Clin Exp Immunol, 1994 May, 96(2), 238 - 44 Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection; Soboslay PT et al.; The present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years . The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments . In vitro cellular responses to O . volvulus antigen (OvAg) were highest (P < 0.01) in untreated control individuals exposed to infection, but negative for mf of O . volvulus (endemic normals) . Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P < 0.05) at 84 months p.i.t . in amicrofilaridermic than in microfilaria-positive onchocerciasis patients . In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals . Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2, IL-4 and interferon-gamma (IFN-gamma) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-gamma were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients . OvAg-specific production of IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t . At three months p.i.t . the titres of circulating OvAg-specific IgG1-3 had increased (P < 0.05), but they then continuously declined with repeated treatments . Only IgG1 and IgG4 bound to OvAg of mol . wt 2-12 kD at 1 month p.i.t., while recognition of OvAg of mol . wt 10-200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3-6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter . These results suggest that onchocerciasis-associated immunosuppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-gamma in amicrofilaridermic individuals may contribute to controlling O . volvulus infection. Hepatology, 1994 May, 19(5), 1241 - 4 The immunostimulant OK-432 enhances liver regeneration after 90% hepatectomy in rats; Kato K et al.; The effect of reticuloendothelial system activation on liver regeneration after 90% hepatectomy was investigated . OK-432, a killed streptococcal preparation that increases reticuloendothelial system activity, was administered to rats before 90% partial hepatectomy . Pretreated rats showed marked improvement in long-term survival: 87% (18 of 23) survived beyond 42 hr, compared with only 44.2% (24 of 52) of controls (p < 0.05) . Survival was determined by means of life-table analysis and regeneration response by means of bromodeoxyuridine labeling index of hepatic DNA . OK-432 pretreatment had significantly increased bromodeoxyuridine labeling index 18, 24, and 42 hr after partial hepatectomy (p < 0.05) . The results indicate that reticuloendothelial system activation by OK-432 before 90% partial hepatectomy enhances liver regeneration and improves survival, but these factors may not be related . The improved survival may be because of less infection in macrophage-stimulated animals or more rapid clearance of hypotension-causing vasoactive compounds. J Pak Med Assoc, 1994 May, 44(5), 116 - 8 Acute glomerulonephritis in children; Shiva F et al.; Acute glomerulonephritis (AGN) remains fairly common in the developing world although its frequency has declined in the industrial countries . The pattern of AGN was studied in one hundred hospitalised children . We recorded an increased prevalence in school age, i.e., 6-15 years (75%) and the occurrence of a streptococcal infection (90%), most often a pharyngeal infection (86%), one to three weeks preceding the illness . The problems that needed specific management during the acute phase were hypertension (39%), encephalopathy (5%) and ARF with hyperkalemia, 2% of the patients needing haemodialysis . Most of our patients (98%) recovered with 2% progressing to RPGN . The excellent prognosis of AGN with proper management emphasises the need for optimal care during the acute phase in the hospitalised children. Baillieres Clin Rheumatol, 1994 May, 8(2), 429 - 38 The immunopathology of psoriasis; Barker JN; Psoriasis is a common chronic skin disorder affecting 2% of the general population . Present evidence strongly suggests that it is an immunologically mediated disease; the evidence includes the results of disease association studies linking psoriasis to certain MHC antigens and immunohistochemical studies revealing early influx into lesions of activated T lymphocytes . Accumulation of these cells in skin is mediated by upregulated expression of leukocyte adhesion molecules on vascular endothelium and epidermal keratinocytes and by production of proinflammatory and chemotactic cytokines . Activation of cell-mediated immune mechanisms in lesional skin is highlighted by the increased antigen-presenting capacity of Langerhans cells isolated from psoriatic skin compared to normal skin . The nature of the antigens precipitating psoriasis, however, remains unknown although a role for streptococcal superantigens has been postulated . These studies have led to the belief that immunotherapy may hold great promise for the treatment of psoriasis . Indeed both cyclosporin A and FK506 are effective therapies and evidence suggests that anti-CD4 antibodies may be of great value. Comput Med Imaging Graph, 1994 May-Jun, 18(3), 213 - 6 Necrotizing fasciitis and myositis: a case report; Razi-Syed S et al.; Necrotizing fasciitis is a relatively rare, potentially life-threatening infection involving the subcutaneous tissues . We report a case of group A streptococcal necrotizing fasciitis/myositis in which CT played an important role in differential diagnosis. Biosci Biotechnol Biochem, 1994 May, 58(5), 839 - 42 Development and characterization of macrophage hybridomas derived from murine peritoneal exudate cells; Ashikaga T et al.; Mouse macrophage (Mphi) hybridoma clones were generated by somatic cell hybridization of myeloma X63 cells (H-2d) with C57BL/6 (H-2b) peritoneal exudate cells elicited with a streptococcal preparation, OK432, or thioglycollate medium . Although they hardly adhered to plastic dishes and could not be morphologically distinguished from parental X63 tumor cells, the clones retained Mphi characteristics . These included phagocytosis and production of lysozyme and nonspecific esterase, suggesting that they were hybridomas derived from Mphi . Some of them expressed various levels of Ia antigen and Fc receptor . Because they induced proliferation of T cells from Balb/c mice but not those from C57BL/6 mice, the Ia antigen of Mphi hybridoma was assumed to be derived from peritoneal Mphi . The level of proliferation induction was correlated to the level of Ia antigen expression . Several clones produced a factor that cytostatically inhibited growth of murine mammary carcinoma and was serologically identified with arginine deiminase. J Immunol, 1994 May 1, 152(9), 4375 - 87 Immunological mimicry between N-acetyl-beta-D-glucosamine and cytokeratin peptides . Evidence for a microbially driven anti-keratin antibody response; Shikhman AR et al.; We discovered recently that a subset of mouse anti-streptococcal mAbs cross-reacted with N-acetyl-beta-D-glucosamine (GlcNAc) and certain cytoskeletal proteins, and recognized both carbohydrate and peptide antigenic determinants . To further study the nature and biologic significance of immunologic mimicry between carbohydrate and peptide Ags, eight human hybridomas secreting anti-GlcNAc mAbs were produced by in vitro stimulation of PBL with streptococcal peptidoglycan-polysaccharide complexes and pokeweed mitogen . All human anti-GlcNAc mAbs described in this study were shown to express marked cross-reactivity with keratin from human skin in the ELISA and Western immunoblot . Mapping of the mAbs with overlapping synthetic decapeptides of the entire amino acid sequence of human cytokeratin 14 revealed that human anti-GlcNAc mAbs recognized specific cytokeratin decapeptides . Four human anti-GlcNAc mAbs recognized a single cytokeratin decapeptide whereas two mAbs reacted with several individual peptide epitopes in different fragments of cytokeratin 14 . In addition, two mAbs, 1.C8 and 9.B12, reacted with multiple cytokeratin decapeptides, predominantly in the head domain of the molecule, and their reactivity correlated with positive binding of the mAbs to cytokeratin 14 in the Western immunoblot and with positive staining of human epidermis in the indirect immunofluorescent assay . Finally, we demonstrated that Abs to keratin and synthetic keratin decapeptides were induced in BALB/c mice immunized with GlcNAc-BSA but not with BSA, suggesting that the anti-keratin Ab response in vivo may be driven by nonkeratin Ags containing terminal O-linked GlcNAc. Biochemistry, 1994 Apr 19, 33(15), 4721 - 9 Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal protein G and comparison with NMR; Gallagher T et al.; The structure of the 56-residue B1 immunoglobulin-binding domain from streptococcal protein G has been determined in two different crystal forms . The crystal structures were deduced by molecular replacement, based on the structure of the B2 domain (Brookhaven accession code 1PGX) . Final R values are 0.174 and 0.198 for orthorhombic and trigonal forms, for diffraction data from 6.0 to 2.07 A and from 6 to 1.92 A, respectively . The orthorhombic crystals have an unusually high packing density for protein crystals, with Vm = 1.66 and a solvent content of 26% . The protein structure is found to be very similar (rms deviation 0.25 A for 56 C alpha's) in the two crystal forms, with an efficiently packed hydrophobic core between a four-stranded beta-sheet and a four-turn alpha-helix . The B1 domain has the same fold and general structure as the B2 domain (rms deviations 0.36 and 0.39 A), despite the six residue differences between them . The crystallographic models differ from NMR-derived models in several local regions, primarily in the loop involving residues 46-51; other significant variations are observed in the helix and in the structure of bound water . The primary crystal contact is the same in both crystal forms, involving both sheet edges to form extended beta-sheets throughout the crystals. Ann Emerg Med, 1994 Apr, 23(4), 818 - 22 Serious group A beta-hemolytic streptococcal infections complicating varicella; Cowan MR et al.; STUDY OBJECTIVE: To alert practicing emergency physicians to an important and possibly increasing relationship between life-threatening group A beta-hemolytic streptococcal (GABHS) infections and children recovering from varicella . DESIGN: A case series of six patients managed from January through March 1993 . SETTING: A university-affiliated pediatric specialty emergency department . TYPE OF PARTICIPANTS: Six previously healthy immunocompetent children between 1 and 5 years of age seen in our ED over a nine-week period . RESULTS: Six children had onset of varicella two days to two weeks before developing a serious life-threatening GABHS infection . Children presented with clinical symptoms of invasive GABHS infection with bacteremia (one patient); streptococcal toxic shock syndrome with negative blood culture (two), pneumonia with pleural effusion and streptococcal toxic shock syndrome (one), pneumonia with pleural effusion (one), and pyomyositis of the thigh (one) . Four of six patients required intensive care admissions and aggressive support of vital signs . All six survived . CONCLUSION: Emergency physicians should be aware of the association between varicella and serious GABHS infections and be prepared to recognize and aggressively manage serious complications should they occur. J Trauma, 1994 Apr, 36(4), 589 - 91 Gangrenous streptococcal myositis: case report; Hird B et al.; Streptococcal infection of the large skeletal muscles is a rare but often rapidly fatal condition that may occur for no apparent reason . Nonsteroidal anti-inflammatory drugs may have an adverse effect on outcome . A high index of suspicion is the key to early diagnosis. Eur J Immunol, 1994 Apr, 24(4), 916 - 22 Lymphokine production induced by streptococcal pyrogenic exotoxin-A is selectively down-regulated by pooled human IgG; Skansen-Saphir U et al.; The influence of pooled human IgG preparations for intravenous use (IVIg) on cytokine production induced by streptococcal pyrogenic exotoxin-A (SPE-A) was studied at the single-cell level using cytokine-specific monoclonal antibodies and indirect immunofluorescence or immunohistochemical staining . Mononuclear cells from healthy adult blood donors were stimulated with SPE-A alone or in the presence of IVIg . IVIg was added either prior to stimulation or 24 h after initiation of cultures, in an attempt to evaluate whether IVIg treatment could influence an already established systemic streptococcal disease . Cells were harvested after 48 or 72 h of culture and stained for the following cytokines: interleukin(IL)-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-2, tumor necrosis factor interferon(IFN)-gamma and TNF-alpha and TNF-beta and granulocyte macrophage-colony-stimulating factor . Stimulation with SPE-A lead to extensive lymphokine and monokine production . With the addition of IVIg prior to stimulation there was a strong reduction of blast transformation and an almost complete inhibition of lymphokine production, in particular in the synthesis of IFN-gamma and TNF-beta while the synthesis of IL-1 and IL-8 was either unaffected or increased . Adding IVIg 24 h after SPE-A stimulation also resulted in reduced blast transformation and decreased synthesis of IFN-gamma and TNF-beta . These results indicate an immunomodulatory potential by IVIg on streptococcally induced T cell activation and lymphokine production. Gastroenterology, 1994 Apr, 106(4), 960 - 72 Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats; McCall RD et al.; BACKGROUND/AIMS: Subserosal injection of purified group A streptococcal peptidoglycan-polysaccharide (PG-APS) induces chronic relapsing granulomatous enterocolitis and systemic inflammation in susceptible inbred Lewis rats but only transient intestinal injury in Buffalo and Fischer rats . Cecal interleukin 1 (IL-1) and IL-1 receptor antagonist (IL-1ra) expression was measured in inbred rats displaying differential susceptibility to experimental enterocolitis . METHODS: The ileum and cecum of Lewis, Buffalo, and Fischer rats were subserosally injected with purified PG-APS or albumin . IL-1 and IL-1ra messenger RNA (mRNA) and protein (IL-1 only) were measured 1 or 27 days later . PG-APS-injected Lewis rats were treated with recombinant human IL-1ra . Kinetics of IL-1 and IL-1ra mRNA expression were studied in peritoneal cells . RESULTS: All rats strains developed acute inflammation with increased cecal concentrations of IL-1 beta and IL-1ra mRNA . Lewis rats developed chronic enterocolitis and had higher IL-1 and IL-1ra mRNA tissue levels than Buffalo or Fischer rats, which displayed no chronic inflammation . IL-1 beta and IL-1ra were produced by submucosal granulomas and correlated with inflammation . IL-1 alpha protein levels paralleled IL-1 beta mRNA expression . IL-1ra treatment attenuated acute and chronic enterocolitis, adhesions, and arthritis . PG-APS induced IL-1 and IL-1ra expression in peritoneal cells from Lewis and Fischer rats . CONCLUSIONS: Bacterial cell wall polymers stimulate IL-1 and IL-1ra expression in vivo and in vitro . These counterbalancing cytokines are increased in experimental enterocolitis and have important immunoregulatory roles in intestinal inflammation. Infect Immun, 1994 Apr, 62(4), 1336 - 47 Analysis of genes encoding two unique type IIa immunoglobulin G-binding proteins expressed by a single group A streptococcal isolate; Boyle MD et al.; An emm-like gene (emmL) and a fcrA gene from group A streptococcal strain 64/14 (emmL64/14 and fcrA64/14) were amplified by PCR and force cloned into the heat-inducible expression vector pJLA 602 . The emmL gene encoded a recombinant protein that bound human IgG1, IgG2, and IgG4 in a nonimmune fashion . This is the reactivity profile of a type IIa IgG-binding protein . The emmL64/14 gene product was antigenically similar to the previously identified high-molecular-weight type IIa IgG-binding protein of strain 64/14 and had an N-terminal sequence identical to that of the wild-type protein . The fcrA gene also encoded a recombinant protein with type IIa functional activity . This protein was similar to the lower-molecular-weight type IIa IgG-binding protein previously isolated from strain 64/14 and was antigenically distinct from the higher-molecular-weight type IIa protein encoded by the emmL64/14 gene . The sequences for both genes including the intervening regions are presented . The emmL gene demonstrates significant homology to other class I emm and emmL genes expressed by opacity factor-negative group A streptococcal isolates . The fcrA gene was found to be homologous to other fcrA genes normally present in opacity factor-positive group A isolates . The sequence upstream of the fcrA gene and the intervening sequence between the end of the fcrA gene and the start of the emmL gene were similar to those reported for other fcrA genes. Am Surg, 1994 Apr, 60(4), 296 - 9 Eikenella corrodens as an intra-abdominal pathogen; Danziger LH et al.; Eikenella corrodens is a facultative anaerobe found as normal flora in the oral cavity, gastrointestinal system, and genitourinary tracts . It is most often associated with infections of the head and neck or those due to human bite wounds . However, the organism can be an important pathogen in intra-abdominal infections . Our case report and review of the literature revealed 19 cases of E . corrodens infections of the intra-abdominal cavity . The most common intra-abdominal site of infection was the appendix, noted in seven of the 19 reported cases . Abscess formation was noted in 15 of the 19 reports . The clinical course of the infection in most patients appeared to be indolent, evolving over several days . The majority (11 of 19) of patients described in these cases were less than 25 years old . E . corrodens is usually found concomitantly with other organisms . There appears to be a specific association between E . corrodens and streptococcal species . The drugs of choice for treatment of infections due to E . corrodens are ampicillin, penicillin, or a second generation cephalosporin . This organism is resistant to drugs traditionally active against anaerobic organisms, such as clindamycin and metronidazole. Sci China B, 1994 Apr, 37(4), 454 - 61 Engineered bacterial Fc receptors; Cai SY et al.; Five new-type Fc receptor molecules were constructed based on streptococcal protein G (SpG) and staphylococcal protein A (SpA) . These protein molecules contain one to six Fc binding domains to immunoglobulins which are structurally different from native SpG or SpA . Their expression levels reached 17-30% of the total bacterial proteins after heat induction in E . coli . Immunodiffusion and ELISA results showed that the engineered protein TG (184 amino acid residues) composed of three SpG C3 domain could bind more broadly and efficiently than the native SpG to the IgGs of human, goat, rabbit, etc., and its optimal pH for binding became wider (pH5-8) compared with the SpG (pH5); and the protein TGA (357AA), fused by protein TG and the A, B, C domains of SpA, displayed both the binding pattern of SpG and SpA. J Autoimmun, 1994 Apr, 7(2), 243 - 61 Identification of cardiac autoantigens in human heart cDNA libraries using acute rheumatic fever sera; Eichbaum QG et al.; Antigenic mimicry or cross-reactivity between Group A streptococcal antigens and cardiac autoantigens may initiate an autoimmune response resulting in cardiovascular damage in acute rheumatic fever . This study describes a molecular biological approach to the identification of such cross-reactive cardiac antigens . Two human heart cDNA libraries were constructed in the expression vector lambda gt11 and screened with patient sera, monoclonal antibodies and rabbit immune sera cross-reactive with streptococcal and cardiac antigens . Using the serum of a patient with a recurrent acute attack of rheumatic fever containing high titres of antibodies cross-reactive with both sets of antigens, we were able to identify three positive clones with insert sizes of 1.0 kb, 1.4 kb and 0.9 kb in these libraries . Acute rheumatic fever (ARF) sera reacted more strongly with these autoantigen clones than did normal sera . Autoantibodies eluted from the purified plaques of all three clones displayed different patterns of cross-reactivity against immunoblots of streptococcal M5, M6, M19 and M24 protein extracts . The cDNA inserts were sequenced and compared with known sequences in the EMBL and Genbank databases . One clone was 98% homologous with human cytokeratin 8 and showed homologies of 40 to 50% with human cardiac heavy chain myosin, tropomyosin and streptococcal M5 protein--all members of the alpha-helical coiled-coil family of proteins . Another clone was completely homologous to the G-protein alpha-subunit of adenyl cyclase, whilst the sequence of the third clone was not found in any of the data banks. Pediatr Nephrol, 1994 Apr, 8(2), 223 - 9 Syndromes with renal failure and shock; Levin M; Renal failure occurs commonly in children with shock, coagulopathy and multi-organ failure . Successful management of these patients requires not only management of the renal failure, but recognition and treatment of the underlying process . In addition to common and well-recognised causes of renal failure and shock, such as Gram-negative sepsis, there are a number of syndromes which are either less well recognised or confined to specific geographic locations . This article reviews the clinical and epidemiological features of the syndromes with shock and renal failure, focusing on the more recently recognised syndromes such as staphylococcal and streptococcal toxic shock syndrome, haemorrhagic shock and encephalopathy syndrome and viral haemorrhagic fevers. Pediatr Nephrol, 1994 Apr, 8(2), 214 - 5 Serum complement levels before and after the onset of acute post-streptococcal glomerulonephritis . A case report; Strife CF et al.; Low serum C3, properdin, and C5 levels found in the acute stage of acute post-streptococcal glomerulonephritis (APSGN) indicate the presence of aggressive complement activation . We followed serum complement component levels in a child hospitalized with erysipelas who developed APSGN on the 2nd hospital day . Her initial serum sample, obtained prior to the clinical onset of nephritis, had a low properdin level and normal C3 and C5 levels despite the presence of C3 splitting activity . Two days later she developed gross hematuria and subsequent sera contained low C3, properdin, and C5 levels, as is usual in APSGN . These observations suggest that complement activation, predominantly through the alternative pathway, precedes the clinical onset of APSGN. J Immunol Methods, 1994 Mar 29, 170(1), 37 - 45 Solid-phase antigen density and avidity of antibodies detected in anti-group B streptococcal type III IgG enzyme immunoassays; Feldman RG et al.; Two enzyme immunoassays which measure anti-group B streptococcal type III capsular carbohydrate IgG antibodies were compared . One utilised poly-L-lysine conjugated coating antigen while the other used tyraminated coating antigen . Both carbohydrate antigens appeared to be antigenically identical but the poly-L-lysine based assay gave significantly lower values for some sera . Sera were identified which had low and high avidity anti-group B streptococcal type III IgG antibodies by the thiocyanate elution method . These antibodies gave results on a dilution range of coating concentrations consistent with their relative avidity . Comparison of dilution ranges of the two conjugates used for coating suggests that the poly-L-lysine conjugate coats with a ten-fold lower efficiency than the tyramine conjugate and therefore detects only higher avidity antibodies . Four fractions containing different relative avidities of affinity-purified IgG were produced from a single serum . These fractions behaved in the same manner as sera containing antibodies of different avidities . The results of this study suggest that the method of polysaccharide conjugation in enzyme immunoassays may affect the antigen concentration on the solid phase and thence the detection of antibodies of various avidities. J Crit Care, 1994 Mar, 9(1), 34 - 46 The effects of intravenous L-arginine supplementation on systemic and pulmonary hemodynamics and oxygen utilization during group B streptococcal sepsis in piglets; Rudinsky B et al.; PURPOSE: In these investigations, three questions were addressed . First, to what extent did inhibition of endothelium-derived relaxation factor (EDRF) mimic the hemodynamic disturbances noted in a piglet model of neonatal group B streptococcal (GBS) sepsis? Second, to what extent would an attempt to augment EDRF production reverse the hemodynamic effects of continued GBS infusion in septic piglets? Third, to what extent would an attempt to augment EDRF production affect hemodynamics in piglets who were not septic . METHODS: Six experimental protocols were studied in a total of 25 piglets . The extent to which inhibition of EDRF resembled GBS sepsis was determined by comparing hemodynamic observations during (1) EDRF inhibition (using a competitive inhibitor of nitric oxide synthase, N-nitro-L-arginine {NNLA}, 80 mg/kg) with (2) GBS infusion . Next, the extent to which an attempt to augment EDRF production would reverse hemodynamic effects of neonatal GBS sepsis was addressed by comparing hemodynamic observations during (3) administration of pharmacological doses (300 mg/kg) of the EDRF precursor L-arginine (L-ARG) in piglets receiving continuous GBS infusion with (4) continuous GBS infusion in piglets who did not receive L-ARG . Finally, to provide an additional comparison for the protocols described above, the effects of (5) L-ARG in piglets pretreated with NNLA were compared with (6) L-ARG infusion in normal piglets, who had received neither GBS nor NNLA . RESULTS: Both NNLA and GBS increased systemic and pulmonary vascular resistance and decreased systemic cardiac output . For equivalent reductions in cardiac output, GBS preferentially vasoconstricted the pulmonary versus systemic circulation, whereas NNLA produced equivalent vasoconstriction in both circulations . During continuous GBS infusion, L-ARG attenuated the progressive increase in systemic and pulmonary vascular resistance, pulmonary artery pressure, and pulmonary vascular resistance/systemic vascular resistance . L-ARG infusion in nonseptic, non-NNLA-treated piglets had no significant effect on any hemodynamic variable . L-ARG infusion in piglets pretreated with NNLA restored hemodynamic values towards those of piglets treated with L-ARG alone . CONCLUSIONS: EDRF inhibition with NNLA appeared to model GBS infusion partially but not completely . L-ARG appeared to produce desirable hemodynamic effects during GBS sepsis when compared with the consequences of ongoing GBS infusion without L-ARG . Given the constellation of increased pulmonary and systemic vascular resistance often observed during neonatal GBS sepsis in human infants, all these effects of L-ARG, if extrapolated from our piglets to the clinical arena, would appear to be beneficial . Particularly in the context of deleterious consequences resulting shunting or right ventricular decompensation from increased afterload), L-ARG administration might prove clinically useful. Hautarzt, 1994 Mar, 45(3), 179 - 83 {Schoenlein-Henoch purpura associated with chronic post-traumatic osteomyelitis}; Anegg B et al.; In Schonlein-Henoch purpura, a distinctive form of leucocytoclastic vasculitis, immune complex deposits in vessel walls characteristically contain IgA . Complement activation, neutrophil chemotaxis and the subsequent destruction of vessel walls make up the pathologic substrate behind the clinical symptoms, which are characterized by palpable purpura lesions, renal and gastrointestinal symptoms and arthralgias . Viral infections, malignant neoplasms and drugs, but especially streptococcal infections, are incriminated as possible causes of the disease . A case of Schonlein-Henoch purpura associated with chronic osteomyelitis is described . It is note-worthy insofar as there is only one similar case reported in the literature. J Infect Dis, 1994 Mar, 169(3), 658 - 61 The presence of M protein in nontypeable group A streptococcal upper respiratory tract isolates from Southeast Asia; Tran PO et al.; Previous studies have suggested that group A streptococcal strains from southeast Asia, serotypically different from temporally related North American and European isolates, may represent unrecognized M serotypes . Sixty non-M typeable group A streptococcal upper respiratory tract isolates from Thailand were evaluated for the presence of M protein using a modification of the direct serum bactericidal test . Of them, 59 (98%) grew rapidly in human blood . Typeability by T agglutination and opacity factor production did not influence their growth in blood . It was concluded that these isolates produce M protein and likely represent previously uncharacterized M serotypes . Identification of such non-M typeable strains is important in understanding the epidemiology and pathogenesis of group A streptococcal infections and their sequelae in areas of the world where they remain a significant health problem and will also be necessary in the development of a vaccine with global efficacy. Am J Med, 1994 Mar, 96(3), 211 - 9 Evaluation of new clinical criteria for the diagnosis of infective endocarditis; Bayer AS et al.; PURPOSE: The clinical diagnosis of infective endocarditis (IE) can be difficult . A new diagnostic schema for IE (the Duke criteria) has been proposed, utilizing clinical, microbiologic, and echocardiographic data . We evaluated the Duke criteria in a cohort of prospectively enrolled patients suspected of having IE and compared the diagnostic efficiency of these criteria with the previously published criteria of von Reyn . PATIENTS: Sixty-three febrile patients with suspected IE at a non-referral, municipal hospital were evaluated . All patients had the following parameters defined: the presence and nature of underlying heart disease; recent abuse of intravenous drugs; peripheral stigmata of IE; blood culture results; findings on two-dimensional transthoracic and transesophageal echocardiography (TTE, TEE); and the results of open heart surgery . RESULTS: Twelve of 63 patients underwent open heart surgery, at which time IE was pathologically confirmed in 10 patients and excluded in 2 patients . All 10 patients with pathologically confirmed IE were classified as "clinically definite" by Duke criteria, whereas 5 of 10 were rejected by von Reyn criteria (p < 0.05) . Among the remaining 51 patients suspected of IE and evaluated by both von Reyn and Duke clinical criteria, significantly more cases were classified as "definite" IE by Duke criteria than by von Reyn criteria (p < 10(-5)) . Similarly, significantly fewer cases were rejected as IE by the Duke criteria as compared with the von Reyn criteria (p < 10(-6) . Duke criteria were also significantly better at diagnosing IE than von Reyn criteria in the following clinical settings: suspected right-sided IE (p < 0.01); suspected left-sided IE (p = 0.014); suspected culture-negative IE (p < 10(-2); and IE complicating Staphylococcus aureus or viridans streptococcal bacteremias (p < 10(-5); p < 0.05, respectively) . Among 30 cases defined as clinically definite by the Duke criteria, the presence of blood culture positivity and echocardiographically defined vegetations was important in this classification of 77% and 57% of cases, respectively . Among the 17 patients in the clinically definite category with vegetative endocarditis observed by echocardiography, 7 (41%) had vegetations defined only by TEE . CONCLUSION: The Duke criteria are superior to the von Reyn criteria for the clinical diagnosis of IE, predominantly reflecting use of two-dimensional echocardiographic demonstration of valvular vegetations in the Duke schema. Am J Obstet Gynecol, 1994 Mar, 170(3), 910 - 7 Intrapartum chemoprophylaxis of perinatal group B streptococcal infections: a critical review of randomized controlled trials; Ohlsson A et al.; The purpose of this overview was to critically appraise all published randomized, controlled trials evaluating the efficacy of intrapartum chemoprophylaxis in reducing perinatal group B streptococcal infections . The Oxford Database of Perinatal Trials, Medline, Excerpta Medica, and personal files were used for the literature search . By means of present inclusion criteria to select relevant articles, two independent researchers identified nine randomized, controlled trials . Three trials were excluded because of duplicate publication, one because the randomization process was violated, and one because the outcome data were collected retrospectively . The quality of the methods of the four accepted trials was poor, and because of basic flaws meta-analyses of trial results were not performed . Results of three studies showed a statistically significant reduction in neonatal group B streptococcal colonization rates with intrapartum chemoprophylaxis . Although a trend toward a reduction in proved neonatal infection was reported in three studies, each lacked the power to reach statistical significance . Intrapartum chemoprophylaxis to reduce perinatal group B streptococcal infections is not supported by conclusive evidence from well designed and conducted randomized, controlled trials. Obstet Gynecol, 1994 Mar, 83(3), 367 - 71 An analysis of the cost-effectiveness of selected protocols for the prevention of neonatal group B streptococcal infection; Yancey MK et al.; OBJECTIVE: To determine the expected neonatal outcome in a hypothetical obstetric population with various screening and intrapartum management protocols for the prevention of neonatal group B streptococcal infections . METHODS: We used decision analysis to investigate the performance of various antenatal and intrapartum group B streptococcal screening protocols combined with selective or universal intrapartum antibiotic prophylaxis in preventing neonatal early-onset group B streptococcal disease . Population characteristics, screening test performance, and treatment efficacy profiles were abstracted from previous investigations . RESULTS: In the absence of screening or treatment, the estimated neonatal attack rate and mortality rate were 3.6 and 0.60 cases per 1000 neonates, respectively . Universal antenatal screening at 26-28 weeks' gestation and selective intrapartum prophylaxis (treatment of colonized women with risk factors) or nonselective prophylaxis (treatment of all colonized women) had attack rates of 1.64 and 1.08 and mortality rates of 0.21 and 0.18 cases per 1000 neonates, respectively . Rapid intrapartum screening and selective prophylaxis had an estimated attack rate of 1.92-2.58 and a mortality rate of 0.26-0.40 cases per 1000 neonates, with results dependent upon the time required to attain test results . Similarly, rapid intrapartum screening and nonselective prophylaxis had an attack rate of 1.44-2.30 and a mortality rate of 0.24-0.38 cases per 1000 neonates . Empirical prophylaxis of all women delivering prematurely, regardless of culture status, had an attack rate of 2.40 and mortality rate of 0.36 cases per 1000 neonates . CONCLUSIONS: Under ideal circumstances, antenatal group B streptococcal screening at 26-28 weeks' gestation with vaginal-rectal cultures and subsequent intrapartum prophylaxis is associated with lower projected neonatal attack and mortality rates than protocols using rapid intrapartum screening methods . However, in a non-research population, difficulties frequently encountered with antenatal screening procedures may minimize these differences. Aust N Z J Surg, 1994 Mar, 64(3), 194 - 6 Streptococcal myonecrosis: survival by aggressive surgical management; Allen CP; Eight consecutive cases of skeletal muscle infections due to streptococcal species are presented . The clinical presentation of the condition and recommendations for treatment by early recognition and aggressive, early surgical intervention together with high doses of penicillin are discussed . Advancing age was associated with poor survival rates. J Mol Biol, 1994 Jan 21, 235(3), 983 - 1002 Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins; Abagyan R et al.; Two major components are required for a successful prediction of the three-dimensional structure of peptides and proteins: an efficient global optimization procedure which is capable of finding an appropriate local minimum for the strongly anisotropic function of hundreds of variables, and a set of free energy components for a protein molecule in solution which are computationally inexpensive enough to be used in the search procedure, yet sufficiently accurate to ensure the uniqueness of the native conformation . We here found an efficient way to make a random step in a Monte Carlo procedure given knowledge of the energy or statistical properties of conformational subspaces (e.g . phi-psi zones or side-chain torsion angles) . This biased probability Monte Carlo (BPMC) procedure randomly selects the subspace first, then makes a step to a new random position independent of the previous position, but according to the predefined continuous probability distribution . The random step is followed by a local minimization in torsion angle space . The positions, sizes and preferences for high-probability zones on phi-psi maps and chi-angle maps were calculated for different residue types from the representative set of 191 and 161 protein 3D-structures, respectively . A fast and precise method to evaluate the electrostatic energy of a protein in solution is developed and combined with the BPMC procedure . The method is based on the modified spherical image charge approximation, efficiently projected onto a molecule of arbitrary shape . Comparison with the finite-difference solutions of the Poisson-Boltzmann equation shows high accuracy for our approach . The BPMC procedure is applied successfully to the structure prediction of 12- and 16-residue synthetic peptides and the determination of protein structure from NMR data, with the immunoglobulin binding domain of streptococcal protein G as an example . The BPMC runs display much better convergence properties than the non-biased simulations . The advantage of a true global optimization procedure for NMR structure determination is its ability to cope with local minima originating from data errors and ambiguities in NMR data. Arch Intern Med, 1994 Jan 10, 154(1), 26 - 34 Gram-positive organisms and sepsis; Bone RC; In recent years, the importance of gram-negative organisms in the genesis of sepsis has been emphasized . However, this emphasis may no longer be correct; recent studies show an increasing incidence of gram-positive sources of sepsis, and its is possible that these cases may predominate in the coming years . This increase results from more than just a greater prevalence of infection--it appears that gram-positive organisms may also be more virulent in fomenting the disease, as can be evidenced by the emergence of streptococcal toxic shock syndrome and the resurgence of acute rheumatic fever . This may result from the ability of gram-positive organisms to produce more inflammation-causing cell wall constituents, as well as unbound exotoxins . Despite the recent emphasis on gram-negative causes, sepsis resulting from gram-positive sources is increasingly common . Research on these causes of sepsis should be encouraged. Cancer Chemother Pharmacol, 1994, 33(5), 366 - 70 Postoperative chemotherapy including intraperitoneal and intradermal administration of the streptococcal preparation OK-432 for patients with gastric cancer and peritoneal dissemination: a prospective randomized study; Sugimachi K et al.; We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination . The patients were prospectively randomized and a valid statistical assessment could be made for 109 . Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4, for 1 year . Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i.p . for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals . There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432 . There was no difference in the toxicity rate between the groups . In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination. Immunopharmacology, 1994 Jan-Feb, 27(1), 31 - 41 Augmented local immunity in the liver by a streptococcal preparation, OK432, related to antitumor activity of hepatic macrophages; Mise M et al.; The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of hepatic macrophages . We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha, beta, and TNF alpha in the liver . The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation reached a maximal level at 3 h . TNF production of hepatic macrophages was also increased by the intravenous injection of OK432 . Furthermore, OK432 significantly increased the proportion of IL-2 receptor-positive hepatic macrophages . As for antitumor activity in the liver being augmented by OK432, the cytotoxic and cytostatic activity of hepatic macrophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in the liver after the inoculation of tumor cells via the portal vein . These findings, which indicate that OK432 has various immuno-stimulating actions on hepatic macrophages, leading to the augmentation of antitumor activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activation of hepatic macrophages. Acta Otolaryngol Suppl, 1994, 511, 214 - 7 Neutrophil activating activity of tonsillar cells from patients with tonsillitis; Ohta N et al.; The previous paper demonstrated that tonsillar cells cultured in vitro in the presence or absence of a streptococcal preparation, OK-432, produce factors that activate various neutrophil functions . In the present study, examination was made of the factor productivity of tonsillar cells from patients with chronic tonsillitis of varying severity, and palmoplantar pustulosis (PPP) . Tonsillar cells from patients with severe tonsillitis and PPP incubated with culture medium alone produced a much greater amount of active factors compared with those from patients with mild tonsillitis . When tonsillar cells were incubated in the presence of OK-432, augmentation in factor production by the addition of OK-432 was less in former than latter cases, suggesting that factor production from tonsils correlates with the course of inflammation in this organ. Acta Otolaryngol Suppl, 1994, 511, 208 - 13 Effects of supernatant from tonsillar cell culture on neutrophil functions; Ohta N et al.; The palatine tonsil is the most important element of Waldeyer's ring as a defense mechanism against various microorganisms . The neutrophils are the initial active participants in bacterial infection and inflammation, but their interaction with other cellular participants is poorly understood . To clarify this point, the effects of culture supernatant from human tonsillar cells on the peripheral neutrophil function were investigated . Supernatants from tonsillar cells were incubated in the presence or absence of streptococcal preparation (OK-432) enhanced chemiluminescence, adherence, phagocytosis, chemotaxis, and superoxide production of human peripheral neutrophils . The results suggest that tonsils play an important role in the regulation of neutrophil function. Curr Opin Cardiol, 1994 Jan, 9(1), 121 - 9 Acquired heart disease in children; Bezold LI et al.; Recent advances have been made in understanding Kawasaki disease, acute rheumatic fever and rheumatic heart disease, cardiomyopathy, and acquired immunodeficiency syndrome . Immune-mediated tissue injury in Kawasaki disease is likely caused by response to a superantigen . Persistent functional and anatomic coronary abnormalities may lead to silent ischemia and increase the risk of early atherosclerotic heart disease . Intravenous immunoglobulin therapy is clearly beneficial, but specific therapy awaits further definition of the etiology and pathophysiology of Kawasaki disease . Recently updated diagnostic criteria for Kawasaki disease and acute rheumatic fever are discussed . Advances in the understanding of genetically determined abnormal immune responses to streptococcal pharyngitis may help explain acute rheumatic fever manifestations . Further advances have been made in the elucidation of the pathophysiology of cardiomyopathy, particularly the role of viruses and genetic factors . Angiotensin-converting enzyme inhibitors appear to improve survival in dilated cardiomyopathy . Controversy regarding the possible myocardial depressant effect of zidovudine in human immunodeficiency virus infection is discussed. Nephrologie, 1994, 15(1), 17 - 20 {Acute interstitial nephritis and streptococcal infection}; Kolko A et al.; Two patients with acute renal failure and streptococcal erysipela are reported . In both cases, renal biopsy showed acute interstitial nephritis with a predominantly mononuclear infiltrate . Beta lactam antibiotic without steroid therapy was followed by complete recovery of renal function . It seems likely that some cases of AIN related to infection are erroneously attributed to antibiotic hypersensitivity. Mol Microbiol, 1994 Jan, 11(2), 363 - 74 Horizontal gene transfer in the evolution of group A streptococcal emm-like genes: gene mosaics and variation in Vir regulons; Whatmore AM et al.; Most M type 5 group A streptococcal strains were found to contain a single emm-like gene between virR and scpA (the Vir regulon), but two distinct emm-like genes were identified in the Vir regulon of the M5 strain NCTC8193 . The complete sequences of both of these genes were determined . One, called emm5.8193, was shown to be a minor variant of the previously described emm5 gene from strain Manfredo . The second, designated enn5.8193, expresses an IgG-binding protein when cloned in Escherichia coli . A comparison of enn5.8193 with emm-like gene sequences from other strains indicated that it has a mosaic structure, consisting of distinct segments originating from emm-like genes in different OF+ and OF- strains . These data provide the first clear evidence that the horizontal transfer of emm-like sequences between distinct strains contributes to the evolution of group A streptococcal emm-like genes and Vir regulons. Int J Immunopharmacol, 1994 Jan, 16(1), 7 - 17 Enhancement of polymorphonuclear leukocyte (PMN) function by OK-432; Ueta E et al.; The influence of OK-432, a streptococcal preparation, on human polymorphonuclear leukocytes (PMN) was examined . OK-432 increased O2- generation was also observed when PMN were cultured with 10(-2)KE/ml OK-432 for 1 h and then stimulated with phorbol myristate acetate or formyl-metionyl-leucil-phenylalanine (FMLP) . In addition, PMN O2- generation was promoted by culture supernatants of peripheral blood mononuclear cells (PBMC) incubated with 10(-3) or 10(-2) KE/ml OK-432 . Furthermore, OK-432 (10(-3)-10(-2) KE/ml) enhanced the chemiluminescence of FMLP- and PMA-stimulated PMN . However, nitroblue tetrazolium reduction and myeloperoxidase activity were only minimally enhanced . Not only the candidacidal activity of PMN but also antibody-dependent cell-mediated cytotoxicity against Candida and Raji cells were enhanced in correspondence with the increased generation of reactive oxygen species . Culture of PMN or PBMC for 24 h with OK-432 resulted in a concentration-dependent increase in the substantial production of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha . OK-432 also enhanced granulocyte-macrophage colony stimulating factor and gamma-interferon generation by leukocytes in a dose-dependent manner . Our research indicates that OK-432 enhances PMN function directly as well as via the promotion of cytokine production, and suggests that these effects of OK-432 could be beneficial in immunosuppressed patients. Protein Sci, 1994 Jan, 3(1), 15 - 21 Investigation of the backbone dynamics of the IgG-binding domain of streptococcal protein G by heteronuclear two-dimensional 1H-15N nuclear magnetic resonance spectroscopy; Barchi JJ Jr et al.; The backbone dynamics of the immunoglobulin-binding domain (B1) of streptococcal protein G, uniformly labeled with 15N, have been investigated by two-dimensional inverse detected heteronuclear 1H-15N NMR spectroscopy at 500 and 600 MHz . 15N T1, T2, and nuclear Overhauser enhancement data were obtained for all 55 backbone NH vectors of the B1 domain at both field strengths . The overall correlation time obtained from an analysis of the T1/T2 ratios was 3.3 ns at 26 degrees C . Overall, the B1 domain is a relatively rigid protein, consistent with the fact that over 95% of the residues participate in secondary structure, comprising a four-stranded sheet arranged in a -1, +3x, -1 topology, on top of which lies a single helix . Residues in the turns and loops connecting the elements of secondary structure tend to exhibit a higher degree of mobility on the picosecond time scale, as manifested by lower values of the overall order parameter . A number of residues at the ends of the secondary structure elements display two distinct internal motions that are faster than the overall rotational correlation time: one is fast (< 20 ps) and lies in the extreme narrowing limit, whereas the other is one to two orders of magnitude slower (1-3 ns) and lies outside the extreme narrowing limit . The slower motion can be explained by large-amplitude (20-40 degrees) jumps in the N-H vectors between states with well-defined orientations that are stabilized by hydrogen bonds.(ABSTRACT TRUNCATED AT 250 WORDS) Kekkaku, 1994 Jan, 69(1), 21 - 5 {Henoch-Schönlein purpura associated with pulmonary tuberculosis}; Mishima Y et al.; A 34-year-old man was admitted to our hospital because of cough and fever . Chest radiograph showed multiple cavities mainly on the right lung . His sputum was positive for acid-fast bacilli on smear, and he was treated with daily isoniazide, rifampicin and streptomycin . Antituberculous treatment was successfully performed, so acid-fast bacilli of his sputa disappeared on smear and culture . Five months later, he developed a purpuric lesions over both legs accompanied by low grade fever and arthralgia, but proteinuria and abdominal pain could not be observed . Laboratory findings showed a normal platelet count and a normal bleeding time . High levels of serum IgG, IgA, C3 and C4 were evident . ASLO and ASK titer were elevated and they markedly increased within two weeks . A direct invasion of the vessel wall by tubercle bacilli is deniable because antituberculous treatment was successfully continued . Henoch-Schonlein purpura was diagnosed judging from these findings . High levels of ASLO and ASK suggest a preceding streptococcal infection for developing purpura but a possible infectious focus could not be identified . He was treated with 15 mg of prednisolone daily for two weeks and the lesion was subsided . The effect of prednisolone suggests that a subsequent antigen-antibody interaction caused by a streptococcal infection may participate in the formation of the purpura. Surg Today, 1994, 24(1), 54 - 8 OK-432-combined adoptive immunotherapy as a prognostic factor in peritoneal metastasis from gastric cancer; Mise K et al.; Prognostic factors, such as preoperative status, intraoperative findings, and postoperative treatments, were evaluated in 61 patients with peritoneal metastasis from gastric cancer treated in our facility between 1979 and 1991 . Since 1986, 23 patients have been treated with OK-432-combined adoptive immunotherapy (AIT) . OK-432-combined AIT is a sequential treatment via a catheter inserted into the abdominal cavity, using a streptococcal preparation, OK-432, followed by the transfer of lymphocytes cultured with T cell growth factor and sonicated tumor extract . A univariate analysis showed that six factors consisting of: (1) age, (2) resection of primary lesion, (3) grade of peritoneal metastasis or serosal invasion, (4) chemotherapy, (5) OK-432, and (6) OK-432-combined AIT influenced survival . The survival of the patients given OK-432-combined AIT (median survival time; MST = 7.5 months) was significantly (P = 0.0267) longer than that of those not receiving OK-432-combined AIT (MST = 4.3 months) . A multivariate analysis showed that the most significant factors associated with survival were chemotherapy, resection of the primary lesion, and OK-432-combined AIT . Since these three factors are all therapeutic procedures, the use of combination therapy including OK-432-combined AIT is thus expected to prolong the survival of gastric cancer patients with peritoneal metastasis. Biol Neonate, 1994, 66(2-3), 128 - 36 Influence of disease state on oxygen transport in newborn piglets; Hammerman C; Optimally, oxygen delivery (DO2) should be sufficient to provide for adequate oxygen consumption (VO2) while avoiding O2 toxicity . Physiologically a critical level of DO2 has been described, below which decreases in oxygen supply begin to impair VO2, leading to venous hypercarbia and tissue acidosis . We predicted that this critical level would be influenced by factors such as underlying disease state and oxygen needs . Newborn piglets were exposed either to hypoxia (n = 6) or to group-B beta-hemolytic streptococcal sepsis (n = 6) . Hemodynamic parameters were measured; DO2 and VO2 were calculated and compared within and between the groups . 'Critical DO2' was defined as the point at which decreases in DO2 began to produce concomitant decreases in VO2 . This was observed at 9 ml/kg/min in hypoxic vs . 21 ml/kg/min in septic piglets . The 'critical Vsat' was defined as the venous O2 saturation beyond which tissue acidosis, as defined by base excess, developed . 'Critical VsatS' were 17% for hypoxic vs . 21% for septic animals . In summary, septic newborn piglets had higher critical DO2 and critical Vsat than hypoxic piglets, implying that they became oxygen supply dependent and developed tissue acidosis at higher levels of DO2 and Vsat, respectively. Surg Today, 1994, 24(6), 506 - 11 The elevation of plasma soluble tumor necrosis factor receptor levels by TNF induction therapy for patients with malignancy; Abe Y et al.; Soluble tumor necrosis factor receptor (sTNF-R) is known to inhibit patient immunity via specific binding with the TNF molecule . To examine the possible involvement of sTNF-R in cancer immunotherapy, the plasma levels of sTNF-R of both 55 kDa and 75 kDa origins were estimated when TNF was induced in patients with malignancy using both a polysaccharide preparation (Lentinan) and a streptococcal preparation (OK-432) . The pretreatment plasma levels of the 55 kDa and 75 kDa sTNF-R were 1.04 +/- 0.53 and 1.06 +/- 0.34 ng/ml (mean +/- SE), respectively . The plasma levels of TNF were undetectable before treatment . The plasma sTNF-R levels peaked 2 h after the administration of OK-432 and followed the same pattern as the TNF levels in plasma . Both TNF and sTNF-R nearly returned to pretreatment levels at 16 h after the induction of TNF . The peak plasma levels of the 55 kDa and 75 kDa sTNF-R were 2.46 +/- 0.95 and 3.03 +/- 0.88 ng/ml, respectively, but they did not correlate with the plasma TNF levels . When peripheral white blood cells were cultured with the addition of lipopolysaccharide in vitro, an elevation of the 72 kDa sTNF-R was detected . Thus, the plasma source of this soluble receptor can at least be partly attributed to the white blood cells . However, the 55 kDa sTNF-R showed little increase in the cultures, and its source remains unknown . We should therefore be aware of the elevation of plasma sTNF-R levels by the induction therapy of TNF for patients with malignancies because of the immunosuppressive effect of sTNF-R. Int Urol Nephrol, 1994, 26(5), 573 - 7 Cytokine secretion by peripheral blood monocytes from patients with acute poststreptococcal glomerulonephritis; Matsumoto K; We have measured the release of interleukin-1 beta (IL-1) and tumour necrosis factor-alpha (TNF) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of two patients with acute poststreptococcal glomerulonephritis (AGN) and 16 healthy controls . We have demonstrated that spontaneous and LPS-induced cytokine release correlated with disease activity in the AGN patients . We speculate that in vivo streptococcal infection itself may alter peripheral blood monocyte cytokine secretion. Arch Anat Cytol Pathol, 1994, 42(3-4), 163 - 70 Perinatal death and thymus gland; Agapitos E et al.; Three hundred (300) cases of perinatal death were autopsied and the thymus was removed for histologic examination . The histologic findings were classified into five groups: a) normal-mature thymus, b) involutional changes--"Starry sky" pattern, c) involutional changes--intense lymphocytic depletion, d) hypoplasia--aplasia, e) agenesis . The perinatal deaths were classified into five groups according to Wigglesworth's classification: 1) normally formed macerated stillborn neonates, 2) congenital malformations, 3) conditions associated with immaturity, 4) asphyxial conditions developing in labor, 5) other specific conditions (e.g . known-beta-hemolytic streptococcal infection or a fatal inborn error of metabolism) . The main objective was to identify a possible correlation between sex, gestational age, birth weight, thymus weight, histologic features of the thymus and cause of death . In conclusion, a strong correlation was found between: a) weight of thymus and gestational age, b) weight of thymus and birth weight, c) weight of thymus and its histologic features, d) histologic features of thymus and cause of death, e) weight of thymus and cause of death, f) gestational age and cause of death . No correlation was found between: a) gestational age and histologic features of thymus, b) birth weight and histologic features of thymus, c) weight of thymus and sex, d) histologic features of thymus and sex, e) cause of death and sex. Medicina (B Aires), 1994, 54(3), 193 - 8 {Infective endocarditis and drug addiction}; De Rosa A et al.; A total of 103 patients (P) with infectious endocarditis (IE) were treated during the period 1982-1993; 72% of them were male . Mean age was 46.4 (SD 19.7) . Eighteen patients were intravenous drug addicts (D) (17.5%) . The first case of drug addiction in the IE group was seen in 1986; since then, there was a steady increase of this condition, reaching 50% of all cases . The average age of D patients was 28.17 +/- 8.15 years significantly lower than that corresponding to non-drug addicts (ND), 48.64 +/- 19.5 (p < 0.00001) . The infection was located mainly in the left heart of the ND (93%), and in the right heart of the D (78%), the difference being statistically significant . All the cases of left IE occurred on previously damaged valves . Right location in ND was found in all cases in immunosuppressed individuals being treated for systemic diseases, except in one patient having an endocavitary pacemaker . No differences were found between ND and D with regard to the presence of fever, cutaneous manifestations, splenomegaly or cerebrovascular accident . Differences were noted, however, in the case of respiratory involvement, which showed a significantly higher frequency in D (38.9% versus 12.9%; p < 0.014) . Blood cultures were positive in 81.6% of the total number of patients, no difference being found between the two groups . Staphylococcal infections were predominant in D (44%) and streptococcal infections in ND (48%), the difference being statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) J Pediatr, 1994 Jan, 124(1), 9 - 16 Persistence of acute rheumatic fever in the intermountain area of the United States; Veasy LG et al.; We report our 8-year experience with the resurgence of acute rheumatic fever during the years 1985 through 1992 . The records of 274 confirmed cases referred to Primary Children's Medical Center were reviewed . The clinical features including the presence of the Jones criteria, demographic data, preceding streptococcal infection, and the use of echocardiographic studies were tabulated and assessed . Patients came predominantly (84%) from middle-class families with access to medical care . Only 46 patients (17%) sought medical attention for a preceding sore throat . Carditis evident by auscultation was the dominant major manifestation in 68% of the cases . Echocardiography demonstrated mitral regurgitation that was not audible in 15 (47%) of 32 patients who had only polyarthritis at onset and in 30 (57%) of the 53 who had pure chorea . The incidence of acute rheumatic fever has been declining since the peak of the outbreak in 1985 but is continuing in the intermountain area at rates comparable to those of the 1960s. Rev Chir Orthop Reparatrice Appar Mot, 1994, 80(6), 551 - 4 {Necrotizing fasciitis of the foot . An unknown surgical emergency . Apropos of a case}; Rapp E et al.; INTRODUCTION: The purpose of this study was to review the literature concerning Necrotizing Fasciitis (N.F.) and to discuss a typical case where late diagnosis led to severe consequences . MATERIAL AND METHODS: A young male patient with no pertinent medical history, progressively developed a large swelling of his foot and severe pain 3-4 days following a simple contusion . The absence of an entry site lead to local incision without microbiological study . The patient developed blistering on the leg, then septic shock necessitating amputation . DISCUSSION: N.F . is an infectious necrosis of the sub-cutaneous tissue appearing frequently in surgical or post traumatic contexts . Streptococcal origin is classical but multibacterial anaerobic infection is more and more frequently observed . An entry site is not always found while the affected site becomes red, hot and painful . Evolution is extremely rapid with the appearance of blisters and cutaneous necrotic sites and a severe alteration in the general condition of the patient . The extent of sub-cutaneous necrosis is larger than the affected area of skin . N.F . is a surgical emergency . Treatment consists of complete debridement, sometimes very extensive and mutilating . High dose intra-venous antibiotic therapy is necessary while the benefits of hyperbaric therapy are discussed . Because of the lack of specific clinical signs, diagnosis is difficult and is often made too late . The rapidity of the evolution shows that vital and functional prognosis is better with early diagnosis and treatment even for patients without associated pathology . The rate of mortality is approximately 50 per cent . CONCLUSION: Better information of practitioners allowing a rapid clinical diagnosis could improve the prognosis which is still life-threatening in 1994. Autoimmunity, 1994, 19(3), 179 - 91 Localization of {14C} labeled anti-streptococcal cell membrane monoclonal antibodies (anti-SCM mAb) in mice; Lange CF; Six different hybridomas secreting anti-SCM mAb and one control mAb were placed into adult mice along with {14C} amino acids for biosynthetically labeling . After sacrifice, the 14C mAb ascites along with serum, heart, kidney, lung and skeletal muscle were recovered . Tissue associated specific radio-activity (SpAc) and microscopic structural analyses were performed . Confirmation of mAb specificity was by both immunodot blots as well as Western blot analysis . Peritoneal injection of measured doses of anti-SCM mAb yielded tissue SpAc confirming their in vitro specificities . Two of the mAb showed strong reactivity to both renal (GBM) and lung basement membrane (LBM), two were mainly GBM reactive and two showed polyreactivity with a marked reactivity to a Z-line antigen . Autoradiographic light microscopy confirmed that the anti-SCM mAbs bound to both GBM and LBM and to Z-line antigen . Titrated doses of the mAb yielded autoradiographic confirmation in which the grain number on the GBM and LBM increased with increasing dose of mAb for all mAb except the control . This effect was not seen in the muscle tissues but anatomical localization at the Z-line was consistent . The major significance of these studies is the demonstration that circulating antibodies to SCM can react in vivo with normal mammalian antigens adding confirmation to the in vitro specificity of these cross-reactive anti-SCM mAbs. Int J Immunopharmacol, 1994 Jan, 16(1), 19 - 28 Recombinant human granulocyte colony-stimulating factor augments cytotoxicity of OK-432-induced polymorphonuclear leukocytes; Inoue M et al.; Polymorphonuclear leukocytes (PMNs) recovered from the peritoneal cavity of mice treated with the streptococcal preparation OK-432, exhibited strong cytotoxicity after the in vitro addition of Nocardia rubra cell wall skeleton (N-CWS) . In this study, we investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could augment the cytotoxicity of OK-432-induced PMNs after the addition of N-CWS in vitro . PMNs recovered from the peritoneal cavity of 8- to 10-week-old, male C3H/He mice induced by intraperitoneal (i.p.) injection of 50 KE/kg (1 KE = 0.1 mg) of OK-432 were used in a 51Cr release assay against MM46 mammary carcinoma cells . While addition of rhG-CSF in vitro did not augment the cytotoxicity of OK-432-induced PMNs, marked augmentation of the cytotoxicity of OK-432-induced PMNs was observed following a single subcutaneous (s.c.) or i.p . injection of 125 micrograms/kg of rhG-CSF . The effect of in vivo administered rhG-CSF was dependent on the timing of the injection with respect to OK-432 administration and differed from s.c . or i.p . injections . Interestingly, the cytotoxicity of OK-432-induced PMNs was rather weak following consecutive s.c . or i.p . administration of rhG-CSF for 7-14 days . H2O2 is likely involved in mediating the cytotoxicity of OK-432-induced PMNs since activity was significantly reduced by the in vitro addition of low concentration of catalase . Generation of H2O2 by the PMNs correlated with cytotoxicity . These results suggest that in vivo administration of rhG-CSF augments the cytotoxicity of OK-432-induced PMNs in a time dependent fashion and that H2O2 plays an important role in mediating their cytotoxicity. Clin Obstet Gynecol, 1993 Dec, 36(4), 832 - 42 Management of group B streptococcal disease in pregnancy; Katz VL; GBS is a bacterium that may cause devastating disease . The puzzle of GBS management revolves around the fact that the organism colonizes 15-30% of women, yet produces infection in only 1-3% of the women who are colonized . Neonatal infection is acquired from the maternal genital tract . It ascends across the cervix into the amniotic cavity and also may be acquired during delivery . Manifestations of disease in the fetus and neonate may be out of proportion to those in the mother . Treatment strategies involve the screening all pregnant women with cultures at 26-28 weeks' gestation and rapid tests at the time of labor . Rapid testing has not proven successful, although current research should provide effective and sensitive rapid tests by the end of the decade . Once a woman is known to be GBS positive in labor, there are two options . Most investigators recommend giving chemoprophylaxis only to women who are at high risk for GBS infection--women with preterm labor, ruptured membranes for longer than 12-18 hours, or intrapartum fever higher than 37.5 degrees C . Others advocate treating all GBS carriers regardless of risk status . Treatment of mothers in labor eradicates vaginal carriage of GBS, though it does not eradicate GBS from the lower digestive tract . Intrapartum chemoprophylaxis decreases the incidence of neonatal colonization and significantly decreases the risk of infant disease . In the future, GBS infection probably will be prevented with immunoprophylaxis and vaccination. Eur J Immunol, 1993 Dec, 23(12), 3173 - 80 Generation of a novel CD8+ cytotoxic T lymphocyte that requires soluble factor to lyse autologous antigen-presenting cells; Yoshizumi H et al.; We reported the existence of high and low responders to the streptococcal cell wall antigen (SCW) in the human population . To analyze the mechanism of the low responsiveness to SCW at the cellular level, we established SCW-specific CD4+ T cell lines . During the course of generation of a SCW-specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8) . They proliferated in the presence of autologous monocytes and IL-2, without SCW . HYCD8 lysed autologous monocytes and Epstein-Barr virus-transformed B lymphoblastoid cell line (BLCL) . This cytotoxic activity was specifically inhibited by an anti-HLA class I framework monoclonal antibody and restricted by HLA-B52 or B54 specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCL . It was unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 10(4) Da) produced mainly by B cells, which could not be replaced by known cytokines and their mixtures . We thus describe novel HLA class I-restricted cytotoxic CD8+ T cells that kill antigen-presenting cells in a soluble factor-dependent manner. Cell Immunol, 1993 Dec, 152(2), 348 - 57 Preservation of the specificity of superantigen to T cell receptor V beta elements in the absence of MHC class II molecules; Kotb M et al.; Superantigens interact with specific V beta elements of the T cell receptor and consequently activate all T cells bearing those elements . The ability of superantigens to stimulate T cells depends on the presence of APC that express MHC class II molecules on their surface . The question we are addressing is: do superantigens have to be seen in context of MHC class II molecules, or can they be recognized directly by T cell-receptor elements? We have previously shown that the APC requirement for the stimulation of T cells by the streptococcal superantigen, pep M5, can be bypassed by the addition of PMA and cytokines or by crosslinking CD28 molecules . Here we asked if the response of APC-depleted T cells to this superantigen is V beta-restricted and whether in the presence of PMA and cytokines the specificity of pep M5 to V beta elements is altered . We provide evidence that in the absence of APC, but in the presence of PMA and cytokines, the specificity of pep M5 to V beta elements is identical to that observed when APC are present, with V beta 2, V beta 4, and V beta 8 being significantly expanded . In addition, we ruled out the possibility that the response is due to a minor contamination with APC or to the expression of DR molecules on T cells because anti-HLA class II monoclonal antibodies did not block the reconstituted response, whereas they totally abrogated the response in the presence of APC . We conclude that pep M5 does not have to complex with MHC class II molecules in order to interact with specific V beta elements . In addition, we propose that the inhibitory effects of the anti-class II antibodies when APC are present may be due to preventing pep M5 from binding and activating APC, thereby blocking the production of costimulatory molecules necessary for T cell activation by this superantigen. Clin Immunol Immunopathol, 1993 Dec, 69(3), 318 - 23 Prevention of type I diabetes with lymphotoxin in BB rats; Takahashi K et al.; We previously reported that nonspecific immunomodulations with a streptococcal preparation (OK-432), an inducer of tumor necrosis factor (TNF), or with recombinant TNF prevented development of insulin-dependent diabetes mellitus (IDDM) in animal models (NOD mice and BB rats) . Recently we have further reported that lymphotoxin (LT), a cytokine with functional and structural characteristics similar to those of TNF, also protected NOD mice from diabetes . In this study, we have extended our observation on the LT to BB rats . Male and female BB/Wor rats were treated intraperitoneally with recombinant human LT three times a week from 4 to 11 weeks of age . The cumulative incidence of diabetes by 14 weeks of age was 24/30 (80.0%) in nontreated control rats, whereas it was 10/26 (38.5% vs control, P < 0.01) and 4/29 (13.8% vs control, P < 0.0001) in the rats treated with 1 x 10(3) and 1 x 10(4) of LT, respectively . There was no significant difference in nonfasting blood glucose levels and body weights between nontreated control and LT-treated rats, which were nondiabetic . In the LT-treated rats, intensity of insulitis was significantly reduced in comparison with the nontreated rats . Concanavalin A-stimulated TNF/LT productivity of spleen cells was significantly lower in BB/Wor and BB/Sendai rats than in Wistar rats or other normal rat strains . On the other hand, there was no difference between BB/Sendai and Wistar rats in the in vivo TNF/LT productivity induced with LPS or with IFN-gamma plus LPS, and the TNF/LT productivity of these rats was lower on stimulation with LPS alone, but higher with IFN-gamma plus LPS than the other normal rats . These results indicate that treatment with LT, as well as TNF, modulated autoimmunity and prevented development of IDDM in BB/Wor rats which may be low producers of TNF/LT. Antimicrob Agents Chemother, 1993 Dec, 37(12), 2754 - 5 Effect of scrubbing and irrigation on staphylococcal and streptococcal counts in contaminated lacerations; Howell JM et al.; We studied the effects of scrubbing with poloxamer 188 (SCR), irrigating with povidone iodine (PI), and scrubbing followed by irrigation (SCR-PI) on staphylococcal and streptococcal counts in inoculated guinea pig lacerations . PI irrigation and SCR-PI significantly lowered streptococcal counts (P < 0.05) . Staphylococcal counts were not different from those in controls. Mol Phylogenet Evol, 1993 Dec, 2(4), 281 - 92 Molecular evolution of the staphylococcal and streptococcal pyrogenic toxin gene family; Van den Bussche RA et al.; The pyrogenic toxin (PT) family is composed of the staphylococcal enterotoxins (SE), the toxic shock syndrome toxin, and the streptococcal pyrogenic exotoxins (SPE) . Whereas considerable effort has focused on characterization of PTs due to their unique biological properties, our understanding of the evolution of this gene family is incomplete . Phylogenetic relationships for members of the PT family were estimated by examining the previously reported nucleotide sequences of the genes encoding SPEA, SPEC, SEA, SEB, SEC1, SEC2, SEC3, SED, and SEE . Additionally, we present and analyze sequence data on seven previously unreported sec genes . Within the PT family, sequence divergence was partitioned in a hierarchical fashion such that mean sequence divergence ranged from 1.179 among all 16 toxin genes, 0.443 among those restricted to Staphylococcus, and 0.028 among the genes encoding 10 variants of Type C SE . Results of this study are interpreted as suggesting that the PT family consists of two large clades . One clade consists of the staphylococcal toxins SEA, SEE, and SED, being closely related to the streptococcal toxin SPEC, whereas the other clade depicts close relationships of the staphylococcal toxins SEC and SEB with the streptococcal toxin SPEA. Tokai J Exp Clin Med, 1993 Dec, 18(3-6), 127 - 31 Evaluation of prognoses of patients with gastric cancer by the responsiveness of peripheral blood lymphocyte to OK432 in vitro; Shimura T et al.; The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients . When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05) . In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05) . There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9% . In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001) . The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis. Infect Immun, 1993 Nov, 61(11), 4835 - 41 Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells; Hulse ML et al.; Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated . A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay . The results demonstrated that capsule attenuated the invasion process . Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GBS capsular polysaccharide . Polyclonal type III GBS capsule antibody inhibited invasion by COH1 but did not affect invasion by the capsule mutants . Serotypes Ia, Ib, Ia/c, II, and III all invaded respiratory epithelial cells but demonstrated some strain variation in magnitude of invasion . These observations led us to conclude that type III capsular polysaccharide was not essential for invasion of respiratory epithelial cells by GBS and that bacterial factors other than capsule were responsible for respiratory epithelial cell invasion. J Clin Immunol, 1993 Nov, 13(6), 415 - 23 Henoch-Schoenlein purpura due to streptokinase; Zilliox AP et al.; The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after receiving streptokinase as thrombolytic therapy for an acute myocardial infarction . Renal biopsy revealed mesangial hypercellularity with deposits of IgA . Skin biopsy also revealed IgA deposition . Immunological studies showed evidence of sensitization to streptokinase . Elevated IgG, IgA, IgM, and IgE antistreptokinase antibodies were detected in the acute serum . Positive immediate skin reactivity to streptokinase was also present . Serum precipitins to streptokinase disappeared when IgA was removed from the serum . Positive staining with biotinylated streptokinase was seen in the skin in the same pattern of distribution as IgA . These findings strongly support the role of streptokinase and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient . A control group of streptococcal-infected patients showed no immune response to streptokinase . Another control group of streptokinase-treated patients, who had no untoward reaction, had elevated immunoglobulin classes and precipitins to streptokinase . However, the precipitating antibody was IgG and streptokinase skin tests were negative. Clin Exp Dermatol, 1993 Nov, 18(6), 537 - 9 Serious group A streptococcal infections complicating cryotherapy to lip haemangiomas; Armstrong AL et al.; Cryotherapy is a safe and effective way of treating haemangiomas of the oval cavity and lips without complications in adults in a reported series . Two cases of serious group A streptococcal infection after cryotherapy in two children are reported . In conclusion it is likely that these children were undiagnosed carriers for the organism . Pre-operative nasopharyngeal swabs would have identified this and prevented the complications which occurred. Br J Dermatol, 1993 Nov, 129(5), 514 - 20 Restricted T-cell receptor V beta gene usage in the skin of patients with guttate and chronic plaque psoriasis; Lewis HM et al.; A strong association between acute guttate psoriasis and group A, beta-haemolytic streptococcal infections is well established . Furthermore, streptococcal M proteins and toxins have been shown to act as superantigens, stimulating subpopulations of T lymphocytes expressing particular V beta families . We have therefore studied the possible role of streptococcal superantigens in psoriasis by staining peripheral T lymphocytes and skin sections from patients with guttate or chronic plaque psoriasis for the expression of nine TCR V beta families, using a range of monoclonal antibodies . A marked over-representation of V beta 2+ T lymphocytes was observed in the dermis and epidermis of patients in both groups, when compared with T lymphocytes in their peripheral blood . A less marked dermal increase in V beta 5.1+ T lymphocytes was also observed in these patients . These findings are consistent with the involvement of a superantigen, possibly streptococcal, in the pathogenesis of psoriasis. Vet Clin North Am Food Anim Pract, 1993 Nov, 9(3), 489 - 98 Environmental mastitis; Smith KL et al.; Environmental mastitis affects all dairy farms and generally is the major mastitis problem on modern, well managed dairy farms . Control measures effective against contagious pathogens are of little value in controlling of environmental pathogens . Control of environmental mastitis is achieved by reducing exposure of teat ends to environmental pathogens and by maximizing the resistance of the cow to intramammary infection . Significant sources of environmental pathogens are organic bedding materials, manure covered alleyways, and wet or damp areas in barns, exercise lots, or pastures . Milking time hygiene can influence teat-end exposure . In general, exposure is minimized when all areas of the environment are clean, cool, and dry . Resistance is maximized by providing a stress-free environment that minimizes teat-end injury, and by feeding balanced diets sufficient in vitamin E and selenium . Antibiotic therapy during lactation or the dry period is of little value in the control of environmental mastitis in dairy herds, with the exception of preventing environmental streptococcal infection during the early dry period . Effective vaccines may help reduce the impact of environmental mastitis in the near future. J Exp Med, 1993 Nov 1, 178(5), 1531 - 9 Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen; Bette M et al.; The polyclonal stimulation of T cells by bacterial superantigens is involved in the pathogenesis of the toxic shock syndrome in certain staphylococcal and streptococcal infections . Here we describe the onset and kinetics of superantigen-induced cytokine production in situ in spleens of normal BALB/c mice monitored at the level of cytokine mRNA expression by in situ hybridization . Messenger RNAs for interleukin 2 (IL-2), interferon gamma, and tumor necrosis factors (TNF) alpha and beta were not expressed at detectable levels in spleens of unstimulated animals but became visible already 30 min after intraperitoneal application of 50 micrograms staphylococcal enterotoxin B . All mRNA levels showed peak expression approximately 3 h after injection and a slow decrease up to 24 h after injection . Expression of the mRNAs was restricted to the T cell-dependent area of the periarteriolar lymphatic sheets of the spleen . Interestingly, TNF-alpha mRNA showed a biphasic response, the early appearing mRNA had the same localization as the other mRNAs, whereas after 3 h TNF-alpha mRNA showed a broader distribution indicating a second cell population producing TNF-alpha . The expression of IL-2 and TNF proteins in the serum increased in parallel to the observed mRNA changes with a slight delay . The presence of macrophages was not required for the expression of the cytokine mRNAs in the spleen as the expression was unchanged in macrophage-depleted mice . Only the second phase of TNF-alpha mRNA expression was abrogated in such animals . The expression of all mRNAs was completely suppressed by prior administration of cyclosporin A . These data show that nonphagocytic cells are the essential superantigen-presenting cells in vivo and indicate that at least part of the pathogenetic TNF-alpha is T cell derived. Circulation, 1993 Nov, 88(5 Pt 1), 2198 - 205 Does endomyocardial biopsy aid in the diagnosis of active rheumatic carditis? Narula J, Chopra P, Talwar KK, Reddy KS, Vasan RS, Tandon R, Bhatia ML, Southern JF. BACKGROUND . Carditis is the only component of rheumatic fever that leads to permanent disability . The diagnosis of carditis is presently made by using composite clinical criteria based on the revised Jones' criteria . Since myocardial involvement is an important component of rheumatic carditis, right ventricular endomyocardial biopsies were performed in 54 patients with clinical acute rheumatic fever and quiescent rheumatic heart disease to evaluate the role of biopsy for the diagnosis of rheumatic carditis . METHODS AND RESULTS . In 11 of the 54 patients, clinical consensus was certain about rheumatic fever and carditis based on the revised Jones' criteria (group 1) . Histomorphological abnormalities in these patients were scarce . The diagnostic features of rheumatic myocarditis including Aschoff nodules or histiocytic aggregates were encountered in 3 patients (27%) . Lymphocytic infiltration was sparse . A majority of patients demonstrated myocyte degeneration, interstitial degeneration, or occasional interstitial mononuclear cell infiltration, but since these histopathological lesions may occur in other conditions also, they were considered nondiagnostic . In 33 of the 54 patients with preexisting rheumatic heart disease, the diagnosis of carditis was suspected based on varied clinical presentations . Since previous cardiac findings were not available in these patients, the clinical diagnosis of carditis could not be made without equivocation (group 2) . Twenty-three patients presented with unexplained acute onset of congestive heart failure and evidence of recent streptococcal infection (group 2A) . While 13 of them had one or more other major manifestations, 10 patients had only minor manifestations . Mimetic carditis was suspected in the remaining 10 of 33 patients based on carditis having occurred in previous episodes of rheumatic fever (group 2B) . The endomyocardial biopsy provided confirmatory evidence of rheumatic myocarditis in 9 patients of group 2A but in none of the 10 patients with suspected mimetic carditis . Nondiagnostic myocyte or interstitial alterations were frequently observed in group 2 . Ten of the 54 patients had no clinical evidence of active carditis (group 3) . No histological alterations diagnostic of rheumatic carditis were noted in these patients . Twenty-two follow-up biopsies were performed in the first 10 consecutive patients . Diagnostic histiocytic aggregates or Aschoff nodules were observed in initial biopsies in 4 of 10 patients, and nonspecific myocyte or interstitial alterations were observed in 9 . All patients with diagnostic changes in initial biopsy demonstrated fibrohistiocytic nodules in 6- or 12-week biopsy samples . Nondiagnostic alterations, similar to those seen in acute cases, were present in 5 of 8 patients at 6 weeks, 5 of 8 patients at 12 weeks, and 3 of the 6 patients at 24 weeks despite the presumed adequate immunosuppressive therapy . No complications related to biopsy were encountered . CONCLUSIONS . The present study highlights the low frequency of diagnostic features in the biopsy specimens of patients with definite clinical rheumatic carditis . Although such alterations are not observed in patients with chronic rheumatic heart disease, endomyocardial biopsy does not appear to provide additional diagnostic information where clinical consensus is certain about diagnosis of rheumatic carditis . Our study, however, substantiates the concept of carditis underlying unexplained congestive heart failure of acute onset in patients with preexisting rheumatic heart disease and elevated antistreptolysin-O titers. Cytokine, 1993 Nov, 5(6), 595 - 603 Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, OK-432: role of IL-8 for neutrophil infiltration; Tsuchiya I et al.; When OK-432, a well-known streptococcal preparation for an anti-tumour drug, was administered into the pleural cavity of patients with malignant pleurisy, a rapid and prominent leukocytosis, predominantly consisting of neutrophils, was observed in the cavity . Neutrophil infiltration usually peaked 6-9 h after OK-432 administration, and levelled down after 24 h . Prior to the neutrophil accumulation, transient but marked elevation of various inflammatory cytokine levels including IL-1 beta, TNF-alpha, IL-8 and G-CSF was observed . In particular, IL-8 levels increased more than 10-fold, while GM-CSF did not change significantly . A good correlation between IL-8 levels and neutrophil chemotactic response was observed particularly during 0-3 h . Specific neutralization or removal of IL-8 by antibody column abrogated half of the neutrophil chemotaxis, while neutralization of C5a removed around 40% . Sequential removal of IL-8 and C5a abrogated totally 80% of chemotaxis, confirming that these two factors are mostly responsible for the neutrophil chemotaxis in the pleural fluids . These results have suggested that rapid neutrophil infiltration induced by OK-432 in vivo is ascribable largely to IL-8 and in part to C5a. Zhonghua Kou Qiang Yi Xue Za Zhi, 1993 Nov, 28(6), 365 - 7, 384 {Direct effect of streptococcal preparation 722 (Sapylin) on squamous cell carcinoma (Tca8113) cells of human tongue in vitro and in vivo}; He RG; When the Tca8113 cells contacted with streptococcal preparation 722 in 0.2-1.0 KE/ml concentration directly and continuously in Vitro, the ability of colony-forming of the cells was lost . Using time lapse microcinematographic study it was confirmed that this agent has a direct cytostatic activity on Tca8113 cells, but it was also confirmed that this activity was reversible after 4 days . Effect of 722 on transplantable tumor of Tca8113 cells in nude mice with different routes (ip, id, it) had no-response . The results suggest that the effect of 722 preparation on antitumor in Vivo must have a complete immune function in the host. Neurology, 1993 Nov, 43(11), 2400 - 3 Mozart's chronic subdural hematoma; Drake ME Jr; No commemoration of the bicentennial of Mozart's death would be complete without some consideration of that premature yet predictable demise . Mozart's premonitions of death are well known and apparently played a role in the composition of the K.626 Requiem and perhaps other works . His death has traditionally been ascribed to infectious causes, chiefly rheumatic fever or post-streptococcal glomerulonephritis, exacerbated by intemperance and chronic penury . Pathology has been difficult because of his supposed burial in a pauper's grave, the location and contents of which were later supposedly lost . Mozart's burial place in St . Mark's Cemetery in Vienna was known and, in the parlance of the day, "reorganized" a decade later, as the occupants of plots were disinterred to make room for the more recently decreased . A skull believed to the Mozart's was saved by the successor of the gravedigger who had supervised Mozart's burial, and then passed into the collections of the anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg) . Forensic reconstruction of soft tissues related to this skull reveals substantial concordance with Mozart's portraits . The skull suggests premature closure of the metopic suture, which has been suggested on the basis of his physiognomy . A left temporal fracture and concomitant erosions raise the question of chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting he experienced in 1790 and 1791 . Aggressive bloodletting to treat suspected rheumatic fever could have decompensated such a lesion to produce his death on December 5, 1791. J Immunol, 1993 Oct 15, 151(8), 4344 - 51 Suppression of monocyte function and differential regulation of IL-1 and IL-1ra by IL-4 contribute to resolution of experimental arthritis; Allen JB et al.; IL-4 has diverse effects on hematopoietic cells, including the ability to suppress certain mononuclear cell functions . To evaluate the effect of IL-4 on the evolution of acute and chronic arthritis, murine recombinant IL-4 was administered systemically to animals receiving an arthropathic dose of group A streptococcal cell wall fragments . Daily treatment with IL-4 had a minimal effect on the acute phase, but significantly suppressed the chronic, destructive phase . By 4 wk after initiation of disease, the articular index of IL-4-treated animals was reduced > 60% (articular index = 4 +/- 0.9) compared with the untreated rats (11.5 +/- 0.48, p < 0.001) . A substantial decrease in the influx of inflammatory cells and virtual elimination of pannus and erosions occurred after IL-4 therapy . Associated with the reduced accumulation of mononuclear leukocytes was a decrease in their proinflammatory functions including cytokine production and reactive oxygen intermediate metabolism . These observations are consistent with the selective effects of IL-4 on phagocytic cell function demonstrated in vitro . Furthermore, IL-4 induced gene expression for IL-1ra, a protein that antagonizes the action of IL-1 by binding to the IL-1 receptor without agonist activity . Through an expanding spectrum of effects on monocyte-macrophage phenotypic and functional parameters, IL-4 is emerging as an important inhibitor of cell-mediated immune responses and pathogenic processes. J Mol Biol, 1993 Oct 5, 233(3), 331 - 5 Identification of the contact surface of a streptococcal protein G domain complexed with a human Fc fragment; Gronenborn AM et al.; The B1 domain of streptococcal protein G interacts with the C-terminal fragment of the heavy chain of immunoglobulin G (IgGFc) . The binding site for the protein G domain on the antibody fragment is in close proximity or overlapping with that determined for staphylococcal protein A . The interaction of the B1 domain with IgGFc was investigated by 1H-15N correlation spectroscopy . The major interaction site on the B1 domain comprises parts of beta-strand 3 as well as the alpha-helix . Comparison with the crystal structure of the protein A/IgGFc complex suggests that the mode of interaction in the two complexes is analogous, despite the lack of sequence or structural similarity between two antibody binding proteins. J Infect Dis, 1993 Oct, 168(4), 915 - 21 Poststreptococcal anti-myosin antibody idiotype associated with systemic lupus erythematosus and Sjögren's syndrome; McCormack JM et al.; Anti-myosin antibodies are found in acute rheumatic fever (ARF), a sequela of group A streptococcal infection . An antiidiotypic serum was produced that was specific for idiotopes expressed by anti-myosin antibodies in ARF (anti-My1) . Studies indicated that idiotypic determinants detected with this serum were present in anti-myosin antibodies and absent from normal human immunoglobulins that lacked specificity for myosin . Anti-My1 was tested against sera from patients with other types of autoimmune diseases as well as uncomplicated streptococcal infections . Sera from systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), and poststreptococcal acute glomerulonephritis patients demonstrated idiotypic reactivity with anti-My1 . Affinity-purified anti-myosin antibodies from SLE, SS, and ARF sera also reacted strongly with anti-My1, indicating that immunoglobulins produced in these diseases share idiotypic determinants . The data demonstrated an association of the My1 idiotype with poststreptococcal sequelae and the two autoimmune diseases SLE and SS. J Pediatr Surg, 1993 Oct, 28(10), 1370 - 4; discussion 1374-5 Bladder pressure monitoring significantly enhances care of infants with abdominal wall defects: a prospective clinical study; Lacey SR et al.; Increased intraabdominal pressure (IAP) has been demonstrated to cause intestinal and renal ischemia in both animals and humans . Neonates undergoing closure of anterior abdominal wall defects are at risk for these complications from markedly increased IAP, which are putatively responsible for a 13% to 20% mortality . In an effort to decrease morbidity and mortality we performed a 4-year prospective clinical study to determine if monitoring IAP using bladder pressure (BdP) measurements would significantly improve perioperative care in infants with abdominal wall defects . Forty-two consecutive infants with gastroschisis (28) and omphalocele (14) were prospectively studied . Intraoperative and serial postoperative measurements of BdP were obtained from an indwelling bladder catheter using a standard pressure transducer . Methods of initial closure, as well as manipulations in sedation, paralysis, and silo reduction, were selected to keep BdP < 20 mm Hg . Bladder pressure monitoring significantly altered the management of 64% of our patients, particularly those with gastroschisis (74%) . Thirteen patients with gastroschisis underwent staged closure; in 7 (54%) this decision was based on high BdP even though bowel reduction was mechanically possible . Elevated BdP influenced the closure method and timing of silo reductions in 5 of 14 (42%) infants with omphalocele . There were no episodes of renal failure or refractory oliguria . There were three patients in a single cluster who developed uncomplicated, nonsurgical necrotizing enterocolitis late in their respective courses . One patient whose bowel was placed in a silo had severe hypotension associated with group B streptococcal sepsis and subsequently developed necrotic bowel despite low BdP.(ABSTRACT TRUNCATED AT 250 WORDS) Zhonghua Yi Xue Za Zhi (Taipei), 1993 Oct, 52(4), 229 - 34 Treating carcinomatous pleural effusion by intrapleural injection of OK-432 in patients with non-small-cell lung cancer; Chao TY et al.; The effect of intrapleural injection of OK-432, a streptococcal preparation, for management of carcinomatous pleural effusion was investigated in patients with non-small cell lung cancer (NSCLC) . Ten patients, including 5 men and 5 women with performance status 2-3(ECOG) and average age of 66.4 years, received OK-432 for different times after the tumor burden in effusion was relieved with adequate drainage . The response rate was 100% in terms of decreased reaccumulation of pleural fluid, improvement of general status, and disappearance of tumor cells in the fluid . The adverse effects of this treatment were mild-including fever, chills, chest pain and nausea-and all were tolerable to patients . Median survival time was 4.5 months after treatment . This preliminary report indicates that intrapleural injection of OK-432 is an effective alternate method for management of carcinomatous pleural effusion to improve the quality of life for terminally ill cancer patients. Antimicrob Agents Chemother, 1993 Oct, 37(10), 2228 - 30 Augmentation of murine tumor necrosis factor production by amphotericin B in vitro and in vivo; Tokuda Y et al.; Murine peritoneal macrophages were preincubated with amphotericin B (AMPH) and were then stimulated with bacterial lipopolysaccharide or streptococcal preparation (OK432) . These macrophages produced a large amount of tumor necrosis factor . When administered to mice, the priming activity of amphotericin B for tumor necrosis factor production in vivo was also observed. Pediatr Nephrol, 1993 Oct, 7(5), 543 - 7 Risks of peritoneal membrane failure in children undergoing long-term peritoneal dialysis; Andreoli SP et al.; Children undergoing long-term peritoneal dialysis are at risk for membrane injury, necessitating conversion to hemodialysis . We analyzed the incidence and risk factors for membrane failure (inadequate ultrafiltration with or without peritoneal adhesions and decreased peritoneal surface area) in 68 children maintained with peritoneal dialysis for more than 3 months at our institution . The overall incidence of membrane failure was 16.2% (11/68) . Kaplan-Meier estimates of peritoneal membrane survival were 88% at 24 months, 72% at 36 months, 65% at 48 months, and 52% at 60 months . Logistic regression analysis demonstrated that the risk of membrane failure increased with the number of episodes of peritonitis (odds ratio 1.61) . The rate of peritonitis was 1 per 7.02 patient months in children who developed membrane failure compared with 1 per 9.18 patient months in children without membrane failures but the rate of peritonitis was not predictive of membrane failure (P = 0.09) . Multiple logistic regression analysis demonstrated that peritonitis caused by Pseudomonas aeruginosa or alpha streptococcal organisms were independent predictors of membrane failure . We conclude that peritoneal membrane survival declines substantially with time on peritoneal dialysis and that membrane failure is associated with peritonitis, particularly peritonitis caused by Pseudomonas aeruginosa and alpha streptococcal organisms . The mechanism(s) of membrane injury are unknown but may be related to the inflammatory response initiated during peritonitis. Arch Dermatol, 1993 Oct, 129(10), 1267 - 9 Acquired purpura fulminans induced by alcohol and acetaminophen . Successful treatment with heparin and vitamin K; Guccione JL et al.; Purpura fulminans is a rare syndrome of progressive hemorrhagic necrosis of the skin that may present as a dermatologic emergency . It most commonly affects children during the convalescent phase of a streptococcal infection or a viral exanthem . In adults, it may be associated with sepsis or acquired causes . Its pathogenesis has challenged physicians for decades . It has been discovered that purpura fulminans is almost always associated with disseminated intravascular coagulation and can occur in subjects with inherited or acquired deficiencies of the protein C anticoagulant pathway . Patients with liver compromise may also be potential candidates for coagulopathies secondary to hepatic dysfunction and impaired protein synthesis . It is widely recognized that individuals who consume alcohol on a long-term basis may develop severe hepatotoxicity from ingestion of therapeutic doses of acetaminophen (500 to 1000 mg every 4 to 6 hours) . We have observed a patient with chronic alcoholism in whom hepatotoxicity and purpura fulminans developed secondary to the ingestion of acetaminophen. Am J Gastroenterol, 1993 Oct, 88(10), 1729 - 33 A role for culture in diagnosis of Helicobacter pylori-related gastric disease; Schrader JA et al.; In this study, our objective was to determine the presence of Helicobacter pylori and other rapid urease-positive (RUP) organisms in gastric biopsies in 70 patients, 30 of whom had ulcers or erosions . A retrospective chart review was undertaken to correlate diagnostic tests (culture and direct urease) with results of endoscopic examination and the patient's clinical information . Eleven of 70 (15.7%) patients' biopsies were positive by both culture and direct urease for H . pylori, seven (10%) patients' biopsies were positive by culture only, and eight (11.4%) biopsies by direct urease only . Of 30 patients with ulcers (esophageal, antral, stomach, or duodenal), 15 had evidence of H . pylori infection by culture and/or direct urease test . In addition, patients with a positive direct urease test but a negative culture for H . pylori were more likely to have other rapid urease-positive organisms (RUP) isolated from their gastric biopsy cultures than patients with negative results from both tests . Conclusions: As a result of problems associated with commonly used diagnostic tests, a combination of tests performed on multiple biopsies is more sensitive and specific for the diagnosis of H . pylori infection than any single test . The common occurrence of RUP streptococcal and staphylococcal species in gastric biopsy tissue is demonstrated and proposed as a cause of false-positive direct urease tests. JAMA, 1993 Sep 22-29, 270(12), 1442 - 8 Comparison of prevention strategies for neonatal group B streptococcal infection . A population-based economic analysis; Mohle-Boetani JC et al.; BACKGROUND--Intrapartum antibiotics can prevent early-onset neonatal group B streptococcal (GBS) disease but have not been widely used . Obstacles include difficulty in implementing screening for GBS colonization and uncertainty about cost-effectiveness . The GBS vaccines for disease prevention are now being developed . METHODS--We developed a decision analysis model and used standard cost-effectiveness and cost-benefit analysis methods . We compared the outcomes and costs of the recent practice of no intervention with those expected for three prevention strategies: (1) intrapartum antibiotics administered to colonized women with labor complications, (2) an alternative strategy that does not require screening but uses epidemiologic criteria and labor complications to target intrapartum antibiotics, and (3) maternal vaccination . We used data from multistate population-based surveillance to estimate the potential impact of each strategy on disease and costs in the United States . RESULTS--Intrapartum antibiotic prophylaxis of high-risk women identified by screening could prevent approximately 3300 cases (47% of neonatal disease) annually in the United States and could save approximately $16 million in direct medical costs . Chemoprophylaxis of high-risk women identified using epidemiologic criteria could potentially be equally effective (3200 cases prevented) and would avoid the logistical difficulties of screening; the net savings would be approximately $66 million . Vaccinating 80% of pregnant women with a vaccine that prevents 80% of cases among infants born at or after 34 weeks of gestation would prevent approximately 4100 neonatal cases annually with a net savings of $131 million . CONCLUSIONS--Universal prenatal screening for GBS and chemoprophylaxis of colonized women with labor complications is likely to be cost-beneficial in the United States . Development of alternative strategies should be further explored for populations in which GBS screening is impractical . Continued development of a GBS vaccine is an important public health priority. N Z Med J, 1993 Sep 8, 106(963), 381 - 3 Sore throat presentation and management in general practice; Kljakovic M; AIMS . To compare the characteristics of sore throat patients with their having normal throat, to measure the incidence of beta-haemolytic streptococcal growth in both groups, and to determine the clinical outcomes of treating sore throat patients without the aid of a throat swab . METHOD . Patients were from a suburban general practice . A three phased prospective study of consecutive patients with sore throats as their primary complaint, or with normal throats . RESULTS . Patients presented with a sore throat at a rate of 45 per 1000 consultations and those with normal throats presented at a rate of 379 per 1000 consultations . 43% of normal throat patients were male compared to 34% with sore throat (chi 2 = 4.62, p < 0.02) . The incidence of beta-haemolytic streptococcal growth in sore throat patients was 123 per 1000 consultations per year . 23% of people 14 years and younger had a positive growth compared to 9% of people over 14 years of age . (chi 2 = 5.04, df = 1, p < 0.05) . The sore throat presentation peaked over the late autumn to early winter months (June-July) but the beta-haemolytic streptococcal infection rate remained low throughout the year . A history of pain for less than three days and fever, and on examination large neck glands and pus on the tonsils were all positive clinical features for beta-haemolytic streptococcal infection . However use of clinical criteria alone meant 73% of patients with no beta-haemolytic streptococcal infection were falsely treated . CONCLUSION . Research is needed to develop guidelines for the management of sore throats in general practice. J Periodontal Res, 1993 Sep, 28(5), 346 - 53 Effect of anaerobiosis and sulfide on killing of bacteria by polymorphonuclear leukocytes; Granlund-Edstedt M et al.; Anaerobic microorganisms in periodontal pockets produce toxic amounts of hydrogen sulfide . The capacity of polymorphonuclear leukocytes to kill a capsulated and a non-capsulated variant of a group B streptococcal strain was studied in presence and absence of sulfide . The killing was equally efficient under aerobic and anaerobic conditions . However, in presence of sulfide the killing of the capsulated variant of the strain was significantly inhibited . Since this strain required higher serum concentrations to be killed by the polymorphonuclear leukocytes, it suggested that sulfide interfered with the opsonization of the bacteria . The capacity of sulfide to split the disulfide bonds of complement factor 3 and immunoglobulin G, deposited on the bacterial surface, was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . There was no detectable effect of 2 mM sulfide on immunoglobulin G . However, sulfide released from opsonized bacteria the beta-chain of C3b C3bi, and the C-terminal part of the alpha-chain of C3bi . This region of the alpha-chain of C3bi has been suggested to bind to the complement receptor 3 of polymorphonuclear leukocytes . The beta-chain of C3b/C3bi may augment the binding of opsonized bacteria to the complement receptors of polymorphonuclear leukocytes . The formation of sulfide by the microflora of the periodontal pockets may provide conditions for t