isolates there were only a limited correlation between genetic relatedness measured by multilocus enzyme electrophoresis and expression of the same capsule type . However, isolates with highly related pulsed-field gel electrophoresis patterns always shared the same serotype and highly related allele profiles . Calculation of the index of association suggests a freely recombining population structure with epidemic spread of successful clones. J Periodontal Res, 1996 Apr, 31(3), 195 - 204 Clinical, microbiological and immunological profile of healthy, gingivitis and putative active periodontal subjects; Tanner A et al.; Thirteen periodontally healthy subjects were monitored clinically for 6-12 months . Clinical measurements at 6-weekly intervals included duplicate PD measurements, presence of plaque, redness, and bleeding on probing . Baseline measurements consisted of 2 visits 1 wk apart . Microbial samples were taken from 11 of the subjects who had completed at least 8 months of monitoring . Levels of serum antibodies to 12 periodontal species were determined from 10 subjects . Standard deviations of replicate PD measurements, computed for each subject, ranged from 0.2-0.3 mm over the monitoring period . Plaque and redness increased during monitoring, and showed a weak association with PD change . Baseline and follow-up distributions of PD changes indicated that changes of > 1.5 mm could reasonably be considered to represent active sites . Five subjects demonstrated at least 1 site deepening by 1.5 mm over the period monitored, and these were considered putative active subjects . Sites from 2 subjects showed PD increases in the 6 wk just before sampling, and these were considered to represent active sites . Species associated with putative active subjects included Actinomyces naeslundii, Veillonella parvula, Selenomonas noxia and Prevotella nigrescens . Streptococcus sanguis, S . gordonii and Peptostreptococcus micros were associated with inactive subjects . S . gordonii and S . oralis were associated with health, whereas P . nigrescens was associated with gingivitis . Elevated serum antibodies were detected to A . actinomycetemcomitans in 4 subjects . The predominant microbiota of putative active subjects included some species previously associated with gingivitis, and some species previously associated with progressing periodontitis. J Pediatr Surg, 1996 Apr, 31(4), 477 - 80 OK-432 therapy for lymphangioma in children: why and how does it work? Ogita S, Tsuto T, Nakamura K, Deguchi E, Tokiwa K, Iwai N. Intralesional injection of OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) is safe and effective therapy for lymphangioma . The authors evaluated the mechanism of this therapy in 6 patients who had cystic lymphangioma . The intracystic fluid of the cystic lymphangioma was aspirated before and after (on days 1 and 4) the OK-432 therapy . Changes in cell populations and cytokine productions in each aspirated fluid were analyzed . White blood cells in the intracystic fluid increased markedly in number . Before OK-432 therapy, 96% of the intracystic white blood cells were lymphocytes, and the remaining were neutrophils and macrophages . On day 1, the percentages of neutrophils and macrophages increased to 72% and 21%, respectively . On day 4, the percentage of lymphocytes increased to 72% . Flow cytometry analysis using monoclonal antibodies showed that the number of natural killer cells (CD56+) and T cells (CD3+) had increased . The activity of cytotoxic tumor necrosis factor (TNF) and interleukin-6 increased immediately after OK-432 injection and remained high in titer until day 4 . These findings suggest that the white blood cells induced and activated by OK-432, and the cytokines (including TNF) produced by these cells increased the endothelial permeability, and thus the accelerated lymph drainage and increased lymph flow let to shrinkage of the cystic spaces. Eur J Clin Microbiol Infect Dis, 1996 Apr, 15(4), 344 - 6 In vitro activity of ceftizoxime, ceftazidime, cefuroxime, ceftriaxone, cefotaxime, and penicillin against Streptococcus pneumoniae as determined by three quantitative methods; Barry AL et al.; E-test, broth microdilution, and agar dilution susceptibility tests were used to evaluate penicillin and five extended-spectrum cephalosporins against 196 strains of Streptococcus pneumoniae with different levels of penicillin resistance . Oxacillin disk tests corresponded to minimum inhibitory concentrations of penicillin determined by the E-test better than those generated by broth microdilution or agar dilution methods . Relative potency of the study drugs was as follows: cefotaxime = ceftriaxone > penicillin > cefuroxime > ceftizoxime > ceftazidime. Arch Pediatr, 1996 Apr, 3(4), 335 - 41 {Clinical course and treatment of pleural empyema in children}; Bremont F et al.; BACKGROUND: Purulent pleurisy has become rare . It is often masked by previous antibiotic treatment so that functional prognosis may be poor . PATIENTS AND METHODS: Twenty children with purulent pleurisy of the large cavity admitted from 1987 to 1993 were included in the study: there were nine infants (age 5 to 18 months) with pleuro-pulmonary staphylococcal infection (group I) and 11 children (4-13 years) (group II) . Clinical, biological, bacteriological and radiologic findings were analysed retrospectively as was the outcome . RESULTS: Patients of group I were admitted in poor general condition . X-ray showed moderate effusion and characteristic signs of staphylococcal infection . The bacteria identified in seven patients (77%) was S aureus . Recovery was rapid with antibiotics and simple local treatment . X-rays were normal two months after hospital discharge in seven patients (77%) . One infant presented cicatricial bullous emphysema which required segmental resection . Patients of group II were admitted for moderate respiratory signs after a relatively long delay (14 days) since the onset of symptoms . X-rays showed considerable effusion in all and mediastinal shift in five patients (45%) . Streptococcus pneumoniae was identified in one patient only . Local treatment of empyema was difficult; the effusion, already fibrinous, required repeated use of chest tubes in eight cases and surgical decortication in three . X-rays, performed 2 months after hospital discharge, were normal in only three patients . Long-term course was nevertheless favorable since chest X-rays at 5 months were normal in all children of both groups . CONCLUSIONS: Early recognition of purulent pleurisy is important in children aged over 3 years to ensure effective drainage before the effusion becomes fibrinous . All patients in whom the first tube was inserted after more than 10 days had a difficult follow-up requiring repeated chest drainages or surgery . Ultrasonography was a useful aid for diagnosis and local treatment . Computed tomography was useful for adapting treatment after several days of course. J Vet Med Sci, 1996 Apr, 58(4), 369 - 72 An enzyme-linked immunosorbent assay (ELISA) for the detection of antibody against Streptococcus suis type 2 in infected pigs; Kataoka Y et al.; An ELISA test for the detection of antibody against S . suis type 2 in pigs was developed and applied to field sera . The best sensitivity and specificity of ELISA were obtained when a purified polysaccharide antigen was used . It showed no cross reaction with sera against other serotypes of S . suis and other pathogenic bacteria . A total of 264 sera were collected from 20 pig farms and examined with the antibody against S . suis type 2 . In the affected farms, 17.0% of pigs tested were positive, 9.8% in the adjacent farms, but only 3.4% in the free farms . The difference of the positive percentages between the affected and the free farms was statistically significant (P < 0.05). Dan Med Bull, 1996 Apr, 43(2), 173 - 85 Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins; Rabbani GH; The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) . The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin . Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied . The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC . All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs . Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects . It appeared that berberine was more effective in ETEC diarrhoea than in cholera . However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects . Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone . Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera . It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera . Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea . For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea . Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes . In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions. Acta Odontol Scand, 1996 Apr, 54(2), 92 - 5 High strontium addition to chlorhexidine-fluoride gel does not increase its caries-preventive effect in rats; Spets-Happonen S et al.; One hundred Osborne-Mendel rats were weaned at the age of 21 to 22 days, inoculated with Streptococcus mutans in the mouth, and fed a semisynthetic diet for the next 43 days . The control group received no treatment . The study groups received gel applications on their molars with placebo, chlorhexidine-fluoride (CXF), CXF plus 50 ppm Sr, or CXF plus 250 ppm Sr daily for the first 21 days of the experiment Although caries was significantly reduced by CXF and CXF plus 50 ppm Sr treatments, the Sr additive did not significantly improve the caries-preventive effect of CXF . The addition of 250 ppm Sr to the CXF gel seemed markedly to weaken the effect of CXF. Microb Pathog, 1996 Apr, 20(4), 225 - 33 Deletion and reintroduction of glucosyltransferase genes of Streptococcus mutans and role of their gene products in sucrose dependent cellular adherence; Fujiwara T et al.; Streptococcus mutans has three kinds of glucosyltransferases (GTases), i.e . GTase-I, GTase-SI and GTase-S . These enzymes co-operatively synthesize adhesive glucan from sucrose, which contributes to firm adherence of growing organisms to solid surfaces . In this study, the genes encoding GTase-I (gtfB) and GTase-SI (gtfC) of S . mutans MT8148 (serotype c) were inactivated by the insertion mutagenesis by allelic exchange . Three types of isogenic mutants lacking either GTase-I, GTase-SI or both, respectively were isolated . Sucrose dependent cellular adherence of these mutants were significantly lower than that of the parent . Adherence of GTase-SI deficient mutant was lower than that of GTase-I deficient mutant . We then generated Escherichia coli-Streptococcus shuttle vectors carrying the gtfB and gtfC gene . The shuttle vector containing the gtfB gene was transformed into the GTase-I deficient mutant . Western blot analysis of the transformant revealed that GTase-I protein was fully expressed . Sucrose dependent adherence of the transformant increased but did not reach that of the parent . Similarly, the shuttle vector containing the gtfC gene was transformed into the GTase-SI deficient mutant . The expression of GTase-SI and sucrose dependent adherence of the transformant was revealed to be at a level similar to those by the parent . These results indicated that GTase-SI does play an essential role in the production of adhesive glucan that can lead to firm cellular adherence to solid surfaces. Microb Pathog, 1996 Apr, 20(4), 213 - 24 Streptococcus pyogenes infection in mice; Husmann LK et al.; We inoculated 5 to 7-week-old female C3HeB/FeJ mice with Streptococcus pyogenes strain B514-Sm (type M50) by both an intranasal and intratracheal route and characterized the resulting illness . Following intranasal inoculation, the animals developed signs of illness within 1 to 8 days post-inoculation which correlated with acute, suppurative, bronchopneumonia during histopathologic analysis; however, the relationship of response to dose was non-linear, as seen previously in a small group of mice . Intratracheal inoculations were then performed to increase the quantitative reliability of the model . Following intratracheal inoculation, the animals succumbed to an illness that was indistinguishable from that seen after intranasal inoculation, and the incidence of pneumonia followed a steep dose response curve . The dose at which 50% of the animals exhibited signs of respiratory illness within 72 h was 1.0 x 10(7) colony forming units . All of the animals that appeared ill had lung lesions as determined by gross and histopathologic examination . Bacteraemia followed pneumonia in two-thirds of the intratracheally inoculated animals, indicating that the S . pyogenes had crossed tissue barriers . We hope that this model will be useful in future studies concerning the role of suspected streptococcal virulence factors in the later stages of pathogenesis of invasive S . pyogenes infection. Vaccine, 1996 Apr, 14(5), 439 - 45 A simple, quantitative, reproducible avidin-biotin ELISA for the evaluation of group B streptococcus type-specific antibodies in humans; Basham LE et al.; Type-specific antibodies to the capsular polysaccharides (CP) of group B Streptococcus (GBS) are protective . Historically, the radioactive antigen-binding assay (RABA) has been used to determine GBS antibody levels . This method measures total immunoglobulin and employs the use of radioactive materials . We have developed an avidin-biotin ELISA that is less hazardous and is able to measure GBS Ia, Ib, II or III CP specific IgG . To avoid inconsistent binding to the plate, the CPs from GBS Ia, Ib, II and III were derivatized using adipic acid dihydrazide (ADH) and subsequently biotinylated without altering their antigenic epitopes and bound to avidin coated plates . Plasma from three different human subjects immunized with a tetravalent CP vaccine were used to prepare IgG references for Ia, II and III, respectively, thus rendering the assay quantitative for those types . The assay is able to detect nanograms per milliliter of GBS Ia, Ib, II or III specific antibody . This method is reproducible, sensitive and correlates with RABA by 76%. New Microbiol, 1996 Apr, 19(2), 133 - 40 Effect of sucrose consumption on level of Streptococcus mutans in saliva; Petti S et al.; The aim of the present paper was to study whether sucrose consumption may affect the level of salivary Streptococcus mutans . The study was justified by the disagreement between results of "in vitro", animal and human experiments and results of epidemiological studies made on study-populations . According to experimental research, sucrose availability promotes Streptococcus mutans selection and development in the oral cavity . On the other hand, the results of epidemiological studies run counter to these experiments . In the present study, the main reasons for this disagreement were investigated and identified . From this, an epidemiological study was performed, taking into account these potentially confounding factors . The results show that sucrose consumption is actually able to promote Streptococcus mutans selection and development in the oral cavity, thus increasing the risk of dental caries. Pharm Res, 1996 Apr, 13(4), 583 - 7 The effect of formulation on the antimicrobial activity of cetylpyridinium chloride in candy based lozenges; Richards RM et al.; PURPOSE . The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges . METHODS . In vivo activity was investigated using six volunteers by determining the reduction in colony forming units recoverable from the oropharynx after sucking each lozenge separately on different days . In vitro determinations investigated the relative activity of aqueous solutions of the lozenges, the effect on activity of additional active ingredients, pH and lozenge base ingredients against separate inocula of each of the test organisms Staphylococcus aureus, Streptococcus pyogenes and Candida albicans . RESULTS . Both in vivo and in vitro results showed that the pH of the dissolved lozenge solution was the single most influential readily adjustable formulation parameter which significantly influenced the activity of cetylpyridinium chloride activity in candy based lozenges . CONCLUSIONS . Lozenges containing cetylpyridinium chloride as the active ingredient should be formulated at a pH greater than 5.5. Kansenshogaku Zasshi, 1996 Apr, 70(4), 366 - 70 {A case of infective endocarditis with purpura and macroscopic hematuria as initial manifestations}; Masuda T et al.; A 44-year-old female admitted to our hospital because of fever, purpura and macroscopic hematuria . She had been diagnosed as having ventricular septal defect (VSD) . She noticed purpura with pain on bilateral legs and macroscopic hematuria since September 18, 1994 . Three weeks later she also manifested a fever . Physical examination of admission revealed numerous purpura and leg edema . Laboratory data showed macroscopic hematuria, marked anemia (Hb 3.3 g/dl), leukocytosis, azotemia (Cr 2.7 mg/dl) and positive acute phase reactants . Increased serum immune complex level and hypocomplementemia were also found . The diagnosis of allergic purpura was made initially, but positive blood culture of Streptococcus mitis and the detection of vegetation attached to the right ventricular wall near the ostium of the VSD made the definite diagnosis of infective endocarditis (IE) . Chemotherapy with PCG was started for two weeks but with no effect . The chemotherapy was altered to panipenem/betamipron with a daily dose of 3 g, Then, her fever fell and purpura, macroscopic hematuria and renal failure gradually disappeared . In this case, the cause of renal manifestations was considered to be immune complex glomerulonephritis . This is the first report of IE with macroscopic hematuria due to immune complex glomerulonephritis. Acta Paediatr Jpn, 1996 Apr, 38(2), 128 - 31 Outbreak of acute glomerulonephritis in children: observed association with the T1 subtype of group A streptococcal infection in northern Kyushu, Japan; Masuyama T et al.; Group A streptococcal infection is associated with the occurrence of acute glomerulonephritis (AGN) and rheumatic fever (RF) . A surveillance study in the Saga area, in northern Kyushu, Japan, showed a small variation in the reported number of group A streptococcal infections in the period 1988-94 . However, of the AGN cases reported in this period, more than half were observed in 1992 . In order to examine whether some change had occurred in the serotype distribution of Streptococcus pyogenes during the period, patients in the Saga area diagnosed as having group A streptococcal infection and patients with AGN or RF were analyzed . Serological T-typing of S . pyogenes was carried out for patients with group A streptococcal infections, and the association between the occurrence of AGN or RF and the distribution of each different T subtype was analyzed . M-typing of S . pyogenes was also carried out and the correlation between T and M types was examined . From 1988 to 1994, the annual number of patients with group A streptococcal infections in the Saga area showed a small variation, range 65-100 patients/year . Of the 42 patients with AGN and three with RF observed in this period, 27 with AGN (64%) and one with RF (33.3%) were detected in 1992 . Only the T1 subtype increased in 1992; the other T subtypes showed little variation in incidence . The number of patients with the T1 subtype was significantly correlated with the occurrence of AGN by regression analysis (P < 0.01) . Of the 170 subjects tested for both T and M subtypes, 44 of the 45 T1-typed subjects had the M1 protein . Our epidemiological study suggested that the T1 subtype of streptococcal infection was associated with an outbreak of AGN in 1992 in the Saga area. Hepatology, 1996 Apr, 23(4), 719 - 23 Spontaneous bacterial empyema in cirrhotic patients: a prospective study; Xiol X et al.; Spontaneous bacterial empyema (SBEM) is an infection of a preexisting hydrothorax in cirrhotic patients and has seldom been reported . To determine its incidence and primary characteristics, all cirrhotic patients with pleural effusion underwent thoracentesis at our hospital either on admission or when an infection was suspected . Pleural fluid (PF) study included biochemical analysis, polymorphonuclear (PMN) leukocyte count, and culture by two methods: conventional and modified (inoculation of 10 mL of PF into a blood culture bottle at the bedside) . SBEM was defined according to previously reported criteria: PF culture positive or PMN count greater than 500 cells/micro L, and exclusion of parapneumonic effusions . Sixteen of the 120 (13 percent) cirrhotic patients admitted with hydrothorax had 24 episodes of SBEM . In 10 of the 24 episodes (43 percent), SBEM was not associated with spontaneous bacterial peritonitis (SBP) . PF culture was positive by the conventional method in 8 episodes (33 percent) and by the modified method (blood culture inoculation) in 18 (75 percent) (P = .004, McNemar) . The microorganisms identified in PF were Escherichia coli in 8 episodes, Streptococcus species in 4, Enterococcus species in 3, Klebsiella pneumoniae in 2, and Pseudomonas stutzeri in 1 . All episodes were treated with antibiotics without inserting a chest tube in any case . Mortality during treatment was 20 percent . We conclude that SBEM is a common complication of cirrhotic patients with hydrothorax . Almost half of the episodes were not associated with SBP; thus, thoracentesis should be performed in patients with cirrhosis, pleural effusion, and suspected infection . Culture of PF should be performed by inoculating 10 mL into a blood culture bottle at the bedside. J Bacteriol, 1996 Apr, 178(8), 2455 - 8 Quinine specifically inhibits the proteolipid subunit of the F0F1 H+ -ATPase of Streptococcus pneumoniae; Munoz R et al.; Streptococcus pneumoniae is uniquely sensitive to quinine and its derivatives, but only those alkaloids having antimalarial properties, i.e., those in the erythro configuration, also possess antipneumococcal activity . Quinine and related compounds inhibit the pneumococcal H+ -ATPase . Quinine- and optochin-resistant pneumococci showed mutations that change amino acid residues located in one of the two transmembrane alpha-helices of the c subunit of the F0F1, H+ -ATPase. J Pediatr, 1996 Apr, 128(4), 531 - 5 Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease; Steele RW et al.; OBJECTIVE: Because of susceptibility to severe pneumococcal infection, children with sickle cell disease (SCD) routinely receive penicillin prophylaxis . Increasing rates of penicillin resistance have been reported throughout the world . Our objective was to assess the prevalence of nasopharyngeal colonization with Streptococcus pneumoniae and to assess the antimicrobial susceptibility of the organisms in children with SCD . STUDY DESIGN: Nasopharyngeal cultures for S . pneumoniae were obtained from all children with SCD attending clinics in a statewide university-based network . Background colonization rates were determined in children attending day care centers in some of the same locations . All recovered S . pneumoniae organisms were tested for susceptibility to penicillin, and all resistant strains were examined for susceptibility to other antibiotics . RESULTS: Overall nasopharyngeal pneumococcal colonization rates among children with SCD were 12% . Colonization was associated with age less than 2 years (p <0.001) and day care attendance for more than 20 hr/wk (p = 0.00005) . More than half of these strains (62%) were resistant to penicillin, 33% having intermediate resistance (minimal inhibitory concentration 0.06 to 1 microgram/ml) and 29%, high level resistance (minimal inhibitory concentration > or = 2.0 microgram/ml) . Penicillin resistance was associated with penicillin prophylaxis (p <0.01) . Many of these organisms were also resistant to other classes of antibiotics . CONCLUSIONS: Although penicillin prophylaxis and pneumococcal vaccine for patients with SCD have reduced overall nasopharyngeal colonization and disease caused by S . pneumoniae (p <0.001), a higher percentage of colonizing strains are now resistant both to penicillin and to other antimicrobial agents (p <0.01) . Newer strategies for preventing disease and early management of suspected pneumococcal infection in these children must be developed. Am J Respir Crit Care Med, 1996 Apr, 153(4 Pt 1), 1339 - 46 Distinct roles for pneumolysin's cytotoxic and complement activities in the pathogenesis of pneumococcal pneumonia; Rubins JB et al.; Pneumolysin, the major Streptococcus pneumoniae cytotoxin, contributes to the early pathogenesis of invasive pneumococcal pneumonia by facilitating intrapulmonary bacterial growth and invasion into the blood . Pneumolysin is a multifunctional toxin, with distinct cytolytic ("hemolytic") and complement-activation ("complement") activities that have been mapped to several regions of the molecule . To characterize the specific contributions of pneumolysin's hemolytic and complement properties to the pathogenesis of pneumococcal pneumonia, we compared the in vivo effects of type 2 S . pneumoniae mutant strains, which produce pneumolysins deficient in these activities . The absence of either pneumolysin's hemolytic or complement activities rendered mutant strains less virulent than the wild-type strain during pulmonary infection . Pneumolysin's hemolytic activity correlated with acute lung injury and bacterial growth at 3 and 6 h after endotracheal instillation . In contrast, pneumolysin's complement activity correlated with bacterial growth and bacteremia at 24 h after pulmonary infection . Pneumolysin's complement activity was not associated with the degree of alveolar-capillary injury or recruitment of leukocytes during initial pulmonary infection . However, pneumolysin's complement activity inhibited killing of mutant bacteria in an in vitro complement-dependent neutrophil killing assay . Thus, both pneumolysin's hemolytic and complement activities made specific contributions to the early pathogenesis of pneumococcal pneumonia at different stages of infection and by different mechanisms. Br J Cancer, 1996 Apr, 73(8), 917 - 23 Streptococcal glycoprotein-induced tumour cell growth inhibition involves the modulation of a pertussis toxin-sensitive G protein; Yoshida J et al.; We studied the mechanism of anti-tumour action of sulphydryl glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes in vitro . SAGP rapidly inhibited the incorporation of nucleic acid precursors into murine fibrosarcoma (Meth A) cells before it inhibited the cell growth . SAGP-induced cell growth inhibition was diminished by incubating the cells with pertussis toxin (IAP), whereas the SAGP activity was augmented by incubating the cells with cholera toxin (CTX) . Meth A cells exposed to SAGP underwent an increase in labelling of the alpha-subunit of an inhibitory guanine nucleotide-binding (Gi) protein in a subsequent IAP-catalysed {32P}ADP ribosylation of the cell membrane fraction . Gi alpha labelling was not increased either in the membrane from the Meth A cells exposed to heat-inactivated SAGP or in the membrane from L929 cells exposed to SAGP, in which growth was also unaffected . By contrast, SAGP caused no alteration in labelling the alpha-subunit of stimulatory guanine nucleotide-binding (Gs) protein in a subsequent CTX-catalysed ADP ribosylation of membrane fractions of Meth A and L929 cells . The amount of intracellular cAMP was decreased slightly in Meth A cells incubated with SAGP . Although the precise roles of Gs protein and adenylate cyclase in the cell growth inhibition induced by SAGP are not clear, these findings suggested that the modulation of Gi protein is involved in such SAGP-induced cellular events as the inhibition of nucleic acid synthesis and cell growth inhibition. J Bacteriol, 1996 Apr, 178(7), 1788 - 92 Separation of abnormal cell wall composition from penicillin resistance through genetic transformation of Streptococcus pneumoniae; Severin A et al.; Compared with most penicillin-susceptible isolates of Streptococcus pneumoniae, penicillin-resistant clinical isolate Hun 663 contains mosaic penicillin-binding protein (PBP) genes encoding PBPs with reduced penicillin affinities, anomalous molecular sizes, and also cell walls of unusual chemical composition . Chromosomal DNA prepared from Hun 663 was used to transform susceptible recipient cells to donor level penicillin resistance, and a resistant transformant was used next as the source of DNA in the construction of a second round of penicillin-resistant transformants . The greatly reduced penicillin affinity of the high-molecular-weight PBPs was retained in all transformants through both genetic crosses . On the other hand, PBP pattern and abnormal cell wall composition, both of which are stable, clone-specific properties of strain Hun 663, were changed: individual transformants showed a variety of new, abnormal PBP patterns . Furthermore, while the composition of cell walls resembled that of the DNA donor in the first-round transformants, it became virtually identical to that of susceptible pneumococci in the second-round transformants . The findings indicate that genetic elements encoding the low affinity of PBPs and the penicillin resistance of the bacteria are separable from determinants that are responsible for the abnormal cell wall composition that often accompanies penicillin resistance in clinical strains of pneumococci. Infect Immun, 1996 Apr, 64(4), 1450 - 3 Human pro- and anti-inflammatory cytokine patterns induced by Streptococcus pyogenes erythrogenic (pyrogenic) exotoxin A and C superantigens; Muller-Alouf H et al.; The superantigenic streptococcal erythrogenic toxins A and C (ETA/SPEA and ETC/SPEC) elicit the production by human peripheral blood mononuclear cells of substantial amounts of Th1-derived cytokines (interleukin-2 {IL-2} and gamma interferon) as well as anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) . In contrast, very low levels of IL-4 and no alpha interferon were induced . The production of these cytokines after stimulation with Streptococcus pyogenes heat-killed bacteria and lipopolysaccharide from gram negative bacteria differed qualitatively and quantitatively from that elicited by the superantigens. Infect Immun, 1996 Apr, 64(4), 1140 - 5 Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model; Sato K et al.; Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models . To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and into autolysin-negative derivative (A-1) . Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains . During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF) . Procaine penicillin G was given as 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h . Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears . Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection . Interleukin (IL)-1beta and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant . Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modes additional pneumolysin effect . Investigation strategies that limit the release of these products or neutralize them warrant further investigation. J Infect Dis, 1996 Apr, 173(4), 901 - 8 Genetic and phenotypic diversity among isolates of Streptococcus pyogenes from invasive infections; Chaussee MS et al.; To determine if recent cases of invasive group A streptococcal disease were caused by strains with a unique characteristic, 117 isolates Streptococcus pyogenes from patients with a variety of diseases, including necrotizing fasciitis and toxic shock syndrome, were analyzed . Significant genomic heterogeneity was observed among selected isolates, as determined using pulsed-field gel electrophoresis . The frequency of the bacteriophage-associated streptococcal erythrogenic toxin genes A and C (speA and speC) among the isolates was 44% (49/112) and 34% (38/112), respectively . Forty-three percent of speA-positive isolates produced streptococcal erythrogenic toxin (SPE) A in vitro . Seventy-six percent (85/112) of isolates produced SPE B in vitro, and in contrast to SPE A, little variation in the concentration of SPE B in broth culture supernatants was detected . The genetic and phenotypic heterogeneity observed among isolates from recent cases of severe infection does not support a clonal basis for the resurgence of invasive streptococcal infections. J Infect Dis, 1996 Apr, 173(4), 888 - 95 Properties of IgG-binding proteins expressed by Streptococcus pyogenes isolates are predictive of invasive potential; Raeder R et al.; Recent clinical Streptococcus pyogenes isolates of the M1 serotype can be grouped according to the IgG-binding properties of their M proteins . One group expressed an IgG-binding M1 protein reactive with human IgG1, IgG2, IgG3, and IgG4 (type IIo); the other expressed a protein with predominant reactivity with human IgG3 alone (type IIb) . Both IgG-binding protein phenotypes were equally resistant to phagocytosis in human blood; however, when they were injected into a skin air sac on outbred CD1 mice, all mice injected with M1 isolates of the type IIo phenotype were dead within 70 h, while only 40% of those injected with M1 isolates of the type IIb phenotype died within the same period . Bacteria recovered from the spleens of animals that died after injection with type IIb phenotype isolates demonstrated a change in their IgG-binding profile and were indistinguishable, in vitro or in vivo, from isolates displaying the type IIo phenotype. Dtsch Med Wochenschr, 1996 Mar 22, 121(12), 369 - 74 {Infectious thyroiditis as initial manifestation of embolizing endocarditis of the aortic valve}; Hofbauer LC et al.; HISTORY AND CLINICAL FINDINGS: A 47-year-old patient was admitted to hospital with fever (39.2 degrees C), weight loss and sore throat . The right thyroid area was painful on palpation . INVESTIGATIONS: The erythrocyte sedimentation rate was 56/86 mm, white blood cell count 10,600/l, with shift to the left and toxic granulations . Blood culture grew Streptococcus mitis; the echocardiogram showed vegetations on the aortic valve . Therefore aortic valve endocatidits was suspected . Ultrasound examination of the thyroid gland showed an echo poor area with an enlarged thyroid artery; thyroid cytodiagnosis was unremarkable . TREATMENT: The fever quickly subsided on administration of penicillin G (7.5 mill I.U . three times daily) and tobramycin (80 mg three times daily) for two weeks, followed by penicillin G in the same dosage for four more weeks . Vancomycin was then given for two weeks (1 g twice daily intravenously) . The aortic valve vegetations were no longer seen three weeks after onset of treatment . Two months after discharge the thyroid and heart were normal on ultrasound examination . CONCLUSION: Bacterial thyroiditis was caused by embolisation to the thyroid artery from vegetations on the aortic valve in aortic valve endocarditis, probably due to carious teeth. J Biol Chem, 1996 Mar 22, 271(12), 6832 - 8 Structural organization of the major autolysin from Streptococcus pneumoniae; Usobiaga P et al.; LytA amidase is the best known bacterial autolysin . It breaks down the N-acetylmuramoyl-L-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae and requires the presence of choline residues in the cell-wall teichoic acids for activity . Genetic experiments have supported the hypothesis that its 36-kDa chain has evolved by the fusion of two independent modules: the NH2-terminal module, responsible for the catalytic activity, and the COOH-terminal module, involved in the attachment to the cell wall . The structural organization of LytA amidase and of its isolated COOH-terminal module (C-LytA) and the variations induced by choline binding have been examined by differential scanning calorimetry and analytical ultracentrifugation . Deconvolution of calorimetric curves have revealed a folding of the polypeptide chain in several independent or quasi-independent cooperative domains . Elementary transitions in C-LytA are close but not identical to those assigned to the COOH-terminal module in the complete amidase, particularly in the absence of choline . These results indicate that the NH2-terminal region of the protein is important for attaining the native tertiary fold of the COOH terminus . Analytical ultracentrifugation studies have shown that LytA exhibits a monomer <--> dimer association equilibrium, through the COOH-terminal part of the molecule . Dimerization is regulated by choline interaction and involves the preferential binding of two molecules of choline per dimer . Sedimentation velocity experiments give frictional ratios of 1.1 for C-LytA monomer and 1.4 for C-LytA and LytA dimers; values that deviated from that of globular rigid particles . When considered together, present results give evidence that LytA amidase might be described as an elongated molecule consisting of at least four domains per subunit (two per module) designated here in as N1, N2, C1, and C2 . Intersubunit cooperative interactions through the C2 domain in LytA dimer occur under all experimental conditions, while C-LytA requires the saturation of low affinity choline binding sites . The relevance of the structural features deduced here for LytA amidase is examined in connection with its biological function. Ugeskr Laeger, 1996 Mar 18, 158(12), 1679 - 82 {An outbreak of Streptococcus pyogenes infections in institutions for the mentally retarded in Greater Copenhagen 1995}; Kristensen B et al.; The largest reported outbreak of infections due to Streptococcus pyogenes, M-type 18, in recent years is described . Ninety persons at institutions for mentally retarded (73% residents) had infections due to the epidemic strain . Pharyngitis and scarlatina were the most common infections . Six patients died, five having a streptococcal toxic shock syndrome . During the outbreak an intensive surveillance was carried out together with improved infection control measures and prompt culturing of residents and employees before antimicrobial treatment . The primary outbreak was confined but a secondary outbreak could not be prevented . This was probably due to difficulties in implementing proper isolation precautions in this setting. Lancet, 1996 Mar 16, 347(9003), 718 - 23 Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya; Gilks CF et al.; BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries . Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction . We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease.METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992 . 587 participants were HIV positive and 132 remained HIV negative . Set protocols were used to investigate common presentations . Cases were identified clinically and radiographically . Streptococcus pneumoniae and other pathogens were diagnosed by culture . FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5) . In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years . By serotyping, most recurrent events were re-infection . A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11% . Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae . At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes . During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL {123}) . The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66) . Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae . INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa. Arch Intern Med, 1996 Mar 11, 156(5), 572 - 4 Serious bacterial infections after endoscopic procedures; Schlaeffer F et al.; Transient bacteremia during and after endoscopic procedures is a well- documented phenomenon, but complicated bacteremia such as endocarditis in patients at risk is considered to be extremely rare . The recommendations for prophylaxis before endoscopy in patients with valvular heart disease were recently released . We discuss 16 cases of complicated bacteremia that developed after endoscopy (eight cases previously published in the literature and eight cases we encountered) . The endoscopic procedures were gastroscopy (five cases), sclerotherapy (six cases), sigmoidoscopy (three cases), and esophageal dilation (two cases) . Fourteen patients had underlying disease: valvular heart disease (six patients), cirrhosis of the liver (five patients, one of whom also had a prosthetic knee), valvular heart disease and cirrhosis of the liver (two patients), and gastric carcinoma (one patient) . The organisms involved were Streptococcus viridans (six cases), streptococcus group D (three cases), Streptococcus pneumoniae (two cases), Streptococcus microaerophilicus (two cases), Staphylococcus aureus (two cases), and Cardiobacterium hominis (one case) . The patients presented with the following infections: endocarditis (12 patients), spontaneous bacterial peritonitis (two patients), septic arthritis (one patient), and brain abscess (one patient) . The outcome was good in 15 patients; one patient died . Patients with valvular heart disease, cirrhosis of the liver, ascites, malignancies, or prosthetic joints who undergo endoscopic procedures should be considered for antibiotic prophylaxis. Proc Natl Acad Sci U S A, 1996 Mar 5, 93(5), 2014 - 8 T-cell epitope analysis using subtracted expression libraries (TEASEL): application to a 38-kDA autoantigen recognized by T cells from an insulin-dependent diabetic patient; Neophytou PI et al.; Studies on circulating T cells and antibodies in newly diagnosed type 1 diabetic patients and rodent models of autoimmune diabetes suggest that beta-cell membrane proteins of 38 kDa may be important molecular targets of autoimmune attack . Biochemical approaches to the isolation and identification of the 38-kDa autoantigen have been hampered by the restricted availability of islet tissue and the low abundance of the protein . A procedure of epitope analysis for CD4+ T cells using subtracted expression libraries (TEASEL) was developed and used to clone a 70-amino acid pancreatic beta-cell peptide incorporating an epitope recognized by a 38-kDa-reactive CD4+ T-cell clone (1C6) isolated from a human diabetic patient . The minimal epitope was mapped to a 10-amino acid synthetic peptide containing a DR1 consensus binding motif . Data base searches did not reveal the identity of the protein, though a weak homology to the bacterial superantigens SEA (Streptococcus pyogenes exotoxin A) and SEB (Staphylococcus aureus enterotoxin B) (23% identity) was evident . The TEASEL procedure might be used to identify epitopes of other autoantigens recognized by CD4+ T cells in diabetes as well as be more generally applicable to the study low-abundance autoantigens in other tissue-specific autoimmune diseases. Vet Rec, 1996 Mar 2, 138(9), 205 - 7 Bacterial pneumonia associated with corticosteroid therapy in three horses; Mair TS; Three horses developed severe pulmonary infections while being treated with systemic corticosteroids for other diseases . Two of them had an immune-mediated skin disease, compatible with a diagnosis of pemphigus foliaceus, and one had severe chronic obstructive pulmonary disease . Case 1 developed diffuse pneumonia from which Streptococcus zooepidemicus and Bacteroides melaninogenicus were isolated, and it responded to antibiotic therapy . Case 2 developed septicaemia, pulmonary thrombosis and pneumonia associated with Escherichia coli, and died during a peracute illness with signs of disseminated intravascular coagulation . Case 3 developed focal pneumonia from which S zooepidemicus was isolated . This horse was destroyed at the owner's request and no treatment was attempted. Int Endod J, 1996 Mar, 29(2), 108 - 12 Adherence of Streptococcus gordonii to smeared and nonsmeared dentine; Love RM; The purpose of this study was to investigate the adherence of Streptococcus gordonii to smeared and nonsmeared dentine and to assess the influence of patent dentinal tubules on bacterial retention . In order to examine bacterial adherence, 10 non-smeared (group 1) and 10 smeared samples (group 2) of outer root dentine were prepared from teeth exhibiting dentine sclerosis . Ten non-smeared samples from inner coronal root dentine that did not exhibit sclerosis were prepared in order to study the influence of patent tubules on bacterial retention (group 3) . Cells of the bacterium were radioactively labelled and an adhesion assay was performed . The number of bacteria adhering to the dentine surface was determined by scintillation counting . The results show that the number of bacteria adhering to both smeared and non-smeared outer sclerotic dentine was low (0.3% of inoculum), and there was no significant difference between the groups (P > 0.3) . A significantly higher number of bacteria was retained on the inner non-smeared coronal root dentine (P < 0.0001) compared to groups 1 or 2 . The results suggest that dentinal smear layers do not enhance or impede bacterial adherence to the dentine matrix . Dentinal surfaces with patent dentinal tubules retain more bacteria than a smeared surface. Afr J Med Med Sci, 1996 Mar, 25(1), 31 - 9 Experimental model for Porphyromonas gingivalis infection in animals; Eke PI et al.; A virulence model suitable for studying the dynamics of Porphyromonas gingivalis infection, including the pathogenicity of P . gingivalis in experimentally induced infections of multiple organs was developed using mouse and hamster . Virulence of P . gingivalis strains was expressed contrastingly in subcutaneous (sc) infection in the Murine abscess model (MAM) and the Hamsters abscess model (HAM) . Subcutaneous infection in the MAM was characterized by a gravity abscess, spreading from the primary site of inoculation downwards, frequently erupting as a secondary lesion . In contract, s.c . P . gingivalis infection in HAM was characterized as a palpable localized abscess at the primary site of inoculation . When the Semi-Solid Agar (SSA) was added to the mono-culture of P . gingivalis, reproducibility of infection in both models was enhanced . P . gingivalis culture supplemented with haemin, or combined with oral Actinomyces viscosus had its virulence overtly enhanced and often fatal in the MAM . Menadione, Eh reducing agents and mixture with the Streptococcus or A . neaslundii did not potentiate virulence in either mode . Transtracheal challenge of the lungs of hamster with P . gingivalis initiated an early pneumonitis and later sequelae of necrosis and abscess formation . Also, abscess was induced by direct inoculation of P . gingivalis in the muscles, liver and testes, but did not induce intra-abdominal abscesses . In conclusion, the HAM applied with the SSA procedure caused a localized P . gingivalis tissue infection with practical advantages for quantitative and qualitative studies of P . gingivalis infections . This study also demonstrates the pathogenic potential of P . gingivalis by reproducing similar infections in multiple anatomical sites. Clin Diagn Lab Immunol, 1996 Mar, 3(2), 227 - 9 Purification and seroreactivity of pneumococcal surface adhesin A (PsaA); Tharpe JA et al.; Pneumococcal surface adhesin A (PsaA) is a 37-kDa common protein antigen of Streptococcus pneumoniae . In the present study, the protein was purified so that its immunoreactivity could be determined . PsaA was released and purified from cells by lysis in the presence of n-laurylsarcosine; this was followed by ammonium sulfate precipitation and subsequent preparative isoelectric focusing . A capture antibody enzyme-linked immunosorbent assay was used to determine the immunoreactivity of purified PsaA . The assay had a 67% sensitivity for sera from patients with bacteremic pneumococcal pneumonia . A specificity of 97% was estimated on the basis of a lack of reactivity with sera from patients with pneumonia caused by other organisms . PsaA is a potential vaccine candidate and may be useful as an antigen in a diagnostic assay for pneumococcal disease. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1996 Mar-Apr, 37(2), 135 - 7 Group B streptococcal cellulitis of perineum and lower abdomen: report of one case; Chen HJ et al.; This report describes a 4-week-old female baby with disseminated group B streptococcus (GBS) infection . The illness began as a swelling with violaceous hue of perineum and lower abdomen, a manifestation that may be falsely attributed to a traumatic injury . GBS septicemia, meningitis and cellulitis of lower abdomen was confirmed by cultures . This case illustrated an unusual presentation of GBS infection as cellulitis of lower abdomen . The presence of concurrent septicemia and meningitis in this case indicated that a more extensive diagnostic work-up and a more aggressive therapeutic approach are needed for young infants with cellulitis. J Neurosurg Sci, 1996 Mar, 40(1), 53 - 8 Surgical treatment of subdural empyema: a critical review; de Falco R et al.; Between 1990 and 1992 six cases of subdural empyema were surgically treated at the Neurosurgical Division of Emergency Department of Cardarelli Hospital in Naples . Three cases were associated with paranasal sinusitis and three cases with otitis media . Headache and fever were the presenting symptoms in all cases; in only two cases they were associated with seizures and altered mental status . CT scans showed convexity low density collections in five cases and multilocalized pus collection in one; concurrent paranasal or mastoid infections were visualized as well . The organisms responsible for the subdural empyema were Peptococcus in four cases, Streptococcus and anaerobius in the other two cases . In five cases surgical treatment consists in pus drainage by selective burr hole and placement of a subdural small silicon tube for local antibiotic therapy . In one case with a loculated diffuse empyema, craniotomy was performed in order to provide a better access to all the localizations . In all cases drainage of the wound and intravenous antibiotic therapy were used . Paranasal sinus drainage or mastoidectomy performed by the otolaryngologist when a localized collection of pus was present, grave a quicker regression of symptoms . A full recover of the original neurological status was achieved in all cases; a 20 months mean followup confirms the results. Biopolymers, 1996 Mar, 38(3), 339 - 53 A flexible model for the cell wall polysaccharide of Streptococcus mitis J22 determined by three-dimensional 13C edited nuclear overhauser effect spectroscopy and 13C-1H long-range coupling constants combined with molecular modeling; Xu Q et al.; We report on the conformation of a tetrasaccharide fragment in the repeating subunit of the cell wall polysaccharide of Streptococcus mitis J22, a receptor for the lectin of Actinomyces viscosus T14V in a bacterial coaggregation that is important in the ecological interactions of oral bacteria . Although there is considerable overlap of the 1H-nmr signals, some cross peaks can be extracted from conventional two-dimensional nuclear Overhauser effect spectroscopy (NOESY) data on the polysaccharide . These data cannot be fit to a single conformation of the tetrasaccharide fragment . Therefore we have prepared a polysaccharide sample fully enriched in 13C from which we have determined accurate NOESY cross-peak volumes in a three-dimensional heteronuclear-resolved spectrum that allows accurate determination of many more NOESY cross peaks than does conventional two-dimensional spectroscopy . We have also used the 13C enriched polysaccharide to measure accurate values of long-range 13C-1H coupling constants that can be correlated with glycosidic dihedral angles . Molecular modeling calculations on the polysaccharide fragment, including molecular dynamics simulations, identify multiple low-energy conformations . This result is to be contrasted with previous calculations on blood group oligosaccharides in our laboratory using similar methods that showed relatively rigid conformations with little flexibility of the glycosidic linkages . The present NOESY and 3JCH data can be reconciled with a model for the antigenic tetrasaccharide in which three distinct conformations are in fast exchange . We propose that some carbohydrate epitopes such as those of the blood group oligosaccharides are relatively rigid while others such as the tetrasaccharide fragment in these studies exhibit much greater flexibility. J Clin Microbiol, 1996 Mar, 34(3), 592 - 6 Combinational detection of autolysin and penicillin-binding protein 2B genes of Streptococcus pneumoniae by PCR; Ubukata K et al.; PCR was used to identify penicillin resistance in 1,062 clinical isolates of Streptococcus pneumoniae . Three sets of primers were designed to amplify (i) a 240-bp fragment of the penicillin-binding protein (PBP) 2B gene (pbp2b) of penicillin-susceptible S . pneumoniae (PSSP), (ii) a 215-bp fragment of the class A mutations of the pbp2b gene present in penicillin-resistant S . pneumoniae, and (iii) a 286-bp fragment of the class B mutation . In addition, a set of primers that amplify 273 bp of the autolysin (lytA) gene was applied in combination with the above to identify S . pneumoniae . Of 621 isolates for which MICs of penicillin were < or = 0.06 mu g/ml, 614 (98.9%) were ascertained as having DNA fragments amplified by the PSSP primers . Of 441 isolates for which MICs of penicillin were > or = 0.125 mu g/ml, a class A mutation was detected in only 8 (1.8%), a class B mutation was detected in 310 (70.3%), and neither class A nor class B mutations were found in the remaining 123 (27.9%) . However, when analysis was limited to isolates for which MICs of penicillin were > or = 1.0 mu g/ml, 247 isolates (89.8%) of 275 were found to possess a class B mutation . When PBPs were analyzed in 12 isolates with unclear mutations of the pbp2b gene by using {3H}benzylpenicillin, low affinity to PBP 2B was observed in them all . These findings suggest that a pbp2b mutation other than class A or class B is present in these isolates . These results also indicate that it may be possible to identify PSSP and penicillin-resistant S . pneumoniae by applying PCR using a combination of primers to detect the susceptible pbp2b gene, resistant pbp2b gene mutations, and the lytA gene. Public Health, 1996 Mar, 110(2), 81 - 4 A prolonged outbreak of streptococcal infection among workers at a meat plant; Sims P et al.; We describe an outbreak of skin sepsis due to an erythromycin-resistant strain of Streptococcus pyogenes in workers at a meat plant . The outbreak began among butchers in the boning room but subsequently spread to other groups of workers in the plant . Despite the introduction of additional control measures, the outbreak persisted for 7 months and affected 46/194 staff with 'hands on' occupations . Spread of infection from the plant to a retail butcher was documented. Klin Padiatr, 1996 Mar-Apr, 208(2), 47 - 52 {Bacterial endocarditis in childhood}; Zacherl S et al.; BACKGROUND: Bacterial endocarditis in childhood is a rare but serious disease . The group of children with congenital heart disease at risk to develop bacterial endocarditis increases, because more children survive with advanced medical and surgical management . Rheumatic Fever as predisposing heart disease decreases and is of reduced importance . PATIENTS: From 1983 to 1993 16 patients in the age of 0.3 to 17.6 years (mean 10.6 years) were received by the Department of Pediatric Cardiology of the University Children's Hospital Vienna with the diagnosis "bacterial endocarditis" . A congenital heart disease was known previously in 13 cases: 4 children had VSD, 2 children had Tetralogy of Fallot, 1 child had a single ventricle and an infundibular pulmonary stenosis, 4 children had pulmonary atresia, 1 child had a cleft of the mitral valve, and 1 child had a coronary artery fistula . Moreover, 1 child had a mitral valve prolapse with valvular regurgitation as a consequence of Marfan-Syndrome . 6 children with congenital heart disease had been treated surgically previously . METHODS: Medical data of all patients with the diagnosis of "bacterial endocarditis" between 1983 and 1993 were analysed . It was this period when echocardiography was used for the first time to contribute to diagnosis and course control . RESULTS: In 11 of 16 cases positive blood cultures were obtained . Mostly Streptococcus viridans (4 cases) and Staphylococcus aureus (3 cases) were isolated . During the parenteral therapy with antibiotics 9 children suffered as a side effect from a drug induced fever and/or decreasing leucocytes and thrombocytes or a rash . In addition to the antibiotic therapy 8 children were treated surgically . One child died immediatly after the operation . 15 of the 16 patients with endocarditis survived . CONCLUSIONS: With children with known heart disease the recommendations for the prevention of bacterial endocarditis have to be strictly followed and every long ongoing feverish disease has to be carefully examinated. Microbiology, 1996 Mar, 142 ( Pt 3), 695 - 705 Exclusion of long heterologous insertions and deletions from the pairing synapsis in pneumococcal transformation; Pasta F et al.; We have studied the mode of recombination of six insertions during genetic transformation of Streptococcus pneumoniae . The six heterologous insertions are located at the same site in the ami locus of the pneumococcal chromosome; insertion sizes range from 4 to 1374 bp . With respect to single-point markers we found that the number of transformants in one-point crosses is reduced, while the number of wild-type transformants in two-point crosses is drastically increased, what we call hyper-recombination . The magnitude of the shift is correlated with the size of the insert . This effect could result either from a special repair pathway of multibase heteroduplexes or from the exclusion of multibase heterologous insertions out of the pairing synapsis . To test these hypotheses we have used insertions in two kinds of three-point crosses . The repair model predicts that the excess of wild-type transformants remains in one set of crosses but is suppressed in the second set . The results we obtained are reversed, ruling out the hypothesis of a repair process, but in agreement with predictions based on the exclusion model . Moreover, we have re-examined the situation of deletions, our previous results suggesting that deletions were likely to be converted at the heteroduplex step . Genetic evidence we obtained in this work no longer supports this hypothesis . Thus, long heterologous insertions are partly excluded at the pairing step. Zentralbl Bakteriol, 1996 Mar, 283(3), 332 - 9 Postantibiotic effect of penicillin on Streptococcus anginosus; Do Amaral MM et al.; We studied the postantibiotic effect of penicillin G on bacterial growth of two strains of Streptococcus anginosus by optical density readings of the cultures and by counting the numbers of viable cells . Duration of the effect of the drug in concentrations equivalent to the MICs after exposure for 2 h was 3.4 and 3.5 h . The production of streptococcal substances was examined during the postantibiotic phase . The antibiotic caused an increase in deoxyribonuclease and a decrease in both free and cell-bound hemolysin activities of one strain . The other strain displayed an increase in hyaluronidase and both free and bound hemolysin production. Zentralbl Bakteriol, 1996 Mar, 283(3), 328 - 31 Susceptibility to antimicrobial agents of Streptococcus suis capsular type 2 strains isolated from pigs; Seol B et al.; The minimal inhibitory concentrations (MICs) for thirty-three epidemiologicaly unrelated clinical isolates of Streptococcus suis capsular type 2 were determined in relation to ampicillin, ampicillin-sulbactam, amoxicillin, clavulanate-amoxicillin, penicillin G, cephalexin, gentamicin, streptomycin, erythromycin, tylosin and doxycycline, using the microtitre broth dilution procedure described by the U.S . National Committee for Clinical Laboratory Standards (NCCLS) . Gentamicin was the most active compound tested, with an MIC for 90% of the strains tested (MIC(90)) of 0.4 mg/L . Overall, 70% of strains were resistant to doxycycline (MIC(90) > or = 100.0 mg/L), followed by penicillin G (51% of strains) (MIC(90) + or = 100.0 mg/L) . Resistance to amoxicillin and ampicillin was 36.4% (MIC(90) 12.5 mg/L) and 33.3% (MIC(90) 50.0 mg/L), respectively . 15.2% of S . suis strains were resistant to streptomycin, tylosin and cephalexin with MIC90 values of 25.0 mg/L, 12.5 mg/L and 25.0 mg/L, respectively . A combination of ampicillin and sulbactam (MIC(90) 6.3 mg/L) and a combination of amoxicillin and clavulanate (MIC(90) 3.1 mg/L) as well as erythromycin (1.6 mg/L) were of the same efficacy, with a total of 9.1% resistant S . suis strains . This high percentage of resistance to doxycycline and penicillin G precludes the use of these antibiotics as empiric therapy of swine diseases. Clin Infect Dis, 1996 Mar, 22(3), 437 - 40 Risk factors for isolation of Streptococcus pneumoniae with decreased susceptibility to penicillin G from patients infected with human immunodeficiency virus; Meynard JL et al.; We conducted a retrospective study of all hospitalized human immunodeficiency virus (HIV)-infected patients from whom a strain of Streptococcus pneumoniae was isolated (n = 45) between January 1992 and September 1994, in order to determine the clinical manifestations and outcome of and risk factors for infection by S . pneumoniae with decreased susceptibility to penicillin G . Such strains were isolated from 14 patients (31%), of whom 8 had pneumonia, 2 had bronchial superinfection, 2 had sinusitis, and 2 were colonized . All infected patients made a clinical recovery regardless of the MIC of the isolate . Indexes of HIV disease stage (CD4+ cell count and p24 antigenemia), antiretroviral treatment, and hospital admission in the previous 3 months did not influence the susceptibility of the isolates . For HIV-infected patients, treatment with antibacterial agents--particularly trimethoprim-sulfamethoxazole--in the previous 3 months is associated with an increased risk for isolation of S . pneumoniae with decreased susceptibility to penicillin G (relative risk, 5.0; 95% confidence interval, 1.9-13.3). Am J Respir Cell Mol Biol, 1996 Mar, 14(3), 217 - 24 Polymorphonuclear leukocyte (PMN) migration in streptococcal pneumonia: comparison of older PMN with those recently released from the marrow; Lawrence E et al.; In acute bacterial pneumonia, polymorphonuclear leukocytes (PMN) sequester in the lung and migrate into the alveolar airspaces . These local events are accompanied by a systemic response that includes release of PMN from the bone marrow into the circulation . The present study was designed to compare the sequestration and migration of these newly released PMN with those already in the circulation in a model of acute streptococcal pneumonia in rabbits . PMN were labeled in the mitotic pool in the marrow by administration of 5'-bromo-2'-deoxyuridine (BrdU 100 mg/kg) and the labeled cells were detected in blood and tissues by immunohistochemistry . The proportion of BrdU-labeled PMN (PMN BrdU) that sequestered and migrated in the lung tissue infected with Streptococcus pneumoniae and the uninfected lung was measured using morphometric techniques . The results show an increase in the proportion of PMN BrdU (6.0 +/- 1.0% to 17.3 +/- 3.8%, P<0.05) in the circulation 5 h following the induction of a pneumonia and the PMN expressed a higher concentration of L-selectin (9.3 +/- 0.7 to 14.9 +/- 0.8 MFI, P<0.05) . The proportion of PMN BrdU in the control tissue was not different from the proportion in the systemic circulation (11.4 +/- 1.6%) . The PMN BrdU increased in the pneumonic site at 5 h (19.9 +/- 3.4%, P<0.05) and 8 h (26.6 +/- 1.5%, P<0.05) after treatment . Only 2.8 +/- 0.3% and 2.8 +/- 0.6% of the PMN that migrated into the airspace at 5 and 8 h were PMN BrdU . We conclude that PMN released into the circulation as part of the systemic response to a local streptococcal pneumonia sequester normally but may be slow to migrate into the airspaces at the inflammatory site. Mol Microbiol, 1996 Mar, 19(5), 1035 - 45 The mmsA locus of Streptococcus pneumoniae encodes a RecG-like protein involved in DNA repair and in three-strand recombination; Martin B et al.; We describe the characterization of a mutant strain of Streptococcus pneumoniae previously isolated on the basis of its sensitivity to Methyl Methane Sulphonate (MMS) . The mutant strain also exhibited increased sensitivity to UV light and to X-rays, together with a reduced capacity for recombination and Hex-mediated generalized mismatch repair . We show that the original mutant contains two unlinked mutations in the mmsA and in the pms genes . The mmsA wild-type region was cloned and the nucleotide sequence of the mmsA gene was determined . mmsA encodes a polypeptide of 671 amino acids related to a large family of DNA-RNA helicases, with the highest similarity to Escherichia coli RecG, a protein involved in the branch migration of Holliday junctions . A plasmid carrying the intact mmsA coding region was shown to restore UV resistance to E . coli recG mutant strains . An mmsA-null mutant constructed by insertion of a chloramphenicol-resistance gene exhibited a 25-fold reduction in recombination during transformation . We suggest that MmsA recognizes and branch migrates three-strand transformation intermediates to extend donor-recipient heteroduplex regions . The mmsA-null mutant exhibited the other phenotypes of the original mutant, apart from mismatch-repair deficiency and, in addition, an alteration in colony-forming ability was noticed . In the pms mutant background, all phenotypes caused by the mmsA mutation were attenuated . Therefore, the pms mutation, although it affected mismatch repair and, to some extent, DNA repair and recombination, acted as a suppressor of the mmsA mutation. Nihon Kyobu Shikkan Gakkai Zasshi, 1996 Mar, 34(3), 341 - 4 {Saprophytic pleuritis with Candida parapsilosis}; Nakagawa Y et al.; A 73-year-old man was admitted to our hospital with pneumonia in the right S6 induced by Streptococcus milleri and with left pleural thickening . He had histories of diabetes mellitus for 30 years and pulmonary tuberculosis 35 years ago . The pneumonia resolved completely after administration of ceftazidime and clindamycin for 10 days, but the pleural thickening remained and computed tomography revealed that it was an encapsulated effusion without calcification . An aspirate was turbid yellow with a high concentration of lipids, and consisted of dominant crystals and scattered cells, 80% of which were yeasts and 20% of which were macrophages phagocytizing them . Only Candida parapsilosis developed in culture . The same silent pleural shadow was identified on chest X-ray films obtained over the previous 7 years . The persistent pleuritis was diagnosed as saprophytic infection with C . parapsilosis. J Pediatr, 1996 Mar, 128(3), 319 - 23 Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis; Manco-Johnson MJ et al.; OBJECTIVE: The objective