Eur J Pediatr, 1996 Mar, 155(3), 168 - 72 Mitral regurgitation may be related with previous streptococcal infection; Wahid MR et al.; We measured anti M protein antibody (AMPA) titres in children with idiopathic mitral regurgitation (MR), streptococcal infection, rheumatic fever (RF), post-streptococcal acute glomerulonephritis (AGN) and normal healthy children . We investigated the association of MR with streptococcal infection and whether high AMPA titres can be used as persisting evidence of previous streptococcal infection . AMPA titres were measured with an enzyme-linked immunosorbent assay . We found significantly higher antibody titres in patients with MR and in streptococcal infection, RF, and AGN than in healthy controls . In the MR group (n = 15), 54% patients had AMPA titres above the 90th percentile value that was found in normal controls . An elevated AMPA titre persisted for a long period even when the anti-streptolysin O titres had declined to normal in RF patients . Our data suggest that the high AMPA titres in MR should be further investigated to clarify the probable association with previous streptococcal infection . CONCLUSION: High AMPA titre is a risk factor for developing complications after streptococcal infection . Our serological evidence suggests that in some patients, MR may be related to previous streptococcal infection. Antimicrob Agents Chemother, 1996 Mar, 40(3), 809 - 11 Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis; Vermot D et al.; Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats . Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula . Clarithromycin was marginally superior to clindamycin against small amounts of inocula . Clarithromycin may be considered for endocarditis chemoprophylaxis in human. Anal Biochem, 1996 Mar 1, 235(1), 61 - 72 Fiber-optic fluorometric sensing of polymerase chain reaction-amplified DNA using an immobilized DNA capture protein; Mauro JM et al.; A fiber-optic assay for amplified DNA products has been developed . Modifications of the DNA capture strategy described previously by Kemp et al . {Proc . Natl . Acad . Sci . USA 86, 2423-2427 (1989)} were made that allowed selective binding of DNA labeled during the amplification process to the sensing surface of fused silica fibers . The gene for a chimeric protein composed of the IgG-binding beta 2 subdomain of streptococcal protein G fused with the DNA binding domain of yeast GCN4 was constructed, and this PG/GCN4 protein was overexpressed in Escherichia coli . The purified protein was noncovalently bound to IgG-modified fibers utilizing strong and specific interactions between the protein G beta 2 domain and goat IgG that had been covalently immobilized on the fiber surface . Nanomolar concentrations of amplified DNA labeled with the fluorophore tetramethylrhodamine and the AP-1 consensus nucleotide sequence recognized by GCN4 (5'-ATGACTCAT) were rapidly and selectively bound within the evanescent zone of multimode laser-illuminated fibers . Signal from unincorporated fluorescent PCR primer was negligible . Individual fibers could be used for multiple sequential assays, since the fluorescent double-stranded DNA was rapidly and completely stripped from their surfaces with high salt solutions, leaving the IgG-PG/GCN4 DNA binding complex intact to accept another PCR sample. J Rheumatol Suppl, 1996 Mar, 44, 56 - 60 Combination therapy in rheumatoid arthritis: the animal model perspective; Oliver SJ et al.; Attempts to improve antirheumatic agent efficacy have resulted in exploration of treatment protocols with combinations of 2 or more agents . Hypothetically, an ideal combination therapy would have greater efficacy and less toxicity than any of its component agents used individually . However, even a limited number of available drugs can produce a daunting number of possible combination protocols, each requiring clinical evaluation . Intelligent selection of combination protocols, based on a firm understanding of each agent's specific mechanism(s) of action, may help identify potentially useful regimens . Autoimmune animal models of inflammatory synovitis provide a unique opportunity to study the etiology, pathophysiology, and treatment of rheumatoid arthritis (RA) . Induction of chronic inflammatory synovitis in susceptible inbred strains can allow for in vivo study under reproducible controlled conditions, using experimental protocols not possible in humans . Although animal models can only approximate human rheumatic disease in its complete form, they are nonetheless important for developing new therapeutic strategies . We review the 3 most common animal models of RA, the streptococcal cell wall, adjuvant, and collagen arthritis rat models . Surprisingly, few published studies evaluate combination therapy in RA animal models . We discuss these investigations, which use interventions aimed at angiogenesis, microtubule function, and immune regulation, as examples of animal models to assess and develop effective therapeutic combinations of antirheumatic agents. Int J Fertil Menopausal Stud, 1996 Mar-Apr, 41(2), 115 - 23 Vaginitis: diagnosis and management; Faro S; The various conditions that give rise to vaginitis include specific and nonspecific entities, such as candidiasis, trichomoniasis, bacterial vaginosis, group B streptococcal vaginitis, purulent vaginitis, volvodynia, and vestibulitis . The patient with chronic vaginitis usually develops this condition because of a misdiagnosis . It is critical that patients who have chronic vaginitis be thoroughly evaluated to determine if there is a specific etiology and whether their condition is recurrent or persistent, or is a reinfection . This also must include obtaining a detailed history, beginning with the patient's best recollection of when she felt perfectly normal . The physician must have an understanding of a healthy vaginal ecosystem and what mechanisms are in place to maintain the equilibrium . The vaginal ecosystem is a complex system of micro-organisms interacting with host factors to maintain its equilibrium . The endogenous microflora consists of a variety of bacteria, which include aerobic, facultative and obligate anaerobic bacteria . These organisms exist in a commensal, synergistic or antagonistic relationship . Therefore, it is important to understand what factors control the delicate equilibrium of the vaginal ecosystem, and which factors, both endogenous and exogenous, can disrupt this system . It is also important for the physician to understand that when a patient has symptoms of vaginitis it is not always due to an infectious etiology . There are situations in which an inflammatory reaction occurs but the specific etiology may not be determined . Thus, it is important that the physician not rush through the history or the examination. Intern Med, 1996 Mar, 35(3), 203 - 6 Tricuspid valve endocarditis with large vegetations in a non-drug addict without underlying cardiac disease; Iwama T et al.; We report a case of gamma-streptococcal tricuspid valve endocarditis in a patient with no history of intravenous drug abuse . Echocardiography revealed large vegetations on the anterior and septal cusps . The patient had persistent fever and recurrent septic pulmonary embolism despite prolonged antibiotic therapy . However tricuspid valve replacement was successful. Eur J Clin Microbiol Infect Dis, 1996 Mar, 15(3), 206 - 210 Rapid detection of group B streptococcal colonization of the genital tract by a commercial optical immunoassay; Carroll KC et al.; The performance of a commercial optical immunoassay (OIA) was compared at two institutions with that of routine agar and broth culture methods for the detection of group B streptococcal (GBS) colonization of the genital tract . The Strep B OIA (Bio Star, USA) was used to test 962 vaginal swabs from pregnant women for the presence of GBS antigen . The prevalence of GBS vaginal colonization in this population was 22.4% . The OIA results were compared with those of culture on trypticase soy agar with 5% sheep blood (TSA) and broth enhanced culture (Lim broth) . Sensitivity and specificity values of the OIA method compared to TSA culture alone were 82.5% and 91.8%, respectively . The sensitivity of the OIA method was equivalent to that of TSA culture (62.4% vs . 64.4%; p > 0.5, chi 2 = 0.01) when the data were compared with broth culture . The extent of colonization affected the sensitivity of the OIA method: 100% of 4+, 94% of 3+, 96% of 2+, and 63% of 1+ TSA plates were detected by the OIA test . The commercial OIA method demonstrated sensitivity equivalent to that of TSA culture for the detection of GBS colonization . The OIA test offers two additional advantages over culture: reduced time required to obtain results (30 min vs . days) and the ability to detect GBS antigen in samples with compromised viability . The results of this study suggest that the Strep B OIA test can be a useful diagnostic tool in the management of early-onset GBS disease. Infection, 1996 Mar-Apr, 24(2), 164 - 7 Streptococcal toxic shock syndrome in a postpartum woman . Case report and review of the literature; Jorup-Ronstrom C et al.; A case of streptococcal toxic shock syndrome in a 29-year-old postpartum woman is described . The patient presented with hypotension, coagulation defects, adult respiratory distress syndrome and scarlet exanthema as a complication of hemolytic group A streptococcal endometritis . One hundred and twenty-two other cases of streptococcal toxic shock syndrome in the literature are reviewed and the criteria of the syndrome discussed . Streptococcal toxic shock syndrome seems to be increasing along with more frequent invasive streptococcal infections in several countries . It is therefore important to recognize and treat the infection as early as possible to minimize the risk of mortality. Diagn Microbiol Infect Dis, 1996 Mar, 24(3), 125 - 8 Rapid detection of group B streptococcal antigen from vaginal specimens using a new Optical ImmunoAssay technique; Park CH et al.; A total of 531 vaginal specimens were used to evaluate a new Optical ImmunoAssay (OIA) screening technique for the rapid detection of group B streptococcal antigen . The results of the OIA test, the ICON Strep B membrane immunoassay (Hybritech ICON), and conventional culture on sheep blood agar (direct TSA) were compared to broth enhanced culture . Results obtained from the OIA test, ICON, and direct TSA yielded 72, 39, and 68 positives, respectively, as compared to 100 positives using the Lim broth culture method as the standard . The Optical ImmunoAssay technique is as sensitive as the conventional plating method and is capable of providing results in 30 minutes. Cancer Res, 1996 Mar 1, 56(5), 1104 - 10 Induction of autologous tumor killing by heat treatment of fresh human tumor cells: involvement of gamma delta T cells and heat shock protein 70; Wei Y et al.; Autologous tumor killing (ATK) has been implicated as an important prognostic factor in cancer patients since the ability of blood lymphocytes to kill freshly isolated autologous tumor cells was strongly associated with good prognosis of the patients . The present study was designed to induce or enhance ATK sensitivity of fresh human tumor cells by heat stress . Brief exposure of fresh human tumor cells to elevated temperature increased their susceptibility to lysis by autologous blood lymphocytes in a short-term (51)Cr release assay . In addition, the heat-elevated ATK sensitivity was confirmed by clonogenic assays . An increase in ATK was observed with unstimulated lymphocytes in 42% of the cases and OK432 (streptococcal preparation)-activated lymphocytes in 80% of the cases . Stimulation of blood lymphocytes with autologous, heat-stressed tumor cells and OK432 resulted in an increase in number of gamma delta T cells, which was associated with elevated ATK activity against the stressed tumor cells . At the clonal level, three gamma delta T-cell clones (V gamma 9/V delta 2+) proliferated in response to autologous, heat stressed tumor cells and/or OK432 and exhibited elevated cytotoxicity against the tumor cells . Western blot analysis revealed an increased expression of heat shock protein (HSP) 70 in heat- treated tumor cells . Some of them expressed HSP70 on their surfaces . The elevated cytoxicity against heat-stressed tumor cells was inhibited by treatment of targets with anti-HSP70 monoclonal antibody (mAb) or of effector cells with anti-V delta2 mAb . Reactivity of gamma delta T cells to autologous, heat- stressed tumor cells was also inhibited by anti-HSP70 mAb . These results indicate that exposure to heat of tumor cells induces ATK susceptibility, especially to OK432-activated effector cells, and suggest that gamma delta T cells may be involved in ATK against stressed tumor cells through recognition of HSP70 on the target cells. Public Health Rep, 1996 Mar-Apr, 111(2), 104 - 13 Racial disparities in preterm births . The role of urogenital infections; Fiscella K; OBJECTIVES: To evaluate the impact of urogenital infections on the racial gap between black and white women in preterm birth rates . METHODS: A computer-assisted search of the medical literature was conducted through MEDLINE aided by a manual bibliographic search of published articles and relevant books . Estimates of the relative risk for preterm birth were extracted from published studies for the following infections: N . gonorrhea, syphilis, trichomoniasis, Chlamydia trachomatis, Group B streptococcal vaginal colonization, asymptomatic bacteriuria, genital mycoplasmas, and bacterial vaginosis . Estimates of the prevalence among black and white women by race for each of these infections were extracted from published studies . The attributable risk for preterm birth for selected infections was then calculated for the black and white populations and the impact on the racial gap in preterm births was estimated . RESULTS: Only bacterial vaginosis and bacteriuria appear to be established risk factors for preterm births . Significantly higher rates of bacterial vaginosis among black women may account for nearly 30% of the racial gap in preterm births . Higher rates of bacteriuria among black women may account for roughly 5% of the gap . CONCLUSION: Although these findings are limited by the reliability of published estimates of prevalence and relative risk for these infections, treatment of infections during pregnancy, particularly bacterial vaginosis, offers hope for reducing the racial gap in preterm births. Clin Immunol Immunopathol, 1996 Mar, 78(3), 283 - 90 Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-gamma in enhancement of surface expression of ICAM-1 on tumor cells in vivo; Kitsuki H et al.; The intracavitary injection of OK-432, a streptococcal preparation, has been shown to be an effective immunotherapy for patients with malignant effusion . We found that this therapy increases surface expression of intercellular adhesion molecule-1 (ICAM-1) on tumor cells, and that the degree of increased ICAM-1 was correlated with therapeutic effects . In the present study, we investigated the ability of OK-432-induced inflammatory cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), to enhance ICAM-1 expression . We treated 17 patients who had a malignant effusion with OK-432 . At 24 hr after OK-432 injection, ICAM-1 levels on tumor cells were increased significantly in responders except in one case (n=9), whereas no change was evident in nonresponders except in two cases (n=8) . Induced maximum levels of IFN-gamma in responders were significantly higher than those in nonresponders . In contrast, there was no significant difference in the induced TNF-alpha or IL-1 beta levels between the two groups . Two types of cultured tumor cells derived from responder patients were successfully established from the 17 different tumor cells in effusion . We performed an in vitro study using these cultured tumor cells . Treatment of the two cultured tumor cells with recombinant IFN-gamma, but not recombinant TNF-alpha or IL-1 beta, significantly increased their ICAM-1 expression to a clinically detectable level . Direct treatment of the tumor cells with cell-free effusion samples obtained from the same patients 24 hr after the therapy successfully increased ICAM-1 expression and this action was blocked completely only by a pretreatment with anti-IFN-gamma mAb . Our results suggests that in this therapy IFN-gamma plays a crucial role in enhancing ICAM-1 expression by tumor cells and that induced IFN-gamma levels may be a useful marker for evaluation of the therapeutic effect. Acta Paediatr Jpn, 1996 Feb, 38(1), 8 - 11 Evaluation of the therapy for streptococcal pharyngitis using Abbott Test Pack strep A; Kayaba H et al.; A total of 953 children (511 boys and 442 girls) with streptococcal pharyngitis diagnosed with Abbott Test Pack Strep A (ATPSA) or throat cultures were analyzed . ATPSA specimens were repeatedly obtained until ATPSA turned negative during or after the treatment . The percentage of positive ATPSA specimens reached the lowest value (9.2%) on the fourth day of the course of the treatment, which indicates the acquisition from an infected individual is probably uncommon after the initial treatment . Bacteriological treatment failure (positive ATPSA after 14 days of treatment) occurred in 4.1% of the children . Out of 953 subjects studied, 216 (22.7%) had recurrent infections . More than 30% of the recurrent infections occurred within 2 months after initial infection . ATPSA is useful for establishing a rapid diagnosis and confirming the bacteriological success of the treatment. Mol Microbiol, 1996 Feb, 19(3), 429 - 41 M-related protein (Mrp) contributes to group A streptococcal resistance to phagocytosis by human granulocytes; Podbielski A et al.; The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis . Direct evidence of this was only provided for GAS strains which expressed a single M protein . The majority of GAS express additional, structurally similar M-related proteins, Mrp and Enn, which have been described as IgG- and IgA-binding proteins . To determine the involvement of Mrp and M protein in phagocytosis resistance, the mrp and emm genes from serotypes M2, M4, and M49 as well as from M-untypeable strain 64/14 were insertionally inactivated . The mrp and emm mutants were subjected to direct bactericidal assays . As judged by numbers of surviving colony-forming units, all mutant strains with the exception of the mrp4 mutant exhibited reduced multiplication factors as compared to the isogenic wild-type strains . Subsequent analysis of phagocytosis by flow cytometry, measuring association of BCECF/AM-labelled bacteria and granulocytes, paralleled the results from direct bactericidal assays regardless of whether isolated granulocytes or whole blood were utilized . Resistant wild-type GAS strains bound to less than 24% of granulocytes, whereas phagocytosis-sensitive controls attached to more than 90% of the white blood cells . 40 to 60% of the granulocytes associated with the mrp and emm mutants within 1 h of co-incubation . Kinetic data suggested that attachment to granulocytes proceeds faster for emm mutants than for corresponding mrp mutants . By adding a dihydro-rhodamine123 stain and measuring fluorescence induced by oxidative burst, the experimental data suggested that bacteria bound to granulocytes were also engulfed and integrated into phagolysosomes . Thus, these data indicated that, if present, both mrp and emm gene products contribute to phagocytosis resistance by decreasing bacterial binding to granulocytes. Pediatr Res, 1996 Feb, 39(2), 336 - 42 Persistent elevation of immunoglobulin G titer against the C region of recombinant group A streptococcal M protein in patients with rheumatic fever; Mori K et al.; To analyze the immune response to the C region of group A streptococcal M protein in patients with rheumatic fever (RF), we cloned the structural gene for the C region of type 12 M protein and produced recombinant C region of M protein . IgG titers against the C region of M protein were measured by ELISA from sera of patients with RF (n = 10), uncomplicated streptococcal pharyngitis (n = 26), and age-matched controls (n = 49) . IgG titers against the C region were significantly higher in patients with RF than in controls or patients with uncomplicated streptococcal pharyngitis (43 versus 1.5 or 1.8 micrograms/mL, p < 0.01) . Studies using overlapping synthetic peptides of the C region demonstrated that increased IgG reactivity was observed against the amino-terminal halves of the C repeat blocks (C1, C2) in RF, indicating that these domains are the main immunodominant epitopes in the C region. Pediatr Infect Dis J, 1996 Feb, 15(2), 151 - 6 Risk factors for invasive group A streptococcal infections in children with varicella: a case-control study; Peterson CL et al.; OBJECTIVE: To identify characteristic clinical manifestations and potential risk factors for invasive group A streptococcal (GAS) disease in children with varicella . DESIGN AND PARTICIPANTS: A case-control study was conducted in Los Angeles and Orange Counties, CA . Cases were children with varicella who developed invasive GAS disease between January 1 and May 3, 1994 (n = 25) . Controls were acquaintance, neighborhood or schoolmate children with uncomplicated varicella during the study period (n = 62) . Cases were compared with controls with regard to underlying illness, child care practices, parental home health practices, health care-seeking behaviors, sociodemographic characteristics and clinical characteristics . RESULTS: Controlling for age we found that cases were more likely than controls: (1) to be cared for in the home vs . out-of-home child care (odds ratio (OR), 4.4 (95% confidence interval (95% CI), 1.1 to 17)); (2) to report having asthma (OR, 6.2 (95% CI, 1.2 to 41.0)) and to be taking albuterol (OR, 11.6 ((95% CI, 1.0 to 581)); (3) to be secondary varicella cases within a household (OR, 7.3 (95% CI, 2.2 to 25)); (4) to report fever after Day 2 of varicella; and (5) to have contacted their health care provider later than controls (Day 3.8 rather than Day 1.7, P < 0.001) . CONCLUSIONS: To our knowledge this is the first case-control study exploring potential risk factors for invasive GAS disease in children with varicella . Both previously healthy children with varicella and those with underlying medical problems, including asthma, may be at increased risk for GAS complications . Interventions should be targeted to parents and health care providers to increase awareness of early signs and symptoms of invasive GAS disease in children with varicella . Additional studies are needed to confirm the associations suggested by this study between GAS complications of varicella and asthma, in-home child care, secondary vs . primary varicella household cases and delayed contact with medical care providers. Pediatr Infect Dis J, 1996 Feb, 15(2), 146 - 50 Invasive group A streptococcal infections in children with varicella in Southern California; Vugia DJ et al.; OBJECTIVE: To describe demographic and clinical features of invasive group A streptococcal (GAS) infections in children with varicella in Southern California in early 1994 . METHODS: From hospitals of Los Angeles and Orange Counties, children with invasive GAS infections after varicella between January 1 and April 8, 1994, were identified by hospital infection control nurses . Medical records of patients were reviewed, and any available GAS isolate was further tested . RESULTS: Twenty-four cases were identified; 54% were male, 50% were Hispanic and the median age was 3 years (range, 0.5 to 8) . Four cases died before hospitalization . The other 20 were hospitalized for a median of 10 days (range, 4 to 50): 14 presented with cellulitis (1 with concomitant epiglottitis), 2 with myositis/necrotizing fasciitis, 2 with pneumonia and 2 with bacteremia without apparent source . Five had evidence of multiorgan involvement including two patients fulfilling criteria of streptococcal toxic shock-like syndrome . Of 19 patients with blood cultures, 10 (53%) had GAS bacteremia . Onset of GAS infection was suggested, as a median, on Day 4 of varicella, with fever, vomiting and localized swelling being commonly reported . The mean maximum temperature on the day of admission was 39.4 degrees C (102.9 degrees F) . Four GAS isolates were M1T1 and one was M3T3 . Five isolates produced streptococcal pyrogenic exotoxins A and B . CONCLUSIONS: Invasive GAS disease, including streptococcal toxic shock-like syndrome, is a serious complication of varicella . Physicians should be alert for the complication of GAS when fever and localized swelling or signs of cellulitis develop 3 days or more after the onset of varicella . Widespread use of varicella vaccine may decrease invasive GAS infections in this setting. Int J Immunopharmacol, 1996 Feb, 18(2), 141 - 53 Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma; Mukai S et al.; We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma . C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad . Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days . These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v . injection of 2-4 x 10(5) viable BL6 cells . The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer . Transfer of IVS cells from mice immunized by s.c . injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003) . These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003) . Functional IVS cells required in vitro stimulation with tumor cells . However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells . These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells . The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma. Aust N Z J Med, 1996 Feb, 26(1), 49 - 53 Anti-streptokinase antibodies and streptokinase resistance in an Aboriginal population in northern Australia; Urdahl KB et al.; BACKGROUND: Thrombolytic treatment with streptokinase in acute myocardial infarction has proven to be safe and effective in Caucasian populations with relatively low levels of anti-streptokinase IgG and streptokinase resistance . Higher levels of antibodies, as seen in previous recipients of streptokinase therapy, cause more adverse reactions and may result in lower efficacy . AIMS: To examine the levels of anti-streptokinase IgG and streptokinase resistance in a population subjected to endemic streptococcal infections . METHODS AND RESULTS: Thirty Aboriginal adults from a remote community in Northern Australia with endemic streptococcal infections and 15 non-Aboriginal adults from an urban community without endemic infections participated in this study . Aboriginal adults exhibited levels of anti-streptokinase IgG and streptokinase resistance that, respectively, were almost 20 and 15 times greater than the values of non-Aboriginal adults . At least 23% of Aboriginal adults had sufficiently high levels of streptokinase resistance to neutralise a standard 1.5 million unit dose of streptokinase . CONCLUSIONS: Aboriginal adults from a remote community had dramatically elevated levels of anti-streptokinase IgG and in vitro streptokinase resistance . Prospective studies are needed to assess the clinical relevance of streptokinase resistance in populations from areas with endemic streptococcal infection. Rev Rhum Engl Ed, 1996 Feb, 63(2), 119 - 23 Bacterial endocarditis revealed by infectious discitis; Pascaretti C et al.; A study of 30 patients admitted for infectious discitis identified four cases with concomitant bacterial endocarditis . All four patients were male and had concomitant streptococcal septicemia . Two patients had known aortic valve disease . The vertebral infection was located to the thoracic or lumbar spine . Ultrasonography disclosed aortic lesions in all four patients and mitral lesions in two . Management consisted of intravenous antimicrobial therapy for four weeks followed by a three-month course of oral antimicrobial therapy . The outcome of the discitis was favorable within the usual period of time . However, the endocardial lesions continued to progress, and three patients rapidly required valve replacement . Analysis of available data in the 30 patients with discitis showed that half the patients with streptococcal discitis also had bacterial endocarditis and that the latter condition developed in all the patients with streptococcal discitis and a history of valve disease . A number of risk factors were identified . An echocardiogram should be done routinely in patients with infectious discitis and risk factors for bacterial endocarditis. Eur J Biochem, 1996 Feb 1, 235(3), 543 - 8 Backbone dynamics of a domain of protein L which binds to immunoglobulin light chains; Wikstrom M et al.; Protein L is a multidomain protein expressed at the surface of some strains of the anaerobic bacterial species Peptostreptococcus magnus . The molecule interacts with the variable domain of immunoglobulin (Ig) light chains through five repeated homologous domains denoted B1 to B5 . The fold of the Ig-light-chain-binding B1 domain of protein L (PLB1) has been shown to comprise an alpha-helix packed against a four-stranded beta-sheet and therefore resembles the structure of the IgG-binding domains of streptococcal protein G . In the present study, amide-proton exchange and 15N-relaxation NMR measurements were performed on the B1 domain to investigate its backbone mobility . It was shown that the folded portion of PLB1 is rigid with no regions of significantly higher flexibility than average . The N-terminus, however, is highly flexible consistent with earlier studies on the solution structure of PLB1 . Comparison of the amide-proton-exchange data with similar measurements performed on the IgG-binding domains of protein G indicates that the two proteins have different exchange behaviors in their second beta-strands . Both protein G and L employ this region of their structures for binding to immunoglobulins since the interaction of protein G and protein L with IgG Fab and the Ig light chain, respectively, involves residues from the second beta-strand. J Am Acad Dermatol, 1996 Feb, 34(2 Pt 1), 229 - 34 Eosinophilic panniculitis: diagnostic considerations and evaluation; Adame J et al.; BACKGROUND: Eosinophilic panniculitis is characterized by a prominent infiltration of subcutaneous fat with eosinophils . It has been identified in patients who have a variety of associated clinical conditions . OBJECTIVE: Our purpose was to describe clinical conditions associated with eosinophilic panniculitis . METHODS: We describe five patients with eosinophilic panniculitis . These patients had a variety of clinical conditions including arthropod bites, gnathostomiasis, and polyarteritis nodosa . We review the literature on patients with eosinophilic panniculitis . RESULTS: Eosinophilic panniculitis most often presents as a nodule . Gnathostomiasis, leukocytoclastic vasculitis, and erythema nodosum appear to be the most common conditions associated with eosinophilic panniculitis . Other disorders include atopic and contact dermatitis, eosinophilic cellulitis, injection granuloma, arthropod bites, streptococcal and other bacterial infections, toxocariasis, B- and T-cell lymphoma, and refractory anemia with excess blasts . CONCLUSION: Once a diagnosis of eosinophilic panniculitis has been established, appropriate evaluation for an associated clinical condition should be performed. Postgrad Med, 1996 Feb, 99(2), 211 - 4, 219-22 Recurrent streptococcal pharyngitis . Using practical treatment options to interrupt the cycle; Ruoff GE; Most family physicians have seen cases like this: A child is brought in with pharyngitis, which responds to antibiotic therapy . Soon the mother comes in with fever and a sore throat . She also recovers with therapy, but soon she's back with the child, who has pharyngitis again . Dr Ruoff explains why streptococcal infection recurs and how to assess probability so treatment can be started without waiting for test results . He also discusses alternatives to standard penicillin therapy, some of which may avoid the problems of noncompliance. Cancer Immunol Immunother, 1996 Feb, 42(2), 127 - 31 Combination immunotherapy with OK-432, recombinant granulocyte-colony-stimulating factor and recombinant interleukin-2 for human hepatocellular carcinoma; Himoto T et al.; The antitumor effects of immunotherapy using streptococcal preparations (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) and recombinant interleukin-2 (rIL-2) were examined for human hepatocellular carcinoma (HCC) . Following subcutaneous injection of OK-432 (2 KE) and rG-CSF (50-60 microg), low-dose intratumoral administration of OK-432 (3-12 KE) was performed . Thereafter, 2 x 10(5) JRU of rIL-2 was subcutaneously injected . This therapeutic regimen was repeated twice . Serum alpha-fetoprotein levels were markedly decreased in three of seven patients with HCC by this treatment . Post-therapeutic histological examination revealed that trabecular cords or pseudoglandular arrangements of tumor cells were completely disordered in all cases and that extensive infiltration of lymphocytes into the tumor stroma was present in five cases . The number of CD4- and CD57-positive cells among tumor-infiltrating lymphocytes after immunotherapy was significantly higher than that in patients without immunotherapy (P <0.01) . These findings suggest that even a small intratumoral injection of OK-432 can induce extensive infiltration of helper/inducer and natural killer cells into the tumor stroma when combined with subcutaneous injection of OK-432, rG-CSF and rIL-2 and that these cells might play important roles in tumor cytotoxicity. J Mol Biol, 1996 Jan 19, 255(2), 275 - 88 An unusually long-lived antisense RNA in plasmid copy number control: in vivo RNAs encoded by the streptococcal plasmid pIP501; Brantl S et al.; The main regulator of pIP501 replication is an antisense RNA (RNAIII) that induces transcriptional attenuation of the essential RNAII . Previous studies identified the termination point in vivo and demonstrated attenuation in vitro . This in vivo analysis confirms the appearance of attenuated RNAII dependent on RNAIII . Half-lives and intracellular levels of RNAII and RNAIII were determined: in a Bacillus subtilis cell harboring a wild-type pIP501 plasmid, approximately 50 molecules RNAII and 1000 to 2000 molecules of RNAIII were measured, respectively . The half-life of RNAII was in the range of that of other target RNAs, whereas that of RNAIII (approximately 30 minutes) was unusually long, representing a so far unprecedented case of a metabolically stable antisense RNA regulating plasmid copy number . Long antisense RNA half-life is predicted to yield sluggish control and instability of maintenance . We propose a model for how plasmid pIP501 may avoid this problem by using both the repressor CopR and the antisense RNAIII for control . Four stem-loop mutants of RNAII/RNAIII with elevated copy numbers were characterized for in vitro antisense/target RNA binding, RNAIII half-life, incompatibility, and attenuation in vivo . Two classes were found: interaction mutants and half-life mutants . The former suggest a key function for loop LIII of RNAIII as recognition loop in the primary steps of RNAII/RNAIII interaction. FEBS Lett, 1996 Jan 8, 378(2), 190 - 4 The serum albumin-binding domain of streptococcal protein G is a three-helical bundle: a heteronuclear NMR study; Kraulis PJ et al.; Streptococcal protein G (SPG) is a cell surface receptor protein with a multiple domain structure containing tandem repeats of serum albumin-binding domains (ABD) and immunoglobulin-binding domains (IgBD) . In this paper, we have analysed the fold of ABD . Far-UV circular dichroism analysis of ABD indicates high helical content (56%) . Based on an analysis of nuclear magnetic resonance 13C secondary chemical shifts, sequential and short-range NOEs, and a few key nuclear Overhauser effects, we conclude that the ABD is a three-helix bundle . The structure of the ABD is, thus, quite different from the IgBD of protein G {Gronenborn, A.M . et al . (1991) Science 253, 657-661} . This strongly suggests that the ABD and the IgBD of SPG have evolved independently from each other . However, the fold of ABD is similar to that of the IgBD of staphylococcal protein A, possibly indicating a common evolutionary ancestor, despite the lack of sequence homology. Acta Otolaryngol Suppl, 1996, 523, 75 - 7 Cytokine expression and production by tonsillar lymphocytes; Harabuchi Y et al.; Expression of various cytokines in the tonsillar compartments, and in vitro cytokine production and cytokine mRNA expression by tonsillar lymphocytes (TL), were investigated . In immunohistological analysis, a wide variety of cytokines such as interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-10 was expressed intensively in the lymphoepithelial symbiosis (LES) . A certain number of cells producing IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha was distributed not only in the LES but also in the extrafollicular area . A significant amount of IL-6, IFN-gamma, and TNF-alpha was detected by enzyme-linked immunosorbent assay in the culture supernatants of TL cultured with streptococcal antigen, even without any mitogens . Furthermore, mRNA of IL-6, IFN-gamma, and TNF-alpha was determined by reverse transcription polymerase chain reaction on the TL freshly isolated and with streptococcal stimulated antigen, whereas, production of IL-1 alpha, IL-4, and IL-5, and expression of their mRNA were not found on TL with or without streptococcal stimulation . These data indicate that tonsils are highly active immunological organs containing a wide variety of cytokine-producing cells, and suggest that IFN-gamma, TNF-alpha, and IL-6 may play an important role on the immune response to bacteria in the tonsil. Biotherapy, 1996, 9(4), 189 - 97 Improvement of glucose tolerance with immunomodulators on type 2 diabetic animals; Zhu XP et al.; Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal models . We extend this therapy to non-insulin-dependent diabetes mellitus (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM, was recovered by allogenic bone-marrow transplantation that also prevented IDDM in animal models . An i.p . or i.v . injection of streptococcal preparation (OK-432) lowered fasting blood glucose (FBG) levels and markedly improved glucose tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose loading routes (oral, i.v . or i.p.), while an i.v . injection of BCG improved FBG and GTT for more than 4 wks without body weight loss . The improvement of FBG and GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar fatty rats . Among various cytokines possibly induced by OK-432 and BCG, IL-1 alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay mice, whereas IL-2 and IFN gamma did not . There were no differences between the OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of insulin-induced decrease in blood glucose levels, and muscle glycogen synthase activities . As to insulin secretion, there is a tendency that the OK-432-treatment less that 1 week did not affect insulin levels during GTT, whereas the treatment more than 2 weeks increased the insulin levels . Thus, cytokine-inducers improved FBG and glucose tolerance of NIDDM animals probably via cytokines . The results imply a role of the cytokines in glucose tolerance of NIDDM, although precise immune and metabolic mechanisms remain to be elucidated. Reumatizam, 1996, 43(1), 16 - 24 {Polyarteritis nodosa--cutaneous or systemic form? Possible role of bacterial superantigens in the onset of systemic disease}; Malcic I et al.; A boy with diagnostically unclear vasculitis was described, in which development of the disease points out the presence of cutaneous form of poliarteritis nodosa . Nevertheless, there are also signs for systemic form of the disease . His symptoms are marked cutaneous eruptions of the livedo reticularis type, recidives of erythema nodosum on the limbs and trunk, even on the cheeks, sometimes accompanied with fever, arthralgias, myalgias and cutaneous ulcera on the places of mechanical pressure (elbows), but also with monotopic ventricular premature beats and sporadic microhaematuria . Clinical development of the disease and differential diagnosis exclude other autoimmune disorders with great probability . The positive finding of cANCA has pointed out the diagnosis of vasculitis . Microscopical analysis of the skin didn't reveal any pathological changes . In the boy's disease is interposed a streptococcal infection, and maybe, tuberculosis . The paper deals with wide spectrum of diseases in differential diagnosis, and also with a possible role of bacterial superantigens in the genesis of autoimmunity. Scand J Infect Dis, 1996, 28(5), 497 - 501 6-day amoxicillin versus 10-day penicillin V for group A beta-haemolytic streptococcal acute tonsillitis in adults: a French multicentre, open-label, randomized study . The French Study Group Clamorange; Peyramond D et al.; We compared the efficacy and safety of amoxicillin 1 g b.i.d . for 6 days and penicillin V 1 MU t.i.d . for 10 days in the treatment of group A beta-haemolytic streptococcal (GABHS) tonsillitis in adults . 342 patients with acute tonsillitis and a positive test for streptococcal antigen were included in a multicentre, randomized, open-label study; 338 patients were evaluable in an intention-to-treat analysis, and 234 with a positive throat swab culture in a per-protocol analysis . In the per-protocol analysis, the GABHS eradication rate at the end of treatment was comparable in the two groups: 92% (115/125) on amoxicillin and 92.7% (101/109) on penicillin (p = 0.95), as were the clinical success rates of 96% and 95.4%, respectively (p = 0.92) . At the follow-up visit (day 28-32), 90.8% of patients treated with amoxicillin and 92.6% of those treated with penicillin V were free of GABHS (p = 0.85) . Sore throat disappeared significantly faster on day 2 (p = 0.039) in the amoxicillin group . The intention-to-treat analysis gave similar clinical results . Tolerability was good in both groups . The efficacy and safety of amoxicillin 1 g b.i.d . for 6 days were not statistically different from those of penicillin V 1 MU t.i.d . for 10 days in the treatment of streptococcal tonsillitis in adults. J Perinat Med, 1996, 24(5), 531 - 8 Neonatal early onset group B streptococcal infection . A nine-year retrospective study in a tertiary care hospital; Adriaanse AH et al.; Retrospectively, morbidity and mortality of neonatal early onset group B streptococcal (GBS) infection were established . Risk factors and prognostic factors were determined . Between 1985 and 1993, 78 patients with early onset GBS disease were identified . The overall mortality rate was 23% . In 60 of 73 cases (82%) at least one of the investigated risk factors was present . Low birth weight was not an independent risk factor . Outcome of 44 of 60 survivors (73%) at the age of at least one year was obtained . Almost 30% of them had sequelae . The most important were spastic disorders and delayed psychomotor development . In 42% of patients with symptoms of GBS-infection within six hours after birth sequelae occurred . There were no sequelae among patients with symptoms after 6 hours . All 9 severely brain damaged infants showed symptoms shortly after birth . Mortality and adverse outcome rate were higher in infants with low gestational age or low 5 minute Apgar scores . Early treatment resulted in less mortality, but not in less sequelae . GBS-sepsis still causes significant mortality and leaves a substantial number of survivors damaged . Alertness to GBS-infection, even in the absence of risk factors, remains crucial for early treatment and good outcome. Acta Otolaryngol Suppl, 1996, 525, 135 - 41 Final report of a randomized controlled study with streptococcal preparation OK-432 as a supplementary immunopotentiator for laryngeal cancer; Kimura T et al.; We conducted a randomized controlled study of streptococcal preparation OK-432 on 120 newly identified cases of laryngeal squamous cell carcinoma who were registered at 10 participating institutions between November 1984 and October 1989 . The patients were divided into two groups: those in early stages (stage I or II) and those in advanced stages (stage III or IV); these groups were further subdivided into an immunotherapy group (receiving OK-432) and a control group (who did not receive OK-432) . The usefulness of OK-432 was studied using the sealed envelope method . The basic therapy for all cases was radiotherapy and, when required, surgery . As adjuvant therapy, 5Fu or derivatives were administered to all cases from the beginning of the treatment period to one year after the basic therapy, with the exception of cases in whom side effects were serious enough to contraindicate use of the drug . The target administration period was 5 years . Of the initial 120 cases, 11 cases were disqualified (3 cases of double cancer and 8 of incomplete primary therapy) and the remaining 109 were used for evaluation . The 5-year survival rate and the 5-year recurrence-free rate were 76% and 84%, respectively, in the immunized groups (both the early and advanced groups), whereas the same rates for the control groups were 78% and 75% . There was a tendency for the immunized groups to enjoy a slightly longer recurrence-free period . Over a 24-month observation period the immunized group always had higher levels of peripheral leukocytes and peripheral lymphocytes; this difference was significant for the first 21 months . Inhibition of bone marrow function is sometimes observed with radiotherapy . It is hoped that, if this inhibition can be mitigated, it will be possible to assist the compromised immune system and maintain a certain level of immune performance which will prevent recurrence and improve survival rate . In the present study we observed a tendency of the lower recurrence rate in the immunized group, and we hypothesize that OK-432 is effective in extending the recurrence-free period. Acta Otolaryngol Suppl, 1996, 525, 125 - 8 Histological effect of intranodal injection of the streptococcal preparation OK-432 for cervical lymph node metastases of malignant head and neck tumors; Suzuki K et al.; To investigate the histological effect of intranodal injection of the streptococcal preparation OK-432, we performed intranodal injection in 4 patients with cervical lymph node (CLN) metastases of malignant head and neck tumors (squamous cell carcinoma (SCC) of the oropharynx, SCC of the parotid gland, malignant lymphoma, and rhabdomyosarcoma of the nasal cavity) . An initial dose of 5 klinische Einheit (KE) and a maintenance dose of 10 KE of OK-432 were administered into each metastatic or residually involved CLN twice a week . The total dose of OK-432 ranged from 105 KE to 395 KE and the number of administrations ranged from 11 to 40 . Post treatment histological examination of excised tissue specimens revealed no tumor cells; there was only fibrosis and inflammatory cell infiltration . These findings suggest that intranodal injection of OK-432 can be utilized for treatment of relatively small CLN metastases of malignant head and neck tumors. Scand J Infect Dis Suppl, 1996, 100, 72 - 82 Clinical and immunological considerations in Epstein-Barr virus-associated diseases; Andersson J; Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment . Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself . However, despite an extensive immune response, 90% of tested IM patients (n = 36) had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this time . Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days after onset of disease (human leukocyte antigen-restricted cytotoxicity against EBV-infected B-cells) . Thus, development of a specific cytotoxic response was a gradual and slow process . Assessment of cytokine pattern, at the single cell level, was performed by immunocytochemical technique and by enzyme-linked immunosorbent assay . This revealed an increased production of interleukin (IL)-2, interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM patients . Those with disseminated disease were characterized by lack of IFN-gamma production . This loss was selective since in vitro stimulation with superantigen, such as streptococcal pyrogenic exotoxin A, induced a normal response . These patients lacked signs of EBV-specific T-cell cytotoxicity in vitro . Treatment with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and oral aciclovir, 800 mg 5 times daily, has shown promising results in some patients . Cytokine production in tonsil tissue in 4 patients with fulminant IM and respiratory tract obstruction showed a concomitant expression of IL-2, IFN-gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4 IL-1alpha, IL-beta and TNF alpha . The number of IL-2, IFN-gamma, IL-6 and TNF beta producing cells was significantly higher compared to tonsil tissue obtained from children with tonsillar hypertrophy . Thus, IM is associated with extensive local cytokine production . It is suggested that this extensive cytokine production is closely involved in the pathology of IM and that patients with atypical IM have a dysregulation in the cytokine network . However, the mechanism by which EBV-infected B-lymphocytes triggers this cytokine cascade is still unknown . These findings show the need for evaluation of patients with immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the introduction of new immunoregulatory treatment strategies. Infection, 1996 Jan-Feb, 24(1), 43 - 6 Streptococcal toxic shock-like syndrome . Report of two cases from Italy; Girelli CM et al.; Two cases of streptococcal toxic shock-like syndrome that occurred at our hospital are described . They represent the second and third cases reported from Italy . Both patients were women, had a portal of entry from cutaneous infection of a limb and suddenly developed high degree fever, severe hypotension, necrotizing fasciitis, acute renal failure, hepatic damage, thrombocytopenia and bleeding from a stress-related duodenal ulcer . One patient was leukopenic . The first patient needed resuscitation in the intensive care unit and emergency surgical debridement of the affected limb, whereas the second improved with medical therapy, but needed duodenal surgery for uncontrolled bleeding . Both patients slowly recovered and survived . Finally, a short update on the pathogenesis of the syndrome is also presented. J Rheumatol, 1996 Jan, 23(1), 44 - 51 Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis; Cuchacovich M et al.; OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA . This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein . To investigate a potential correlation between the high levels of anti-LTSRPA antibodies in sera of patients with rheumatoid arthritis (RA) and the perpetuation of the immune response characteristic of this disease, we analyzed their capacity to activate complement and the process of binding to the serum lectin mannan binding protein (MBP) . METHODS: We used a radioimmunoassay to evaluate immune complexes between anti-LTSRPA IgG and FN, plasmin degraded FN, or the LTSRPA peptide for their capacity to activate complement C5 to C5a . Purified human serum lectin MBP was used to quantify the degree of exposed mannose or N-acetylglucosamine residues in the Fc region of anti-LTSRPA IgG of patients with RA and healthy controls . RESULTS: Anti-LTSRPA IgG from patients with RA have a greater capacity to activate complement C5 to C5a when bound to either the LTSRPA peptide or plasmin degraded FN in vitro . We found a very strong correlation between the complement activating capacity of the RA immune complexes and their binding to MBP . CONCLUSION: The enhanced capacity of RA anti-LTSRPA IgG immune complexes to activate complement C5 to C5a is directly correlated with their binding capacity to MBP . As MBP binding depends on exposed mannose or N-acetylglucosamine residues in the Fc region of the IgG molecule, these studies suggest that defective glycosylation of circulating anti-SK IgG may play a role in the etiology of RA. Acta Paediatr, 1996 Jan, 85(1), 104 - 5 Systemic group B streptococcal disease in neonates and young infants in Norway 1985-94; Aavitsland P et al.; In the period 1985-94, 237 out of 575,248 (0.41 per 1000) live born infants in Norway were reported to suffer culture-confirmed systemic group B streptococcal disease before their 90th day of life . The annual incidence increased from 0.20 per 1000 live births in 1985 to 0.64 in 1994, due solely to an increase in cases with an onset before the seventh day of life . Future studies should address the possible causes of this increase. Dermatology, 1996, 192(2), 125 - 8 Effect of prophylactic benzathine penicillin on mucocutaneous symptoms of Behçet's disease; Calguneri M et al.; BACKGROUND . Recent studies point out a probable role of streptococcal antigens in the pathogenesis of Behcet's disease (BD) . This has led to the proposal of benzathine penicillin as a therapeutic modality in BD . OBJECTIVE . A prospective study was conducted to compare the efficacy of colchicine and colchicine + benzathine penicillin treatments on mucocutaneous manifestations of BD . METHODS . 60 patients (group I) were given colchicine alone and 94 (group II) were given colchicine + benzathine penicillin . Frequency, number, duration and severity of oral aphthous ulcers, genital ulcers and erythema nodosum were determined before and after treatment . RESULTS . In group I, all parameters of oral ulcers and the frequency and healing time of genital ulcers and erythema nodosum decreased significantly . In group II, all parameters of oral aphthous ulcers, genital ulcers and erythema nodosum were significantly improved . When treatment results in the two groups were compared, the decrements in the frequency and duration of oral ulcers and erythema nodosum and the frequency of genital ulcers were significantly greater in group II than in group I (p < 0.05) . CONCLUSION . We conclude that prophylactic benzathine penicillin combined with colchicine is more effective in controlling mucocutaneous manifestations of BD than colchicine alone. Pediatr Res, 1996 Jan, 39(1), 55 - 63 Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets; Rudinsky BF et al.; We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment . Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2 (PaCO2) approximately 40 torr) . CBF was assessed by internal carotid artery blood flow (ICBF) . Group 1 (n = 5) received a continuous infusion of STREP for 4 h (2.0-8.0 x 10(7) org/kg-min) . Group 2 (n = 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion . Group 3 (n = 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter . Cerebral vascular reactivity to acute hypercarbia (PaCO2 approximately 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation . We found that 4 h of STREP infusion caused CO to fall significantly (634 +/- 121 to 324 +/- 172 mL/min, group 1; 600 +/- 68 to 291 +/- 80 mL/min, group 2) and BP to fall significantly (104 +/- 20 to 57 +/- 4 mm Hg, group 1; 91 +/- 11 to 53 +/- 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 +/- 181 to 375 +/- 159 mL/min) and BP (104 +/- 14 to 60 +/- 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2 . At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 +/- 10.8 to 21.0 +/- 7.3 mL/min) and group 2 (22.9 +/- 9.9 to 13.1 +/- 4.3 mL/min), but not in nonseptic group 3 (23.1 +/- 7.4 to 19.6 +/- 6.3 mL/min) . At baseline, hypercarbia induced an increase in ICBF (% delta ICBF = 68.7 +/- 13.0% in group 1, 62.2 +/- 15.6% in group 2, and 87.7 +/- 34.0% in group 3) . After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 +/- 23.2% (group 1) . Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as % delta ICBF fell during hypercarbia by -10.9 +/- 17.7% (group 2) . In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8 +/- 23.2%, not significantly different from baseline, but significantly different from the decrease in % delta ICBF in groups 1 and 2 . We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets . This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids. Clin Infect Dis, 1996 Jan, 22(1), 130 - 2 Streptococcal meningitis as a complication of diagnostic myelography: medicolegal aspects; Gelfand MS et al.; Bacterial meningitis is a rare complication of myelography . Most reported cases of bacterial meningitis are caused by a wide variety of streptococcal species, but the source of these organisms is uncertain . We recently participated in the defense of two legal cases arising from this complication . We discuss the medicolegal aspects of streptococcal meningitis that is a complication of myelography. Scand J Infect Dis, 1996, 28(2), 139 - 42 Incidence and severity of group A streptococcal bacteremia in a medical center in Israel, 1981-1994; Livni G et al.; To determine recent trends in the incidence and severity, group A streptococcal (GAS) bacteremia was studied over the last 14 years (1981-1994) . There were 116 events of GAS bacteremia, representing 1.7% of all bacteremic episodes, without an increase in recent years . A total of 108 patients were available for study . Underlying conditions were found in 95 patients (88%), including mainly malignant diseases, chronic obstructive pulmonary disease, congestive heart failure and diabetes mellitus . A source of the bacteremia was noted in 71 patients (66%), with skin and soft tissue infection being the major portal of entry . All isolates were susceptible to penicillin . Overall mortality was 21% . Mortality had not increased in recent years, but depended significantly on several clinical factors: increased age; admission temperature; source of bacteremia (highest for GAS bacteremia without an identified source); and underlying conditions (highest for diabetes mellitus and chronic pulmonary disease, absent for patients with no underlying disease) . This study shows that neither the incidence nor the severity of GAS bacteremia has increased in recent years . Severity is significantly affected by the source of bacteremia and the presence of underlying conditions. Protein Sci, 1996 Jan, 5(1), 174 - 7 Rapid screening for structural integrity of expressed proteins by heteronuclear NMR spectroscopy; Gronenborn AM et al.; A simple and rapid method based on 15N labeling and 1H-15N heteronuclear single quantum coherence spectroscopy is presented to directly assess the structural integrity of overexpressed proteins in crude Escherichia coli extracts without the need for any purification . The method is demonstrated using two different expression systems and two different proteins, the B1 immunoglobulin-binding domain of streptococcal protein G (56 residues) and human interleukin-1 beta (153 residues) . It is shown that high quality 1H-15N correlation spectra, recorded in as little as 15 min and displaying only cross-peaks arising from the overexpressed protein of interest, can be obtained from crude E . coli extracts. Scand J Rheumatol, 1996, 25(3), 127 - 31; discussion 132-3 Towards understanding the pathogenesis of rheumatic fever; Carapetis JR et al.; Acute rheumatic fever results from an immunological response to group A streptococcal infection, but the exact nature of this response, and of the underlying host and organism characteristics, continues to evade researchers . Earlier models of rheumatic fever pathogenesis emphasised the importance of humoral immunity, but more recent work suggests that cellular immunity may play a primary role . Greater understanding of these disease mechanisms is allowing researchers to move towards the development of a vaccine for rheumatic fever. J Orthop Trauma, 1996, 10(3), 149 - 55 Fatal group A streptococcal infection with toxic shock syndrome: complicating minor orthopedic trauma; Mills WJ et al.; Since 1987, reports have appeared of a streptococcal toxic shock syndrome in various clinical settings . None have appeared in the orthopaedic literature . Between 1989 and 1991 at our institution three patients with relatively minor orthopaedic injuries or procedures died of group A streptococcal infections complicated by toxic shock syndrome . The manifestations of this syndrome included rapid progression of systemic sepsis, necrotizing soft-tissue infections, acute renal failure, adult respiratory distress syndrome, and coagulopathy . All three patients died despite aggressive resuscitative measures and surgical debridement . Optimal treatment of this life-threatening process requires early recognition, aggressive surgical debridement, appropriate antibiotic management, and intensive care unit support. Int J Immunopharmacol, 1995 Dec, 17(12), 963 - 71 Adoptive immunotherapy of poorly immunogenic tumors with in vitro sensitized cells generated by intratumoral administration of biological response modifiers; Mukai S et al.; We investigated the efficacy of intratumoral administration of biological response modifiers (BRM) in induction of in vitro sensitized (IVS) cells for adoptive immunotherapy of the poorly immunogenic MCA 102 sarcoma and B16-BL6(BL6) melanoma . We used the bacterial immunoadjuvant Nocardia rubra cell wall skeleton (N-CWS), and a streptococcal preparation, OK-432, for MCA 102 and BL6, respectively . After C57BL/6(B6) mice were inoculated subcutaneously (s.c.) with viable MCA 102 or BL6 tumor cells in the foot-pad, mice were injected intratumorally (i.t.) with N-CWS ranging from 10 to 400 micrograms or OK-432 ranging from 1 to 100 micrograms . Draining popliteal lymph nodes (LN) were harvested 7 days after i.t . administration of BRM, and LN cells were cultured with irradiated tumor cells in the presence of IL-2 for 11 days . These IVS cells (7.5 x 10(6) or 2 x 10(6)) were transferred intravenously (i.v.) to B6 mice with 4 day pulmonary metastases established by i.v . injection of viable MCA 102 cells (1 x 10(6)) or viable BL6 cells (3 x 10(5)) . The mice were also received intraperitoneally 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer . The transfer of IVS cells from mice immunized by i.t . injection of 100 micrograms of N-CWS 1 week after inoculation of tumor cells significantly reduced MCA 102 pulmonary metastases, compared with control IVS cells without administration of N-CWS . Moreover, the transfer of IVS cells from mice immunized by i.t . injection of 10 micrograms of OK-432 3 days after inoculation of tumor cells significantly reduced BL6 pulmonary metastases compared with control IVS cells without administration of OK-432 . The administration of N-CWS resulted in no enhancement of in vitro cytotoxicity . Although the administration of 10 micrograms of OK-432 augmented in vitro cytotoxicity of IVS cells against BL6, cytotoxic activity was lower than that of IVS cells immunized with N-CWS . The major phenotype was CD8+ cells in IVS cells immunized with N-CWS or OK-432 . These results suggest that i.t . administration of N-CWS and OK-432 facilitates the production of sensitized T-cells, and this administration route of BRM may be useful in the adoptive immunotherapy of human cancer. J Paediatr Child Health, 1995 Dec, 31(6), 493 - 4 Prevention of early onset group B streptococcal sepsis in the newborn; Vigneswaran R et al.; There is an urgent need for strategies to prevent early onset group B streptococcal sepsis in the newborn . The most effective mechanism is the identification of maternal carriers of the organism and interruption of transmission during labour . Vaginal culture is currently the most reliable method for the identification of carriers . Antibiotic prophylaxis for known carriers in labour has been demonstrated to be effective as standard management practice in a number of Australian institutions and is the best available strategy at this stage. Biochem Mol Med, 1995 Dec, 56(2), 176 - 9 Comparison of human VDAC1 with streptococcal streptokinase and bovine bactericidal permeability increasing protein: role of structural information in identifying functionally significant domains; McCabe KM et al.; Comparison of the primary amino acid sequence of the human X-linked voltage-dependent anion channel, with other sequences in data base searches, identified regions of similarity in streptococcal streptokinase and bovine bactericidal permeability increasing protein . These regions of similarity were in different areas of the protein and were relatively short . However, examination of an empirically derived structural model of the channel showed that each region of similarity in streptokinase and bovine bactericidal permeability increasing protein corresponded to contiguous transmembrane domains within the channel protein . We speculate that these transmembrane domains may be functionally significant for streptokinase and bovine bactericidal permeability increasing protein . These investigations demonstrate the need for incorporation of information regarding secondary, tertiary, and quaternary structures, as well as function, in algorithms used for database searches. Med Hypotheses, 1995 Dec, 45(6), 575 - 87 Immunological influences in attention-deficit disorder and schizophrenia; is there a link between these two conditions? Holden RJ, Pakula IS. This paper aims to explore the influence of the immune system on the pathobiochemistry of movement disorders (Tourette syndrome, obsessive compulsive disorders and attention-deficit disorder, with and without hyperactivity) and schizophrenia . In children, a temporal relationship has been observed between contraction of a group A beta-hemolytic streptococcal infection and subsequent presentation with one of the movement disorders . Pathology investigations reveal that elevated antineuronal antibodies are associated with movement disorders . Similarly, elevations in interleukin-1 beta and interleukin-6 have been reported in schizophrenia . It is now known that the immune system can be activated by conditions other than a viral or bacterial infection, such as: neurological insult, neurotoxicity--endogenous and environmental, neurotransmitter and cholesterol dysregulation . These latter avenues of immune system activation will be explored with respect to schizophrenia. Scand J Prim Health Care, 1995 Dec, 13(4), 257 - 60 The economic cost of a streptococcal tonsillitis episode; Roos K et al.; OBJECTIVE: To estimate the cost of a streptococcal tonsillitis episode from the data of a questionnaire . SETTING: Five primary health centres in the west of Sweden . PARTICIPANTS: 101 consecutive patients treated for streptococcal tonsillitis . MAIN OUTCOME MEASURE: The cost estimation included costs for physician visit and drug, travel costs to and from the primary health centre, cost of lost production resulting from the patient's or the guardian's absence from work for physician visit or sick-leave, and cost of telephone consultation with a physician or nurse . RESULTS: The period of illness was on average seven days, time to recovery after treatment five days, and the mean period of sick-leave 2.5 days . The total cost of a tonsillitis episode was about SEK 3,300 (385 USD) . Of this sum, the cost for the antibiotic accounted for only 3% and loss of production for 75% . CONCLUSION: Differences in the cost of drugs only have a minor influence on the total cost, while factors causing loss of production, such as efficacy and side effects of the drug, have a greater influence . Economic evaluation of pharmaceuticals will be more relevant in the future, and in the search for the most effective treatment, cost effective studies will be integrated with clinical trials. Eur Heart J, 1995 Dec, 16(12), 1968 - 74 Procedures associated with infective endocarditis in adults . A case control study; Lacassin F et al.; OBJECT: To assess the relative risk of infective endocarditis associated with various procedures and the protective efficacy of antibiotic prophylaxis by a case-control study . BACKGROUND: Recommendations for the prevention of infective endocarditis are based on the hypothesis of a relationship between procedures and infective endocarditis which is supported by anecdotal reports and data from experimental models . METHODS: Cases met the Von Reyn's diagnostic criteria modified with echocardiographic and macroscopic findings Controls were recruited from cardiology or medicinal wards . Cases (n = 171) and controls were matched as regards sex, age and underlying cardiac condition . They were requested to indicate all the medical, surgical or dental procedures within the previous 3 months . Among potential confounding factors, infectious episodes and skin wounds in the previous 3 months were reported . Antibiotic prophylaxis administration was documented for type, dosage, duration and administration schedule . RESULTS: Cases significantly more frequently than controls had undergone at least one procedure (matched odds ratio, 1.6; 95% confidence interval, 1.01 to 2.53) . Dental procedures considered as a whole were not associated with an increased risk, although scaling and root canal treatment showed a trend towards a higher risk of infective endocarditis (P = 0.065) . Among non-dental procedures, only surgery appeared to be at risk (matched odds ratio, 4.7; 95% confidence interval, 1.02 to 22) . Considering all procedures, the risk of infective endocarditis increased significantly with the number of procedures . While general co-morbid conditions did not differ between the two groups, cases significantly more frequently than controls had experienced an infectious episode or a skin wound . In multivariate analysis, only infectious episodes and skin wounds significantly increased the risk of infective endocarditis . Scaling was the only independent risk factor for viridans streptococcal infective endocarditis . The 46% protective efficacy of antibiotic prophylaxis was not significant . CONCLUSIONS: Procedures do increase the risk of infective endocarditis . The interpretation of the apparent low risk associated with dental procedures may be as a result of the current practice of antibiotic prophylaxis . Our data suggest that surgery should be more clearly mentioned in future guidelines, and reemphasize that a rigorous treatment of any focal infection in cardiac patients is mandatory . From the efficacy rate of antibiotic prophylaxis,it can be estimated that the overall incidence of infective endocarditis might be reduced by 5 to 10% in France by appropriate use of antibiotic prophylaxis in cardiac patients. Z Lymphol, 1995 Dec, 19(2), 55 - 7 {Anasarca caused by rheumatic carditis}; Ruger K; Report of a 55-year-old-male patient with most serious anasarca caused by insufficiency right heart . The reason of the heart failure was probably rheumatic carditis caused by streptococcal infections which followed recurrent erysipelas both legs with phleblymphedema . The necessity of consistent antibiotic treatment of the erysipelas, that's the only possibility to avoid more difficult secondary complications like this case of rheumatic carditis showed . The treatment of insufficiency heart was followed by physical decongestive therapy of the phleblymphedema of the legs . After a treatment period of 12 weeks a water loss of 112 kg and reduction of abdominal circumference from 250 cm to 150 cm could be achieved. Pneumologie, 1995 Dec, 49(12), 674 - 7 {Primary germ cell tumors of the mediastinum}; Theegarten D et al.; This is a report on 5 cases of mediastinal germ cell tumours . Of three mature teratomas seen in a 48-year old male and a 21-year old and 19-year old female, one was asymptomatic, another one associated with streptococcal pneumonia and the third associated with progressive cough irritation . In addition, a seminoma was seen in a male of 58 years of age and a yolk sac tumour (mesonephroma type 2) in a male of 23 years . Whereas in mature teratomas surgical resection can be considered sufficient, resection combined with chemotherapy should be performed in patients suffering from malignant germ cell tumours, and in addition also radiotherapy in case of seminoma . This approach may result in a significant improvement of the prognosis in malignant mediastinal germ cell tumours. Protein Sci, 1995 Dec, 4(12), 2605 - 15 Structural and dynamic characterization of the urea denatured state of the immunoglobulin binding domain of streptococcal protein G by multidimensional heteronuclear NMR spectroscopy; Frank MK et al.; The structure and dynamics of the urea-denatured B1 immunoglobulin binding domain of streptococcal protein G (GB1) has been investigated by multidimensional heteronuclear NMR spectroscopy . Complete 1H, 15N, and 13C assignments are obtained by means of sequential through-bond correlations . The nuclear Overhauser enhancement, chemical shift, and 3JHN alpha coupling constant data provide no evidence for the existence of any significant population of residual native or nonnative ordered structure . 15N relaxation measurements at 500 and 600 MHz, however, provide evidence for conformationally restricted motions in three regions of the polypeptide that correspond to the second beta-hairpin, the N-terminus of the alpha-helix, and the middle of the alpha-helix in the native protein . The time scale of these motions is longer than the apparent overall correlation time (approximately 3 ns) and could range from about 6 ns in the case of one model to between 4 microseconds and 2 ms in another; it is not possible to distinguish between these two cases with certainty because the dynamics are highly complex and hence the analysis of the time scale of this slower motion is highly model dependent . It is suggested that these three regions may correspond to nucleation sites for the folding of the GB1 domain . With the exception of the N- and C-termini, where end effects predominate, the amplitude of the subnanosecond motions, on the other hand, are fairly uniform and model independent, with an overall order parameter S2 ranging from 0.4 to 0.5. J Exp Med, 1995 Dec 1, 182(6), 1833 - 45 Superantigen binding to a T cell receptor beta chain of known three-dimensional structure; Malchiodi EL et al.; The three-dimensional structure of an unglycosylated T cell antigen receptor (TCR) beta chain has recently been determined to 1.7 A resolution . To investigate whether this soluble beta chain (murine V beta 8.2J beta 2.1C beta 1) retains superantigen (SAG)-binding activity, we measured its affinity for various bacterial SAGs in the absence of MHC class II molecules . Dissociation constants (KDs) were determined using two independent techniques: surface plasmon resonance detection and sedimentation equilibrium . Specific binding was demonstrated to staphylococcal enterotoxins (SEs) B, C1, C2, and C3 and to streptococcal pyrogenic exotoxin A (SPEA), consistent with the known proliferative effects of these SAGs on T cells expressing V beta 8.2 . In contrast, SEA, which does not stimulate V beta 8.2-bearing cells, does not bind the recombinant beta chain . Binding of the beta chain to SAGs was characterized by extremely fast dissociation rates (> 0.1 s-1), similar to those reported for certain leukocyte adhesion molecules . Whereas the beta chain bound SEC1, 2, and 3 with KDs of 0.9-2.5 microM, the corresponding value for SEB was approximately 140 microM . The much weaker binding to SEB than to SEC1, 2, or 3 was surprising, especially since SEB was found to actually be 3- to 10-fold more effective, on a molar basis, than the other toxins in stimulating the parental T cell hybridoma . We interpret these results in terms of the ability of SEC to activate T cells independently of MHC, in contrast to SEB . We have also measured SE binding to the glycosylated form of the beta chain and found that carbohydrate apparently does not contribute to recognition, even though the N-linked glycosylation sites at V beta 8.2 residues Asn24 and Asn74 are at or near the putative SAG-binding site . This result, along with the structural basis for the V beta specificity of SEs, are discussed in relation to the crystal structure of the unglycosylated beta chain. Science, 1995 Nov 10, 270(5238), 980 - 2 Guidelines for protein design: the energetics of beta sheet side chain interactions; Smith CK et al.; To determine the interaction energy between cross-strand pairs of side chains on an antiparallel beta sheet, pairwise amino acid substitutions were made on the solvent-exposed face of the B1 domain of streptococcal protein G . The measured interaction energies were substantial (1.8 kilocalories per mole) and comparable to the magnitude of the beta sheet propensities . The experimental results paralleled the statistical frequency with which the residue pairs are found in beta sheets of known structure. Gene, 1995 Nov 7, 165(1), 57 - 60 Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase; Ashbaugh CD et al.; Inosine monophosphate dehydrogenase (IMPDH) is an essential enzyme in the biosynthesis of purines . We cloned a group A streptococcal (GAS) DNA fragment containing an open reading frame similar to other bacterial guaB genes encoding IMPDH . The GAS guaB consists of 1479 nucleotides encoding a protein of 493 amino acids . Expression of the GAS guaB in an Escherichia coli guaB mutant restored IMPDH activity, confirming the function of the gene product and demonstrating that the GAS enzyme is active in a heterologous bacterial host . Restriction mapping and Southern hybridization analysis of GAS chromosomal DNA localized guaB to a site approximately 5 kb from the hasA and hasB genes which encode enzymes necessary for hyaluronic acid capsule synthesis. Mol Microbiol, 1995 Nov, 18(3), 569 - 78 Identification of a plasminogen-binding motif in PAM, a bacterial surface protein; Wistedt AC et al.; Surface-associated plasmin(ogen) may contribute to the invasive properties of various cells . Analysis of plasmin(ogen)-binding surface proteins is therefore of interest . The N-terminal variable regions of M-like (ML) proteins from five different group A streptococcal serotypes (33, 41, 52, 53 and 56) exhibiting the plasminogen-binding phenotype were cloned and expressed in Escherichia coli . The recombinant proteins all bound plasminogen with high affinity . The binding involved the kringle domains of plasminogen and was blocked by a lysine analogue, 6-aminohexanoic acid, indicating that lysine residues in the M-like proteins participate in the interaction . Sequence analysis revealed that the proteins contain common 13-16-amino-acid tandem repeats, each with a single central lysine residue . Experiments with fusion proteins and a 30-amino-acid synthetic peptide demonstrated that these repeats harbour the major plasminogen-binding site in the ML53 protein, as well as a binding site for the tissue-type plasminogen activator . Replacement of the lysine in the first repeat with alanine reduced the plasminogen-binding capacity of the ML53 protein by 80% . The results precisely localize the binding domain in a plasminogen surface receptor, thereby providing a unique ligand for the analysis of interactions between kringles and proteins with internal kringle-binding determinants. J Dairy Sci, 1995 Nov, 78(11), 2366 - 74 Environmental streptococcal intramammary infections of the bovine mammary gland; Todhunter DA et al.; Characteristics of environmental streptococcal IMI were investigated over a 7-yr period for a herd in total confinement . A total of 374 new environmental streptococcal IMI was detected . Approximately 50.5% of IMI were new in the dry period, and 49.5% were new in lactation . The rate of new IMI was .00312 IMI/cow day during the dry period and .00054 IMI/cow day during lactation . The percentages of cows and quarters with an environmental streptococcal IMI present at calving were 10.6 and 3.2%, respectively . The percentage of heifers with an environmental streptococcal IMI at calving was similar to that for cows . The rate of new environmental streptococcal IMI was greater during the 1st mo of lactation than during the remainder of lactation . The rate of IMI during late lactation was higher for older cows than for either heifers or cows in second lactation . The rate of environmental streptococcal IMI during the dry period and during lactation was greatest during summer . The mean days of lactation that cows were infected for all IMI was 12.3 d . Approximately 41% of IMI had a duration of < 8 d . Stage of lactation, season of the year, and parity influenced the rate of new IMI. Baillieres Clin Rheumatol, 1995 Nov, 9(4), 653 - 71 Innovative treatment approaches for rheumatoid arthritis . T-cell regulation; Choy EH et al.; There is considerable evidence to implicate T cells in the pathogenesis of rheumatoid arthritis (RA) . They initiate and sustain inflammation and therefore are attractive targets for immunotherapy . Several strategies targeting T cells have been tried in RA . The use of monoclonal antibodies to deplete T cells have been used extensively but with little success . Studies have shown that T cell depleting antibodies produce profound peripheral blood lymphopenia but they are less effective in depleting lymphocytes in the joint . Since clinical efficacy is likely to depend on depleting almost all synovial lymphocytes, high doses of monoclonal antibodies would have to be given . However, the invariably severe peripheral blood lymphopenia induced by such a regimen is likely to result in profound immunosuppression . Therefore, this strategy has been abandoned and recent attempts have been made to induce tolerance in RA . In animal models of RA, treatment with high dose non-depleting anti-CD4 monoclonal antibody protects them from arthritis induced by injection of streptococcal cell wall . In addition, it leads to a state of anergy which protects the animals from arthritis induction without further treatment with anti-CD4 monoclonal antibody . This is currently being used in clinical trials of RA . Other tolerance inducing treatment strategies include T cell or T cell receptor vaccination and oral tolerance . The former is particularly difficult since the rheumatoid arthritogenic antigen and the pathogenic T cell remain unknown . The latter has shown promise in placebo controlled trials although the ideal dosage remains unknown . The mechanism of action of oral tolerance involves either immunosuppressive T cell cytokines, T cell anergy or depletion. Clin Infect Dis, 1995 Nov, 21(5), 1220 - 7 Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone; Carapetis J et al.; We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993 . Forty-two cases were identified . There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs . 20%, respectively, with an 88% complication rate over the last 12 months) . Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed . An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates . Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable . Invasive GAS disease in Melbourne has become increasingly aggressive . Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains. Microvasc Res, 1995 Nov, 50(3), 397 - 416 Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia; Walker DC et al.; The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation . Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes . The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact . The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts . Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs . We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium . We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts . We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells . From there, neutrophils migrate into the alveolar airspace. Mol Immunol, 1995 Nov, 32(16), 1235 - 43 Characterization of a type II'o group A streptococcal immunoglobulin-binding protein; Pack TD et al.; The opacity factor positive M type 2 group A streptococcal isolate, A207, expresses a unique functional type II'o IgG-binding protein which reacts with all four human IgG subclasses and rabbit IgG . In order to determine the gene product or products responsible for this activity, three genes of the vir regulon from this isolate were cloned, expressed and analysed . The fcr A2 gene coded for a protein binding hyman IgG1, IgG2 and IgG4 but not IgG3 . The enn2 gene coded for a protein reacting exclusively with human IgA, while the emmL2 gene product bound IgG1, IgG2, IgG3 and IgG4 as well as rabbit but not horse or pig IgG . The IgG3-binding activity of the EmmL2 protein was functionally indistinguishable from the Form 1 IgG3-binding activity present in heat extracts of group A isolate A207. J Okla State Med Assoc, 1995 Nov, 88(11), 472 - 4 Streptococcal necrotizing fasciitis ("flesh-eating strep infection"); Schwartz SN et al.; Streptococcal necrotizing fasciitis, popularized in the lay literature as the "flesh-eating infection" has gained great notoriety . Necrotizing fasciitis may be lethal not only due to its severity, but also because of difficulty in diagnosis during its early stages . Absence of immunity against certain streptococcal proteins increases the severity of infection . Necrotizing fasciitis may be distinguished from other streptococcal skin and soft tissue infections by clinical examination, imaging studies, and biopsy . Treatment requires a combined medical-surgical approach. J Clin Invest, 1995 Nov, 96(5), 2106 - 12 Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis; Leung DY et al.; Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis . Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection . This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens . Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families . Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05) . The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets . Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response . All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion . These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s). Dig Dis Sci, 1995 Nov, 40(11), 2398 - 406 Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer activity in the liver; Shiratori Y et al.; We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice . In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined . The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice . Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice . An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complement in vitro . Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver . On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complement in vitro, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Immunol Immunopathol, 1995 Nov, 77(2), 119 - 26 Superantigens in Kawasaki syndrome; Leung DY et al.; Kawasaki syndrome (KS) is an acute multisystem vasculitis of infancy and early childhood associated with the development of myocarditis and coronary artery abnormalities . Despite the widely held belief that KS is caused by an infectious agent, there remains considerable controversy over its etiology . Recent immunologic and microbiologic studies suggest a potential role for staphylococcal and streptococcal toxins (superantigens) in the pathogenesis of KS . Confirmation of these findings could result in more effective diagnostic and therapeutic approaches to this common cause of acquired heart disease in children. Zhonghua Nei Ke Za Zhi, 1995 Oct, 34(10), 687 - 9 {An approach to the diagnosis of recurrent attack of rheumatic fever in patients with rheumatic heart disease}; Huang C; In order to evaluate recurrent attack of rheumatic fever (RARF) in patients with rheumatic heart disease (RHD), 97 patients with diagnosis of RHD for two years and more were included in this study . Progression of the lesions of cardiac valves was found in every case by comparing the echocardiographic and Doppler findings at present and two years ago . The history of the initial attack of acute rheumatic fever or the appearance of RHD were reviewed . The present complaints at admission and necessary laboratory procedures were studied . The data showed that 75 of the 97 patients had history of initial attack of ARF and the remaining 22 were symptomless with indolent carditis or carditis of insidious onset two years ago . In this admission, only 25 of the 97 patients had ARF in the Jones criteria were followed strictly, while the remaining 72 did not fulfill the criteria . It is suggested that if there is evidence of recent group a streptococcal infection, the conditions for diagnosis of RARF are as follows: 1) When one major or more than two minor criteria are present in a patient with RHD, a definite diagnosis of RARF may be made . 2) A presumptive diagnosis of RARF may be made, when a patient presents one minor criteria and several other manifestations such as anemia, abdominal pain, rapid sleeping pulse rate, tachycardia out of proportion to fever, malaise, epistaxis, precordial pain and an elevated level of IgG, IgA, C3 and circulating immune complexes. Int J Immunopharmacol, 1995 Oct, 17(10), 841 - 8 Tumor necrosis factor production by human T-cells stimulated with bacterial superantigens; Imanishi K et al.; Tumor necrosis factor (TNF) production from T-cells stimulated with superantigenic exotoxins, staphylococcal enterotoxin B and streptococcal pyrogenic exotoxin A was investigated in the presence of cells bearing distinct isotypes of HLA class II molecules . The main T-cell subset for TNF production was investigated in parallel . Similarly high levels of TNF production were induced upon stimulation with the toxins in the presence of DR+ or DQ+ cells, but only marginal levels of TNF production were induced in the presence of DP+ cells . Although both CD4+ T-cells and CD8+ T-cells produced TNF-alpha and TNF-beta in response to toxin stimulation in the presence of HLA class II+ cells, the former T-cell subset was the major source of producers of TNF-alpha and TNF-beta. Clin Infect Dis, 1995 Oct, 21(4), 977 - 80 Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome? Stevens DL. Anecdotal reports suggest an association between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and the progression of invasive group A streptococcal infections to shock and multiorgan failure . There is a biochemical rationale that could support this theory . Though NSAIDs are frequently used to relieve pain or reduce fever, they also attenuate granulocyte functions such as chemotaxis, phagocytosis, and bacterial killing . In addition, findings in recent studies involving human volunteers injected with endotoxin suggest that pretreatment with NSAIDs enhances production of tumor necrosis factor, which leads to higher blood levels of this cytokine, probably by preventing feedback inhibition by prostaglandin E2 . Thus, NSAIDs may contribute to the sudden onset of shock, organ failure, and aggressive infection by inhibiting neutrophil function, augmenting cytokine production, and attenuating the cardinal manifestations of inflammation. Proteins, 1995 Oct, 23(2), 256 - 63 Metal search: a computer program that helps design tetrahedral metal-binding sites; Clarke ND et al.; We describe a computer program (Metal Search) that helps design tetrahedrally coordinated metal binding sites in proteins of known structure . The program takes as input the backbone coordinates of a protein and outputs lists of four residues that might form tetrahedral sites if wild-type amino acids were replaced by cysteine or histidine . The program also outputs the side chain dihedral angles of the amino acids and the coordinates of the predicted metal ion . The only function evaluated by Metal Search is the ability of side chains to meet simple geometric criteria for formation of a tetrahedral site, but these criteria are sufficient to produce a manageably small list that can then be evaluated by other means . The program has been used in the introduction of zinc binding sites in the designed four-helix bundle protein alpha 4 and in the B1 domain of streptococcal protein G, and in both cases the tetrahedral coordination of a bound metal ion has been confirmed (Klemba, M., Gardner, K . H., Marino, S., Clarke, N.D., and Regan, L., Nature: Structural Biology 2:368-373, 1995). Endocr J, 1995 Oct, 42(5), 675 - 81 17 alpha-Hydroxyprogesterone suppresses neovascularization induced by HPLC-purified ovarian hyaluronic acid-like glycosaminoglycan in mice; Okada M et al.; HPLC-purified glycosaminoglycans (hpGAG) prepared from extracts of non-luteal mouse (JcL:ICR strain) ovaries were assayed for neovascularization by implanting Elvax films, containing test samples, on the lateral wall of the sheath of m . rectus abdominis in adult female mice of the same strain . Neovascularization occurred in a dose-dependent manner, and was characterized by capillary outgrowth extending into the tissue surrounding the implant . The single major peak of purified GAG on a column of TSK gel DEAE got out of order after treatment with streptococcal hyaluronidase or nitrous acid . The activity of this fraction was also greatly reduced when treated with streptococcal hyaluronidase or nitrous acid . When hpGAG was embedded in the implant with 17 alpha-hydroxyprogesterone at a dose of 20 micrograms/film, neovascularization induced by means of hpGAGs was suppressed . Progesterone at a dose of 50 micrograms/film did not suppress the neovascularization induced by ovarian hpGAG . These findings suggest that 17 alpha-hydroxyprogesterone suppresses the angiogenic activity of hyaluronic acid-like hpGAG in the ovary. J R Coll Surg Edinb, 1995 Oct, 40(5), 328 - 9 Streptococcal myositis and the acute abdomen: a case report; Segar A et al.; Spontaneous streptococcal myositis, previously rare, is now reported more frequently . The condition is caused by overwhelming group A beta-haemolytic streptococcal infection and is not necessarily fatal. J Anat, 1995 Oct, 187 ( Pt 2), 271 - 7 Antibodies against proteins of streptococcal hyaluronate synthase bind to human fibroblasts and are present in patients with rheumatic fever; Prehm S et al.; Antibodies directed against the streptococcal 42 kDa hyaluronate synthase and a 56 kDa auxiliary protein bound to the surface of intact human fibroblasts in vitro . Staining was most prominent during the detachment phase of mitosis . In eukaryotic plasma membranes a 52 kDa protein was recognized by the antiserum against the 56 kDa streptococcal protein . Since the cross-reacting proteins could be involved in immunological mimicry between streptococcal and human antigens leading to heart cell necrosis, the reactivity of sera from patients with rheumatic fever was compared with that of sera from healthy or streptococcal infected persons . The sera from patients with rheumatic fever showed a higher reactivity against the 56 kDa protein than those from healthy persons or from patients with an antibiotic treated streptococcal infection . This difference was not observed for the 42 kDa protein . These sera were able to lead to cell lysis in the presence of complement. Br J Rheumatol, 1995 Oct, 34(10), 942 - 5 Cutaneous leucocytoclastic vasculitis: a clinical and aetiological study; Jessop SJ; Cutaneous vasculitis may be the presenting sign in many different clinical disorders . The aetiology and clinical and laboratory findings were recorded in 69 consecutive patients with cutaneous leucocytoclastic vasculitis . Underlying connective tissue disease or malignancy was found in 19 patients . Evidence of recent streptococcal infection was detected in 24 patients . Application of the classification criteria proposed by the American College of Rheumatology (ACR) identified 35 patients with Henoch-Schonlein purpura (HSP) and 42 with hypersensitivity vasculitis (HSV) . Thirty-three subjects fulfilled criteria for both HSP and HSV. Scand J Immunol, 1995 Oct, 42(4), 433 - 41 Allosteric and temperature effects on the plasma protein binding by streptococcal M protein family members; Cedervall T et al.; Most group A streptococcal strains bind immunoglobulins (Ig) and fibrinogen to their cell walls . It is shown in this paper that the Ig-binding of three different strains was much weaker at 37 degrees C than at room temperature (20 degrees C), whereas the fibrinogen binding was unaffected by temperature . The binding properties and molecular sizes of two purified group A streptococcal cell surface proteins from the M protein family were studied at various temperatures, M1 protein with affinity for IgG, fibrinogen and albumin, and protein Sir22 with affinity for IgA and IgG . Both proteins appeared as monomers which bound all their ligands, including fibrinogen, very weakly at 37 degrees C, and as strongly binding dimers at 10 and 20 degrees C . Furthermore, the results demonstrated that the plasma protein binding of the bacterial proteins was allosterically regulated, i.e . the binding of a ligand to one site modulated the binding of a ligand to a second site . For example, the binding of albumin or IgG to purified M1 protein at 10 and 20 degrees C strongly enhanced the binding of fibrinogen at 37 degrees C . This indicates that the high affinity dimer form of the bacterial proteins can be stabilized at 37 degrees C, a possible explanation for the strong fibrinogen binding of whole bacteria . Finally, the sizes and binding properties of three M1 protein fragments were studied and the results indicated that the centrally located C-repeats, which are conserved among the members of the M protein family, are important for the formation of the high-affinity dimers of the bacterial proteins. Pediatrics, 1995 Oct, 96(4 Pt 1), 758 - 64 Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals . Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association; Dajani A et al.; Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis . Diagnosis of GAS pharyngitis is best accomplished by a throat culture . Penicillin (either oral penicillin V or injectable benzathine penicillin) remains the treatment of choice, because it is cost effective, has a narrow spectrum of activity, has long-standing proven efficacy, and GAS resistant to penicillin have not been documented . Various macrolides, oral cephalosporins, and other beta-lactam agents are acceptable alternatives, particularly in penicillin-allergic individuals . The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention) . The duration of prophylaxis depends on the number of previous attacks, the time lapsed since the last attack, the risk of exposure to streptococcal infections, the age of the patient, and the presence or absence of cardiac involvement . Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals . This report is an update of a 1988 statement by this committee . It expands on the previous statement, includes more recent therapeutic modalities, and makes more specific recommendations for the duration of secondary prophylaxis. Br J Ophthalmol, 1995 Oct, 79(10), 888 - 91 Paediatric post-traumatic endophthalmitis; Alfaro DV et al.; AIMS--A retrospective analysis of children with post-traumatic endophthalmitis was performed to determine if microbiological differences exist between this disease in the paediatric population compared with this disease in adults . METHOD--Twelve cases of post-traumatic endophthalmitis in children were analysed to determine characteristics of this disease in youth . Patient ages varied from 18 months to 13 years; the mean age was 8 years . Gram positive organisms were isolated in eight eyes, Gram negative organisms from four eyes, fungus from one eye, and negative cultures in three eyes . The most common isolates were streptococcal species (56.6%) and staphylococcal species (22.2%) . Vitrectomy was performed on eight (66.7%) eyes . RESULTS--Visual acuity of 20/200 or better was obtained in eight eyes (66.7%) . Three eyes had vision less than 5/200 . One eye developed phthisis bulbi . Nine (75%) patients were younger than 10 years of age, and six (66.7%) of these nine obtained a final visual acuity of 20/200 or better . CONCLUSION--Useful vision can be obtained in children with post-traumatic endophthalmitis with early, aggressive treatment . The microbiology of paediatric post-traumatic endophthalmitis differs from adult disease with streptococcal species as the most common infecting organisms. Med J Aust, 1995 Sep 18, 163(6), 302 - 6 Early-onset group B streptococcal infections in Aboriginal and non-Aboriginal infants . Australasian Study Group for Neonatal Infections; Relapsing invasive group B streptococcal infection in adults; Department of International Health, Johns Hopkins University, Baltimore, MD 21205, USAOBJECTIVE: To study recurrent group B streptococcal infection in adults . DESIGN: Patients with more than one reported group B streptococcal infection were identified through active surveillance for this infection . Sterile-site group B streptococcal isolates were evaluated for serotype and molecular subtyping using restriction endonuclease analysis of chromosomal DNA (REAC) . SETTING: All acute-care hospitals in Maryland . PATIENTS: Nonpregnant residents of Maryland 18 years of age or older . RESULTS: 22 adults had at least two group B streptococcal episodes that were separated by 2 to 95 weeks (mean, 24 weeks) . Of 395 patients with invasive group B streptococcal infection who survived the first episode and were followed for at least 1 year, 17 (4.3% {95% CI, 2.6% to 6.9%}) had more than one episode . Several patients were found to have endocarditis or osteomyelitis during the second episode . Group B streptococcal isolates from both episodes were obtained from 18 of 22 patients . Of the 18 isolate pairs, 13 (72% {CI, 46% to 90%}) had identical REAC patterns; the probability that at least 13 matches would be found by chance alone was less than 0.000001 . Among patients with recurrent infection caused by the same strain, the interval between episodes was shorter (mean, 14 weeks) than that among patients with recurrent infection caused by another strain (mean, 43 weeks; P = 0.05) . CONCLUSIONS: