Eur J Immunogenet, 1997 Dec, 24(6), 423 - 30 Hierarchy of SPEA presentation to T cells by mouse MHC haplotypes; Charlton FG et al.; The ability of splenic antigen-presenting cells (APC) from nine independent mouse major histocompatibility complex (MHC) haplotypes to present recombinant streptococcal exotoxin A (rSPEA) to heterogeneous T cells and mouse T cell clones were compared using proliferation assays . We report that there is marked variation between MHC haplotypes, which can be ranked as follows: H2z > H2s = H2f = H2p = H2r = H2k > H2d > H2b = H2q . In some haplotypes both A and E molecules bind rSPEA with low affinity . In addition, we show that presentation is preferentially by E molecules in haplotypes where A and E are coexpressed, but that A alleles also bind and present rSPEA, based on inhibition of responses by anti-E and anti-A mAbs . Furthermore, using strains of mice which fail to express E, we demonstrate that A(s) and Af present rSPEA with high efficiency, whereas Aq and Ab are the least efficient of all haplotypes . The results suggest that there is significant variation in the ability of different alleles of both E and A molecules to bind and present rSPEA. Zh Mikrobiol Epidemiol Immunobiol, 1998 Jan-Feb, (1), 40 - 5 {The scientific, organizational and methodological bases for the epidemiological surveillance of streptococcal group A infection in a large city}; Filatov NN et al.; These investigations have made it possible to establish the extent and scale of the spread of streptococcal infection (group A) and its socioeconomic importance in Moscow, a great mega-police of the world . The deterioration of the epidemiological situation in recent years, accompanied by an increase in morbidity and mortality caused by streptococcal infection, has been demonstrated . The program and conceptual foundations of epidemiological surveillance on this infection in Moscow are presented . The aspects of epidemiological surveillance (informational and analytical, diagnostic, administrative) have been indicated and described . The order and direction of their realization have been determined. Semin Immunol, 1998 Feb, 10(1), 5 - 13 The role of infection in the pathogenesis of autoimmune disease; Rose NR; Autoimmune disease has long been considered a shadow following infectious diseases . Epidemiological evidence shows that rheumatic fever follows streptococcal infection and Trypanosoma cruzi infection is the instigator of Chagas' disease . There is, however, very little information of the mechanism by which such a train of events is initiated . Autoimmunity, in a form of autoantibodies, is common after many infections and may well result from the mimicking of host proteins by antigens of the infectious agent . There are, however, few if any examples in humans where molecular mimicry gives rise to autoimmune disease . The progression from benign autoimmunity to pathogenic autoimmune disease depends upon the balance of cytokines produced during the inflammatory process accompanying infection . In many autoimmune diseases, the cytokine profile favors the proinflammatory cytokines, IFN-gamma and IL-1, which support the production of disease . A searching study of cytokine profiles during infection may offer a promising approach to avoiding the harmful consequences of post-infection autoimmune responses. Curr Opin Pediatr, 1998 Feb, 10(1), 73 - 6 Childhood osteomyelitis and septic arthritis; Wall EJ; The diagnosis, treatment, and monitoring of septic arthritis or osteomyelitis in children has become more streamlined in recent years . C-reactive protein appears to be a better laboratory study than sedimentation rate in the diagnosis of bone or joint infection and in monitoring a patient's clinical response to antibiotics . Oral antibiotics may be rapidly substituted for intravenous antibiotics in patients who have a identifiable sensitive organism, who show rapid clinical improvement, and who show rapid normalization of C-reactive protein . The physician must remain alert for resistant organisms, highly virulent organisms (post-varicella streptococcal infections) and rare organisms. Dermatology, 1997, 195(4), 404 - 7 Atrial myxoma syndrome mimicking Ehrmann-Sneddon syndrome; Weisshaar E et al.; Livedo racemosa with cerebrovascular lesions has been described as Ehrmann-Sneddon syndrome . The etiopathogenetic factors provoking the vascular lesions, however, are of high diversity reaching from mechanical to autoimmune causes . We present a male patient with typical livedo racemosa, muscle pain and feeling of coldness of the forearms . By dermatohistopathology and magnetic resonance tomography of the brain, Ehrmann-Sneddon syndrome could be confirmed . At this time a chronic streptococcal infection could be diagnosed . Antibiotics, anticoagulants and vascularity-supplying therapy improved the clinical and subjective symptoms . Six months later, the patient developed dizziness, vision disorder, hypesthesia of the right forehead, malaise and weight loss . A further diagnostic workup including echocardiography revealed a myxoma of the left atrium . This report illustrates the association of Ehrmann-Sneddon syndrome with cardiac myxoma and points out that cardiac diagnostic examination should be included when dealing with small-vessel involvement of the brain. Clin Infect Dis, 1998 Mar, 26(3), 631 - 8 Varying titers of neutralizing antibodies to streptococcal superantigens in different preparations of normal polyspecific immunoglobulin G: implications for therapeutic efficacy; Norrby-Teglund A et al.; Inasmuch as normal intravenous polyspecific immunoglobulin G (IVIG) neutralizes the activity of a wide spectrum of superantigens, it may be an efficient adjunctive therapy for diseases associated with superantigen-producing organisms, including severe group A streptococcal diseases . The neutralizing activity against purified superantigens, streptococcal pyrogenic exotoxins (Spe), and a mixture of superantigens present in culture supernatant of clinical group A streptococcal isolates was determined for five IVIG preparations . A significant variation among different IVIG preparations (P < .05) and different lots of the same IVIG brand (P < .044) was found . Neutralization of SpeA activity was significantly lower than that of other streptococcal superantigens (P < .05); however, there was no correlation between SpeA binding and SpeA neutralizing activity in different IVIGs . Plasma samples obtained from patients after IVIG infusion varied in their titers of neutralizing antibodies to culture supernatants prepared from their respective isolates, and this variation paralleled differences in the neutralizing titer of the IVIG lot administered to each patient studied . The study suggests that complete neutralizing activity may be achieved by optimizing the type and/or dose of IVIG used in treatment. Clin Infect Dis, 1998 Mar, 26(3), 584 - 9 Invasive group A streptococcal disease in Taiwan is not associated with the presence of streptococcal pyrogenic exotoxin genes; Hsueh PR et al.; We reviewed the clinical features of 44 patients with invasive group A streptococcal (GAS) disease who were treated at two teaching hospitals in southern Taiwan from 1991 to 1994 . Genes encoding streptococcal pyrogenic exotoxin types A (speA), B (speB), C (speC), and F (speF) and serotypes of M1, M6, and M12 were determined by polymerase chain reaction to target specific sequences in the 44 isolates recovered from these patients and in 28 isolates recovered from upper respiratory sites in 28 additional patients during the study period . The protease activity of these isolates was tested by using the casein plate method . Of the 44 patients with invasive diseases, 25 (57%) had no obvious underlying diseases, and 14 (32%) had preexisting neoplastic diseases or had previously used steroids . Twenty-five patients (57%) presented with cellulitis or necrotizing fasciitis, 24 (55%) had bacteremia, and eight (18%) had streptococcal toxic shock syndrome (STSS) . Eight patients (18%) died of invasive GAS disease; seven had STSS, and seven had underlying diseases . All eight patients died within 48 hours after hospitalization . The presence of speA, speC, or speF was not implicated in any particular clinical syndrome in patients with invasive GAS disease . High-level protease activity and the M1 serotype of the isolates were significantly associated with the clinical signs of STSS and with mortality . M1 serotype and protease activity, as well as host immune status, might play significant roles in the pathogenesis of invasive GAS disease in Taiwan. Adv Dent Res, 1997 Apr, 11(1), 69 - 74 Host-pathogen interactions in bacterial endocarditis: streptococcal virulence in the host; Herzberg MC et al.; To identify streptococcal genes that are expressed during experimental endocarditis, we developed a promoter-less dual reporter gene-fusion (amy, cat) plasmid, pAK36 . Chromosomal DNA from S . gordonii V288 was digested with Sau3A1 . The resulting fragments were ligated into pAK36 . Following transformation into S . gordonii, the library of random gene fusion clones was inoculated into a rabbit to induce experimental endocarditis . Chloramphenicol treatment effected positive selection . Upon euthanization of the rabbits, the valvular vegetations were excised in a sterile field . Surviving clones were isolated and screened in vitro for chloramphenicol sensitivity and negative amylase activity . From the 48 randomly picked, double-negative clones, DNA was isolated and analyzed by Southern hybridization with labeled pAK36 probe . Different insertion patterns were identified, suggesting that no fewer than 13 S . gordonii genes were induced . Therefore, S . gordonii genes are induced during experimental endocarditis, which may contribute to virulence. J Immunol Methods, 1997 Dec 29, 210(2), 125 - 35 Fusions to the cholera toxin B subunit: influence on pentamerization and GM1 binding; Liljeqvist S et al.; The cholera toxin B (CTB) subunit has been used extensively in vaccine research as a carrier for peptide immunogens due to its immunopotentiating properties, where coupling has been obtained either by genetic fusion or chemical conjugation . For genetically fused immunogens both N- and C-terminal fusions have been used . Only shorter extensions have previously been evaluated and in some reports these fusions have impaired the biological functions of CTB, such as the ability to form pentamers and to adhere to its cell receptor, the GM1 ganglioside . Here we report the first systematic study where the same fusion partner has been used for either C-terminal, N-terminal or dual fusions to CTB . The serum albumin binding region (BB, approximately 25 kDa) from streptococcal protein G, which is known to fold independently of N- or C-terminal fusions, was selected as fusion partner . The three fusion proteins CTB-BB, BB-CTB and BB-CTB-BB were expressed in Escherichia coli, where they were efficiently secreted to the periplasmic space, and could be purified by affinity chromatography on human serum albumin (HSA) columns . The CTB fusion proteins were compared for their ability to form pentamers, by gel electrophoresis and size-exclusion chromatography, and it was concluded that all three fusion proteins were able to pentamerize . Interestingly, the C-terminal fusion to CTB showed most efficient pentamerization, while the dual fusion was much less efficient . Purified pentamer fractions from all three fusions where found to react to a monoclonal antibody described to react only to pentameric forms of CTB . In addition, the purified pentamer fractions were analyzed in an enzyme-linked immunosorbent assay (ELISA) for their ability to bind GM1, and it was found that the C-terminal fusion (CTB-BB) showed significant GM1-binding, but that also the N-terminal and dual CTB fusion proteins bound GM1, although less efficiently . The implications of the results for the design and use of CTB fusion proteins as subunit vaccines are discussed. Scand J Immunol, 1998 Mar, 47(3), 218 - 22 Do chickens immunized with bacterial immunoglobulin G-binding proteins produce rheumatoid factor-like antibodies? Boyle MD, Vogel L, Sisson S, Raeder R. An association between the production of rheumatoid factor (RF)-like antibodies in animals immunized with bacterial immunoglobulin (Ig)G-binding proteins has been noted . Three potential explanations have been proposed: (1) altered host IgG due to binding of the immunogen; (2) B-cell superantigenic properties of the binding proteins; and (3) idiotype-anti-idiotype response leading to an antibody which acts as an antigen mimic . In order to distinguish among these possibilities, it is necessary to carry out studies in animals whose IgG does not react with the IgG-binding protein immunogen . Consequently, we have determined the effects of immunizing chickens with a purified group C streptococcal IgG-binding protein, FcRc, a bacterium expressing this protein, and appropriate control immunogens . The results of these studies provided evidence for production of specific antibodies to FcRc in groups of chickens immunized with either the pure protein or bacteria expressing the protein . No significant association with production of RF-like antibodies was noted, favouring the altered IgG-binding explanation for the association between RF-like antibodies and immunization with the bacterial IgG-binding proteins. W V Dent J, 1995 Jan, 69(1), 16 - 21 Cephalosporin vs penicillin; Nguyen TT et al.; The correlation between late infection of an orthopedic prosthesis and a dental bacteremia remains controversial . Transient bacteremia does occur after dental treatment, usually involving streptococcal bacteria, but many orthopedic surgeons choose an anti-staphylococcal agent as their prophylactic antibiotic of choice . This article reports the results of a recent survey designed to determine, from orthopedic surgeons, antibiotic premedication coverage and, specifically, the rationale for a chosen regimen for patients having dental surgery . The responses showed no common agreement for the choice of a specific antibiotic and little rationale regarding the need for prophylaxis. Microb Pathog, 1997 Dec, 23(6), 347 - 55 Inactivation of single genes within the virulence regulon of an M2 group A streptococcal isolate result in differences in virulence for chicken embryos and for mice; Schmidt KH et al.; An M2 streptococcal isolate and isogenic mutants in which either the emm or mrp gene was insertionally inactivated were tested for virulence using either a mouse model or a chicken embryo model . The results of the studies using the mouse model demonstrated that neither the emm nor mrp gene products had a significant effect on virulence when mice were challenged via the i.p . route . However, when the bacteria were injected into the skin the emm gene product was identified as a virulence factor . In parallel studies in the chicken embryo model the mrp gene product was found to be a major virulence factor, while a minor contribution to virulence could also be attributed to the emm gene product . The importance of these gene products to virulence was noted when the chicken embryo were injected either i.v or when the bacteria were placed on top of the chorioallantoic membrane . The direct comparison of a single wild type group A organism and its paired isogenic mutants in two animal models suggests that different combinations of bacterial factors are required to overcome host defense strategies associated with different animal species . J Natl Med Assoc, 1998 Feb, 90(2), 109 - 14 Seroprevalence of antibodies to group B streptococcal polysaccharides in Gambian mothers and their newborns; Suara RO et al.; In developing countries, little is known about the relationship between group B streptococcal (GBS) colonization in pregnant women and serum antibody levels to capsular polysaccharide antigens of these organisms . This study examined the prevalence of antibodies to two polysaccharides of GBS, Ia and III, in 124 Gambian women with known GBS colonization at delivery and their newborns . Mean antibody levels in maternal-cord serum pairs were 4.06 +/- 0.25 micrograms/mL and 2.64 +/- 0.20 micrograms/mL for type Ia GBS, and 1.1 +/- 0.52 microgram/mL and 0.78 +/- 0.43 microgram/mL for type III GBS . Women colonized with type V GBS had significantly higher antibody levels to type III GBS than did noncolonized women, but no difference was found when these groups were compared for antibody levels to type Ia GBS . Women > or = 20 years had significantly higher antibody levels to type III GBS compared with younger women and those colonized by other GBS serotypes . Maternal antibodies to types la and III GBS were transferred across the placenta to newborns . The rarity of GBS disease in Gambia and other developing countries may be due to the prevalence of maternally derived GBS antibodies, the low prevalence of colonization with serotype III strains, or other undefined factors. Proc Natl Acad Sci U S A, 1998 Feb 17, 95(4), 1562 - 7 Molecular picture of folding of a small alpha/beta protein; Sheinerman FB et al.; We characterize, at the atomic level, the mechanism and thermodynamics of folding of a small alpha/beta protein . The thermodynamically significant states of segment B1 of streptococcal protein G (GB1) are probed by using the statistical mechanical methods of importance sampling and molecular dynamics . From a thermodynamic standpoint, folding commences with overall collapse, accompanied by formation of approximately 35% of the native structure . Specific contacts form at the loci experimentally inferred to be structured early in folding kinetics studies . Our study reveals that these initially structured regions are not spatially adjacent . As folding progresses, fluid-like nonlocal native contacts form, with many contacts forming and breaking as the structure searches for the native conformation . Although the alpha-helix forms early, the beta-sheet forms concomitantly with the overall topology . Water is present in the protein core up to a late stage of folding, lubricating conformational transitions during the search process . Once 80% of the native contacts have formed, water is squeezed from the protein interior and the structure descends into the native manifold . Examination of the onset of side-chain mobility within our model indicates side-chain motion is most closely linked to the overall volume of the protein and no sharp order-disorder transition appears to occur . Exploration of models for hydrogen deuterium exchange show qualitative agreement with equilibrium measurement of hydrogen/deuterium protection factors. Orv Hetil, 1998 Feb 15, 139(7), 361 - 8 {How to proceed in the age of increasing antibiotic resistance?}; Katona Z et al.; The authors examined the infection control activity, the quality of basic health care of 6906 patients in 44 praxis . The mass of accomplished treatments was compared with the virtual mass of desirable treatments according to up-to-date considerations . The presumptive purposivity and expectable efficiency of the realised treatments didn't satisfy the justly expected professional claims . The decrease in quality was basically due to the cognitive dissonance (deficiencies of cognition and/or erroneous adoptation of theoretical and practical knowledge) of physicians . The unnecessarily prescribed (polypragmatic) and simultaneously purposeless broad spectrum of antibiotic treatments ran to two-third of the total--mainly in the cases or viral and beta-hemolytic Streptococcal infections; the number of antibacterial treatments was three times more than needed . Better compromise could be reached by the introduction of quality control in the field of infection treatments in the basic health care system . Spreading of the antibiotic resistance cannot be prevented without of quality assurance in the field of infection control and without the wide use of a more reasonable kind of treatment practice. J Leukoc Biol, 1998 Mar, 63(3), 359 - 63 Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls; Schrier DJ et al.; Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cell-mediated monoarticular arthritis ill female Lewis rats . Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and that the early phase of swelling is neutrophil-dependent . Neutrophil depletion or passive immunization with antibodies to P-selectin or macrophage inflammatory protein-2 reduced the intensity of ankle edema and the influx of neutrophils . After the first few days, however, the arthritic response is mediated primarily by mononuclear cells . Joint tissues showed up-regulation of mRNA for monocyte chemotactic protein-1 (MCP-1), which could be inhibited in part by anti-IL-4; treatment of rats with antibodies to IL-4 or MCP-1 significantly suppressed development of ankle edema and histopathological evidence of inflammation . Antibodies to interferon-gamma or IL-10 had no effect . Treatment with anti-MCP-1 also suppressed influx of (111)In-labeled T cells into the ankle joint . These data suggest that the late, mononuclear-dependent phase of SCW-induced arthritis in female Lewis rats requires cytokines that up-regulate MCP-1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint. Lung, 1998, 176(2), 123 - 31 Lung function and bacterial proliferation in experimental neonatal pneumonia in ventilated rabbits exposed to monoclonal antibody to surfactant protein A; Herting E et al.; Surfactant protein A (SP-A) increases the resistance of surfactant to inhibition by plasma and other proteins . In a previous study we found that a monoclonal anti-SP-A antibody (R 5) increased the sensitivity of surfactant to inhibition by fibrinogen in vivo and in vitro . SP-A has been shown to stimulate microbial phagocytosis and killing by alveolar macrophages . We hypothesized that using R 5 to inactivate SP-A in an animal model mimicking congenital group B streptococcal (GBS) pneumonia might result in increased bacterial proliferation and a deterioration in lung function . Newborn near term rabbits were delivered by Cesarean section, anesthetized, tracheotomized, and ventilated for 5 h in a plethysmograph system allowing measurement of dynamic lung-thorax compliance . Postnatally the animals received one intratracheal injection (5 ml/kg) of R 5, nonspecific IgG, or normal saline . At 30 min all animals received a standard dose of an encapsulated GBS strain by intratracheal injection . The number of bacteria (mean log10 CFU/g lung +/- S.D.; CFU = colony forming unit) was evaluated in lung homogenates . Histologic lung sections were judged by light microscopy . Bacterial proliferation was similar in rabbits treated with the monoclonal antibody (9.33 +/- 0.39; n = 14) and in control animals receiving saline (9.16 +/- 0.35; n = 14) or nonspecific IgG (9.26 +/- 0.31; n = 11) . No significant differences were noted on the histologic analysis or in measurements of lung function . We conclude that intratracheal instillation of a monoclonal anti-SP-A antibody did not increase bacterial proliferation in GBS-infected newborn rabbits . These findings suggest that SP-A does not play an important role in protection against encapsulated GBS strains in the neonatal period. J Infect Dis, 1998 Mar, 177(3), 692 - 700 Inducible nitric oxide synthase and the effect of aminoguanidine in experimental neonatal meningitis; Leib SL et al.; This study explored the role of inducible nitric oxide (NO) synthase (iNOS) in an infant rat model of group B streptococcal meningitis . Brain iNOS activity increased during meningitis (P < .001), and iNOS was detected by immunocytochemistry in the walls of meningeal vessels and cells of the cerebrospinal fluid (CSF) inflammation . Animals treated with iNOS inhibitor aminoguanidine (AG; 130 mg/kg every 8 h) had reduced NO production (P < .05), higher CSF bacterial titers (P < .05), and increased incidence of seizures (P < .01) compared with untreated infected animals . AG also increased areas of severe hypoperfusion in the cortex (31% +/- 14% in controls vs . 56% +/- 16% in AG; P < .01) and the extent of cortical neuronal injury, both when administered at the time of infection (P < .05) and in established meningitis (P < .02) . Thus, NO produced by iNOS may be beneficial in this model of experimental meningitis by reducing cerebral ischemia. Bone Marrow Transplant, 1998 Jan, 21(2), 173 - 80 Early gram-positive bacteremia in BMT recipients: impact of three different approaches to antimicrobial prophylaxis; Arns da Cunha C et al.; Antimicrobial prophylaxis against gram-positive bacteremia (GPB) following BMT may prevent infections but promote antimicrobial resistance . In a sequential cohort study involving 289 consecutive BMT recipients we compared three protocols for prevention of GPB (vancomycin prophylaxis, penicillin/cefazolin prophylaxis, and no specific GPB prophylaxis) with respect to incidence of GPB, mortality, and vancomycin use . GPB was associated with increased mortality (27% vs 15%; P = 0.02), but contributed to only five of 52 deaths in the study population, and only one of 15 subjects with viridans streptococcal bacteremia developed fatal septic shock . Vancomycin prophylaxis reduced the incidence of GPB (11%) compared to penicillin/cefazolin (27%) or no prophylaxis (40%) (all P < 0.03), but did not significantly reduce mortality . The incidence of fungemia, gram-negative bacteremia, and infection-associated mortality was unaffected by GPB prophylaxis . Vancomycin use was substantially greater in the vancomycin prophylaxis group . We conclude that in comparison with vancomycin prophylaxis, BMT support regimens that do not include vancomycin prophylaxis allow reduced overall vancomycin use without an apparent increase in early post-BMT mortality, despite the greater associated frequency of GPB. Eur J Obstet Gynecol Reprod Biol, 1998 Jan, 76(1), 61 - 4 Increased maternal mortality in The Netherlands from group A streptococcal infections; Schuitemaker N et al.; OBJECTIVE: To assess genital tract sepsis-related maternal mortality in The Netherlands during 1983-1992 . STUDY DESIGN: A nationwide Confidential Enquiry into the causes of maternal death . RESULTS: Genital tract sepsis-related maternal mortality during 1983-1987 was 0.11 per 100,000 live births (1/893,998) and 0.93 per 100,000 live births (9/968,990) during 1988-1992 . The relative risk of dying due to sepsis in the second 5-year period as compared to the first period was 10.1 (1/72 versus 9/72 maternal deaths; 95% CI 1.3-82.3; P < 0.01) . CONCLUSIONS: Also in The Netherlands an increase of death due to genital tract sepsis has been observed since the 1980s. Plasmid, 1998, 39(1), 63 - 76 Identification of a DNA cytosine methyltransferase gene in conjugative transposon Tn5252; Sampath J et al.; The nucleotide sequence of the 3.5-kb right junction fragment of the streptococcal conjugative transposon Tn5252 was obtained . The DNA fragment was found to carry four putative genes one of which displayed a high degree of similarity to prokaryotic 5C-cytosine methyltransferases carrying multiple sequence specificities . No cognate endonuclease gene was detected in the sequenced DNA . Purified methylase polypeptide synthesized in a T7 promoter-controlled overexpression system was found to lack methylase activity while the cell extracts of host cells containing the recombinant plasmid carrying the methylase gene were active . In vivo mutations in the methylase gene did not seem to affect the transferability of the element. Rozhl Chir, 1997 Sep, 76(9), 458 - 60 {Rapidly progressing streptococcal sepsis in a patient after transplantation of a cadaver kidney}; Veselsky Z et al.; The authors submit the case-history of an adverse rapidly progressing phlegmon and septicaemia in a patient after transplantation of a cadaverous kidney with a functional graft . The patient was admitted repeatedly to the Transplantation Centre of the Urological Clinic, Faculty Hospital Hradec Kralove with acute cellular rejection for corticosteroid treatment. Med Pregl, 1997 Sep-Oct, 50(9-10), 387 - 90 {Psoriatic arthritis: case report of acute HLA-B27 positive polyarthritis preceding the onset of typical skin changes}; Lenert P et al.; Psoriasis usually occurs many years before development of arthritis . This is a case report of a patient with acute polyarthritis affecting both peripheral joints and the left sacroiliac joint, preceding the appearance of typical skin manifestations for almost two months . A 44-year-old male mechanic was admitted to our institution for acute additive polyarthritis . Inflammatory synovitis primarily affected large peripheral joints (knees, ankles) in an asymmetrical pattern, with a concomitant development of unilateral sacroiliitis and later with asymmetrical involvement of several proximal and distal interphalangeal joints of the hands and feet . There were also signs of enthesopathy of the right heel . Arthritis was not proceeded by infection of the lower genital or gastrointestinal tract or serological and bacteriological evidences of streptococcal or HIV infection . Laboratory findings showed an erythrocyte sedimentation rate (92 in the first hour), positive histocompatibility antigen HLA-B27 and an increased level of acute phase reactants . Almost two months after affecting the locomotor system a typical psoriatic rash developed, first affecting the scalp and then spreading over the trunk and extremities . It was accompanied by severe onychodystrophy . The patient underwent intensive treatment with methylprednisolone (1.5 mg/kg) and cyclosporine A with significant results. Adv Dent Res, 1997 Nov, 11(4), 388 - 94 The use of X-ray photoelectron spectroscopy for the study of oral streptococcal cell surfaces; van der Mei HC et al.; Physicochemical and structural properties of microbial cell surfaces play an important role in their adhesion to surfaces and are determined by the chemical composition of the outermost cell surface . Many traditional methods used to determine microbial cell wall composition require fractionation of the organisms and consequently do not yield information about the composition of the outermost cell surface . X-ray photoelectron spectroscopy (XPS) measures the elemental composition of the outermost cell surfaces of micro-organisms . The technique requires freeze-drying of the organisms, but, nevertheless, elemental surface concentration ratios of oral streptococcal cell surfaces with peritrichously arranged surface structures showed good relationships with physicochemical properties measured under physiological conditions, such as zeta potentials . Isoelectric points appeared to be governed by the relative abundance of oxygen- and nitrogen-containing groups on the cell surfaces . Also, the intrinsic microbial cell-surface hydrophobicity by water contact angles related to the cell-surface composition as by XPS and was highest for strains with an elevated isoelectric point . Inclusion of elemental surface compositions for tufted streptococcal strains caused deterioration of the relationships found . Interestingly, hierarchical cluster analysis on the basis of the elemental surface compositions revealed that, of 36 different streptococcal strains, only four S . rattus as well as nine S . mitis strains were located in distinct groups, well separated from the other streptococcal strains, which were all more or less mixed in one group. Clin Otolaryngol, 1997 Dec, 22(6), 532 - 5 Streptococcal tonsillitis and its association with psoriasis: a review; England RJ et al.; Lancefield group A streptococcal upper respiratory tract infections are well known to be precursors of a number of disease processes . That they frequently herald a first attack of guttate psoriasis or a reactivation of chronic plaque psoriasis is well recognized, though this is perhaps more true among dermatologists than otolaryngologists . This paper briefly summarizes the historical background, recent research into, and current understanding of the connection between the two pathological phenomena. Am J Psychiatry, 1998 Feb, 155(2), 264 - 71 Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases; Swedo SE et al.; OBJECTIVE: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal {GABHS}) infections (PANDAS) . METHOD: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities . RESULTS: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD) . The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common . Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%) . Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure . CONCLUSIONS: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections . The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies. Protein Sci, 1997 Nov, 6(11), 2359 - 64 Design of an expression system for detecting folded protein domains and mapping macromolecular interactions by NMR; Huth JR et al.; Two protein expression vectors have been designed for the preparation of NMR samples . The vectors encode the immunoglobulin-binding domain of streptococcal protein G (GB1 domain) linked to the N-terminus of the desired proteins . This fusion strategy takes advantage of the small size, stable fold, and high bacterial expression capability of the GB1 domain to allow direct NMR spectroscopic analysis of the fusion protein by 1H-15N correlation spectroscopy . Using this system accelerates the initial assessment of protein NMR projects such that, in a matter of days, the solubility and stability of a protein can be determined . In addition, 15N-labeling of peptides and their testing for DNA binding are facilitated . Several examples are presented that demonstrate the usefulness of this technique for screening protein/DNA complexes, as well as for probing ligand-receptor interactions, using 15N-labeled GB1-peptide fusions and unlabeled target. Br J Dermatol, 1997 Sep, 137(3), 331 - 8 Antigen-independent expansion of T cells from psoriatic skin lesions: phenotypic characterization and antigen reactivity; Horrocks C et al.; The pathogenesis of psoriasis appears to depend on T cells, which have been proposed to mediate the disease through an autoimmune process . To test this hypothesis we have propagated four T-cell lines from biopsies of psoriatic skin lesions by antigen-independent methods . Flow cytometric immunophenotyping showed the lines to be composed mainly of CD4-positive, alpha beta T-cell receptor (TCR)-positive cells, which secreted a cytokine profile suggestive of predominant T-helper type 1 (Th1) status . Analysis of TCR variable region (V beta) usage revealed two- to eight-fold increases in the expression of certain V beta species in lesional lines as compared with autologous peripheral blood mononuclear cells (PBMC), with the increased V beta species being expressed on more than 5% of cells in two of the lines . Lines were also used to test for responses to a range of epidermal antigen preparations in the presence of irradiated autologous PBMC as antigen-presenting cells . The lines failed--to proliferate in response to psoriatic lesional stratum corneum extracts, dispase-separated normal human epidermal extracts, and an epidermal keratin preparation before and after trypsinization, in spite of good proliferative responses to anti-CD3 which indicated that the lines were not anergic . In addition, the lines and PBMC from normal volunteers and the patients with psoriasis gave little or no response to recombinant streptococcal M protein . Thus, in spite of accumulating evidence for selective expansion of certain V beta-expressing T cells in psoriatic lesions, epidermal autoantigens have not been identified by using a bioassay which depended largely on the proliferation of lesional CD4-positive cells . The role of streptococcal M protein, which bears some homology with epidermal keratin is also open to question, at least in chronic plaque psoriasis . Further work is therefore required to obtain direct evidence that autoimmune processes are important in the pathogenesis of chronic plaque psoriasis. Rev Med Chir Soc Med Nat Iasi, 1995 Jul-Dec, 99(3-4), 231 - 4 {The streptococcal and staphylococcal toxic shock syndrome . Comments on 4 cases}; Mihalache D et al.; Between 1989 and 1995 in the Hospital of Infectious Diseases from Iasi have been diagnoses 4 cases of streptococcal/staphylococcal toxic syndrome . Three patients have been grown up and one child . Two of them were immunocompromised hosts (cirrhosis, lung tuberculosis, alcoholism) . The gate of entry was cutaneous in 3 cases and probably mucous in the 4th case . The clinical symptoms were fever, generalized erythematous rush followed by desquamation, low arterial pressure with oliguria, tachycardia, jaundice moderate, elevated ALAT . The bacteriological diagnosis was confirmed by isolating the pathogen agent from the erysipelatous placard and from blood culture . The evolution of the illness was nefavourable in 2 cases . The cause of the death was the MSOF (multiple systemic organic failure). Arch Pediatr Adolesc Med, 1998 Jan, 152(1), 35 - 40 Neonatal early-onset Escherichia coli disease . The effect of intrapartum ampicillin; Joseph TA et al.; BACKGROUND: Maternal intrapartum ampicillin has been recommended for the prevention of neonatal group B streptococcal disease . OBJECTIVES: To assess the effect of this practice, if any, on neonatal early-onset Escherichia coli infection and to delineate the clinical characteristics of infected neonates . PATIENTS AND METHODS: All neonates with early-onset E coli infection who were born at Cook County Children's Hospital, Chicago, Ill, from January 1, 1982, through December 31, 1993, were identified from a microbiological register of all neonatal bacteremias and infections . Because intrapartum ampicillin use increased in our hospital since 1988, infection and case fatality rates from 1982 through 1987 (period 1) were compared with data from 1988 through 1993 (period 2) . We studied maternal risk factors, clinical characteristics of infected neonates, and microbiological sensitivities of E coli isolates . RESULTS: Early-onset E coli infection was diagnosed in 30 of 61,498 live births . The overall infection rate (0.49 per 1000 live births) did not change significantly during the 2 time periods (0.37 per 1000 live births during period 1 vs 0.62 per 1000 live births during period 2, P = .21; chi 2 test); however, there was an increase in the infection rate in neonates weighing between 1501 and 2500 g . Infected neonates had a clinical syndrome that was indistinguishable from early-onset group B streptococcal infection; respiratory distress was the single most frequent finding in 73% (22/30) infected neonates . An increase in the proportion of infections caused by ampicillin-resistant E coli was observed during period 2 (12/18) compared with period 1 (3/12, P = .03; Fisher exact test) . During period 2, 61% (11/18) of mothers of infected neonates received intrapartum ampicillin compared with 17% (2/12; P = .02) during period 1 . Overall, a higher proportion of neonates born to ampicillin-treated women had ampicillin-resistant infection (12/13 vs 3/17; P < .001) . Mothers of 10 of 15 neonates with ampicillin-resistant infection had received more than 2 doses of intrapartum ampicillin . The difference between the prevalence of intrapartum fever in mothers with sensitive organisms (40%, or 6/15) and resistant organisms (93%, or 14/15) was also significant (P = .003) . All 6 early-onset E coli-related deaths were due to ampicillin-resistant organisms; 4 of the 6 mothers received intrapartum ampicillin . CONCLUSIONS: We have shown a shift of early-onset E coli infection from a less fulminant disease caused by ampicillin-sensitive organisms to a more fulminant disease caused by ampicillin-resistant organisms . Increased use of maternal intrapartum ampicillin therapy may account for these changes . In the absence of evidence for group B streptococcal disease, clinicians should consider the possibility of ampicillin-resistant E coli infection in critically ill neonates born to women with a history of intrapartum fever and treatment with intrapartum ampicillin. J Lab Clin Med, 1998 Jan, 131(1), 93 - 102 Streptococcal and staphylococcal superantigen-induced lymphocytic arteritis in a local type experimental model: comparison with acute vasculitis in the Arthus reaction; Abe Y et al.; Many pathogenic bacteria produce superantigenic exotoxins . To study their pathogenetic role, in particular to test whether these toxins are able to induce vasculitis, we developed a local-type experimental model in rabbits . Toxins were injected along the intermediate auricular artery of the ear . The histology of ear skin, including the artery, was examined after single or repeated injections . Repeated injections of streptococcal erythrogenic toxins produced chronic-type arteritis characteristic of lymphocytic infiltration, whereas single injection induced no acute-type vasculitis . Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 also induced the same type of arteritis, although weaker in degree . In human patients these lesions are similar to those of Kawasaki disease, a systemic vasculitis with unknown etiology . The Arthus reaction to human serum albumin in immunized rabbits included acute-type vasculitis similar to polyarteritis nodosa when examined in this model . Microvasculitis lesions similar to leukoclastic vasculitis were combined in the Arthus reaction but not in the superantigen-induced lesions . Our experimental model described here is widely applicable to the study of the etiology and pathogenesis of human diseases involving vasculitis lesions. Pediatrics . 1998 Feb;101(2):E2. Does culture confirmation of high-sensitivity rapid streptococcal tests make sense? A medical decision analysis; Webb KH; OBJECTIVE: Since the 1990 publication of a decision analysis, in which the treatment of pharyngitis in children was evaluated, a number of assumptions important in that analysis have changed . Updating many of the assumptions and costs used in that analysis to reflect the conditions currently found in a large, suburban pediatric practice, a cost-effectiveness analysis was performed in which four strategies for the treatment of pharyngitis were considered: treat all, high-sensitivity antigen test, culture, and high-sensitivity antigen test with culture confirmation . DESIGN: Decision analysis . RESULTS: Using microbiology data from the 13 published studies in which a high-sensitivity antigen test (Strep A OIA; BioStar Inc., Boulder, CO) and blood agar plate culture were evaluated against a variety of gold standards, the sensitivity and specificity of the high-sensitivity antigen test were 89.1% and 95%, respectively . The sensitivity and specificity of blood agar plate throat culture were 83.4% and 99%, respectively . Penicillin V was used as the treatment of choice for uncomplicated pharyngitis; erythromycin was used in cases of penicillin allergy . Rates of suppurative and nonsuppurative complications reflect those currently seen in the United States . Other assumptions and cost data were taken from a large, suburban pediatric practice and its affiliated tertiary care medical center, except where noted . Despite the potential induction of resistance and the high number of allergic reactions associated with the treat-all strategy, this strategy had the lowest average cost per patient encounter and was the most cost-effective in terms of dollars per suppurative and nonsuppurative complication prevented . Of the strategies in which a diagnostic test was used, the high-sensitivity antigen test strategy had the lowest average cost and was the most cost-effective . The high-sensitivity antigen test with culture confirmation strategy had the highest average cost and was the least cost-effective . In the sensitivity analyses, a number of assumptions used in the original model were varied within a reasonable range . Under most conditions, the treat-all strategy remained the most cost-effective strategy used . One notable exception: when the wholesale cost of the antibiotic exceeded $10.76, as would be seen if any cephalosporin were used as the primary therapy of uncomplicated pharyngitis, the high-sensitivity antigen test strategy became the most cost-effective strategy . Under most conditions, the high-sensitivity antigen test strategy was the most cost-effective of the strategies in which a diagnostic test was used . Notable exceptions included: 1) conditions in which there was a low probability of streptococcal infection, 2) the use of an antigen test whose sensitivity is inferior to that of culture, and 3) during an epidemic of acute rheumatic fever . Culture confirmation of a negative high-sensitivity antigen test is the most cost-effective testing strategy only under conditions in which the probability of acute rheumatic fever approaches those levels last seen in the United States more than 40 years ago . CONCLUSIONS: Although most cost-effective, the treat-all strategy is not recommended because of concerns about antibiotic resistance, which could not be included in the model, and the high number of allergic reactions found in children who did not have streptococcal infection . Use of the high-sensitivity antigen test without culture confirmation of all negative results was the most cost-effective strategy in which a diagnostic test was used with respect to prevention of suppurative and nonsuppurative complications of streptococcal pharyngitis . Culture confirmation of negative high-sensitivity antigen tests was not cost-effective under any of those conditions currently seen in the United States. Microbiol Immunol, 1997, 41(11), 895 - 900 Serologic evidence that streptococcal superantigens are not involved in the pathogenesis of Kawasaki disease; Morita A et al.; Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology and is associated with marked activation of T cells and monocyte macrophages, leading to the assumption that superantigens are involved in its pathogenesis . To determine if an association exists between streptococcal superantigens and KD, we examined serum antibody responses to superantigens in sera from 50 paired acute and convalescent KD patients using purified recombinant streptococcal superantigens, such as SPEA, SPEC, SSA and MF . We found a very low frequency of detection of anti-superantigen antibodies by ELISA and no marked IgG seroconversion to each superantigen, indicating the absence of a serological relationship between toxin-producing streptococcal infection and the onset of KD. Med Clin (Barc), 1997 Nov 1, 109(15), 588 - 91 {Sweet's syndrome: a study of 16 cases}; Ginarte M et al.; We performed a retrospective analysis of the records of 16 patients diagnosed in our dermatology service as Sweet's syndrome (SS), with the aim of describing their clinical findings and associations, and comparing our results with previous ones . The mean age was 51, and 82% were female . A previous infection was recorded in 5 cases (31%) (gastroenteritis, primary pulmonary tuberculosis, upper airways infection, wound infection, and streptococcal pharyngitis) . Two patients (12%) suffered from a malignant neoplasia (acute myeloid leukemia and prostatic neoplasia), another patient had a coincident bout of acute ulcerative colitis with pyoderma gangrenosum, and a third one referred previous ingestion of diclofenac and intense sun exposure . Most patients had their lesions localized on the upper extremities (75%), fever was present in 8 cases (50%), arthralgia in six (37%), and erythema nodosum in five (31%) . The most frequent laboratory finding was an elevated sedimentation rate (93% had values over 20 mm/h), and only 44% of patients had leukocyte counts over 10 x 10(9)/l . Urinanalysis was abnormal in one third of the patients, and chest roentgenograms, performed in ten patients, were all normal . Most of the patients were treated with low doses of oral prednisone (30 mg/day) with good results . The disease recurred in 25% of the patients. Radiat Oncol Investig, 1997, 5(6), 283 - 8 Effect of combination treatment of 15 cGy total body irradiation and OK-432 on spontaneous lung metastasis and mitogenic response of splenocytes in mice; Hosoi Y et al.; We investigated whether the combination treatment of 15 cGy total body irradiation (TBI) and a streptococcal preparation, OK-432, synergistically suppresses spontaneous lung metastasis and augments phytohemagglutinin (PHA) and concanavalin A (Con A) responses of splenocytes in WHT/Ht mice . TBI with 15 cGy was carried out 20 days after subcutaneous injection of squamous cell carcinoma cells into a hind leg . Lung colony number was counted 40 days after tumor injection . For PHA and Con A responses, mice were killed 4 hr after 15 cGy TBI . The combination treatment of 15 cGy TBI and OK-432 was most effective when OK-432 was administered 2 days before 15 cGy TBI . The combination treatment decreased the lung colony number to 29.9% of the control number . OK-432 slightly increased the PHA and Con A responses, and 15 cGy TBI did not increase them . However, when these two were combined, the PHA and Con A responses were significantly increased to 393% and 278% of the control levels, respectively . It was suggested that TBI and OK-432 acted synergistically in suppressing the lung metastasis and mitogenic response of splenocytes. Mil Med, 1997 Dec, 162(12), 798 - 801 The effect of a rapid kit for detection of streptococcal pharyngitis on the accuracy of the physicians' diagnoses; Bar-Dayan Y et al.; BACKGROUND: In the last decade, the accuracy of rapid tests for detection of group A streptococcal antigen was evaluated in laboratory and clinical settings, and the tests were suggested as an alternative to the traditional throat culture . METHODS: We evaluated 19 patients with a preliminary diagnosis of nonstreptococcal pharyngitis and 13 patients with a preliminary diagnosis of streptococcal pharyngitis . The physician performed a rapid latex agglutination test (Detect A Strep), took throat culture from all of the patients, reconsidered the preliminary diagnosis, and made a working diagnosis . A clinical score was calculated for each patient during data analysis . The accuracy of the physicians' preliminary diagnoses was compared with the accuracy of the scoring system, with the accuracy of the latex agglutination test, and with the accuracy of the physicians' working diagnoses . RESULTS: The scoring system, the physicians' preliminary diagnoses, the latex agglutination test, and the physicians' working diagnoses correlated significantly with throat culture results (p < or = 0.05) . The efficiency of the physicians' preliminary diagnoses was 75% compared with an efficiency of 69% of the clinical scoring system, an efficiency of 66% of the latex agglutination test, and an efficiency of 69% of the physicians' working diagnoses . The physician changed the preliminary diagnosis only for two patients as a result of the latex agglutination test results; ironically, however, the preliminary diagnosis was correct in both of these cases . CONCLUSION: The use of a rapid test for the diagnosis of group A streptococcal antigen under normal working conditions did not improve the accuracy of the physician's diagnosis, so the use of the latex agglutination test in this study was not cost-effective. J Pathol, 1997 Nov, 183(3), 359 - 68 Glomerular proliferating cell kinetics in acute post-streptococcal glomerulonephritis (APSGN); Oda T et al.; To investigate the time sequence of glomerular cell proliferation in acute human glomerulonephritis, renal biopsy tissues were examined from 15 acute post-streptococcal glomerulonephritis (APSGN) patients (who were biopsied 1-31 days after onset), using an immunoperoxidase technique with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and various cell surface markers . Few, if any, PCNA+ cells were observed in normal glomeruli, but many cells were positive for PCNA in the acute phase of APSGN . Glomerular PCNA+ cells were observed either within glomerular tufts, or lining Bowman's capsule (parietal epithelial cells); the number of positive cells tended to decrease exponentially as the disease duration increased (r = -0.91, P < 0.0001) . PCNA+ cells within glomerular tufts were further identified by double immunostaining . PCNA was not found in PMN or T cells, but a small proportion of macrophages were PCNA+ . Most of the remaining PCNA+ cells were resident glomerular cells; the proportion of PCNA+ endothelial cells (CD31+) was over 80 per cent in the early phase, but as the disease continued the proportion of mesangial cells (alpha-smooth muscle actin+) increased to about half of the total PCNA+ cells within the tuft . These data indicate that the hypercellular glomeruli in APSGN are due not only to immune cell infiltration, but also to resident glomerular cell proliferation, probably induced by locally produced growth factors. An Med Interna, 1997 Oct, 14(10), 523 - 4 {Poststreptococcal reactive arthritis: a benign complication of a common infection}; Monte Secades R et al.; Poststreptococcal reactive arthritis (PSRe A) is a sterile synovitis associated to the evidence of previous streptococcal infection . PSRe A has different clinical features from those observed in rheumatic fever . Regarding systemic complications, PSRe has in general a good prognosis . A new case is described and the literature is reviewed in this article. Infect Immun, 1998 Jan, 66(1), 315 - 21 Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model; Nordstrand A et al.; Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN) . To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN . Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice . In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains . After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed . Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection . These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade . Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity . Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition. J Clin Psychiatry, 1997, 58 Suppl 14, 39 - 45; discussion 46-7 New developments in the treatment of obsessive-compulsive disorder; Leonard HL; The treatment of obsessive-compulsive disorder (OCD) has changed dramatically in the last 10 years . Currently, the serotonin reuptake inhibitors (SRIs) and the serotonin selective reuptake inhibitors (SSRIs) are considered the "first choice" agents for pharmacologic treatment of OCD, although few head-to-head comparisons exist between any two specific agents . Strategies for nonresponders and partial responders to the SRI/SSRIs are reviewed . The only agents that have shown significant improvement as augmenting agents to an SRI/SSRI in systematic trials have been clonazepam and haloperidol . Predictors of response to pharmacotherapy have been limited, but several reports have found that an early age at onset of OCD has been associated with a poorer response to medications . Long-term maintenance medication may be necessary for some, although behavioral therapy may improve the need for extended pharmacotherapy . Cognitive behavioral therapy, specifically exposure with response prevention, still remains an effective and important component of treatment for many . One of the newest developments is the identification of a pediatric subtype of OCD characterized by prepubertal acute onset after group A beta-hemolytic streptococcal pharyngitis . Investigation trials with these children include immunomodulatory therapies and penicillin treatment and prophylaxis . If a unique subgroup of children with OCD can be identified, then novel treatments may prove effective and have a role in long-term prophylaxis. J Clin Immunol, 1997 Nov, 17(6), 472 - 7 Clinical trial of immunostimulation with a biological response modifier in unexplained recurrent spontaneous abortion patients; Katano K et al.; We determined clinically whether a killed streptococcal preparation (KSP), a biological response modifier, is as effective as paternal lymphocyte immunotherapy for unexplained recurrent pregnancy abortion (RSA) therapy . The success rate of adverse pregnancy in the study group of 23 RSA cases, who were administered low doses of KSP before and during early pregnancy, was statistically compared with that in a control group of 205 women who received paternal lymphocyte immunotherapy . The association of natural killer (NK) cell activity in the peripheral blood with pregnancy outcome was also assessed . The success rate in the study group was 73.9% (17/23), compared to 75.1% (154/ 205) observed for the controls (not significant) . Most of the successful cases exhibited low levels of NK cell activity in the peripheral blood . Immunotherapy with low doses of KSP is as effective as that with paternal lymphocytes, providing a simple and safe alternative therapy for unexplained RSA . Suppression of NK cell activity by some immunoregulatory mechanism was also found to have potential benefit in terms of a successful pregnancy outcome. J Exp Ther Oncol, 1996 Jul, 1(4), 242 - 50 Profile of T-cell receptor V beta gene usage of cytotoxic T cells induced by intrapleural administration of a streptococcal preparation, OK432, in malignant effusions; Miyahara E et al.; T-cell receptor (TCR) gene rearrangements were analyzed in tumor-infiltrating lymphocytes (TIL) using the reverse transcription-polymerase chain reaction (RT-PCR) to determine whether oligoclonal expression of TCRV beta occurs in TIL, and if so, whether it is involved in the clinical response and mechanisms of locoregional immunotherapy using a streptococcal preparation, OK432 . Patients with malignant effusion of various origins were treated with intrapleural administration of OK432, and clinical responses were assessed by cytological and chest X-ray examinations . Pleural exudate cells (PEC), obtained before and after the administration of OK432 (designated as pre- and OK432-PEC, respectively), were subjected to TCR analysis . Both pre-PEC and OK432-PEC showed highly diverse expressions of TCRV beta gene usage in either type of PEC . The frequency of TCRV beta 20 gene expression in OK432-PEC was significantly higher than in pre-PEC . Moreover, the over-expression of the TCRV beta 20 gene usage was also induced in the peripheral blood lymphocytes and pre-PEC of patients by in vitro OK432 stimulation, but not in the PBL of one healthy volunteer . Single-strand conformational polymorphism (SSCP) analysis revealed the clonotypes of these TCRV beta 20 genes . Autologous tumor-specific killing activity could be detected in OK432-PEC and was significantly reduced by treatment with a TCRV beta 20-specific monoclonal antibody . These findings suggest that the rearrangement of TCRV beta 20 gene usage may be involved in the autologous tumor-specific action of malignant effusions in the treatment with OK432. Can J Cardiol, 1997 Oct, 13(10), 895 - 6 Tricuspid endocarditis following a Papanicolaou smear: case report; Mong K et al.; Infective endocarditis is an uncommon complication of obstetrical and gynecological practice and has not been reported in the literature to be associated with Papanicolaou smears . The authors report a nonintravenous drug user who developed group B streptococcal endocarditis of the tricuspid valve following a routine Papanicolaou smear . She required surgical excision of the valve and replacement after failed antibiotic therapy. Chest, 1997 Dec, 112(6), 1693 - 7 Diverse presentation of aberrant origin of the right subclavian artery: two case reports; Bisognano JD et al.; Aberrant origin of the right subclavian artery occurs in up to 1% of the population and can result in a wide range of symptoms . In this report, two cases of this anomaly are presented . In the first case, a patient developed fatal group A streptococcal aortitis . In the second case, the patient complained of chronic cough and intermittent dyspnea . The embryologic genesis of this abnormality is discussed and the current literature is summarized . Although relatively uncommon, it is important to consider this vascular anomaly in the differential diagnosis of patients with dysphagia, dyspnea, chest pain, fever, or mediastinal widening evidenced on chest roentgenography. Br J Haematol, 1997 Dec, 99(3), 580 - 8 A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies . International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC); Hann I et al.; The object of this study was to determine whether there were any differences between the 'typical' child with fever and neutropenia and their adult counterpart with regard to infection type and outcome, by analysis of 3080 patients, including 759 children < 18 years of age and 2321 adults . These represented patients randomized in previous trials, between 1986 and 1994, which compared empirical antibiotic regimens for fever in neutropenic patients . There were fewer childhood acute myeloid leukaemia patients than adults but more acute lymphoblastic leukaemia cases and more with solid tumours undergoing intensive myelosuppressive therapy . The children were less likely to be undergoing first induction therapy but the relative incidence of patients receiving relapse schedules or maintenance therapies were not significantly different in the two age groups . Children less frequently had a defined site of infection than adults and where they had a defined site there were more upper respiratory tract but fewer lung infections . There was a similar low incidence of shock at presentation in the two groups but the children's median neutrophil count was lower, and their median duration of granulocytopenia before the trial was shorter . The incidence of bacteraemia was similar, but clinically documented infection was less frequent and fever of unknown origin consequently more common in children . Children developed more streptococcal bacteraemias and fewer staphylococcal bacteraemias than adults (P=0.003) but the relative incidence of various gram-negative species was similar (P=0.57) . In general, the children had a better overall success rate and lower mortality than adults . Death from infection was only 1% in children versus 4% in adults (P=0.001), and time to defervescence was shorter in children . In the younger age group, univariate logistic regression models showed high temperature, prolonged neutropenia before the trial and shock as prognostic indicators for the presence of bacteraemia . Solid tumour patients were significantly less likely to have a bacteraemia . Multivariate analysis confirmed the independent prognostic value of these indicators . Using the logistic equation of the selected model, the overall discriminant ability was poor . However, it was possible to identify a small subgroup without shock or high fever and with a short prior duration of neutropenia which carries a particularly low risk of bacteraemia, who could be considered for early discharge, monotherapy and shortened courses of antibodies, in prospective trials. Biochemistry, 1997 Nov 25, 36(47), 14277 - 83 An early intermediate in the folding reaction of the B1 domain of protein G contains a native-like core; Park SH et al.; The folding kinetics of a 57-residue IgG binding domain of streptococcal protein G has been studied under varying solvent conditions, using stopped-flow fluorescence methods . Although GB1 has been cited as an example of a protein that obeys a two-state folding mechanism, the following kinetic observations suggest the presence of an early folding intermediate . Under stabilizing conditions (low denaturant concentrations, especially in the presence of sodium sulfate), the kinetics of folding shows evidence of a major unresolved fluorescence change during the 1.5 ms dead time of the stopped-flow experiment (burst phase) . Together with some curvature in the rate profile for the single observable folding phase, this provides clear evidence of the rapid formation of compact states with native-like fluorescence for the single tryptophan at position 43 . In refolding experiments at increasing denaturant concentrations, the amplitude of the sub-millisecond phase decreases sharply and the corresponding slope (m value) is only about 30% lower than that of the equilibrium unfolding curve indicative of a pre-equilibrium transition involving cooperative unfolding of an ensemble of compact intermediates . The dependence on guanidine hydrochloride concentration of both rates and amplitudes (including the equilibrium transition) is described quantitatively by a sequential three-state mechanism, U {symbol: see text} I {symbol: see text} N, where an intermediate (I) in rapid equilibrium with the unfolded state (U) precedes the rate-limiting formation of the native state (N) . A 66-residue fragment of GB1 with an N-terminal extension containing five apolar side chains exhibits three-state kinetic behavior virtually identical to that of the 57-residue fragment . This is consistent with the presence of a well-shielded native-like core excluding the N-terminal tail in the early folding intermediate and argues against a mechanism involving random hydrophobic collapse, which would predict a correlation between overall hydrophobicity and stability of compact states. Obstet Gynecol, 1997 Dec, 90(6), 901 - 6 Opportunities for prevention of perinatal group B streptococcal disease: a multistate surveillance analysis . The Neonatal Group B Streptococcal Disease Study Group; Rosenstein NE et al.; OBJECTIVE: To evaluate the potential impact of ACOG and Centers for Disease Control and Prevention (CDC) consensus strategies for the prevention of perinatal group B streptococcal disease . METHODS: We evaluated cases of early-onset group B streptococcal disease identified by active surveillance during 1995, in four areas in North America with an aggregate 186,000 births per year . We reviewed the hospital records of mothers and infants and any prenatal records available on site . Cases were determined to be preventable based on whether group B streptococcal screening could have been performed prenatally, sensitivity of screening, presence of obstetric complications, and opportunity to administer antibiotics . RESULTS: We reviewed records for 245 of 246 infants with early-onset group B streptococcal disease in the surveillance areas . Most of the 53 case-mothers who delivered preterm and 192 who delivered full-term had had at least one prenatal visit (83% and 99%, respectively) . Few case-mothers had prenatal group B streptococcal screening cultures, although compliance was high for other prenatal screening tests . Fifty-four percent of case-mothers had a recognized obstetric risk factor for group B streptococcal disease: labor or rupture of membranes at less than 37 weeks, rupture of membranes for 18 hours on longer, or temperature 38C or greater . The estimated preventable portion of early-onset group B streptococcal cases was 78% for the screening-based approach (range 74% to 82% by area), compared with 41% for the risk-based approach (range 39% to 53% by area) . CONCLUSION: Comprehensive implementation of either of the recommended prevention strategies could potentially prevent a substantial proportion of early-onset group B streptococcal disease. Am J Obstet Gynecol, 1997 Nov, 177(5), 1024 - 9 International Multicentre Term Prelabor Rupture of Membranes Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term; Seaward PG et al.; OBJECTIVES: Our purpose was to determine significant predictors for the development of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term . STUDY DESIGN: Logistic regression analysis with odds ratios and 95% confidence intervals was used to determine the significant predictors of clinical chorioamnionitis and postpartum fever in women with prelabor rupture of membranes at term enrolled in this study . The study recently compared in a randomized controlled trial four strategies of management: induction with oxytocin, induction with prostaglandin, expectant management, and, if failed, induction with oxytocin or prostaglandin . RESULTS: The following variables were significantly associated with clinical chorioamnionitis: (1) number of digital vaginal examinations: > 8, 7 to 8, 5 to 6, 3 to 4 (vs 0 to 2) (odds ratio 5.07, 3.80, 2.62, 2.06); (2) duration of active labor: > or = 12, 9 to < 12, 6 to < 9 hours (vs < 3 hours) (odds ratio 4.12, 2.94, 1.97); (3) meconium-stained amniotic fluid (odds ratio 2.28); (4) parity of 0 (odds ratio 1.80); (5) time from membrane rupture to active labor: > or = 48, 24 to < 48 hours (vs < 12 hours) (odds ratio 1.76, 1.77); and (6) group B streptococcal colonization (odds ratio 1.71) . Variables significantly associated with postpartum fever were (1) clinical chorioamnionitis (odds ratio 5.37), (2) duration of active labor: > or = 12, 9 to < 12, 6 to < 9, 2 to < 6 hours (vs < 3 hours) (odds ratio 4.86, 3.53, 3.46, 3.04), (3) cesarean section, operative vaginal delivery (odds ratio 3.97, 1.86), (4) group B streptococcal colonization (odds ratio 1.88), and (5) maternal antibiotics before delivery (odds ratio 1.94) . CONCLUSIONS: Increasing numbers of digital vaginal examinations, longer duration of active labor, and meconium staining of the amniotic fluid were the most important risk factors for the development of clinical chorioamnionitis in women with prelabor rupture of membranes at term . The most important risk factors for the development of postpartum fever were clinical chorioamnionitis, increasing duration of active labor, and cesarean section delivery. Infect Immun, 1997 Dec, 65(12), 5209 - 15 Differential induction of Th1 versus Th2 cytokines by group A streptococcal toxic shock syndrome isolates; Norrby-Teglund A et al.; The majority of group A streptococcal (GAS) isolates from patients with streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) express numerous virulence factors, including several superantigens (SAgs) . Purified SAgs are potent inducers of inflammatory (Th1) cytokines that contribute to the pathogenesis of severe infections . However, GAS-infected individuals are likely to be exposed to a mixture of GAS SAgs as well as other virulence factors produced by the bacteria, and therefore, our goal was to characterize the mitogenic and cytokine induction profiles of this mixture . All GAS isolates tested had brisk mitogenic activity and induced potent cytokine responses, with higher frequencies of Th1 than Th2 cytokine-producing cells . The mitogenic activity produced in culture supernatants of three selected clinical GAS isolates was significantly different, but no marked difference was found in their overall cytokine induction profiles . However, significant differences (P < 0.0062) were noted in the induction of Th2 cytokines between GAS supernatants and recombinant streptococcal pyrogenic exotoxin A (rSpeA), suggesting that the presence of other SAgs and/or the production of additional virulence factors may alter the overall cytokine induction profile of SAgs . A significant individual variation in the level of proliferative and cytokine responses to the same GAS culture supernatants or to rSpeA was noted . Individuals with higher frequencies of cells producing Th2 cytokines mounted lower levels of Th1 cytokine responses, and vice versa . Furthermore, quantification of the intensity and cell area of interleukin-1beta (IL-1beta)-producing cells by image analysis revealed that individuals with higher Th2 responses had significantly lower IL-1beta production (P < 0.0001) than the individual with a strong Th1 response . Differences in the ability to induce Th1 versus Th2 cytokines, as well as the individual variations in cytokine responses to streptococcal SAgs, may play a central role in determining the severity of invasive GAS infections. Eur J Pediatr, 1997 Nov, 156(11), 851 - 3 Conditions currently associated with erythema nodosum in Swiss children; Hassink RI et al.; A review was made of the 36 paediatric patients in whom the diagnosis of erythema nodosum had been established between 1977 and 1996 at the Department of Paediatrics, University of Bern, Switzerland . Infectious diseases were associated with erythema nodosum in 20 (including 10 streptococcal infections) and non-infectious inflammatory diseases in 8 patients . None of the 36 patients had tuberculosis or had been exposed to sulphonamides, phenytoin or hormonal contraceptives . There were eight patients in whom either the associated disease was not diagnosed, or there was no other disease . Conclusion: Most cases of erythema nodosum are nowadays caused by non-mycobacterial infectious diseases or by non-infectious inflammatory diseases. Clin Pediatr (Phila), 1997 Nov, 36(11), 617 - 24 Management of asymptomatic term neonates whose mothers received intrapartum antibiotics--Part 2: Diagnostic tests and management strategies . Center of Disease Control and Prevention}; Allen SR; The evaluation of the potentially septic newborn is often a source of frustration for practitioners . In the past, it has often been standard practice to evaluate and treat empirically all neonates whose mothers received antibiotics during labor, regardless of whether the infant had any signs or symptoms suggestive of infection . With the advent of recommendations for intrapartum antibiotic therapy to prevent early-onset neonatal group B streptococcal infections, this strategy is no longer practicable because too many infants would thus be evaluated and treated needlessly . This two-part review addresses the issues involved in managing asymptomatic newborns whose mothers received intrapartum antibiotics . Part I, published separately, reviewed the rationale behind strategies for preventing intrapartum transmission of bacterial infection . This final part addresses the evaluation and management of the newborn . A number of diagnostic tests are often used in looking for bacterial infections in the neonate . Unfortunately, none of these is both rapid and reliable . A clinical pathway provided here can serve as a useful guide for the clinician, but uncertainty will always remain . Ultimately, each practitioner must determine the degree of risk or uncertainty that he or she can accept on the basis of clinical experience. Biotherapy, 1997, 10(2), 99 - 106 Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patients; Wakasugi T et al.; We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen . In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen . Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses . Phenotypic analysis of splenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to patients treated with OK-432 alone or untreated patients . Splenic T cells from patients treated with OK-432 plus fibrinogen showed significantly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p < 0.05), and culture of these splenic T cells with recombinant IL-2 induced the expansion of lymphokine-activated killer cells . These results demonstrate that local immunotherapy with a mixture of OK-432 and fibrinogen effectively augumented splenic antitumor immunity in gastric cancer patients. Arch Mal Coeur Vaiss, 1997 Jul, 90(7), 981 - 5 {Epidemiological course of cardiovascular diseases in developing countries}; Bertrand E; Though the environmental and medical conditions are very different, similar population characteristics can be observed in the developing countries . The mean age of the population is young . Most people have a rural way of life, but migrations towards towns result in a disorganized urbanization and in habits more predisposing to cardiovascular diseases . Care access is often difficult for the patients . With respect to risk factors, smoking is increasing, hypertension is highly prevalent and severe, a trend towards obesity is frequent in medium or high economical level people . S or C hemoglobin diseases seem to be associated with coronary heart disease . In spite of very insufficient statistical data, it appears that: cardiovascular disease mortality is increasing when total mortality is decreasing: ischemic and hypertensive heart diseases are increasing when streptococcal or nutritional heart diseases are stabilizing or decreasing . The authors seem to be the different developing countries in respect to the crossing of these curves . Some countries have not reached the crossing . Subsaharan Africa for instance . Others have gone beyond the crossing, some Asian countries for instance . Other countries seem to be at the intersection (Mediterranean or Latin American countries) . But many countries suffer the double burden of increasing and decreasing diseases . There is a general lack of prevention owing to other competing priorities and also to economical, social and educational difficulties . However in some developing countries feasibility and efficacy of preventive measures have been proved. Arch Mal Coeur Vaiss, 1997 Jul, 90(7), 975 - 80 {Anti-streptokinase antibodies}; Helft G et al.; The use of thrombolytics has significantly improved the management of patients with acute myocardial infarction but available molecules remains imperfect: restoration of normal coronary patency in about half the cases, risks of reocclusion, risk of bleeding . Streptokinase (SK), which is the least expensive agent, has disadvantages as do the other thrombolytics . SK, an immunogenic bacterial protein, has another feature: administration of SK leads to an immunitory response with the production of specific anti-streptokinase antibodies . These anti-streptokinase antibodies may interfere with the future administration of a compound containing SK either by inducing an allergic response or by neutralising the SK and making it ineffective . Moreover, anti-streptokinase antibodies, the result of previous streptococcal infections, are present in the circulation . Although the prevalence of anti-streptokinase antibodies in the general population, especially coronary patients at risk of myocardial infarction, is not well known and their potentially harmful effects are even less well known . In particular, the platelet aggregant effect in vitro of these antibodies in the presence of SK was not taken into account in the trials studying the influence of anti-streptokinase antibodies in the results of thrombolysis by SK . The anti-lytic effect of anti-streptokinase antibodies is well documented . For this reason, it is not recommended to readminister SK in patients who have previously been thrombolysed with a product containing SK. Rev Prat, 1997 Sep 1, 47(13), 1438 - 41 {Cutaneous eruptions of streptococcal and staphylococcal origin}; Cribier B; Scarlet fever consists in a diffuse exanthem associated with mucous changes . Classical scarlet fever is rare now, but other severe streptococcal infections have become more frequent, such as streptococcal toxic shock syndrome . The scarlatiniform exanthem and the shock observed in this disease are due to a streptococcal pyrogenic exotoxin . Exfoliative toxins secreted by Staphylococcus aureus are responsible for the tender erythema and cutaneous scaling characteristic of staphylococcal scalded skin syndrome of infancy . The so-called staphylococcal scarlet fever is probably an attenuated variant of this disease . Toxic shock syndrome toxin 1 (TSST1) is another staphylococcal toxin implied in the staphylococcal toxic shock syndrome . This disease is characterized by general symptoms and a scarlatiniform exanthem which are due to the effects of TSST1, acting as a superantigen. J Infect Dis, 1997 Oct, 176(4), 992 - 1000 Invasive group A streptococcal infections in North Carolina: epidemiology, clinical features, and genetic and serotype analysis of causative organisms; Kiska DL et al.; During 1994 and 1995, an increase in the number and severity of group A streptococcal (GAS) infections was noted in North Carolina . Ninety-six patients had GAS recovered from blood and other sterile body fluids, abscesses, and soft tissue . The overall case fatality rate was 11% but was much higher in patients with toxic shock syndrome (55%) and necrotizing fasciitis (58%) . Recent invasive GAS isolates were compared with pre-1994 invasive isolates and temporally related pharyngeal isolates by M protein serotyping, pulsed field gel electrophoresis (PFGE), and polymerase chain reaction amplification of the streptococcal pyrogenic exotoxin A gene . Serotypes M1 and M3 accounted for 50% of recent invasive isolates (1994-1995) and 58% of pharyngeal isolates (1994) . The latter isolates demonstrated PFGE patterns that were identical to invasive M1 and M3 strains, suggesting that pharyngeal infections may have served as a reservoir for virulent GAS clones. Clin Pediatr (Phila), 1997 Oct, 36(10), 563 - 8 Management of asymptomatic term neonates whose mothers received intrapartum antibiotics--Part 1: Rationale for intrapartum antibiotic therapy; Allen SR; The evaluation of the potentially septic newborn is often a source of frustration for practitioners . In the past, it has often been standard practice to evaluate and treat empirically all neonates whose mothers received antibiotics during labor, regardless of whether the infant had any signs or symptoms suggestive of infection . With the advent of recommendations for intrapartum antibiotic therapy to prevent early-onset neonatal group B streptococcal infections, this strategy is no longer practicable because too many infants would thus be evaluated and treated needlessly . This two-part review addresses the issues involved in managing asymptomatic newborns whose mothers received intrapartum antibiotics . This first part reviews the rationale behind strategies for preventing intrapartum transmission of bacterial infection . The administration of intravenous antibiotics to laboring mothers appears to reduce the incidence of group B streptococcal infections in neonates . Additionally, intrapartum antibiotic therapy for maternal chorioamnionitis may inhibit transmission of infection to the infant . Part 2--to be published separately--will address the evaluation and management of the newborn. Gene, 1997 Sep 15, 197(1-2), 47 - 64 Identification and transcriptional analysis of a Treponema pallidum operon encoding a putative ABC transport system, an iron-activated repressor protein homolog, and a glycolytic pathway enzyme homolog; Hardham JM et al.; We have characterized a 5.2-kilobase (kb) putative transport related operon (tro) locus of Treponema pallidum subsp . pallidum (Nichols strain) (Tp) encoding six proteins: TroA, TroB, TroC, TroD, TroR and Phosphoglycerate mutase (Pgm) . Four of these gene products (TroA-TroD) are homologous to members of the ATP-Binding Cassette (ABC) superfamily of bacterial transport proteins . TroA (previously identified as Tromp1) has significant sequence similarity to a family of Gram-negative periplasmic substrate-binding proteins and to a family of streptococcal proteins that may have dual roles as substrate binding proteins and adhesins . TroB is homologous to the ATP-binding protein component, whereas TroC and TroD are related to the hydrophobic membrane protein components of ABC transport systems . TroR is similar to Gram-positive iron-activated repressor proteins (DesR, DtxR, IdeR, and SirR) . The last open reading frame (ORF) of the tro operon encodes a protein that is highly homologous to the glycolytic pathway enzyme, Pgm . Primer extension results demonstrated that the tro operon is transcribed from a sigma 70-type promoter element . Northern analysis and reverse transcriptase-polymerase chain reactions provided evidence for the presence of a primary 1-kb troA transcript and a secondary, less abundant, troA-pgm transcript . The tro operon is flanked by a Holliday structure DNA helicase homolog (upstream) and two ORFs representing a purine nucleoside phosphorylase homolog and tpp15, a previously characterized gene encoding a membrane lipoprotein (downstream) . The presence of a complex operon containing a putative ABC transport system and a DtxR homolog indicates a possible linkage between transport and gene regulation in Tp. Adv Exp Med Biol, 1997, 418, 863 - 8 Group A and group B streptococcal vaccine development . A round table presentation; Dale JB et al.; The data presented above provide a broad overview of ongoing work to develop vaccines against group A and group B streptococcal infections . The encouraging results of human trials with conjugate group B polysaccharide vaccines suggest that this approach will lead to a safe and effective method for preventing these devastating infections in newborn infants . The results of preclinical studies of the various strategies to develop group A streptococcal vaccines are also encouraging . Whether one approach will be more advantageous or efficacious than another will need to await clinical trials . Nevertheless, we predict that in the next decade we will make significant strides in preventing streptococcal infections and their complications. Adv Exp Med Biol, 1997, 418, 635 - 7 Surface protein expression in group B streptococcal invasive isolates; Ferrieri P et al.; Results from characterization of 211 GBS isolates from early-onset disease indicated that serotypes Ia, III and V accounted for almost 80% of the isolates, and that alpha was the protein most often expressed . Each of the common polysaccharide types had a characteristic predominant protein expression pattern: alpha for Ia, R4 for type III and R1+R4 for type V isolates . Expression of alpha protein was always mutually exclusive of R proteins . The presence of more than one species of R by a given isolate was confirmed by IEP . In addition, PAGE/WB studies verified the multiple MW forms of R1, and the variation from strain to strain in the highest form of R4 that we had previously reported . Our data not only showed the great complexity of the GBS cell surface but also demonstrated the advantage of using both type polysaccharides and surface-localized proteins as markers for characterization of GBS strains. Mol Immunol, 1997 Apr, 34(6), 433 - 40 Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins; Cooper JA et al.; An approach to mapping antigenic B cell epitopes within alpha-helical coiled coil proteins has been developed and applied to two proteins: Streptococcal M protein and C . elegans paramyosin protein UNC-15 . Overlapping peptides derived from an alpha-helical coiled coil conformational epitope were embedded between helical flanking peptides derived from the completely unrelated GCN4 leucine zipper peptide . The resulting chimeric peptides exhibited helical propensity . Chimeric peptides were tested for antigenicity (recognition by antibody) or immunogenicity (production of appropriate antibody response) . A conformational epitope within the Streptococcal M protein recognised by three mAbs spanned 12 residues . Analysis of chimeric peptides based on C . elegans UNC-15 has enabled fine mapping of the minimal B cell epitope recognised by monoclonal antibody NE1-6B2 to seven non-contiguous residues (spanning 15 residues); the footprint of contact residues involved in antibody recognition being restricted to the hydrophilic face of the helix and covering five helical turns . This chimeric peptide epitope when coupled to diphtheria toxoid was highly immunogenic in mice and antisera recognised the conformationally dependent native peptide epitope . This approach has the potential to map conformational epitopes and design minimal epitopes for use as vaccine candidates. Clin Infect Dis, 1997 Sep, 25(3), 574 - 83 Diagnosis and management of group A streptococcal pharyngitis: a practice guideline . Infectious Diseases Society of America; Bisno AL et al.; This is the second in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee . The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline . The targeted providers are pediatricians, family practitioners, and internists . The targeted patients and setting for the acute pharyngitis guideline are pediatric, adolescent, and adult outpatients with a complaint of sore throat . Funding was provided by the IDSA . Panel members represented experts in adult and pediatric infectious diseases . The guidelines are evidence-based . A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed . The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council . An executive summary, algorithms, and tables highlight the major recommendations . Indicators of quality will assist in guideline implementation . The guideline will be listed on the IDSA home page at http://www.idsociety.org. J Nutr, 1997 Oct, 127(10), 1989 - 92 The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B streptococcal sepsis in neonatal rat pups; Rayon JI et al.; Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators . The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups . Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil . On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam . On postnatal d 7, pups were either injected with 1 x 10(7.5) GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition . Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group . Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005) . These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators. Ugeskr Laeger, 1997 Sep 1, 159(36), 5368 - 71 {Food-borne streptococcal epidemics}; Jespersen NB et al.; Approximately two days after a high school final year farewell party a striking number of pupils and teachers became ill with pharyngitis . The regional public health medical office carried out a questionnaire study with a control group of younger pupils . The regional food control unit studied the preparation and handling at food . Some bacterial cultures received from general practitioners were identified by the regional clinical-microbiological laboratory . Seventy-six percent of the 216 exposed pupils who answered (94% response rate) against 15% of 238 answering in the control group (83% response rate) became ill . The peak incidence was two days after the party . The infectious agent was beta-haemolytic streptoccoci group-A, T-type 25 . A salad made of pasta and vegetables that were not cooked and handled properly must have been the vehicle of infection although no salad was left for cultivation . Salads made of pasta must be prepared with great care and effectively cooled . When suspecting a food-borne epidemic, clinicians should immediately inform the regional public health medical office, and the municipal food control unit must take part in the investigations . It is important that bacterial cultures are identified by the regional clinical-microbiological laboratory . It should be considered to make it mandatory that the involved personnel accepts clinical examination and microbiological sampling in cases of suspected food-borne infection. Proc Natl Acad Sci U S A, 1997 Sep 16, 94(19), 10172 - 7 Probing the role of packing specificity in protein design; Dahiyat BI et al.; By using a protein-design algorithm that quantitatively considers side-chain packing, the effect of specific steric constraints on protein design was assessed in the core of the streptococcal protein G beta1 domain . The strength of packing constraints used in the design was varied, resulting in core sequences that reflected differing amounts of packing specificity . The structural flexibility and stability of several of the designed proteins were experimentally determined and showed a trend from well-ordered to highly mobile structures as the degree of packing specificity in the design decreased . This trend both demonstrates that the inclusion of specific packing interactions is necessary for the design of native-like proteins and defines a useful range of packing specificity for the design algorithm . In addition, an analysis of the modeled protein structures suggested that penalizing for exposed hydrophobic surface area can improve design performance. Mol Gen Genet, 1997 Aug, 255(5), 467 - 76 Mutational analysis of a site-specific recombinase: characterization of the catalytic and dimerization domains of the beta recombinase of pSM19035; Canosa I et al.; The beta recombinase encoded by the streptococcal plasmid pSM19035, which shows 28 to 34% identity with DNA resolvases and DNA invertases, can catalyze formation of deletions or inversions between properly oriented target sites . We have constructed a number of site-directed mutations at residues that are conserved between the beta protein and other DNA recombinases of the resolvase/invertase family . The analysis of the recombination and DNA-binding ability of each mutant protein shows that the mutations affect the catalytic activity and, in two cases, the dimerization of the protein . The results suggest that the beta protein probably mediates recombination by a catalytic mechanism similar to that proposed for the resolvase/invertase family . Since the beta recombinase differs from DNA resolvases and DNA invertases in its lack of bias towards either of these reactions, the results presented support the hypothesis that its unique properties might depend on details of the architecture or assembly of the recombination complex . In addition, two beta protein mutants that can no longer form dimers in solution have provided new insights into the way the protein binds to DNA. Br J Rheumatol, 1997 Aug, 36(8), 909 - 11 Long-term follow-up of juvenile-onset cutaneous polyarteritis nodosa associated with streptococcal infection; Till SH et al.; Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries . Although predominantly an adult disease, PAN is well described in children . It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tract, lungs and kidneys, and a limited form in which disease is confined to the skin, muscles, joints and peripheral nerves . In either case, streptococcal infection has been implicated by a positive throat swab or a significant increase in either antistreptolysin O (ASOT) or antihyaluronidase titres . The limited form is thought to run a benign course, but little has been written about its long-term outcome . We describe two patients who developed a cutaneous vasculitis following a probable streptococcal infection . Both have run a relapsing and remitting course with significant elevations of ASOT and in one, at least, prophylactic penicillin has had a strikingly beneficial effect . In both patients, the disease seems to have receded during childhood, only to recur, retaining its original form, in adult life . Their current ages are 22 and 19 yr, respectively. J Infect Dis, 1997 Sep, 176(3), 693 - 7 Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis; Bogdan I et al.; To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in neuronal injury in experimental group B streptococcal meningitis, infected neonatal rats were treated with a monoclonal antibody against TNF-alpha (20 mg/kg intraperitoneally) or saline given at the time of infection . Histopathology after 24 h showed necrosis in the cortex and apoptosis in the hippocampal dentate gyrus . Treated animals had significantly less hippocampal injury than did controls (P < .001) but had similar cortical injury and cerebrospinal fluid (CSF) inflammation . The antibody was then administered directly intracisternally (170 microg) to test whether higher CSF concentrations reduced inflammation or cortical injury . Again, hippocampal apoptosis was significantly reduced (P < .01), while cortical injury and inflammation were not . Thus, TNF-alpha played a critical role in neuronal apoptosis in the hippocampus, while it was not essential for the development of inflammation and cortical injury in this model. J Infect Dis, 1997 Sep, 176(3), 560 - 9 Challenge of BALB/c mice with respiratory syncytial virus does not enhance the Th2 pathway induced after immunization with a recombinant G fusion protein, BBG2NA, in aluminum hydroxide; Corvaia N et al.; The polypeptide of aa 130-230 of the G protein (G2Na) of respiratory syncytial virus (RSV) was fused to BB, the albumin-binding region of streptococcal G protein, producing BBG2Na, which induced protective immune responses in rodent models . Evaluation of the immune response in mice immunized with BBG2Na in the adjuvant alhydrogel revealed high amounts of interleukin (IL)-5 and some IL-4 in splenocytes restimulated in vitro . This is compatible with a Th2 response . The activation of the Th2 pathway in such mice was further supported by the detection of IL-5 and G2Na-specific IgE in vivo . Of interest, in contrast to immunization with formalin-inactivated RSV, immunization of mice with BBG2Na followed by intranasal RSV challenge did not lead to increased production of IL-5- or G2Na-specific IgE . However, IgG1- and IgG2a-specific antibodies were boosted . These results demonstrate that the Th2 pathway is not enhanced by RSV challenge in BBG2Na-immunized mice. Am J Obstet Gynecol, 1997 Aug, 177(2), 268 - 71; discussion 271-3 Characteristics of successful claims for payment by the Florida Neurologic Injury Compensation Association Fund; Stalnaker BL et al.; OBJECTIVES: Our purpose was to examine the obstetric characteristics of claims paid by the State of Florida after the birth of a neurologically impaired child . STUDY DESIGN: The Florida Birth Related Neurological Injury Compensation plan is a no-fault alternative to litigation for compensation after a catastrophic neurologic birth injury . The plan has specific criteria for inclusion . We retrospectively analyzed claims for compensation that were accepted and paid (n = 64) after a birth-related neurologic injury . Simple description statistics were compiled for the relative frequencies of various obstetric correlates found in successful claims for payment . RESULTS: Seventy percent of infants (45) were delivered by cesarean section and 15 of 19 vaginal deliveries (79%) were operative (forceps or vacuum), yielding a 94% operative delivery rate . A persistent nonreassuring fetal heart rate tracing was seen before delivery in all cases . The 5-minute Apgar score was < or = 6 in 91% of deliveries and the 10-minute Apgar score was < 6 in 86% of deliveries . When first examined in the labor and delivery suite, 17 women had a nonreassuring fetal heart rate, and a nonreassuring tracing developed in labor in 47 . Nine attempts at vaginal birth after a cesarean section led to a uterine rupture . Seven of these deliveries were either inductions or augmentations against an unfavorable cervix . Forty-five percent (27) of deliveries were associated with meconium-stained amniotic fluid, including 17 infants with meconium aspiration syndrome . There were three shoulder dystocias and four infants with group B streptococcal sepsis . In eight cases (12.5%), there appeared to be a breach of the published standard of care, which contributed to the poor outcome . CONCLUSION: Most of these cases should not have been eligible for compensation in a traditional tort-based system because the applicable standard of care was not breached . Meeting the published standard for perinatal care failed to prevent these devastating neurologic injuries . Obviously, not all intrapartum injuries can be prevented; however, if we are to prevent similar injuries in the future, we will need to examine the clinical management in these or similar case for clues to develop novel strategies to respond to intrapartum emergencies . An unexpected finding was the frequency of catastrophic birth injuries after an attempted vaginal birth after cesarean section with the predominance of these deliveries associated with oxytocin stimulation against an unripe cervix . It is apparent that the push to lower cesarean section rates is not without some risk. Pediatr Res, 1997 Sep, 42(3), 268 - 72 Association of toxic shock syndrome toxin-secreting and exfoliative toxin-secreting Staphylococcus aureus with Kawasaki syndrome complicated by coronary artery disease; Leung DY et al.; Kawasaki syndrome (KS) has been reported to be associated with selective expansion of Vbeta2+ T cells and either staphylococcal toxic shock syndrome toxin-1 or streptococcal pyrogenic exotoxin C in uncomplicated cases . However, there have been no previous studies on the role of superantigens in KS associated with coronary artery disease, the major complication of this illness . The present study characterized bacteria isolated from three acute KS patients who developed coronary artery disease . Staphylococcus aureus secreting either TSST-1 (n = 3) or exfoliative toxin A (n = 1), both known to stimulate expansion of Vbeta2+ T cells, were isolated from all three patients . The percent Vbeta2+ T cells was determined in three patients with coronary artery disease . On presentation, one patient demonstrated reduction, whereas the other two showed expansion, of Vbeta2+ T cells . Repeat analyses of the latter two children showed their percent Vbeta2+ T cells to decrease toward normal . These observations suggest that coronary artery disease in KS may result from superantigenic stimulation of Vbeta2+ T cells . This is also the first demonstration of an association of staphylococcal exfoliative toxin with acute KS . The observation that three different bacterial toxins associated with KS are potent activators of Vbeta2+ T cells suggests an important role for this T cell subset in the pathogenesis of this autoimmune disease. Obstet Gynecol, 1997 Sep, 90(3), 347 - 52 The pediatric costs of strategies for minimizing the risk of early-onset group B streptococcal disease; Fargason CA Jr et al.; OBJECTIVE: To estimate the pediatric costs associated with the Centers for Disease Control and Prevention (CDC) guidelines for the management of infants born to mothers receiving intrapartum antimicrobial prophylaxis for prevention of early-onset group B streptococcal disease . METHODS: For an annual United States birth cohort of 3.95 million infants, we estimated the cost of pediatric care provided to full-term asymptomatic infants when pediatricians followed the CDC algorithm for the management of infants exposed to intrapartum antimicrobial prophylaxis under culture-based and risk factor-based maternal care approaches . We calculated the relative contribution of pediatric costs to the total costs of preventing a case of early-onset group B streptococcal sepsis . RESULTS: Total pediatric costs were $41 million for a culture-based approach and $33 million for a risk factor-based approach . Hospital and physician costs accounted for more than 78% of this total . The majority (over 95%) of the pediatric costs were associated with vaginal deliveries . Incorporating pediatric costs into previous cost-effectiveness analyses increased the cost per sepsis case averted by as much as 51% for culture-based strategies and by as much as 112% for risk factor-based strategies . Pediatric costs varied with the average length of stay for full-term infants and with the average cost of a hospital day . CONCLUSION: Substantial pediatric costs are associated with the implementation of an obstetric strategy for minimizing the risk of early-onset group B streptococcal disease . Such costs should be included in future cost-effectiveness analyses of different strategies for minimizing the risk of group B streptococcal disease in newborns. Oncology, 1997 Sep-Oct, 54(5), 414 - 23 Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432; Aoyagi H et al.; OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan . We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer . To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan . OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively . Lentinan showed no direct anticancer effect in vitro . We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR . Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR . We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59 . The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells . These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer. J Exp Med, 1997 Aug 4, 186(3), 375 - 83 The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action; Li PL et al.; Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates Vbeta2-bearing human T cells, but is inactive in mice . SPE-C binds with high affinity to both human HLA-DR and murine I-E molecules, but not to murine I-A molecules in a zinc-dependent fashion . Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II alpha-chain binding site common to all other bacterial superantigens . Despite this, SPE-C cross-links MHC class II to induce homotypic aggregation of class II-bearing B cells . Nondenaturing sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH . These data support a recent crystal structure of SPE-C and reveal yet another mechanism by which bacterial superantigens ligate and cross-link MHC class II. J Trop Pediatr, 1997 Aug, 43(4), 204 - 7 Anionic charge abnormalities of red blood cells and proteinuria in glomerulonephritides; Ramjee G et al.; We studied alcian blue (AB) binding to red blood cells (RBC) {ABRBC} in 89 children and adults with a variety of glomerular diseases . ABRBC was significantly reduced in the group as a whole when compared with healthy controls (P < 0.001) . A moderate correlation between the degree of proteinuria and ABRBC was detected in the children with renal disease (r = 0.43, P < 0.001), but not in adult patients . A significant reduction in ABRBC was detec