Int Arch Allergy Appl Immunol, 1989, 90(1), 37 - 42 The biological response modifier OK-432 (a streptococcal preparation) inhibits the development of autoimmune kidney disease in NZB/W F1 hybrid mice: possible involvement of tumor necrosis factor; Mihara M et al.; OK-432 (a streptococcal preparation) has been widely used for cancer immunotherapy in Japan . It is a potent immunostimulator, activating macrophages and T lymphocytes, and increasing the production of TNF and several other cytokines in both humans and animals . In the present study, we evaluated the prophylactic effect of OK-432 on the development of autoimmune kidney disease in NZB/W F1 (BWF1) mice . The mice were given 0.5 or 2.0 KE ('klinische Einheit'; clinical unit) of OK-432 intraperitoneally every week from 21 weeks of age to the time of death . The control group received the same volume of saline (vehicle) . OK-432 delayed the development of proteinuria and prolonged the survival of these mice dose dependently . At 49 weeks, 33.3% of control mice were alive, whereas 55.6% in the 0.5-KE- and 75% in the 2.0-KE-treated mice were alive . In the control group, the serum cholesterol level increased due to the development of glomerulonephritis . In contrast, mice treated with OK-432 had significantly lower levels of serum cholesterol . The serum levels of anti-DNA and anti-TNP antibodies were not affected by OK-432 administration . OK-432 induced the production of tumor necrosis factor (TNF)-alpha in the peritoneal fluid in the BWF1 mice . These results indicate that the effect of OK-432 in preventing the development of autoimmune disease in the mice may result from the stimulation of the endogenous TNF-alpha production. Vestn Akad Med Nauk SSSR, 1989, (6), 91 - 5 {Streptococcal infections, anti-streptococcal immunity and rheumatism in the builders and operators of Baikal-Amur trunk line}; Satybaldyev AM et al.; The authors studied the dynamic of the indices of antistreptococcal immunity in 2750 builders and operation staff in various settlements in the BAM region; temporary loss of working capacity due to acute angina and rheumatic fever in 25172 persons in Tynda station; rheumatic fever morbidity rate among newly arrived population in 1974-1984 . It was shown that situation in the BAM region reflects the complicated situation in interrelationship between social, geographical, biological and medical factors. J Mol Cell Cardiol, 1989 Jan, 21(1), 61 - 6 Antibodies to a streptococcal cell wall adjuvant structure persist in patient with chronic rheumatic heart disease; Bahr GM et al.; Sera from 50 patients with chronic rheumatic heart disease were analysed by an enzyme linked immunosorbent assay for the presence of antibodies to the streptococcal minimal adjuvant moiety, muramyl dipeptide (MDP) . The T-cell responsiveness to this structure was also studied in vitro, using the lymphocyte transformation test . Fifty four percent of the patients possessed anti-MDP antibodies in their sera when examined 5 to 25 years after the initial rheumatic attack . Such antibodies were found only in 5 to 6% of sera from healthy controls or from patients with cardiac disease of non-rheumatic origin . There was neither antigenic nor mitogenic stimulation by MDP of the T-cells from peripheral blood of chronic rheumatic heart disease patients or controls . The results point to a lifetime persistence of anti-MDP antibodies in rheumatic fever and rheumatic heart disease . Possible mechanisms by which detectable levels of such antibodies are maintained in rheumatic heart disease are discussed. Eur J Immunol, 1989 Jan, 19(1), 169 - 76 T cell interactions generated by synthetic peptides covalently linked to a carrier; Childerstone A et al.; We have attempted to extend the synthetic peptide-carrier bridge concept of T cell-B cell interaction to T cell-T cell interaction . DNA synthesis of human CD4 cells that were sensitized in vivo to a native streptococcal antigen (SA) was stimulated in vitro with synthetic peptides (SP) derived from the sequence of native SA . The SP were linked to tetanus toxoid (TT) as a carrier which was recognized by primed T cells . The uptake of {3H}thymidine was significantly greater when stimulated with covalently linked SP-TT than that with non-covalently mixed SP and TT . The TT- and SP-sensitized CD4 cells were then enriched and depleted by panning on TT- or SP-treated monocyte layers . When TT-enriched CD4 cells were reconstituted with SP-enriched cells, {3H}thymidine uptake was significantly greater with the linked SP-TT than with the mixed SP and TT . However, reconstitution of the TT-enriched with SP-depleted CD4 cells or the converse failed to increase significantly DNA synthesis by cells stimulated with the linked SP-TT . The production of interleukin 2 (IL 2) and expression of IL 2 receptors were then assayed to examine any difference in stimulation between TT and SP . Both IL2 and IL2 receptors were diminished and delayed when T cells were stimulated with SP as compared with TT . The results suggest that epitope-linked clusters of monocytes, TT-sensitized CD4 and SP-sensitized CD4 cells enable IL2 released by the TT-sensitized CD4 cells to stimulate the SP-sensitized CD4 cells that produce inadequate amounts of IL2 . Indeed, addition of recombinant IL2 to T cells stimulated with mixed SP and TT induces an increase in DNA synthesis which becomes similar to that resulting from stimulation with the linked SP-TT. Taiwan Yi Xue Hui Za Zhi, 1989 Jan, 88(1), 38 - 42 Color flow mapping in perimembranous ventricular septal defect with left ventricular-to-right atrial shunts; Wu MH et al.; The natural history of ventricular septal defect (VSD) varies with the exact location of the defect and also with the tissue changes surrounding it . Seven cases of perimembranous trabecular VSD were noted during color Doppler echocardiographic examination to have left ventricular-to-right atrial (LV-to-RA) shunts in association with aneurysmal transformation of VSD . Repeated cardiac catheterization documented the role of aneurysmal transformation in the increase of LV-to-RA shunts . A VSD located near the antero-septal commissure was diagnosed in all cases by echocardiography from the apical 5-chamber and parasternal inflow views . Echocardiographic signs of LV-to-RA shunts are high velocity backward turbulence in the RA without the presence of an elevated right ventricular systolic pressure and a two-directional turbulence through the "transformed" VSD . Corrective surgery confirmed the diagnosis in one case . Another case was complicated by an episode of viridans streptococcal endocarditis . The significance of LV-to-RA shunts in perimembranous trabecular VSD remains unknown. Taiwan Yi Xue Hui Za Zhi, 1989 Jan, 88(1), 32 - 7 Surgical treatment of prosthetic valve endocarditis; Chang H et al.; From January 1980 to June 1987, a total of 16 consecutive patients underwent surgical therapy in addition to an antimicrobial regimen for prosthetic valve endocarditis at the National Taiwan University Hospital . The ages ranged from 26 to 55 years, with a mean of 40 . Nine of these 16 patients (56%) were men and 7 (44%) women . The infected valve prostheses were located at the aortic position in 5 patients, at the mitral position in 6 patients and at both mitral and aortic position in 5 patients . Among the total of 21 infected valve prostheses, 19 were bioprosthetic tissue valves and only 2 were mechanical valve prostheses . Hospital death occurred in 5 patients with an early mortality rate of 31% . Among them, 1 had fungal infection, 2 had streptococcal infection, and 2 had enterococcal infection . Four patients died of low cardiac output due to extensive myocardial involvement and one patient died of uncontrollable upper gastrointestinal bleeding . Late mortality occurred in 1 patient with fungal endocarditis and the cause of death was clinical deterioration due to multiple organ failure . The follow-up period ranged from 7 to 93 months . Except for one who was lost to follow-up, all of the patients survived in good condition without any complication. Bull Soc Pathol Exot Filiales, 1989 Jan, 82(1), 21 - 8 {32 cases of recurrent localized edema on return from the Tropics}; Bourgeade A et al.; Thirty-two patients have been hospitalised in Marseilles since 1979 for recurrent oedema following their return from a tropical region . In spite of strong suspicion, the diagnosis of Loa loa was confirmed only five times . One patient was diagnosed with filariasis due to Mansonella perstans . The diagnosis of loiasis was usually presumptive and there were often wide variations in the laboratory findings . Two patients were thought to have an allergic reaction to diethylcarbamazine . Another patient was felt to have an allergy to streptococcal antigen . One patient who had lived in the Extreme Orient presented with an inflammatory fasciitis . Two patients presented with neurological manifestations: one with eosinophilic meningo-encephalitis, one with a neuropathy of the median nerve . In one case, the oedema was attributed to congenital lymphoedema. J Med Assoc Thai, 1989 Jan, 72 Suppl 1, 35 - 8 Acute glomerulonephritis in children: a prospective study; Tapaneya-Olarn W et al.; Fifty-six patients with acute glomerulonephritis were studied prospectively during 1984 . Their ages ranged from 10 months to 14 years old with the peak age range between 5 to 9 years . Most of them had edema, hypertension, hematuria with or without proteinuria and had low serum complement . Azotemia was found in 45 per cent of the cases . Serologic evidence for streptococcal infection was positive in 68 per cent and only 6 per cent had positive culture . Edema and hypertension were all resolved within 2 weeks . All patients that were followed up had normal serum complement by the 6th week, normal BUN, Scr by one year . The hematuria disappeared by 6 months and proteinuria by 2 months in 50 per cent of the cases . By the 4th year only one patient had microscopic hematuria and mild proteinuria with normal serum creatinine, normotension and no edema . In conclusion, in Thailand AGN is still a common kidney disease in children but with prompt and proper treatment its prognosis is still very good. Int J Immunopharmacol, 1989, 11(1), 21 - 8 Activation of murine peritoneal macrophages by saikosaponin a, saikosaponin d and saikogenin d; Kumazawa Y et al.; Macrophage activation by saikosaponins and saikogenins was investigated and compared with that by other saponins and macrophage stimulants . Saikosaponins a and d induced a marked cell accumulation in the peritoneal cavity when administered intraperitoneally . Among saikosaponins and saikogenins tested, saikosaponin d significantly activated peritoneal macrophages in terms of enhancement of phagocytic activity, increased level of cellular lysosomal enzyme (acid phosphatase), induction of cytostatic activity and expression of Ia antigen on the cell surface . The activities of saikosaponin d were much stronger than those of typical saponins ginsenoside Rg1 and glycyrrhizin and almost comparable with or somewhat weaker than those of lipopolysaccharide, a streptococcal preparation OK-432 and formalin-killed Propionibacterium acnes, indicating that saikosaponin d is a potent macrophage activator. Can J Public Health, 1989 Jan-Feb, 80(1), 38 - 41 Pharyngitis 1987: a survey of physicians' attitudes and practices in southern Alberta; Berger PC et al.; A questionnaire survey concerning Streptococcal pharyngitis was completed by 85 southern Alberta family physicians . The data revealed a significant trend to overtreat pharyngitis with antibiotics because of the unreliability of clinical diagnosis and the lack of diagnostic manoeuvres with suitable ability to influence management . These data and a further questionnaire survey directed to the appreciation of other bacterial pharyngitides, demonstrate the importance of laboratory reports in biasing treatment, and further suggest that significant overtreatment of non-Streptococcal pharyngitis also occurs. Folia Med Cracov, 1989, 30(1-2), 71 - 7 {Effect of Zovirax on the course of Varicella-zoster virus (VZV) infections in children with decreased immune response}; Czajka H et al.; In 21 children with weakened immune response++ (18 patients after immunosuppression and/or after radiotherapy because of neoplastic disease, 1 patients with diagnosed hepatitis chronica persistens, 1 patient with streptococcal septicemia and one infant with protein deficiency and severe anemia) Zovirax was applied in treatment of Varicella virus infection . Clinical observation showed a positive effect of Zovirax in treatment of VZV infection which was manifested by a milder course of the infection and disappearance symptoms . Better effects were obtained when the treatment was started in the first 72 hours of infection. Br J Dermatol, 1989 Jan, 120(1), 107 - 11 Acute acral pustulosis; Hoffmann TJ et al.; We report a patient with a pustular eruption in an acral distribution that developed abruptly 4 days after a streptococcal pharyngitis . The histology showed an intraepidermal vesicle filled with neutrophils with an underlying lymphocytic vasculitis . Direct immunofluorescence demonstrated heavy deposition of C3 within the vessel walls . In addition, circulating immune complexes were found. Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S53 - 61 Infections in compromised hosts: considerations on prevention; Klastersky J; Compromised patients are predisposed to the acquisition of resistant bacteria from the hospital environment . In compromised hosts, gram-negative bacillary and staphylococcal infection is often nosocomial, being a result of the severity of the underlying disease and frequent and/or prolonged hospitalizations . The level of colonization of these patients by gram-negative bacilli can be reduced by the use of effective antibiotics administered to the oropharyngeal area or administered orally, by careful handwashing by the hospital personnel and the administration of low microbial diets to the patients . Infections caused by Staphylococcus epidermidis can be reduced by careful attention to i.v . devices; for the streptococcal infections, no clearly effective prophylaxis is available, as the mechanisms of acquisition have not been elucidated . Administration of non-absorbable antibiotics has been used for gastro-intestinal decontamination in order to prevent gram-negative infections in granulocytopenic patients . These regimens are poorly tolerated and have been replaced by the quinolones and cotrimoxazole . This latter drug is also effective for the prevention of Pneumocystis carinii infections . There is no consensus about the optimal prevention of fungal infections, especially as far as Aspergillus is concerned . For the prevention of infections caused by Candida spp., systemically absorbed imidazoles such as ketoconazole are probably effective . The infections caused by cytomegalovirus can be prevented by sero-negative blood products . In seropositive patients, ganciclovir or acyclovir might be active to some extent . Immune globulins can prevent Herpes zoster-Varicella infections and acyclovir is effective in preventing Herpes simplex virus infections. Arch Oral Biol, 1989, 34(1), 55 - 64 Acid-base pH curves in vitro with mixtures of pure cultures of human oral microorganisms; Wijeyeweera RL et al.; Pure cultures of microorganisms commonly found in supragingival plaque were incubated alone and in combinations to determine the bacterial contribution to the pH-fall-pH-rise that is the central characteristic of the Stephan-curve pH change seen in plaque in vivo after brief exposure to a sugar solution . To avoid the complicating conditions of saliva flow and plaque diffusion, experiments were done with bacterial suspensions in incubations in vitro . In an initial experimental series where each microorganism was incubated only with glucose, all but a few produced the initial pH fall . Some also showed a subsequent small, sharp rise in the pH which then quickly levelled off; this was due to metabolism of endogenous substrate accumulated by most microorganisms during their growth in culture . When arginolytic and non-arginolytic bacteria were each then incubated with both glucose and arginine present (the glucose substrate to stimulate a pH fall and the arginine to stimulate a pH rise), the non-arginolytic gave a progressively more acidic pH response with progressive increase in the cell concentration, whereas the arginolytic bacteria produced a much smaller and variable pH decrease with similar cell concentration increase . Mixing pure cultures of either arginolytic or non-arginolytic bacteria gave acid-base pH responses similar to those of their respective pure cultures, whereas mixing arginolytic with non-arginolytic bacteria resulted in an approximate averaging of their different curves . The organisms present in highest proportion in a mixture had the greatest effects . The outcome of mixing the most numerous streptococcal and actinomyces species found normally in supragingival plaque indicated that the well-established difference in the acidity level of the Stephan pH response of caries-active and caries-inactive plaques could be due to differences in the proportions of their arginolytic and non-arginolytic members. Arerugi, 1989 Jan, 38(1), 49 - 56 {Serum interleukin-2 receptor in patients with Kawasaki disease}; Matsubara T; Serum levels of soluble interleukin 2 receptor (IL-2R) were determined by a sandwich enzyme immunoassay in 42 patients during the acute phase and in 30 at the convalescent phase of Kawasaki disease, 5 with streptococcal infection, 13 with anaphylactoid purpura, 7 with various vasculitis and also in 16 healthy children . In addition, we analysed the population of peripheral blood mononuclear cells in 18 of 42 patients with KD using a fluorescence-activated cell sorter . Serum IL-2R levels in patients with KD were increased in the acute phase and return to the normal range in the convalescent phase . The increased serum IL-2R levels during the acute phase correlated with the percentage of peripheral blood helper/inducer T cells among the mononuclear cells . Serum IL-2R levels were increased in patients with measles who were examined as the infectious disease (viral) controls . However, serum IL-2R levels were increased neither in patients with anaphylactoid purpura nor in other diseases with vasculitis . These results suggest that immunological activation accompanied by the release of IL-2R from helper T cells in KD is similar measles virus infection and differs from vasculitis. Biull Eksp Biol Med, 1989 Jan, 107(1), 77 - 80 {Monoclonal autoantibodies to different epithelial structures of the thymus gland obtained by the immunization with streptococcal group A antigens}; Drobyshevskaia EI et al.; By the indirect immunofluorescence method it was shown to which epithelial thymus structures monoclonal antibodies (mAT) reacting with the different epidermal structures are directed . These mAT related to the autoantibodies were obtained earlier, as a result of lymphoid cells polyclonal activation, by the immunization of BALB/c mice with streptococcal group A nonspecific protein antigens of the cell wall . It was shown that mAT A6/1, reacting with the basal layer of the skin epithelium are directed to the epithelium of the cortical and medullar thymus zones, which is regarded as the so called endocrinal epithelium . These mAT, by the study with immunoblotting method, react with the protein of mV SOkD, B5/1 mAT to the skin epithelium, on the thymus sections react with the single cells around the Hassel bodies. Am J Dis Child, 1989 Jan, 143(1), 102 - 4 The diagnosis of group A, beta-hemolytic streptococcal pharyngitis in the office setting . Rapid latex test vs throat culture; Taubman B et al.; We compared a rapid latex agglutination test with cultures of throat specimens to diagnose group A beta-hemolytic streptococcal pharyngitis in an office setting . The throat cultures were interpreted by two pediatricians independently and evaluated by a reference laboratory . Five hundred seventy-two children participated in the study . The latex agglutination test had a sensitivity of 89.4% and a specificity of 85.7% . Cultures of throat specimens obtained in the office had a sensitivity of 91.9% and a specificity of 91.7% when interpreted by investigator 1, and a sensitivity of 90.0% and a specificity of 95.1% when interpreted by investigator 2 . There was no statistically significant difference between the numbers of false-negative results generated by the two procedures . We conclude that although somewhat less specific, the latex test is as sensitive as cultures of throat specimens in the office setting. J Exp Med, 1989 Jan 1, 169(1), 269 - 83 Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever; Bessen D et al.; The antigenic relatedness of surface-exposed portions of M protein molecules derived from group A streptococcal isolates representing more than 50 distinct serotypes was examined . The data indicate that the majority of serotypes fall into two major classes . Class I M protein molecules share a surface-exposed, antigenic domain comprising the C repeat region defined for M6 protein . The C repeat region of M6 protein is located adjacent to the COOH-terminal side of the pepsin-susceptible site . In contrast, Class I M proteins display considerably less antigenic relatedness to the B repeat region of M6 protein, which lies immediately NH2-terminal to the pepsin site . Surface-exposed portions of Class II M proteins lack antigenic epitopes that define the Class I molecules . Studies in the 1970s demonstrated that M protein serotypes can be divided into two groups based on both immunoreactivity directed to an unknown surface antigen (termed M-associated protein) and production of serum opacity factor . These two groups closely parallel our current definition of Class I and Class II serotypes . Both classes retain the antiphagocytic property characteristic of M protein, and Class II M proteins share some immunodeterminants with Class I M proteins, although the shared determinants do not appear to be exposed on the streptococcal surface . Nearly all streptococcal serotypes associated with outbreaks of acute rheumatic fever express M protein of a Class I serotype . Thus, the surface-exposed, conserved C repeat domain of Class I serotypes may be a virulence determinant for rheumatic fever. Infect Immun, 1989 Jan, 57(1), 291 - 4 Toxic shock syndrome-associated staphylococcal and streptococcal pyrogenic toxins are potent inducers of tumor necrosis factor production; Fast DJ et al.; Toxic shock syndrome-associated staphylococcal and streptococcal exotoxins were tested for an ability to induce the production of tumor necrosis factor (TNF) . Staphylococcal enterotoxins B and C1, along with streptococcal pyrogenic exotoxin A, all induced TNF production in a dose-dependent manner, with production peaking on the average at 3 days but continuing over the 6 days tested . This time course of exotoxin-induced TNF production contrasts with the 1-day peak-2-day duration observed with endotoxin as the stimulus and may be significant to development of toxic shock syndrome. Biotherapy, 1989, 1(3), 197 - 206 Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes and in vivo IL2 against advanced murine plasmacytoma; Kan N et al.; BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT) . The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective . Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT . Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA . Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes . This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect. Adv Enzyme Regul, 1989, 29, 247 - 65 Methotrexate in rheumatoid arthritis: studies with animal models; Kerwar SS et al.; The present studies have shown that low doses of methotrexate can suppress the inflammation and joint destruction associated with animal models of arthritis . The antiinflammatory effects of methotrexate are probably related to its inhibitory effect on chemotaxis . At the low doses used, methotrexate does not induce systemic immunosuppression . In methotrexate-treated rats, an improvement in IL-2 synthesis is observed and increases in IL-2 levels are expected to improve cell mediated immunity . Suppressor cells appear to be very sensitive to methotrexate . Macrophage function is modulated by methotrexate . All of these effects including the effects on joint destruction are probably due to inhibition of DHFR activity of critical cells that are involved in the pathogenesis of rat arthritis induced either by adjuvant or by streptococcal cell walls . Some of these effects have been extended to human arthritis but additional studies are required to understand how low dose methotrexate exerts its beneficial effects in humans. Eur J Cardiothorac Surg, 1989, 3(3), 262 - 6 Follow-up after coronary revascularisation in patients with renal transplants; Shafei H et al.; Seven patients underwent coronary revascularisation 12-145 months (mean: 63.4 months) after receiving cadaver renal transplants . There was no operative mortality and in all patients satisfactory renal function was maintained perioperatively . Hospital stay ranged from 7 days to 10 days (mean: 8 days) . During the period of follow-up (5-72 months, mean: 35 months): one patient remained angina-free at 7 months postoperatively; one patient developed meningitis with Listeria monocytogenes 9 weeks after surgery, and died of streptococcal septicaemia 11 weeks later . The other five patients (71.4%) developed recurrence of angina requiring antianginal therapy, and three of them sustained myocardial infarctions . Three patients developed intermittent claudication, two of whom sustained acute leg ischaemia . Two patients developed heart failure, one of whom died 38 months postoperatively . In four patients who were restudied with cardiac catheterisation and coronary angiography (2-17 months postoperatively) there was evidence of progression of the coronary arterial disease in three, although all coronary grafts were patent . Renal function remained satisfactory in 5 patients, and deteriorated in two patients; in one secondary to advanced heart failure; and in one as a terminal event secondary to septicaemia . Although patients with renal transplants can safely undergo open cardiac procedures, the long-term results of coronary surgery are adversely affected by the progressive disease from which they suffer. Immunopharmacol Immunotoxicol, 1989, 11(2-3), 257 - 68 Killing of tumor cells with pleiotropic drug resistance by OK432-activated effector cells; Allavena P et al.; The inactivate streptococcal preparation OK432 activates the cytotoxic function of natural killer (NK) cells . Moreover, it induces cytotoxic activity against freshly isolated tumor cells . The present study was aimed at assessing whether OK432-activated effector cells expressed cytotoxicity against tumor cells pleiotropically resistant to cancer chemotherapy agents . OK432-treated lymphoid cells killed the multidrug resistant (MDR) LOVO DX line as efficiently as drug sensitive parental LOVO N carcinoma line . Effector cells involved in killing MDR cells were low density large granular lymphocytes with NK functions . Activation of effector cells has the potential to complement conventional cytoreductive therapy by eliminating residual-tumor cells surviving and resistant to chemotherapy. Scand J Infect Dis, 1989, 21(6), 669 - 73 Pharmacokinetic comparison of two models of endocarditis prophylaxis with amoxycillin; Paulsen O et al.; From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in a single dose, it has been deduced that serum concentrations above 0.12 mg/l should be maintained for at least 10 h after antibiotic administration . Since concentrations above this level are reported to occur following an oral dose of 3 g of amoxycillin, this doses for prophylaxis has become widely accepted in USA and the UK, and presently also in Sweden . Nevertheless, in individuals who cannot tolerate a high single dose of amoxycillin, there is need for an alternative dosage regimen . In the present study, we have compared the pharmacokinetics in 12 healthy volunteers, of a single dose of 3 g of amoxycillin with those of 1 g as single dose or combined with 1 g of probenecid . The combination resulted in an AUC twice as large as that achieved after 1 g of amoxycillin, and was slightly, but not significantly, larger than that after 3 g . However, amoxycillin concentrations above 0.12 mg/l were sustained for almost 14 h with the combination as compared to 10.4 hours following 3 g of amoxycillin only (p less than 0.001) . Thus, the combination should be a convenient alternative in patients unable to tolerate a higher oral dose of amoxycillin, and in situations when an antibacterial effect of longer duration is desired. J Basic Microbiol, 1989, 29(6), 395 - 8 Physical maps of the streptococcal bacteriophage A25 and C1 genomes; Pomrenke ME et al.; A physical map of the group A streptococcal bacteriophage A25 genome was constructed using data obtained from restriction enzyme digestion analysis of purified DNA . Phage A25 was 34.6 kb in size and was digested with several enzymes which generated the following number of fragments: AvaI (3), EcoRI (2), HindIII (4), HaeII (10), HindII (22), HpaI (11), and PvuII (8) . Restriction enzymes BamH1, PstI, and SaI did not cleave phage A25 DNA . A physical map of the group C streptococcal phage C1 genome was also constructed . Phage C1 was 16.9 kb in size and was cleaved by the following enzymes to give the indicated number of fragments: EcoRI (8), HaeII (10), HaeII (4), HaeII (10), HindIII (5), HpaI (8), PvuII (3), and SalI (2) . Restriction enzymes AvaI, AvaII, BamH1, EcoRV, HpaII, and PstI did not cleave phage C1 DNA. Ciba Found Symp, 1989, 143, 21 - 30; discussion 30-40, 281-5 Identification and regulation of the eukaryotic hyaluronate synthase; Prehm P; Hyaluronate synthesis is required for fibroblast detachment in mitosis and migration . It is regulated by the activity of the synthase which is localized at the inner side of plasma membranes . The synthase was identified as a 50 kDa protein by immunological cross-reaction with the streptococcal enzyme and by affinity labelling . Transformation of fibroblasts by Rous sarcoma virus activated the synthase by enhanced transcription and phosphorylation . The synthase was a natural target of pp60v-src kinase. Antibiot Khimioter, 1989 Jan, 34(1), 52 - 6 {Experimental study of the antibacterial activity and chemotherapeutic efficacy of the novel glycopeptide eremomycin}; Malikova IV; The study of antibacterial and chemotherapeutic activity of eremomycin, a novel glycopeptide antibiotic showed that it inhibited the growth of gram positive and acid fast microbes . The antibacterial spectrum of the novel glycopeptide was close to that of ristomycin and vancomycin . However, the in vitro antibacterial activity of eremomycin was 2-10 times higher than that of ristomycin and vancomycin . It also inhibited the growth of oxacillin resistant microbes at concentrations 5.20 times lower than those of vancomycin and ristomycin . By the therapeutic efficacy in albino mice with staphylococcal or streptococcal sepsis eremomycin was 2-4 times as superior as vancomycin and ristomycin and by the chemotherapeutic indices it was more than 10 times as superior. Int J Immunopharmacol, 1989, 11(2), 117 - 28 Treatment of malignant ascites and pleurisy by a streptococcal preparation OK-432 with fresh frozen plasma--a mechanism of polymorphonuclear leukocyte (PMN) accumulation; Kato H et al.; A single injection of a streptococcal preparation, OK-432, with fresh frozen plasma (FFP) (or fresh human serum) into the peritoneal or pleural cavity for the treatment of malignant ascites or pleurisy resulted in a complete reduction of ascitic fluid or pleural effusion in 5 out of 11 patients . FFP was used a further source of complement for the effective accumulation of antitumor polymorphonuclear leukocytes (PMNs) by complement-derived chemotactic factors in the cavity . C5a increased in the fluids 3-9 h after the injection and preceded a massive increase in PMNs . C1 inhibitor (C1INH) and C3b inactivator (C3bINA) decreased in several cases 6 h after the treatment . Chemotactic arachidonic acid metabolites, thromboxane B2(TXB2) as a characteristics of TXA2, and leukotriene B4(LTB4) also increased at the same time even in cases where C5a changed only minimally, and may play a role in accumulating antitumor PMNs in the cavity. Drugs Exp Clin Res, 1989, 15(1), 21 - 3 Teicoplanin: Part 1 . An evaluation of the concentrations seen in serum and the subcutaneous fat of the relatively ischaemic lower limb following a single intravenous bolus; Antrum RM et al.; Teicoplanin is a new antibiotic currently undergoing clinical evaluation . Consecutive patients undergoing elective vascular surgery (n = 28) were randomised to receive a single intravenous bolus of 400 mg teicoplanin 1, 3, 6 or 12 h prior to surgery as prophylaxis against Gram-positive infection . Serum and fat antibiotic levels were measured and found to exceed the established MICs for common staphylococcal and streptococcal infections for at least 12 h following administration . This suggests that teicoplanin would be a useful choice of antibiotic in the prophylaxis and treatment of appropriate infections in elective surgery . By extrapolation, teicoplanin would also be of use in the prophylaxis and treatment of suitable infections seen in traumatised patients. Nat Immun Cell Growth Regul, 1989, 8(5), 290 - 300 Mechanism of polymorphonuclear leukocytes accumulation examined using inhibitors of complement and arachidonic acid cascade in rats treated with OK-432; Kato H et al.; When the streptococcal preparation OK-432 was intraperitoneally injected for the treatment of carcinomatous peritonitis, antitumor polymorphonuclear leukocytes (PMNs) accumulated in the peritoneal cavity . We examined the mechanism of this PMN accumulation using an in vivo system in rats . FUT-175, EDTA and K76 inhibited C5a generation by OK-432 in vitro, but EGTA, prednisolone and inhibitors of arachidonic acid cascade did not . In in vivo experiments, EDTA, FUT-175, antirat C3 serum and K76 reduced the accumulation of PMNs onto filter membranes, when these reagents were reacted with OK-432 for 3 h through filter membranes placed on the turned rat peritoneum . EGTA failed to inhibit PMN accumulation . Prednisolone, indomethacin, OKY046 and AA861 inhibited PMN accumulation in a dose-dependent manner . These inhibitions of PMN accumulation were confirmed by histological examination . It was concluded that complement-derived chemotactic factor C5a generated by OK-432 induced PMN accumulation in association with chemotactic arachidonic acid metabolites. Immunol Suppl, 1989, 2, 21 - 4; discussion 25 HLA-linked immune suppression in humans; Sasazuki T et al.; There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985) . However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988) . This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive . In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans. Immunopharmacol Immunotoxicol, 1989, 11(1), 33 - 53 Mechanism of induction of endogenous tumor necrosis factor in ascites of ovarian cancer patients by OK-432, a streptococcal preparation; Mori H et al.; In four ovarian cancer patients with malignant ascites, 10 KE of OK-432 was intraperitoneally administered four times every other day for priming, and 40 KE of OK-432 in a single dose by the same route on day 13 for triggering . The changes in peripheral blood monocytes and intraperitoneal macrophages and the production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) and ascitic lymphoid cells (ALC) were examined . In two of the four patients in whom TNF was induced in the ascites, the TNF production by PBMC and ALC was noted during priming, and after triggering, an increase in both the number of intraperitoneal macrophages and the TNF production by ALC was noted . In two other patients in whom TNF was not detected in the ascites, the ratio of intraperitoneal macrophages to ALC did not change throughout the whole period, and the TNF production by ALC was not augmented . These findings suggest that the priming administration of OK-432 can induce both intraperitoneal macrophages and peripheral blood monocytes into a primed state, and the triggering administration of OK-432 can increase the number of intraperitoneal OK-432-primed macrophages and induce TNF release from these cells. Cancer Immunol Immunother, 1989, 29(4), 255 - 60 Augmented induction of antitumor cells in vivo by cyclophosphamide fails to benefit antitumor resistance of the host; Ryoyama K et al.; The present study was designed to examine whether cyclophosphamide augmented induction of antitumor cells and antitumor resistance in C57BL/6 mice pretreated with mitomycin-C-treated EL4 cells (EL4MMC) plus OK-432, a streptococcal preparation . C57BL/6 mice were pretreated with EL4MMC (10(7} plus OK-432 (2.5 KE) i.p . twice at 1-week intervals . When the mice received an i.p . injection of cyclophosphamide at 200 mg/kg 2 days before the last treatment, the antitumor activity of their spleen cells and peritoneal exudate cells (PEC) was effectively augmented 7-8 days after the last treatment . Splenic antitumor activity disappeared 15 days after the last treatment whereas augmented antitumor activity of the PEC was detected even 28 days after the last treatment . This cyclophosphamide effect was dose-dependent and 200 mg/kg was the most effective among the doses tested . If the EL4MMC plus OK-432 treatment was injected at a s.c . site, it was also effective in combination with cyclophosphamide . The antitumor activity of the PEC from s.c.-pretreated mice, however, was lower than that from i.p.-pretreated mice . Despite the fact that cyclophosphamide effectively augmented induction of antitumor cells in C57BL/6 mice pretreated with EL4MMC plus OK-432, it diminished rather than augmented, under all conditions tested, the ability of the mice to resist a challenge of live EL4 cells . Reduction of antitumor resistance by cyclophosphamide was also observed in an experimental system of a semi-syngeneic host (BDF1) tumor (EL4) . These results indicate that augmentation of in vivo induction of certain kinds of antitumor cells does not necessarily result in a beneficial augmentation of the host's ability to resist tumor growth. Cancer Immunol Immunother, 1989, 29(2), 79 - 86 Role of interleukin-2 and interferon-gamma in induction of activated natural killer cells from mice primed in vivo and subsequently challenged in vitro with the streptococcal preparation OK432; Yamaue H et al.; The natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432 . Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-gamma . As the anti-(mouse IFN-gamma) monoclonal antibody but not anti-(mouse IFN-alpha) antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response . The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D . The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432 . The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells . The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-gamma . These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma. Vestn Akad Med Nauk SSSR, 1989, (11), 12 - 7 {Use of group A-specific polysaccharide antigen conjugated with protein carrier for detection of specific anti-polysaccharide antibodies}; Burova LA et al.; Group-A specific polysaccharide antigen has been obtained by extraction of streptococcal suspension using 4N NaNO2 and glacial acetic acid, conjugated with bovine serum albumin using CNBr . Testing of the preparation with a set of rabbit anti-sera by enzyme immunoassay (EIA) and passive hemagglutination reaction (PHR) revealed its antigenic specificity both in direct experiments and in N-acetyl-D-glucosamine absorption . Forty-seven sera of EIA-studied individuals and 35 sera of PHR-studied ones, all with group-specific polysaccharide antigen, were examined . Immune reactions showed the broad spectrum of antibody titres in the studied sera . Complete correlation of anti-polysaccharide antibodies detected by the two techniques was observed in the sera with high specific antibody titres . A possibility to use the obtained group-A specific polysaccharide antigen to detect anti-polysaccharide antibodies in the sera of streptococcal infection patients is discussed. J Immunol, 1988 Dec 15, 141(12), 4276 - 82 Fc region-dependence of IgG3 anti-streptococcal group A carbohydrate antibody functional affinity . I . The effect of temperature; Greenspan NS et al.; Previous studies have demonstrated that IgG3 anti-streptococcal group A carbohydrate (GAC) mAb bind to the surfaces of heat-killed, pepsin-digested group A streptococcal cells in an Fc region-dependent cooperative manner . This form of positive cooperative binding of antibody to Ag was hypothesized to result from noncovalent association of Fc regions of antibodies bound close to one another on the Ag surface . Because IgG3 Fc regions are self-aggregating and IgG3 molecules are frequently cryoprecipitable, we have now investigated the effect of temperature on the binding, and cooperative binding, of IgG3 anti-GAC mAb to solid-phase (sp) Ag . The Ag used was a covalent conjugate of N-acetyl-D-glucosamine (GlcNAc; the epitopes on GAC) and BSA . The main findings were: 1) IgG3 anti-GAC mAb bind to sp GlcNAc-BSA to greater extents at lower temperatures, 2) IgM anti-GAC mAb and Fab and F(ab')2 fragments, derived from an IgG3 anti-GAC mAb, bind to sp GlcNAc-BSA to comparable extents at different temperatures, 3) idiotope-expressing IgG3 anti-GAC mAb bind to sp anti-idiotope to comparable extents at different temperatures, and 4) unlabeled IgG3 anti-GAC mAb enhance the binding of radiolabeled IgG3 anti-GAC mAb to sp GlcNAc-BSA, and the degree of this enhancement is greater at lower temperature . These, and additional results, support the conclusion that for some sp Ag the functional affinities of IgG3 antibodies, are influenced by the Fc region in a temperature-dependent manner. Antiviral Res, 1988 Dec 11, 10(6), 299 - 304 Antiherpes activity of the immunomodulator OK-432, a streptococcal preparation, in immunosuppressed mice; Ikeda S et al.; The antiviral activity of OK-432, an antitumor agent originating from Streptococcal preparations, against herpes simplex virus type 2 (HSV-2) was investigated in mice immunosuppressed by cyclophosphamide (CY) . Intraperitoneal administration of OK-432 to mice 1 day after treatment with 200 mg CY/kg prevented death due to HSV-2 encephalitis in a dose-dependent manner . When the immunosuppressed mice were given OK-432 prior to HSV-2 infection, both by the intraperitoneal route, virus growth in the peritoneal cavity was significantly suppressed . Following with OK-432, the number of macrophages in immunosuppressed mice was increased to a significantly greater extent than the numbers of lymphocytes and polymorphonuclear leukocytes . The intrinsic antiviral activity of macrophages against HSV-2 as well as the natural killer (NK) activity against YAC-1 target cells was significantly enhanced by OK-432 in immunosuppressed mice. Postgrad Med J, 1988 Dec, 64(758), 965 - 7 Scarlet fever can mimic toxic shock syndrome; Brook MG et al.; We describe a patient who presented with a widespread erythematous rash, diarrhoea, confusion, pre-renal uraemia and hyponatraemia . The diagnosis of staphylococcal toxic shock syndrome seemed likely as she was menstruating and there was no evidence of pharyngitis . A rising ASO titre confirmed a streptococcal aetiology and thus 'toxic' scarlet fever . Toxic shock syndrome and toxic scarlet fever are compared. Hinyokika Kiyo, 1988 Dec, 34(12), 2111 - 4 {An experience of OK-432 intradermal administration in superficial bladder tumors}; Tsujihashi H et al.; A streptococcal preparation, OK432 was evaluated as the adjuvant immunotherapeutic agent for superficial bladder tumors . Twenty-nine cases were treated with complete transurethral resection and then randomized prospectively into two groups . One group had adjuvant therapy of OK432 intradermal administration and another group had no adjuvant therapy . OK432 administration significantly reduced the recurrence rates as compared to the control group . Although further studies were required for its full significance, in a short-term study, OK432 intradermal administration produced a beneficial effect in reducing the recurrence rates. J Biol Response Mod, 1988 Dec, 7(6), 596 - 607 TNF induces endogenous TNF in vivo: the basis of EET therapy as a combination of rTNF together with endogenous TNF; Inagawa H et al.; Enough amounts of tumor necrosis factor (TNF) in mice serum for the therapy were observed by treatment with 100 units of recombinant human TNF-alpha (rHuTNF-alpha) followed by administration of OK-432 (a streptococcal preparation) . Optimal time interval between rTNF and OK-432 to produce endogenous TNF was 3 h, and priming activity of rTNF persisted for at least 10 h . The same effect was observed using novel human recombinant TNF-SAM2 (rHuTNF-SAM2) developed by our group . Production of endogenous TNF using rTNF-alpha or rTNF-SAM2 as a priming reagent was almost equal among various mice strains . Induced TNF in mice serum was completely neutralized by anti-MuTNF antiserum, but not by anti-HuTNF monoclonal antibody . rMuTNF could also induce the priming state; however, the dose-response kinetics of the priming effect to produce endogenous TNF was different between rHuTNFs and rMuTNF-alpha, suggesting species specificity among rTNFs used . The therapeutic effect against Meth A and MH134 tumors in mice treated by rHuTNFs in combination with OK-432 was superior to that by single administration of either OK-432 or rHuTNFs or by successive administrations of OK-432 . Especially, the antitumor effect against MH134 hepatoma was superior to that of any other treatment using known biological response modifiers so far experienced . These results suggest that such combination antitumor therapy as rTNF together with OK-432 should be applicable to cancer patients. Aust Paediatr J, 1988 Dec, 24(6), 357 - 61 Persistent pulmonary hypertension of the newborn treated with hyperventilation: clinical features and outcome; John E et al.; Twenty-seven infants with severe persistent pulmonary hypertension of the newborn were seen in 33 months . Asphyxia with or without meconium aspiration was the cause in the majority of cases . Other causes were group B streptococcal sepsis and acute fetal blood loss . The mortality rate was 11% . Twenty-three of the 24 survivors were followed . Their age at follow-up ranged 12-37 months . The mean score for mental development was within the normal range while that for psychomotor development was 1 standard deviation below normal . Seven infants were judged to be at risk of attention deficit disorder . Predictor variables related to these outcomes were cardiotocography, meconium aspiration, first pH, highest PaCO2 after resuscitation and mother's education . All infants except one were perceived as normal by their parents. Clin Exp Immunol, 1988 Dec, 74(3), 365 - 70 Immunosuppressive macrophages induced by arthropathic peptidoglycan-polysaccharide polymers from bacterial cell walls; Regan DR et al.; Rats injected with peptidoglycan-polysaccharide polymers derived from group A streptococcal cell walls (PG-APS) develop a chronic, remittant, erosive synovitis . Spleen cells from injected rats failed to proliferate when stimulated in vitro by Con A or PHA, unless nylon wool adherent cells were first removed . The suppression could also be reversed by removing phagocytic cells which had ingested carbonyl iron . Cells from control rats were suppressed in vitro by co-culture with unfractionated or nylon wool-adherent cells from PG-APS injected rats, and the suppressor activity was still expressed after exposure of the suppressor cells to 3,000 rad of irradiation . Addition of catalase and indomethacin to cultures only partially reversed the suppression . T lymphocytes from rats given a single arthropathic dose of PG-APS remained suppressed for at least 86 days after injection . Cells from rats given a low, non-arthropathic dose of PG-APS did not become suppressed . Cells from the Buffalo rat, which is resistant to development of PG-APS-induced chronic arthritis, showed less suppression than cells from the susceptible Lewis and Sprague-Dawley rat strains. Eur J Immunol, 1988 Dec, 18(12), 1959 - 64 Human immune response to group A streptococcal carbohydrate (A-CHO) . III . Comparison of the efficiencies of anti-idiotopic antibody and of nominal antigen in the induction of IgM anti-A-CHO-producing B cells; Bloem AC et al.; In this study the efficiencies of a monoclonal anti-idiotopic (Id) antibody (anti-Id498) and of various preparations of nominal antigen in the induction of an antigen-specific human B cell response in vitro were compared . Anti-Id498 recognizes a recurrent, binding site-related Id present on IgM antibodies with specificity for N-acetyl-D-glucosamine, the immunodominant group of streptococcal group A carbohydrate (A-CHO) . We have previously shown that anti-Id498 induces IgM anti-A-CHO secretion from B cells of donors that possess Id-498+ antibodies in their serum . A-CHO was presented to B cells either in soluble or insoluble form, i.e . coupled to beads or as intact bacteria . Purified blood B cell populations from three Id+ healthy donors with high numbers of circulating anti-A-CHO B cells were used and antibody-producing B cells are enumerated in a single-cell assay (spot ELISA) . The data show that anti-Id498 was superior in the induction of IgM anti-A-CHO-secreting B cells in two donors (factor 4.6 and 13.5 as compared to the most efficient antigenic stimulation) . In the third donor antigen stimulation was slightly more efficient than anti-Id but only with Sepharose-bound A-CHO and not with soluble A-CHO or intact bacteria . The increase of specific B cells induced after stimulation with anti-Id498 could be abolished after addition of autologous T cells in two donors . On the contrary, an enhancement of the specific response was observed after addition of autologous T cells in antigen-stimulated cultures . Neither suppression nor enhancement were induced by addition of irradiated T cells. Pediatr Infect Dis J, 1988 Dec, 7(12), 847 - 54 Clinical evaluation of a latex agglutination test for streptococcal pharyngitis: performance and impact on treatment rates; Lieu TA et al.; The accuracy and clinical utility of a latex agglutination test were compared with anaerobic throat culture on selective media for detection of Group A streptococcal pharyngitis in an urban pediatric emergency department . Among 255 symptomatic cases prevalence of positive culture was 29% and antigen test sensitivity was 55% . Among 100 asymptomatic controls prevalence of positive culture was 20% and antigen test sensitivity was 20% . Controls with positive cultures and cases with false negative antigen tests had significantly fewer colonies on culture than cases with true positive antigen tests (P less than 0.01) . Symptoms and clinical findings were not associated with antigen test result or number of colonies on culture . Eighty percent of patients with positive cultures received treatment when the antigen test was used as an adjunct to culture, compared with a 57% treatment rate among the subgroup in whom follow-up treatment was attempted based on positive culture results alone (P less than 0.05) . We conclude that: (1) the antigen test had lower sensitivity in routine clinical use than previously reported; (2) the high rate of false negative tests may result, in part, from a high proportion of specimens with low colony counts; and (3) the availability of the antigen test as an adjunct to culture significantly increased treatment rates. Pediatr Infect Dis J, 1988 Dec, 7(12), 836 - 47 Correlation of clinical and pathologic findings in early onset neonatal group B streptococcal infection with disease severity and prediction of outcome; Payne NR et al.; This study analyzed the clinical characteristics of 69 neonates who were admitted to the University of Minnesota Hospital between January, 1972, and June, 1984, with early onset Group B streptococcal infection (EOGBS) and determined those features associated with fatal infection . The incidence of EOGBS was 1.6 cases/1000 live births among 7960 inborn infants; the mortality rate for inborn and outborn infants was 28% . Multivariate analysis identified five features adequately predicting fatal outcome: birth weight less than 2500 g, absolute neutrophil count less than 1500 cells/mm3, hypotension, apnea and a pleural effusion on the initial chest radiographs . With these five variables and an initial blood pH less than 7.25, a clinical score was constructed that correctly predicted outcome in 93% of patients in this study (87% sensitivity, 95% specificity) . Autopsy findings in 16 of 19 infants with fatal EOGBS suggested that surfactant deficiency respiratory distress syndrome was common in preterm infants with EOGBS and contributed to their higher mortality compared with term infants. Clin Perinatol, 1988 Dec, 15(4), 831 - 50 Antimicrobial prophylaxis of neonatal group B streptococcal sepsis; Boyer KM et al.; This article reviews available studies on prevention of neonatal group B streptococcal infections with antimicrobial prophylaxis . The data show that short-term administration of ampicillin to parturients with prenatal streptococcal colonization and perinatal risk factors effectively prevents these serious infections . A strong case can be made for prenatal screening for group B streptococcal carriage to identify mothers whose babies are at risk. Am J Pathol, 1988 Dec, 133(3), 623 - 9 Neutrophil mobilization induced by complement fragments during experimental group B streptococcal (GBS) infection; Shigeoka AO et al.; Degradation products of the third component of complement have been reported to have the ability to mobilize leukocytes from the marrow and induce leukocytosis . The effect of C3d,g preparations on neutrophil responses in a neonatal rat model of group B streptococcal infection in which neutrophil mobilization from the marrow is inadequate has been evaluated . Dimeric and monomeric fragments of C3d,g were isolated from human serum; the identity of the C3d,g preparations was confirmed by SDS-PAGE, Western blotting, and N-terminal amino acid sequencing . Uninfected neonatal rats responded to intraperitoneal injection of C3d,g with a peripheral blood neutrophilia at 30 minutes and 4 hours after inoculation . C3d,g, which lacks intrinsic chemotactic activity, enhanced the local accumulation of neutrophils in the peritoneal cavity of infected, but not uninfected, neonatal rats . In addition, myeloid cell release from the marrow of isolated femurs of neonatal rats receiving C3d,g was significantly enhanced . Thus, the effect of C3d,g in this model was to mobilize marrow cells and induce peripheral leukocytosis . Chemotactic factors released at the site of infection then resulted in the local accumulation of these inflammatory cells . Complement-derived components capable of releasing marrow myeloid elements may play a major role in determining the outcome of bacterial infection in the immature host. Presse Med, 1988 Nov 19, 17(41), 2175 - 8 {Epidemiology of glomerular diseases in a region in France . Changes as a function of periods and the age of patients}; Simon P et al.; Between January 1, 1976 and December 31, 1987, a histological diagnosis of primary glomerular disease was made in 420 patients born and living at the time of diagnosis in a region of France with some 400,000 inhabitants . The prevalence of glomerular disease during that span of time was 1 in 1,000 . The annual incidence of the disease was evaluated separately for 3 consecutive 4-year periods: period A (1976-79), period B (1980-83) and period C (1984-87) . Within each of these 3 periods the number of patients with primary glomerular disease was 138, 148 and 115 respectively, and the figures for annual incidence were 8.6, 9.2 and 7.2 respectively in 100,000 . Idiopathic IgA glomerulonephritis was the most common of primary glomerular diseases (34.2 per cent), and its annual incidence remained the same throughout the 3 periods: 2.6, 3.2 and 2.8 in 100,000 . The incidence of membranoproliferative glomerulonephritis (7 per cent) decreased from 1980 onward (1.2, 0.5 and 0.3 in 100,000) while that of idiopathic proliferative glomerulonephritis (GNPI) with crescents slightly increased (0.25, 0.7 and 0.5 in 100,000) . Acute streptococcal glomerulonephritis virtually disappeared during periods B and C . Lipoid nephrosis was significantly less frequent in period C, whereas secondary membranous glomerulonephritis progressed . There was no significant difference between the 3 periods as regards the incidence of other primary glomerular diseases . All histological types of the primary diseases became more frequent in elderly people . Thus, the overall frequency of primary glomerular diseases decreased slightly during the last 4 years, but it increased in the population aged over 65 and diminished in the younger population. Allergol Immunopathol (Madr), 1988 Nov-Dec, 16(6), 413 - 5 Cellular immunity in lobomycosis (keloidal blastomycosis); Pecher SA et al.; The cellular immune response of twelve patients from the Brazilian Amazon basin with lobomycosis were assessed . Delayed skin reaction to bacterial and fungal antigens, skin allograft rejection, and sensitization to dinitrochlorobenzene were studied . Ninety-two percent of the patients were not reactive to dinitrochlorobenzene after sensitization; skin allograft rejection occurred in an average of 17 days . Delayed skin reaction to streptococcal, staphylococcal, trichophytin and candida antigens was negative in the majority of the patients . Reactivity to mycobacterial antigens, however, was very high . The results suggest that patients with lobomycosis are partially cellular immunodeficient. Scand J Prim Health Care, 1988 Nov, 6(4), 219 - 23 Clinical assessment of pharyngitis in general practice; Hjortdahl P et al.; The present study investigates the feasibility of the clinical differentiation between patients with beta-haemolytic streptococcal pharyngitis from those with pharyngitis caused by other agents, based on the patients' symptoms, symptom duration, and the clinical findings . Twenty-four general practitioners recruited 225 patients for the study . Fifty-six patients had positive and 169 patients negative group A beta-haemolytic streptococcal throat cultures . Twenty-two patients in the streptococcal group and 76 patients in the non-streptococcal group were initially correctly diagnosed based on an overall clinical assessment (sensitivity 0.39, specificity 0.55 and accuracy 0.51) . This is as accurate as "flipping a coin" . Similar figures were found with regard to the individual symptoms (accuracy 0.38-0.68) and clinical findings (accuracy 0.36-0.65) . Taking the duration of symptoms into account and applying discriminant function analysis did not significantly improve these figures . In order to obtain a sufficiently accurate diagnosis in general practice, the use of the new rapid agglutination test for streptococcal identification is recommended. Pediatr Infect Dis J, 1988 Nov, 7(11), 765 - 9 Evaluation of the throat culture as a follow-up for an initially negative enzyme immunosorbent assay rapid streptococcal antigen detection test; Lewey S et al.; In a study of the efficacy of following up an initially negative enzyme immunosorbent assay (EIA) rapid streptococcal antigen detection test with a throat culture, 2 double swabs (4 total) were obtained from 264 pediatric patients with sore throats . Although a throat culture was more specific (97%) than the EIA (89%), the sensitivity (87%) and negative predictive value (97%) of a single EIA was the same as that of a single throat culture . A follow-up throat culture was more accurate than a follow-up EIA . We conclude that the office EIA tested results in more false positives but misses no more true positives than a single throat culture processed by a well-controlled microbiology laboratory . If a follow-up technique is used for an initially negative EIA rapid streptococcal antigen detection test, the throat culture is the superior test and would be equally applicable following an initially negative throat culture or EIA. J Infect, 1988 Nov, 17(3), 201 - 4 Early-onset neonatal group B streptococcal septicaemia in siblings; Carstensen H et al.; At each of two consecutive deliveries, a woman gave birth to a baby that developed early-onset group B streptococcal (GBS) septicaemia . A low titre of serum antibodies to the type of the infecting GBS and persistence of the organism in the mother were demonstrated . This case confirms that mothers of GBS infected infants are at high risk of their future babies being similarly infected. Cutis, 1988 Nov, 42(5), 406 - 11 Elephantiasis nostras: an eight-year observation of progressive nonfilarial elephantiasis of the lower extremity; Sanders LJ et al.; An eight-year follow-up of a progressive case of nonfilarial elephantiasis affecting the lower extremity and a review of the literature is presented . The natural history and management of this disorder are discussed, together with recommendations to assist the clinician in early identification an treatment . Elephantiasis nostras is characterized by chronic enlargement of a limb, resulting from lymphatic blockage secondary to recurrent attacks of streptococcal lymphangitis . Each subsequent attack results in greater edema of the limb . Without appropriate intervention the cycle continues until the deformity is greatly exaggerated . Control of edema an infection is important in preventing the recurrent lymphangitis that will eventually result in grotesque enlargement of the limb . Photographic documentation and serial circumferential limb measurements are recommended to document progression of the disease and effectiveness of treatment. Am J Kidney Dis, 1988 Nov, 12(5), 340 - 7 Worldwide perspective of IgA nephropathy; Levy M et al.; It is becoming evident that IgA nephropathy (IgAN) is the most common glomerular disease, and a frequent cause of end-stage renal failure in both white and Asian populations . Its significance as a public health problem is not known since little epidemiologic research is available in most countries . The apparent geographic variations in the percentage of IgAN in kidney biopsy specimens may reflect different clinical policies for diagnostic tests . As a consequence, the frequency of IgAN cannot be accurately extrapolated from these data for any given population . The highest percentages, reported in Singapore and Japan, may be influenced by the systematic screening of urines in both countries . By contrast, IgAN has been detected rarely in blacks either from the United States or from Africa . However, biopsies are performed infrequently in African patients with only microscopic hematuria . Such ethnic differences may suggest a possible role of genetic factors in the etiology of IgAN . As shown recently in France and Italy, antibiotic therapy of streptococcal infections apparently has not influenced the percentage of IgAN in kidney biopsy specimens . These facts and the rarity of the glomerulonephritis in blacks suggest that infections may not be responsible for the etiology of IgAN . The traditional search for causal agents should be approached more vigorously . It will require innovative epidemiologic efforts to understand the mechanisms by which multiple factors (environmental and genetic) acting together influence the risk of disease. J Rheumatol, 1988 Nov, 15(11), 1672 - 6 Augmentation of cytotoxic activity by mitogens in rheumatic heart disease; Gray ED et al.; Natural killer cell activity and alterations in cytotoxicity after culture with streptococcal blastogen A and phytohemagglutinin (PHA) were examined in patients with inactive rheumatic heart disease (RHD) and control patients . Natural cytotoxic activity of mononuclear cells (MNC) did not differ between RHD and control patients with either peripheral blood or tonsils . In cultured blood MNC the level of cytotoxic activity stimulated by blastogen A was significantly greater in patients with RHD at all effector:target cell ratios . These differences in cytotoxic activity were not observed with cultured tonsillar MNC . In similar experiments with a different group of patients, culture with PHA or blastogen A both produced a significantly greater increase in cytotoxic activity in blood MNC from patients with RHD . The increase was significantly lower with PHA than with blastogen A . The ability of mitogens to differentially augment cytotoxic activity in cells from the blood of patients with RHD implies that a population of cells exists in these patients that could be activated during acute rheumatic fever to play a role in pathogenesis. J Immunol, 1988 Oct 15, 141(8), 2755 - 9 Defective production of and response to IL-2 in acute human falciparum malaria; Ho M et al.; Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA) . This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas . To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation . The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied . Soluble IL-2R levels were measured in acute and convalescent sera . Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection . IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag . The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells . In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera . These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P . falciparum malaria. J Immunol, 1988 Oct 15, 141(8), 2668 - 73 Hyperimmunization alters Fc gamma antigenicity . Linkage to glycosylation; Murray JS et al.; Rabbits were hyperimmunized with streptococcal vaccine to produce hyperimmune (HI) IgG, and both HI IgG and autologous preinoculation (PI) IgG were used to prepare Fc gamma . mAb raised against these, and deglycosylated PI Fc gamma preparations were subsequently used to determine if antigenic differences existed between autologous HI and PI Fc gamma . Although the majority of mAb examined did not discriminate between the two sources of Fc gamma, several mAb exhibited remarkable specificity for autologous HI Fc gamma . We did not detect any mAb which exhibited the converse specificity . Of the mAb chosen for study, all except one appeared specific for determinants located in C gamma 2; the exception specifically reacted with pFc', and did not discriminate between the two Fc preparations . Importantly, partial deglycosylation of autologous PI Fc gamma led to equivalent reactivity with previously HI-specific mAb . The results of this study provide immunologic evidence that abnormal C gamma 2 structures exist prior to and reach serologically detectable levels during the hyperimmune response in these animals, apparently as a result of glycosylation pattern alterations within the Fc region . Such autoantigenic differences could account for the induction of RF under these conditions, and perhaps in certain human arthritic diseases as well. N Z Med J, 1988 Oct 12, 101(855), 625 - 6 Acute streptococcal necrotising fasciitis; Frankish PD et al.; Two cases of acute streptococcal necrotising fasciitis are reported . Both patients were taking nonsteroidal antiinflammatory drugs when they developed this infection . Urgent surgical debridement was undertaken and resulted in a successful outcome in both patients . The clinical and histopathological features of this condition are reviewed. Ophthalmology, 1988 Oct, 95(10), 1404 - 10 Coagulase-negative staphylococcal endophthalmitis . Increase in antimicrobial resistance; Davis JL et al.; The predicted sensitivities of common organisms guide initial antibiotic therapy in endophthalmitis . The authors suspected a change in the expected sensitivity of coagulase-negative staphylococci when three cases of endophthalmitis due to multiply resistant organisms failed to respond to intravitreal cefazolin and gentamicin . The authors reviewed 48 cases from 1982 to 1986, compared these with 28 cases from 1973 to 1981, they found increased resistance to gentamicin (35 versus 0%, P less than 0.05) and increased resistance to methicillin (27 versus 19%) . Eight cases were resistant to both antibiotics, including the three clinical failures . Final vision was unrelated to antimicrobial resistance . Since cephalosporins may be ineffective clinically against methicillin-resistant staphylococci, concomitant gentamicin resistance may render intravitreal cefazolin and gentamicin inadequate for their treatment . No isolates were resistant to vancomycin . Vancomycin and aminoglycoside, used intravitreally in the initial management of endophthalmitis, would be anticipated to provide better coverage than cefazolin and aminoglycoside for endophthalmitis due to the staphylococci, as well as for infections due to streptococcal and bacillus species. Zh Mikrobiol Epidemiol Immunobiol, 1988 Oct, (10), 59 - 64 {Evaluation of lymphocyte cooperative interaction with neutrophils by the stimulation of lymphokine production in erysipelatous inflammation}; Tsoi IG; In erysipelatous inflammation lymphocytes were found to secrete lymphokine, both spontaneously and in response to in vitro stimulation with streptococcal allergen . The secreted lymphokine enhanced the oxygen-dependent metabolism of neutrophils . The lymphokine formation observed in this study depended on the clinical form of the disease . The character of the effect produced by lymphokine was determined by the initial state of target cells (macrophages). Chest, 1988 Oct, 94(4), 688 - 93 Effect of smoking on natural killer cell activity in the lung; Takeuchi M et al.; We investigated the effect of smoking on natural killer (NK) cell activity and distribution in bronchoalveolar lavage fluid (BALF) and blood . Initially, BALF NK cell activity was lower than the blood NK cell activity both in non-smokers (NS) and smokers (S) . Following 24 hour culture, NK cell activity markedly increased in NS but not in S . Percentage distribution of Leu-7+ cells and Leu-11+ cells in BALF was similar in NS and S . But the BALF NK cell activity was significantly augmented by IL-2 or OK-432 (a streptococcal preparation) in NS . It appears that smoking reduces NK cell activity in BALF . It is conceivable that the low NK cell activity in BALF in S might contribute to increased incidence of infection and malignancy in smokers. Cell Immunol, 1988 Oct 1, 116(1), 216 - 29 T cell responses to streptococcal antigens in rats: relation to susceptibility to streptococcal cell wall-induced arthritis; van den Broek MF et al.; In order to investigate the immunological mechanism of the chronic phase of streptococcal cell wall (SCW)-induced arthritis in Lewis rats, we compared the SCW-specific T cell response in arthritis-susceptible (female Lewis) and resistant (F344) rats . We present evidence that this T cell response is absent in F344 rats, while it is clearly present in Lewis rats . The T cell response was analyzed both in the spleen and in lymph nodes . In addition, we show, that injection of SCW in the F344 rat induces a general unresponsiveness in this strain: the response to mitogen was severely suppressed in SCW-injected F344 rats and, furthermore, when SCW was coinjected with ovalbumin, the response to ovalbumin was depressed . The fact that priming with ovalbumin alone induces a normal response in the F344 rat to both mitogen and ovalbumin implies that the observed abnormality after SCW priming is not a general immunological defect in this strain . Additionally, we demonstrate that adherent cells of both Lewis and F344 exert negative effects on an in vitro T cell response after injection with SCW, and that F344-adherent cells are more potent in this effect . Removal of OX8-positive cells leads to a restoration of the SCW-specific T cell response in SCW-injected F344 rats, indicating that the expression of this response is controlled by (SCW-specific?) suppressor T cells . Our results provide suggestive evidence for the obligatory role of SCW-specific T cells in the expression of chronic joint inflammation after systemic injection of SCW. J Clin Lab Immunol, 1988 Oct, 27(2), 87 - 90 Persistence of heart reactive antibodies (HRA) in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) patients; Shastry P et al.; Heart Reactive Antibodies (HRA) of IgG and IgM classes were investigated in 79 patients in four clinically classified groups . Group I comprised of 16 children with Acute Rheumatic Fever (ARF) and Group II consisted of 15 cases with active Rheumatic Heart Disease (RHD) . Twenty seven cases of ARF and RHD in remission and 21 adults with quiescent RHD were included in Groups III and IV respectively . Control groups comprised of 14 normal, healthy, donors and eight Post Streptococcal Acute Glomerular Nephritis (PSAGN) cases . Low levels of HRA of IgG and IgM classes were detected in control groups . The overall incidence of HRA of IgG and IgM classes was 82.28 and 39.24% respectively in the patient group . An increased frequency of HRA-IgM antibodies was observed in Groups I, III and IV (p less than 0.01, 0.001 and 0.025 respectively) . All the four groups demonstrated a highly significant increase in incidence of HRA--IgG class (p less than 0.0005) . Persistence of high titres of HRA-IgG class in ARF and RHD is reported in the paper. J Biochem (Tokyo), 1988 Oct, 104(4), 600 - 5 Purification and characterization of a lectin-like molecule specific for galactose/N-acetyl-galactosamine from tumoricidal macrophages; Oda S et al.; A lectin-like molecule (macrophage lectin) was purified from murine peritoneal exudate macrophages which had been induced with an antitumor streptococcal preparation, OK-432 . The purified macrophage lectin from both 3H-labeled and unlabeled macrophages after rechromatography on a beta-D-galactose-Bio-Gel P-100 column gave a broad single band corresponding to 45-60 kDa on SDS-polyacrylamide gel electrophoresis (SDS-PAGE) . The broadness of this band was due to high N-glycosylation of the lectin, because the lectin gave a compact band corresponding to 35 kDa on SDS-PAGE after deglycosylation . The lectin required Ca2+ for binding and showed an optimum pH of around 6 . The sugar specificity of the lectin was examined by means of an inhibition assay using simple sugars and neoglycoproteins . The lectin was found to be specific for D-galactose/N-acetyl-D-galactosamine, and not inhibited with D-mannose or N-acetyl-D-glucosamine at all . The lectin was detected on the surface of OK-432-elicited and thioglycolate-elicited macrophages, but it was not detected on resident macrophages . Moreover, the binding of tumor cells to macrophages was inhibited by the addition of the purified lectin to the binding mixture . These results suggest that this lectin is expressed on the surface of activated macrophages, and that it participates in the interaction between tumoricidal macrophages and tumor cells. Int J Cardiol, 1988 Oct, 21(1), 51 - 8 Immunological abnormalities in children with acute rheumatic carditis and acute post-streptococcal glomerulonephritis; Benatar A et al.; Immunological functions were investigated in 10 children with acute rheumatic fever and 11 children with acute nephritis to try and elucidate the cause of heart damage in acute rheumatic fever . Children with acute rheumatic fever and carditis showed an increase in serum IgG, IgA and antistreptococcal antibodies during the acute stage . Lymphocyte transformation responses to phytohaemagglutinin and streptococcal antigens were reduced but this was due to a serum suppressor effect . After recovering from acute rheumatic fever a lymphocytosis and an increased lymphocyte blastogenic response to streptococcal antigen were found . T-cells, T-helper cells and T-suppressor cells showed some changes in acute rheumatic fever but these were not statistically significant in our study . None of the changes in immunological responses that were seen in acute rheumatic fever were found in acute nephritis . These results support the hypothesis that an abnormal immune response to streptococcal products is involved in the development of carditis and the other phenomena observed in acute rheumatic fever. Can J Microbiol, 1988 Oct, 34(10), 1109 - 15 Analysis of antibiotic susceptibility and extrachromosomal DNA content of Ruminococcus albus and Ruminococcus flavefaciens; Champion KM et al.; Seventeen Ruminococcus albus and Ruminococcus flavefaciens strains have been screened for naturally occurring antibiotic resistance, as determined by zones of inhibition from antibiotic disks . These strains were also examined for extrachromosomal DNA content . All strains screened are resistant to low levels (10-200 micrograms/mL) of streptomycin . In contrast to the previously reported data, we have found that R . flavefaciens C-94 is now susceptible to both kanamycin and tetracycline . However, R . flavefaciens FD-1 is not susceptible to kanamycin (minimum inhibitory concentration (MIC) = 40 micrograms/mL) . Furthermore, R . albus 8 is resistant to tetracycline (MIC = 40 micrograms/mL), and erythromycin (MIC = 100 micrograms/mL) . Six freshly isolated strains showed resistance to tetracycline (35-70 micrograms/mL), and all tetracycline-resistant strains also showed resistance to minocycline . None of these Ruminococcus determinants share homology with the streptococcal tetL, tetM, or tetN determinants . All 17 strains were screened for extrachromosomal DNA content . Nine different techniques for the detection and isolation of extrachromosomal DNA were tested . However, owing to difficulties in demonstrating or isolating plasmid DNA, it has not been possible to determine if these antibiotic resistance genes are plasmid borne . Evidence is presented to suggest that the presence of oxygen may affect the quality of the DNA obtained from Ruminococcus. J Oral Maxillofac Surg, 1988 Oct, 46(10), 857 - 61 Experimental endocarditis following dental extractions in rats with periodontitis; Overholser CD et al.; This study analyzed the development of bacterial endocarditis following dental extraction in rats with periodontal disease . Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars, and placing the animals on a high sucrose diet . Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hours later the maxillary first molars were extracted . The animals were killed 72 hours after the extractions . In rats with periodontal disease induced for 10 and 14 weeks, extractions resulted in an incidence of bacterial endocarditis of 24% and 50%, respectively, most of which were due to streptococcal species (two were caused by Staphylococcus {corrected} aureus) . The difference, though not statistically significant (p = 0.10, chi 2 with Yates correction), shows a trend toward increased incidence of endocarditis with increasing severity of periodontal disease . This model demonstrates that one can reliably induce bacterial endocarditis after dental extractions in rats with periodontal disease. Eur J Clin Microbiol Infect Dis, 1988 Oct, 7(5), 681 - 3 Comparative in vitro activity of the two new 4-quinolones S-25930 and S-25932 against gram-positive bacteria isolated from cancer patients; Rolston KV et al.; The in vitro activity of S-25930 and S-25932, two new quinolone antimicrobial agents, against 306 gram-positive organisms representing 12 bacterial species, was evaluated and compared with the activity of ciprofloxacin, difloxacin, enoxacin, amifloxacin and A-56620 . Both agents were active against staphylococcal species (including methicillin-resistant and coagulase-negative isolates), Bacillus spp . and group JK diphtheroids . They were less active against streptococcal species and Listeria monocytogenes . Their activity against most isolates was superior to that of amifloxacin, enoxacin and difloxacin and similar to that of ciprofloxacin and A-56620. J Antimicrob Chemother, 1988 Oct, 22(4), 549 - 56 Comparative efficacy and toxicity of roxithromycin and erythromycin ethylsuccinate in the treatment of streptococcal pharyngitis in adults; Melcher GP et al.; Roxithromycin is a novel oxime ether derivative of erythromycin . Previous studies have demonstrated similar in-vitro activity for roxithromycin and erythromycin . Roxithromycin has improved pharmacokinetic properties and may be a useful alternative agent for infections where erythromycin is indicated . We compared the efficacy and toxicity of roxithromycin and erythromycin ethylsuccinate in the treatment of streptococcal pharyngitis in adults . We also assessed compliance with treatment between the two agents . Roxithromycin and erythromycin ethylsuccinate were equally effective in resolving the symptoms and signs of pharyngitis . Erythromycin ethylsuccinate was superior to roxithromycin in achieving microbiological cure (90% vs . 33%, respectively) . No differences were observed in toxicity or compliance with treatment between the two agents . Based on this prespective clinical trial, roxithromycin is not considered to be an acceptable alternative agent for acute streptococcal pharyngitis in adults. Pediatr Infect Dis J, 1988 Oct, 7(10), 683 - 6 Prognosis of children with poststreptococcal reactive arthritis; De Cunto CL et al.; Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia . We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients . During the initial episode all had arthritis or arthralgia and a documented streptococcal infection . None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months) . One patient developed classic ARF with valvulitis 18 months after the initial episode . Two children had later episodes of arthritis and two had at least one additional episode of arthralgia . Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered. J Exp Med, 1988 Oct 1, 168(4), 1403 - 17 Bacterial cell wall-induced immunosuppression . Role of transforming growth factor beta; Wahl SM et al.; Group A streptococcal cell wall (SCW)-injected rats exhibit a profound immunosuppression that persists for months after the initial intraperitoneal injection of SCW . The goal of this study was to determine the mechanisms for the suppressed T lymphocyte proliferative responses in this experimental model of chronic inflammation . When spleen cell preparations were depleted of adherent cells, restoration of T cell proliferative responses to Con A and PHA occurred, implicating adherent macrophages in the regulation of immunosuppression . Furthermore, macrophages from SCW-treated animals, when cocultured with normal spleen cells in the presence of Con A or PHA, effectively inhibited the proliferative response . Supernatants from suppressed spleen cell cultures were found to inhibit normal T cell mitogenesis . Taken together, these results implicated a soluble macrophage-derived suppressor factor in the down regulation of T cell proliferation after exposure to SCW in vivo . Subsequent in vitro studies to identify this suppressor molecule(s) revealed the activity to be indistinguishable from the polypeptide transforming growth factor beta (TGF-beta) . Furthermore, TGF-beta was identified by immunolocalization within the spleens of SCW-injected animals . The cells within the spleen that stained positively for TGF-beta were phagocytic cells that had ingested, and were presumably activated by, the SCW . These studies document that TGF-beta, previously shown to be a potent immunosuppressive agent in vitro, also effectively inhibits immune function in chronic inflammatory lesions in vivo. Fam Pract, 1988 Sep, 5(3), 200 - 8 Management of streptococcal pharyngitis: the conundrum of acute rheumatic fever; Hutten-Czapski P; The incidence of acute rheumatic fever in the residents of three counties in Ontario (population 507,300) from 1975 to 1986 inclusive was 0.17 hospitalized cases per 100,000 population (0.4 per 100,000 for 5- to 19-year-olds) . Indigent patients (0.6 per 100,000) and North American Indians (2 per 100,000) had substantially higher rates . This experience is in marked contrast to recent outbreaks of acute rheumatic fever in areas of the United States, but is similar to experience in the United Kingdom . The implications of this data on the current management of the streptococcal sore throat is reviewed, showing the complexities of real-life prevention of acute rheumatic fever. J Clin Oncol, 1988 Sep, 6(9), 1440 - 9 Acute immunologic effects of interleukin-2 therapy in cancer patients: decreased delayed type hypersensitivity response and decreased proliferative response to soluble antigens; Wiebke EA et al.; We prospectively evaluated responses to recall antigen in ten cancer patients undergoing immunotherapy and correlated these responses with in vitro proliferation data . Before therapy, eight of ten patients responded normally to at least two of seven antigens of a multitest system (greater than or equal to 2 mm induration at 48 hours), with a mean induration score of 17.9 +/- 4.4 mm and 2.7 +/- 0.5 positive responses per patient . This decreased to 5.9 +/- 2.7 mm (P = .01) and 1.2 +/- 0.5 responses (P = .03) after a week of interleukin-2 (IL-2) therapy, and further to 0.7 +/- 0.7 mm and 0.1 +/- 0.1 positive responses during a second week of therapy consisting of IL-2 plus activated autologous lymphocytes (P less than .01) . The in vitro proliferation indices for lymphocytes obtained before skin test application were significantly less after IL-2 compared with pretreatment for concanavalin A ({con-A} Miles Laboratory, Elkhart, IN) stimulation (3.3 +/- 0.7 to 1.3 +/- 0.1; P = .03) and in mixed lymphocyte culture (MLC) (41.5 +/- 8.5 to 16.8 +/- 3.8; P = .02), and during the second week of therapy for in vitro IL-2 stimulation (83.3 +/- 16.8 to 42.9 +/- 12.0; P less than .01) . When skin responses were directly compared with in vitro proliferation data, a significant correlation was observed for tetanus (r = .75; P less than .01), streptococcal antigen (r = .83; P less than .01), tuberculin (r = .83; P less than .01), and candida (r = .78; P less than .01) . Thus, significant decreases in skin test responses and in vitro proliferation were demonstrated after therapy compared with pretreatment . Flow cytometry revealed marked increases in T-lymphocyte numbers after IL-2 alone (973 +/- 252 to 3,436 +/- 754 cells/mL; P less than .01) and IL-2 receptor-bearing cells (105 +/- 28 to 983 +/- 215; P less than .01), but not in numbers of B-lymphocytes or monocytes . Induced anergy to skin test antigens was seen during a period of relative and absolute T-lymphocyte expansion . We conclude that immunotherapy with high-dose IL-2 with or without activated lymphocytes results in a decreased response to recall antigens during a period in which lymphoid cells with nominal activation markers (Tac, DR) increase. Acta Neurol Scand, 1988 Sep, 78(3), 206 - 9 Chorea and lupus anticoagulant: a case report; Okseter K et al.; A 16-year-old girl was hospitalized apparently with Sydenham's chorea . Laboratory investigations failed to reveal any sign of preceding streptococcal infection . However, lupus anticoagulant was demonstrated in plasma . Complete remission followed combined therapy with corticosteroid and anticoagulant drugs . Since the treatment of chorea in systemic lupus erythematosus associated with lupus anticoagulant is completely different from that of Sydenham's chorea, the case illustrates the importance of a thorough laboratory investigation. Eur J Obstet Gynecol Reprod Biol, 1988 Sep, 29(1), 39 - 40 Fatal disseminated intravascular coagulation secondary to streptococcal cervicitis; Paraskevaides EC et al.; A case of beta haemolytic Group A streptococcal cervicitis causing disseminated intravascular coagulation, bacteraemic shock, and death in a 57 year old woman is presented. Pathol Biol (Paris), 1988 Sep, 36(7), 885 - 7 {Evaluation of a fast test for direct research on streptococcal group A from pharyngeal samples}; Fellah H et al.; Importance of streptococcal pharyngitis rapid diagnosis is increasing . 645 patients with pharyngoamygdalitis were tested . The correlation between bacteriologic culture and rapid test is 86%, the sensibility of the test is 68%, its specificity is 92%, while the predictive positive and negative values are 75% and 90% . These results show the interest of the rapid test for the diagnosis of streptococcal pharyngitis. Prostaglandins Leukot Essent Fatty Acids, 1988 Sep, 33(3), 191 - 8 The role of leukotrienes in the late hemodynamic manifestations of group B streptococcal sepsis in piglets; Goldberg RN et al.; In order to evaluate the role of leukotrienes in group B streptococcal (GBS) sepsis we studied the effect of a leukotriene receptor antagonist, FPL 57231, on the late hemodynamic changes occurring secondary to an infusion of live GBS . Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 x 10(7) org/kg/min) while systemic arterial (Psa) and pulmonary artery pressures (Ppa) were measured . To separate the effects of the lipoxygenase products of arachidonic acid from those of the cyclooxygenase by-products, animals in control and treatment groups received indomethacin, a cyclooxygenase blocking agent, 15 min after the infusion of GBS was begun . In addition to GBS and indomethacin, treatment animals received a 30 min infusion of FPL 57231 starting 120 min after the bacterial infusion was begun . All study animals responded to bacteria within 15 min with marked elevation in pulmonary artery pressure (X +/- SD) (12 +/- 3 to 49 +/- 5 mmHg; p less than .01), and a decline in PaO2 (84 +/- 9 to 49 +/- 5 mmHg; p less than .01) and cardiac output (0.29 +/- 0.04 to 0.18 +/- .07 liter/min/kg; p less than .01) . These changes were reversed by indomethacin . Subsequent values remained relatively stable until approximately 90 min when a gradual decrease in cardiac output (CO) and PaO2, and an increase in Ppa, and calculated systemic (SVR) and pulmonary (PVR) vascular resistances occurred . After the initial increase in TxB2 and 6-keto-PGF1 alpha, indomethacin treatment resulted in return of these values to baseline with no further increase throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS) Arthritis Rheum, 1988 Sep, 31(9), 1156 - 64 Suppression of streptococcal cell wall-induced arthritis by a potent protease inhibitor, bis(5-amidino-2-benzimidazolyl)methane; Geratz JD et al.; Bis(5-amidino-2-benzimidazolyl)methane, a powerful synthetic trypsin inhibitor, proved to be highly effective in suppressing the arthritis induced by streptococcal cell wall fragments in Lewis rats . It reduced not only the degree of synovitis, osteitis, and hematopoietic hyperplasia in the distal extremities, but also the degree of associated granulomatous inflammation in the liver . The results suggest that trypsin-like proteases play an important role in this arthritis model and that inhibitors may be useful in the treatment of similar arthritic conditions in humans. Infect Immun, 1988 Sep, 56(9), 2518 - 20 Nucleotide sequence of streptococcal pyrogenic exotoxin type C; Goshorn SC et al.; The nucleotide sequence of the gene speC, encoding streptococcal pyrogenic exotoxin type C (SPE C), was determined . The gene encoded a mature protein of 208 amino acids, with a calculated molecular weight of 24,354 . The mature amino acid sequence of SPE C was analyzed for homology with the amino acid sequences of streptococcal pyrogenic exotoxin type A, the staphylococcal enterotoxins, and toxic shock syndrome toxin-1 . Of these, SPE C shared the greatest amount of homology with streptococcal exotoxin type A. Diabetes, 1988 Sep, 37(9), 1188 - 94 Treatment with streptococcal preparation (OK-432) suppresses anti-islet autoimmunity and prevents diabetes in BB rats; Satoh J et al.; We have recently shown that a streptococcal preparation (OK-432) inhibits insulitis and prevents diabetes in nonobese diabetic (NOD) mice, an animal model of insulin-dependent diabetes mellitus (IDDM) . We extended this study to another model of IDDM, namely BB rats . Male and female BB rats were injected weekly with 0.2 mg OK-432 i.p . starting from 5 to 6 wk and continuing through 20 or 30 wk of age . The cumulative incidence of IDDM over 20 wk in the OK-432-treated BB rats (4 of 54, 7.4%) was significantly (P less than .01) lower than that found in the nontreated BB rats (13 of 47, 27.7%) . We examined some of these rats as follows . All of the OK-432-treated BB rats tested showed normal glucose levels before and after oral glucose administrations, as did the nontreated and nondiabetic BB rats . Histological examination of pancreatic sections revealed that the OK-432-treated rats retained a greater number of intact islets without infiltration of the mononuclear cells than did the nontreated BB rats . A preliminary in vitro study further demonstrated that the cytotoxic activities of spleen cells against a rat insulinoma cell line, RIN, were suppressed in the OK-432-treated rat . However, the treatment of BB rats with OK-432 showed no suppressive effects in the spleen cell number, the responsiveness of spleen cells to concanavalin A, the populations of OX19+, W3/25+, and OX8+ peripheral blood lymphocytes, or in the titers of cell surface antibody against RIN . These results suggest that a nonimmunosuppressive immunomodulator such as OK-432 may be useful as an agent for immunotherapy of IDDM. J Neurosurg, 1988 Sep, 69(3), 455 - 8 Infection-related spontaneous atlantoaxial dislocation in an adult . Case report; Clark WC et al.; This paper reports the third described case of infection-related atlantoaxial subluxation in an adult . Like most of the similar cases seen in the pediatric literature, this case was associated with a parapharyngeal beta-hemolytic streptococcal abscess . Based upon this experience, the authors advocate intravenous antibiotic therapy and 1) immediate reduction followed by application of a halo brace; 2) immobilization in a halo brace for at least 3 months; and 3) a C1-2 wiring and fusion procedure for patients who fail this trial of conservative therapy. Pediatrics, 1988 Sep, 82(3 Pt 2), 492 - 5 Carbamazepine: an alternative drug for the treatment of nonhereditary chorea; Roig M et al.; Five patients with a moderate to severe degree of nonhereditary chorea were successfully treated with standard anticonvulsant doses of carbamazepine . In two cases, the cause of chorea was related to a streptococcal infection . In another patient, the involuntary movements appeared seven days after severe head injury . The cause in the remaining two patients could not be determined with certainty, despite extensive laboratory investigations . Improvement began within four to 15 days after the initiation of therapy . No side effects were noticed in four patients throughout treatment (3 months to 36 months) . In one patient, the medication had to be discontinued after 17 days, because of an allergic cutaneous rash . In view of our results, we propose that carbamazepine be considered as an alternative drug for the treatment of nonhereditary chorea. J Exp Med, 1988 Sep 1, 168(3), 971 - 82 Immunogenicity of liposome-bound hyaluronate in mice . At least two different antigenic sites on hyaluronate are identified by mouse monoclonal antibodies; Fillit HM et al.; Hyaluronate (HA) was previously demonstrated to be immunogenic in rabbits . The immunogenicity of HA in mice was studied . Hyaluronidase-digested streptococcal HA (IA1) covalently linked to liposomes (IA1-liposomes) were produced for immunization . Mice immunized with IA1-liposomes developed measurable serum antibodies to IA1, while mice immunized with IA1 in Freund's adjuvant did not . mAbs produced by two stable hybridomas (10G6 and 5F11) from mice immunized with IA1-liposomes produced IgG antibody reactive with HA in ELISA . 10G6 had a much higher avidity for liposome-bound IA1 than free IA1, while 5F11 did not, suggesting that the mode of presentation of IA1 is important in HA immunogenicity and antigenicity . Both mAbs recognized terminal HA immunodeterminants exposed by hyaluronidase treatment . Sonication had no effect on HA reactivity for either mAb . However, ascorbic acid treatment significantly reduced the antigenicity of HA for mAb 5F11, but not 10G6 . Only 10G6 was inhibited by glucuronic acid . Electrostatic forces appear to play a role in the binding site of 5F11, but not 10G6 . 5F11 crossreacts with heparan sulfate and phosphorylcholine, while 10G6 did not crossreact with any glycosaminoglycans or phosphorylated compounds tested . These results confirm that HA is immunogenic . They suggest that the mode of presentation of HA is important for the induction of the immune response, and in HA antigenicity . At least two different antigenic sites on HA were demonstrated . 10G6 recognizes a terminal HA antigenic site expressed on IA1-liposomes that contains glucuronic acid in its immunodominant site . 5F11 recognizes an HA antigenic site in which electrostatic forces appear to play a role, is sensitive to ascorbic acid treatment, and is crossreactive with heparan sulfate . The use of mAbs should facilitate immunologic studies of HA. Schweiz Med Wochenschr, 1988 Aug 27, 118(34), 1202 - 8 {Infectious pneumopathies in immunodepressed patients . Value of the study of bronchoalveolar lavage fluid}; Konfino SO et al.; During a period of 16 months 26 fluid specimens obtained by broncho-alveolar lavage (BAL) in 24 immunocompromised patients were examined . This material included 13 HIV positive patients and 11 patients presenting malignant hemopathies (MH), of whom 7 had had a blood marrow transplantation . The BAL fluid was divided into two equal parts, one of which was sent to the Institute of Pathology and the other to the Laboratory of Bacteriology of Geneva University Hospital . In some cases a transbronchial biopsy was also studied . Eight out of 13 HIV positive patients presented a Pneumocystis carinii infection and one a cytomegalovirus (CMV) infection (associated with atypical mycobacteria infection) . In another case streptococcal pneumonia was observed . In 3 patients, analysis of the BAL fluid failed to yield a diagnosis . In the 11 patients with MH, 2 cases of CMV, 2 infections with Candida albicans and one with Aspergillus fumigatus were found . In 2 patients the pneumopathy was due to bacterial infection . Four BAL fluids failed to yield a diagnosis; however, in one of these transbronchial biopsy revealed interstitial pneumonia of unknown origin . On the basis of our material and comparison with clinica, radiological and serological data, it appears that BAL fluid analysis is a helpful and rapid diagnostic aid in infectious pneumopathies of immunocompromised patients . This is especially true of AIDS patients in whom the most common pulmonary complication is Pneumocystis carinii pneumonia . However, success of the analysis requires close cooperation between clinician, bacteriologist and pathologist. Vet Rec, 1988 Aug 20, 123(8), 193 - 5 Pre-chemotactic and chemotactic properties of uterine fluid from mares with experimentally induced endometritis; Pycock JF et al.; Streptococcal endometritis was induced experimentally in pony mares during oestrus . Uterine fluid was collected 30, 60, 120 or 240 minutes later and tested for its effect on the in vitro morphology and chemotaxis of equine neutrophils by two independent methods . The maximal response occurred between 30 and 60 minutes after infection and persisted until 240 minutes . The chemo-attractant contained both heat labile and heat stable components and the latter appeared to be active at low concentrations. Health Phys, 1988 Aug, 55(2), 433 - 6 Metallothionein induction: a measure of radioprotective action; Matsubara J; Mice treated to induce metallothionein (MT) synthesis in the liver prior to irradiation were resistant to radiation; this also was true of mice that had a portion of skin surgically removed or an immunomodulator administered . Mice given Mn, Cd or Zn subcutaneously prior to irradiation showed increased tolerance to an LD50 level (6-8 Gy) of x rays compared with controls that received no pretreatments (p less than 0.01) . All the mice were evaluated during a 30-d postirradiation period . Weight loss in control mice peaked two weeks after irradiation, whereas body weight in mice pretreated with Mn continued to increase after irradiation with x rays . The normal level of MT in mouse liver (25 micrograms g-1 tissue) increased to 70 micrograms g-1 liver tissue in mice irradiated with 6.3-Gy x rays . However, following subcutaneous injection of Cd, Mn or Zn, or intraperitoneal injection of OK-432 (Picibanil, a killed streptococcal preparation, obtained from Chugai Pharmaceutical Co., Ltd., Tokyo, Japan), MT levels in liver increased by a factor of 2-8 compared to irradiated that were not treated with the reagents listed above . The mortality rate of mice with a surgically excised 2 X 2-cm2 portion of dorsal skin or of those administered OK-432 was lower than that of controls, and MT levels in liver (150-400 micrograms g-1 tissue) were higher than those of irradiated mice that were not surgically treated . These results suggest that the body's protective action against radiation correlates with the biosynthesis of MT, or that MT acts as a scavenger of radiation-induced peroxides. Infect Immun, 1988 Aug, 56(8), 2101 - 8 Systemic uptake and intestinal inflammatory effects of luminal bacterial cell wall polymers in rats with acute colonic injury; Sartor RB et al.; The systemic uptake and local intestinal inflammatory potential of luminal bacterial cell wall polymers in rats with normal and acutely inflamed colons were measured . Rats were injected intracecally with either 125I-labeled group A streptococcal peptidoglycan-polysaccharide complexes or equal amounts of Na125I, after either nonspecific colonic injury with 4% acetic acid or injection with buffer . The colons of rats injected with peptidoglycan-polysaccharide had higher inflammatory scores than Na125I-injected rats, a greater incidence of mucosal ulceration and transmural inflammation after acetic acid injury, and an increased frequency of focal accumulations of inflammatory cells in the lamina propria and submucosa after buffer injection . Radioactivity in the liver, spleen, and mesenteric lymph nodes was higher in the colon-injured rats that received peptidoglycan-polysaccharide 48 h before tissue collection than in the noninjured rats (P less than 0.002) . Group A streptococcal polysaccharide antigen concentration within the liver, spleen, and mesenteric lymph nodes, measured by enzyme-linked immunosorbent assay, was significantly higher in the colon-injured rats that received cell wall polymers than in noninjured rats . These results indicate that luminal bacterial cell wall polymers with well-described inflammatory and immunoregulatory potential can cross injured colonic epithelia and are capable of initiating and potentiating intestinal inflammation. Pediatr Infect Dis J, 1988 Aug, 7(8), 581 - 7 Group A streptococcal infection in children younger than three years of age; Levin RM et al.; We evaluated 758 sick children younger than 3 years of age for Group A beta-hemolytic streptococcal (GABHS) upper respiratory infection (URI) to determine the usual clinical presentation of the disease in this age group, indications for culture and the optimal site(s) from which to isolate the organism . GABHS infection was documented in 35 subjects (4.6%) . The classic presentation (as proposed in the 1940s) of GABHS URI in children younger than 3 years of age was not confirmed by this study . In 32 of the GABHS cases there were pharyngitis, common cold symptoms or both, and these were associated with acute otitis media 10 times and with otitis media with effusion 3 times . Clinical impetigo was associated with GABHS URI (4 of 32 cases) . GABHS URI would not have been documented in 6 of 32 cases if cultures of the anterior nares had not been performed . Children between 18 and 36 months of age were more likely to have GABHS disease than were younger children . Hoarseness and vomiting occurred less frequently in children younger than 36 months with GABHS infection than in those of that age who had non-beta-hemolytic streptococcal illnesses . A history of two or more siblings at home or a family member with a recent streptococcal infection and the presence of irritability, a reddened throat or palate or uvular edema were each associated with GABHS URI . We concluded that sick children between 18 and 36 months of age with a reddened throat should have cultures taken of the throat and anterior nares for GABHS.(ABSTRACT TRUNCATED AT 250 WORDS) AIDS, 1988 Aug, 2(4), 291 - 7 Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy; Ballet JJ et al.; T-cell mediated and humoral responses directed to microbial antigens were investigated, at the time of the initial visit, in a group of 139 patients with HIV-1-related persistent generalized lymphadenopathy (PGL) enrolled in a longitudinal study . In vivo and in vitro cell-mediated responses to tuberculin were lower in patients than in controls . Differences were not significant for candidin and streptococcal antigen in vitro, whereas higher responses were observed in the patient group for cytomegalovirus antigen . Following immunization, a subgroup of patients did not have a significantly raised serum antitetanus antibody level, whereas in vitro lymphocyte proliferative responses to tetanus toxoid were lower than in controls . No association was found between these abnormalities and other immunological parameters, including the blood level of CD4+ lymphocytes . Lower responses to most microbial antigens were observed in patients with HIV-1-related symptoms in addition to lymphadenopathy, or the patients who progressed to AIDS in the 2 years following the study . Moreover, intravenous drug users showed higher r