Streptococcal

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 the bacteria to escape important parts of the host immune system.

Curr Opin Rheumatol, 1993 Sep, 5(5), 651 - 7
Infectious diseases affecting the musculoskeletal system in children and adolescents; Dressler F; Many infectious organisms can lead to musculoskeletal symptoms in children . This article reviews recent studies on rheumatic fever, invasive group A streptococcal infections, septic infections of bones and soft tissues, reactive arthritides caused by viruses, fungi or bacteria, and Lyme disease . The search for etiologic organisms in chronic arthritis continues . Although Koch's postulates are not fulfilled in most cases of infectious arthropathies, progress has been made in diagnosing and treating these diseases.

Prim Care, 1993 Sep, 20(3), 639 - 53
Preterm birth; LeFevre ML et al.; Preterm birth is a major cause of infant morbidity and mortality . Although limited data exist to support efforts to prevent preterm birth, some specific interventions have merit . Strategies targeted at identification of early preterm labor and tocolysis have generally been unrewarding . Neonatal morbidity associated with preterm birth can be reduced with the use of corticosteroids, antibiotics for group B streptococcal colonization of the vagina, and transport of the mother to a tertiary care institution prior to delivery.

Breast Cancer Res Treat, 1993 Sep, 27(3), 203 - 10
Intrapleural adaptive immunotherapy for breast cancer patients with cytologically-confirmed malignant pleural effusions: an analysis of 67 patients in Kyoto and Shiga Prefecture, Japan; Kan N et al.; Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively . The patients received their first thoracentesis between 1980 and 1990 . Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2 . Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1) . Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p < 0.01) . Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p < 0.001) difference in survival . Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p < 0.005) factor to prolong the survival of the patients among several prognostic factors . Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Sep-Oct, (5), 83 - 7
{Autoimmune reactions in diseases of streptococcal etiology}; Bala MA et al.; In this work 98 cases of streptococcal tonsillitis and 361 cases of erysipelas were studied . As revealed in this study, in relapsing forms of streptococcal infection antibodies to cross-reacting antigens of the infective agent appear in the blood . The synthesis of antibodies to the basal layers of skin epithelium was accompanied by an increase in the concentration of medium-size immune complexes, 0-cell population and by a decrease in the number of T suppressors . The mechanism of the development of the autoimmune process in relapsing forms of streptococcal infection is discussed.

P N G Med J, 1993 Sep, 36(3), 246 - 8
Acute streptococcal pharyngitis misdiagnosed as faucial diphtheria: a cautionary lesson; Brown N et al.; A confirmed case of diphtheria has not been reported in Papua New Guinea for many years, though it should be considered dormant rather than extinct . Thus, most clinicians nowadays are unfamiliar with the classical features of the disease . We report a case of streptococcal pharyngitis which had several features of diphtheria leading to unnecessary and potentially harmful intervention . Some words of caution and various recommendations are made.

Afr J Med Med Sci, 1993 Sep, 22(3), 79 - 83
Group B streptococcal carriage among parturients and their neonates in Zaria, Nigeria; Uhiara JE; In an epidemiological study of Group B streptococcal (GBS) carriage carried out on 100 mothers and their newborns in Zaria, 14 mothers were found to be vaginal and perineal carriers while 13 infants were found to be colonised at birth . The colonization rate of infants born to colonised mothers was 93% . The results also showed no association between carriage of (GBS) and frequency of coitus, polygamous union, multiparity, low educational status and lack of prenatal care . In terms of morbidity, neither the colonised women nor the infants developed clinical GBS infection . The study also revealed that all the GBS isolated were sensitive to penicillin and resistant to sulphatriad . The findings suggest that although carriage is fairly high in this environment, GBS is not a common cause of perinatal infection.

J Am Soc Nephrol, 1993 Aug, 4(2), 235 - 42
Detection of platelet-activating factor in plasma of patients with streptococcal nephritis; Mezzano S et al.; The purpose of this study was to evaluate whether platelet-activating factor (PAF) is released in the plasma of patients with acute poststreptococcal glomerulonephritis, because previous studies have shown an involvement of platelets in the active phase of this disease . The results of this study indicate that PAF bioactive material is released in significant amounts in the plasma of 49 out of 50 patients with acute poststreptococcal glomerulonephritis . The observed release of PAF was not a direct consequence of the bacterial infection, because it was minimal or absent in patients with streptococcal infection without glomerular involvement . PAF bioactive material extracted and purified from the plasma of patients was shown to be chemically and biologically identical to the synthetic C-16 PAF (1-O-hexadecyl-2-acetyl-sn-glyceryl 3-phosphorylcholine).

Clin Infect Dis, 1993 Aug, 17 Suppl 1, S200 - 1
Susceptibility of mycoplasmas to antimicrobial agents: clinical implications; McCormack WM; Mycoplasmas are susceptible to antimicrobial agents that affect DNA, RNA, protein synthesis, or the integrity of the cell membrane . Mycoplasmas are not susceptible to agents that interfere with synthesis of folic acid or that act on the cell wall . Tetracyclines, erythromycin, clindamycin, chloramphenicol, aminoglycosides, and fluoroquinolones have been shown to have activity against one or more mycoplasmal species . Tetracycline-resistant isolates of Mycoplasma hominis and Ureaplasma urealyticum contain DNA sequences homologous to the streptococcal determinant tetM . Resistance to tetracycline in vitro is associated with failure of tetracycline treatment to eradicate M . hominis and U . urealyticum from the human urogenital tract.

Pediatr Nephrol, 1993 Aug, 7(4), 379 - 86
Activated C3 (C3b) in the nephritic glomerulus; Pan C et al.; An autoradiographic technique was developed to assess in the nephritic glomerulus the relative amount of C3 which is in the activated form, C3b, compared with the inactivated form, iC3b . Frozen renal biopsy sections from children and young adults with glomerulonephritis were assessed for the C3b fraction of total C3, using a radiolabeled monoclonal anti-C3c . Grain counts with this antibody, before and after reacting the section with 0.0002% trypsin, gave the relative amounts of total C3 and C3b, respectively . C3b was found in all diseases studied . To explain its presence, glomerular C3b acceptors which would restrict C3b inactivation were sought by immunofluorescence studies . C3b acceptor candidates were: IgG in aggregated form, IgA as found in the IgA nephropathies and the C3/C5 convertase, C4b,2a,3b . In acute post-streptococcal glomerulonephritis and membranoproliferative glomerulonephritis type III, diseases in which these acceptors were lacking, it is postulated that the nephritis strain-associated protein and absence of membrane cofactor protein, respectively, may be responsible for C3b deposition . The phlogistic effect of C3b is mediated largely by one of its products, C5b-9 . However, the C3b: total C3 ratio failed to correlate with indices of glomerular inflammation, probably in part because the ratio is not a measure of total glomerular C3b.

Gan To Kagaku Ryoho, 1993 Aug, 20(10), 1349 - 54
{Tissue and serum levels of 5-FU in the patients with head and neck malignant tumors--influence of a streptococcal preparation OK-432}; Suzuki K et al.; Concentrations of Tegafur, 5-FU, and Uracil were measured in the tissues and serum of 32 patients with malignant head and neck tumors after administration of UFT or UFT and OK-432 . Of the 32 patients, 15 patients were treated with UFT alone and 17 patients with a combination of UFT and a clinical dose of OK-432 . The level of 5-FU was higher in the tissues and serum in the patients who received the combined administration of UFT and OK-432 than in those the received UFT alone . In particular, levels of 5-FU in tumor tissue and metastatic lymph node tissue were higher than 0.05 micrograms/g even 14.6 hours after the last administration of UFT . No significant undesirable interactions between UFT and OK-432 were exhibited during combination therapy of these agents in clinically administered doses . From our satisfactory results, clinical cures would be expected by the combined immuno-chemotherapeutic action of these agents.

J Immunol, 1993 Aug 1, 151(3), 1419 - 29
Localization of an immunologically functional region of the streptococcal superantigen pepsin-extracted fragment of type 5 M protein; Wang B et al.; Ten overlapping synthetic peptides, spanning the entire amino acid sequence of pepsin-extracted type 5 M protein, (pep M5), were used to delineate regions within this molecule that are important for the mitogenic activity of this streptococcal superantigen . Two of the overlapping peptides, SM5-8 and SM5-10, blocked the response of T cells to pep M5 in a dose-dependent manner . Neither peptide was toxic to T cells, but SM5-8 exhibited nonspecific inhibition of the T-cell response to either superantigen or polyclonal mitogens . In contrast, the inhibition by SM5-10 was pep M5-specific . Analysis of TCR V beta gene usage of the pep M5 response in the presence and absence of SM5-10 revealed that this peptide preferentially blocks the expansion of pep M5-specific V beta elements . The degree of inhibition of V beta expansion varied from one individual to the other, reflecting their TCR repertoire . SM5-10 did not significantly inhibit the response of T cells to other streptococcal superantigens . The data suggest that the region represented by SM5-10 of the pep M5 is important for superantigenic activity . In addition, the ability of this synthetic peptide to inhibit the response to pep M5 provides evidence that the mitogenic response is indeed mediated by this superantigen and is not a result of contamination with other streptococcal superantigens.

Cathet Cardiovasc Diagn, 1993 Aug, 29(4), 322 - 4
Catheter lavage and drainage of pneumococcal pericarditis; Thavendrarajah V et al.; An 88 year old woman with streptococcal pneumonia developed purulent pericarditis and cardiac tamponade despite treatment with antibiotics . Percutaneous pericardial drainage was effected with a 6 French pigtail catheter inserted via the subxyphoid approach . Catheter drainage was continued for 7 days in conjunction with systemic antibiotics . Catheter patency was maintained with antibiotic lavage . Immediate hemodynamic improvement followed the initial pericardial drainage . Fever, leukocytosis, and sepsis resolved during the course of therapy . The patient recovered fully from the closed space bacterial infection without additional surgical drainage . There has been no recurrence of streptococcal infection and no echocardiographic evidence of recurrent pericardial effusion after 3 months of follow-up . Indwelling catheter drainage combined with antibiotics may be an effective substitute for surgical drainage in the treatment of streptococcal pericarditis.

Arch Fam Med, 1993 Aug, 2(8), 866 - 9
Comparison of an immunochromatographic method for rapid identification of group A streptococcal antigen with culture method; Ehrlich TP et al.; OBJECTIVES: To compare the sensitivity and specificity of Concise Strep A (Hybritech, San Diego, Calif), an immunochromatographic group A streptococcal rapid antigen detection system, with a two-plate culture method for the diagnosis of streptococcal pharyngitis, and to evaluate the need for routine back-up culture when this rapid test is used . DESIGN: Throat cultures were obtained from 351 children with acute pharyngitis by duplicate rayon-tipped swabs held in parallel and vigorously rubbed against both tonsils and the posterior pharyngeal wall . One swab was tested for group A streptococcal antigen by a registered licensed laboratory technologist in the pediatrician's office . The other swab was streaked over each of two sheep blood agar plates, one of which was enhanced with trimethoprim in combination with sulfamethoxazole . The plain sheep blood agar plate was then incubated in a candle-extinguish jar . The enhanced agar plate was placed in a gas-pack anaerobic jar . Both plates were incubated for up to 48 hours at 35 degrees C . SETTING: A six-person group pediatric practice . PARTICIPANTS: Three hundred fifty-one children . RESULTS: The Concise Strep A antigen detection test produced 129 positive results . Only six of the 129 were not confirmed by culture method . There were four false-negative rapid streptococcal antigen detection test results, all of which were found after a single overnight incubation . The sensitivity for the Concise Strep A test was 96.9% and the specificity was 97.4% . The plain 5% sheep blood agar plate (without trimethoprim and sulfamethoxazole), which was incubated in a candle-extinguish jar, identified 123 (97%) of the 127 positive throat cultures . The second 24-hour incubation and use of trimethoprim and sulfamethoxazole agar were not rewarding for this study . CONCLUSIONS: Concise Strep A, a polyclonal antibody test, in conjunction with a color immunochromatographic assay for soluble streptococcal carbohydrate antigen A appears to be accurate, sensitive, and specific when throat swabs are carefully obtained and when qualified, licensed laboratory technologists perform the procedure . Further studies should be done to confirm our findings, especially when nurses or office staff perform the rapid test procedure in the office setting . If our findings are confirmed, the use of back-up cultures for negative rapid test results obtained using Concise Strep A would be unnecessary.

Antibiot Khimioter, 1993 Aug-Sep, 38(8-9), 56 - 60
{Use of antibiotics in pediatrics}; Shabalov NP et al.; The problems of an etiotropic approach to the choice of antibiotics in the treatment of infants remain actual and require their solution which is evident from the example of some usual affections: intrahospital pneumonia of newborns, pneumonia of infant outpatients, purulent meningitis, etc . The practice of irrational therapy of some children infections such as streptococcal angina and scarlet fever, whooping cough, intestinal infections, otitis media purulenta, sinusitis is rather common . Attention should be paid to the organization of the bacteriological services and the increase of the physicians qualification in the field of antibiotic therapy and clinical microbiology . It is advisable that chemotherapeutists be included in the staff of certain general hospitals.

J Exp Med, 1993 Aug 1, 178(2), 749 - 54
Suppression of arthritis by an inhibitor of nitric oxide synthase; McCartney-Francis N et al.; Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses . A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions . We show here that NO production is elevated in the inflamed joints of SCW-treated rats . Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology . These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.

Biochem Biophys Res Commun, 1993 Jul 30, 194(2), 819 - 25
Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats; Imamichi T et al.; Rat migration inhibitory factor-related protein 8 (MRP8) and MRP14 were identified during screening of a subtracted cDNA library generated to identify differences in gene expression between LEW/N and F344/N rats . The predicted amino acid sequence of rat MRP8 and MRP14 is 60-80% identical with that from human and mouse . Expression of these genes correlated with chronic inflammation in LEW/N rats, but were absent in F344/N rats which do not develop arthritis in response to streptococcal cell wall peptidoglycan-polysaccharide complexes (SCW) . These differences suggest a role for MRP8 and MRP14 in susceptibility to SCW-induced chronic disease.

Pediatrics, 1993 Jul, 92(1), 39 - 43
Antineuronal antibodies in movement disorders; Kiessling LS et al.; OBJECTIVE . To determine whether children with recent onset of movement disorders (Tourette syndrome, motor and/or vocal tics, chorea, choreiform movements) show evidence of serological antibodies directed against the human central nervous system as previously documented in research on Sydenham's chorea . METHODS . Serum antibodies against previously frozen human caudate nucleus sections were analyzed using a blinded design and immunofluorescent staining methods . The sera of one group of 50 children referred for evaluation of attention deficit hyperactivity disorder, behavior disorders, and learning disabilities (24 with an associated movement disorder) seen between June 1989 and June 1990 were analyzed . The study was replicated in 33 children (21 with an associated movement disorder) seen between June 1990 and November 1990 . RESULTS . In the original sample of 50 children, those with movement disorders were significantly more likely to have evidence of antineuronal antibodies than were those without movement disorders (odds ratio {OR} 4.80, 95% confidence interval {CI} 2.58 to 8.93) . Results of the replication were similar (OR 6.00, 95% CI 2.56 to 14.03) . For the total group, the OR was 5.50, (95% CI 3.54 to 8.99), which is highly significant . The percentage of children with a movement disorder whose sera were strongly positive for antineuronal antibodies (44%) was very similar to that previously found in children with Sydenham's chorea (46%) . Children with movement disorders were also more likely than children without movement disorders to have at least one antistreptococcal titer elevated . CONCLUSIONS . The data strongly suggest an association between antecedent group A beta-hemolytic streptococcal infection as inferred from elevated antistreptococcal titers and the presence of serum antineuronal antibodies, which may, in turn, be linked to childhood movement disorders.

J Infect Dis, 1993 Jul, 168(1), 232 - 5
Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis; Hackett SP et al.; The role of tumor necrosis factor-alpha (TNF alpha) in the pathogenesis of severe bacterial infections has been studied extensively . However, the role of TNF beta, a lymphokine with biologic activities similar to those of TNF alpha, has received little attention . Therefore, the purpose of this study was to examine the production of TNF beta by peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) and the superantigens staphylococcal toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA) . Though LPS was a more potent inducer of TNF alpha than was TSST-1 or SPEA, TSST-1 and SPEA were both more potent inducers of TNF beta . The superantigens TSST-1 and SPEA were more potent inducers of total TNF (TNF alpha and TNF beta) than was LPS . These data suggest that the induction of TNF beta synthesis may be a unique pathway by which superantigens associated with severe streptococcal and staphylococcal infections mediate shock and multiorgan failure characteristic of toxic shock syndrome.

Union Med Can, 1993 Jul-Aug, 122(4), 271 - 3
{Is extracorporeal membrane oxygenation necessary?}; Hamel P et al.; In order to evaluate our hospital center needs for extracorporeal membrane oxygenation (ECMO), a retrospective study was carried out over a two-year-period to determine the mortality rates of infants < or = 35 weeks of gestation and > or = 2000 grams with severe respiratory failure . The data was obtained from a perinatal center that serves a population that has 50,000 newborn deliveries per year . During the period of the study there were 75 infants meeting the above criteria admitted to the NICU with severe respiratory failure (defined as need for mechanical ventilation and 100% O2) . Forty-four patients were excluded because of improvement of their respiratory status on conventional therapy, and 16 were ineligible for ECMO because of their primary diagnosis . Of the 15 infants considered ECMO candidates, there were 2 deaths as a result of streptococcal beta hemolytic septicemia . The result of this study showed that few infants in the population served by this perinatal center would have benefited from ECMO.

Vojnosanit Pregl, 1993 Jul-Aug, 50(4), 343 - 8
{Hypertension in patients with post-streptococcal glomerulonephritis}; Jovanovic D et al.; Sixty two patients with poststreptococcal glomerulonephritis (PSGN), aged 18-22 (mean = 19 +/- 0.5 years) were examined and treated at the Clinic of Nephrology of the M.M.A . from the beginning of 1986 to the end of 1990 . Hypertension (diastolic pressure over 13 kPa, that is, 97.5 mmHg) in the acute phase was found in 59 (95.16%) patients, being of milder degree and short-term course . Transient increase of blood pressure required sometimes a short therapy (with furosemide mainly) . With normalization of the glomerular filtration rate, withdrawal of edema, and normalization of the plasma volume, the blood pressure has been also normalized in the majority of patients (within 3-5 days) . Observing PSGN evolution in the period from 2 to 5 years, hypertension was found in 3 (6.8%) of 44 patients . All three patients had the clear clinical evolution (proteinuria and erythrocyturia) without signs of renal insufficiency . The rebiopsy of the kidneys showed milder morphologic changes which were more manifested compared to the group without hypertension . Hypertension was present in the majority of patients in acute phase of PSGN while it was rarely found during the evolution of the disease and its presence has been poor prognostic sign in evolution since it contributed to development of glomerulosclerosis and later on renal insufficiency.

Int J Gynaecol Obstet, 1993 Jul, 42(1), 55 - 9
Group B streptococcal infections in pregnancy . ACOG Technical Bulletin Number 170--July 1992; Streptococcal endocarditis treated with two-week antibiotic regimen: preliminary report of a partial oral regimen; Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandWe reported 18 consecutive patients with penicillin-sensitive streptococcal IE (infective endocarditis) . Twelve were successfully treated with a 2-wk course of penicillin G sodium (PGS) and gentamicin, the dosages of which were guided by minimal inhibitory concentration, minimal bactericidal concentration and serum bactericidal titer (SBT), followed by another six who were treated equally successfully with a one week PGS followed by a second week of amoxycillin together with the usual 2 wks of gentamicin . It is believed that oral therapy, after the initial 2-3 days of parenteral antimicrobial, may be adequate for penicillin-sensitive streptococcal IE.

Pediatr Res, 1993 Jul, 34(1), 56 - 61
Effect of interleukin-11 with and without granulocyte colony-stimulating factor on in vivo neonatal rat hematopoiesis: induction of neonatal thrombocytosis by interleukin-11 and synergistic enhancement of neutrophilia by interleukin-11 + granulocyte colony-stimulating factor; Cairo MS et al.; IL-11, a new hematopoietic cytokine isolated from primate stromal cells (PU-34), has been shown to act synergistically with IL-3 to induce proliferation of early hematopoietic stem cells and induce in vitro CFU-MEG proliferation . We hypothesize that recombinant human (rh)IL-11 alone or in combination with granulocyte colony-stimulating factor (G-CSF) might modulate newborn in vivo granulopoiesis and thrombopoiesis . Newborn Sprague-Dawley rats were given 14 d of intraperitoneal rhIL-11 (0-250 micrograms/kg x 14 d), rhIL-11 (250 micrograms/kg) + rhG-CSF (5 micrograms/kg simultaneously x 14 d), rhIL-11 x 7 d followed by G-CSF x 7 d, G-CSF x 14 d, PBS/human serum albumin x 7 d followed by G-CSF x 7 d, or PBS/human serum albumin x 14 d . rhIL-11 alone had no effect on the circulating hematocrit or absolute neutrophil count . There was, however, a significant increase in the circulating platelet count after rhIL-11 (100 and 250 micrograms/kg) versus PBS/human serum albumin (d 13: 1241 +/- 54, 1262 +/- 58 versus 939 +/- 38 k/mm3; p = 0.01) . Sequential and simultaneous IL-11 + G-CSF caused a significant increase in the marrow neutrophil reserve and the circulating absolute neutrophil count above that observed when G-CSF alone was administered . IL-11 +/- G-CSF, however, failed to reduce the 96-h mortality rate during experimental group B streptococcal sepsis . These data suggest that IL-11 alone results in a significant elevation in the blood platelet concentration and, in combination with G-CSF, induces an increase in in vivo neonatal rat myelopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann N Y Acad Sci, 1993 Jun 23, 685, 447 - 57
Immunomodulating activity of antifungal drugs; Yamaguchi H et al.; 1 . The immunomodulating activity of antifungal drugs was reviewed . Although results are conflicting, all azole drugs tend to be immunosuppressive, except for fluconazole, which has no immunologic effect . In contrast, the polyene antibiotic amphotericin B (AMPH) is immunostimulatory . 2 . AMPH induced host resistance to Pseudomonas aeruginosa infection in mice, whereas no azole drugs did so . 3 . Polymorphonuclear leukocytes are activated by AMPH, but not by any azole drugs, in terms of the level of their adherence . 4 . No azole drugs induce in vitro tumor necrosis factor alpha (TNF) production by macrophages, whereas AMPH slightly but substantially does so . 5 . AMPH potently primes macrophages in vitro and in vivo so that they produce large amounts of TNF after the secondary stimulation (triggering) by bacterial lipopolysaccharides or a streptococcal preparation used for antitumor immunotherapy, OK432 . 6 . Viable or heat-killed Candida albicans cells are capable of inducing in vitro TNF production by macrophages . This activity of the fungal cells is enhanced by AMPH.

Cell Immunol, 1993 Jun, 149(1), 130 - 43
Differential regulation of group A streptococcal peptidoglycan-polysaccharide (PG-APS)-stimulated macrophage production of IL-1 by rat strains susceptible and resistant to PG-APS-induced arthritis; Bristol LA et al.; The magnitude of the response of rat macrophages to group A streptococcal cell wall peptidoglycan-polysaccharide (PG-APS) stimulation is strain-dependent . A comparison of IL-1 expression between macrophages from a PG-APS-resistant (BUF) and PG-APS-sensitive (LEW) rat strain revealed that while mRNA levels for IL-1 alpha and IL-1 beta were equivalent for the two strains, supernatants from BUF macrophages were less potent than LEW supernatants at stimulating thymocyte proliferation and contained less immunoreactive IL-1 alpha and IL-1 beta protein . BUF and LEW macrophages expressed nearly equivalent levels of IL-1 receptor antagonist (IL-1ra) mRNA and secreted IL-1ra protein in supernatants . The ratio of IL-1/IL-1ra produced by macrophages may influence susceptibility versus resistance to PG-APS and is strongly suggestive of a regulatory role for macrophages in the pathogenesis of PG-APS-induced arthritis.

South Med J, 1993 Jun, 86(6), 615 - 8
Group A streptococcal bacteremia in a mid-south children's hospital; Leggiadro RJ et al.; We reviewed microbiology and infection control records at a Memphis children's hospital from 1982 to 1990 to obtain epidemiologic, clinical, and microbiologic data on group A streptococcal (GAS) bacteremia . Varicella was the underlying condition in 8 of 37 (22%) patients identified and was often associated with severe GAS disease, including toxic shock-like syndrome . Twenty-one of 31 (68%) available blood isolates made GAS pyrogenic exotoxin (SPE) B by Ouchterlony immunodiffusion; gene probes identified speC and speA in 18 (58%) and 8 (26%) isolates, respectively . The B/C toxin profile, identified in 11 (35%) isolates, was the most common profile in this population, and the overall rate for speC was higher than rates recently reported from other areas . Although the clinical significance of the toxin profiles in our population is unclear, these data emphasize the geographic and temporal variability in the microbiologic properties of GAS disease.

Clin Chem, 1993 Jun, 39(6), 1007 - 11
Enzymatic determination of anti-NAD+ glycohydrolase in serum; Gella FJ et al.; A colorimetric method for measuring anti-NAD+ glycohydrolase in human sera has been developed . The assay involves the inhibition of NAD+ glycohydrolase (EC 3.2.2.5) by the antibody and determination of the noninhibited enzyme activity by using an enzymatic amplifying system for NAD+ . The assay is easily carried out and has the additional advantage of a direct relationship between signal and antibody concentration . The results obtained for 100 human sera compare favorably with other tests commonly used to obtain evidence of streptococcal infections or their complications, such as the anti-streptolysin O and the anti-DNase B tests.

J Psychosom Obstet Gynaecol, 1993 Jun, 14(2), 159 - 62
Neuropsychiatric aspects of Sydenham's chorea: a case report; Prasher VP et al.; A case report of a 21-year-old girl developing Sydenham's chorea in pregnancy following a probable streptococcal A infection is reported . Associated neuropsychiatric aspects are discussed . Awareness of this condition is encouraged to prevent possible misdiagnosis.

Z Gesamte Inn Med, 1993 Jun-Jul, 48(6-7), 324 - 31
{Value of thrombolytic therapy in deep venous thrombosis}; Wagner T; Thrombolytic therapy in a large number of patients may prevent post-thrombotic symptoms occurring as late consequences of deep vein thrombosis . In clinical studies, streptokinase either in conventional low dose, longterm, intravenous or in repeated intravenous short term ultra high dose regimens, urokinase and recombinant tissue-type plasminogen activators: all these plasminogen activators have been confirmed to successfully restore the patency of veins . As deep vein thrombosis generally extends over longer distances and are mostly older before being diagnosed, a lysing period of a couple of days must be taken into account . On the other hand, deep vein thromboses aged more than 2 weeks generally are no longer amenable to thrombolytic treatment . Due to their lack of short-term and long-term hazards, thromboses of the arms and the lower legs are not regarded an ideal indication for thrombolysis . Up to now, none of the currently available plasminogen activators has demonstrated superiority over the others, neither in respect of efficacy nor safety . With streptokinase intermittent intravenous ultra-high doses success rates of up to 80% (complete plus partial recanalization) can be achieved within a three-day treatment period . For its accompanying increased hazard of fatal pulmonary embolism, however, it is considered to be contraindicated in patients with pelvine thrombosis . Furthermore, contraindications to streptokinase such as streptococcal infections and prior lysis with streptokinase should always be kept in mind . In these cases streptokinase may be substituted by rt-PA, which, however, in the indication of deep vein thrombosis, is still not well documented today.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur Heart J, 1993 Jun, 14(6), 819 - 25
The incidence and mechanism of hypotension following thrombolytic therapy for acute myocardial infarction with streptokinase-containing agents--lack of relationship to pretreatment streptokinase resistance; Gemmill JD et al.; The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction . Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response . There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups . The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min . Blood pressure changes were well tolerated . Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity . The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated . The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.

J Mol Biol, 1993 May 5, 231(1), 82 - 102
Exploring the limits of precision and accuracy of protein structures determined by nuclear magnetic resonance spectroscopy; Clore GM et al.; The effects of the number, precision and accuracy of interproton distance restraints, of direct refinement against nuclear Overhauser enhancement (NOE) intensities and of the description of the non-bonded contacts on the precision and accuracy of a nuclear magnetic resonance (NMR) protein structure determination have been investigated . The model system employed is the 56 residue immunoglobulin G binding domain of streptococcal protein G . This choice was based on the availability of a very high resolution NMR structure (atomic root-mean-square distribution of the ensemble of 60 calculated structures about the mean co-ordinate positions of 0.25 A for the backbone atoms, 0.65 A for all atoms and 0.39 A for all atoms excluding disordered surface side-chains) . The experimental NMR data set for this structure determination comprised a total of 1058 experimental restraints of which 854 were approximate interproton distance restraints corresponding to all the structurally useful NOEs observable for this protein . The calculations presented in this paper reveal the following . (1) The number of interproton distance restraints constitutes the single most important determinant of both precision and accuracy . The ensemble precision and accuracy improves significantly as the number of interproton distance restraints is increased to an average of approximately 15 per residue, of which approximately 60% involve unique proton pairs; subsequent additions of interproton distance restraints, however, lead to less dramatic improvements as information redundancy sets in . (2) The ratio of ensemble precision to ensemble accuracy (which ranges from 0.5 to 0.7 for the backbone atoms) is approximately independent both of the number, precision and accuracy of the interproton distance restraints, and of whether the structures are refined against interproton distance restraints or directly against NOE intensities . (3) In an ensemble of structures generated from a large number of loose approximate interproton distance restraints (an average of approximately 15 restraints per residue with approximately 60% involving unique proton pairs), the interproton distance vectors corresponding to the restraints are very well defined with approximately 80% of vectors between unique proton pairs having a standard deviation of < or = 0.1 A . (4) The accuracy of the mean co-ordinates of an ensemble of structures is significantly higher than the average accuracy of the individual structures comprising the ensemble . For an average ensemble precision of > or = 0.6 A, the dependence of the accuracy of the mean co-ordinates on ensemble precision is approximately linear.(ABSTRACT TRUNCATED AT 400 WORDS)

J Immunother, 1993 May 4, 13(4), 232 - 42
Purification and characterization of interferon-gamma-inducing molecule of OK-432, a penicillin-killed streptococcal preparation, by monoclonal antibody neutralizing interferon-gamma-inducing activity of OK-432; Okamoto M et al.; An immunoglobulin M mouse monoclonal antibody (MAb) to streptococcal preparation OK-432, TS-2, was generated . The TS-2 MAb showed positive reaction with butanol extract of OK-432 and fungal, branched (1-->3)-gamma-glucans (lentinan and schizophyllan) as well as lipoteichoic acids . Moreover, the interferon (IFN)-gamma-inducing activity of OK-432 was neutralized by TS-2 MAb . The affinity column of butanol extract of OK-432 on CNBr-activated Sepharose 4B-bound TS-2 antibody was prepared and the fractions containing IFN-gamma-inducing activity were eluted . The polysaccharide sample carrying the IFN-gamma-inducing activity with a molecular weight of 700,000 was destroyed by treatment with acid or sodium metaperiodate, but was stable to treatment with heat, alkali, pronase, or neuraminidase . Survival time of human salivary adenocarcinoma-bearing animals given a combination of the polysaccharide sample purified from butanol extract of OK-432 and TS-2 MAb was significantly shorter compared with that of the tumor-bearing animals given only the purified polysaccharide sample of OK-432 . Moreover, a high level of effector cell activity in natural killer (NK) and lymphokine-activated killer (LAK) assays and significant increase of IFN-gamma-positive cells or asialo-GM1-positive cells were detected in the spleen cells from the animals given the polysaccharide sample purified from butanol extract of OK-432 . These findings indicate that the polysaccharide sample purified by the affinity chromatography of butanol extract of OK-432 on CNBr-activated Sepharose 4B-bound TS-2 MAb carries the IFN-gamma-inducing activity of OK-432 and marked antitumor activity.

Klin Lab Diagn, 1993 May-Jun, (3), 29 - 31
{Use of chemiluminescence in predicting suppurative-inflammatory complications in erysipelas and tonsillitis}; Frolov VM et al.; The levels of spontaneous and induced chemiluminescence of whole blood were assessed in 165 patients with erysipelas in the acute period of the infection and in 129 patients followed up for 1 to 6 months after it, as well as in 216 patients with tonsillitis in the acute period of the infection and in 182 ones after it . Induced chemiluminescence was 4-5 times more intensive than spontaneous one in the acute period of streptococcal infections (erysipelas, tonsillitis) during the development of pyo-inflammatory complications; when the disease course was uncomplicated, this difference made up 2.6-3.2 times . During remission of streptococcal infections (in case of recurrences or exacerbations) the initial level of spontaneous chemiluminescence was significantly lowered as against the norm, and the intensity of induced chemiluminescence was 2.35 +/- 0.12 times higher, the normal value being 2.83 +/- 0.15.

Immunology, 1993 May, 79(1), 89 - 94
Distinct IgG1 and IgG3 subclass responses to two streptococcal protein antigens in man: analysis of antibodies to streptolysin O and M protein using standardized subclass-specific enzyme-linked immunosorbent assays; Falconer AE et al.; The IgG subclass composition of antibodies to two streptococcal protein antigens in sera following infection was analysed by enzyme-linked immunosorbent assays (ELISA) . The assays were standardized using 5-iodo-4-hydroxy-nitrophenacetyl (NIP)-specific chimeric antibodies, to permit quantitative comparisons between subclasses . Antibodies to streptolysin O (SLO) were predominantly IgG1, with only minor contributions from the other subclasses . In contrast, antibodies to M protein were distributed between the IgG1 and IgG3 subclasses, and in approximately half the sera IgG3 predominated . The ratio of IgG1:IgG3 was greater for SLO than for M protein in 22/23 sera . Little or no IgG4 antibody was detected to either antigen . Functional affinities of the IgG1 and IgG3 antibodies, determined by inhibition ELISA, were comparable for the two antigens . The demonstration that two protein antigens encountered during streptococcal infection elicit antibody responses with markedly different subclass profiles has implications for IgG subclass regulation and vaccine development.

BMJ, 1993 May 1, 306(6886), 1170 - 2
Treatment of streptococcal pharyngitis with amoxycillin once a day; Shvartzman P et al.; OBJECTIVE--To evaluate treatment of group A beta haemolytic streptococcal pharyngitis with amoxycillin once daily compared with phenoxymethylpenicillin three or four times a day . DESIGN--Randomised controlled study of consecutive patients presenting with symptoms suggestive of group A beta haemolytic streptococcal pharyngitis in whom culture of a throat swab yielded positive results . SETTING--Five family medicine practices . SUBJECTS--157 patients aged over 3 years who required treatment with antibiotics . MAIN OUTCOME MEASURES--Clinical response, bacteriological response, days at work and school lost, and compliance . RESULTS--During the period of the study 393 patients presented with symptoms suggesting streptococcal pharyngitis; 157 of them had throat swabs that yielded positive results on culture . Eighty two were treated with phenoxymethylpenicillin and 75 with amoxycillin . No difference was observed in the clinical response, days at work and school lost (139 days for 64 patients taking phenoxymethylpenicillin v 100 days for 57 patients taking amoxycillin; p > 0.2), or residual positive cultures after two days (6 (7.3%) v 3 (4%); p > 0.5) . A significant difference in the bacteriological response was found after 14 days (5 (6.1%) v 0; p < 0.04) with no positive cultures observed in the amoxycillin group . CONCLUSIONS--These findings support the hypothesis that amoxycillin once daily is as effective as phenoxymethylpenicillin in the treatment of group A beta haemolytic streptococcal pharyngitis.

J Pediatr, 1993 May, 122(5 Pt 1), 727 - 9
T cell activation and cytokine release in streptococcal toxic shock-like syndrome; Nadal D et al.; A 5-year-old girl with streptococcal toxic shock-like syndrome during varicella infection had high levels of tumor necrosis factor alpha and interleukin-6 but no interleukin-1 or interleukin-2 in the serum . Intravenous administration of gamma-globulin coincided with clinical improvement and with reduction of the levels of tumor necrosis factor alpha and interleukin-6 . The data suggest that streptococcal pyrogenic exotoxins trigger synthesis of tumor necrosis factor alpha and interleukin-6 in vivo; intravenously administered gamma-globulin may down-regulate the cytokine response.

Am J Emerg Med, 1993 May, 11(3), 239 - 42
Streptococcal toxic shock-like syndrome presenting with hypoglycemia and reversible paralysis; Rubino DM et al.; A patient with pharyngitis progressive to Toxic Shock-Like Syndrome presented to the emergency department with a chief complaint of lower extremity paralysis . This paraplegia was completely reversed with the administration of intravenous glucose . Hypoglycemia-induced paraplegia has not previously been reported in the medical literature, and this report emphasizes the importance of considering low-blood glucose as a potential etiology for patients who present with these neurological symptoms.

J Bacteriol, 1993 May, 175(9), 2713 - 9
Nucleotide sequence analysis of the termini and chromosomal locus involved in site-specific integration of the streptococcal conjugative transposon Tn5252; Vijayakumar MN et al.; The 47-kb, broad-host-range, streptococcal conjugative transposon Tn5252 is capable of site-specific integration into the pneumococcal chromosome . We present the nucleotide sequence of the terminal regions of the transposon and its target site in the pneumococcal genome . No inverted repeats were found at the termini of the transposon . A 72-bp region of the target was present on either side following the insertion of Tn5252 and appeared to serve as a signal for its integration and excision . The data suggest that the left copy of the 72-bp segment was a part of the conjugative element, the crossover point of integration was nonrandom within this region, and the mechanism of insertion could resemble that of the site-specific temperate phages.

Ann Acad Med Singapore, 1993 May, 22(3), 296 - 9
Review of patients with infective endocarditis of native valves over a five-year period; Lim MC et al.; The clinical characteristics, echocardiographic features, bacteriologic data, morbidity and mortality of patients who were admitted to our hospital with infective endocarditis of their native valves over a five-year period were reviewed . There were 32 patients with a mean age of 38.2 +/- 16.2 years (range: 17 to 71 years) in our study population; 24 patients had underlying valvular abnormalities, six patients had congenital heart disease and two patients had no structural cardiac abnormality . Echocardiography was performed for all patients . Vegetations were absent in three (9.4%) patients, single in 19 (59.4%) patients and multiple in ten (31.3%) patients . Of the 24 (75%) patients who had left-sided endocarditis, mitral valve disease was the commonest valvular abnormality (16 patients) . Ventricular septal defect was the commonest underlying abnormality in patients with right-sided endocarditis . Blood cultures were positive in 26 (81.3%) patients; the commonest organism was streptococcal (16 or 50% patients) . Complications were present in 13 (40.6%) patients, of which eight patients had evidence of embolism, four patients had cardiac failure and one patient had a paravalvular abscess . Four (12.5%) patients died, two as a result of refractory heart failure and two as a consequence of septic embolism . Advances in medicine have resulted in a better outcome for patients with infective endocarditis, however, it remains an important disease with significant morbidity and mortality.

Br J Clin Pract, 1993 May-Jun, 47(3), 169 - 70
Periorbital necrotizing fasciitis: trivial facial injury resulting in cardiac arrest; Kiely PD et al.; Facial injuries in the context of alcohol abuse are a common presentation to casualty departments . While the majority are self limiting, the presence of periorbital or facial oedema should alert physicians to the development of periorbital necrotizing fasciitis . Here, a case illustrates this unusual manifestation of streptococcal infection, and emphasises the rapid onset and devastating systemic and local cosmetic consequences of this condition.

J Gen Microbiol, 1993 May, 139 ( Pt 5), 937 - 48
A critical appraisal of positive cooperativity in oral streptococcal adhesion: Scatchard analyses of adhesion data versus analyses of the spatial arrangement of adhering bacteria; Van der Mei HC et al.; Positive cooperativity is a mechanism proposed to account for the adhesion of bacteria to surfaces . In this paper, two methods that both claim to assess experimentally cooperative phenomena, viz . Scatchard analysis of adhesion data (using adhesion to vials) and analysis of the spatial arrangement of adhering cells (using a flow chamber), were compared and critically evaluated . Three oral strains were used and the substrata involved were glass (hydrophilic) and silicone-coated glass (hydrophobic) employed with or without a salivary coating . Scatchard analysis and near-neighbour analysis of adhering cells yield similar conclusions with regard to the mechanism of adhesion of the cells, provided that adhering cells are sufficiently immobilized under the experimental conditions . In the case of incomplete immobilization, near-neighbour collection results from sliding of adhering cells rather than from cooperative phenomena . Also, the agreement between the conclusions from both methods seems to be better, the more reversibly the cells adhere . Positive cooperativity can be absent or present on saliva-coated substrata with a distinct effect of the substratum hydrophobicity, despite the presence of an adsorbed film . This suggests that a different pellicle develops on a hydrophobic substratum than on a hydrophilic substratum . This is confirmed by our observation that the amino acid composition of salivary films is different on both types of substratum.

J Immunol, 1993 Apr 15, 150(8 Pt 1), 3207 - 14
CD28 delivers costimulatory signals for superantigen-induced activation of antigen-presenting cell-depleted human T lymphocytes; Ohnishi H et al.; The CD28 pathway functions to provide costimulatory signals that are required for TCR-mediated activation of T cells . The role of this pathway in superantigenic stimulation of resting human T cells was investigated in the presence and absence of APC using a streptococcal superantigen, pep M5 . Anti-B7/BB1 mAb inhibited the response of T cells when pep M5 was presented by APC . In the absence of APC, cross-linking CD28 by anti-CD28 mAb provides signals that synergize with APC-derived cytokines and with superantigen resulting in T cell proliferation . Anti-HLA-DR, -DQ mAb blocked the response of T cells to pep M5 presented by APC but had no effect on the response of purified T cells to the superantigen costimulated via CD28 cross-linking . These data show that the CD28 pathway is important for superantigenic stimulation of T cells and that signaling through this pathway can substitute for the APC-associated costimulatory activity that is essential for T cell stimulation . Moreover, the results are consistent with the notion that, in the presence of appropriate costimulation, pep M5 can directly interact with T cells and induce them to proliferate.

Biochemistry, 1993 Apr 6, 32(13), 3381 - 6
Proton nuclear magnetic resonance sequential assignments and secondary structure of an immunoglobulin light chain-binding domain of protein L; Wikstrom M et al.; The 1H NMR assignments have been made for the immunoglobulin (Ig) light chain-binding B1 domain of protein L from Peptostreptococcus magnus . The secondary structure elements and the global folding pattern were determined from nuclear Overhauser effects, backbone coupling constants, and slowly exchanging amide protons . The B1 domain was found to be folded into a globular unit of 61 amino acid residues, preceded by a 15 amino acid long disordered N-terminus . The folded portion of the molecule contains a four-stranded beta-sheet spanned by a central alpha-helix . The fold is similar to the IgG-binding domains of streptococcal protein G, despite the fact that the binding sites on immunoglobulins for the two proteins are different; protein G binds IgG through the constant (Fc) part of the heavy chain, whereas protein L has affinity for the variable domain of Ig light chains.

Curr Opin Immunol, 1993 Apr, 5(2), 272 - 7
Engineered bacterial receptors in immunology; Stahl S et al.; Gram-positive surface receptors, such as staphylococcal protein A ans streptococcal protein G, have been genetically engineered for many applications in the field of immunology, including detection antigens, affinity purification of fusion proteins and display of heterologous epitopes on the surface of bacterial cells.

Acta Paediatr Jpn, 1993 Apr, 35(2), 118 - 23
Serum anti-streptococcal IgA, IgG and IgM antibodies in IgA-associated diseases; Nakatsuka K; Serum anti-streptolysin-O antibody (ASO) and anti-streptococcal polysaccharide antibody (ASP) of IgA, IgG and IgM classes were measured using an enzyme-linked immunosorbent assay in 41 children with IgA nephropathy (Group A), 15 children with uncomplicated anaphylactoid purpura (Group B) and 13 children with purpura nephritis (Group C) . The serum concentrations of the IgA, IgG and IgM classes were measured by single radial immunodiffusion . When compared with sex- and age-matched controls, the concentrations of serum IgA (but not of IgG or IgM) were significantly increased in the three groups studied . The titers of ASO of the IgA and IgM classes, and those of ASP of the IgA and IgG classes, were significantly increased in Group A . In Group B, only the ASP titers of the IgA class were significantly increased . No significant difference was noted in the titers of either ASO or ASP of any class in Group C . Thus, increased antibody response in IgA nephropathy is not restricted to IgA . Anaphylactoid purpura with or without renal disease appears to be different in its humoral anti-streptococcal response from IgA nephropathy.

J Antibiot (Tokyo), 1993 Apr, 46(4), 668 - 75
N63-carboxamides of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin and deglucoteicoplanin; Malabarba A et al.; The synthesis and biological properties of a series of N63-carboxamides of 15-N-alkylated derivatives of teicoplanin A2 (CTA) and its aglycone (TD) are described . Among the compounds, those carrying hydrophilic groups or ionizable amino functions on the N15-alkyl chain are more soluble in water than parent N15-methylated or unmodified amides . Selected compounds were more active in vitro than CTA or TD, and a few of them were also slightly more efficacious in vivo than the parent antibiotics in streptococcal septicemia in the mouse . Their degree of activity varied with the structure and length of the N15-alkyl chains.

Can J Vet Res, 1993 Apr, 57(2), 79 - 88
Clinical and pathological findings in dogs following supralethal total body irradiation with and without infusion of autologous long-term marrow culture cells; Abrams-Ogg AC et al.; We developed a canine model for autologous bone marrow transplantation (AuBMT) with long-term marrow culture (LTMC) cells . Marrow was harvested from nine normal dogs . Harvests from dogs 2-7 were placed into 21 day LTMC . Cells in LTMC from dogs 4-7 were labelled with the neomycin phosphotransferase gene neo . Dogs were given 60Co total body irradiation (TBI) and then infused with LTMC cells: dog 1 received 500 cGy TBI and 2.08 x 10(8)/kg uncultured marrow cells . Dogs 2-7 received 600-800 cGy TBI and 0.07-0.45 x 10(8)/kg LTMC cells . Dogs 8 and 9 received 600 and 800 cGy TBI, respectively, but no infusion of marrow or LTMC cells . For all dogs, profound myelosuppression developed during week 1 and pyrexia developed during week 2 . Enrofloxacin was given from one day before TBI until a peripheral neutrophil count > 1.0 x 10(9)/L was achieved, which eliminated Escherichia coli from feces . Dogs 1, 2 and 5-9 also received gentamicin and/or combination beta-lactam antibiotics . Numerous platelet transfusions were needed to control hemorrhages in all dogs except dog 1 . Dog 1 achieved neutrophils > 1.0 x 10(9)/L on day 15, while dogs 2 and 5-9 achieved this count on days 33-48 . Dogs 3 and 4 died on days 17 and 18, respectively, of beta-hemolytic streptococcal sepsis and hemorrhage, with no evidence of hematopoiesis at necropsy . The marker gene, neo, was documented in lymphoid and myeloid cells of dogs 5-7 up to 21 months post-AuBMT . Our studies indicate that dogs can recover following supralethal TBI and can survive the delayed engraftment associated with AuBMT using LTMC cells, if they receive intensive platelet and antimicrobial therapy . Used prophylactically for such therapy, enrofloxacin achieved selective intestinal decontamination, but did not prevent sepsis when used as the sole antimicrobial agent during myelosuppression . Furthermore, our studies indicate that infused LTMC cells, at the above doses, can contribute to hematopoietic recovery, but are not essential for recovery following TBI, and do not shorten the period of prolonged profound myelosuppression induced by TBI.

J Paediatr Child Health, 1993 Apr, 29(2), 144 - 5
Perianal group A streptococcal infection; Guppy DH; Four cases of perianal group A streptococcal infection presented with typical features of this condition; but because of lack of recognition appropriate therapy was delayed . Once group A streptococcal infection was diagnosed there was a high frequency of relapses . The need for prolonged treatment is illustrated.

Pediatr Infect Dis J, 1993 Apr, 12(4), 275 - 9
Cefpodoxime proxetil vs . penicillin V in pediatric streptococcal pharyngitis/tonsillitis; Dajani AS et al.; This multicenter, randomized, parallel treatment, observer-blinded study was designed to evaluate the safety and efficacy of cefpodoxime proxetil (5 mg/kg twice daily for 10 days) compared with penicillin V (13.4 mg/kg three times daily for 10 days) for treatment of Group A streptococcal pharyngitis and tonsillitis in pediatric patients . Clinical and microbiologic results were evaluated before therapy, during therapy (Study Days 3 to 5), at the end of therapy (Study Days 14 to 18) and at long term follow-up (Study Days 30 to 32) . Both drugs were well-tolerated in 578 patients evaluable for safety . Mild gastrointestinal complaints were noted in 6.7% of 386 cefpodoxime-treated patients and in 5.2% of 192 penicillin-treated patients . In 413 patients evaluable for efficacy, both treatment regimens resulted in comparably favorable clinical outcome; cure rates were 83.8% for 275 cefpodoxime-treated patients and 77.5% for 138 penicillin-treated patients . However, eradication of S . pyogenes at end of therapy was significantly higher with cefpodoxime (93.1%) than with penicillin (81.2%) (P < 0.01) . Cefpodoxime proxetil provides an effective alternative to penicillin V for the treatment of streptococcal pharyngitis and tonsillitis.

Med Decis Making, 1993 Apr-Jun, 13(2), 126 - 32
Using treatment-tradeoff preferences to select diagnostic strategies: linking the ROC curve to threshold analysis; DeNeef P et al.; Selection of optimal diagnostic strategies depends on the accuracy of diagnostic tests, the prevalence of disease, and the relative benefits and harms resulting from test/treatment choices . One can characterize diagnostic strategies according to their net benefit-to-harm ratios . Within the framework of expected-utility theory, the benefit-to-harm ratio is equivalent to the marginal tradeoff between erroneous and correct treatment choices . Consequently, a physician can identify his or her preferred strategy by asking the question: "How many additional treatment errors am I willing to make in order to treat one additional person correctly?" Family physicians were asked to indicate their lowest and highest acceptable tradeoff ratios in a survey about streptococcal pharyngitis . All 53 respondents indicated uncertainty about their preferred treatment-tradeoff ratios . For 58% of respondents, the midpoints of the acceptable range of tradeoff ratios corresponded to generally accepted diagnostic strategies: 1) test all or 2) treat if classic, test all others . In contrast, previously published patient utilities yield a treatment-tradeoff ratio that corresponds to the strategy of treating all cases . The analysis illustrates the linkage between the optimal operating point on a receiver operating characteristic (ROC) curve and the selection of a preferred diagnostic strategy based on treatment thresholds derived from benefit-to-harm ratios . The survey results indicate that physicians can respond directly to questions assessing their preferences for such treatment thresholds . Differences between patients and physicians have significant impacts on choices of test and treatment strategies.

Pediatr Nephrol, 1993 Apr, 7(2), 194 - 5
Cerebral vasculitis in acute post-streptococcal glomerulonephritis; Kaplan RA et al.; Neurological complications in acute post-streptococcal glomerulonephritis (APSGN) have been traditionally attributed to hypertensive encephalopathy . A 9-year-old girl with biopsy-documented APSGN developed seizures at a time she was normotensive and biochemically well balanced . Computed tomography of her brain was consistent with vasculitis, a finding which was also clinically supported by apparent vasculitic involvement of other organ systems . All clinical, laboratory and radiological abnormalities resolved with recovery from the APSGN . We suggest that on rare occasions neurological complications in APSGN may result from involvement of the central nervous system in multiorgan transient vasculitis.

J Pediatr, 1993 Apr, 122(4), 638 - 40
Neonatal sepsis caused by a new group B streptococcal serotype; Rench MA et al.; Two infants with typical clinical presentations for invasive neonatal group B streptococcal disease caused by a new serotype, type V, are described . Organisms of this capsular type should be sought among isolates from sick neonates to evaluate their prevalence and associated patterns of disease.

Infect Immun, 1993 Apr, 61(4), 1194 - 201
Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5; Kotb M et al.; We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release . The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells . The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma) . In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h . pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC) . The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h . Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma . The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB) . SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production . Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma . In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation . These cytokines also play a major role in human T-cell responses to this super antigen.

J Infect Dis, 1993 Apr, 167(4), 979 - 83
Increase in activated T cells and reduction in suppressor/cytotoxic T cells in acute rheumatic fever and active rheumatic heart disease: a longitudinal study; Morris K et al.; In a prospective study, patients with acute rheumatic fever (ARF) and active rheumatic heart disease (ARHD) showed a significant increase in CD4+ T cells, CD22+ B cells, and CD4:CD8 cell ratio but a significant decrease in the percentages of CD8+ and CD3+ T lymphocytes compared with patients with quiescent RHD (CRHD) or streptococcal pharyngitis (SP) and normal controls . The proportion of interleukin-2 receptor (IL-2R)+ (CD25+) cells was higher in peripheral blood mononuclear cell cultures (both before and after phytohemagglutinin stimulation) of ARF and ARHD patients than in those of CRHD or SP patients or controls; this finding persisted up to 48 weeks . In ARF patients, the percentage of CD8+ cells returned to within normal range at 48 weeks . Furthermore, the percentage of IL-2R+ cells correlated positively with the percentage of CD4+ but not of CD8+ lymphocytes, suggesting that helper/inducer T cells are in an immunologically activated state and may account for aberrations in the distribution of lymphocyte populations in peripheral blood of ARF and ARHD patients.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 633 - 6
Efficacy and ocular penetration of sparfloxacin in experimental streptococcal endophthalmitis; Cochereau-Massin I et al.; Gram-positive cocci are the most common pathogens in severe human eye infections . Streptococcal endophthalmitis is a devastating infection, and intravitreal antibiotic therapy is limited by retinal toxicity . Because few systemic antistreptococcal antibiotics penetrate into the vitreous, sparfloxacin, a newer quinolone with improved antistreptococcal activity, might be of interest . We therefore assessed its efficacy by the intravitreal route in a rabbit model of streptococcal endophthalmitis . The vitreal bacterial count (mean +/- standard deviation log10 CFU per milliliter) was significantly reduced after an intravitreal injection of 800 micrograms of sprafloxacin (4.9 +/- 0.7) relative to the counts in untreated control (7.1 +/- 0.7) and pefloxacin-treated (7.8 +/- 1.2) eyes . After systemic administration to rabbits, the maximum concentration of sparfloxacin in serum was 5.6 micrograms.ml-1 and the half-life was 7.5 h . Sparfloxacin exhibited very good penetration ratios in the vitreous (54%), cornea (76%), and lens (36%) . In the vitreous, the levels of sparfloxacin remained greater than the MICs for most gram-positive cocci for up to 18 h . Further experimental studies are warranted to determine the efficacy of systemic sparfloxacin as adjuvant therapy in the treatment of human endophthalmitis.

Childs Nerv Syst, 1993 Apr, 9(2), 117 - 8
A unique presentation of nontraumatic atlantoaxial instability: a case report; Olivero WC; A unique case of a 3-year-old child who presented with neck pain and torticollis following a streptococcal pharyngitis is described . Radiological evaluation revealed dislocation of the synchondrosis between the odontoid and the body of the axis with resultant atlantoaxial instability . This dislocation healed spontaneously over the course of 2 months without any orthotic or surgical treatment.

Kansenshogaku Zasshi, 1993 Apr, 67(4), 305 - 10
{The effect of cefaclor on the nasopharyngeal pathogens in children}; Tomiyama M et al.; Nasopharyngeal specimens were taken from 29 children with acute otitis media, 14 children with chronic sinusitis at acute exacerbation and 2 children with streptococcal pharyngitis who had received cefaclor for 14 days . The study was designed to compare the microbiologic flora of the nasopharynx before the treatment of these diseases with that after the treatment . In this report the subjects were limited to the children who had not received antibiotics within 1 month . Pathogens detected on initial examination were 49 strains consisting of 40 strains of H . influenzae, 3 strains of S . aureus, 5 strains of S . pyogenes, and 1 strain of S . pneumoniae . Two strains were detected in 4 patients . Pathogens remained after treatment in 29 patient, with an unchanged number of pathogens in 12 patients, a decreased number in 14, and microbial substitution in 3 . All of the remaining pathogens were H . influenzae, and minimum inhibitory concentration (MIC) changed in 5 of the 26 patients in whom H . influenzae was detected before and after treatment . In a patients with increased MIC, the strain changed from a sensitive strain with an MIC of lower than 3.13 micrograms/ml to a highly resistant strain with an MIC of 25.0 micrograms/ml or higher . By contrast, in 2 patients with decreased MIC, the strain changed from a highly resistant strain with an MIC of 12.5 micrograms/ml or higher to a sensitive strain with an MIC of lower than 3.13 micrograms/ml . In the other patient, MIC decreased to 3.13 micrograms/ml after it had increased from 3.13 micrograms/ml to 25.0 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Derm Venereol, 1993 Apr, 73(2), 94 - 6
Streptococcal and staphylococcal superantigens (ETA, SEB): presentation by human epidermal cells and induction of autologous T cell proliferation in vitro; Buslau M et al.; Streptococcal and staphylococcal toxins are responsible for skin-related clinical conditions, e.g . scarlet fever and toxic shock syndrome . Skin involvement may result from a hypersensitivity reaction to these toxins; however, their precise mode of action has still to be elucidated . The aim of the present study was to investigate the capacity of human epidermal cells to present streptococcal erythrogenic toxin A (ETA) or staphylococcal enterotoxin B (SEB) to autologous T-lymphocytes in vitro . We found a significant T-lymphocyte proliferation response to minute amounts of ETA (p < 0.01) and SEB (p < 0.02) when co-cultured with freshly isolated autologous human epidermal cells . We suggest that human skin may serve not only as an entry for microbial toxin-producing strains but also as an important target for streptococcal and staphylococcal toxin-binding and subsequent T cell proliferation.

Biull Eksp Biol Med, 1993 Apr, 115(4), 386 - 9
{Group A streptococcal polysaccharide--an inhibitor of the functional activity of T-suppressors induced by Con A in a culture of mononuclear cells of human peripheral blood}; Gnezitskaia EV et al.; It was found that group A streptococcal polysaccharide (A-PS) had no mitogenic effect on the intact human blood mononuclear cells' culture (MNC) and on its proliferation stimulated with ConA . Using a double staining technique for simultaneously determining cell surface phenotype and degree of cell activation by it's ability to include the tetrazolium dye MTT (3-{4,5-dimethylthiazol-2-yl} -2,5-diphenyl tetrazolium bromide) it was established that A-PS decreased the percent of activated (MTT+) cells in the subpopulation of CD8+ and increased the percent of MTT+ cells among CD4+ lymphocytes in the intact MNC . In the MNC stimulated with ConA A-PS caused only one of these effects: it decreased the percent of MTT+ cells in the subpopulation of CD8+ lymphocytes . The correlation was established between the results obtained with MTT-technique and cell transfer test, because the MNC preincubated with ConA and A-PS lost the ability to suppresses MNC proliferation stimulated with PHA . The data obtained supported the assumption that A-PS as a carrier of determinants common with thymus epidermal antigens (factors) may act as it's functional analogue and thus promote the development of autoimmune process during the rheumatic fever.

Biochem J, 1993 Mar 15, 290 ( Pt 3), 791 - 5
The hyaluronate synthase from a eukaryotic cell line; Klewes L et al.; The hyaluronate synthase complex was identified in plasma membranes from B6 cells . It contained two subunits of molecular masses 52 kDa and 60 kDa which bound the precursor UDP-GlcA in digitonin solution and partitioned into the aqueous phase, together with nascent hyaluronate upon Triton X-114 phase separation . The 52 kDa protein cross-reacted with poly- and monoclonal antibodies raised against the streptococcal hyaluronate synthase and the 60 kDa protein was recognized by monoclonal antibodies raised against a hyaluronate receptor . The 52 kDa protein was purified to homogeneity by affinity chromatography with monoclonal anti-hyaluronate synthase.

Am J Cardiol, 1993 Mar 15, 71(8), 640 - 5
Neutralizing antibodies to streptokinase four years after intravenous thrombolytic therapy; Elliott JM et al.; Neutralization antibodies to streptokinase increase to high levels within several days of administration . It is not known how long these high levels persist . The time course of antibody levels needs to be further characterized owing to the increasing need to readminister thrombolytic therapy, and to the possibility that these antibodies may compromise the safety and efficacy of a further dose of streptokinase or streptokinase-containing compounds . In this study, paired streptokinase neutralization titers (in vitro functional assay) and specific antistreptokinase immunoglobulin G (IgG) antibody levels were measured in 145 patients who received streptokinase between 10 and 48 months previously . Serologic evidence of recent streptococcal infection was also sought . Neutralization titers sufficient to inactivate a conventional dose of 1,500,000 units of streptokinase were still present in 50% of patients (95% confidence interval 36-64) at 24 months, 48% (34-62) at 36 months, and 51% (37-71) at 48 months after streptokinase administration . Levels of specific antistreptokinase IgG antibodies also remained constant over the 1- to 4-year period . Neutralization titers were weakly correlated with specific IgG levels (r = 0.35) . Antistreptolysin titers > or = 250 and > or = 333 IU/ml were present in 30% (24-38) and 12% (8-18) of these patients, respectively . Neutralization titers were not correlated with antistreptolysin titers . Neutralizing antibodies (assessed by an in vitro functional assay) remained high in 51% of patients 4 years after intravenous streptokinase administration . It is not known whether persisting high in vitro neutralization titers affect the efficacy and safety of repeat administration of streptokinase or streptokinase-containing compounds.

J Antimicrob Chemother, 1993 Mar, 31 Suppl C, 97 - 102
Clinical efficacy of dirithromycin in pharyngitis and tonsillitis; Muller O et al.; A total of 193 patients with streptococcal pharyngitis/tonsillitis received 500 mg dirithromycin once daily and 196 patients 250 mg erythromycin four times daily for ten days in a double-blind, parallel-group multicentre study . In the dirithromycin treatment group, 97 (50.3%) patients completed the study and were evaluated for efficacy analysis, and 99/196 (50.5%) erythromycin-treated were evaluated for efficacy of treatment . Favourable clinical responses to treatment (cure or improvement of symptoms) at the post-therapy visit (three to five days after therapy completion) occurred in 89 (91.7%) dirithromycin- and 93 (93.9%) erythromycin-treated patients . Bacteriological response was favourable (pathogen eliminated in 81 (83.5%) dirithromycin- and 87 (87.9%) erythromycin-treated patients . At late post-therapy (three to five weeks after treatment) 82/89 (92.1%) dirithromycin- and 90/93 (96.8%) erythromycin-treated patients had a favourable clinical response . Bacteriological response at late post-therapy was favourable in 77 (86.5%) dirithromycin- and 85 (94.4%) erythromycin-treated patients . No deaths occurred during or after treatment, and the serious events experienced by three dirithromycin- and one erythromycin-treated patients were unrelated to treatment . Five patients taking dirithromycin and seven taking erythromycin discontinued treatment prematurely, mainly due to gastrointestinal disturbances . Adverse events that occurred in 2% or more of patients in each treatment group were mainly gastrointestinal (diarrhoea, abdominal pain, nausea and vomiting); headache and rash were also reported . No significant differences in clinical laboratory data were detected that were considered to be drug-related.

Infect Dis Clin North Am, 1993 Mar, 7(1), 97 - 115
Ceftriaxone and outpatient treatment of infective endocarditis; Francioli PB; There are a total of 8000 cases of infective endocarditis yearly in the United States . Central nervous system metastatic infections are not uncommon in infective endocarditis . Because ceftriaxone is highly bound to serum proteins, there is concern that the drug is highly bound to serum proteins, there is concern that the drug might not penetrate well in the core of an infected vegetation . To date, there are two published studies on the treatment of nonenterococcal streptococcal endocarditis by ceftriaxone in humans . Ceftriaxone appears to be an attractive alternative antibiotic therapy to conventional regimens in the treatment of streptococcal endocarditis.

Biotechniques, 1993 Mar, 14(3), 424 - 34
Solid-phase gene assembly of constructs derived from the Plasmodium falciparum malaria blood-stage antigen Ag332; Stahl S et al.; A general method for solid-phase gene assembly on streptavidin-coated magnetic beads has been developed . The introduction of biotin in the 5'-end of the initiation oligonucleotide enables anchoring to the bead by means of the streptavidin-biotin interaction . The immobilization of one oligonucleotide enables controlled, stepwise annealing/ligation of successive 5'-phosphorylated oligonucleotides to rapidly build up predesigned gene constructs . In this report, we have assembled gene constructs of different lengths derived from the Plasmodium falciparum malaria blood-stage antigen Ag332 . The encoded gene products were subsequently expressed in Escherichia coli using two parallel expression systems based on staphylococcal protein A and streptococcal protein G, respectively.

Exp Parasitol, 1993 Mar, 76(2), 134 - 45
Plasmodium falciparum: the immune response in rabbits to the clustered asparagine-rich protein (CARP) after immunization in Freund's adjuvant or immunostimulating complexes (ISCOMs); Sjolander A et al.; The Plasmodium falciparum clustered asparagine-rich protein (CARP) is a merozoite-associated antigen which contains approximately 30% asparagine . Analysis of the DNA sequences located 5' of the cloned 1.4-kb CARP gene in the P . falciparum genome suggests that this gene fragment may encode the complete CARP and that the gene product is a protein of M(r) 50,000 . To analyze the immunogenicity of CARP, the gene was expressed as a fusion protein with staphylococcal protein A (SpA-CARP) . Immunization of rabbits with SpA-CARP in Freund's complete adjuvant (FCA) resulted in a strong antibody response against CARP as measured in ELISA . This response was efficiently boosted and sustained over a long time while that induced by two immunizations with SpA-CARP in ISCOMs was weak and of shorter duration . In both instances, the antibody levels against CARP were further increased by a second booster injection consisting of either SpA-CARP or CARP fused to the serum albumin-binding region (BB) of streptococcal protein G (BB-CARP) in PBS, indicating that immunizations with SpA-CARP in FCA or ISCOMs had induced a CARP-specific immunological memory . Boosting with BB-CARP in PBS was more efficient than boosting with SpA-CARP in PBS . In all rabbits, the antibodies obtained after the booster with CARP in PBS were the most efficient inhibitors of merozoite invasion in vitro . The antisera reacted with the intracellular parasite in immunofluorescence and with a band of M(r) 50,000 in immunoblotting while several high-molecular-weight components as well as the one of M(r) 50,000 were immunoprecipitated . The specificity of the antibody responses varied between the different rabbits as indicated in ELISA, with short synthetic peptides representing different CARP sequences . Taken together, the results suggest that a previously cloned genomic DNA fragment may encode the complete P . falciparum blood-stage antigen CARP and that CARP is immunogenic in rabbits both when administered in FCA or ISCOMs.

Arch Ophthalmol, 1993 Mar, 111(3), 377 - 9
Bacterial endophthalmitis following sutureless cataract surgery; Miller KM et al.; We examined a patient who developed group G streptococcal endophthalmitis following phacoemulsification with intraocular lens implantation and sutureless wound closure . Pathologic examination of the enucleated globe 1 month after surgery revealed an intense suppurative reaction centered in the anterior chamber and an open surgical wound filled with fibrinopurulent granulation tissue . Inadequate draping, a high number of instruments passing into and out of the eye during surgery, and wound testing for water tightness with viscoelastic substance in the eye were observed on a videotape of the surgery.

Int J Pediatr Otorhinolaryngol, 1993 Mar, 26(2), 181 - 4
Spontaneous tonsillar bleeding; secondary to acute tonsillitis in children; Shatz A; Serious spontaneous tonsillar bleeding in three children was considered with respect to cause(s) and therapy . In two of the children the cause was related to streptococcal infection, and to hemophilus in the third child . A clinical and laboratory follow-up on our diagnosis indicated an infectious cause in each instance, inducing superficial vascular wall erosion . In our clinic the incidence of this relatively rare medical phenomenon in 254 cases of acute tonsillitis, has been only 1.2% . The children were successfully treated with conservative local treatment, such as cauterization and systemic antibiotics.

Scand J Immunol, 1993 Mar, 37(3), 343 - 8
Human B lymphocyte in vitro response to the group B streptococcal type III capsular carbohydrate; Feldman RG et al.; Anti-group B streptococcal type III polysaccharide-specific human B cells from the peripheral circulation can be activated and detected in an in vitro culture system . It is possible to detect both IgM- and IgG- producing cells from both seropositive and seronegative donors . The specificity of the response was demonstrated by inhibition with excess liquid phase antigen and the use of related but antigenically distinct control antigens . The response was absent without the addition of T cells, optimal at 10% and 25% T cells respectively for IgM- and IgG-secreting cells, and undetectable using 50% T cells . The optimal antigen concentration for in vitro B-cell activation is 2.5 x 10(-4) micrograms/ml . Cells from 5 of 6 seropositive donors and 3 of 7 seronegative donors produced specific IgM antibody after culture with antigen . We conclude that the control of the human antibody response to the group B streptococcal type III polysaccharide is influenced by T cells . The response seen in the culture system may be of value in assessing future vaccine candidates designed to prevent neonatal infections.

Diabetes, 1993 Mar, 42(3), 398 - 404
Prevention of autoimmune diabetes with lymphotoxin in NOD mice; Seino H et al.; We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats . In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes . The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively . Intensity of insulitis was slightly reduced in the long-term LT-treated mice . LT productivity by ConA-stimulated spleen cells was examined in vitro . Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females . The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice . However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Exp Immunol, 1993 Mar, 91(3), 429 - 36
Enhancement of IL-1, IL-2 production and IL-2 receptor generation in patients with acute rheumatic fever and active rheumatic heart disease; a prospective study; Morris K et al.; In a prospective study, patients with quiescent rheumatic heart disease (CRHD), streptococcal pharyngitis (SP) and healthy normal subjects produced comparable amounts of IL-1 and IL-2, but acute rheumatic fever (ARF) patients produced significantly elevated amounts of IL-1 and IL-2 at all intervals up to 48 weeks . In active rheumatic heart disease (ARHD), IL-1 activity returned to within normal range at 48 weeks, but IL-2 activity remained persistently elevated compared with CRHD, SP and healthy age- and sex-matched volunteers . CD4+ T lymphocytes were significantly increased in the peripheral blood of ARF and ARHD patients . The amount of IL-2 produced by ARF and ARHD patients correlated with the percentage of helper T lymphocytes (CD4+ cells) but not with the percentage of suppressor/cytotoxic T lymphocytes (CD8+ cells) . Moreover, pre- and post-phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from ARF and ARHD patients contained higher proportions of IL-2R+ (CD25+) cells than those from patients with SP, CRHD and normal individuals, which persisted up to 48 weeks . The percentage of CD25+ cells in both types of PBMC cultures directly correlated with the percentage of CD4+ cells and not with CD8+ cells in active rheumatic patients only . These findings indicate that the immune response in ARF and ARHD patients is skewed to produce activated helper T cells that release IL-2 which drives the accumulation of more T helper cells . The result is an undamped helper T cell response in the peripheral blood of these patients.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Mar-Apr, (2), 57 - 63
{Streptococcal respiratory infection in large organized children's collectives and experience in optimizing its prevention}; Obernikhin IM et al.; Epidemiological analysis of the manifestations of respiratory streptococcal infection in the all-year-round pioneer camp "Ocean" over 1984-1990 and in similar large organized groups of children revealed some common regularities manifested as consecutively repeating morbidity rises in acute respiratory diseases, tonsillitis, scarlet fever over a year (rotations 1-3 and 9) . Time course of the disease incidence over each rotation (month) had a specific pattern as well . Trials of our newly developed system of prevention and treatment with tomicid showed its high effectiveness, which manifested by a drop in the morbidity level and changes in the structure and dynamics of respiratory streptococcal infection.

Infect Immun, 1993 Mar, 61(3), 1062 - 8
Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins; Robinson JH et al.; We have previously defined major histocompatibility complex (MHC) class II-restricted T-cell epitopes from the carboxy-terminal region of group A streptococcal type 5 M protein . In this report, T-cell responses to one of these epitopes have been characterized in detail . T-cell clones from recombinant M5-immunized mice and popliteal lymph node cells from peptide-immunized mice were used to show that sM5{300-319} is recognized in the context of I-A alleles of four of nine independent MHC class II haplotypes: I-Ad, I-Af, I-Ak, and I-As . This epitope was also recognized by both helper (Th2) and inflammatory (Th1) subsets of murine T cells . The I-Ad-restricted epitope recognized by BALB/c mice was mapped to the 12-amino-acid peptide sM5{308-319} and was shown to provide helper function for an immunoglobulin G anti-peptide antibody response in BALB/c mice . Anti-peptide antibody was shown to be specific for M5{304-315} but failed to recognize intact rM5, suggesting that the conformation of the epitope differed between peptide and protein . However, the results demonstrate that overlapping epitopes can be the focus for both immunoglobulin G antibodies and the T cells which augment their production . Comparison of the available sequences for M proteins indicated that the T-cell epitope within M5{300-319} was highly conserved between M types and hence may elicit helper function for protective antibody responses to a wide range of M types . T-cell epitopes from conserved regions of M proteins which are recognized in the context of multiple MHC haplotypes have potential for the design of multivalent streptococcal vaccines.

Mol Cell Biochem, 1993 Feb 17, 119(1-2), 67 - 71
Cardiac contractile proteins and autoimmune myocarditis; Izumi T et al.; Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed . In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease . Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated . Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis . First of all, the role of cardiac myosin has been strongly emphasized . But, the antigen determinants: epitope proteins remain unclear . Either cross-activity to the streptococcal M protein and/or the alpha-helical coiled-coil protein may be an important factor to determine antigenicity . In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable . Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.

Fukuoka Igaku Zasshi, 1993 Feb, 84(2), 58 - 67
{Generation of a monoclonal antibody specific to human T cell receptor V beta 22, and analysis of peripheral blood T cell repertoire utilizing this monoclonal antibody}; Okamoto Y; A murine monoclonal antibody, R1-21, against a HLA-DR4 restricted CD4+ T cell line specific to streptococcal cell wall (SCW) Ag was generated . R1-21 reacted with about 50% of the HLA-DR4 restricted CD4+ T cell line . R1-21 distinguished a diversity of TCR because it reacted with a small population of peripheral T lymphocytes, induced proliferative response in peripheral blood lymphocytes, immunoprecipitated a cell surface molecule of 80 kDa in non-reduced condition and 45 and 40 kDa in reduced condition, and the immunoprecipitates with R1-21 was precleared with a known anti-TCR mAb . Sequence analysis of cDNA clones corresponding to TCR alpha and beta genes derived from R1-21 positive and negative T cell lines revealed that R1-21 recognized a V beta 22 gene product . By utilizing R1-21, it was found that V beta 22 positive cells existed 3.80 +/- 0.94% and 3.56 +/- 0.59% in healthy adult and neonatal cord blood T lymphocytes, respectively, and a V beta 22 gene product was skewed expressed on CD4+ T cells . (CD 4/CD 8 ratio: 1.69 +/- 0.57).

Voen Med Zh, 1993 Feb, (2), 33 - 6, 80
{Angina morbidity in an organized collective with a periodic turnover of its personnel}; Sobolev VI et al.; The article studies the average angina morbidity in the military unit during 9 years which resulted in 48.4% (scarlet fever--0.34%) . Laboratory diagnostics is needed to make the estimation of streptococcal infection which has an acute respiratory infectious character during its clinical course . Among the whole number of patients 89.2% have come through this illness for one time, 9% twice, and 4.8%--three times . The dynamics of the angina morbidity had a periodical cycle of 2-3 years which was independent from the morbidity cycle of local civilian population . The authors show a statistic dependency between average morbidity index and the quantity of servicemen in one dormitory, its square and volume per one man . Application of "time before illness" index for 24 months made it possible to disclose the phase character in the development of streptococcal infection among personnel of the same call-up period . The general tendency towards reduction of the morbidity index was accompanied with regular upgrades of the infection after each spring or autumn renovation of personnel.

Hybridoma, 1993 Feb, 12(1), 143 - 7
Chicken anti-protein G for the detection of small amounts of protein G; Larsson A et al.; Streptococcal protein G, similar to staphylococcal protein A, is the Fc-binding proteins that seems best suited for affinity-purification of mouse, rat or human monoclonal antibodies . We have developed a sandwich-ELISA for monitoring of protein G leakage from such columns . It utilizes microtitre plates coated with chicken anti-protein G to capture protein G, and biotinylated chicken anti-protein G to detect bound protein G . Chicken IgG is one of a very few IgG that does not show any Fc reactivity with protein G . It is thus possible to make an antigen-specific assay for protein G . This assay can be used to detect protein G in IgG containing solutions, such as monoclonal antibody preparations . The method can be used to detect 1 x 10(-7) g protein G/1 in the presence of human serum or human IgG.

Int J Epidemiol, 1993 Feb, 22(1), 62 - 71
Cardiac mortality in Alaska's indigenous and non-Native residents; Davidson M et al.; Cardiac disease mortality in Alaska, from both ischaemic and rheumatic heart disease, is of interest given the high consumption of fish and high streptococcal disease rates in the indigenous population . Uniformly coded underlying cause-of-death data for the period 1979-1988, compared with that from 1955-1965, indicated that deaths from all cardiac diseases combined, have been increasing in Alaska Natives over the past 30 years . Recent mortality from all cardiac, ischaemic, and rheumatic heart diseases in Alaska Natives were 80%, 61%, and 202% of those corresponding levels in Alaskan whites, whose cardiac mortality closely profiles US whites . Alaska Native men aged 30-45 years had higher overall mortality rates for cardiac diseases than did whites because of higher mortality rates of rheumatic heart disease and cardiomyopathy . Elderly Alaska Native men had lower rates than whites, reflecting less ischaemic heart disease mortality . The lowest levels of ischaemic heart disease mortality, less than one-third that of US whites, occurred in Alaskan Eskimos who lived in an area with documented patterns of high salmon consumption by individuals with high blood concentrations of omega-3 fatty acids . Elevated mortality from non-ischaemic heart disease and previously documented genetic markers suggest associations deserving further study.

J Pediatr Surg, 1993 Feb, 28(2), 135 - 7
A clinical-pathological study of nonsurvivors of newborn ECMO; Weber TR et al.; Extracorporeal membrane oxygenation (ECMO) is an important means of supporting newborns with respiratory failure . While short- and long-term follow-up of ECMO survivors has been thoroughly addressed, there is no systematic study of nonsurvivors . Nineteen nonsurvivors of newborn ECMO with autopsy results are divided into two groups: group 1: 12 patients who had intracranial lesions as the primary cause of death (hemorrhage 8, encephalomalacia 2, infarct 2); and group 2: 7 patients with nonintracranial primary causes of death . Patients in group 1 were significantly more acidotic, hypotensive, and smaller in age and birth weight pre-ECMO . Among group 2 patients, two with diaphragmatic hernia died of primary pulmonary disease (diffuse alveolar damage, pulmonary hypoplasia and necrosis, bronchopneumonia) . One of 2 patients with persistent fetal circulation (PFC) was treated with massive doses of tolazoline and suffered fatal gastrointestinal hemorrhage and ischemic necrosis of heart, spleen, testes, and adrenals . The other PFC patient had severe pulmonary interstitial fibrosis . Two patients with meconium aspiration and a patient with streptococcal sepsis had diffuse pulmonary damage and multiple organ failure (renal medullary necrosis, and infarcts of adrenal, spleen, liver) . In this series, intracranial pathology was the most common cause of death in ECMO patients, related to gestational age, acidosis, hypoxia, and size, but probably unrelated to carotid ligation.

J Neurol, 1993 Feb, 240(2), 121 - 3
Sydenham chorea: clinical, EEG, MRI and SPECT findings in the early stage of the disease; Heye N et al.; An 18-year-old man suffered from acute Sydenham chorea appearing coincidently with beta-haemolytic streptococcal throat infection . Imaging techniques documented lesions of basal ganglia and substantia nigra . In the early course of the disease vascular lesions may be important pathogenetic mechanisms of this acquired movement disorder.

Am J Clin Oncol, 1993 Feb, 16(1), 9 - 13
High-dose carboplatin and mitoxantrone with autologous bone marrow support in the treatment of advanced breast cancer; Broun ER et al.; Ten patients with Stage II (four) and Stage IV (six) breast cancer were enrolled in a trial of conventional-dose induction therapy followed by high-dose therapy with autologous bone marrow support . Cyclophosphamide, methotrexate, and 5-fluorouracil were given to best response or five courses (Stage II) . Those patients without progression were eligible for the high-dose portion of the protocol, which consisted of carboplatin 1,500 mg/m2 and mitoxantrone at either 40 mg/m2 (first five patients) or 50 mg/m2 . Two patients did not receive the high-dose portion of the treatment due to progression on induction therapy (one) and insurance refusal (one) . Of the remaining eight patients who completed the high-dose portion of the protocol, three were Stage II, of whom one died of transplant-related complications, one progressed, and one is alive and free of disease 24 months after therapy . Of the five Stage IV patients, two achieved a partial remission, one of whom died of progressive disease 1 year after therapy and the other died of BMT-related complications; of the other three Stage IV patients, one had stable disease and died at +9 months, one with progression died at +3 months, and one died of BMT-related causes . Overall, three patients died of infectious complications, with two having alpha streptococcal septic shock syndrome.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 314 - 6
Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension; Nahata MC et al.; Azithromycin is an azalide antibiotic . On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin . However, little about the pharmacokinetics of azithromycin in children is known . The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis . Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5 . Each child fasted overnight before receiving the final dose on day 5 . Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose . Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method . The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively . Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively . Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

J Clin Invest, 1993 Feb, 91(2), 553 - 65
Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and fibroblast growth factor-1 in situ in synovial tissues of patients with rheumatoid arthritis and Lewis rats with adjuvant or streptococcal cell wall arthritis; Sano H et al.; Fibroblast growth factor (FGF)-1 and PDGF-B-like factors have been implicated in the pathobiology of RA and animal models of this disease . Since the receptors for FGF-1 and PDGF are tyrosine kinases, we examined the expression of tyrosine phosphorylated proteins (phosphotyrosine, P-Tyr) in synovial tissues from patients with RA and osteoarthritis (OA), and rats with streptococcal cell wall (SCW) and adjuvant arthritis (AA) . Synovia from patients with RA and LEW/N rats with SCW and AA arthritis, in contrast to controls, stained intensely with anti-P-Tyr antibody . The staining colocalized with PDGF-B and FGF-1 staining . Comparative immunoblot analysis showed markedly enhanced expression of a 45-kD P-Tyr protein in the inflamed synovia . Treatment with physiological concentrations of dexamethasone suppressed both arthritis and P-Tyr expression in AA . P-Tyr was only transiently expressed in athymic nude Lewis rats and was not detected in relatively arthritis-resistant F344/N rats . These data suggest that (a) FGF-1 and PDGF-B-like factors are upregulated and may induce tyrosine phosphorylation of proteins in vivo in inflammatory joint diseases, (b) persistent high level P-Tyr expression is T lymphocyte dependent, correlates with disease severity, and is strain dependent in rats, (c) corticosteroids, in physiological concentrations, downregulate P-Tyr expression in these lesions.

Biochim Biophys Acta, 1993 Jan 22, 1180(3), 283 - 8
Streptokinase and human fibronectin share a common epitope: implications for regulation of fibrinolysis and rheumatoid arthritis; Gonzalez-Gronow M et al.; Rheumatoid arthritis is a disease characterized by a destructive inflammatory process in joints . Fibronectin (FN) is present at a high concentration in rheumatoid synovial tissue and it is a chemoattractant for inflammatory cells . FN fragments also play significant and specific roles in promoting inflammation . In the present study, we demonstrate that FN and the streptococcal plasminogen activator streptokinase (SK) share a common epitope which is recognized by both a rabbit anti-SK IgG and a human anti-SK IgG isolated from the serum of a rheumatoid arthritis patient . This cross-reactive antibody was present in the plasma of 40 patients with rheumatoid arthritis . The region of homology is present in a 90-kDa FN fragment generated by plasmin (Pm) digestion of FN . Amino terminal sequence analysis of this fragment demonstrates that it contains the cell binding domain of FN and the domain responsible for plasminogen binding . The epitope common to SK and FN is not reactive in native FN and it is exposed as a consequence of Pm digestion . It is, however, exposed in native SK . Examination of the sequences of FN and SK indicates a region of homology containing the sequence LTSRPA . This sequence, moreover, is present in the 90-kDa FN fragment generated by Pm digestion . The sequence is present in the amino terminal domain of SK which is essential for its ability to serve as a plasminogen activator . LTSPRA coupled to a carrier protein also reacts with anti-SK antibodies obtained from rabbit or the plasma of patients with rheumatoid arthritis . These studies suggest that the Pm-generated FN 90-kDa fragment may react with circulating antibodies originally elicited by streptococcal infections . These immune complexes may play a role in the etiology of rheumatoid arthritis.

Scand J Infect Dis, 1993, 25(2), 177 - 83
Assessment of clinical features predicting streptococcal pharyngitis; Meland E et al.; A total of 133 patients who consulted 4 general practitioners in Bergen 1988/89 for sore throat were examined . 8 clinical parameters with expected predictive value for identifying streptococcal tonsillopharyngitis were recorded . Clinical examination was validated against bacteriologic examination at a microbiological laboratory . The prevalence of streptococcal infection (group A, C and G) was 29% . An algorithm was constructed which identifies 3 groups with varying probabilities of streptococcal infection . A positive predictive value of 62% in the group with highest prevalence and a negative predictive value of 90% in the group with lowest prevalence was found . The consequences of performing a confirmative test only on patients in the group with uncertain prediction for streptococcal disease was elaborated . Although slightly reduced accuracy was demonstrated, due to diminished sensitivity, selective testing is recommended . Another algorithm was constructed for use in situations where no confirmative testing is available . The positive predictive value in the group with highest probability of streptococcal infection was 51%, and the negative predictive value in the group with lowest probability was 84%.

Biotherapy, 1993, 6(1), 41 - 9
The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from gastric or colorectal cancers; Satoh K et al.; Twenty-four patients with liver metastases from gastric or colorectal cancer were treated with OK-432-combined adoptive immunotherapy (AIT) . Lymphocytes isolated from regional lymph nodes or peripheral blood were cultured with medium containing T cell growth factor and sonicated tumor extract antigen (SE-Ag) for 9-13 days . The cultured lymphocytes were transferred mainly through the hepatic artery after the administration of OK-432, a streptococcal preparation . Sixteen of the 24 patients received a low dose of anti-cancer agents between the OK-432 injection and cell transfer . When cultured without SE-Ag, regional lymph node lymphocytes (RLNL) showed significantly (P < 0.05) higher cytotoxic activity against autologous tumor cells and, on the contrary, lower cytotoxic activity against K562 than peripheral blood lymphocytes (PBL) . When cultured with SE-Ag, cytotoxicity of RLNL against autologous tumor cells was nearly equivalent to that of PBL . The blastogenesis of fresh PBL to SE-Ag was significantly (P < 0.05) augmented after the OK-432-combined AIT . Two patients showed complete response and 4 patients showed partial response among 19 patients who had evaluable lesions . Five patients whose liver metastases were resected were treated with OK-432-combined AIT as an adjuvant therapy . To date they are alive without recurrence in the liver.

Surg Today, 1993, 23(1), 13 - 20
The possible use of spleen cells for the adoptive immunotherapy of cancer patients; Katano M et al.; The possible use of spleen-derived mononuclear cells (SPMC) for the intentional and economical adoptive immunotherapy of cancer patients was studied . SPMC were obtained from spleens resected surgically from patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP) . When SPMC were cultured in recombinant interleukin 2 (rIL2), SPMC, in the form of interleukin-activated killer spleen cells (IL-SP) proliferated in six of eight cases . CD8+ lymphocytes were the major expanding cell population in most SPMC cultures and IL-SP showed a significant cytolytic activity against cultured tumor cells during cell proliferation . When cultured with a streptococcal preparation, OK-432, for 24 to 48 h, SPMC showed cytotoxic activity against tumor cells and were expressed as OK-432 activated killer spleen cells (OK-SP) . The effects of supernatants from IL-SP and OK-SP on tumor cell growth were also examined . The supernatants from IL-SP and OK-SP significantly inhibited cell growth in 3 and 10 out of 11 cases, respectively, while those from OK-SP showed higher growth inhibitory activity than those from IL-SP . The results of this study indicate the potential of SPMC as effector cells for the adoptive immunotherapy of cancer patients.

Scand J Infect Dis, 1993, 25(1), 1 - 6
Group B streptococcal meningitis in adults: case report and review of the literature; Sarmiento R et al.; A case of group B streptococcal meningitis in an adult is presented with a review of 42 other cases reported in the English literature since 1940 . Their median age was 58 years (72.5% were older than 45 years) . Male/female ratio was 0.9:1, with male predominance in patients older than 60 years (76.5%) . Predisposing illnesses were common but 13.9% of cases reported had no identifiable risk factor . Encephalopathy and bacteremia were frequent (81.3% and 94.4% respectively) and many patients (30%) had other foci of infection . Gram stain of cerebrospinal fluid was positive in 75% of cases . Mortality was 18.4% and 9.7% of survivors had bilateral hearing loss . Thus, this review illustrates that group B streptococcal meningitis in adults is a rare disease which occurs among high risk individuals . It is characterized by frequent encephalopathy, prevalence of other foci of infection and bacteremia with an outcome similar to other types of purulent meningitides.

J Craniomaxillofac Surg, 1993 Jan, 21(1), 30 - 7
Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients; Kubota E et al.; Both cell-mediated and cytokine-mediated antitumor activities were induced in peripheral blood mononuclear cells (PBMC) in short-term culture with streptococcal preparation, OK-432 . Kinetic analysis of OK-432-activated killer activity (OKAK) showed that it reached a plateau level much faster (by 48 h of culture) than that detected in PBMC stimulated with recombinant interleukin 2 (rIL-2) (lymphokine-activated killer: LAK) . We also found that the tumor growth inhibitory factor (TGIF) activity was produced in the culture supernatant (CSN) of the OK-432-activated PBMC (OK-MC) and the activity synchronously increased with augmentation of OKAK activity . The TGIF activity was rarely found in the CSN of rIL-2-stimulated PBMC . The TGIF activity detected in CSN of OK-MC was further characterized as derived from a cytokine different from interferon gamma (IFN gamma), tumor necrosis factor (TNF), or lymphotoxin (LT) by a neutralization test using monoclonal antibodies to these cytokines . These 48-h-cultured-OK-MC were adoptively transferred (adoptive immunotherapy: AIT) into 19 head and neck cancer patients either alone or in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined . AIT was performed by intra-arterial or intratumoral administration of OK-MC . There were no significant side effects observed in this treatment . In these patients, approximately 1-10 x 10(7) cells were transferred into the tumor burden . Of the 19 patients, 17 had primary cancer, and in 6 (6/17;35%) of them complete remission (CR) of the tumor was obtained . Partial remission (PR) was attained in 9 of the 17 patients (9/17; 53%), giving the overall response rate of 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Medicine (Baltimore), 1993 Jan, 72(1), 1 - 10
Group B streptococcal meningitis in adults; Dunne DW et al.; Group B streptococcal (GBS) meningitis is a frequent entity in neonates but an uncommon cause of meningitis in adults . Retrospective analysis at our institution identified 4 adult cases over the last 25 years; an additional 46 cases from the literature were reviewed . A bimodal age distribution paralleling that seen in other severe GBS infections was observed . Clinical presentation was not unlike meningitis due to other pyogenic organisms, although a higher percentage of patients presented with less than 24 hours of symptoms . Forty-three percent of patients had no underlying illnesses . Concomitant bacteremia was present in 83% of patients . The overall mortality was 27% and was limited exclusively to patients with co-morbid illnesses . Meningitis in adults due to GBS should be considered in the immunocompetent as well as the immunocompromised host.

J Okla State Med Assoc, 1993 Jan, 86(1), 7 - 12
Symposium on antimicrobial therapy . IV . The cephalosporins; Greenfield RA; Hopefully this review has brought some cephalosporin contentment to replace cephalosporin confusion . From the classification of these antibiotics in Table 1, we have made some significant reductions . One should know how to use cefazolin for staphylococcal/streptococcal infections and for surgical prophylaxis . One should know that cephalexin is massively overused, and really now not all that useful an agent . Cefuroxime is a useful agent for beta-lactamase producing H . influenzae infections . Cefotetan has a role in surgical prophylaxis in ob/gyn and represents the best antianaerobic activity of the cephalosporins; although no cephalosporin is a primary drug for anaerobic infections . Cefuroxime axetil or cefprozil can be useful for comparatively minor infections due to beta-lactamase producing H . influenzae . A third generation cephalosporin represents a reasonable alternative, in certain situations, to aminoglycoside therapy for infections due to multiply drug-resistant Gram-negative bacilli . Ceftazidime is an alternative antipseudomonal beta-lactam antibiotic . Despite the lack of indications for use of cephalosporins as drugs of choice, rational use of these agents can provide safe, effective, and efficient therapy for a variety of infectious diseases . They will likely remain an important part of the physicians' antimicrobial armamentarium for the foreseeable future.

Clin Pediatr (Phila), 1993 Jan, 32(1), 20 - 4
Group D streptococcal bacteremia in children . A review of 72 cases in 12 years; Bonadio WA; A review was conducted of 72 cases of pediatric group D streptococcal (GDS) bacteremia treated at our institution during a 12-year period . These 72 cases represented 90% of all instances in which this organism was isolated by blood culture (in eight others, GDS was considered a contaminant); the rate of isolation of this organism relative to all positive blood cultures during this time period was 1.3% . Infection was nosocomially acquired in 25 cases; 18 occurred in an intensive care unit . At the time their positive blood culture was obtained, 25 patients were afebrile and 10 patients were receiving parenteral antibiotic therapy to which the isolate exhibited in vitro susceptibility . In 31 cases, GDS was isolated by blood culture in conjunction with another organism, most frequently Staphylococcus epidermidis . Underlying medical conditions or foci of infection associated with GDS bacteremia were identified in 65 patients; the most common were the presence of an indwelling central venous catheter (23), a variety of lesions of the gastrointestinal tract (21), and pulmonary infiltrate (15) . Bacteremia was associated with GDS meningitis in three patients who had had no prior neurosurgical procedure . The overall mortality rate was 20%; nearly two thirds of all deaths occurred in patients younger than 1 year of age.

J Exp Med, 1993 Jan 1, 177(1), 225 - 30
Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta; Wahl SM et al.; Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response . In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis . Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis . Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p < 0.001) . Moreover, suppression of the acute arthritis achieved with a single injection of antibody was sustained into the chronic, destructive phase of the disease (on day 18, AI = 0.93 +/- 0.07 vs . AI = 2.6 +/- 0.5; p < 0.01) . The decreased inflammatory index associated with anti-TGF-beta treatment was consistent with histopathologic and radiologic evidence of a therapeutic response . These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology . Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.

Biotherapy, 1993, 6(2), 103 - 12
Augmentation of antitumor immunity in regional lymph nodes by local immunotherapy; Sakita I et al.; We have previously reported that the antitumor effect of OK-432, a streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (OK-432/fbg) {1} . In order to elucidate the effects of this immunotherapy on regional lymph nodes (RLN), we carried out both morphological and functional analyses of the RLN from colonic cancer patients treated with OK-432/fbg . Computer-aided morphometry revealed that the maximal cross-sectional areas and the broadest diameters of the RLN were significantly greater (p < 0.01) in patients who had undergone local immunotherapy than in patients who had not . The component structures of RLN, such as sinus, follicle and paracortex, were all enlarged in the OK-432/fbg-treated patients, and necrosis of metastatic tumors was observed . RLN lymphocytes recovered from OK-432/fbg treated patients showed elevated reactivity to phytohemagglutinin (PHA) and the stimulation index was clearly higher than that of control patients . Flow cytometric analysis revealed a predominance of T-cells, especially CD4 subsets, and higher positivity for both CD25 and HLA-DR . Furthermore, RLN lymphocytes killed more effectively K562 and Daudi cells in the patients who had had immunotherapy . These results suggest that the effect of local immunotherapy with OK-432/fbg is not restricted to the site of injection but extends to the lymph nodes, and contributes to tumor regression through the augmentation of cellular immunity.

Microbiol Immunol, 1993, 37(4), 271 - 9
Development and evaluation of capture enzyme-linked immunosorbent assays for detection of immunoglobulin G and M antibodies to group A streptococcal antigens; Hayashi S et al.; Capture enzyme-linked immunosorbent assays (ELISAs) were developed to detect immunoglobulin G and M antibodies to group A streptococcal (GAS) antigens, streptolysin O, streptokinase, and group A carbohydrate . The sensitivities and the specificities of the IgM capture ELISAs to each GAS antigen were high enough to distinguish the patients with GAS infections (diagnosed as GAS pharyngitis or scarlet fever) from the control groups (healthy people and patients with pharyngitis from whom GAS could not be isolated) . On the other hand, the specificities of the IgG capture ELISAs were not very effective in diagnosis of GAS infections . When the capture ELISA and an indirect ELISA detecting IgM antibodies to group A carbohydrate were compared, false-positive reactions due to rheumatoid factor occurred in the indirect ELISA, but did not occur in the capture ELISA . These results indicate that the capture ELISA works better than the indirect ELISA in detecting the IgM antibody, and that the IgM capture ELISA to GAS antigen provides a rapid and highly reliable serodiagnosis for GAS infections employing only a single serum.

Adv Exp Med Biol, 1993, 336, 449 - 53
Antineutrophil-cytoplasmic-autoantibodies in poststreptococcal nephritis; Mezzano S et al.; Sera from 210 patients with APSGN, were tested for the presence of ANCA (IgG-isotype) . Indirect immunofluorescence (IF) on ethanol fixed human PMNs was used, and for those positive sera, ELISA kits for PR3 (Proteinase 3) and MPO (Myeloperoxidase) was performed . ANCA were detected in 9% (18 out of 210 cases) in a predominantly diffuse cytoplasmic staining pattern in 14 cases (77%), and in a perinuclear pattern in the remaining 4 cases (22%) . Anti-MPO was found in 4 cases (C-ANCA 3; P-ANCA 1) and anti-PR3 was always negative . The presence of ANCA was significantly associated with a more severe glomerular disease as assessed by the serum creatinine value and the crescents formation . Longitudinal studies performed in 11 cases have shown that raised levels of these autoantibodies may persist for at least six months, without relationship with disease activity . Further studies are required to dilucidate the specificity of these autoantibodies, and if its presence is either an epiphenomenon of the heterogeneous humoral immune response in streptococcal infection, or they play some pathogenic role in APSGN.

Eur J Cancer, 1993, 29A(11), 1542 - 6
Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma; Kikkawa F et al.; OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas . To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy . Within each stratum, patients were divided randomly into OK-432 and control groups . 85 patients received OK-432 and 92 patients did not . No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group . In stage IIb, a significant difference was observed between the OK-432 and control groups . This difference, however, could be attributed in part to the different incidence of the lymph node metastasis . In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Fukuoka Igaku Zasshi, 1993 Jan, 84(1), 15 - 24
{Analysis of autoreactive CD8+ T cells against antigen presenting cells}; Yoshizumi H; We reported the existence of high and low responders to streptococcal cell wall antigen (SCW) in human population . To analyze the mechanism of low responsiveness to SCW at the cellular level, we previously 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+ CTLs . Once the CTL was established as a line (HYCD8), they proliferated in the presence of autologous monocytes and IL-2 without SCW . HYCD8 lysed autologous monocytes and EBV transformed B lymphoblastoid cell line (BLCL) . This cytotoxic activity was specifically inhibited by an anti-HLA class I framework mAb and restricted by HLA-B specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCLs . Although HYCD8 contained perforin in the cytoplasm, this HLA-class I restricted cytotoxicity was observed only in the presence of the supernatant of cultured PBLs which could not be replaced by known cytokines and their mixtures . The biological activity of the soluble factor for cytotoxic activity (SFCA) was purified in a single peak fraction by HPLC . Thus, HYCD8 down-regulated the proliferation of SCW specific CD4+ T cells through killing autologous APCs in SFCA dependent manner suggesting a unique immunoregulatory role of autoreactive CD8+ CTLs in immune responses.

Biotherapy, 1993, 6(4), 245 - 50
Bone metastasis as a prognostic factor in breast cancer patients with liver metastasis given OK-432-combined adoptive immunotherapy via the hepatic artery; Kan N et al.; The outcome in 31 patients with liver metastases from breast cancer given OK-432-combined adoptive immunotherapy via the hepatic artery was analyzed . Patients received intraarterial OK-432, a streptococcal preparation, followed by the transfer of autologous lymphocytes cultured with autologous tumor extract and interleukin-2 for 9-13 days . Liver lesions were evaluable in 11 of the 12 patients with bone metastasis (group A) and in 16 of the 19 patients without bone metastasis (group B) . Complete response (CR) in the liver was attained in 8 patients in group A, but in only 1 in group B (p < 0.01) . In group A, radiological features of all metastatic foci of bone improved after CR in the liver . Moreover, the median survival time (MST) of group A (20 months) was longer (p = 0.06) than that of group B patients with extra-hepatic metastasis (n = 12; MST = 6 months), while group B patients with liver metastasis alone (n = 7) showed a MST similar to that of group A . Thus, loco-regional immunotherapy via the hepatic artery was found to be useful in controlling both liver and bone metastasis from breast cancer . Moreover, in breast cancer patients with liver metastasis, bone metastasis appears to be a prognostic factor associated with good response to this immunotherapy.

Dakar Med, 1993, 38(1), 93 - 6
{Antibiotic sensitivity of germs isolated from cellulitis of dental origin in Senegal (results of a survey of 49 cases)}; Dia-Tine S et al.; Irregular results sometimes found during antibiotic treatment of perimaxillar cellulitis, conducted the authors to study bacteriology of these infections from dental origin . This study confirmed the aero and anerobic polymicrobism of these cellulitis . Antibiograms realised in 49 cases showed occurrence of streptococcal and anaerobic germs resistance to antibiotics usually prescribed . A nearly constant success of other antibiotics allowed the authors to define a first intention antibiotherapy for the treatment of these infections.

Drugs, 1993, 45 Suppl 3, 73 - 80
Use of the quinolones for the prophylaxis and therapy of infections in immunocompromised hosts; Maschmeyer G; The prevention and treatment of infections are major issues of supportive care in patients with haematological malignancies . Because of their broad antimicrobial activity, the use of fluoroquinolones for prophylaxis in neutropenic patients has been extensively studied . In comparison with placebo, norfloxacin reduces the incidence of Gram-negative infections, whereas Gram-positive bacterial and fungal infections remain unaffected . Ofloxacin and enoxacin also bacterial and fungal infections remain unaffected . Ofloxacin and enoxacin also produce a reduction in fever and documented infections . In randomized studies comparing ciprofloxacin with cotrimoxazole (trimethoprim/sulfamethoxazole) plus colistin (each in combination with nonabsorbable antifungal agents), conflicting results were obtained . The incidence of documented Gram-negative bacterial infections was markedly reduced by ciprofloxacin prophylaxis; however, the number of Gram-positive infections may increase dramatically . Combining ciprofloxacin with a macrolide antibiotic in an attempt to prevent streptococcal infections can result in breakthrough bacteraemias due to resistant Gram-positive pathogens . Empirical antimicrobial therapy after quinolone prophylaxis should also be directed against microorganisms susceptible to quinolones, since sustained eradication by oral administration cannot be assumed with certainty . Clinical trials comparing intravenous quinolones in combination with aminoglycosides with widely used standard regimens for the treatment of infections in cancer patients indicate equivalent efficacy; however, in studies of ciprofloxacin alone, response rates were significantly lower compared with standard combinations . Therefore, quinolone monotherapy as empirical treatment in febrile neutropenic patients cannot be recommended.

Ann Trop Paediatr, 1993, 13(1), 65 - 72
Office diagnosis and management of group A streptococcal pharyngitis employing the rapid antigen detecting test . A 1-year prospective study of reliability and cost in primary care centres; Majeed HA et al.; The impact of introducing the rapid antigen detecting test for the diagnosis of group A streptococcal pharyngitis in primary care centres and the direct and comprehensive cost-effectiveness of four alternative strategies for the management of group A streptococcal pharyngitis and the prevention of rheumatic fever were assessed in a 1-year prospective randomized study, carried out in children between the ages of 5 and 14 years . Data from the study showed that the test was easy to perform and reliable when introduced as a service in primary care . The strategy of using the rapid antigen detecting test and a 10-day oral penicillin course for diagnosis and treatment proved to be the safest and most cost-effective . If compliance with a 10-day course of oral penicillin is unlikely to be achieved, the strategy of introducing the test and treatment by intramuscular benzathin penicillin G proved to be the second best cost-effective alternative . In developing countries, where acute rheumatic fever is still common and the cost of the test and a 10-day course of penicillin may prove to be formidable, a strategy of treating all children with pharyngitis with intramuscular benzathin penicillin G seems to be the most cost-effective . The strategy of diagnosing group A streptococcal pharyngitis on clinical grounds proved to be the worst.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Jan-Feb, (1), 73 - 7
{Inducers of autoimmune reactions in patients with trigeminal neuralgia}; Mordvinov GV; The antigenic determinants of proteins contained in normal nervous tissue and some microorganisms were studied by the method of immunoblotting . Nervous tissue was found to contain antigens, common with some Mycobacterium tuberculosis antigens having molecular weights (MW) of 104, 90, 68, 40, 34, 28 kD and some antigens contained in staphylococcal and streptococcal proteins with MW of 274, 163, 63, 50 kD . In serum samples taken from trigeminal neuralgia patients autoantibodies to cross-reacting determinants of microbial and nerve proteins with MW of 84, 76, 66, 64, 44, 40, 38, 28 kD were detected . These autoantibodies were absent in the sera of healthy persons . The conclusion was made that the autoantibodies under study might play a certain role in the pathogenesis of pangs in such patients.

J Biol Chem, 1992 Dec 15, 267(35), 25583 - 8
Protein LG: a hybrid molecule with unique immunoglobulin binding properties; Kihlberg BM et al.; Immunoglobulin (Ig)-binding bacterial proteins have attracted theoretical interest for their role in molecular host-parasite interactions, and they are widely used as tools in immunology, biochemistry, medicine, and biotechnology . Protein L of the anaerobic bacterial species Peptostreptococcus magnus binds Ig light chains, whereas streptococcal protein G has affinity for the constant (Fc) region of IgG . In this report, Ig binding parts of protein L and protein G were combined to form a hybrid molecule, protein LG, which was found to bind a large majority of intact human Igs as well as Fc and Fab fragments, and Ig light chains . Binding to Ig was specific, and the affinity constants of the reactions between protein LG and human IgG, IgGFc fragments, and kappa light chains, determined by Scatchard plots, were 5.9 x 10(9), 2.2 x 10(9), and 2.0 x 10(9) M-1, respectively . The binding properties of protein LG were more complete as compared with previously described Ig-binding proteins when also tested against mouse and rat Igs . This hybrid protein thus represents a powerful tool for the binding, detection, and purification of antibodies and antibody fragments.

J La State Med Soc, 1992 Dec, 144(12), 579 - 80
Atraumatic severe streptococcal axillary cellulitis; Bizette GA et al.; Axillary streptococcal cellulitis is rare but has been known to clinicians for years . Usually associated with trauma, it may, however, occur in previously healthy individuals who for unknown reasons can be slowly responsive to appropriate antibiotics.

Singapore Med J, 1992 Dec, 33(6), 597 - 9
Streptococcal pharyngitis in a primary care clinic; Foong HB et al.; A study to determine the sensitivity and specificity of the Directogen Group A Streptococcal Test was carried out in a primary care clinic in University Hospital, Kuala Lumpur . The study also looked at the prevalence of streptococcal pharyngitis in the clinic . We found that the rapid test has a sensitivity of 90.9% and a specificity of 90.7% . Viral pharyngitis is the commonest form (63%) of pharyngitis followed by Group A Beta haemolytic streptococcal pharyngitis (14.2%) . The presence of exudates, tonsillar enlargement and the presence of tender cervical lymph nodes have a significantly higher association with streptococcal pharyngitis.

Pediatr Ann, 1992 Dec, 21(12), 835, 839 - 42
An international comparison of the prevalence of streptococcal infections and rheumatic fever in children; Kassem AS et al.; Differences in the socioeconomic standards of living remain an important and feasible partial explanation for the difference in incidence of rheumatic fever following GABHS infection in Egyptian compared with American children . However, past and ongoing studies of the epidemiology, diagnosis, and treatment of GABHS infections in Egypt, the United States, and elsewhere suggest other significant factors are relevant . Additional knowledge about the rheumatogenic GABHS serotypes that are most prevalent in all countries is an important area where additional research is needed . Streptococcal research will help not only in improving the quality of primary prevention of rheumatic fever, but also in developing streptococcal vaccines.

Pediatr Ann, 1992 Dec, 21(12), 816 - 20
The resurgence of acute rheumatic fever in the United States; Congeni BL; Several areas in the United States have experienced significant outbreaks of acute rheumatic fever . Reasons for the reappearance of acute rheumatic fever are incompletely understood but may relate to changes in the organism . Fortunately, however, GABHS has remained exquisitely susceptible to penicillin . Given the resurgence in cases of acute rheumatic fever, the practicing physician needs to be vigilant in diagnosing and ensuring adequate treatment of acute streptococcal pharyngitis . In addition, acute rheumatic fever must be considered in a patient who presents with a new onset murmur, a migratory polyarthritis, chorea, or a rash suggestive of erythema marginatum.

Mol Microbiol, 1992 Dec, 6(23), 3501 - 10
Characterization of the minimal origin required for replication of the streptococcal plasmid pIP501 in Bacillus subtilis; Brantl S et al.; By using deletional analysis the origin of replication, oriR, of the streptococcal plasmid pIP501 in Bacillus subtilis has been mapped at a position immediately downstream of the repR gene . Determination of both the right and left border of oriR allowed the definition of a sequence of a maximum of 52 nucleotides which theoretically constitutes the minimal origin of replication . Recently, the start point of leading-strand synthesis of the closely related plasmid pAM beta 1 has been mapped at a position which is located exactly in the middle of this sequence (Bruand et al., 1991) . The function of oriR did not depend on its location downstream of the repR gene . Translocation of oriR-containing fragments to other regions of the plasmid proved to be possible . The smallest translocated fragment that still reconstituted autonomous replication was 72bp in size . This fragment was also active in directing the replication of an Escherichia coli plasmid in B . subtilis when the RepR protein was supplied in trans from a repR gene integrated into the host chromosome . The transformation efficiency of plasmids carrying translocated oriR fragments showed a certain dependence on the fragment length and orientation . The DNA sequence of oriR included an inverted repeat, both branches of which appeared to be essential for oriR function . The repeats of oriR shared sequence similarity with a repeat located upstream of promoter pII, which has been suggested to be involved in autoregulation of repR expression.

Epidemiol Infect, 1992 Dec, 109(3), 349 - 60
Selective decontamination in bone marrow transplant recipients; Guiot HF et al.; Patients undergoing bone marrow transplantation become immunocompromised for various reasons . Deep granulocytopenia, induced by conditioning (chemotherapy and total body irradiation), renders the patient at risk for serious bacterial and fungal infections . Our strategy for prevention of these infections by selective decontamination (SD) is the result of more than 15 years of clinical experience and research . The combination of antibiotics, used as standard SD (neomycin, polymyxin B, pipemidic acid and amphotericin B), with the application of local antimicrobial agents eliminates aerobic Gram-negative rods, Staphylococcus aureus and Candida spp . from the mucosal surfaces of the digestive tract, while the majority of the anaerobic flora persist and support colonization resistance (CR) . The antibiotics used either are not resorbed or do not yield therapeutic serum concentrations . Antibiotics which induce therapeutic serum concentrations, such as ciprofloxacin and cotrimoxazole, are only used for SD on a limited scale . When Gram-negative rods persist despite intake of the standard regimen, ciprofloxacin is given until these persisting rods are eliminated . If the patients cannot swallow the oral regimen, i.v . cotrimoxazole is given temporarily . Streptococcal infections are prevented by the i.v . administration of penicillin for 14 days starting on the first day after cytotoxic treatment (conditioning for bone marrow transplantation) . The combination of SD and systemic prophylaxis has been shown to be adequate; the major problem then remaining is a relatively mild catheter-associated infection with coagulase-negative staphylococci.

Clin Nephrol, 1992 Dec, 38(6), 305 - 10
Failure to detect unique reactivity to streptococcal streptokinase in either the sera or renal biopsy specimens of patients with acute poststreptococcal glomerulonephritis; Mezzano S et al.; Using purified group A streptokinase (SKA) as the antigen, ELISA assays were carried out on the sera of normal unaffected children, acute poststreptococcal glomerulonephritis patients (APSGN) and acute rheumatic fever patients (ARF) . The results demonstrate that antibody titers to SKA increase with age in normal children and by age 8 years the vast majority of children have antibodies to SKA . APSGN patients did not demonstrate unique reactivity to SKA when compared to ARF patients either at time of onset of disease or during convalescence . Polyclonal and monoclonal antibodies to SKA which recognize both group A and C streptokinase failed to detect the presence of streptokinase in the biopsy sections obtained from ten well-documented APSGN patients . We conclude that there is no unique reactivity to group A streptokinase in the sera of APSGN patients . Furthermore, we failed to demonstrate the presence of streptokinase in the biopsy specimens of an early case of APSGN patients.

Infect Immun, 1992 Dec, 60(12), 5025 - 9
Relative abilities of distinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B; Imanishi K et al.; The relative ability of distinct isotypes of human leukocyte antigen class II molecules to bind streptococcal pyrogenic exotoxins A and B (SPE A and SPE B, respectively) was investigated by a direct-binding assay with 125I-labeled toxin for SPE A and by a functional assay system measuring the accessory cell activity of human leukocyte antigen class II transfectants in toxin-induced T-cell activation for SPE A and SPE B . SPE A binding was observed in L cells transfected with DQw1 genes . By contrast, it was not detected in L cells transfected with DR2, DR4, DPw4 or DP(Cp63) genes . All the transfectants supported SPE-induced interleukin-2 production by human T cells except the DP transfectants for SPE B . Levels of accessory cell activity were low in the DP transfectants induced by stimulation with SPE A and in the DR and DP transfectants induced by SPE B . The results indicate that SPE A and SPE B bind well to DQ molecules, less well to DR molecules, and very weakly to DP molecules.

Eur J Immunol, 1992 Dec, 22(12), 3091 - 5
Immunomodulation of streptococcal cell wall-induced arthritis . Identification of inflammatory cells and regulatory T cell subsets by mercuric chloride and in vivo CD8 depletion; van den Broek MF et al.; Streptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis which can be induced in susceptible Lewis rats by one intraperitoneal injection of a sterile, aqueous suspension of SCW . The chronic phase of the disease is dependent on T cells . Mercuric chloride is an immunomodulating agent, causing autoimmunity in BN rats, but an OX8+ cell-mediated immunosuppression in Lewis rats . Therefore, we investigated the effect of mercuric chloride, whether or not combined with in vivo OX8 depletion, on SCW-induced arthritis in Lewis rats . We show that (a) depletion of OX8+ cells leads to a more chronic arthritis with a more rapid onset, (b) treatment with mercuric chloride induces a rapidly developing disease which is not chronic, and (c) treatment with mercuric chloride and OX8+ cell depletion induces an arthritis with a very rapid onset and enhanced chronicity . Together with histological data this suggests an important role for OX8+ T cells in controlling both the acute and chronic phase of the disease . In addition, mercuric chloride seems to induce an early activation of T cells resulting in an enhanced onset of disease, which is controlled later by enhanced activation of OX8+ cells.

J Hosp Infect, 1992 Dec, 22(4), 271 - 8
Endophthalmitis at the Bristol Eye Hospital: an 11-year review of 47 patients; Hassan IJ et al.; We reviewed data from 47 patients who were treated for endophthalmitis at our hospital during the 11-year period 1980-90 . The most common clinical features were hypopyon (75%), diminished vision (72%), ocular pain (68%), discharge (57%), corneal oedema (51%), conjunctival injection (49%), abnormal red reflex (34%), corneal ulcer (32%) and corneal perforation (6%) . A total of 54 isolates were obtained from 41 (87%) of the 47 patients . Gram-positive bacteria were more common (72%), than Gram-negative organisms (22%) . Two cases were due to fungi, and herpes simplex virus was isolated from one case . The two most common Gram-positive organisms were coagulase-negative staphylococci (25%), and Staphylococcus aureus (11%), while Pseudomonas aeruginosa predominated among the Gram-negative bacteria isolated (15%) . Mixed bacterial species were obtained from 29% of the infected patients, including one from whom Vibrio fluvialis was isolated . Predisposing factors included ocular surgery (60%)--mostly for cataract extraction (47%), penetrating trauma (15%) and periocular (15%) or systemic (11%) infections . All patients received antibiotics (generally chloramphenicol and/or a beta-lactamase-stable penicillin plus an aminoglycoside) prior to culture, when treatment was adjusted according to specific aetiological agents . Seventy-nine per cent of patients received topical or systemic steroids . Vitrectomy (diagnostic and therapeutic) was performed on 21% of patients . Sixty-three per cent of culture-positive patients lost vision (no perception of light) in the affected eye, compared to 17% of culture-negative cases (P < 0.05 Fisher exact test) . Similarly, a better visual outcome (acuity of 6/12 or better) was associated with coagulase-negative staphylococcal infection than with streptococcal or fungal infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Pharmacother, 1992 Dec, 26(12), 1522 - 3
Erythromycin base-induced rash and liver function disturbances; Shirin H et al.; OBJECTIVE: To report a case of erythromycin base-induced rash and liver function disturbances . CASE SUMMARY: A patient with erythema nodosum and high antistreptolysin-O titers was treated with erythromycin on the assumption that occult streptococcal infection was the cause of the erythema nodosum . Forty-eight hours after the initiation of therapy the patient developed fever, severe generalized rash, pruritus, and cholestatic and hepatocellular liver function disturbances . Extensive evaluation to determine the cause of liver function disturbances was unrevealing . Marked improvement was noticed within days after cessation of erythromycin . DISCUSSION: Case reports in the literature on the adverse effects of erythromycin and its derivatives were reviewed . The possible immunologic mechanism involved is postulated . CONCLUSIONS: Erythromycin base must be added to the list of erythromycin derivatives that can cause rash and liver function disturbances . The concomitant appearance of fever, rash, jaundice, and liver function disturbances raises the possibility of hypersensitivity as the mechanism for the liver disturbances.

J Electron Microsc (Tokyo), 1992 Dec, 41(6), 475 - 9
Scanning electron microscopy of proteoglycans in metaphyseal cartilage; Dell' Orbo C et al.; Alcian blue (AB) was used for scanning electron microscope investigations on metaphyseal cartilage . In the pericellular area three-dimensional network connecting the cell membrane surface to the lacunar wall is evident . The network is formed by very long rod-like filaments about 50 nm thick . The segments may be interpreted as the proteoglycans (PGs) of the pericellular area . In the pericellular area in hypertrophic and degenerative zones, the rod-like segments are closely connected to "chain granules" which are the morphological expression of Ca-P non crystalline compounds . The rod-like segments are not at all evident either in glutaraldehyde-osmium fixed fragments or in predigested-(streptococcal hyaluronidase and chondroitinase) AB stained ones . It is concluded that AB is a good method to detect the three-dimensional spatial disposition of cartilage PGs.

Eur Heart J, 1992 Dec, 13(12), 1720 - 3
Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up; Sieck JO et al.; The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously . We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion . Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels . Urinalysis showed RBC casts . Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex . Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment.

J Clin Invest, 1992 Dec, 90(6), 2555 - 64
Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis; Crofford LJ et al.; Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent . Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors . Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli . Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall- and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats . Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats . CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites . We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH . In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation . Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site . These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis . These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems.

Bone Marrow Transplant, 1992 Nov, 10(5), 457 - 62
Escalating sequential high-dose carboplatin and etoposide with autologous marrow support in children with relapsed solid tumors; Santana VM et al.; Thirty patients with relapsed pediatric solid tumors received high-dose carboplatin and etoposide with autologous marrow support in a dose-escalation trial . These patients had received extensive prior treatment, which included both cisplatin and etoposide in 25 cases . Six patient cohorts received carboplatin in doses of 1200-2100 mg/m2 and etoposide in doses of 960-1500 mg/m2 . All courses were associated with severe neutropenia and thrombocytopenia . The median times from bone marrow infusion to granulocyte recovery (> 0.5 x 10(9)/l) and platelet recovery (> 50 x 10(9)/l) were 33 and 28 days, respectively, with similar findings for all dosage levels . The frequency of non-hematologic toxicities was generally low, although hyponatremia (Na+ < 129 mEq/l) was seen in one-third of the courses . Hepatoxicity was dose-limiting and was significantly associated with the cumulative prior cisplatin dose (p = 0.006) . There were four toxic deaths (CNS hemorrhage, alfa-streptococcal sepsis, Candida sepsis, and enterocolitis) . Eleven patients received a second course of therapy; toxicity profiles and times to hematologic recovery were similar for the two courses . Clinical responses were observed at all dosage levels . Eleven of 26 evaluable patients achieved a clinical response (one complete, 10 partial) . The majority of responses were in patients with neuroblastoma (six of 16) or Hodgkin's disease (two of three) . For phase II clinical trials, we recommend dosages of 2100 mg/m2 of carboplatin and 1500 mg/m2 of etoposide for children with prior cumulative cisplatin exposure < 960 mg/m2 . This carboplatin dose represents a three- to four-fold increase over pediatric doses tolerated without bone marrow support.

Biochemistry, 1992 Nov 3, 31(43), 10449 - 57
1.67-A X-ray structure of the B2 immunoglobulin-binding domain of streptococcal protein G and comparison to the NMR structure of the B1 domain; Achari A et al.; The structure of the B2 immunoglobulin-binding domain of streptococcal protein G has been determined at 1.67-A resolution using a combination of single isomorphous replacement (SIR) phasing and manual fitting of the coordinates of the NMR structure of B1 domain of streptococcal protein G {Gronenborn, A . M., et al . (1991) Science 253, 657-661} . The final R value was 0.191 for data between 8.0 and 1.67 A . The structure described here has 13 residues preceding the 57-residue Ig-binding domain and 13 additional residues following it, for a total of 83 residues . The 57-residue binding domain is well-determined in the structure, having an average B factor of 18.0 . Only residues 8-77 could be located in the electron density maps, with the ends of the structure fading into disorder . Like the B1 domain, the B2 domain consists of four beta-strands and a single helix lying diagonally across the beta-sheet, with a -1, +3 chi, -1 topology . This small structure is extensively hydrogen-bonded and has a relatively large hydrophobic core . These structural observations may account for the exceptional stability of protein G . A comparison of the B2 domain X-ray structure and the B1 domain NMR structure showed minor differences in the turn between strands and two and a slight displacement of the helix relative to the sheet . Hydrogen bonds between crystallographically related molecules account for most of these differences.

Hinyokika Kiyo, 1992 Nov, 38(11), 1299 - 304
{Treatment of advanced renal cell carcinoma with interferon alpha and OK-432 (streptococcal preparation)}; Shinoda M et al.; A total of 12 patients with advanced renal cell carcinoma received interferon alpha (3 million units intramuscularly 6 times weekly) and OK-432 (5 KE (Klinische Einheit) intramuscularly twice weekly) . Metastatic lesions appeared before operation in six patients and after operation in six patients . Among them 5 patients had received interferon therapy and this combination therapy was started after the judgment of progressive disease for interferon therapy . Eleven pulmonary and 5 bone metastases were evaluable . The median duration of the combination therapy was 89.3 weeks . There were 4 partial responses and no complete responses among the 12 patients, giving a response rate of 33.3% . The median duration of response was 25 months, with a range of 6 to 54 months . Responses were seen predominantly in patients in whom metastases appeared after operation (3 of 4 responders) . However, regarding the individual organs, two complete and 2 partial responses were observed among 11 pulmonary metastases and 2 partial responses among 5 bone metastases . The survival period after discovery of the metastasis was 10 to 67 months and the 5-year survival rate was 70.5% . Almost all patients had fever and induration at the injection site . Other side effects included leukopenia, anorexia, and depression . This combination therapy is thought to be effective against bone or other organs metastasis resistant to interferon alone.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S89 - 95
Evaluation of new anti-infective drugs for the treatment of infective endocarditis . Infectious Diseases Society of America and the Food and Drug Administration; Wilson WR et al.; These guidelines describe the design and implementation of clinical trials to assess the safety and efficacy of anti-infective drugs for the treatment of infective endocarditis . Identification and enrollment of patients in clinical trials is based on a modification of traditional criteria . To accrue a sufficient number of patients, only those with streptococcal or staphylococcal endocarditis should be included in studies . Results of treatment with approved drugs allow for projection of expected bacteriologic cure rates and survival rates . Prospective randomized, double-blind studies are recommended . These guidelines are based on the premise that future protocols may include shorter courses of therapy, combinations of drugs, or progression from parenteral to oral therapy . Clinical response is judged as cure, failure, or indeterminate; there is no "improved" category . Microbiologic response is categorized as eradication, persistence, or relapse . When a patient has shown no clinical evidence of active disease for a protracted period, there may be no need to perform a posttreatment blood culture; for such patients, the microbiologic response is termed presumptive eradication . Several months of follow-up may be necessary to detect late relapses.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S62 - 88
Evaluation of new anti-infective drugs for the treatment of respiratory tract infections . Infectious Diseases Society of America and the Food and Drug Administration; Chow AW et al.; These guidelines deal with the evaluation of anti-infective drugs for the treatment of respiratory tract infections . Five clinical entities are described: streptococcal pharyngitis and tonsillitis, otitis media, sinusitis, bronchitis, and pneumonia . A wide variety of microorganisms are potentially pathogenetic in these diseases; these guidelines focus on the bacterial infections . Inclusion of a patient in a trial of a new drug is based on the clinical entity, with the requirement that a reasonable attempt will be made to establish a specific microbial etiology . Microbiologic evaluation of efficacy requires isolation of the pathogen and testing for in vitro susceptibility . Alternatively, surrogate markers may be used to identify the etiologic agent . The efficacy of new drugs is evaluated with reference to anticipated response rates . Establishment of the microbial etiology of respiratory tract infections is hampered by the presence of "normal flora" of the nose, mouth, and pharynx, which may include asymptomatic carriage of potential pathogens . This issue is addressed for each category of infection described . For example, it is suggested that for initial phase 2 trials of acute otitis media and acute sinusitis tympanocentesis or direct sinus puncture be used to collect exudate for culture . Acute exacerbations of chronic bronchitis also present difficulties in the establishment of microbial etiology . These guidelines suggest that clinical trials employ an active control drug but leave open the possibility of a placebo-controlled trial . For pneumonia, the guidelines suggest the identification and enrollment of patients by the clinical type of pneumonia, e.g., atypical pneumonia or acute bacterial pneumonia, rather than by etiologic organism or according to whether it was community or hospital acquired . For each respiratory infection, the clinical response is judged as cure, failure, or indeterminate . Clinical improvement is not acceptable unless quantitative response measures can be applied.

J Infect, 1992 Nov, 25(3), 299 - 302
Streptococcal necrotising fasciitis; Weinbren MJ et al.; Three cases of streptococcal necrotising fasciitis are described . Its relative rarity and the lack of superficial inflammation leading to diagnostic difficulty is emphasised . The diagnosis is readily confirmed microbiologically but the clinician should bear in mind that antibiotics may not be curative and that surgery is often required.

Br Heart J, 1992 Nov, 68(5), 449 - 53
Streptokinase resistance: when might streptokinase administration be ineffective?
Buchalter MB, Suntharalingam G, Jennings I, Hart C, Luddington RJ, Chakraverty R, Jacobson SK, Weissberg PL, Baglin TP.
OBJECTIVE--(a) To develop an assay for streptokinase resistance . (b) To determine the prevalence of streptokinase resistance in patients presenting with acute myocardial infarction for the first time . (c) To determine the prevalence of streptokinase resistance in patients after exposure to streptokinase or streptococcal infection . DESIGN--Open, prospective . PATIENTS--30 healthy volunteers . 40 patients admitted to the coronary care unit at Addenbrooke's Hospital with suspected acute myocardial infarction, 12 patients 12 months after streptokinase treatment, eight patients 24 months after streptokinase treatment, and sera from 12 patients with raised anti-streptolysin O (ASO) titres . METHODS--Three assays were used; a dilution neutralisation assay, an enzyme linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) anti-streptokinase antibodies, and an in vitro fibrin plate lysis assay . All measurements were performed on venous blood samples . RESULTS--Neutralisation and IgG antibody titres were positively correlated . Mean (SEM) antistreptokinase concentrations in the 30 controls were 87 (10) U/ml (neutralisation assay) and 28 (6.3) U/ml (ELISA) . Corresponding concentrations in patients before streptokinase were 68 (6.1) U/ml and 18 (4.5) U/ml with a mean fibrin plate assay 117 (7.1)% that of controls . Resistance to streptokinase was detectable in one patient after 72 hours and in all patients by day 10 . By day 10 concentrations were 4388 (919) U/ml, 773 (109) U/ml, and 17 (5.4)% . At both 12 and 24 months resistance was present in 75% of patients . Similarly 66% of high ASO titre sera showed resistance . The fibrin plate lysis assay detected significantly reduced streptokinase dependent fibrinolysis in vitro in the absence of raised total concentrations of antistreptokinase antibodies . CONCLUSIONS--The prevalence of streptokinase resistance in patients presenting with their first myocardial infarction is low . Resistance develops early after treatment and is still present in 75% of patients after 24 months . Retreatment with streptokinase is likely to be suboptimal even after 24 months . The fibrin plate lysis assay detects resistance in patients with normal concentrations of streptokinase antibodies . Streptococcal infection is associated with a high incidence of streptokinase resistance.

Clin Pediatr (Phila), 1992 Nov, 31(11), 642 - 9
Explanations and therapies for penicillin failure in streptococcal pharyngitis; Pichichero ME; A disturbing trend toward penicillin failure has developed in the treatment of streptococcal pharyngitis in some parts of the United States and abroad . A variety of explanations has been proposed to account for these penicillin-treatment failures . With the resurgence of serious complications from streptococcal infection, successful bacteriologic eradication has regained importance . In communities with a high incidence of penicillin failures, alternative antimicrobials should be considered . Cephalosporins, amoxicillin/clavulanate, and the extended-spectrum macrolides represent logical options under such clinical circumstances.

Clin Exp Immunol, 1992 Nov, 90(2), 215 - 8
Cellular immunity in tuberculous pleural effusions: evidence of spontaneous lymphocyte proliferation and antigen-specific accelerated responses to purified protein derivative (PPD); Lorgat F et al.; The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis . The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions . Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology . However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific . These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation . Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions.

Am J Dis Child, 1992 Nov, 146(11), 1324 - 7
Cephalexin and penicillin in the treatment of group A beta-hemolytic streptococcal throat infections; Disney FA et al.; OBJECTIVE--To determine whether cephalexin or penicillin is more effective in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children . DESIGN--Randomized, double-blind, crossover study conducted from 1981 to 1984 . SETTING--Seven pediatric practices in the United States, including private offices and pediatric clinics . PARTICIPANTS--Of the 654 patients, 525 children and adolescents with clinical evidence of tonsillitis or pharyngitis and throat cultures positive for group A beta-hemolytic streptococcal infection were evaluable . Eighty percent of patients completed the study; none were withdrawn because of adverse reaction . SELECTION CRITERIA--Children and adolescents who had acute illness suggestive of group A beta-hemolytic streptococcal infection were enrolled in the study . Treatment was continued if the throat culture was positive for group A beta-hemolytic streptococcal infection . INTERVENTIONS--Four doses of cephalexin and penicillin (27 mg/kg per day) were prescribed to be taken on an empty stomach for 10 days . MEASUREMENTS/MAIN RESULTS--Symptomatic clinical failure occurred in 8% of penicillin-treated patients and in 3% of cephalexin-treated patients . Bacteriologic failure rates were 11% in the penicillin treatment group and 7% in the cephalexin treatment group . The combined treatment failure rate of clinical relapse plus asymptomatic bacteriologic failure was 19% in the penicillin treatment group and 10% in the cephalexin treatment group . Paired antistreptolysin-O titer increased significantly in 62.3% of penicillin-treated patients and in 64.2% of cephalexin-treated patients . Similarly, anti-DNase B titers rose 52.2% in penicillin-treated patients and 52.4% in cephalexin-treated patients . CONCLUSION--Cephalexin is a more effective drug than penicillin in the treatment of group A beta-hemolytic streptococcal throat infection in children.

J Pediatr, 1992 Nov, 121(5 Pt 1), 739 - 42
Recurrent juvenile dermatomyositis and cutaneous necrotizing arteritis with molecular mimicry between streptococcal type 5 M protein and human skeletal myosin; Martini A et al.; An adult patient had a syndrome associating the features of juvenile dermatomyositis and cutaneous polyarteritis nodosa that followed a cyclic course from childhood; recurrences were always associated with a rise of serum antistreptococcal antibodies . Regions of homology between streptococcal type 5 M protein and skeletal myosin were found . These findings suggest that streptococcal infection, possibly through a molecular mimicry mechanism, played a role in the pathogenesis of the disease in our patient.

Anticancer Res, 1992 Nov-Dec, 12(6B), 1941 - 5
Effect of OK-432 on cytotoxic activity in cancer patients without tumor burden; Fujieda S et al.; The present study was designed to determine the optimal therapeutic protocol for OK-432, a streptococcal preparation, and to clarify the kinetics of various immunological parameters following intracutaneous administration of OK-432 in 39 disease-free postoperative patients with early cancer . These patients were randomly divided into 4 groups according to the dose (1KE or 5KE) and the frequency of administration (one or 3 times every other day) of OK-432 . NK activity 3-4 days after the first injection increased significantly in patients whose pretreatment baseline activity was below the lower level of normal values (60 LU) in all study groups (P < 0.05) . The elevation of post-therapeutic NK activity lasted for 2 weeks in the group of patients given repeated injections . The serum content of cytotoxic activity against L-M cells increased significantly after the injection of OK-432 at doses of more than 5 KE doses (p < 0.05) . These findings suggest that repeated injections of OK-432 over a period of a week have important immunotherapeutic results.

Indian J Pediatr, 1992 Nov-Dec, 59(6), 741 - 8
Benzathine penicillin G for rheumatic fever prophylaxis: 2-weekly versus 4-weekly regimens; Kassem AS et al.; Rheumatic fever is still one of the major public health problems in Egypt and the developing countries . It is characterized by a high tendency to recur following streptococcal infections . The use of long acting penicillin for prophylaxis against strep infections was a good achievement in this field, yet, recurrences have been reported in patients following monthly prophylactic programs . Clinical experience in Alexandria have shown for a long time that giving penicillin every 2 weeks is followed by less recurrences of rheumatic fever . Recently, reports came showing that effective penicillin levels are not maintained except for 2 to 3 weeks after the injection . In the present study, we compared two regimens of prophylaxis with 190 patients in the 2-weekly regimen, and 170 patients in the 4-weekly regimen being followed up for 2 consecutive years . Two hundred and sixty nine streptococcal infections occurred during this period . Although the streptococcal infection rate was equal in both groups, the rheumatic fever recurrence rate and the RF attack rate were significantly higher in the group of patients on the 4-weekly schedule . The results of this study have shown the superiority of the 2-weekly schedule in the adequate control of RF recurrences . We suggest that this schedule should be implemented for secondary prophylaxis of rheumatic fever in Egypt and other areas with severe RF.

Eur J Clin Microbiol Infect Dis, 1992 Nov, 11(11), 1032 - 8
Chromosomal gene transfer elements of the Bacteroides group; Salyers AA et al.; Many human colonic Bacteroides strains carry large ( > 60 kbp) chromosomal elements that can transfer themselves from the chromosome of the donor to the chromosome of the recipient . Most of these elements carry a tetracycline resistance gene (tetQ) and many also carry an erythromycin resistance gene (ermF), but at least one cryptic member of the family has been identified . Molecular analysis of excision and integration events has shown that the self-transmissible Bacteroides elements are not transposons but may represent a new class of integrating elements . The Bacteroides elements are most similar to the streptococcal conjugative transposons, such as Tn916 . The Bacteroides Tcr/TcrEmr elements can mobilize DNA that is not contained within the elements themselves . They not only mobilize co-resident plasmids but also cause the excision, circularization and mobilization of discrete unlinked 10-11 kbp segments of chromosomal DNA . Self-transfer and other activities of the Tcr/TcrEmr elements are regulated by tetracycline . Thus, tetracycline not only selects for acquisition of an element but also stimulates element transfer in the first place.

JAMA, 1992 Oct 21, 268(15), 2069 - 73
Guidelines for the diagnosis of rheumatic fever . Jones Criteria, 1992 update . Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association; Crystallization and preliminary X-ray analysis of the complex between a mouse Fab fragment and a single IgG-binding domain from streptococcal protein G; Department of Biochemistry, University of Leicester, U.KThe Fab fragment of a mouse immunoglobulin G1, complexed with a single IgG-binding domain from streptococcal protein G, has been crystallized in a form suitable for analysis by X-ray diffraction . The needle-shaped crystals were grown from polyethylene glycol 4000 using vapour diffusion methods and diffract to 2.3 A resolution . The space group is P2(1)2(1)2(1) (a = 64.5 A, b = 70.5 A and c = 120.1 A), with one Fab-protein G domain complex in the asymmetric unit . Solution of the three-dimensional structure of the complex will permit a detailed analysis of the molecular interactions between protein G and the Fab portion of IgG.

Clin Lab Sci, 1992 Nov-Dec, 5(6), 349 - 53
Self-guided instructional materials in the physician office laboratory; Crowley JR et al.; The effectiveness of systematically designed print-based materials in teaching (a) knowledge of laboratory tests and (b) laboratory test skills to laboratory staff in small office practices was measured . Self-guided packets on Gram stain performance and interpretation, rapid streptococcal testing, and vaginal wet preparations were developed by a multidisciplinary team . A total of 21 staff members (14 treatment, 7 control) in 12 family practice offices with three or fewer physicians participated in the study . A posttest-only control group design was used to determine the effects of using the self-guided instructional packets . The treatment group, in relation to the control, scored significantly higher on tests of knowledge for all packets, demonstrated no difference in scores for Gram stain or streptococcal test skills, and scored significantly higher for identification of elements in photographs of vaginal wet preparations . Results affirmed both the usefulness and limitations of print-based instruction for knowledge level outcomes . For developing laboratory test skills additional forms of instruction are needed.

Harefuah, 1992 Oct, 123(7-8), 258 - 60, 306
{Poststreptococcal reactive arthritis}; Barash J et al.; Reactive arthritis is defined as arthritis of 1 or more joints, in association with infection at a distant site, but without the infective agent being found in the synovial fluid . Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever, have been classified as having poststreptococcal reactive arthritis . We describe 6 patients seen during the winter of 1991 who had various clinical presentations of poststreptococcal reactive arthritis . This condition is considered by some as a distinct disease, but by others as part of the spectrum of acute rheumatic fever.

Protein Expr Purif, 1992 Oct, 3(5), 368 - 73
Purification of recombinant chimeric B72.3 Fab' and F(ab')2 using streptococcal protein G; Proudfoot KA et al.; Streptococcal protein G has been used extensively for the purification of antibodies using the interaction of the Fc region with protein G . Many antibodies also interact with protein G through a low-affinity binding site for the Fab region . The exploitation of this low-affinity interaction for the purification of Fab' fragments is described here . Chimeric mouse-human B72.3 Fab' and F(ab')2 fragments were expressed by CHO cells and purified from CHO cell supernatant using protein G-Sepharose . Since chimeric B72.3 Fab' bound weakly to the protein G-Sepharose it could be separated from F(ab')2 and eluted with a pH 7 wash whereas B72.3 F(ab')2 required elution at pH 2 . Both Fab' and F(ab')2 were recovered with full immunoreactivity and could be further purified using gel-filtration chromatography to greater than 99% purity . This method allows the simple purification of directly expressed Fab' or F(ab')2 fragments from CHO cell supernatant.

Pathol Res Pract, 1992 Oct, 188(7), 908 - 24
The long-term prognosis of the primary glomerulonephritides . A morphological and clinical analysis of 1747 cases; Bohle A et al.; Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present . The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy . 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis . The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present . Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis . No difference in prognosis is found between IgA nephritis and non-IgA nephritis . 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved . The presence of interstitial inflammation and fibrosis worsens the prognosis significantly . 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively) . If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively) . The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively) . From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg% . 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%) . If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10-year RSR, 38%) . The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%) . 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS)

Inflammation, 1992 Oct, 16(5), 485 - 96
Bone-resorbing activity is expressed by rat macrophages in response to arthropathic streptococcal cell wall polymers; Bristol-Rothstein LA et al.; Rat peritoneal macrophages stimulated in vivo by group A streptococcal peptidoglycan-polysaccharide (PG-APS) resorb bone as measured by solubilization of 45Ca from radiolabeled, devitalized bone chips . Activity was strain-dependent and correlated with the susceptibility of rat strains to PG-APS-induced arthritis . PG-APS-stimulated macrophages from the resistant Buf rat strain were not induced to resorb bone, but ingested equivalent concentrations of PG-APS compared to bone-resorbing macrophages from the arthritis-susceptible Lew strain . Resorptive activity peaked at three to five days and decreased to background levels by 10 days after injection . PG-APS-stimulated macrophages from congenitally athymic Lew rats were as effective as macrophages from heterozygous littermates at resorbing bone . Lew macrophages were also responsive to small, nonarthropathic PG-APS polymers generated by mutanolysin digestion . Resident peritoneal macrophages did not respond to stimulation by PG-APS in vitro . Indomethacin at a concentration of 10 micrograms/ml was an effective blockade against PG-APS-induced macrophage bone resorption in vitro, but catalase was ineffective . These results indicate that expression of rat macrophage bone-resorbing activity reflects genetic regulation of the response to PG-APS rather than a defect in ingestion of these polymers and imply that PG-APS-stimulated, bone-resorbing macrophages may contribute to early, initial bone destruction that occurs in inflammatory arthritis.

Eur J Pediatr, 1992 Oct, 151(10), 745 - 7
Unsuspected rheumatic heart underlying group B streptococcal endocarditis at the age of 20 months; Moral L et al.; The case is reported of a 20-month-old girl admitted to our centre for group B streptococcal endocarditis who died of complete atrioventricular block after a week of treatment . There was no history pointing to the presence of a heart disorder . Necropsy disclosed the surprising existence of a vast rheumatic carditis involving essentially the aortic and mitral valves, with bacterial superinfection of the former . The double rheumatic and infectious lesion in such a young patient with infective pseudo-aneurysms of the sinuses of Valsalva makes this an exceptional case.

J Pediatr, 1992 Oct, 121(4), 569 - 72
Prevention of rheumatic fever in Costa Rica; Arguedas A et al.; During the beginning of the 1970s, major changes occurred in Costa Rica in the treatment of streptococcal throat infections . Because of poor compliance with regimens using orally administered agents, intramuscular administration of benzathine penicillin was selected as the standard treatment and throat cultures were eliminated as a prerequisite for prescribing antibiotics . A decline in the incidence of rheumatic fever then occurred . We believe that similar health intervention could be applied in other developing countries.

Eur Heart J, 1992 Oct, 13(10), 1422 - 6
Chlamydial endocarditis: a report on ten cases; Etienne J et al.; Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a result of Chlamydia were seen . All patients were men, with a mean age of 42 years, and none had a history of exposure to Chlamydia psittaci . Symptoms, such as weight loss and anorexia, with fever in eight cases, had persisted for at least 2 months before admission . Haemodynamic failure was present in seven patients, and neurological signs in four . The aortic valve was involved in seven cases, the mitral valve in one and both valves in two . Vegetations, often fingerlike, were observed by echocardiography in nine cases . All patients required valve replacement, and three died in the year following diagnosis . Blood cultures were consistently negative in all cases, and no antibiotics had been given before admission . Significant titres of complement fixing anti-chlamydial antibodies were present in six cases, and micro-immunofluorescence using the three chlamydial species showed cross-reacting antibodies in all nine cases studied, with transient IgM positivity in six cases . Histologically, the leaflets were fibrosed and infiltrated by large macrophages containing dark red granules after Machiavello staining . These granules were specifically stained by immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not by that specific for C . pneumoniae . No organisms were seen after Gram staining, and no positive chlamydial immunofluorescence was seen on sections of valves from patients with staphylococcal or streptococcal endocarditis.

Cancer Res, 1992 Oct 1, 52(19), 5400 - 2
Activation of omental milky spots and milky spot macrophages by intraperitoneal administration of a streptococcal preparation, OK-432; Shimotsuma M et al.; Omental milky spots are omentum-associated lymphoid tissues that cede peritoneal macrophages and participate in the immunity of the peritoneal cavity . We studied the changing surface features of milky spots and milky spot macrophages of Wistar rats, following the i.p . administration of OK-432, a killed streptococcal preparation (1 Klinische Einheit (unit) in 5 ml of phosphate-buffered saline) by the use of scanning electron microscopy . OK-432-activated macrophages demonstrated marked surface membrane activity and migrated through the stomata of the milky spot into the peritoneal cavity . The characteristic features of activated milky spots and milky spot macrophages were noted as early as 3 h following the administration of OK-432, and continued to be observed until 7 days after the injection . By 14 days after the injection, the structural integrity of the milky spot was partially lost . The activation of milky spots and milky spot macrophages by OK-432 provides a convenient in vivo system for the monitoring and study of i.p . cellular events.

J Assoc Physicians India, 1992 Oct, 40(10), 685 - 6
Post streptococcal glomerulonephritis co-existing with acute rheumatic fever--a case report; Narula AS et al.; A case of post streptococcal acute glomerulonephritis co-existing with acute rheumatic fever is reported . The relevant literature is briefly reviewed.

J Protein Chem, 1992 Oct, 11(5), 527 - 38
Restriction in the conformational flexibility of apoproteins in the presence of organic cosolvents: a consequence of the formation of "native-like conformation"; Acharya AS et al.; The influence of n-propanol on the overall alpha-helical conformation of beta-globin, apocytochrome C, and the functional domain of streptococcal M49 protein (pepM49) and its consequence on the proteolysis of the respective proteins has been investigated . A significant amount of alpha-helical conformation is induced into these proteins at pH 6.0 and 4 degrees C in the presence of relatively low concentrations of n-propanol . The induction of alpha-helical conformation into the proteins increased as a function of the propanol concentration, the maximum induction occurring around 30% n-propanol . In the case of alpha-globin, the fluorescence of its tryptophyl residues also increased as a function of n-propanol concentration, the midpoint of this transition being around 20% n-propanol . Furthermore, concomitant with the induction of helical conformation into these proteins, the proteolysis of their polypeptide chain by V8 protease also gets restricted . The alpha-helical conformation induced into alpha- and beta-globin by n-propanol decreased as the temperature is raised from 4 to 24 degrees C . In contrast, the alpha-helical conformation of both alpha- and beta-chain (i.e., globin with noncovalently bound heme) did not exhibit such a sensitivity to this change in temperature . However, distinct differences exist between the n-propanol induced "alpha-helical conformation" of globins and the "alpha-helical conformation" of alpha- and beta-chains . A cross-correlation of the n-propanol induced increase in the fluorescence of beta-globin with the corresponding increase in the alpha-helical conformation of the polypeptide chain suggested that the fluorescence increase represents a structural change of the protein that is secondary to the induction of the alpha-helical conformation into the protein (i.e., an integration of the helical conformation induced to the segments of the polypeptide chain to influence the microenvironment of the tryptophyl residues) . Presumably, the fluorescence increase is a consequence of the packing of the helical segments of globin to generate a "native-like structure." The induction of alpha-helical conformation into these proteins in the presence of n-propanol and the consequent generation of "native-like conformation" is not unique to n-propanol . Trifluoroethanol, another helix-inducing organic solvent, also behaves in the same fashion as n-propanol . However, in contrast to the proteins described above, n-propanol could neither induce an alpha-helical conformation into performic acid oxidized RNAse-A nor restrict its proteolysis by proteases.(ABSTRACT TRUNCATED AT 400 WORDS)

N Z Med J, 1992 Sep 9, 105(941), 355 - 7
The quality of a laboratory test in general practice: the throat swab example; Kljakovic M; AIM: To measure the repeatability, the flow of information, and the data entry error of the throat swab test from a suburban general practice . METHOD: A prospective study of consecutive patients seen in routine consultation for a sore throat as their primary complaint . Repeated throat swabs were taken for each patient . Carbon copies of routine laboratory forms were collected . RESULTS: The kappa statistic for reproducibility of the throat swab test was 0.63 (95% CI 0.50-0.77) . In 5.8% of patients, one swab was positive and the other negative . Information took one day or less to travel to and from the laboratory for 25.7% of patients with a beta-haemolytic streptococcal growth compared to the 9.9% of patients with no growth (chi 2 = 6.17, p < 0.02) . The laboratory received 53% of the swabs on the day they were taken . Delays in getting the swabs to the laboratory occurred when swabs were taken in the afternoon session or on weekends . Monday morning gave the quickest return . Data entry errors were found on 15.9% of patient forms . CONCLUSION: The quality of the throat swab test needs improvement in the suburban general practice context.

Arch Intern Med, 1992 Sep, 152(9), 1881 - 4
Community-acquired invasive group A beta-hemolytic streptococcal infections in Zuni Indians; Benjamin EM et al.; BACKGROUND--Outbreaks of invasive group A beta-hemolytic streptococcal (GABS) infections have recently been reported . We observed a high incidence of invasive GABS disease among Native Americans at a small rural community hospital between 1982 and 1991 . METHODS--A retrospective chart review was performed, and all cases of invasive GABS disease were studied for their clinical features . RESULTS--Sixteen cases of invasive GABS infection were identified during the 10-year study period . The rate of invasive GABS infection was 13.3 cases per 100,000 population per year . Mortality was 25% . Nearly half of the patients presented with systemic signs of sepsis without any obvious source of infection . CONCLUSIONS--Our experience documents a high rate of invasive GABS infections in a defined Native American population . To determine whether this population has a unique susceptibility to GABS disease requires further study.

Proc Natl Acad Sci U S A, 1992 Sep 1, 89(17), 7910 - 4
Hagfish humoral defense protein exhibits structural and functional homology with mammalian complement components; Hanley PJ et al.; A genomic clone and cDNA fragment encoding a portion of a humoral recognition molecule from the hagfish were isolated and sequenced . The serum protein has previously been described as having structural features that are immunoglobulin-like . Amino acid sequence obtained from the 77-kDa H1 heavy chain facilitated the isolation of a genomic clone containing at least two coding regions . Through use of primers derived from the genomic sequences, a 231-base-pair cDNA fragment was obtained by PCR from liver RNA . Comparison of the deduced 120-amino acid sequence from the N terminus of H1 with known protein sequences revealed substantial sequence similarity with the beta chain of the murine fourth complement component C4 and with the related third and fifth complement molecules C5 and C3 and the major histocompatibility complex-encoded sex-limited protein . Observation of structural and functional similarities associated with the sequence similarity indicate that these molecules share an evolutionary relationship: the polypeptide chain structure of hagfish complement-like protein (CLP) resembles that of C4; CLP contains a hidden thioester group on the 70-kDa chain; CLP binds to streptococcal cells and enhances the phagocytosis of yeast by hagfish leukocytes . These data suggest that CLP forms part of a non-clonally-derived complement-related humoral defense system in the hagfish.

Postgrad Med, 1992 Sep 1, 92(3), 133 - 6, 139-42
Resurgence of rheumatic fever in the United States . The changing picture of a preventable illness; Ayoub EM; The recent resurgence of rheumatic fever reported in eight locations in the United States after years of decline has several noteworthy characteristics . Most patients were children of families in high- to middle-income brackets with ready access to medical care . In four of the outbreaks, the majority of patients were adults, who were more likely than children to have arthritis and less likely to have Sydenham's chorea . Many patients had no clinical history of streptococcal pharyngitis . Rheumatic fever developed in some patients despite antibiotic treatment for streptococcal pharyngitis . Analysis of the outbreaks supports the following conclusions: No population is exempt from rheumatic fever . Physicians should be diligent in performing throat cultures in cases of suspected streptococcal pharyngitis . The efficacy of orally administered penicillin in preventing rheumatic fever should be reexamined, and oral antibiotics that are potentially more effective should be sought.

J Infect Dis, 1992 Sep, 166(3), 635 - 9
Neonatal mouse model of group B streptococcal infection; Rodewald AK et al.; Neonatal mice were infected with type III group B streptococcal (GBS) strain M781 by the intraperitoneal route . Age-related susceptibility to challenge was seen within the first 5 days of life . Quantitative blood cultures demonstrated a rapid increase in bacterial numbers during the first 30 h after challenge . Infected pups showed clinical signs of septicemia, and most succumbed within 48 h of challenge . Histopathologic evaluation of the neonates showed bacterial infection within 1 day after challenge . Pregnant adult mice were given a single inoculation of serum raised in rabbits against a tetanus toxoid-conjugated type III GBS polysaccharide vaccine . This serum passively protected 100% of the offspring . This neonatal mouse model of GBS infection and protection may be suitable for study of various forms of intervention.

Infect Immun, 1992 Sep, 60(9), 3747 - 55
Immune cell lethality induced by streptococcal pyrogenic exotoxin A and endotoxin; Leonard BA et al.; Streptococcal pyrogenic exotoxin (SPE) A has many effects on the immune system, including immunolethality, which is characterized by a significant decrease in circulating immune cells as well as depletion of the spleen and lymph nodes prior to death of experimental animals . In this report, characterization of the mechanism of immunolethality has been undertaken . Synergistic induction of immunolethality was observed in vitro when human lymphocytes were treated with both SPE A and lipopolysaccharide (LPS) . The same effect was demonstrated in the absence of a mitogenic response with the murine T-cell receptor, as well as in the absence of antigen-presenting cells and their secreted cytokines . The addition of antigen-presenting cells did not significantly affect lethality . SPE A directly interacted with LPS through interaction with ketodeoxyoctonate as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and iodinated exotoxin overlays . This interaction was demonstrated to be important for immunolethality, since simultaneous addition of SPE A and LPS was required, whereas sequential addition of SPE A and LPS did not result in lethality . LPS appeared to be acting, in part, to enhance the cell-binding ability of SPE A, since SPE A could only be detected in A.E7 cell membrane preparations after simultaneous incubation with SPE A and LPS.

Clin Pediatr (Phila), 1992 Sep, 31(9), 549 - 53
Review of mupirocin ointment in the treatment of impetigo; Leyden JJ; The introduction of mupirocin ointment gives the pediatrician a reliable topical alternative to oral antibiotic therapy for group A streptococcal and staphylococcal impetigo . It is as effective as oral antibiotics and is associated with fewer adverse effects . In superficial skin infections that are not widespread, mupirocin ointment offers several advantages . It is highly active against the most frequent skin pathogens, even those resistant to other antibiotics, and the topical route of administration allows delivery of high drug concentrations to the site of infection.

J Clin Immunol, 1992 Sep, 12(5), 362 - 70
Cold-dependent activation of complement: recognition, assessment, and mechanism; Mathews KP et al.; Cold-dependent activation of complement (CDAC) is a phenomenon characterized by low hemolytic complement activity in chilled serum . Complement component levels are normal when measured immunologically, and there is normal hemolytic activity in EDTA plasma or serum maintained at 37 degrees C . Little attention has been paid to CDAC except in Japan, and current unfamiliarity with it, even by clinical immunologists, can lead to confusion and unnecessary laboratory tests . A 66-year-old patient with a complex medical history is described whose complement tests showed abnormalities characteristic of CDAC . Evidence for classical complement pathway activation in the cold was obtained by CH50 measurements, by hemolytic C4 determinations, by C4a, C3a, and C4d generation, and by quantitating C1s-C1r-(C1 inhibitor)2 complexes . A good correlation was observed among these parameters . Cryoprecipitates were absent . CDAC activity has persisted for over 5 years and is greater at 13 than at 4 degrees C . Activation is ablated by heating at 56 degrees C and restored by the addition of C1 to the heated serum . Adsorption by streptococcal protein G-Sepharose and precipitation by 2.5% polyethylene glycol support the hypothesis that CDAC is caused by aggregated IgG . The CDAC factor(s) also induces complement activation in normal serum but has not interfered with Raji cell or C1q binding tests or with FACS analysis . More limited studies of a second individual experiencing CDAC yielded similar results.

Infection, 1992 Sep-Oct, 20(5), 301 - 8
Loracarbef versus penicillin V in the treatment of streptococcal pharyngitis and tonsillitis; Muller O et al.; Ten-day, double-blind, randomized, parallel treatment regimens of loracarbef (200 mg capsule twice daily or 15 mg/kg/day oral suspension in two divided doses up to a maximum of 375 mg/day; n = 169) and penicillin V (250 mg capsule four times daily or 20 mg/kg/day suspension in four divided doses up to a maximum of 500 mg/day; n = 175) were compared in the treatment of group A beta-haemolytic streptococcal (GABHS) pharyngitis and tonsillitis . Post-therapy clinical responses were similar for evaluable patients in both treatment groups: 97.4% of the loracarbef group (101/115 patients cured and 11/115 improved) and 96.0% of the penicillin group (101/124 patients cured and 18/124 improved) . A statistically significant difference in the pathogen elimination rate was noted between treatment groups: post-therapy throat cultures were negative for GABHS in 94.8% (109/115) of loracarbef-treated patients compared with 87.1% (108/124) of penicillin-treated patients (p = 0.040) . Loracarbef and penicillin V were comparable in terms of safety . Headache and nausea/vomiting were the most common events reported during therapy (nausea/vomiting were slightly less common in the loracarbef group) . Three patients in each group were discontinued from the study due to drug-related adverse events; one due to rash in the loracarbef group and one due to rash and one due to vomiting in the penicillin group . These data support the conclusion that loracarbef twice daily is more effective in eradicating GABHS than penicillin V four times daily, and the two drugs are comparable in safety and clinical efficacy in the treatment of GABHS pharyngitis and tonsillitis.

Am J Perinatol, 1992 Sep-Nov, 9(5-6), 435 - 40
Hemodynamic effects of combining epinephrine with nitroglycerin or nitroprusside during group B streptococcal sepsis in piglets; Rudinsky B et al.; Septic shock in young children is often characterized by clinical findings consistent with a reduction in cardiac index (CI) and elevation of systemic vascular resistance index (SVRI) . In this context, infusion of inotropic agents, alone or in combination with vasodilators, has been recommended . We have utilized group B streptococcal (GBS) infusion in piglets to develop a model of low-CI/high-SVRI septic shock, and report here the effects of the combination of epinephrine (EPI) plus either nitroglycerin (NG) or nitroprusside (NP) in this model of infant sepsis . Piglets were anesthetized, intubated, and ventilated . All piglets received GBS continuously for 90 minutes and were further divided into three experimental groups . Group 1 received NG 16 micrograms/kg.min plus EPI 2 micrograms/kg.min; group 2 received NP 10 micrograms/kg.min plus EPI 2 micrograms/kg.min, and group 3 received 0.9% sodium chloride (saline) only . CI, which fell for all three groups at the onset of GBS infusion, rose significantly in group 2 animals (but not in groups 1 and 3) . This effect was mediated entirely by an increase in myocardial stroke volume . Aortic blood pressure, initially unaffected by GBS infusion, rose significantly in both group 1 and 2 compared with group 3 . SVRI, which rose for all three groups at the onset of GBS infusion, was further markedly elevated in group 1 (but not in groups 2 and 3) . Pulmonary artery pressure and pulmonary vascular resistance index, both significantly increased after GBS infusion, were reduced in group 2 but not groups 1 and 3 . These observations illustrate the potential for unexpected, and possibly detrimental, hemodynamic consequences when vasoactive agents are combined in young septic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Scand J Prim Health Care, 1992 Sep, 10(3), 223 - 5
An evaluation of a commercial co-agglutination test for the diagnosis of group A streptococcal tonsillitis in a family practice; Andersen JS et al.; The result of a rapid co-agglutination test was compared with the clinical diagnosis of group A streptococcal tonsillitis, a laboratory culture from the throat serving as the correct result . The study was carried out in a family practice, with two GPs partaking: it included 105 consecutive patients . The outcome of the rapid test was significantly correlated to the degree of growth determined by throat culture, and it was superior to the clinical judgement . The statistical analysis of the results of the rapid test revealed (95% confidence limits in brackets) a specificity of 97% (91-100), sensitivity of 68% (48-84), a positive predictive value of 90% (70-99), and a negative predictive value of 89% (81-95) . Although the co-agglutination test was superior to the clinical diagnosis, the sensitivity of this test is rather low when compared with other recently evaluated rapid tests for use in family practice.

J Emerg Med, 1992 Sep-Oct, 10(5), 607 - 16
Adult and pediatric pharyngitis: a review; Vukmir RB; Acute pharyngitis is frequently encountered in the ambulatory care setting . Although usually of viral etiology, streptococcal disease is the focus of diagnostic efforts, in light of significant suppurative and nonsuppurative sequelae . The traditional symptoms of fever, adenopathy, and pharyngeal exudate are suggestive, but not diagnostic of streptococcal pharyngitis . Thus, the importance of diagnostic testing, including Group A beta hemolytic strep antigen screen and culture, is emphasized . Recent innovations in therapy include modification of antibiotic dosing regimens and use of cephalosporins to improve patient compliance.

Curr Opin Dent, 1992 Sep, 2, 81 - 4
The role of oral microorganisms in cancer therapy; Martin MV et al.; It has been assumed that the principal changes that occur in the oral flora during cancer therapy are yeast and gram-positive coccal proliferation . Recent studies have shown that treatment with topical antifungals or disinfectants has failed to relieve such complications as irradiation mucositis that occur during anticancer therapy . Thus, many of the oral lesions observed during treatment are not due to candidiasis or streptococcal infection . It has been shown that anticancer therapy impairs or reduces the carriage defense of the oropharynx and is accompanied by colonization and proliferation of gram-negative bacilli . It is argued that if oral infectious complications are to be prevented during anticancer therapy, then the selective elimination of gram-negative bacilli may be indicated.

Crit Care Nurs Clin North Am, 1992 Sep, 4(3), 487 - 93
Group B streptococcal infection in the newborn; Fuller RA; This article reviews the immunologic and microbiologic characteristics of the group B streptococcal organism, perinatal acquisition, clinical presentation, and therapy . A discussion of immunoglobulin transfusion therapy is included, and a case study is presented.

J Infect Dis, 1992 Sep, 166(3), 574 - 9
Molecular epidemiology of group B streptococcal infections: use of restriction endonuclease analysis of chromosomal DNA and DNA restriction fragment length polymorphisms of ribosomal RNA genes (ribotyping); Blumberg HM et al.; Epidemiologic investigation of group B streptococcal (GBS) infections has been limited by the lack of a discriminatory typing system . Therefore, the use of restriction endonuclease analysis of chromosomal DNA (REAC) and DNA restriction fragment length polymorphisms of rRNA genes (ribotyping) to subtype molecularly GBS isolates associated with human invasive disease was investigated . Chromosomal DNA of selected GBS isolates was initially digested with 24 different restriction enzymes . HhaI gave the best discrimination of hybridization banding patterns (ribotypes) and was used with all study isolates . Ribotyping and REAC differentiated among isolates of the same and different serotypes . Nine ribotype patterns were noted among the 76 isolates studied, including 4 among serotype Ia/c and 4 additional ribotypes among serotype III isolates . Epidemiologically related isolates (e.g., mother-infant or twin-twin pairs) had identical REAC and ribotype patterns . Epidemiologically unrelated isolates with the same ribotype usually had different REAC patterns, suggesting that REAC may be a more sensitive technique for strain differentiation . REAC and ribotyping were reproducible and proved to be successful molecular epidemiologic methods for subtyping GBS.

J Heart Valve Dis, 1992 Sep, 1(1), 92 - 101
Chronic rheumatic heart disease in India: a reappraisal of pathologic changes; Chopra P et al.; Rheumatic heart disease contributes to significant cardiac morbidity and mortality in India . The disease predominantly affects the valvular endocardium culminating in crippling valvular deformities, preferentially involving the mitral valve which may be severely affected in children and young adults . This appears to be unique to India and has been termed juvenile mitral stenosis . It is characterized by cardiomegaly, refractory congestive heart failure, and marked by elevated pulmonary vascular pressures and a progressive, fulminant clinical course . Autopsies of patients dying of rheumatic heart disease revealed that the mitral valve was most commonly afflicted either alone or in combination with the aortic and tricuspid valves in 31.6% and 52.8%, respectively . Organic involvement of the tricuspid valve was documented in 38.4% of cases . The extent and severity of the disease process was most marked in the mitral valve, followed by the aortic and tricuspid valves . Mitral valves showed various degrees of calcification, moderate or severe calcification being observed in 36.4% . Chronic inflammatory cell infiltration was observed in both calcified and non-calcified valves . The phenotypic profile of the inflammatory cells by immunohistochemical staining revealed a significant number to be T-helper/inducer lymphocytes . Lungs from cases of mitral stenosis exhibited prominent vascular and parenchymal changes . Pulmonary vessels revealed moderate to marked medial hypertrophy of the medium sized branches of the pulmonary artery . Dilatation lesions were also seen in a few cases . The most striking parenchymal change was the prominent smooth muscle in the bronchoalveolar walls . The extent and severity of the vascular and parenchymal changes were more marked in juvenile patients . The presence of inflammatory cells in cases of chronic heart disease reflects a possible ongoing insult/injury to some persistent antigenic stimulus by beta hemolytic streptococcal antigens that have primed the various target tissues . Further study of surface characteristics of various mesenchymal cells may help in understanding the nature and pathogenesis of this serious cardiac problem.

J Med Primatol, 1992 Sep-Oct, 21(7-8), 371 - 4
Gestational diabetes mellitus in a cynomolgus monkey with group A streptococcal metritis and hemolytic uremic syndrome; Wagner JD et al.; Gestational diabetes mellitus was diagnosed retrospectively in a ten-year-old female cynomolgus monkey . The mother developed severe purulent group A streptococcal metritis resulting in fetal sepsis . After parturition, the mother died from signs consistent with hemolytic uremic syndrome.

Immunol Today, 1992 Sep, 13(9), 362 - 7
Group A streptococcal M proteins: virulence factors and protective antigens; Robinson JH et al.; Rebecca Lancefield described group A streptococcal M proteins over 50 years ago, and they have remained at the forefront of investigations into streptococcal pathogenicity to the present day . As described in this review, they form cell surface fibrils with several functions, ranging from resisting phagocytosis and inducing host-crossreactive antibodies, to presenting the host immune system with an accessible protective antigen.

Science, 1992 Aug 21, 257(5073), 1073 - 8
The origin of plagues: old and new; Krause RM; Viruses and bacteria emerge in new and old forms to cause disease epidemics . Some microorganisms recur when changing life-styles (including increased international travel) offer new opportunities; others arise from new genetic variations . These various epidemics connect the future with the past, offering lessons for guarding the health of generations to come--lessons learned from diseases such as tuberculosis, toxic shock syndrome, Lyme disease, streptococcal infection, influenza, and acquired immunodeficiency syndrome (AIDS) . The public must be vigilant to the possibility of new epidemics, learn more about the biology and epidemiology of microbes, and strengthen systems of surveillance and detection.

Biochemistry, 1992 Aug 18, 31(32), 7243 - 8
Kinetic analysis of folding and unfolding the 56 amino acid IgG-binding domain of streptococcal protein G; Alexander P et al.; The 56 amino acid B domain of protein G (GB) is a stable globular folding unit with no disulfide cross-links . The physical properties of GB offer extraordinary flexibility for evaluating the energetics of the folding reaction . The protein is monomeric and very soluble in both folded and unfolded forms . The folding reaction has been previously examined by differential scanning calorimetry (Alexander et al., 1992) and found to exhibit two-state unfolding behavior over a wide pH range with an unfolding transition near 90 degrees C (GB1) at neutral pH . Here, the kinetics of folding and unfolding two naturally occurring versions of GB have been measured using stopped-flow mixing methods and analyzed according to transition-state theory . GB contains no prolines, and the kinetics of folding and unfolding can be fit to a single, first-order rate constant over the temperature range of 5-35 degrees C . The major thermodynamic changes going from the unfolded state to the transition state are (1) a large decrease in heat capacity (delta Cp), indicating that the transition state is compact and solvent inaccessible relative to the unfolded state; (2) a large loss of entropy; and (3) a small increase in enthalpy . The most surprising feature of the folding of GB compared to that of previously studied proteins is that its folding approximates a rapid diffusion controlled process with little increase in enthalpy going from the unfolded to the transition state.

West J Med, 1992 Aug, 157(2), 133 - 8
Molecular mimicry--hypothesis or reality?
Tsuchiya N, Williams RC Jr.
A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis . Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin . How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders . In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.

Hepatology, 1992 Aug, 16(2), 469 - 78
Inhibition of hepatic metastasis of colon carcinoma by asialo GM1--positive cells in the liver; Shiratori Y et al.; This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432) . Administration of OK432 increased the number of asialo GM1-positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein . Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases . In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma . However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases . In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration . These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver.

Am Heart J, 1992 Aug, 124(2), 305 - 14
Lack of influence of pretreatment antistreptokinase antibody on efficacy in a multicenter patency comparison of intravenous streptokinase and anistreplase in acute myocardial infarction; Fears R et al.; Antistreptokinase antibodies present in patients as a result of previous streptococcal infections might theoretically influence the thrombolytic response to streptokinase or anistreplase . The potential influence of antibody, measured as antigen binding to immunoglobulin G, was investigated in a randomized, double-blind, multicenter patency comparison of intravenous streptokinase (1.5 million units/60 minutes) and intravenous anistreplase (30 units/2 to 5 minutes) in patients with acute myocardial infarction . Antibody results were evaluated in 333 patients (from a total study population of 370 patients) less than 76 years of age with ECG evidence of ST segment elevation who could be treated within 4 hours of the onset of symptoms . Variations in pretreatment circulating levels of antibody did not influence angiographically defined early coronary patency rates (Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, measured at a mean of 140 minutes after therapy was begun) for either streptokinase or anistreplase . Similarly the lytic response represented by systemic plasminogen activation and measured as changes in plasma plasminogen and fibrinogen levels after dosing (at mean times of 90 minutes and 24 hours) was not correlated with baseline antibody levels . Furthermore, pretreatment antibody was not a risk factor for poor outcome in response to streptokinase or anistreplase (reocclusion within 24 hours, in-hospital death, or stroke) and did not correlate with hypotension or allergic-type reactions recorded as adverse events . In conclusion, within the population limits defined by the inclusion and exclusion criteria of the study (patients were excluded if they had received streptokinase or anistreplase within the previous 6 months), pretreatment antistreptokinase immunoglobulin G is not a significant determinant of the efficacy response to streptokinase or anistreplase.

Gan To Kagaku Ryoho, 1992 Aug, 19(10 Suppl), 1601 - 4
{Effect of endoscopic local injection of OK-432 on regional lymph nodes in gastric cancer patients}; Ogawara T et al.; The effects of OK-432, a streptococcal preparation, administered intratumorally (OK-432 i.t.) on the change of lymphocyte subsets of regional lymph nodes were investigated in 26 gastric cancer patients . The results were as follows: 1) In the proximal lymph nodes, both non-metastatic and metastatic lymph nodes, and the proportion of CD3+ cells were slightly increased . 2) In the proximal lymph nodes without metastasis, the proportion of CD4+2H4+ cells and CD4+4B4- cells was increased about 10% . 3) In 4 of 15 patients who had metastatic lymph nodes macroscopic changes of the tumor and necrosis of metastatic lymph nodes by OK-432 i.t . were observed . In these lymph nodes CD8-CD11+ cells increased over 40% . These data suggested that the lymph node lymphocyte reaction by OK-432 i.t . may differ between metastatic lymph nodes and non-metastatic lymph nodes.

Clin Infect Dis, 1992 Aug, 15(2), 277 - 84
Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings; Schwartz B et al.; The spread of group A streptococcal infection to close contacts of infected persons is well recognized . With the resurgence of invasive group A streptococcal infections, there is an increased potential for clusters of patients with invasive disease . We reviewed data collected since December 1988 at the Centers for Disease Control (Atlanta) to identify clusters of infection in which one or more patients had invasive disease . Twelve family clusters were identified . Infection in index cases included the toxic shock-like syndrome and septicemia . Infection in family contacts included invasive infections, pharyngitis, or asymptomatic carriage . Most invasive disease occurred in adults, while the majority of noninvasive infections were in children . Five nosocomial clusters with spread of infection from patients to hospital personnel were documented . All index patients had the toxic shock-like syndrome; secondary infections included the toxic shock-like syndrome, pneumonia, bullous cellulitis, lymphangitis, and pharyngitis . Clusters of invasive infections also were identified in five nursing homes . Pneumonia, cutaneous infections, and the toxic shock-like syndrome occurred most commonly . Clustering by nursing home unit occurred in three outbreaks . In hospitals and nursing homes, improved infection control will likely decrease secondary spread; in families, spread of disease may be prevented by identifying and treating those harboring the organism or by chemoprophylaxis . Studies that characterize the rate of secondary infection are needed before definitive recommendations can be made.

Am J Obstet Gynecol, 1992 Aug, 167(2), 342 - 4; discussion 344-5
Experience with mepivacaine paracervical block in an obstetric private practice; Goins JR; OBJECTIVE: The objective of this study was to determine the efficacy and safety of mepivacaine paracervical block in term, low-risk obstetric patients . STUDY DESIGN: Over a 3-year period all term, low-risk obstetric patients in the author's private practice were offered mepivacaine paracervical block anesthesia . One hundred eighty-two patients received 200 mg mepivacaine with each block . The patients who declined paracervical block were used as a control group to compare Apgar scores, subject to chi 2 analysis . RESULTS: Initial injections were 97.3% successful . Average duration of anesthesia was 59.7 minutes with the first injection . Fetal bradycardia occurred in 13.2% with an average duration of 4.5 minutes . The slightly higher incidence of low Apgar scores at 1 and 5 minutes in the study group was not statistically significant . One neonatal death occurred secondary to group B streptococcal sepsis in the study group . CONCLUSION: Mepivacaine paracervical block remains an anesthetic option in low-risk patients . The high success rate is limited by its short duration of action and the incidence of fetal bradycardia.

J Clin Pharmacol, 1992 Aug, 32(8), 686 - 91
Single-dose antibiotic therapy: what has the past taught us?
Carbon C.
The proper dosage schedule of antibiotics has generally been determined empirically, due to the difficulty of clinical trials . Initially, the dosage was chosen to allow high sustained levels greater than MIC in the blood . Antibiotics (beta lactams, tetracyclins, macrolides) were given at high doses three to six times daily, whatever their kinetic properties . The data obtained by Eagle3 with beta lactams in animal models of streptococcal and treponemal infections outlined the importance of interval between doses on the in vivo efficacy . They also showed that increasing the dose of penicillin had a positive effect on the bactericidal activity only through the persistence of effective levels (greater than MIC) at the site of infection . Further illustrations were given through experimental and clinical studies with beta lactams or other compounds on different types of infections: LRTIs, UTIs, meningitis, and endocarditis . The importance of both dynamic (i.e., pattern of bactericidal effect) and kinetic (elimination half-life) parameters was thus further identified . Information on toxicity with some compounds with a narrow therapeutic index, such as aminoglycosides, indicated that increasing the dose to enhance efficacy had some limitations . This led to numerous studies on the relations between concentration and toxicity, stating that nephro- or ototoxicity were not directly related to peak level in serum . Experimental studies showed that OD administration of aminoglycosides was both more efficient and less toxic than the multiple-dose regimen of the same daily amount . Economic considerations progressively justified attempts to both reduce the dose and the work load related to multiple administrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycopathologia, 1992 Aug, 119(2), 73 - 6
Partial suppression of cell mediated immunity in chromoblastomycosis; Fuchs J et al.; The cellular immune response of 8 patients from the Brazilian Amazon region with chromoblastomycosis was analyzed . Primary immunological responses of patients were tested by contact sensitization to 2,4-dinitro-chlorobenzene (DNCB), or rejection of first set skin allografts . 2 of 8 patients were reactive to DNCB after sensitization, and skin allograft rejection occurred in an average of 14 days . Capacity of patients to mount recall immunological responses was measured by skin testing with two fungal antigens and three bacterial antigens . Delayed skin reaction to trichophytin and candida antigens was negative in the majority of the patients . However, reactivity to mycobacterial (tuberculin), and bacterial (staphylococcal, streptococcal) antigen was high, or only slightly diminished respectively . The data suggest that patients with chromoblastomycosis have suppressed nonspecific, cell mediated immunity for some antigens (skin allografts, DNCB, fungal antigens), while reactivity to bacterial and mycobacterial antigens is not impaired.

Monatsschr Kinderheilkd, 1992 Aug, 140(8), 490 - 2
{Has post-streptococcal glomerulonephritis disappeared?}; Latta K et al.; We report on 21 children with poststreptococcal glomerulonephritis (PSGN) . The diagnosis was based on clinical and laboratory criteria . 19/21 had a clinically apparent throat infection initially, but only 6 received antibiotic treatment . Initial symptoms were: macrohematuria (20/21), edema (10/21), arterial hypertension (6/21), reduced creatinine-clearance (11/21), and proteinuria (18/21) . No Patient was dialyzed . After an interval of 0.3 to 25 months 19 children are asymptomatic . All patients have normal creatinine-clearances; none is hypertensive . The present data show that PSGN has not disappeared in Mid-Europe . Remarkable acute disturbances occurred, which healed in almost all cases . The importance of accurate bacteriologic diagnosis and adequate therapy is emphasized.

J Bacteriol, 1992 Aug, 174(16), 5204 - 10
Cloning, sequence analysis, and expression in Escherichia coli of a streptococcal plasmin receptor; Lottenberg R et al.; Plasmin(ogen) receptors are expressed by many gram-positive and gram-negative bacteria . We previously isolated a plasmin receptor from a pathogenic group A streptococcal strain (C . C . Broder, R . Lottenberg, G . O . von Mering, K . H . Johnston, and M . D . P . Boyle, J . Biol . Chem . 266:4922-4928, 1991) . The gene encoding this plasmin receptor, plr, was isolated from a lambda gt11 library of chromosomal DNA from group A streptococcal strain 64/14 by screening plaques with antibodies raised against the purified streptococcal plasmin receptor protein . The gene was subcloned by using a low-copy-number plasmid and stably expressed in Escherichia coli, resulting in the production of an immunoreactive and functional receptor protein . The DNA sequence of the gene contained an open reading frame encoding 335 amino acids with a predicted molecular weight of 35,787 . Upstream of the open reading frame, putative promoter and ribosomal binding site sequences were identified . The experimentally derived amino acid sequences of the N terminus and three cyanogen bromide fragments of the purified streptococcal plasmin receptor protein corresponded to the predicted sequence encoded by plr . The deduced amino acid sequence for the plasmin receptor protein revealed significant similarity (39 to 54% identical amino acid residues) to glyceraldehyde 3-phosphate dehydrogenases.

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