Streptococci

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 responses than homosexual patients, possibly because of the influence of previous infections on immunological responses to microbial antigens.

J Thorac Cardiovasc Surg, 1988 Jul, 96(1), 133 - 40
Reparative approach for right-sided endocarditis . Operative considerations and results of valvuloplasty; Yee ES et al.; From 1981 to 1986, 12 patients were operated on for right-sided endocarditis after the failure of initial medical treatment (five staphylococcal, three streptococcal, two fungal, one gram-negative, and one mixed organism) . The sources of infection were intravenous drugs in six patients, central catheters in two, and malformations in four . Preoperatively, 10 of 12 (83%) of these patients were in class III or IV . Reparative or reconstructive approaches, including valvuloplasty, were attempted for all these right-sided endocarditis lesions and were hemodynamically effective in 10 of 12 (83%) patients . The low right-sided intracardiac pressures and the three-leaflet configuration (one pulmonary and nine tricuspid valves) have lent themselves to this approach . Extensive annular invasion and multileaflet infections were technical limitations in the remaining patients . The overall outcome was favorable during the mean follow-up period of 25 months (hospital mortality 1/12, 8.3%; late death 1/11, 9%) . Reparative or reconstructive approaches for right-sided infective endocarditis should be considered and can be successfully achieved . Their advantages include (1) improved hemodynamics, (2) low recurrence, and (3) favorable long-term results without staged or simultaneous prosthetic valve replacement.

Postgrad Med, 1988 Jul, 84(1), 203 - 6, 211-4
Streptococcal pharyngitis . What's new; Tanz RR et al.; Group A beta-hemolytic streptococcal pharyngitis continues to be a major problem and accounts for a large number of physician visits . The recent resurgence of acute rheumatic fever in several areas in the United States underlines the need to accurately diagnose and correctly treat streptococcal pharyngitis . Appropriate treatment with antibiotics effectively prevents rheumatic fever . Early institution of treatment also leads to prompt alleviation of symptoms . The "gold standard" for diagnosing group A streptococcal pharyngitis is the throat culture . Newer rapid diagnostic tests may be used, but the clinician must recognize that there are a substantial number of false-negative tests (low sensitivity) . Therefore, patients with negative rapid tests should have standard throat cultures as well . Patients with positive rapid tests should be treated with appropriate antibiotics, as should patients with positive throat cultures . Patients with signs and symptoms that are highly suggestive of streptococcal pharyngitis can also be treated, pending throat culture results . Penicillin continues to be the drug of choice for treatment, and American Heart Association guidelines suggest the use of oral penicillin V for ten days or intramuscular benzathine penicillin G . Alternative antibiotics commonly used include erythromycin and various cephalosporins . Throat cultures need not be obtained from most patients after therapy . However, some patients may seem to be having frequent streptococcal infections or may be recognized as asymptomatic carriers . Carriers may be considered for therapy with intramuscular benzathine penicillin G plus oral rifampin.

Am J Pathol, 1988 Jul, 132(1), 38 - 48
Hyperplastic synoviocytes from rats with streptococcal cell wall-induced arthritis exhibit a transformed phenotype that is thymic-dependent and retinoid inhibitable; Yocum DE et al.; It has been suggested that streptococcal cell wall-induced arthritis in LEW/N rats resembles a localized neoplasm consisting of, in part, a proliferative and invasive population of fibroblast-like synoviocytes . To further pursue this concept, the synoviocytes from diseased rats were characterized in situ and in vitro for various parameters of "transformation." The spindle-shaped synoviocytes were found throughout the synovium and were the predominant cell type at sites of invasion of bone and cartilage by synovium . They stained intensely for vimentin, a microfilament prominently expressed in immature and transformed mesenchymal cells . They stained variably for Ia antigens and did not exhibit T cell surface antigens nor did they stain with histochemical stains characteristic of monocytes or granulocytes . Electron microscopy confirmed their fibroblastlike morphology and suggested high grade metabolic activity . In primary culture, the abnormal synoviocytes were adherent, grew rapidly and did not contact inhibit . Moreover, they grew under anchorage-independent conditions . These abnormal growth characteristics were inhibited by all-trans retinoic acid . Finally, explants of the arthritic synovium formed short-lived tumorlike nodules in athymic nude mice . These observations, considered in the context of other data, support the concept that the pathologic process represents a thymic-dependent, nonmalignant, locally invasive inflammatory neoplasm.

Diagn Microbiol Infect Dis, 1988 Jul, 10(3), 181 - 4
Sero group C streptococcal infection in intravenous drug abusers: a report of two cases; Kramer ED et al.; Two cases of group C streptococcal bacteremia in intravenous drug abusers are described . Both patients had joint involvement and may have been immunocompromised . The literature pertinent to this organism is briefly reviewed.

Handchir Mikrochir Plast Chir, 1988 Jul, 20(4), 218 - 9
{Unusual healing of tendon sheath tuberculosis by intercurrent streptococcal phlegmon}; Pfeiffer KM; Tuberculosis of the flexor tendon sheaths in western industrial countries is rare . The author presents a case with an exceptional course and an unexpected outcome . A sixty-five year old woman suffered from tuberculosis of the flexor tendon sheath of her little finger . Appropriate tuberculostatic treatment was impossible due to damage of liver cells by chronic hepatitis . An open wound with positive cultures of mycobacterium tuberculosis persisted over eight months despite local and systemic treatment . It was only after an incidental streptococcal infection of the wound--resembling an erysipelas--that the tuberculous germs disappeared . The result was rapid healing with return of limited but useful function of the hand.

Immunology, 1988 Jul, 64(3), 391 - 5
IgD antibodies to DNP are specifically induced in ascitic fluid after intraperitoneal immunization; Steele MG et al.; The induction characteristics of IgD in serum and other body fluids are poorly understood . Here we report that Freund's complete adjuvant (FCA), when used in intraperitoneal (i.p.) immunization, resulted in significantly higher levels of IgD and specific IgD antibodies in ascitic fluid than in the serum of the same animals . This was in sharp contrast to the distribution of IgM and kappa light chain-bearing immunoglobulins (kappa Ig) between these compartments . Female rats were immunized subcutaneously (s.c.) on Day 0 with 1:1 FCA mixed with either 2,4 dinitrophenyl group A streptococcal vaccine (DNP-GASV), 2,4 dinitrophenyl ovalbumin (DNP-OVA), or saline . A week later (and weekly thereafter) they were boosted i.p . with these antigens mixed with FCA 1:9 . Eleven of sixteen rats produced some ascites by Day 21, and 15/16 by Day 28 . Total immunoglobulin and specific antibodies for the heavy-chain isotypes IgD and IgM and for kappa Ig were measured by ELISA . Between immunization groups no significant differences were observed in total immunoglobulin levels . Subcutaneous immunization with 1:1 FCA caused a significant two- to six-fold increase in serum IgD by Day 7 (P less than 0.01), while no change occurred with serum IgM or kappa Ig . Ascitic fluid collected on Day 21 had significantly high levels of IgD than that of serum IgD (P less than 0.01), with a mean level nine times that of the serum . In contrast, levels of total IgM, kappa Ig and total protein were significantly lower in ascitic fluid than in serum (all P less than 0.05) . The high levels of IgD in ascitic fluid disappeared in Day 28 ascitic fluid, while IgM and kappa Ig levels were relatively unchanged . The ratio of ascitic fluid to serum IgD anti-DNP was 9.8 for the DNP-GASV-immunized group on Day 21, and 23.9 for the DNP-OVA-immunized group on day 28 . The same ratios for IgM anti-DNP and kappa Ig anti-DNP were much lower, ranging from 0.4 to 2.3 and 0.3 to 3.3, respectively.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S356 - 9
Structure, function, and genetics of streptococcal M protein; Fischetti VA et al.; Streptococcal M protein is a coiled-coil fibrillar structure extending about 60 nm from the cell wall . From DNA sequencing of the M6 protein gene, it has been determined that the C-terminal end contains a membrane anchor and an adjacent cell wall stabilization domain, both of which are similar to C-terminal regions of surface proteins in other gram-positive organisms . Studies with monoclonal antibodies revealed that the C-terminal half of the protein is conserved among M proteins of different serotypes, whereas the N-terminal half varies . The M protein contains tandem repeats, which, through homologous recombination, are responsible for the observed size variation of the M proteins from different streptococcal strains . M protein size mutants occur in a laboratory-grown culture at a frequency of 1/2,000 colony-forming units . DNA sequence analysis of the M gene in size mutants derived from a single strain suggests that sequence changes which result from homologous recombination may play a role in the antigenic variation of M protein.

S Afr Med J, 1988 Jun 18, 73(12), 709 - 10
High-dose oral amoxycillin in the treatment of infective endocarditis; Chetty S et al.; Oral antibiotic therapy for infective endocarditis is not yet widely accepted . A study was undertaken to assess the efficacy of oral amoxycillin in this condition . Fifteen patients were treated with high-dose oral amoxycillin for 6 weeks . Twelve responded to treatment and remain well at 3 years . There were 3 deaths--1 at day 7 due to sudden aortic cusp rupture, and 2 late deaths due to pulmonary and cerebral embolism respectively . There was 1 relapse of streptococcal prosthetic valve endocarditis 8 weeks after oral treatment, but this responded to conventional intravenous therapy . Oral amoxycillin is effective in uncomplicated streptococcal endocarditis, and should not be used with prosthetic valve infections.

J Chromatogr, 1988 Jun 10, 441(2), 323 - 33
Analysis of the amino acid and sugar composition of streptococcal cell walls by gas chromatography-mass spectrometry; Gilbart J et al.; A procedure for determining the amino acid and sugar composition of streptococcal peptidoglycan-polysaccharide complexes by capillary gas chromatography-mass spectrometry (GC-MS) was established . Amino acids are analysed as butyl heptafluorobutyl derivatives and sugars as alditol acetates . These two different groups of compounds are derivatized independently but chromatography in both cases utilizes the same OV-1701 fused-silica capillary column which simplifies GC-MS analysis . The butyl heptafluorobutyl procedure incorporates new pre- and post-derivatization clean-up steps . Additionally, selected-ion monitoring MS allows amino acids to be readily analysed without interference from background noise.

Pediatr Emerg Care, 1988 Jun, 4(2), 92 - 6
Evaluation of children with fever greater than or equal to 104 degrees F in an emergency department; Marcinak JF; Two hundred five children with a temperature greater than or equal to 104 degrees F seen in a pediatric emergency department were studied over a six-month fall-winter period to determine the patterns of illness and hospitalization . Children over five years composed a large group (38%) of patients admitted . The proportions of patients with viral and bacterial illnesses (40 and 45%) were similar, as were hospitalization rates for the two types of illnesses (11 and 14%) . The hospitalization rates did not change if pneumonias were considered all bacterial or all viral . Chest x-rays were done in 103 patients, and pneumonia was diagnosed in 26 with 18 (69%) occurring in children older than 24 months . There were 10 adolescents greater than or equal to 12 years, five of whom had Group A streptococcal pharyngitis . Blood cultures were drawn in 85 patients, and bacteremia occurred in 12 patients, all younger than 24 months . This study shows that significant illnesses and a high proportion of hospitalizations occurred in children of all ages, particularly in children older than five years.

Int J Cardiol, 1988 Jun, 19(3), 384 - 6
Spontaneous splenic rupture as complication of infective endocarditis; Pringle SD et al.; A case is reported of spontaneously ruptured spleen occurring as a fatal complication of Group B streptococcal endocarditis, despite control of infection with antibiotics and early surgery.

Clin Orthop, 1988 Jun, (231), 225 - 8
Group B beta-hemolytic streptococcal osteomyelitis of the heel . A case report; Doberstein C et al.; Staphylococcus aureus is the most frequently reported, though not the only, causative organism in children who have osteomyelitis . In an 11-year-old child with osteomyelitis of the calcaneus, the etiologic agent was identified as a Group B beta-hemolytic streptococcal organism . This organism seems not to have been previously reported as the cause of osteomyelitis in the heel.

Zh Mikrobiol Epidemiol Immunobiol, 1988 Jun, (6), 76 - 80
{Effect of a streptococcal allergen on the rosette-forming capacity of the T-lymphocytes in erysipelas patients}; Tsoi IG et al.; The reaction of antigen-dependent E-rosette formation with the hemolytic streptococcal antigen in erysipelas patients is indicative of the ambiguous role of the specific immunological transformation of the body in respect of the infective agent antigens in different clinical forms of the disease and is of prognostic importance as regards the chronic transformation of the infectious process and the development of the relapses of the disease.

Jpn J Antibiot, 1988 Jun, 41(6), 673 - 85
{Clinical results of a rokitamycin dry syrup in pediatric infections}; Kawauchi K et al.; Clinical efficacies of a new macrolide antibiotic, rokitamycin (RKM, TMS-19-Q), were studied in acute pediatric infections . Responses to the RKM administration were evaluable in 62 out of 68 patients consisted of 7 patients with pharyngitis (efficacy rate of 85.7%, 6/7 patients), 4 with bronchitis (25.0%, 1/4), 9 with tonsillitis (100%, 9/9), 13 with mycoplasmal pneumonia (100%, 13/13), 13 with hemolytic streptococcal infections (92.3%, 12/13), 14 with pneumonia (57.1%, 8/14), one with pertussis (100%, 1/1) and another with Chlamydia pneumonia (100%, 1/1) thus an overall efficacy rate of 82.3% was achieved . Urticaria was observed in one of the patients as an adverse reaction to the drug, while abnormal laboratory test results were noted in 3 patients, but none of such changes were severe . The drug, even when administered in combination with a theophylline preparation, exerted no effects on the serum concentration of the latter.

Eur J Cell Biol, 1988 Jun, 46(2), 316 - 26
Peripheral actin filaments control calcium-mediated catecholamine release from streptolysin-O-permeabilized chromaffin cells; Sontag JM et al.; Adrenal medullary chromaffin cells were permeabilized by treatment with a streptococcal cytotoxin streptolysin O (SLO) which generates pores of macromolecular dimensions in the plasma membrane . SLO did not provoke spontaneous release of catecholamines or chromogranin A, a protein marker of the secretory granule, showing the integrity of the secretory vesicle membrane . However, the addition of micromolar free calcium concentration induced the corelease of noradrenaline and chromogranin A, indicating that secretory products are liberated by exocytosis . Calcium-dependent exocytosis from SLO-permeabilized cells required Mg-ATP and could not occur in the presence of other nucleotides . The pores generated by the toxin were large enough to introduce proteins, e.g., immunoglobulins, but also caused efflux of the cytosolic marker lactate dehydrogenase . Despite this, the cells remained responsive to calcium for up to 30 min after permeabilization, indicating that they retained their secretory machinery . In the search for a functional role of cytoskeletal proteins in the secretory process, we used SLO-permeabilized cells to examine the localization of filamentous actin, using rhodamine-phalloidin, and that of the actin-severing protein, gelsolin, using specific antibodies . It was found that both F-actin and gelsolin were exclusively localized in the subplasmalemmal region of the cell . We examined the relationship between actin disassembly, the elevation of intracellular calcium and secretion in SLO-treated cells . F-Actin destabilizing agents such as cytochalasin D or DNase I were found to potentiate calcium-stimulated release . The maximal effect was observed at low calcium concentrations (1-4 microM) and at the later stages of the secretory response (after 10 min stimulation) . In addition, using rhodamine-phalloidin, we observed that calcium provoked simultaneously both cortical actin disassembly and catecholamine release in SLO-permeabilized cells . These results demonstrate that a close relationship exists between the secretory response and actin disassembly and provide further evidence that intracellular calcium controls the subplasmalemmal cytoskeletal actin organization and thereby the access of secretory granules to exocytotic sites.

Nucleic Acids Res, 1988 May 25, 16(10), 4667 - 77
Comparison of the leader sequences of four group A streptococcal M protein genes; Haanes-Fritz E et al.; The 5' portions and flanking sequences of genes encoding types 1, 12, 24, and 6 M proteins were compared . Although the DNA sequences encoding the amino-termini of the mature M proteins had no obvious similarity, upstream sequences, and those encoding the signal peptides (leader sequences) of the four M protein genes had considerable similarity . In general, the 5' ends of all the leader sequences were more conserved than the 3' ends, although the M6 and M24 leader sequences had identical 3' ends . Sequence similarity among the deduced amino acid sequences of the four signal peptides was more extensive than the corresponding DNA sequences . We found that strict DNA similarity among all four sequences extended only to the ends of the hydrophilic amino-terminal regions of the signal peptides, but that amino acid sequence conservation continued to the ends of the respective hydrophobic cores . With the exception of the M6 and M24 sequences, the regions adjacent to the signal peptidase cleavage sites were highly variable.

Zh Mikrobiol Epidemiol Immunobiol, 1988 May, (5), 72 - 7
{Capacity of mononuclear cells to produce a factor that promotes E-rosette formation in different clinical forms of erysipelas}; Tsoi IG; The author has examined the capacity of mononuclear cells in peripheral blood samples obtained from erysipelas patients for the in vitro secretion of E-rosette formation promoting factor (E-RPF) in response to polyclonal stimulation with phytohemagglutinin (PHA) P or antigenic stimulation with hemolytic streptococcal allergen . At the acute stage of the disease, mononuclear cells spontaneously secreted E-RPF in a half of the examined patients; at the same time, a statistically significant decrease in the PHA-induced secretion of E-RPF was observed, especially in patients with the primary bullous form and relapses of erysipelas . The optimum lymphokine production in response to PHA in patients with primary erysipelas was observed simultaneously with a low level of spontaneous lymphokine production, while in relapses it was significantly suppressed at all levels of the spontaneous secretion of E-RPF . The antigen-stimulated secretion of E-RPF was observed more frequently in patients with primary bullous erysipelas, while in bullous relapses it was completely absent . At the early stage of convalescence the intensity of the spontaneous secretion of E-RPF decreased, while the PHA-induced secretion of E-RPF enhanced . In relapses the secretion of E-RPF in response to stimulation with the specific allergen remained at a low level, while in convalescents having had primary erysipelas the level of this secretion was high . These data indicate that mononuclear cells in the peripheral blood essentially differ in their capacity to secrete E-RPF in response to polyclonal and antigenic stimulation in various clinical forms of erysipelas.

Arch Dis Child, 1988 May, 63(5), 536 - 40
Quantitative bacterial flora of acute appendicitis; Roberts JP; A quantitative bacteriological study of the appendix wall of 43 children admitted to this unit showed no significant differences between the flora of the histologically normal and acutely inflamed appendices . Bacteroides species, Escherichia coli, and streptococcal species were the commonest organisms isolated and were found in counts of 10(3) to 10(8) organisms per gram of tissue . Bacteroides species were most commonly the dominant flora in both normal and inflamed appendices . The lack of increased counts of organisms in acute inflammation of the appendix suggests an unfavourable environment to bacterial proliferation making primary bacterial infection an unlikely aetiological factor in the pathogenesis of appendicitis.

J Immunol, 1988 May 1, 140(9), 2964 - 9
Exacerbation of arthritis by IL-1 in rat joints previously injured by peptidoglycan-polysaccharide; Stimpson SA et al.; The arthropathic activity of mouse recombinant IL-1 (mrIL-1) after intraarticular (i.a.) injection into rat ankles was investigated . Nanogram quantities of either mrIL-1 alpha or mrIL-1 beta induced an acute transient arthritis . Arthritis induced by i.a . mrIL-1 developed more rapidly and was more severe in ankles previously injured by i.a . injection of group A streptococcal peptidoglycan-polysaccharide (PG-APS) fragments . In addition, a protracted pain response, as judged by severe limping, occurred 60 to 90 min after mrIL-1 injection into joints previously injured by PG-APS or 4 to 6 h after mrIL-1 injection into naive joints . The severity of arthritis was related to the mrIL-1 dose . Arthropathic activity of mrIL-1 alpha was neutralized by goat anti-mouse IL-1 alpha IgG, and the activity of both the alpha and beta preparations was heat labile . Repeated episodes of acute inflammation were induced by repeated i.a . injection of mrIL-1 . In naive ankles this led to chronic synovitis without histologic evidence of erosions . However, in joints previously injured by PG-APS, repeated mrIL-1 injection induced a more severe chronic synovitis with a 50% incidence of early pannus formation and limited marginal erosions of cartilage and subchondral bone . Thus, mrIL-1 induces an acute exacerbation of arthritis in joints previously injured by PG-APS and repeated exposure of these joints to mrIL-1 promotes chronic erosive synovitis . These studies provide evidence for an in vivo function of IL-1 and are consistent with its role as one of the mediators in the local regulation of inflammation in recurrences of arthritis induced by bacterial cell wall polymers.

Arch Pathol Lab Med, 1988 May, 112(5), 545 - 9
Immunohistochemical studies on local antitumor effects of streptococcal immunopotentiator, OK-432, in human solid malignant tumors; Sugenoya A et al.; Immunocytochemical techniques were used to clarify the local inhibitory effects of a streptococcal immunopotentiator, OK-432, against solid malignant tumor growth . Natural killer (NK) cells and fibronectin were chosen as immunostaining markers to demonstrate the antitumor effects . Immunocytochemical staining was performed by the avidin-biotin-peroxidase complex method . These investigations demonstrated that (1) local administration of OK-432 seems to promote a marked induction of NK cells and fibroblasts around or entering into the cancerous lesions and (2) the cancer cell-killing effect of NK cells and the fibronectin-enriched stromal reaction augmented by the injection of OK-432 suggest at least the possibility of protection against neoplastic growth with invasion and the spread of distant or nodal metastases of solid carcinomas.

Ann Otol Rhinol Laryngol, 1988 May-Jun, 97(3 Pt 1), 243 - 6
Comparison of the microbiology of group A and non-group A streptococcal tonsillitis; Brook I et al.; We studied the microbial flora of tonsils removed from 20 children who suffered from recurrent group A beta-hemolytic streptococcal (GABHS) tonsillitis and 20 who had tonsillar hypertrophy following recurrent non-GABHS tonsillitis . Similar polymicrobial aerobic and anaerobic flora were recovered from the cores of the tonsils in each group . beta-Lactamase-producing bacteria (BLPB) were recovered more often in the group with GABHS . This difference was due mostly to the lower incidence of beta-lactamase-producing strains of Branhamella catarrhalis and Bacteroides sp in hypertrophic tonsils following non-GABHS tonsillitis . beta-Lactamase-producing Staphylococcus aureus was found with equal frequency in both groups . These findings demonstrate that although BLPB are recovered more often in recurrently inflamed tonsils following GABHS infection, BLPB also can be found in hypertrophic tonsils following non-GABHS tonsillitis.

Tohoku J Exp Med, 1988 May, 155(1), 11 - 21
Significance of activation of reticuloendothelial function after hepatectomy in cirrhotic rats; Nakagawa K et al.; Effect of hepatectomy on the prognosis of cirrhotic rats prepared by oral administration of thioacetamide was studied from the standpoint of the reticuloendothelial function and energy metabolism of the liver . OK-432, a streptococcal preparation, was used to activate reticuloendothelial functions . Administration of OK-432 to cirrhotic rats prior to 70% hepatectomy significantly prevented the elevation of serum GOT, GPT and LDH, the prolongation of blood coagulation and the decrease of serum complement level . Hepatic ATP synthesis and RNA content were significantly increase by the use of OK-432 . These findings suggest that activation of reticuloendothelial functions at the time of massive hepatectomy in cirrhotic rats may diminish hepatic injury, maintain serum complement level, and improve protein synthesis of the liver.

J Biol Chem, 1988 Apr 15, 263(11), 5075 - 82
Complete amino acid sequence of streptococcal PepM49 protein, a nephritis-associated serotype . Conserved conformational design among sequentially distinct M protein serotypes; Khandke KM et al.; The complete amino acid sequence of PepM49, a peptic fragment of the group A streptococcal type 49 M protein, the antiphagocytic cell surface molecule of the bacteria, is described . This fragment retains the opsonic antibody epitope of the native molecule . The sequence of PepM49, as determined by automated Edman degradations of the uncleaved molecule, and its tryptic and chymotryptic peptides, consists of a total of 143 residues (Mr = 17,187) . PepM49, a nephritis-associated M protein serotype, exhibits significant internal homology in its sequence . However, identical sequence repeats of the kind seen in the rheumatic fever-associated serotypes M5, M6, and M24, are absent in PepM49 . PepM49 exhibits varying degrees of homology with the M5, M6, and M24 proteins, which is consistent with the existence of variable and conserved regions in the M protein molecule . Predictive analysis as well as CD measurements revealed a high propensity of the PepM49 molecule to assume an alpha-helical conformation . Furthermore, a heptad periodicity of the nonpolar residues, a characteristic of alpha-helical coiled-coil proteins, extends over the entire length of the PepM49 protein . The differences in the nonpolar residue distribution divide the PepM49 sequence into three distinct domains, similar to those seen earlier in the M5 and M6 proteins . Together, these studies establish a conserved conformational design for the sequentially diverse M protein serotypes . However, the pattern of heptad periodicity in the PepM49 protein is quite distinct from that present in the PepM5 and M6 proteins, suggesting distinct differences in structural features among conformationally similar M protein serotypes . This may have relevance to the pathological differences associated with these M protein serotypes.

Acta Chir Scand, 1988 Apr, 154(4), 323 - 4
Acute spontaneous streptococcal myositis . Case report; Jansen JE et al.; Streptococcal myositis of the acute spontaneous type is extremely rare . To the best of our knowledge, this report describes the first case in which a patient has survived, and reviews the differential diagnosis . The treatment is primarily surgical.

Pediatr Infect Dis J, 1988 Apr, 7(4), 262 - 6
Epidemic patterns of infectious diseases from the results of the surveillance of infectious diseases in Japan; Nakamura Y et al.; Epidemic patterns of 12 infectious diseases based on the data derived from the surveillance system of infectious diseases in Japan are analyzed . Weekly numbers of patients per one monitor station (general clinics and hospitals) are calculated by prefecture . Based on these data, the patterns of epidemic are classified into five categories: Category 1, nationwide outbreak of short duration (rotavirus enteritis, hand-foot-mouth disease and herpangina); Category 2, nationwide outbreak of long duration (varicella); Category 3, concurrent outbreaks in several districts (rubella and erythema infectiosum); Category 4, epidemic of long duration in several prefectures at different times (measles, mumps, pertussis, streptococcal infection and atypical pneumonia); Category 5, unclear epidemic pattern (exanthema subitum).

J Biol Response Mod, 1988 Apr, 7(2), 212 - 28
Monoclonal antibody to the streptococcal preparation OK-432: tissue OK-432 localization and analysis of interaction between OK-432 and macrophages or NK cells in human salivary adenocarcinoma-bearing nude mice given OK-432; Sato M et al.; An immunoglobulin M mouse monoclonal antibody (MAb) to the streptococcal preparation OK-432, TS-1, was generated . The TS-1 antigen is a carbohydrate epitope . This antigen is stable upon fixation and embedding in paraffin . The tissue and cellular OK-432 localization in human salivary adenocarcinoma-bearing nude mice given OK-432 intratumorally was examined by various methods according to the immunological procedures using the purified TS-1 MAb . The presence of OK-432 antigen recognized by TS-1 MAb was clearly observed in the tumor as well as the spleen and lung 24 or 48 h after OK-432 administration, whereas transfer of OK-432 from the site of injection to the organs, such as liver and kidney, was rarely seen . The presence of OK-432 antigen in some immunocompetent cells, as defined by Mac-1 antigen or asialo GM1 antigen, was observed by the double-antibody labeling technique in the tumor and spleen from tumor-bearing nude mice . Moreover, interaction between OK-432 and macrophages or natural killer (NK) cells in relation to expression of interferon (IFN) in tumor-bearing nude mice given OK-432 was observed . Consequently, significant increases of Ia-positive or Ia-negative macrophages, NK cells as well as IFN-alpha/beta- or IFN-gamma-positive cells in the tumor and/or spleen were found when compared with those without OK-432 administration.

Gan To Kagaku Ryoho, 1988 Apr, 15(4 Pt 2-1), 755 - 62
{Immunotherapy of gastric cancer}; Kan N et al.; Two immunotherapeutic methods were developed as adjuvant therapy for gastrointestinal malignancies, one using oral administration of a streptococcal preparation, OK-432, and the other with adoptive immunotherapy (AIT), local transfer of IL2-cultured and autologous lymphocytes, combined with local preadministration of OK-432 . Tsuchitani and Nio in our laboratory have revealed experimentally that oral OK-432 stimulates tumor-specific and non-specific immune mechanisms of gut-associated lymphoid tissues and inhibits the growth of some murine syngeneic tumors that were transplanted into cecal patches . The clinical efficacy of oral OK-432 on gastric cancer patients has been examined by a controlled randomized trial involving a total of about 1000 cases . Oral OK-432 (5KE, once a week) was revealed to be significantly effective in curatively resected group but not effective in non-curatively resected group . Ten consecutive patients with peritoneal dissemination of gastric cancer were treated with intraperitoneal OK-432 and AIT . AIT was performed by transferring autologous lymph node-lymphocytes cultured for 13 days with crude IL2 and tumor-extract . The survival of the treated patients was significantly longer (50% survival period exceeded 1 year) than that of historical control (95 cases, 50% survival period was 5 months) . These immunotherapeutic methods are expected to be useful for multidisciplinary therapy of gastric cancer by a combination of each method with other therapeutic methods.

Semin Hematol, 1988 Apr, 25(2), 140 - 58
Clinical uses of intravenous immunoglobulins; Berkman SA et al.; Immunoglobulins are an important component of host defense against infections . They also play a central role in immune regulation . A wide spectrum of human diseases is associated with decreased or abnormal regulation of immunoglobulin levels . Recently IV preparations of immunoglobulin have become available for clinical studies . There are already substantial data indicating a useful role for IV immunoglobulin in patients with primary hypogammaglobulinemia, neonates predisposed to group B streptococcal infections, individuals with ITP, children with Kawasaki disease, and bone marrow transplant patients predisposed to CMV infections . Promising data have been reported in burn patients and in individuals with CLL; these data require confirmation . Potential areas for future investigation include AIDS, autoimmune disorders, and viral disorders other than CMV.

Pediatr Res, 1988 Apr, 23(4), 352 - 6
Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel; Truog WE et al.; Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel . In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 X 10(8) GBS/kg/h in ten 2- to 3-wk-old piglets . The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching . Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, were assayed in arterial blood . Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 +/- 2 to 34 +/- 4 torr (p less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01) . Arterial hypoxemia developed (p less than 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt . Thromboxane B2 levels increased 10-fold . Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables . In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance . However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred . Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion . Thromboxane B2 levels were decreased 30 min after dazmegrel (p less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)

J Mol Recognit, 1988 Apr, 1(2), 69 - 74
Analysis and use of the serum albumin binding domains of streptococcal protein G; Nygren PA et al.; Streptococcal protein G is an IgG-binding receptor with a molecular weight of 63 kDa as predicted from the sequence of the corresponding gene . Here we show that a truncated recombinant protein of 23 kDa still has IgG-binding capacity and also interacts specifically with human serum albumin (HSA) . This demonstrates that protein G is a bifunctional receptor . To investigate the structures needed for IgG- and albumin-binding, different parts of the receptor molecule were produced in E . coli using a coupled expression/secretion system . Affinity chromatography, using IgG or HSA immobilized on Sepharose, showed that the two binding activities are structurally separated . From these experiments, it was concluded that a region of 64 amino acid residues is sufficient for albumin-binding . The structure of this part of the protein suggests either a divalent or a trivalent binding capacity . The specific interaction to albumin was used to purify a heterologous protein by affinity chromatography to yield a pure fusion protein in a one-step procedure . The implication of this novel affinity system as a tool to facilitate protein immobilization and purification is discussed.

Jpn J Exp Med, 1988 Apr, 58(2), 109 - 14
Adoptive immunotherapy in tumor-bearing mice with OK-432-induced killer cells; Ujiie T; Murine spleen cells cultured for 3 or more days in medium with streptococcal preparation OK-432 became cytotoxic in vitro against several allogeneic and syngeneic tumor cells . These cytotoxic cells were designated OK-432-induced killer (OIK) cells . This study examined the in vivo antitumor efficacy of OIK cells in adoptive immuno- and immunochemo-therapy in mice bearing syngeneic tumors, such as EL-4 lymphoma, Meth-A fibrosarcoma, and MOPC-31C plasmacytoma . OIK cells neutralized these tumor cells, as shown by Winn-type tests, and the cell transfer prolonged the survival of mice inoculated intraperitoneally (ip) with EL-4 or Meth-A cells . Concomitant administration of OK-432 plus recombinant interleukin 2 (rIL-2) significantly improved the therapeutic efficacy of the transferred OIK cells . In mice inoculated with 1 x 10(4) EL-4 cells, chemoimmunotherapy consisting of ip administration of 200 mg/kg cyclophosphamide on day 3 followed by treatment with OIK cell (1 x 10(7)) transfer and with OK-432 (50 KE/kg) plus rIL-2 (50 units/mouse) 6 hr later and on day 6, prolonged the survival . Therefore, the immunotherapy with OIK-cell transfer followed by administration of OK-432 and rIL-2 may be clinically useful as an adjunct of cytoreductive chemotherapy for cancer.

Pediatr Nephrol, 1988 Apr, 2(2), 219 - 23
Complement profiles in acute post-streptococcal glomerulonephritis; Wyatt RJ et al.; It is well known that the hypocomplementemia of acute post-streptococcal glomerulonephritis (APSGN) is characterized by markedly reduced serum concentrations of C3 and moderately reduced levels of C5 and properdin (P) . However, the extent of the activation of the classical pathway is not well defined and only limited data are available concerning serum concentrations of terminal components other than C5 . In serial serum specimens from 14 children with APSGN, the presence and extent of C4 activation was directly assessed by measurement by rocket immunoelectrophoresis for C4 and C4 (C4d/C4 ratio) . Elevated values for this ratio, indicating C4 activation, were found in 8 of 14 of the initial serum specimens, and in some patients the ratio remained elevated for several weeks . In contrast, the serum C4 level was low in only 1 specimen (the specimen with the highest C4d/C4 ratio) . However, in 10 patients C4 concentrations within the normal range rose in serial serum specimens . Serum C2 concentrations were depressed in the initial specimens from 5 patients . The concentrations of 13 other complement component and control proteins were also measured in these specimens . Levels of terminal components, other than C5, in the initial serum specimens were normal except for depressed C8 in 3 of 13 patients and depressed C6 in 1 of 14 . Of these 4 individuals, 3 had the lowest C3 levels in the study . It is concluded that the classical complement pathway is frequently activated in patients with APSGN early in the condition and that subtle abnormalities in C6 and C8 levels occasionally occur.

Am J Infect Control, 1988 Apr, 16(2), 60 - 5
Use of a clinical decision rule to diagnose streptococcal pharyngitis in hospital employees; DeNeef P; Some people with pharyngitis have clinical findings that are suggestive of either streptococcal or nonstreptococcal disease . In this study the published results of the accuracy of a clinical decision rule are used to calculate the probable outcomes of withholding antibiotics from some hospital employees or giving others treatment presumptively without testing for group A streptococcal disease . Cost-benefit analysis shows explicitly how selective testing results in a trade-off among costs, the number of people given treatment unnecessarily, and the number with untreated disease that may spread within the hospital . The best strategy depends on judgment, taking into account the nature of the employee's patient contact, the needs of the hospital, and the resources for infection control.

J Biol Chem, 1988 Mar 25, 263(9), 4323 - 7
Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G; Eliasson M et al.; Chimeric Fc receptors, consisting of the IgG-binding domains of both staphylococcal protein A and streptococcal protein G, were constructed . An efficient bacterial expression system was used to produce the recombinant proteins, which vary in size and number of IgG-binding domains . The purified receptors were analyzed by immunodiffusion and a competitive enzyme-linked immunosorbent assay to establish the relative binding strength to various polyclonal and monoclonal immunoglobulins from different species . The results demonstrate that protein A and protein G have complementary binding patterns and that the chimeric receptors retain the binding capacities of both the parental constituents . This suggests that these novel chimeric receptors might be versatile reagents for immunochemical assays.

Vet Rec, 1988 Mar 19, 122(12), 271 - 4
An investigation of mastitis due to S agalactiae, S uberis and M smegmatis in a dairy herd; Thomson JR et al.; Subclinical mastitis caused by streptococcal infections affected 27 of 83 cows in a commercial dairy herd . Between three and six weeks after intramammary treatment of these cows with cloxacillin, 16 (59 per cent) of the treated cows developed acute clinical mastitis associated with Mycobacterium smegmatis . None of the untreated cows was affected . Infected quarters were moderately hypertrophied and fine clots were present in the milk for three to four weeks . No cows showed systemic signs of illness . Studies carried out over 12 months showed that infected cows shed M smegmatis for three to four months and affected quarters remained hypertrophied in all but one cow after 12 months . The mean milk cell count of affected quarters fell slowly from 4,850,000/ml in the acute stage to 810,000/ml five months later and 620,000/ml 12 months later, suggesting that the organism persisted in the udder . The estimated mean loss in lactation yield for cows with M smegmatis mastitis was 10.8 per cent . Losses were greatest when the hind quarters were involved (mean 28 per cent for cows with both hind quarters affected) . Ten of the 16 affected cows were ultimately culled owing to serious reductions in yield.

J Immunol, 1988 Mar 15, 140(6), 2008 - 15
Nutritionally variant streptococcal serotype I antigen . Characterization as a lipid-substituted poly(ribitol phosphate); George M et al.; Initial characterization of the nutritionally variant streptococcal serotype I amphipathic polymer indicated an estimated m.w . of 360,000 for the aggregated form of the molecule, whereas the dissociated form had an estimated m.w . of 38,000 based on dextran m.w . standards . In addition, SDS-PAGE indicated an amphiphile with a stepladder appearance made up of several components with m.w . larger than the major electrophoresis components of LPS or lipoteichoic acid . Chemically, the serotype I amphiphile appeared to be a lipid-substituted poly(ribitol phosphate) with galactose and alanine substitution on the ribitol phosphate backbone . This report represents the first characterization of a bacterial amphiphile with a chemical composition and structure as proposed here . As is the case with other bacterial amphiphiles, the nutritionally variant streptococcal serotype I amphiphile was found both intra- and extracellularly . Finally, immunofluorescence studies demonstrated that the amphiphile was expressed on the cell surface.

Med Hypotheses, 1988 Mar, 25(3), 141 - 5
Acute local inflammation causing generalized increased ground substance viscosity: guttate psoriasis, Reiter's syndrome, adjuvant disease, cancer regression; Stone OJ; It is known that at sites of acute inflammation there is increased ground substance formation and fibroblast proliferation . There is also increased serum glycoprotein following localized acute inflammation . The author proposes that a severe acute inflammatory response in a localized area of the body induces a generalized increase in ground substance viscosity (generalized ground substance adaptive phenomenon) . This would increase host resistance to invasion and heighten the inflammatory response . There are multiple clinical and experimental facts which could be explained by this response . These include guttate psoriasis, pustular psoriasis, pustular bacterid of Andrew's, Reiter's syndrome, and others . This response would include some aspects of adjuvant disease . Increased generalized ground substance viscosity could also explain the beneficial effects of streptococcal cell fractions and streptococcal infections on tumor regression . A number of other clinical observations could be explained . Connective tissue-activating peptide released at the inflammation site could be having a systemic effect . It could be generally beneficial to have generalized increased ground substance viscosity when acute inflammation is occurring in a localized area . A few patients who already have a highly reactive inflammatory level could develop excess inflammation especially at sites of trauma, or preexisting inflammation.

J Clin Periodontol, 1988 Mar, 15(3), 193 - 9
The antibacterial effect of toothpastes on the salivary flora; Moran J et al.; Both past and presently available toothpastes contain potential antimicrobial agents which could have a beneficial effect in the prevention of plaque and gingivitis . If these preparations were to be effective clinically, some effect on salivary bacteria would also be expected . This cross-over study measured salivary bacterial counts and the presence or absence of residual antibacterial activity in saliva following tooth brushing with 7 commercially available toothpastes, and moreover, compared their effect with that produced by a chlorhexidine gel . Generally, all toothpaste products produced a reduction in aerobic, anaerobic and streptococcal counts with a hexetidine containing toothpaste producing the largest and longest lasting reduction . In contrast, an enzyme containing toothpaste and an amine fluoride toothpaste, had little effect on bacterial counts . The chlorhexidine gel produced the largest reduction in salivary counts, which was evident for at least 5 h following brushing . Residual antibacterial activity in saliva was only evident immediately following brushing with the hexetidine toothpaste, but for the chlorhexidine gel, was present up to 90 min following brushing . The findings of this study have illustrated the limited antibacterial activity of presently available toothpastes on the salivary flora compared to chlorhexidine, and as such, would tend to question the relative benefit of toothpaste in preventing periodontal disease through an antimicrobial effect.

J Immunol, 1988 Feb 15, 140(4), 1212 - 7
Sequences of the VH and VL regions of murine monoclonal antibodies against 3-fucosyllactosamine; Kimura H et al.; Many mAb that bind the carbohydrate antigenic determinant 3-fucosyl-lactosamine (3-FL), Gal beta 1-4{Fuc alpha-3}GlcNAc-R have been raised in BALB/c mice, and we are studying the structure and regulation of these antibodies . In this report, we present the first information about their amino acid sequences and the Ig gene segments used to encode them . V regions of the H and L chains of three anti-3-FL antibodies, PMN6, PMN29, and PM81, were sequenced by a combination of mRNA and amino acid sequencing . The L chain sequences of PMN6 and PM81 antibodies indicate that their VK and JK regions are encoded by VK24B and JK1 germ-line genes, respectively . The nucleotide and amino acid sequences of the H chains suggest that the three anti-3-FL antibodies are encoded by the VH441 gene segment of the X24 VH family, and this conclusion was supported by Southern filter hybridization with VH441 and JH3-JH4 probes . PMN29 has at least 11 amino acid substitutions, which is an unusually large amount of somatic mutation for an IgM antibody . Previous analyses of BALB/c genomic libraries with VHX24 and VH441 probes make it unlikely that this VH family contains additional germ-line genes, but this possibility cannot be excluded . All three antibodies use the DQ52 and JH4 gene segments . The single VH and VL gene segments used to encode the anti-3-FL antibodies is in contrast to the multiple VH and VL segments used by antibodies against other carbohydrate Ag such as alpha 1-6 dextran and group A streptococcal carbohydrate . VH441 also encodes the VH regions of antibodies against galactan and levan (beta 2-6 fructosan) . The similarities among VH segments of antibodies against 3-FL, levan, and galactan, and the striking differences in their CDR3 sequences, suggest that CDR3 plays an important role in the formation of the Ag binding site . The use of a single VH segment from the smallest VH gene family by antibodies against at least three different carbohydrate determinants is noteworthy . It raises the possibility that the amino acid sequence encoded by VH441 has some general structural features that make it particularly well adapted for binding to carbohydrate sequences.

N Engl J Med, 1988 Feb 4, 318(5), 280 - 6
Penicillin and the marked decrease in morbidity and mortality from rheumatic fever in the United States; Massell BF et al.; There has been a marked decline in mortality due to rheumatic fever in the United States . We present evidence for the important role of penicillin in changing the severity of rheumatic carditis, beginning about 1946 . Since that year, mortality due to rheumatic carditis has rapidly decreased to zero at the hospital we studied (House of the Good Samaritan, Boston), the rate of loss of all murmurs in patients at the study hospital accelerated simultaneously and exceeded 40 percent by 1970, and the rates of decline in national mortality due to rheumatic carditis accelerated fourfold with the advent of antibiotics . These data, together with reports of recent outbreaks of rheumatic fever, emphasize the importance of continued efforts to diagnose and treat Group A streptococcal pharyngitis.

Immunobiology, 1988 Feb, 176(3), 272 - 89
B cell growth factor (BCGF) secreting human T cell clones reactive to a soluble glycoprotein antigen, streptococcal antigen (SA); Sia DY; A panel of human T cell clones bearing exclusively the helper (T4) phenotype and showing reactivities to a soluble glycoprotein antigen (185,000 dalton Mol . Wt . Streptococcal antigen, SA) is described . Two of these clones namely, SA 1.53 and SA 1.82, are found to co-produce B cell growth factor (BCGF) and interferon-gamma (IFN-gamma) in the absence of interleukin 2 (IL2) upon stimulation with phytohaemagglutinin (PHA) or the specific antigen in the presence of irradiated autologous antigen-presenting cells (APC) . Secretion of the lymphokines is genetically restricted in part by DR molecules that are expressed on the cloned cells and APC . Produced BCGF is differentiated from the BCGF-promoting property of IFN-gamma in that only IFN-gamma activity, but not BCGF activity is removed and inhibited by anti-IFN-gamma antibodies . Exogenous IL2 induces secretion of BCGF and IFN-gamma of the cloned cells, an observation which involves interaction of IL2 with IL2 receptors . An analysis of the proliferative responses to antigen of the T cell clones shows that BCGF-producing clones, unlike those that secrete IL2, fail to proliferate significantly to specific antigen restimulation.

J Hosp Infect, 1988 Feb, 11 Suppl A, 328 - 33
Maternal screening in prevention of neonatal infections: current status and rationale for group B streptococcal screening; Boyer KM; Maternal screening--either selective or universal--is an accepted component of a number of strategies for prevention of congenital and perinatal infections . Using the results of maternal screening at prenatal visits and the presence of perinatal risk factors during labour, neonatal group B streptococcal (GBS) early-onset disease can be prevented by selective intrapartum chemoprophylaxis . Possible variations on this strategy may employ semiquantitative tests for GBS colonization at prenatal visits or, possibly, rapid bacterial diagnosis intrapartum . Based on the incidence and economic impact of GBS disease, selective intrapartum chemoprophylaxis appears cost-effective in United States populations, but may not be so in countries with lower incidence rates.

Zh Mikrobiol Epidemiol Immunobiol, 1988 Feb, (2), 67 - 71
{Experimental study of the immunostimulating properties of tomitsid}; Blinkova LP et al.; Tomicide, a preparation with antibacterial properties, accumulates in the culture medium during the growth of one of streptococcal strains . The injection of the preparation into mice simultaneously with the antigen (sheep red blood cells) produces an adjuvant effect . Tomicide has been found capable of inducing the production of interferon detected in the serum of the animals . During experimental stress created by intensive exercise tomicide prevented a decrease in the normal (anamnestic) level of antibodies, produced an immunostimulating effect and, at the same time, enhanced the total physical endurance of the animals, manifested by an increased duration of swimming.

Immunology, 1988 Feb, 63(2), 247 - 54
Characterization of human T8+ suppressor and contrasuppressor cells, separated by the lectin Vicia villosa; Brines R et al.; The helper function of human T4+ cells acting on autologous B cells, in the presence of monocyte-enriched cells (MEC), has been studied using the hapten-carrier conjugate DNP-streptococcal antigen (DNP-SA) . The antibody response can be suppressed by T8+ cells, but selection of a Vicia villosa lectin-non-adherent (T8VV-) subset enhances the suppressor function . The T8 Vicia villosa lectin-adherent (T8VV+) cells are not suppressive, rather they inhibit the T8VV- cell suppressor function . Sequential reconstitution studies suggest that the target of both T8VV- suppressor-cell and T8VV+ contrasuppressor activity is the T4 helper-inducer cell . This was established after the separation of T4+ cells into Leu 8- helper- and Leu 8+ suppressor-inducer cells . Activation of T8VV- and T8VV+ cells with antigen before reconstitution with fresh lymphocytes and MEC suggests that T8VV- suppressor activity is antigen specific, whereas T8VV+ cell contrasuppressor function is non-specific . We suggest that the human T8+ cells are functionally heterogeneous and consist not only of suppressor and cytotoxic cells but also contrasuppressor cells.

Infect Immun, 1988 Feb, 56(2), 400 - 4
Cross-neutralization of staphylococcal and streptococcal pyrogenic toxins by monoclonal and polyclonal antibodies; Bohach GA et al.; We evaluated cross-reactivity of antibodies against staphylococcal and streptococcal pyrogenic toxins . Monoclonal antibodies against staphylococcal enterotoxin (ET) C1 and streptococcal pyrogenic exotoxin (SPE) A were tested for reactivity with homologous and heterologous pyrogenic toxins in vitro . Ten immunoglobulin G1 anti-ET C1 monoclonal antibodies showed little or no cross-reactivity in an enzyme-linked immunosorbent assay, but many of these could neutralize the mitogenic effect of ET B, SPE A, or both . Two immunoglobulin M anti-ET C1 monoclonal antibodies and eight immunoglobulin M anti-SPE A monoclonal antibodies showed extensive cross-reactivity in the enzyme-linked immunosorbent assay and the mitogenicity neutralization assay . No cross-reactivity was observed with SPE C or toxic shock syndrome toxin 1 . Rabbits immunized against ET B, ET C1, or SPE A were resistant to challenge with the immunizing toxin . In addition, reciprocal immunity was stimulated by the two ETs, and immunity to SPE A provided protection against ET B but not ET C1 . These results show that staphylococcal and streptococcal pyrogenic toxins which share sequence homology have common antigenic determinants which may not be detected in Ouchterlony immunodiffusion assays.

J Immunol, 1988 Jan 15, 140(2), 641 - 5
Genetics and primary structure of V kappa gene segments encoding antibody to streptococcal group A carbohydrate . Comparison of V kappa gene structure with idiotope expression; Lutz CT et al.; Two gene segments, V kappa-25-39 and V kappa-25-47, that encode antibody to streptococcal group A carbohydrate in A/J mice were found to be more than 95% homologous in nucleotide sequence in both coding and noncoding regions . It was previously shown that V kappa-25-39 encodes immunoglobulins that express the IdX and IdI-1 idiotopes, whereas V kappa-25-47 encodes IdX+, and IdI-1- immunoglobulins . V kappa gene segments that were clearly allelic to V kappa-25-47 are used to encode IdX+, IdI-1- anti-group A carbohydrate antibodies by C.B20 mice and likely by C57BL/6 mice . Murine strains that are deficient in IdI-1 idiotope expression were investigated by Southern blotting with a 5' probe from V kappa-25-39 . Two IdI-1-deficient strains, CE/J and C58/J, had a grossly altered V kappa gene segment structure compared with the A/J prototype . In contrast, the IdI-1-deficient strain, C57BL/6, was indistinguishable from A/J with the 5'V kappa-25-39 probe, indicating that more subtle genetic changes account for the loss of IdI-1 expression in C57BL/6 mice . The evolution of V kappa-25-39 and V kappa-25-47 gene segments was deduced by comparison with the homologous V kappa 24B gene segment of Mus pahari . V kappa-25-39 and V kappa-25-47 likely have recently duplicated once in A/J and related strains of laboratory mice and may have duplicated again in CE/J mice . Thus, individual members of the V kappa 24 gene family, to which V kappa-25-39 and V kappa-25-47 belong, are preserved while the number of gene copies expands or contracts . This fact is strong evidence that evolutionary forces have maintained the V kappa 24 gene family, all of which encode antibody specific for carbohydrate found in bacterial pathogens.

Nucleic Acids Res, 1988 Jan 11, 16(1), 115 - 33
Identification of the origin and direction of replication of the broad-host-range plasmid pLS1; Puyet A et al.; The replication origin of the fully sequenced broad-host-range streptococcal plasmid pLS1 has been determined by the use of an in vitro replication system prepared from Escherichia coli, a host in which the plasmid can be established . Replicative intermediates were isolated from reaction mixtures that contained dideoxythymidine triphosphate, thus limiting the average extent of in vitro synthesis . Analysis of HinfI-cleaved intermediates demonstrated that the origin of replication is included within a 443-bp fragment . Replication proceeds unidirectionally in the same direction as transcription of plasmid mRNAs . Isolation of deletion derivatives allowed us to define the replication origin of pLS1 within a region of 284 bp . Replication of pLS1 occurs through single-stranded intermediates by a rolling circle mechanism . Cleavage of supercoiled plasmid DNAs with endonuclease S1 followed by restriction mapping, allowed the positioning of three major specific S1 sites in regions of high potential to form secondary structures . One of these inverted repeats is located in the region where the origin of replication of pLS1 has been defined.

Monogr Allergy, 1988, 23, 225 - 35
Survival of antigen-specific antibody following administration of intravenous immunoglobulin in patients with primary immunodeficiency diseases; Fischer SH et al.; To measure the survival of IgG, IgG subclasses and antigen-specific antibody in immune-deficient patients, we infused 4 patients with X-linked agammaglobulinemia (XLA) and 6 patients with common variable immune deficiency (CVID) with modified immunoglobulin at a dose of 400 mg/kg per month until steady state was reached . Following the 8th monthly infusion, serial samples were obtained and analyzed for serum concentration of IgG, IgG subclasses and for specific antibody activities against a battery of antigens . Half-lives for IgG and IgG subclasses were between 30 and 40 days except for IgG3 which appeared to consist of two populations of molecules, one showing a rapid decay, the other disappearing at a rate suggesting a half life of 22-24 days . Antigen-specific antibodies, including antibodies to HBsAg, cytomegalovirus, pneumococcal polysaccharides and streptococcal group A carbohydrate were similar to that for total IgG . These studies demonstrate that protective antibody titers to infective agents can be maintained for several weeks following high-dose intravenous immunoglobulin infusion.

Nephron, 1988, 49(2), 119 - 21
Medical renal disease in the elderly in a southern Indian hospital; Hariharan S et al.; A review of 85 patients aged 60 years or more, treated in a southern Indian hospital for conditions requiring renal biopsy, showed that diffuse poliferative glomerulonephritis was the most frequent diagnosis, being present in 24 cases of whom 11 had elevated serum streptococcal antibody titres . Infections were also important in 2 patients with amyloidosis secondary to tuberculosis, in 3 patients with acute tubular necrosis following infectious gastroenteritis and in a patient with acute pyaemic interstitial nephritis with septicaemia . Drugs including indigenous medicines were the other important cause of renal disease, being implicated in 11 cases.

Ann Intern Med, 1988 Jan, 108(1), 30 - 5
Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia; Rubin M et al.; STUDY OBJECTIVE: To determine the appropriate role for vancomycin in neutropenic patients with cancer . To review the incidence, types, and outcome of gram-positive infections in a series of neutropenic patients with cancer . DESIGN: Retrospective review . SETTING: Inpatient units of the Medical and Pediatric Oncology Branches of the National Cancer Institute . PATIENTS: Five hundred and fifty consecutive episodes of fever and neutropenia in patients with cancer randomized prospectively on another study to receive either ceftazidime alone or combination antibiotics for initial empirical therapy . INTERVENTION: Intravenous vancomycin (dosage adjusted by serum levels) . MEASUREMENTS AND MAIN RESULTS: Gram-positive organisms were the commonest of the bacterial pathogens isolated (63%) . Of the 53 gram-positive organisms accounting for primary infections (isolated at initial presentation), there were 36 staphylococcal isolates (19 coagulase-negative and 17 coagulase-positive), 13 streptococcal isolates (8 non-group D and 5 group D), and 4 polymicrobial isolates . Of the 22 secondary gram-positive infections (occurring after institution of initial antibiotics), there were 10 streptococcal isolates (9 group D and 1 non-group D), 7 staphylococcal isolates (6 coagulase-negative and 1 coagulase-positive), and 5 polymicrobial isolates . Vancomycin was used to treat 26 of the 53 primary infections, but was begun only after knowledge of the isolate in 25 . Vancomycin was used to treat 17 of the 22 secondary infections, and begun only after knowledge of the isolate in 14 . This approach resulted in no treatment failures for the primary infections, and a single microbiological failure for the secondary infections . There was a tendency towards a greater proportion of secondary gram-positive infections in the monotherapy group compared to the combination therapy group (16 of 282 compared with 6 of 268 respectively, P2 = 0.04 by the chi-squared test); but all were treated successfully . CONCLUSION: Vancomycin need not be included in routine empirical therapy for febrile neutropenic patients, but should be added when clinical or microbiological data suggest the need.

J Bacteriol, 1988 Jan, 170(1), 34 - 41
Nucleotide sequence of the type A staphylococcal enterotoxin gene; Betley MJ et al.; We determined the nucleotide sequence of the gene encoding staphylococcal enterotoxin A (entA) . The gene, composed of 771 base pairs, encodes an enterotoxin A precursor of 257 amino acid residues . A 24-residue N-terminal hydrophobic leader sequence is apparently processed, yielding the mature form of staphylococcal enterotoxin A (Mr, 27,100) . Mature enterotoxin A has 82, 72, 74, and 34 amino acid residues in common with staphylococcal enterotoxins B and C1, type A streptococcal exotoxin, and toxic shock syndrome toxin 1, respectively . This level of homology was determined to be significant based on the results of computer analysis and biological considerations . DNA sequence homology between the entA gene and genes encoding other types of staphylococcal enterotoxins was examined by DNA-DNA hybridization analysis with probes derived from the entA gene . A 624-base-pair DNA probe that represented an internal fragment of the entA gene hybridized well to DNA isolated from EntE+ strains and some EntA+ strains . In contrast, a 17-base oligonucleotide probe that encoded a peptide conserved among staphylococcal enterotoxins A, B, and C1 hybridized well to DNA isolated from EntA+, EntB+, EntC1+, and EntD+ strains . These hybridization results indicate that considerable sequence divergence has occurred within this family of exotoxins.

Int J Tissue React, 1988, 10(1), 1 - 5
Streptococcal cell-wall-induced arthritis in rats: an overview; Wilder RL; The author summarizes research performed by himself and his colleagues to study chronic erosive arthritis by means of injecting fragments of streptococcal cell walls into rats . By study of rat strains resistant and susceptible to various stages of the disease, as well as the effects of therapeutic drugs, information has been obtained on the pathogenesis of the synovitis and on the role of cellular and humoral factors in regulating inflammatory disease.

Proteins, 1988, 3(1), 60 - 9
Conformational characteristics of the complete sequence of group A streptococcal M6 protein; Fischetti VA et al.; M protein is considered a virulence determinant on the streptococcal cell wall by virtue of its ability to allow the organism to resist attack by human neutrophils . The complete DNA sequence of the M6 gene from streptococcal strain D471 has allowed, for the first time, the study of the structural characteristics of the amino acid sequence of an entire M protein molecule . Predictive secondary structural analysis revealed that the majority of this fibrillar molecule exhibits strong alpha-helical potential and that, except for the ends, nonpolar residues in the central region of the molecule exhibit the 7-residue periodicity typical for coiled-coil proteins . Differences in this heptad pattern of nonpolar residues allow this central rod region to be divided into three subdomains which correlate essentially with the repeat regions A, B, and C/D in the M6 protein sequence . Alignment of the N-terminal half of the M6 sequence with PepM5, the N-terminal half of the M5 protein, revealed that 42% of the amino acids were identical . The majority of the identities were "core" nonpolar residues of the heptad periodicity which are necessary for the maintenance of the coiled coil . Thus, conservation of structure in a sequence-variable region of these molecules may be biologically significant . Results suggest that serologically different M proteins may be built according to a basic scheme: an extended central coiled-coil rod domain (which may vary in size among strains) flanked by functional end domains.

Rev Infect Dis, 1988 Jan-Feb, 10(1), 125 - 30
Penicillin prophylaxis for streptococcal infections in United States Navy and Marine Corps recruit camps, 1951-1985; Thomas RJ et al.; Benzathine penicillin G has been used in United States Navy and Marine Corps recruit camps since 1953 to reduce the incidence of streptococcal disease and its nonsuppurative complications-acute rheumatic fever and acute glomerulonephritis . This paper reviews the history of prophylactic penicillin use among U.S . Navy and Marine Corps recruits and discusses the rationale for continuing this practice today.

Int Arch Allergy Appl Immunol, 1988, 85(3), 316 - 21
Antibodies reactive with streptococcal peptidoglycan-polysaccharide complexes in rheumatic fever, subacute bacterial endocarditis and tuberculosis; Evans HB et al.; Serum antibodies reactive with streptococcal peptidoglycan-polysaccharide complexes (PG-PS) have been estimated by enzyme-linked immunosorbent assay in patients with acute rheumatic fever (ARF), tuberculosis (TB) and subacute bacterial endocarditis (SBE) compared with normal age- and sex-matched controls . IgG2 and IgG3 were the predominant subclasses of antibodies in TB and SBE, whereas in ARF IgG1, IgG2 and IgG3 antibodies were detected . IgG4 antibodies were detected only infrequently . Antibodies of the IgG subclasses were detected in a greater proportion of sera when the PG-PS antigen was further purified by extraction with sodium dodecyl sulphate.

An Esp Pediatr, 1988 Jan, 28(1), 23 - 6
{Rapid diagnosis of streptococcal pharyngo-tonsillitis in a primary care unit}; Morlan Sala A et al.; One of the main consulting motives in ambulatory pediatric practice is acute pharyngotonsillitis . This work values the efficacy of a test to confirm rapid diagnosis (30 minutes) of streptococcal pharyngitis . Authors selected 100 children in a office of primary health care whose ages were between two and seven years, from February to July in 1986 . They have considered classical clinical symptoms of pharyngitis and have applied a throat culture and rapid test in all . After comparing test results and culture results, obtained sensibility and specificity have been 80% and 95% (p less than 0.01) respectively . According to these results, they believe on the necessity of a test that permits a rapid diagnosis and which enables to treat acute pharyngitis in a more suitable way in ambulatory pediatrics.

Pediatr Cardiol, 1988, 9(1), 51 - 3
Group B streptococcal endocarditis in a neonate; Agarwala BN; This is a case of bacterial endocarditis and dissecting aneurysm of the ascending aorta secondary to group B streptococcal (GBS) septicemia in a one-mouth-old infant girl who presented with meningitis . A large aortic vegetation and a large dissecting aneurysm of the root of the aorta were detected by two-dimensional (2D) echocardiography . Apparently the infant did not have any preexisting cardiac anomaly . She received intravenous ampicillin for six weeks . She also underwent successful surgery for the replacement of the ascending aorta with an aortic homograft . This occurrence reemphasizes the value of 2D echocardiography in detecting vegetations for endocarditis.

Circ Shock, 1988, 24(1), 35 - 41
Ibuprofen in experimental group B streptococcal shock; Peevy KJ et al.; A rabbit model was used to characterize the effects of high (Group II, 100 mg/kg) and low (Group III, 10 mg/kg) dose ibuprofen in modulating the hemodynamic and hematologic manifestations of group B streptococcal shock . Short-term survival was significantly increased with ibuprofen pretreatment . Ibuprofen failed to prevent GBS-induced shock, although shock was favorably modified in a dose dependent manner . Likewise, GBS-induced increases in 6KPGF1a and TxB2 were not prevented but were modified in Group II at 120 min . However, neutropenia, thrombocytopenia, and acidosis were not prevented by pretreatment with ibuprofen and may have been exacerbated . Thus, ibuprofen modifies but does not prevent GBS-induced hemodynamic and hematologic manifestation.

Cornea, 1988, 7(4), 295 - 9
Ocular streptococcal infections; Jones S et al.; Streptococcal infections are an important cause of corneal ulcers, endophthalmitis, conjunctivitis, and dacryocystitis . We retrospectively reviewed 53 ocular streptococcal infections diagnosed and followed at Wills Eye Hospital between January 1, 1984, and July 1, 1986 . Corneal ulcers (23 of 53; 43%) and endophthalmitis (18 of 53; 34%) constituted a majority of the streptococcal infections in this series . Streptococcal infection was also a common cause of conjunctivitis, but clinical follow-up data were sufficient for inclusion in this series in only a small fraction of conjunctivitis patients (9 of 70; 13%) . Streptococcal corneal ulcers and endophthalmitis were frequently associated with a poor visual outcome . When antibiotic sensitivity testing was done, approximately one third of the streptococcal isolates (13 of 38; 34%) were not sensitive to gentamicin . As topical gentamicin is frequently used by ophthalmologists, the possibility of streptococcal infection should be taken into account in the selection of antibiotics for conjunctivitis, corneal ulcers, endophthalmitis, and prophylaxis.

Acta Cardiol, 1988, 43(2), 121 - 32
A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features; Hollanders G et al.; Microbiological features, diagnostic investigations, treatment, and complication rate in 53 cases of infective endocarditis were reviewed in this study . Infection occurred both on prosthetic (47%) and native valves (38%), while in 15% of the cases no prior valvular disease was known . Streptococcal (38%) and staphylococcal (30%) infections were predominant . In 17% of the cases apparent negative blood cultures were obtained . The most frequent portal of entry was dental infection or manipulation (45%), however in 28% of the patients etiology remained obscure . Major clinical signs and symptoms included heart murmurs (96%), fever (91%), dyspnoea (32%), and splenomegaly (30%) . Echocardiography revealed vegetations in 78%, aortic and mitral valve being nearly equally affected . All patients were medically treated and 53% received antibiotics prior to blood cultures . Associations of ampicillin or penicillin with an aminoglycoside (43%) and penicillinase-resistant antibiotics (30%) were most frequently administered . In 28% of the patients, it was necessary to insert a prosthetic (aortic or mitral) valve . During follow-up, heart failure (28%), embolization (11%), and infections (11%) were the major complications.

Chemotherapy, 1988, 34 Suppl 1, 34 - 8
Short-term treatment of streptococcal tonsillitis with ceftriaxone; Pavesio D et al.; The short-term therapy of streptococcal pharyngotonsillitis and scarlet fever with ceftriaxone (Rocephin) is reported . Sixty children, in whom the clinical diagnosis was confirmed by rapid enzyme immunoassay and smear test, were divided into two randomized groups and treated with a single dose of 50 mg/kg ceftriaxone or 50 mg/kg ceftriaxone on 3 consecutive days . Clinical cure was obtained in 100% of the patients and pharyngeal sterilization in 95%, with no significant differences between the two groups.

Chemotherapy, 1988, 34(6), 512 - 8
Clinical comparison of once-daily cefadroxil and thrice-daily cefaclor in the treatment of streptococcal pharyngitis; Randolph MF; The efficacy of cefadroxil once daily and cefaclor given 3 times daily was compared in 250 pediatric patients with group A beta-hemolytic streptococcal pharyngitis . The duration of the therapy was 10 days . Therapeutic response was based on clinical responses at 24 h and 10 days and throat cultures on days 14, and 21 or 28 . Five (5%) cefadroxil-treated patients and 12 (12%) cefaclor-treated patients were still culture-positive on day 14 . When the patients were stratified according to major differences between treatment groups observed at baseline, a significant difference between the treatment groups in favor of cefadroxil was found on day 14 (p = 0.020) and days 21-28 (p = 0.043) . These data were confirmed by the clinical findings; failure or clinical recurrence occurred in 4.6% of cefadroxil-treated patients versus 22.1% of cefaclor-treated patients . The patients complied with the recommended drug regimen, and none experienced any significant drug-related adverse reactions . The results of this study indicate that cefadroxil given once daily for streptococcal pharyngitis is an effective and well-tolerated antimicrobial agent, and suggest that the desirable pharmacokinetic properties of cefadroxil contribute to this efficacy.

Acta Otolaryngol Suppl, 1988, 454, 286 - 91
Streptococcal antibody: as an indicator of tonsillectomy; Fujikawa S et al.; The significance of antibody for streptolysin-O concerning tonsillectomy was studied . The results obtained were as follows . 1 . The upper limit of ASO titer in 5,121 school children was 250 u and a value of more than 333 u was considered abnormal . But the level of the normal limit was different from year to year . 2 . Among 143 cases with a high ASO titer of more than 833 u, only 12 cases had recurrent tonsillitis . There was no correlation between the tonsillar hypertrophy and the height of streptococcal antibodies . 3 . There was a correlation between the titers determined by ELISA IgG-ASO and ASO in Todd units (r = 0.69), but there was no agreement between the titers determined by ELISA IgM-ASO and ASO in Todd units . 4 . IgM-ASO determined by ELISA showed high levels in cases with early stages of streptococcal infection, focal infection and streptococcal carriers . Cases with high ASO, both IgG- and IgM-subclasses, were considered to have an indicative factor for tonsillectomy.

Genet Epidemiol, 1988, 5(6), 463 - 70
Cell surface markers and cellular immune response associated with rheumatic heart disease: complex segregation analysis; Rich SS et al.; A series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence . Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A . Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.

Pediatrie, 1988, 43(6), 515 - 8
{Pneumococcal pneumonia and septic shock in the newborn infant}; Larchet M et al.; Pneumococcal sepsis and pneumonia in the neonate are rarely reported . They appear either as an early-onset respiratory distress with a high mortality rate or as a delayed infection . The authors describe 3 term neonates with an early respiratory distress syndrome and recall the main points of this severe foeto-maternal infection . Neonatal pneumococcal sepsis is strikingly similar to early-onset group B streptococcal infection . The isolation of the germ in the mother's vaginal flora is hazardous . Such cases suggest that early respiratory support and intensive circulatory resuscitation lead only to a slight decrease in the mortality rate, and thus preventive antibiotherapy is a necessity.

Microbiol Immunol, 1988, 32(6), 621 - 33
Priming activity for chemiluminescence reaction of PMN in the culture supernatant of streptococcal preparation (OK-432)-stimulated spleen cells; Fukase Y et al.; We investigated the effect of supernatant from human spleen cell culture stimulated with a streptococcal preparation, OK-432 (OK sup), on the luminol-dependent chemiluminescence (CL) of human polymorphonuclear leukocytes (PMN) . The fMLP-stimulated CL of PMN was markedly enhanced by the pretreatment with OK sup . This result indicates that OK sup contained the factor(s) that primes fMLP-stimulated CL of PMN . The priming factor(s) in OK sup was partially inactivated by the treatment at 56 C for 30 min and pH 2 or pH 10 treatments . Since the enhancing effect of OK sup on the CL was inhibited by the treatment of sodium azide and the addition of catalase or taurine, it was assumed that OK sup augments the activity of MPO-H2O2-HOCl system of fMLP-stimulated PMN.

Cancer Immunol Immunother, 1988, 27(3), 198 - 204
Induction of tumor growth inhibitory factor (TGIF) in human mononuclear cells by OK-432, a streptococcal preparation; Katano M et al.; A tumor growth inhibitory factor (TGIF) was induced in the culture supernatant from mixed culture of human peripheral blood mononuclear cells (PBMC) and a streptococcal preparation, OK-432, in vitro . The activity generated in the supernatant increased in a time-dependent fashion and first appeared 6 h after the initiation of culture, reaching its maximum around 48 h . The TGIF was cytostatic against seven of ten human tumor targets, but not against three murine tumor targets . Tumor cell growth was inhibited by a transient contact, i.e., 1 h, with TGIF . The TGIF was produced by lymphocytes but not by monocytes, because the activity was usually enhanced by elimination of plastic-adherent cells from the original PBMC fraction . The TGIF was relatively stable against heating at 56 degrees C for 30 min, but the activity was totally destroyed after heating at 70 degrees C for 5 min . The molecular weight of TGIF was estimated to be about 43 x 10(3) daltons by gel filtration . No interferon (IFN) activity was detected in the TGIF-positive fractions obtained by gel filtration, and the TGIF-positive fractions did not inhibit the growth of tumor necrosis factor (TNF)-sensitive mouse L929 cells . The TGIF activity was not significantly affected in neutralizing tests using specific antibodies against human IFN and TNF . The OK-432 was administered i.p . for management of cancer patients with malignant ascites . Ascites-derived mononuclear cells (ASMC) were obtained before and 3 to 5 days after OK-432 injection . The ASMC obtained after the injection produced TGIF in vitro in the absence of OK-432; the preinjection ASMC showed no such production . A positive correlation was found between TGIF-producing activity by ASMC and the effect of OK-432 injection on ascites volume . These results indicate that TGIF is induced in mononuclear cells by OK-432 not only in vitro but also in vivo and plays an important role in inhibition of tumor growth in cancer patients.

Prog Clin Biol Res, 1988, 264, 333 - 6
Group B streptococcal (GBSS) newborn septic shock model: the role of prostaglandins; Short BL et al.; Group B beta hemolytic streptococcal sepsis has many of the characteristics of gram negative sepsis (Hellerqvist, et al., 1981) . This is further shown in the model developed for this study . The newborn piglet septic model developed for this study appears to be an adequate model for group B, beta-streptococcal sepsis characterized by the development of significant hypotension by six hours . As with human sepsis, this model develops hypoglycemia, hemoconcentration as noted by the increased hematocrit, thrombocytopenia and a significant drop in WBC with an increase in immature forms (Wilson, 1986) . The only finding not correlated to the septic newborn is the development of DIC as characterized by an increased PT/PTT and increased FSP . As with other animal models for both gram positive and negative sepsis, the cyclooxygenase inhibitor, indomethacin significantly increased survival out to 72 hours . Previous studies with thromboxane synthetase inhibitors have not shown increased survival, but shunting into the prostacyclin pathway has occurred and the effect of this on survival could not be ruled out (Short, et al., 1983) . The use of a thromboxane receptor site antagonist should not cause this shunt, and thus may help to evaluate the effect of thromboxane blockade . In this model no effect of the receptor site antagonist was noted, but due to the short half-life of this compound, a different dosing schedule may be needed before its efficacy can be determined . In summary, the cyclooxygenase inhibitors do appear to have a protective effect in gram positive sepsis, but the mechanisms of action are still to be determined.

Scand J Infect Dis, 1988, 20(1), 37 - 46
Five versus ten days treatment of group A streptococcal pharyngotonsillitis: a randomized controlled clinical trial with phenoxymethylpenicillin and cefadroxil; Stromberg A et al.; 216 patients aged greater than or equal to 7 years with febrile group A streptococcal pharyngotonsillitis were randomly assigned to 3 treatment groups receiving either phenoxymethylpenicillin for 5 days followed by placebo for 5 days, phenoxymethylpenicillin for 10 days, or cefadroxil for 10 days . 209 patients completed treatment, 70 subjects in each phenoxymethylpenicillin group and 69 in the cefadroxil group . Within 1 week after completion of the antibiotic treatment significantly more recurrences with the same T-type as the initial streptococcal strain occurred in the 5-day treatment group (27%) as compared with the two 10-day groups (6% and 3%, respectively) . The cumulative rate of recurrences (irrespective of T-type) within 2 months from the start of therapy was 55% among patients treated with phenoxymethylpenicillin for 5 days, 24% among those treated for 10 days with this drug and 19% among patients receiving cefadroxil . Obviously, one important factor to avoid recurrence of group A streptococcal pharyngotonsillitis is the length of antibiotic treatment and, in our opinion, it is not advisable to change the current recommendation of 10 days treatment.

Mikrobiyol Bul, 1988, 22(4), 322 - 6
{Direct antigen detection for group A streptococcal pharyngitis: comparison of throat cultures and the direct antigen test}; Soyletir G et al.; In this study, traditional throat culture results and direct antigen detection from throat swabs have been compared with respect to diagnosis of Group A Beta hemolytic streptococcal infections in children with acute pharyngitis who admitted to Marmara University Hospital Pediatrics Department . It has been found that direct antigen test has a sensitivity of 92% and specificity of 98%.

Scand J Clin Lab Invest Suppl, 1988, 191, 21 - 31
Human cysteine proteinase inhibitors . Isolation, physiological importance, inhibitory mechanism, gene structure and relation to hereditary cerebral hemorrhage; Abrahamson M; The isolation and characterization of six human cysteine proteinase inhibitors is reported . Their distribution in human biological fluids is also described and discussed with respect to physiological function . Studies on kininogen and cystatin C with respect to structure-function relationships and, as a result of the cystatin C studies, a general model for the mechanism of cysteine proteinase inhibition by cystatins are presented . The model was used for the construction of synthetic inhibitors which showed good inhibitory properties against papain and the streptococcal cysteine proteinase . Structures of cDNA and gene for normal human cystatin C are accounted for, as well as studies on the cystatin C gene in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA) . As a result of this an RFLP that showed total co-segregation with the disease was found . It was concluded that the disease is caused by a point mutation in the cystatin C structural gene and that the RFLP will be a most useful tool for diagnosis of HCCAA . The production of recombinant cystatin C in E . coli is also reported and its possible use for treatment of HCCAA is discussed.

Scand J Rheumatol Suppl, 1988, 75, 93 - 6
Idiotypic interactions between rheumatoid factors and other antibodies; Johnson PM et al.; An internal network of antibody idiotypes and anti-idiotypes has been considered important in controlling the production of antibodies reactive with exogenous antigens, and a current hypothesis proposes that some autoantibodies may be auto-anti-idiotypes . RF is often associated with bacterial (notably streptococcal) infections, as well as occurring in RA . Experimental animals immunised with streptococcal cell wall peptidoglycan-polysaccharide (PG-PS) complexes produce serum RF-like antibodies . In addition, repeated immunisation of mice with isolated IgM- or IgG-RF also produces an anti-PG-PS response, indicating that RF could act as an anti-idiotype to anti-PG-PS . Serum antibodies reactive with streptococcal PG-PS occur frequently in RA, and are notably of the IgG2 subclass.

Acta Otolaryngol Suppl, 1988, 454, 153 - 62
The distribution of immunocompetent cells in the compartments of the palatine tonsils in bacterial and viral infections of the upper respiratory tract; Bernstein JM et al.; Employing a series of monoclonal antibodies directed against T cell subsets using the avidin-biotin complex method as the immunoperoxidase technique and using fluorescein-conjugated antisera directed against the major immunoglobulins, we have studied the distribution of immunocompetent cells in sections of tonsils from 21 patients with various inflammatory diseases of the tonsils, including Streptococcal tonsillitis, recurrent tonsillitis and tonsillitis associated with infectious mononucleosis . The following conclusions can be made in regard to our study . The percentage of T cells decreases in all compartments of the tonsils with increasing episodes of tonsillitis as well as with infectious mononucleosis and Streptococcal tonsillitis . Similarly, the percentage of HLA-DR positive cells decreases with increasing episodes of tonsillitis and is statistically significant in the mantle zone . The percentage of IgM B cells and IgD B cells tends to increase in the extrafollicular zone and decrease in the mantle zone with increasing episodes of tonsillitis as well as with increasing age . The percentage of IgG and IgA plasma cells is highest in children who have had 3-5 episodes of tonsillitis, but markedly decreases in the follicle and extrafollicular compartments in patients who have had more than 5 episodes of tonsillitis . FACS analysis of B cells in the tonsils and peripheral blood show a marked decrease in IgD in both the tonsil and the peripheral blood and a significant increase of IgG in the peripheral blood . These findings may suggest late clonal expansion of B cells in recurrent tonsillitis and Streptococcal tonsillitis . Finally, the distribution of immunocompetent cells in recurrent tonsillitis, Streptococcal tonsillitis and tonsillitis associated with infectious mononucleosis appears to be independent of age.

J Basic Microbiol, 1988, 28(7), 471 - 80
Survey of the pSM10 family of streptococcal cloning vectors; Laplace F et al.; A survey of the pSM10 family of streptococcal plasmid cloning vectors is provided . These vectors are derived from a macrolide-lincosamide-streptogramin B resistance plasmid and include general cloning vectors, shuttle vectors, helper plasmids, expression vectors, gene fusion vectors and plasmids . Besides describing their general properties, this paper also provides their genetic and physical maps.

Scand J Infect Dis, 1988, 20(4), 407 - 10
Group G streptococcal neonatal septicaemia: two case reports and a brief review of literature; Carstensen H et al.; We present 2 cases of early onset group G streptococcal septicaemia in full term neonates, together with a review of 15 previously reported cases, including 3 late onset cases . Most likely the neonates were infected during passage through the birth canal or had been exposed in utero . In one neonate, meconium aspiration occurred, while in the other prolonged rupture of maternal membranes was a risk factor . Both responded well to treatment with benzylpenicillin and gentamicin . Among the 12 previously reported early onset cases, 5 (43%) had a fulminant course with complications such as progressive respiratory distress, shock, and disseminated intravascular coagulation.

Rev Mal Respir, 1988, 5(5), 523 - 4
{A case of pleuropneumopathy due to Eikenella corrodens}; Moro D et al.; We report the observation of a pleuropneumonia due to Eikenella corrodens in a man of 39 years old suffering from diffuse dilatation of the bronchi . This small micro-aerophilic Gram negative bacillus has rarely been implicated as a cause of pneumonia . It appears that it may often be associated with streptococcal infections and that it becomes a pathogen when the immunity is lowered . Its sensitivity to antibiotics is excellent, particularly vis-a-vis beta-lactams.

APMIS Suppl, 1988, 3, 8 - 12
Immunoglobulin isotype response to the group-A streptococcal carbohydrate in humans; Araj GF et al.; We used an ELISA to determine the levels of specific anti-GAS carbohydrate IgG, IgM and IgA in 34 patients with acute rheumatic fever (ARF) with or without carditis, in 15 patients with acute glomerulonephritis (AGN) and in 18 control patients with noncomplicated GAS pharyngitis . Patients with ARF and AGN showed a significantly higher geometric mean titer as well as a higher frequency of elevated Ig of the IgG, IgM and IgA A-CHO class antibodies during the acute stage of this disease, when compared to controls . The IgM and IgA geometric means of the antibody were higher in ARF with carditis patients as compared to the non-carditis or AGN patients; however, the differences were not significant . In addition a lower frequency of antibody decline was observed in ARF with carditis patients who were seen in follow-up after a 1-year period, supporting previous observations of the persistence of this antibody in patients with rheumatic heart disease.

Monogr Allergy, 1988, 23, 41 - 56
Distribution of IgG subclasses among human autoantibodies to Sm, RNP, dsDNA, SS-B and IgG rheumatoid factor; Yount WJ et al.; The IgG subclass distribution of human autoantibodies to Sm, double-stranded DNA (ds-DNA), ribonucleoprotein (RNP), SS-B (La), and IgG rheumatoid factor (RF) have been determined using sensitive ELISA or by indirect immunofluorescence on Crithidia lucilia in sera from patients with systemic lupus erythematosus (SLE), Sjogren's syndrome, and rheumatoid arthritis . For anti-Sm and anti-RNP, IgG1 was the predominant isotype . For anti-ds-DNA and anti-SS-B, IgG1 and a lesser contribution of IgG3 was found . In contrast, IgG1 and IgG4 were the predominant isotypes of human IgG RF . The preponderance of isotypes noted for these autoantibodies did not extend to the IgG subclass distribution for antibodies to trinitrophenol-bovine serum albumin (TNP), tetanus toxoid (Tet . tox.), pneumococcal polysaccharides (Pneumo), and group A streptococcal cell walls (Strep.) . The restriction of human humoral responses as well as autoantibodies has both pathogenetic and immunoregulatory implications, and suggests that for these autoantibodies, T-cell-dependent responses, probably driven by antigen, are of importance.

Clin Ther, 1988, 10(5), 530 - 5
Erythromycin in acute pharyngitis: a comparison of efficacy and patient tolerance of two twice-daily preparations; Guthrie R; Two hundred sixty-five adult and adolescent patients with possible streptococcal pharyngitis were treated with either erythromycin ethylsuccinate or an enteric-coated erythromycin in a twice-daily dosage schedule . In patients with group A beta-hemolytic streptococcal infection, both preparations achieved a cure rate of 93% . Patients receiving the enteric-coated erythromycin reported significantly more gastrointestinal adverse effects than did the patients receiving erythromycin ethylsuccinate.

Pharmacotherapy, 1988, 8(4), 211 - 9
Therapeutic update on glycopeptide and lipopeptide antibiotics; Rotschafer JC et al.; Glycopeptide antibiotics in the form of vancomycin have been available for almost 30 years . In the past, vancomycin usually was reserved as an alternative agent to treat staphylococcal and streptococcal infection in patients with a penicillin allergy or hemodialysis shunt infection . With the increasing frequency of both methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, now it is often used as a first-line agent . Over a 10-year period, vancomycin sales have increased by almost $1 hundred million . Several new glycopeptide and lipopeptide antibiotics are in various stages of evaluation . While vancomycin resistance to date is a rare phenomenon, these drugs represent a potentially more potent and safer antibiotic alternative to vancomycin . Teicoplanin and daptomycin are two of these investigational agents.

Arkh Patol, 1988, 50(7), 31 - 7
{Enzyme histochemical characteristics of prostaglandin synthetase, adenylate cyclase and cAMP in a focus of inflammation in chronic tonsillitis}; Vartazarian ND; Upon enzyme histochemical evaluation of palatine tonsils removed from 80 patients with chronic tonsillitis it was established that there is a close correlation between activity of prostaglandin synthetase (PG-synthetase), adenylate cyclase (AC), cellular cAMP, pattern of inflammation and the size of streptococcal foci . Enhanced enzymatic activity, elevated content of lymphoid and connective tissue cAMP are associated with minor interstitial streptococcal foci, being a frequent finding in mild inflammation . Low cellular cAMP in high PG-synthetase and AC activity occurs in mild inflammation and large-sized interstitial streptococcal foci . When both enzymatic activity and cellular cAMP are low, torpid inflammation indicates lack of tissue response to microbial invasion resulting in emergence of interstitial streptococcal colonies . In view of the essential role of mediator effects in the inflammation focus, high activity of tonsil PG-synthetase should be considered a major indicator of activated chronic tonsillitis.

Cancer Immunol Immunother, 1988, 27(2), 97 - 102
Cytokines produced by blood mononuclear cells stimulated with the streptococcal preparation OK-432: effect on production by supplementing the medium with xenogeneic serum; Fujii M et al.; Human blood MNC were stimulated for 7 days with a streptococcal preparation, OK-432, in a medium supplemented with either 10% autologous serum (autoserum) or 10% FCS . Cytokines, including IL-2, IL-1, IFN, and TNF in the supernatants, and antitumor cytotoxicity of MNC were analyzed . None of the IL-2 was detectable during the culture in medium with autoserum, although significant enhancement of cytotoxicity was observed at day 1 . On the other hand, production of IL-2 and higher cytotoxicity were induced in the medium with FCS . Even a control culture of MNC unstimulated with OK-432 in the medium with FCS, showed a slight but significant amount of IL-2 and considerable cytotoxicity . However, such a culture in the medium with autoserum showed no such IL-2 production or cytotoxicity . The cytotoxicity induced in the medium with FCS was significantly inhibited by the addition of anti-IL-2 antibody to the culture as well as by the addition of anti-IFN gamma antibody, whereas the cytotoxicity in the medium with autoserum was not inhibited at all by anti-IL-2 antibody . Therefore, the cytotoxicity induced in the medium with FCS included IL-2-induced killer activity, i.e., LAK activity . Similarly, the levels of IL-1, IFN, and TNF production in the supernatants were variable depending on the serum used to supplement the medium . The nonspecific production of IL-2 and the unexpected induction of cytotoxicity were consistently provoked in the medium using several different lots of FCS, but not in the medium with human allogeneic sera or pooled AB serum nor in that with autoserum . It was revealed that the source of sera used to supplement the medium is an important factor affecting the results of analysis of cytokine production and cytotoxicity of MNC induced by certain stimulants.

Immunol Lett, 1988 Jan, 17(1), 13 - 9
Differential regulation of interleukin 2 (IL-2) receptor expression on antigen-specific human T cell clones by IL-2; Sia DY; A panel of human T cell clones bearing exclusively the T4 (helper) phenotype and demonstrating specificity to a well-characterized soluble glycoprotein antigen (185,000 dalton streptococcal antigen, SA) is described . After having been cultured in exogenous interleukin 2 (IL-2) for 7 days in the absence of the specific antigen, two of the clones, namely SA1.4 and SA1.23, show stronger proliferative responses to the ligand as compared to the other T4 clones . Analysis of both the high- and low-affinity IL-2 receptor (IL-2R) levels reveals that IL-2 mediates differential regulation of high affinity IL-2R expression on these antigen-deprived cloned cells . Higher levels of surface expression of the IL-2 binding sites on SA1.4 and SA1.23 as compared to the other clones are observed throughout the 7-day culture period that these lymphocytes are maintained in exogenous IL-2 . All the cloned cells appear to have returned to their "unstimulated states" as noted by their stable low expressions of Tac antigen and high affinity IL-2R . The unstimulated states of SA1.4 and SA1.23 are represented by higher levels of high affinity IL-2R expression . Under the condition in which the cloned cells are exposed to a decreasing concentration of IL-2, SA1.4 and SA1.23 are found to secrete a greater amount of IFN-gamma . The present results therefore suggest that a control mechanism involving the "mutual amplification" of IL-2 and IFN-gamma regulates the differential expression of high affinity IL-2R on antigen-specific T4 clones.

J Immunol, 1988 Jan 1, 140(1), 277 - 82
Human immune response to group A streptococcal carbohydrate (A-CHO) . II . Antigen-independent stimulation of IgM anti-A-CHO production in purified B cells by a monoclonal anti-idiotopic antibody; Bloem A et al.; The paper describes the induction by a monoclonal anti-idiotopic antibody (anti-Id mAb) of specific antibody production to group A streptococcal carbohydrate (A-CHO) in purified human B cells of several unrelated individuals . The anti-Id mAb, designated 16F498 (anti-Id498), recognizes a recurrent idiotope (Id 498) associated with the combining site of human antibodies to N-acetyl-D-glucosamine (GlcNAc), the immunodominant group of A-CHO . Id498 is expressed on IgM anti-GlcNAc antibodies but does not occur on IgG antibodies with the same specificity . It occurs also on a minor population of IgM antibodies without specificity for A-CHO . Id498 was found in 19 of 27 sera from unselected healthy donors and thus seems to be frequently expressed within the adult B cell repertoire . The in vitro induction of anti-A-CHO antibodies was analyzed in human B cells extensively depleted for T cells . Specific antibody secretion required cross-linked anti-Id which was achieved by coupling the mAb to agarose beads . No antibody secretion could be induced by soluble anti-Id (1 and 10 micrograms/ml) . An optimal response required soluble T cell-derived factors which were added as a mixture of recombinant interleukin 2 with a T cell hybridoma supernatant that augments B cell growth and differentiation . Under these conditions an antigen-independent specific increase of IgM anti-A-CHO production (2.6- to 10-fold, or up to 2000 ng/ml respectively) could be induced in blood B cell populations of four of six normal individuals expressing the Id498 at serum level.

Science, 1987 Dec 11, 238(4833), 1573 - 5
Phagocytosis of Candida albicans enhances malignant behavior of murine tumor cells; Ginsburg I et al.; Murine tumor cells were induced to phagocytize either Candida albicans or group A streptococcal cells . The presence of microbial particles within the tumor cell cytoplasm had no effect on in vitro tumor cell growth . However, when Candida albicans-infected tumor cells were injected into syngeneic mice, they formed tumors that grew faster, invaded the surrounding normal tissue more rapidly and metastasized more rapidly than control tumor cells . Tumor cells infected with group A streptococcal particles did not grow faster or show increased malignant behavior . These data indicate that the in vivo behavior of malignant tumor cells can be modulated by microbial particles, which are often present in the microenvironment of the growing tumor.

J Dairy Sci, 1987 Dec, 70(12), 2658 - 65
Multiple infusions of cloxacillin for treatment of mastitis during the dry period; Cummins KA et al.; Efficacy of multiple and single intramammary infusions of benzathine cloxacillin (500 mg/quarter) were compared for treatment of mastitis during the dry period . Treatments were three infusions, one each at 0, 7, and 14 d into the dry period; one infusion at drying off; and no infusions . Cows were grouped (30/treatment) based on previous mastitis history, mean monthly SCC, mature equivalent milk production, and pathogen detected pretreatment . Infected quarters/cow at parturition, posttreatment were 1.26, 1.6, and 2.35 for multiple, single, and no infusion groups, respectively . Milk production and somatic cell count posttreatment were not affected by treatment . Across all genera of microorganism, 75.5, 73.6, and 52.8% of infections were eliminated in the multiple, single, and no infusion groups, respectively . Primary effect of multiple infusions with cloxacillin in the dry period was to prevent new streptococcal infections . Sensitivity tests on staphylococcal isolates indicated that cloxacillin was still an effective dry cow treatment after 7 yr of use in the herd . Resistance to cloxacillin in approximately half the posttreatment staphylococcal isolates appeared to be nonenzyme (penicillinase) dependent . Multiple dry cow treatments with cloxacillin do not offer any advantage over a single treatment.

Isr J Med Sci, 1987 Dec, 23(12), 1228 - 31
Erythema nodosum in the Negev area--a survey of 50 patients; Erez A et al.; Fifty patients in the Negev area with erythema nodosum (EN) were studied retrospectively . The clinical picture and demographic characteristics did not differ markedly from those in the literature . In contrast to most European studies but like those from Egypt, we found streptococcal pharyngitis to be the major cause of EN . Conspicuously, sarcoidosis is a rare cause of EN in the Negev . The low incidence of EN in the Negev--2 cases/100,000 people per year--as opposed to Europe--14 cases/100,000 people per year--is hardly explained by the low occurrence of sarcoidosis in Israel . Other factors, unknown at present, may account for this low incidence.

J Rheumatol, 1987 Dec, 14(6), 1177 - 80
Rapidly fatal pneumococcal septicemia in systemic lupus erythematosus; Van der Straeten C et al.; Streptococcal pneumoniae septicemia was responsible for the deaths of 3 patients with chronic systemic lupus erythematosus . The absence of a spleen likely contributed to sepsis in 2 patients . One patient had been immunized with 14-valent pneumococcal vaccine with a doubling of serum antibody concentrations at one month to all vaccine capsular polysaccharide types except for Types 1 and 12 . The patient died 74 months after immunization of pneumococcal Type 1 sepsis.

Ann Rheum Dis, 1987 Dec, 46(12), 912 - 4
Acute tropical polyarthritis in Zimbabwe: a prospective search for a gonococcal aetiology; Stein CM et al.; Fifteen consecutive patients with acute arthritis were studied . Careful culture and microscopy of swabs from mucosal sites were performed to examine the hypothesis that the acute tropical polyarthritis commonly seen in Zimbabwe is due to undiagnosed gonococcal infection . Rheumatic fever and Reiter's disease accounted for two cases each . Gram negative intracellular diplococci were found in three patients who would otherwise have been diagnosed as having tropical polyarthritis . Except for two of the remaining eight patients, who had raised anti-streptolysin O titres suggesting recent streptococcal infection, no explanation for the arthritis was found . The clinical entity of tropical polyarthritis may not be due to a single aetiological agent.

Jpn Circ J, 1987 Dec, 51(12), 1347 - 9
Antibody titer to group A streptococcal polysaccharide in rheumatic fever and rheumatic heart disease; Fujikawa S et al.; Antibody to group A streptococcal polysaccharide (ASP) is the only antibody of cellular components which is now detectable in clinical practice . Streptococcal polysaccharide is known to have cross-immunity with the glycoprotein of human heart tissue, and has been discussed as a pathogenesis of rheumatic carditis and valvular heart disease . In this study, ASP titer was determined by passive hemagglutination technique in patients with rheumatic fever and rheumatic heart disease . ASP titer showed higher levels in these patients compared to control children, but there was no specificity in rheumatic carditis or rheumatic heart disease.

Cancer Res, 1987 Dec 1, 47(23), 6204 - 9
Production of factor(s) that render polymorphonuclear leukocytes cytostatic from spleen cells stimulated with a streptococcal preparation, OK-432; Kimura S et al.; We previously reported the augmentation of tumor cytotoxicity of polymorphonuclear leukocytes (PMN) by in vivo administration of a streptococcal preparation, OK-432 (S . Watabe et al., J . Natl . Cancer Inst., 72: 1365-1370, 1984) . The present study was undertaken to elucidate the mechanisms of the phenomena . Mouse and rat spleen cells were stimulated in vitro with OK-432 . The culture supernatants from the stimulated spleen cells (OK sup) contained factor(s) that rendered mouse and rat PMN cytostatic {neutrophil activating factor (NAF)} . The stimulation of spleen cells with a small dose of OK-432 (0.05 micrograms/ml) resulted in the production of maximum NAF, and NAF was produced soon (12 h) after OK-432 stimulation . NAF was partially inactivated with 60 degrees C 30-min treatment, and completely inactivated with 100 degrees C 10 min . NAF was sensitive to pH 2 treatment . The treatment of PMN with OK sup for 5 min at 37 degrees C was sufficient to induce cytostatic activity of PMN . That OK sup contained gamma-interferon and recombinant gamma-interferon showed NAF activity indicate that gamma-interferon is a NAF in OK sup.

Jpn J Exp Med, 1987 Dec, 57(6), 333 - 8
Generation of activated killer-like cells by OK-432-mediated production of interleukin 1, interleukin 2, and interferon-gamma in vitro; Ujiie T; Human peripheral blood mononuclear (PBM) cells incubated for 3 or more days in medium containing streptococcal preparation OK-432 developed toxicity to natural killer-resistant tumor cell lines . The generation of cytotoxic cells by OK-432 was potentiated by exogenous lymphokines such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), the former being much more effective than the latter, and was blocked by antibodies to these cytokines such as interleukin 1 (IL-1), IL-2, and IFN-gamma . Although monocyte-depleted PBM cells were barely responsive to OK-432, they gave rise to activated killer (AK) cells after being incubated in medium with both IL-2 and IFN-gamma . Their generation was augmented by exogenous IL-1 but not by OK-432 . These data indicate that AK-like cells are generated from human PBM cells through mediation of IL-1, IL-2, and IFN-gamma produced by OK-432 in vitro.

J Exp Med, 1987 Dec 1, 166(6), 1825 - 35
Human cytotoxic T lymphocytes evoked by group A streptococcal M proteins; Dale JB et al.; Purified group A streptococcal M proteins were used to stimulate peripheral blood lymphocytes from normal adult volunteers . The activated lymphocytes were cytotoxic against cultured human heart cells, as well as liver cells, fibroblasts, and K562 cells, but showed only minimal cytotoxicity against several animal cell types . The cytotoxic activity evoked by type 5 M protein was dose and time dependent . Rabbit antisera against pep M5 that contained heart-crossreactive antibodies partially inhibited cytotoxicity against heart cells, but had no effect on other target cells, suggesting that a fraction of the effector lymphocytes may be recognizing M protein-crossreactive cell surface antigens . All of the cytotoxic activity was recovered from a CD3+ population of lymphocytes obtained from a fluorescence-activated cell sorter, and CD4+ and CD8+ cells were also cytotoxic . M protein-responsive T cell clones were generated that showed specificity for heart and K562 cells, in addition to clones that were cytotoxic against both cell lines . Our data show that streptococcal M protein evokes cytotoxic T lymphocytes against multiple human but not animal target cells . Some of the effector cells may be specific for cultured myocardial cells, but their role in the pathogenesis of rheumatic carditis will require further studies of lymphocytes from patients with acute rheumatic fever and carditis.

Cancer Res, 1987 Nov 15, 47(22), 6000 - 5
In vivo antitumor effect of lymphokine-activated rodent polymorphonuclear leukocytes; Fujii Y et al.; In vivo tumor inhibitory activity of polymorphonuclear leukocytes (PMN) treated in vitro with lymphokine(s) (LK) was investigated with Winn's assay . Culture supernatants of BALB/c mouse spleen cells incubated with a streptococcal preparation, OK-432, were used as an LK source . With the use of a {3H}uridine release assay, RL male-1 tumor cells were lysed to some extent by peritoneal BALB/c mouse PMN treated with this LK preparation . With Winn's assay, LK-treated PMN from BALB/c mice completely inhibited the growth of the admixed syngeneic tumor at a high effector to target ratio, when normal mice were used as recipients . When X-irradiated mice or nude mice were used as recipients, the tumor growth was partially inhibited by admixed LK-treated PMN, but the tumor began to grow gradually and finally killed the recipient mice, even when a high effector target ratio was used . When nude mice which had been given i.v . transfers of nylon wool column effluent spleen cells were used as recipients, the tumor inhibitory activity of LK-treated PMN was recovered to the same level as when normal mice were used as recipients . On the other hand, tumor inhibition by admixed LK-treated PMN in nude mice was not recovered by the transfer of X-irradiated nylon column effluent T-cells . As a mechanism of tumor inhibition by LK-treated PMN, a possible role of LK-treated PMN in reduction of tumor load is discussed.

J Immunol, 1987 Nov 15, 139(10), 3314 - 20
An antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction; Brines RD et al.; We isolated a T8+ T3+ Ia+ clone of cells from the peripheral blood mononuclear cells of a healthy subject . The clone was expanded and maintained with autologous feeder cells, interleukin 2, and a streptococcal antigen . The T8+ clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells, and released a soluble factor . Both the cloned cells and the corresponding soluble factor expressed augmenting helper but not suppressor activity . The augmenting helper activity for B cell antibody synthesis was demonstrable only in the presence of autologous T4 cells . Although stimulation of the T8+ cloned cells was antigen-specific, the resulting soluble factor elicited nonspecific antibody synthesis in the presence of T4 and B cells . The T8+ cloned cell-derived factor was adsorbed by B cells but not by T4 cells . Preliminary studies suggest that the factor has the properties of a B cell growth factor . We suggest that the T8+ population consists of functionally heterogeneous cell subsets, some that have suppressor function and others that augment the T4+ helper-inducer activity in B cell antibody synthesis.

Am J Surg, 1987 Nov, 154(5), 526 - 8
Management of soft-tissue infections of the upper extremity in parenteral drug abusers; Biderman P et al.; Management of extensive soft-tissue infections of the upper extremity in 23 parenteral drug abusers was reviewed . Bacterial cultures most often revealed oral flora, including streptococcal species in 77 percent of patients and anaerobes in 59 percent . Staph . aureus was present in only one patient . Ninety percent of the organisms were sensitive to penicillin and 98 percent to first-generation cephalosporins . Blood culture specimens, obtained at admission, were negative in 15 patients . All patients responded well to operative debridement, excision of involved veins, and local wound care . Surgical debridement is the mainstay of therapy . We believe that intravenous antibiotic therapy with a first-generation cephalosporin should be used in the acute phase for control of surrounding cellulitis and prevention of bacteremia.

Vet Microbiol, 1987 Nov, 15(3), 191 - 9
Reinfection of bovine mammary glands following dry-cow antibiotic therapy; Buddle BM et al.; Dry-cow antibiotic therapy (DCT) was administered to quarters with Staphylococcus aureus or streptococcal infections and the quarters were closely monitored for the presence of new or reactivated mammary infections throughout the dry period and the following lactation . Strains of S . aureus were characterized using a selection of biotyping tests to allow a comparison of S . aureus strains isolated before and after DCT . Cows with 3-4 quarters infected prior to DCT had a high susceptibility to reinfection in the following year . In contrast, for cows with 1-2 quarters infected prior to DCT and for heifers with no previous history of infection, the susceptibility to reinfection or new infection was very low . The majority of the S . aureus infections appearing in the lactation following DCT were due to S . aureus strains which differed from strains isolated prior to DCT, suggesting that these were new infections . Histopathological examination of quarters which had had recurrent S . aureus infections revealed lesions typical of chronic S . aureus mastitis, including extensive lobular fibrosis and atrophy.

Clin Nephrol, 1987 Nov, 28(5), 256 - 60
Rapid development of diffuse crescents in post-streptococcal glomerulonephritis; Fairley C et al.; A 14-year-old boy presented with 3 days of hematuria and oliguria following impetigo . Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with subendothelial electron dense deposits but no crescents . Due to recrudescence of clinical abnormalities after initial improvement, the patient was re-biopsied 10 days later . This biopsy showed circumferential crescents in 83% of the glomeruli . Treatment with intensive plasma exchange, prednisolone, cyclophosphamide and dipyridamole was accompanied by prompt improvement in renal function . The need to carefully monitor the course in patients with acute post-streptococcal glomerulonephritis is emphasized.

J Appl Physiol, 1987 Nov, 63(5), 2024 - 30
Pulmonary response to group B streptococcal toxin in young lambs; Sandberg K et al.; Marked respiratory distress is seen in severe early onset group B beta-hemolytic streptococcal (GBS) disease in newborn infants . To investigate the pathophysiological effects of a polysaccharide toxin from GBS type III cultures, obtained from an infant who died from this disease, young chronically instrumented, unanesthetized lambs were studied with measurements of lung mechanics, lung volumes, ventilation, hemodynamics, and lung vascular permeability . Intravenously administered GBS toxin resulted in a biphasic response with an early threefold increase in total lung resistance, 40% decrease in dynamic lung compliance, and 30% increase in minute ventilation coinciding with hypoxemia, pulmonary hypertension, and fever . A second phase of the response followed consisting of less prominent changes in these variables as well as increased lung lymph protein clearance compatible with increased vascular permeability . The temporal close relationship between marked leukopenia and increased lung lymph thromboxane B2 concentrations to the simultaneously occurring pulmonary hypertension and changes in lung mechanics suggests that leukocytes and thromboxane A2 may be mediators of these GBS toxin-induced effects.

Am Fam Physician, 1987 Nov, 36(5), 169 - 78
Rapid assay kits for common microbiologic agents; Saglio SD et al.; Commercial rapid assay kits are available to assist in making diagnoses such as gonorrhea, rubella, and chlamydial and Group A streptococcal infections . Most assays contain either antigens to detect antibodies or antibodies to detect the antigens of the specific agents . Methods include latex agglutination, enzyme-linked immunosorbent assay, solid-phase enzyme immunosorbent assay and immunofluorescence . Rapid assay kits are best used with an understanding of their principles, their sensitivity-specificity ranges, their limitations and assets, and their cost and shelf life.

South Med J, 1987 Nov, 80(11), 1436 - 8
Fatal group B streptococcal empyema in an adult; George AL Jr et al.; We have reviewed the literature on group B streptococcal empyema in adults and presented an additional case . During the early antibiotic era, this rare infection was described only in women after parturition . Diabetes mellitus or glucose intolerance was present in our patient and in all of the described cases of nonparturient adults . Mortality from this infection was high . The condition differs from classic beta-hemolytic streptococcal (group A) pneumonia and empyema in its predilection for older, more chronically ill persons and in its more frequent nosocomial occurrence.

Infect Immun, 1987 Nov, 55(11), 2658 - 61
Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier; Lise LD et al.; Successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier . Tetanus toxoid (TT) has been proposed because of its safe and widespread use in humans . Paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier . Indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine made with a streptococcal peptide conjugated to TT . Our present study shows that similar results can be observed in mice preimmunized with TT 1 month before the administration of a conjugate containing TT and a Plasmodium knowlesi peptide . Analysis of the isotypic pattern of the antipeptide response showed that the immunoglobulin G1 (IgG1) subclass and especially the IgG2a and IgG2b subclasses were suppressed . In contrast, when a sporozoite peptide from Plasmodium falciparum was coupled to TT, the total antipeptide antibodies and particularly the IgG1 subclass were enhanced by preimmunization by TT . This increase of antipeptide antibodies was correlated with a greater ability of the sera to neutralize sporozoite infectivity . These results indicate that prior exposure to TT does not systematically impair the antibody response against a peptide administered as a peptide-TT conjugate.

J Immunol, 1987 Oct 15, 139(8), 2702 - 7
Modulation of the murine immune response to streptococcal group A carbohydrate by immunization with monoclonal anti-idiotope; Monafo WJ et al.; Using monoclonal anti-idiotopes with previously defined specificities for the variable (V) domain of HGAC 39, a monoclonal antibody against streptococcal group A carbohydrate (GAC), we have studied the effect of anti-idiotope on an anticarbohydrate immune response . Anti-IdI-3a and anti-IdI-3b are anti-idiotopes which recognize binding site-associated determinants, whereas anti-IdX recognizes a framework-associated determinant on the HGAC 39 V kappa domain . Each of three anti-idiotopes elicited a specific idiotope response, as measured by inhibition radioimmunoassay, in A/J and C57BL/6J mice . A single immunization with conjugated anti-IdI-3a elicited an idiotope(+), GAC-binding(+) response in C57BL/6J and (BALB/c X CBA/N)F1 male mice, but not in A/J or (CBA/N X BALB/c)F1 male, X-linked immunodeficient mice . When C57BL/6J mice immunized initially with anti-idiotope were further treated with group A vaccine, those receiving anti-IdX had the greatest increase in anti-GAC activity . Stimulation of an anticarbohydrate response with anti-idiotope may therefore be enhanced by selecting anti-idiotopes against both binding site- and framework-associated determinants.

J Biol Response Mod, 1987 Oct, 6(5), 499 - 511
Role of in vivo scavenger function of macrophages in priming for endogenous production of tumor necrosis factor; Satoh M et al.; The effects of systemic administrations of immune complex, complement activators, and insoluble particles on endogenous production of tumor necrosis factor (TNF) were investigated in mice . Production of serum TNF was triggered by i.v . injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay . Intravenous injection of IgG-opsonized sheep red blood cells (10(8)/mouse) enhanced OK-432-triggered TNF production significantly . This effect was maximal (about 30-fold enhancement) 1.5 to 3 h after the injection and disappeared within 10 h . Complement activators other than immune complex also possessed this activity . Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6 h after its i.v . injection, its effect lasting for 10 h, and disappearing within 24 h . Heat-aggregated IgG and cobra venom factor also had similar enhancing effects . In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production . The enhancement by latex beads (2 microliters volume of solid/mouse) was maximal (about 60-fold) 3 to 6 h after their i.v . injection, was sustained for at least 20 h, and disappeared within 48 h . Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects . Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.

Arch Dis Child, 1987 Oct, 62(10), 1075 - 6
Post-streptococcal glomerulonephritis in Hong Kong; Leung DT et al.; Of 74 paediatric inpatients with acute glomerulonephritis, 58 (78%) had a raised (greater than 1/200) antistreptolysin O titre . Serum C3 concentration was low in 73, but returned to normal within six weeks . Streptococcal infection remains the commonest cause of acute nephritis in children in Hong Kong, possibly due to overcrowded living conditions.

J Clin Microbiol, 1987 Oct, 25(10), 2006 - 7
Porphyrin test as an alternative to benzidine test for detecting cytochromes in catalase-negative gram-positive cocci; Wong JD; A total of 66 strains of gram-positive cocci, including 21 catalase-negative members of the family Streptococcaceae and strains of Stomatococcus mucilaginosus, were investigated for the ability to produce porphobilinogen and porphyrin from delta-aminolevulinic acid as an alternative to the benzidine test for detecting the presence of cytochromes . Production of porphobilinogen correlated 100% with membership in the family Micrococcaceae.

Infect Immun, 1987 Oct, 55(10), 2456 - 60
Physiology of the potentiation of lethal endotoxin shock by streptococcal pyrogenic exotoxin in rabbits; Murai T et al.; Streptococcal pyrogenic exotoxin (SPE) dramatically potentiates the lethal shock induced by gram-negative bacterial endotoxin . To provide further understanding of the mechanism underlying the potentiating effect, the physiological basis for the toxic synergism of the two toxins was investigated . Pretreatment of rabbits with an intravenous (i.v.) dose (10 micrograms/kg of body weight) of SPE greatly enhanced the endotoxin lethality and reduced the 50% lethal dose to less than 5 micrograms of endotoxin per kg . The SPE pretreatment dose caused severe pathophysiological changes in combination with a small i.v . dose of endotoxin (1 microgram/kg) . These changes included transient hyperglycemia followed by profound hypoglycemia, elevation of the blood lipoperoxide level, and an acute increase in plasma beta-glucuronidase activity . These changes were comparable with those in animals given a large i.v . dose of endotoxin (100 micrograms/kg) alone . An injection of SPE alone did not alter any of the parameters described above . These results suggest that SPE renders rabbits more sensitive to extensive pathophysiologic effects of endotoxin, and the potentiating effect on endotoxin lethality may thus involve a general potentiation of physiologic failures . The SPE pretreatment depressed the vascular clearance of a large dose of endotoxin (100 micrograms/kg) but failed to affect that of a small dose of endotoxin (1 microgram/kg) . The data suggest that the potentiating effect is not readily explained solely on the basis of the decreased clearance of endotoxin.

J Fam Pract, 1987 Oct, 25(4), 347 - 53
Selective testing for streptococcal pharyngitis in adults; DeNeef P; Some physicians test for group A streptococcal pharyngitis in all patients who have a sore throat, while others use a variety of clinical strategies to select patients to be tested . Using published data on the accuracy of a clinical decision rule, this benefit-cost analysis compares the calculated outcomes of 21 different management strategies applied to 1,000 hypothetical adults with pharyngitis . Strategies that best accomplish one physician's treatment goals may perform poorly when evaluated in a different practice setting or using different goals . The best strategies are identified for different treatment objectives and for different assumptions about the benefits of treatment so each physician can choose a strategy consistent with his or her preferences.

J Med Virol, 1987 Oct, 23(2), 123 - 33
Cytomegalovirus infections in adult T-cell leukemia patients; Eizuru Y et al.; Cytomegalovirus (CMV) infection frequently occurred in patients with malignant lymphoma of T-cell origin, especially with adult T-cell leukemia (ATL) . This was evidenced by histopathological examination at autopsy, isolation of CMV, and detection of CMV antibodies that indicate recent or active infection . Cellular immune response was suppressed in most ATL patients when examined by skin hypersensitivity reaction to purified protein derivatives (PPD), streptococcal antigens (SuPs), and phytohaemoagglutinin (PHA) . None of the CMV-positive patients reacted to them . Thus, the presence of tumor cells of T-cell origin and the absence of skin hypersensitivity reaction seem to be risk factors for CMV infection . Each CMV isolate exhibited unique DNA fingerprints, suggesting that cross-infection of CMV did not occur among the ATL patients on the same ward.

Gan To Kagaku Ryoho, 1987 Sep, 14(9), 2710 - 5
{Immunobiological studies of interferon-alpha A/D in comparison with a streptococcal preparation, OK-432}; Mizushima Y et al.; In order to clarify the characteristics of interferon-alpha A/D (IFN-alpha) as a biological response modifier (BRM), several immunobiological activities were compared with OK-432 . 1) Both IFN-alpha and OK-432 inhibited the multiplication of Meth-A cells in vitro . 2) IFN-alpha (2 X 10(5) IU, ip) augmented the NK activity of peritoneal exudate cells (PEC) and spleen cells, and the peak of NK activity was observed 1 day after injection . OK-432 (1 KE, ip) augmented the NK activity of PEC, but not of spleen cells, and the peak was 3 days after . 3) Macrophage activating activity was more potent with OK-432 (1 KE) than IFN-alpha (2 X 10(5) IU) . 4) Induction of CTL against alloantigens was augmented by IFN-alpha and OK-432 . 5) By the combination of IFN-alpha with OK-432, a synergistic antitumor effect was obtained against Meth-A ascites tumor . Immunobiological effects of IFN-alpha seemed to be somewhat different from those of OK-432 . Therefore, the combination of the two agents might cause a synergistic antitumor effect.

Pediatrics, 1987 Sep, 80(3), 371 - 4
Acute rheumatic fever in western Pennsylvania and the tristate area; Wald ER et al.; Acute rheumatic fever is reported to have declined and perhaps be vanishing . Prompted by the occurrence of 17 cases of acute rheumatic fever in an 18-month period in 1985 and 1986, we reviewed the records of 243 children with acute rheumatic fever who were cared for at Children's Hospital of Pittsburgh or Mercy Hospital between 1965 and 1986 . Acute rheumatic fever was diagnosed using the modified Jones criteria and cases were classified by major criteria as arthritis, arthritis and carditis, carditis alone, carditis and chorea, chorea alone, and arthritis and chorea . Among the 17 recent patients, 59% had carditis, 30% had chorea, and 24% had arthritis alone . The proportion of children who had particular major manifestations was similar in the last two decades and in 1985 to 1986 . The recent children with acute rheumatic fever ranged in age from 6 to 13 years with a mean and median age of 10 years . There were 16 white children and one Asian child . Only four children lived in an urban setting . When demographic features of the children were contrasted with those in the previous two decades, a decrease in the proportion of children who lived in urban areas and who were black was noted . Four children had a history of preceding sore throat but only three sought medical care; nine children had no memorable illness and four had either a nonrespiratory illness or a respiratory infection without sore throat . This resurgence of rheumatic fever serves as a reminder that a diligent approach to the diagnosis and therapy of streptococcal infections remains essential.

Tokai J Exp Clin Med, 1987 Sep, 12(3), 159 - 65
Effects of oral administration of streptococcal preparation OK-432 on thoracic duct lymphocytes; Hanaue H et al.; One KE of streptococcal preparation OK-432 (PIC) was given orally to 6-week old male Wistar-Imamichi rats twice weekly, and control animals received comparable volumes of saline alone . Samples of thoracic duct lymph and posterior vena caval blood were collected prior to and 4 and 8 weeks following PIC . The T cell count of thoracic duct lymphocytes was about three times greater than that of venous blood specimens, and increased significantly in animals following PIC . Controls showed only a slight increase followed by a decrease, so that by 8 weeks of treatment with PIC, the thoracic duct T cell count revealed a significantly greater number in the PIC group than in the controls . In addition, after 8 weeks the per cent T cell subpopulation in thoracic duct lymph increased significantly in the treated group, but it declined in the control group . Concerning T cell subsets in thoracic duct lymphocytes, the percentage of suppressor/cytotoxic T cells showed a significant elevation in the control group after 4 weeks compared with the treated group . No other blood or lymph variables reached statistical significance in this respect.

Q J Med, 1987 Sep, 64(245), 729 - 37
Renal disease in adult Indians: a clinicopathological study of 2,827 patients; Date A et al.; Nephrotic syndrome was the commonest clinical presentation among 2827 consecutive adult Indian patients from whom adequate kidney biopsies were obtained for suspected renal disease . In 83 per cent of cases the nephrotic syndrome was due to minimal change disease, focal segmental glomerulosclerosis, mesangiocapillary glomerulonephritis, membranous usually secondary to tuberculosis or leprosy, was present in only 34 patients . Acute nephritis, the next most frequent clinical presentation, was due to diffuse endocapillary proliferative, crescentic or mesangial proliferative glomerulonephritis in 88 per cent of cases, almost half of whom had elevated serum streptococcal antibody titres . Eosinophilia showed a highly significant association with diffuse endocapillary proliferative and mesangiocapillary glomerulonephritis . Idiopathic IgA nephropathy was present in only 10, and antiglomerular basement membrane antibody disease in only one, of the 238 patients whose biopsies were studied by immunofluorescence . Complications of pregnancy accounted for 70 per cent of cases of cortical necrosis . Acute gastroenteritis, septicaemia, abortions, snake bite and allopathic and indigenous medicines were important causes of acute tubular necrosis.

Vet Surg, 1987 Sep-Oct, 16(5), 358 - 61
Preservation of skin by refrigeration for autogenous grafting in the horse; Schumacher J et al.; Eighteen stored split thickness meshed skin grafts were applied to surgically created lesions on the metacarpal and metatarsal regions of six horses . Donor skin was harvested from the sternal region, meshed and stored at 4 degrees C in a cell culture medium containing 10% serum . Stored grafts were applied to the wounds at 1, 2, and 3 week intervals . Acceptance of the grafts stored for 1 week was generally poor (1 of 6 grafts), whereas that of the 2 and 3 week old grafts was generally excellent (10 of 12 grafts) . Poor acceptance of the 1 week old grafts was attributed to streptococcal infection of the recipient wounds . Using the storage medium and grafting technique described, excellent acceptance can be expected after graft storage of up to 3 weeks.

Diagn Microbiol Infect Dis, 1987 Sep, 8(1), 25 - 30
Evaluation of a new latex agglutination test for detection of streptococcal antibodies; Heath-Fracica LA et al.; A liposome-enhanced latex agglutination test (Leapstrep, Cooper Biomedical, Inc., Malvern, PA) was evaluated for its efficacy as a screening test for antistreptolysin O (ASO) and antideoxyribonuclease B (ADNB) antibodies . A total of 179 sera were tested by both Leapstrep and reference ASO and ADNB test methods . The Leapstrep test had a sensitivity of 77% and a specificity of 69% for ASO antibodies when compared to a microtiter adaptation of the Todd-Hewitt ASO tube test . It had a sensitivity of 76% and 75% specificity for ADNB antibodies as compared to the ADNB microtiter enzyme neutralization test . The overall sensitivity of Leapstrep for detecting ASO and/or ADNB antibodies was 73% . The Leapstrep test failed to detect elevated levels of ASO and/or ADNB antibodies in eight patients with streptococcal infections or poststreptococcal sequelae . The Leapstrep test appears to have insufficient sensitivity to be recommended as a screening test for streptococcal antibodies.

J Comp Pathol, 1987 Sep, 97(5), 567 - 74
A study of experimental endocarditis in pigs; Dewar HA et al.; In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described . If untreated, the disease runs a protracted course, similar to that in man . Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen . The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions . In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets . It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.

Monatsschr Kinderheilkd, 1987 Sep, 135(9), 642 - 5
{B streptococcal infections in the neonatal period and infancy}; Huckel D et al.; From January 1975 to March 1985 37 newborns and infants with B streptococcal infections were treated in the Pediatric Hospital of the Karl Marx University in Leipzig . The percentage of B streptococcal infections of all neonatal bacterial infections rose in this time from 6.9% to 15.7% . There were 23 early onset type infections and 14 late infections; 12 of the 37 infants died . Septicemia and meningitis were the most important clinical features . The time of beginning of the clinical symptoms in the postnatal period and the results of serotyping suggest a connatal infection in most cases.

Arch Mal Coeur Vaiss, 1987 Sep, 80(10), 1541 - 5
{Endocarditis of the pulmonary valve complicating interventricular communication . Echocardiographic detection}; Castillon G et al.; A 29-year old woman known to have Roger's disease was hospitalized for streptococcal endocarditis with pulmonary embolism and cerebral vascular accident . Echocardiography demonstrated vegetations on the pulmonary valve, and this was confirmed at surgery . Pulmonary valve endocarditis is a rare lesion sometimes occurring as a complication of congenital malformations with ventricular septal defect . Its prognosis is governed not so much by bacterial resistance or haemodynamic repercussions as by the risk of septic pulmonary embolism or systemic embolism . Prophylaxis is essential to avoid this dangerous complication.

J Antimicrob Chemother, 1987 Sep, 20 Suppl A, 119 - 42
Antibiotic prophylaxis of infective endocarditis in the United Kingdom and Europe; Shanson DC; In the U.K . and Europe there are now simple oral chemoprophylaxis recommendations which are likely to be widely complied with by patients, dental and medical practitioners . The main recommendations of the 1982 BSAC Endocarditis Working Party report and the 1985 report of the European Society of Cardiology are similar and involve the administration of a single 3 g dose of oral amoxycillin 1 h before the procedure, or two doses of erythromycin for patients allergic to penicillin . Amoxycillin is more suitable than penicillin V for single dose chemoprophylaxis because of its higher and more persistent serum bactericidal concentrations and lower serum protein binding compared with penicillin V . Controversies about the precautions needed for patients with prosthetic valves are discussed . Erythromycin is associated with more frequent gastrointestinal side-effects and less reliable absorption than amoxycillin . None the less, recent studies suggest that the 1.5 g loading dose of oral erythromycin stearate has an 'immediate' effect in reducing post-extraction streptococcal bacteraemia and appears to be reasonably well tolerated by most adults . In 1986 a few changes have been suggested by the BSAC Endocarditis Working Party and concern the use of alternative oral amoxycillin regimens for patients requiring general anaesthesia, the giving of two administrations of amoxycillin within one month when prophylaxis is required for repeated dental procedures and the slower infusion of intravenous vancomycin to reduce the incidence of adverse reactions . A register of cases of failed chemoprophylaxis' has been started in the U.K . and also in Europe.

Clin Pediatr (Phila), 1987 Sep, 26(9), 453 - 8
A multicenter, randomized, single-blind evaluation of cefuroxime axetil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis; Pichichero ME et al.; Ninety-three children from four pediatric practices, with clinical and bacteriologic evidence of acute Group A beta-hemolytic streptococcal pharyngitis (GABHS) randomly received cefuroxime axetil (60 cases) or phenoxymethyl penicillin (33 cases) . Cefuroxime axetil was given twice daily (125 mg) . Phenoxymethyl penicillin was given three times daily (250 mg) . The treatment groups were similar . Throat cultures were routine 2 to 7 days after the start of therapy and 2 days and 14 days after the end of therapy . The bacterial cure rates were 85 percent (51/60) for cefuroxime axetil, and 88 percent (29/33) for phenoxymethyl penicillin treated patients . Clinical results were comparable in both treatment groups . It was concluded that cefuroxime axetil given twice daily is as effective as phenoxymethyl penicillin given three times daily in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS.

Gan To Kagaku Ryoho, 1987 Aug, 14(8), 2464 - 8
{The management of malignant ascites with a streptococcal preparation, OK-432: relation between the clinical effect and auto-tumor cell killing activity by OK-432-induced ascites-derived lymphocytes}; Katano M et al.; Twelve patients with malignant ascites caused by gastro-intestinal cancer were treated by intraperitoneal administration of OK-432 . Tumor cells from these patients were separated from ascitic fluid and cultured in vitro before OK-432 therapy . OK-432 was given intraperitoneally one to two times a week at doses ranging from 5 to 20 KE suspended in saline . Mononuclear lymphocytes were collected from the fluid at various intervals throughout the therapy . The effect of ascites-derived lymphocytes on ascites-derived autologous tumor cell growth was studied in vitro using microplate assay . Nine (responders) of 12 patients showed complete disappearance or significant reduction of ascitic fluid . Ascites-derived lymphocytes slightly inhibited autologous tumor cell growth only in one case before OK-432 therapy . Lymphocytes collected from ascites after OK-432 injection significantly inhibited auto-tumor cell growth in all of 9 responders . In 3 non-responders, however, auto-tumor cell growth inhibition was found only in one case . Interestingly, lymphocytes from non-responders significantly inhibited the growth of tumor cells taken from responders . Conversely, lymphocytes from responders did not inhibit non-responder-derived tumor cell growth . These findings imply that auto-tumor killing by OK-432-induced lymphocytes may depend more on the condition of the tumor cells than on the condition of the lymphocytes, and that the measurement of auto-tumor killing activity by ascites-derived lymphocytes may be useful as an indicator in OK-432 therapy.

Biull Eksp Biol Med, 1987 Aug, 104(8), 210 - 2
{Preparation of monoclonal antibodies to nuclear DNA of mammalian cells by immunization with group A streptococcal polysaccharide conjugated with synthetic polyelectrolytes}; Drobyshevskaia EI et al.; Monoclonal antibodies (MAb) were obtained by hybridization of spleen cells from BALB/c mice immunized with streptococcal group A polysaccharide (A-PS) conjugated with synthetic polyelectrolytes (PEL) . These MAb reacted with nuclei from human and mouse cells . MAb reacting with nuclei were obtained after prolonged immunization with conjugates and were not formed by hybridization of spleen cells from non-immunized mice or by the immunization with PEL . The investigation of Mab (B1/2 and A5/2) reacting with nuclei has shown that these Mab are directed against DNA and do not react with other tissue substances . No cross-reactions of Mab with A-PS used for immunization have been revealed . Mab B1/2 and A5/2 belong to autoantibodies.

J Pediatr, 1987 Aug, 111(2), 176 - 9
Outbreak of acute rheumatic fever in northeast Ohio; Congeni B et al.; An outbreak of acute rheumatic fever in 23 patients was seen in northeastern Ohio in 1986, with polyarthritis (78%) and carditis (30%) the major manifestations . Results of a questionnaire completed by the parents of all 23 patients indicated that they were generally nonindigent, with good access to medical care, and from a nonurban setting . Records of inpatients with acute rheumatic fever were reviewed for the 10 years prior to 1986 . The clinical manifestations in inpatients from 1976 to 1985 were not significantly different from those of inpatients seen during 1986 . Similar outbreaks have been reported elsewhere, and physicians should be aware of a possible resurgence of classic acute rheumatic fever and ensure compliance with an adequate course of therapy for patients with streptococcal pharyngitis.

Eur J Clin Microbiol, 1987 Aug, 6(4), 426 - 7
Group B streptococcal endocarditis in Down's syndrome; Billheden J et al.; A 36 year old man with Down's syndrome developed group B streptococcal (subtype Ia) mitral endocarditis, which was complicated by widespread abscess formation . He was given antibiotics for one year, and no surgery was performed . Despite the underlying condition, the IgM response and the production of specific antibodies against the bacteria were normal.

Mol Gen Genet, 1987 Aug, 209(1), 15 - 20
Nucleotide sequence of the staphylococcal enterotoxin C1 gene and relatedness to other pyrogenic toxins; Bohach GA et al.; The nucleotide sequence for the structural gene entC1 encoding staphylococcal enterotoxin C1 was determined . The gene contained 801 bp and coded for a protein of 266 amino acids . Of these, 27 comprised the signal peptide . Cleavage of the signal peptide resulted in a mature protein with 239 amino acids and a calculated molecular weight of 27,496 . The nucleotide sequence of entC1 shared considerable homology (74% and 59%, respectively) with genes encoding enterotoxin B and streptococcal pyrogenic exotoxin A . A similar degree of amino acid homology was observed after alignment of the respective proteins . Thus, certain regions of these three toxin molecules possess structural similarities that may be responsible for shared biological properties.

Nucleic Acids Res, 1987 Jul 24, 15(14), 5561 - 80
Initiation signals for the conversion of single stranded to double stranded DNA forms in the streptococcal plasmid pLS1; del Solar GH et al.; We have characterized a region in the streptococcal plasmid pLS1 located between nucleotides 4103 and 4218 which is a signal involved in the conversion of single stranded intermediates of replication to double stranded plasmid forms . This region has a large axis of dyad symmetry resulting in the formation of a secondary structure as revealed by the location of endonuclease S1-cleavage sites in supercoiled covalently closed circular pLS1 DNA . Deletions affecting this region caused a fivefold reduction in plasmid copy number, plasmid instability and the accumulation of single-stranded DNA intermediates . The conversion signal of pLS1 has homologues in other staphylococcal plasmids, sharing a consensus sequence located in the loop of the signal . Computer assisted analysis showed that the signal detected in pLS1 has a high degree of homology with the complementary strand origin of the Escherichia coli single stranded bacteriophages phi X174 and M13.

Gan To Kagaku Ryoho, 1987 Jul, 14(7), 2378 - 80
{Partial response of lung metastases from a renal cancer treated with endogenous tumor necrosis factor}; Kato M et al.; The strong tumor-selective cytocidal action of tumor necrosis factor (TNF) has been observed in vitro and in vivo . Sato et al . have reported that it was possible to induce a primed state of TNF triggering by injection of purified protein derivative (PPD) even a long time after BCG sensitization, suggesting that this treatment could be applied to human patients . In the present study, we achieved a partial response of a metastatic lesion in a patient with renal cancer by the induction of endogenous TNF by PPD and OK-432 (a streptococcal preparation) . This study suggested the possible application of this therapy to also patients with malignant tumor which are highly resistant to any conventional antitumor therapy.

Pediatr Infect Dis J, 1987 Jul, 6(7), 635 - 43
Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin; Pichichero ME et al.; One hundred forty-two children with presumed Group A beta-hemolytic streptococcal (GABHS) pharyngitis were enrolled in a randomized double blind prospective study comparing the consequences of immediate penicillin treatment with treatment delayed for 48 to 56 hours . One hundred fourteen of the enrolled patients were culture-positive . An adverse impact of early antibiotic therapy was noted; the incidence of subsequent infections with GABHS was significantly greater in those treated at the initial office visit with penicillin . In the month following documented evaluation of GABHS, a recurrence occurred 2 times more frequently in those treated with penicillin immediately compared with those for whom treatment was delayed 48 to 56 hours . Late recurrences (beyond 1 month but in the same streptococcal season) occurred 8 times more frequently (P less than 0.035) . Delay in penicillin treatment did not increase GABHS intrafamilial spread . Symptoms of both groups were assessed for 2 days following the initiation of treatment . Both placebo-treated and penicillin-treated groups used aspirin or acetaminophen ad libitum . Penicillin was shown to reduce fever and relieve sore throat, dysphagia, headache, abdominal pain, lethargy and anorexia significantly beyond that achieved with aspirin or acetaminophen alone . Penicillin had no effect on culture-negative cases.

J Gen Intern Med, 1987 Jul-Aug, 2(4), 244 - 50
What a difference a day makes: a decision analysis of adult streptococcal pharyngitis; Hillner BE et al.; With the availability of group A beta-hemolytic streptococcal (GABHS) antigen detection tests, the management of adult pharyngitis is being reassessed . A decision analytic model was developed which considered four strategies: immediate treatment, no treatment, performing a rapid antigen test, or obtaining a bacterial culture . Patient outcomes were expressed in "well" days, which were reduced by the "sick" days associated with adverse reactions to treatment or complications of GABHS infection . When immediate test results are available, testing is the optimal strategy for probabilities of GABHS between 1 and 49 per cent . This range includes almost all patients, using probability estimates based on clinical criteria . The absolute benefit of testing was 0.1 days . The major advantage of a rapid test is the avoidance of penicillin reactions . Variations in the symptomatic benefits of treatment had minimal effects on the analysis . The analysis supports the use of an antigen test for adult patients with pharyngitis.

Jpn J Cancer Res, 1987 Jul, 78(7), 737 - 47
Chemoimmunotherapy of L1210 leukemia with adriamycin, cyclophosphamide, and OK-432, and their effects on the generation of antitumor immunity; Ujiie T; The synergistic effects of combined chemotherapy with adriamycin (ADR) and cyclophosphamide (CY) on L1210 tumors in mice were potentiated by use of a streptococcal preparation, OK-432, in a time- and dose-dependent way . Some mice were cured by treatment with the three agents, and resisted a later challenge by L1210 but not P388 leukemia cells . This immunity was blocked by administration of antimacrophage agents or CY . The effects of OK-432 were also studied with mice sensitized by L1210 cells attenuated with mitomycin C . OK-432 potentiated syngeneic and semi-syngeneic transplantation resistance in vivo and augmented primary and secondary cytotoxicity mediated by spleen cells in vitro . In vivo administration of ADR and CY together enhanced in vivo tumor transplantation resistance and in vitro cytotoxicity was blocked, but this inhibition was reversed by injection of OK-432 . The results suggested that OK-432 acted by increasing the activity of cytotoxic spleen cells against L1210 cells, which are fast-growing and poorly immunogenic, and that this cytotoxicity killed tumor cells that survived the chemotherapy.

Biochemistry, 1987 Jun 16, 26(12), 3524 - 30
Dihydroxypropylation of amino groups of proteins: use of glyceraldehyde as a reversible agent for reductive alkylation; Acharya AS et al.; The mode of derivatization of amino groups of proteins by glyceraldehyde, an aldotriose, depends on the presence or absence of reducing agent . In the presence of sodium cyanoborohydride, the Schiff base adducts of the aldehyde with the amino groups are reduced, and dihydroxypropylation of amino groups takes place (reductive mode) . The reductively glycated lysine residue, N epsilon-(2,3-dihydroxypropyl)lysine, is a substituted alpha-amino alcohol . This alpha-amino alcoholic function of the derivatized lysine should be susceptible to periodate oxidation, and this oxidation is anticipated to result in the regeneration of the lysine residue . This aspect has been now investigated . Indeed, on mild periodate oxidation (15 mM periodate, 15 min at room temperature) of dihydroxypropylated ribonuclease A, nearly 95% of its N epsilon-(2,3-dihydroxypropyl)lysine residues were regenerated to lysine residues . The removal of the dihydroxypropyl groups by periodate oxidation could be accomplished within a wide pH range with little variation in the recovery of lysines . The possible usefulness of this reversible chemical modification procedure in the primary structural studies of proteins was investigated with a tryptic peptide of dihydroxypropylated streptococcal M5 protein, namely, DHP-T4 . This 12-residue tryptic peptide contains one internal N epsilon-(dihydroxypropyl)lysine . The dihydroxypropylated peptide released most of its dihydroxypropyl groups on mild periodate oxidation . Redigestion of the periodate-treated peptide with trypsin generated the two expected peptides, demonstrating the generation of a trypsin-susceptible site . Reductive dihydroxypropylation of amino groups of RNase A resulted in the loss of its enzyme activity, the extent of inactivation increasing with the concentration of the glyceraldehyde used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer, 1987 Jun 15, 59(12), 2027 - 30
The role of adjunctive immunotherapy in superficial bladder cancer; Fujita K; Seventy-eight patients with superficial bladder cancer were entered into a randomized study . A streptococcal preparation, OK-432, was injected into bladder cancers before transurethral resection and instilled into the bladder for 6 months after resection to reduce the recurrence . The control group were only transurethrally resected, as usual . The recurrence rate for patients with primary disease was 3.6 in 100 months for the OK-432 group and 9.1 in 100 months for the control group (P less than 0.05) . In the control group, multiple, large, sessile, and high-grade tumors had high recurrence rates . But in the OK-432 group, overall recurrence rates were low in both high-risk and low-risk patients . Supplementary immunotherapy is especially effective and is recommended in high-risk patients.

Jpn J Exp Med, 1987 Jun, 57(3), 153 - 61
Augmentation by OK-432 of generation of culture-induced killer cells; Ujiie T; A streptococcal preparation, OK-432, injected intraperitoneally, potentiated rejection of L1210 leukemic cells in semiallogeneic BALB/c mice . This increased rejection was further enhanced by a transfer of peritoneal exudate T (PET) cells, but not of spleen cells . Spleen cells incubated in vitro for 3 or more days were as effective as PET cells in stimulating tumor rejection, and were cytotoxic in vitro as tested by a 4-hr 51Cr-release assay . This cytotoxicity was closely related to the OK-432-mediated augmentation of L1210 rejection in vivo . In vitro treatment with OK-432 of spleen cells from intact mice generated nonspecific cytotoxic cells . The cells were nonadherent to plastic, radioresistant, and of Thy-1+, Lyt-1,2-, and asialoGM1+ phenotypes, and were tentatively named OK-432-induced killer (OIK) cells . They were cytotoxic to tumor cells resistant to natural killer (NK) cells, and different from NK cells or lymphokine-activated killer cells . For their generation, macromolecular synthesis and participation of plastic-adherent cells (probably macrophages) were needed . The in vivo growth of L1210 leukemic cells could not be inhibited by simultaneous administration of PET cells primed in vivo with OK-432, of spleen cells primed in vivo with OK-432 and then cultured, or of spleen cells primed in vitro with OK-432 and then cultured (OIK cells) . However, a prophylactic adoptive transfer of these cells was effective in immunocompetent mice as well as in athymic nu/nu mice, but not in mice irradiated with 400 rad . The in vivo activity was attributable mainly to Lyt-1+, -2- cells radioresistant and adherent to nylon wool, which were probably amplifier/helper T cells.

Hinyokika Kiyo, 1987 Jun, 33(6), 832 - 7
{Effect of selective intra-arterial infusion of OK-432 against renal cell cancers}; Fujioka T et al.; In 8 cases of operable renal cancer, selective intraarterial infusion of the streptococcal preparation, OK-432 was performed and its cytocidal effects on the surgical specimens, which were removed on the 8th day after infusion, were investigated histopathologically with immunological parameters of the peripheral blood . The histopathological study revealed a high grade of sinus histiocytosis of the renal pedicle lymph nodes, but the anti-tumor effect on renal tumors was not so marked in any of the 8 cases . OK-Ia-positive lymphoid cells of peripheral blood were increased significantly and Con-A stimulation index of blastogenesis was lowered without any change in the PHA stimulation index after the OK-432 infusion . No serious complications of the selective intraarterial infusion were experienced except for high fever (less than 38 degrees C) . In conclusion, OK-432 selective intraarterial infusion was an effective method for improving regional and systemic immunoactivity, but the cytocidal effect against tumor cells could not be confirmed histopathologically.

J Trop Med Hyg, 1987 Jun, 90(3), 111 - 5
Tests for streptolysin-O antibodies in health and suspected streptococcal infections in Saudi Arabia; Hossain A; 'Upper limits of normal' antistreptolysin-O (ASO) titres were determined in various age groups in Saudi Arabia using the conventional haemolysin and the newer, passive agglutination (Blue-ASO) tests . The upper limit of normal values were found to vary with age, being the highest (166 Todd units or 1:320) among the school age children . Serum samples from 744 patients with various clinical manifestations associated with streptococcal infections such as rheumatic fever, glomerulonephritis, tonsillitis, rheumatoid arthritis and polyarthritis were tested by both methods, with the geometric mean titres (GMT) being determined in each age group . In case of school age children with suspected rheumatic fever, and found positive by the tests, a GMT of 458 Todd units (1:1080) was obtained--much higher than the ASO levels detected in positives with glomerulonephritis or tonsillitis . Apart from its relative simplicity, rapidity and ease of performance, the Blue-ASO test was able to detect positivity in 15% of sera from patients of various age groups with suspected rheumatic fever, polyarthritis and tonsillitis who exhibited insignificant levels of ASO by the haemolysin test.

Clin Immunol Immunopathol, 1987 Jun, 43(3), 314 - 24
The proliferative response of human peripheral blood lymphocytes to group A streptococcal vaccine; Morell A et al.; The proliferative response of human peripheral blood mononuclear cells to group A streptococcal vaccine (strain J17A4) was assessed by measurement of {3H}thymidine incorporation . This was maximal after 7 days in cultures containing 1 X 10(5) lymphocytes . Cells from 33 out of 38 adult donors (87%) yielded stimulation indices between 2.0 and 81 . Responding cells were predominantly of the OKT4+, Ia+, Tac+ phenotype expressed by activated helper T lymphocytes . In contrast, no response was observed in 10 out of 12 samples of cord blood lymphocytes . Addition of conventional rabbit or monoclonal murine anti-Ia (HLA-DR) antibodies to the culture medium abrogated the vaccine-induced proliferative response . Frequencies of responding cells estimated by limiting dilution analysis were between 1 in 2370 and 1 in 4580 lymphocytes . The results suggest that lymphocyte stimulations induced with streptococcal group A vaccine represented an in vitro anamnestic cellular immune response.

Infect Immun, 1987 Jun, 55(6), 1526 - 8
Elimination of group A streptococcal cell walls from mammalian tissues; Gilbart J et al.; The precise levels in mammalian tissues of rhamnose (a constituent of the group-specific polysaccharide) and muramic acid (a constituent of peptidoglycan) at various times after systemic administration of streptococcal cell walls were noted for the first time . The extreme resistance of the streptococcal cell wall to degradation by mammalian enzymes can now be clearly appreciated . The results help explain the chronic nature of certain inflammatory diseases elicited by streptococcal cell wall debris.

Jpn J Exp Med, 1987 Jun, 57(3), 183 - 8
Enhanced generation of OK-432-induced killer cells by interleukin 2; Ujiie T; Spleen cells of untreated mice became nonspecifically cytotoxic after cultivation in the presence of a streptococcal preparation, OK-432, for 3 or more days . The cytotoxic cells, named OK-432-induced killer (OIK) cells, injured a variety of target cells including syngeneic EL-4 cells resistant to natural killer (NK) cells, but not NK-susceptible YAC-1 cells . C57BL/6 splenic cells cultured for 5 days in the presence of both OK-432 and interleukin 2 (IL-2) were highly cytotoxic to both EL-4 and YAC-1 cells, and had Thy-1+, Lyt-1,2-, and asialogGM1+ phenotypes, which were identical with those of OIK cells . A test for competitive inhibition with cold target cells and fractionation by centrifugation onto discontinuous density gradients of Percoll showed that cytotoxic cells generated by OK-432 plus IL-2 comprised at least two populations; the cells in the first population were cytotoxic to EL-4 cells but not to YAC-1 cells, and were smaller in size than those in the second population, which were cytotoxic to YAC-1 cells and had NK morphology . Therefore, generation of OIK cells was augmented by IL-2.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 903 - 6
Randomized, single-blind evaluation of cefadroxil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis; Pichichero ME et al.; A total of 150 children from two pediatric practices with clinical and bacteriologic evidence of acute group A beta-hemolytic streptococcal (GABHS) pharyngitis randomly received cefadroxil monohydrate (75 children) or phenoxymethyl penicillin (75 children) . Cefadroxil was given once daily, while penicillin was given three times daily . The treatment groups were similar in age, sex, race, illness severity, and acute GABHS symptomatology . Throat cultures were routine 3 to 5 days after the start of therapy and 2 and 14 days after the end of therapy . The bacterial cure rates were 90% (62 of 69) for cefadroxil-treated patients and 76% (52 of 68) for penicillin-treated patients . This difference was significant (P less than 0.04) . The clinical response was satisfactory in 91% of cefadroxil-treated patients and 89% of penicillin-treated patients . We conclude that once-daily cefadroxil is at least as effective as three-times-daily penicillin in producing bacteriologic eradication and clinical symptomatic improvement in children with GABHS pharyngitis.

Pediatr Res, 1987 Jun, 21(6), 517 - 23
Effect of group B streptococcal type-specific antigen on polymorphonuclear leukocyte function and polymorphonuclear leukocyte-endothelial cell interaction; McFall TL et al.; Neonatal group B streptococcal pneumonia is a severe disease, often resulting in death . Autopsy findings resemble those of hyaline membrane disease . Numerous organisms may be seen in the alveoli, but few polymorphonuclear leukocytes (PMNs) are found in the areas of bacterial invasion . Aggregated PMNs are often found, however, in the pulmonary capillaries . This study was designed to explore the effect of the group B streptococcal (GBS) type III antigen on PMN chemotaxis and PMN-endothelial cell interactions . Human PMNs were isolated and pretreated with 0.25 to 4 micrograms/ml of GBS type III antigen prior to determining their chemotactic response to the chemoattractants formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, platelet-activating factor, and leukotriene B4 . The GBS antigen caused a concentration-dependent inhibition of formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, and platelet-activating factor-mediated chemotaxis (% inhibition of 38.1 +/- 4.0, 55.5 +/- 3.3, 46.7 +/- 9.7%, respectively; p less than 0.01) . Leukotriene B4-mediated chemotaxis was not significantly depressed (21.2% +/- 7.7 inhibition; NSD) . Group B streptococcal antigen also inhibited formyl-methionyl-leucyl-phenylalanine-induced PMN adherence to endothelial cells in a concentration-dependent fashion when incubations were performed in the absence of serum . In contrast, incubation of GBS type III antigen with serum deficient in antibody to GBS resulted in a marked enhancement of PMN attachment to human endothelial cells . No significant enhancement of adherence was sen with the antigen in the presence of serum containing GBS type III antibody . These data suggest that the GBS type III antigen by itself may inhibit the influx of PMNs into the local site of infection in the alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Pathol Microbiol Immunol Scand {B}, 1987 Jun, 95(3), 203 - 10
Isolation of a specific albumin receptor from a group G streptococcal strain; Wideback K et al.; The albumin receptor, a bacterial cell-wall protein with affinity for albumin, has been isolated from a bovine group G streptococcal strain (DG-8) . Bacterial surface proteins were solubilized by boiling in 0.6M HCl for 5 min . The albumin receptor was isolated by sequential use of ion-exchange chromatography on DEAE-Sephadex A-50 and affinity chromatography on albumin coupled Sepharose 4B . The presence of albumin receptor in various pools and fractions during the isolation was followed by their ability to inhibit the binding of radiolabelled albumin to DG-8 bacteria . A highly purified albumin receptor was obtained according to Western blot analysis . The albumin binding band obtained showed a molecular weight of about 30,000 . The purified receptor did not possess any IgG binding capacity . 50 micrograms albumin receptor was prepared from each gram of bacteria.

Biull Eksp Biol Med, 1987 Jun, 103(6), 707 - 10
{Antibodies reacting with thymus and skin epithelium and antibodies to cell nuclei in immunization with streptococcal group A polysaccharide conjugated with synthetic polyelectrolytes}; Ryzhikova EV et al.; The antibodies to streptococcal group A polysaccharide (A-PS) have been obtained upon immunization of BALB/c mice with A-PS conjugated with synthetic polyelectrolytes (PEL) . Prolonged immunization in the majority of cases revealed antibodies to cross-reactive determinant of A-PS reacting with human and mouse epithelium of the thymus and basal skin layer . These antibodies belong to autoantibodies . Later on, after the beginning of immunization some animals produced antibodies reacting with cellular nuclei . The formation of autoantibodies to nuclei is not related to crossreactions with A-PS, because A-PS do not inhibit these reactions . No antibodies reacting with the epithelial cells or with cellular nuclei have been observed upon immunization with A-PS in Freund adjuvant or with PEL alone . The production of autoantibodies to cellular nuclei is probably a result of immunoregulatory disorders associated with the damage of thymus epithelium by autoantibodies during immunization with A-PS conjugated with PEL.

J Pediatr, 1987 May, 110(5), 783 - 7
Efficacy of benzathine penicillin G in group A streptococcal pharyngitis: reevaluation; Feldman S et al.; The rate of streptococcal eradication after intramuscular administration of benzathine penicillin G in 66 children with acute group A streptococcal pharyngitis was determined and possible reasons for treatment failure explored . Bacteriologic treatment failure, defined as isolation of the same serotype at 3- or 6-weeks follow-up, occurred in eight (12%) patients . The treatment failure rate was 21% in those with immunologically significant infection, versus 8% in those without antibody rises (P greater than 0.1) . All group A beta-hemolytic streptococcal (GABS) strains isolated from patients with treatment failure, both before and after benzathine penicillin G therapy, were exquisitely susceptible to penicillin G (minimum inhibitory concentration less than or equal to 0.02 microgram/mL), and none showed evidence of tolerance (minimum bactericidal concentration less than or equal to 0.04 microgram/mL) . Thus, we found GABS eradication rates to exceed 10% in children given benzathine penicillin G . The failure rate did not appear to be related to enrichment of the patient population with a high proportion of asymptomatic carriers nor to the presence of penicillin-tolerant GABS.

Acta Paediatr Scand, 1987 May, 76(3), 470 - 3
Neonatal group B streptococcal septicaemia in a developing country; Macfarlane DE; During a 3-year study at the neonatal intensive care unit, University Hospital of the West Indies, the incidence of group B streptococcal (GBS) septicaemia was 13.6/1,000 admissions and 1.4/1,000 live births . GBS accounted for 35% of blood culture isolates and was the most frequent cause of septicaemia . Underlying disease or other possible predisposing factors were identified in 16 of 25 neonates with GBS septicaemia . Comparison of early onset and late onset disease indicated an increased incidence of prematurity, prolonged rupture of membranes, and respiratory distress in the former and a predominance of meningitis associated cases in the latter . Mortality was 50% for early onset cases, 29% for late onset cases and 36% overall . Antimicrobial therapy and preventive measures which may be appropriate for a developing country are discussed.

Otolaryngol Clin North Am, 1987 May, 20(2), 311 - 6
Pediatric considerations of infections and inflammations of Waldeyer's ring; Palumbo FM; Acute suppurative streptococcal pharyngitis remains a significant pediatric problem, accounting for much time lost from both school and play . Antibiotic therapy will usually treat the acute symptoms; tonsillectomy is often needed when the inflammation becomes chronic and recurrent.

Clin Immunol Immunopathol, 1987 May, 43(2), 174 - 84
Neutrophil-mediated tumor cell destruction in cancer ascites . II . A OK-432 attracts killer neutrophils through activation of complement C5; Fujimura T et al.; When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, the number of neutrophils with cytotoxic activity against tumor cells was increased in the peritoneal cavity immediately after the OK-432 injection . In order to investigate the underlying mechanisms of such neutrophil accumulation, a possible neutrophil chemotactic activity in ascitic fluid was assayed by a modified Boyden method . The chemotactic activity for neutrophils was found significantly higher 6 hr after the OK-432 injection . OK-432 along had no direct chemotactic activity for neutrophils . The chemotactic activity was generated in vitro when ascitic fluid from patients without OK-432 treatment was incubated with OK-432 for 30 min at 37 degrees C . However, preheating of the fluid at 56 degrees C for 30 min or the addition of EDTA to the fluid resulted in the failure of generation of the chemotactic activity after the incubation with OK-432 . The addition of EGTA did not show a significant effect . The chemotactic activity in ascitic fluid was found near cytochrome c marker (MW 12,400 D), when fractionated by Sephadex G-200 gel chromatography . The chemotactic activity was heat stable, nondialyzable, and neutralized completely with anti-human complement C5 antibodies . These results suggest that C5a generated via the alternative pathway activated by OK-432 may be responsible for the infiltration of killer neutrophils in the peritoneal cavity in patients with malignant ascites when they are treated by the intraperitoneal injection of OK-432.

Cancer, 1987 Apr 15, 59(8), 1409 - 11
Immune hemolytic anemia associated with streptococcal preparation OK-432; Nomura S et al.; In the course of administration of an immunopotentiator, streptococcal agent OK-432, a patient with lung cancer was found to have severe anemia and a strongly positive antiglobulin test . In the absence of the drug, eluates from the patient's erythrocytes reacted strongly by the indirect antiglobulin test with a panel of washed Group O erythrocyte samples . The eluated antibody was composed of monoclonal IgG1-lambda . Upon discontinuing the drug the patient's hemoglobin level increased slowly with concomitant normalization of the reticulocyte count . Although very rare, drug-induced immune hemolytic anemia should be included in the list of adverse effects of immunopotentiators . This is the first reported case of immune hemolytic anemia associated with OK-432.

Arch Dermatol, 1987 Apr, 123(4), 468 - 70
Early detection of streptococcal group antigens in skin samples by latex particle agglutination; Bernard P et al.; The streptococcal group antigens (A to G) were researched in skin biopsy specimens by a latex agglutination technique using commercial (Slidex Streptokit bio-Merieux and Streptex Wellcome) and experimental reagents . Twenty-seven patients with obvious cutaneous infections (12 cases of erysipelas, nine cases of cellulitis, and six cases of necrotizing fasciitis) and 27 age- and sex-matched controls were studied . Our preliminary data demonstrated the possibility of an early diagnosis of streptococcal cutaneous infections involving the deep dermis and/or hypodermis . We used a latex agglutination technique that is quite specific and gives a better sensitivity (0.63) than either conventional bacteriologic cultures on needle aspiration or skin biopsy specimens.

Int J Pediatr Nephrol, 1987 Apr-Jun, 8(2), 69 - 74
Vasculitis in acute streptococcal glomerulonephritis; Bodaghi E et al.; Four children are described with a severe acute streptococcal glomerulonephritis . Olyguria, long term renal failure, arterial hypertension, nephrotic syndrome, unconsciousness, marked anemia, abdominal pain and gastrointestinal bleeding were the most prominent findings . The renal biopsy revealed a diffuse endocapillary glomerulonephritis with crescents and vasculitis . One patient had demonstrated multiorgan vasculitis . The patients were managed by conventional methods, three of them received anticoagulants of whom, two association of prednisolone-cyclophosphamide . All recovered.

J Biol Response Mod, 1987 Apr, 6(2), 169 - 80
Clinical value of immunotherapy with the streptococcal preparation OK-432 in non-small cell lung cancer; Watanabe Y et al.; A streptococcal preparation, OK-432, was employed as the adjuvant immunotherapeutic agent combined with chemotherapy in cases of lung cancer . To evaluate the clinical efficacy of OK-432, patients admitted between 1975 and 1982 were randomized into two groups: an immunochemotherapy, or immunotherapy, group and a chemotherapy, or control, group . For each case, a fixed protocol of chemotherapy was administered using a combination of three drugs . In this study, cases with small cell lung cancer were excluded, and the survival rates of cases with non-small cell lung cancer were evaluated . One hundred fifty-nine cases in the immunotherapy group and 152 cases in the control group were eligible for evaluation of long-term survival rates . When comparing the prognosis of the two groups, statistically significant improvements of the survival rate in the immunotherapy group were noted in the following categories: all cases, resected cases, nonresected cases, resected stage I + II cases, resected stage III + IV cases, completely resected cases, incompletely resected cases, and cases with epidermoid carcinoma . From the results of the present study, it is concluded that OK-432 is a potent immunopotentiative agent in the treatment of lung cancer.

Orthopedics, 1987 Apr, 10(4), 615 - 6
Group C streptococcal arthritis . A case report of equine transmission; Gorman PW et al.; Presented is the third known case of a group C streptococcal arthritis, this case documented in a healthy 42-year-old horse trainer, apparently transmitted by a mare . After a delayed diagnosis, the patient responded favorably to surgical drainage and parenteral penicillin G, but required a manipulation of his knee under general anesthesia . Although rare, group C streptococcal arthritis can occur in hosts with no apparent predisposing factors . Frequent exposure to farm animals may increase the risk.

Med Decis Making, 1987 Apr-Jun, 7(2), 92 - 6
Evaluating rapid tests for streptococcal pharyngitis: the apparent accuracy of a diagnostic test when there are errors in the standard of comparison; Deneef P; The evaluation of new rapid antigen detection tests for streptococcal pharyngitis is complicated by the presence of errors in the standard of comparison . Even "gold standard" throat cultures are not perfectly accurate . This article is an analysis of how errors in the comparison cultures affect the apparent accuracy of new tests for streptococcal pharyngitis . One of the questions addressed is whether throat cultures performed in a physician's office are accurate enough to use as a standard in a clinical trial of a new rapid test . While the accuracy of office cultures is accepted by many to be adequate for diagnostic purposes, this analysis shows that when evaluating a new test stricter conditions must be placed on the accuracy of the cultures used for comparison.

Biull Eksp Biol Med, 1987 Apr, 103(4), 435 - 7
{Monoclonal antibodies against group A streptococcal polysaccharide reacting with basal-cell antigen of tumors histogenetically related to epidermal tissues}; Beletskaia LV et al.; Immunofluorescence of tumour tissues histogenetically related to tissues containing cross-reacting squamous epithelial basal-cell antigen (BCAg) was performed using monoclonal antibodies (McAb) A6/I-D to squamous epithelial basal-cell antigen cross-reacting with group A staphylococcal polysaccharide . BCAg was found in tumour cells arising from surface tissues of the epidermal type (basal-cell cancer, squamous-cell cancer of the skin, esophagus, cervix uteri and other organs) and was not found in glandular tumours (adenocarcinoma of the stomach, intestine, mammary glands) . The results obtained indicate that McAb A6/I-D against cross-reacting BCAg may be used while characterizing the majority of normal epidermal tissues and tumours arising from tissues containing cross-reacting BCAg.

Jpn J Exp Med, 1987 Apr, 57(2), 103 - 15
OK-432-mediated augmentation of antitumor immunity and generation of cytotoxic T lymphocytes; Ujiie T; Sensitization with mitomycin C-treated L1210 or EL-4 tumor cells followed by intraperitoneal injection of a streptococcal preparation OK-432 rendered histocompatible or syngeneic mice immune to the corresponding tumor cells . The antitumor immunity, which was more potent than that induced by attenuated tumor cells alone, was manifested by transplantation resistance to challenge tumor cells, and by cytotoxic activity of spleen cells from the primed mice . The former activity was closely related to the latter, which was found to be mainly due to tumor-specific cytotoxic T lymphocytes . The in vivo immunoaugmentation by OK-432 was susceptible to macrophage toxins such as trypan blue and carragheenins, and was partly dependent on the activity of noncytotoxic Ia-positive peritoneal macrophages . OK-432-mediated enhancement of Ia-positive macrophage functions was confirmed by concanavalin A-blastogenesis and T cell-dependent antibody formation . Allo-reactive cytotoxicity induced in allogeneic or semiallogeneic mice, which had been primed with clonogenic or attenuated tumor cells, was also augmented by concomitant administration of OK-432 . These results suggest that OK-432 augments induction of antitumor immunity and alloreactive cytotoxicity, associated with stimulation of noncytotoxic Ia-positive accessory macrophage activity.

Gan To Kagaku Ryoho, 1987 Apr, 14(4), 1051 - 6
{The effect of OK-432 in the treatment of primary lung cancer}; Kishimoto T et al.; Twenty patients with lung cancer were treated with a streptococcal preparation, OK-432 in addition to various other treatments, and we evaluated the effect of OK-432 in comparison with an equivalent number of patients without OK-432 . With regard to advanced-stage patients, the median survival time of those treated with OK-432 was longer than that of patients without OK-432 . Patients whose PPD or SU-PS skin reactions were positive had a longer survival time than those giving a negative reaction . OK-432 significantly increased the reactions for both PPD and SU-PS . On the other hand, OK-432 did not have any significant effect in increasing the numbers of peripheral lymphocytes and T-cell subsets . Furthermore, there were no effects on tumor markers, such as CEA, beta 2-microglobulin and ferritin . However, OK-432 had a remarkable effect in decreasing immunosuppressive acidic protein.

J Clin Invest, 1987 Apr, 79(4), 1160 - 71
Thymus-dependent and -independent regulation of Ia antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis . Differences in site and intensity of expression in euthymic, athymic, and cyclosporin A-treated LEW and F344 rats; Wilder RL et al.; Euthymic LEW rats, when injected with streptococcal cell walls, exhibited rapid onset development of acute exudative arthritis coincident with enhanced synovial expression of Ia antigen . By 21 d after injection, the expression of Ia was markedly increased compared with basal conditions and paralleled the severity of the later developing proliferative and erosive disease . Immunodeficient athymic and cyclosporin A-treated LEW rats developed only the early phase arthritis, which was again paralleled by synovial Ia expression . Chronic expression of high levels of Ia antigen was not observed . Histocompatible F344 rats, both athymic and euthymic, developed minimal, if any, clinically significant arthritis and did not exhibit the enhanced Ia expression demonstrated in the LEW rats . Our results indicate that enhanced synovial Ia expression parallels clinical disease severity and varies by rat strain, and that the rapid onset enhanced synovial Ia expression is thymus independent, whereas the markedly enhanced chronic phase Ia expression is thymus dependent.

J Leukoc Biol, 1987 Apr, 41(4), 295 - 301
Complement component C3 secretion by mouse macrophage-like cell lines; Goodrum KJ; Secretion of complement component C3 by the mouse macrophage-like cell lines PU5-1.8, J774A.1, RAW264.7, and P388D1 was measured using an enzyme-linked immunosorbent assay for mouse C3 . All cell lines secreted antigenically detectable C3 with the relative secreted C3/10(6) cells/24 h ranked as J774A.1 greater than P388D1 greater than or equal to PU5-1.8 much greater than RAW264.7 . C3 secretion was enhanced two- to fourfold in cultures of all cell lines when treated with lipopolysaccharide, streptococcal cell walls, or lymphokine-containing supernatant fluids of mitogen-stimulated spleen cells . A differential induction of C3 synthesis and secretion was indicated since secreted lysozyme and total cellular protein were not elevated in a manner comparable to C3 . The relative inducibility of cell lines for C3 secretion in either lipopolysaccharide- or cell wall-treated cells could be ranked as PU5-1.8 greater than P388D1 greater than J774A.1 greater than RAW264.7 . C3 secretion was inhibited by cycloheximide or hydrocortisone . Mouse macrophage-like cell lines retain baseline and inducible C3 synthetic activities as do normal macrophages and can serve as homogeneous cultures in which to study regulation of complement biosynthesis.

Biochem Biophys Res Commun, 1987 Mar 13, 143(2), 685 - 90
Proton nuclear magnetic resonance measurement of the amide hydrogen exchange rates of group A streptococcal polysaccharide in H2O; Huang DH et al.; The solvent exchange rates of the acetamido hydrogen of the 2-acetamido-2-deoxy-beta-D-glucopyranosyl unit of group A streptococcal polysaccharide dissolved in H2O have been measured and compared with the corresponding exchange rates in the solvated model compound 1-O-methyl-2-acetamido-2-deoxy-beta-D-glucopyranoside . Amide hydrogen exchange rates were measured at 25 degrees C over a wide pH range by a combination of two separate NMR techniques: the transfer of solvent saturation and the amide hydrogen saturation recovery NMR experiments . The data indicate that the acetamido hydrogen essentially exists in a solvated environment and that its contribution to the conformational stability of this polysaccharide through intramolecular hydrogen bonding is negligible.

Science, 1987 Mar 13, 235(4794), 1392 - 4
Transposition of gram-positive transposon Tn916 in Acholeplasma laidlawii and Mycoplasma pulmonis; Dybvig K et al.; Mycoplasma genetics has been limited by a lack of genetic tools such as selectable markers, methods to transfer DNA, and suitable vectors for cloning . Studies were undertaken to examine the potential of using the streptococcal transposon Tn916 as a mycoplasma genetic tool . The Escherichia coli plasmid pAM120, which contains Tn916, was transformed into Acholeplasma laidlawii and Mycoplasma pulmonis . Transposition of Tn916 into the mycoplasma chromosome apparently occurred by an excision-insertion mechanism . This example shows that newly introduced DNA from other bacteria can be successfully expressed in mycoplasma and that Tn916 should serve as a powerful genetic tool for the study of mycoplasmas.

Postgrad Med J, 1987 Mar, 63(737), 209 - 10
Acute post-streptococcal glomerulonephritis followed shortly by acute rheumatic fever; Kwong YL et al.; A 16 year old girl with post-streptococcal glomerulonephritis developed acute rheumatic fever 19 days afterwards . Previous publications on concurrent post-streptococcal glomerulonephritis and acute rheumatic fever are reviewed.

Inflammation, 1987 Mar, 11(1), 73 - 85
Effect of muralytic enzyme degradation of streptococcal cell wall on complement activation in vivo and in vitro; Janusz MJ et al.; Rats given a single intraperitoneal injection of an aqueous suspension of peptidoglycan-polysaccharide polymers derived from group A streptococcal cell wall (PG-APS) develop a severe, chronic, erosive arthritis which resembles human rheumatoid arthritis . The treatment of PG-APS-injected rats with a single intravenous injection of 0.4 mg of mutanolysin prevents the development of chronic arthritis, even when administration of the enzyme is delayed until severe acute arthritis has developed . PG-APS activates complement both in vitro and in vivo . Digestion of PG-APS with mutanolysin in vitro destroys the ability to activate both the alternate and classical pathways of human serum complement, and the loss of complement activation parallels the extent of PG-APS degradation . There is also a reduction in the in vivo complexing of C3 with PG-APS in the limbs of PG-APS-injected rats treated with mutanolysin, compared to control rats injected with PG-APS and treated with phosphate-buffered saline . This association between loss of arthropathic activity and loss of activation of complement is consistent with the hypothesis that activated complement products form a part of the inflammatory mediators involved in the acute and chronic phases of bacterial cell wall-induced arthritis . This may also partially explain how mutanolysin treatment alleviates cell wall-induced arthritis in the rat.

Clin Nephrol, 1987 Mar, 27(3), 111 - 24
Follow-up studies of three subtypes of acute postinfectious glomerulonephritis ascertained by renal biopsy; Sorger K et al.; Quantitative correlative investigations by means of light, immunofluorescence and electron microscopy carried out in the early phase of the disease on 58 patients (children and adults) with acute postinfectious glomerulonephritis (APGN) formed the basis of subtyping APGN into a starry sky type, a mesangial type and a garland type {Sorger et al . 1982 and 1983} . The subtypes also showed differences in the clinical picture . The garland type was of special interest since most patients had severe proteinuria . This caused us to follow-up the patients with these three subtypes (up to 10 years and 7 months) . Proteinuria proved to be the most reliable follow-up parameter . A comparison of the three groups showed that proteinuria rapidly declined as a rule in the patients with the starry sky and the mesangial patterns . In the garland pattern there were also cases with a complete disappearance of proteinuria, especially in younger patients, but other patients still had a distinct proteinuria after months to years indicating a protracted or chronic course . The morphological findings of the rebiopsies correlated with the clinical courses, especially with the course of proteinuria . The three morphological subtypes are thus significant for estimating the prognosis of APGN, which is favorable as a rule in patients with the starry sky and mesangial types, but much more unfavorable in patients with the garland type . Even if fewer cases with demonstrated streptococcal etiology were found in the garland pattern group, i.e., among patients with the most uncertain prognosis, than in the remaining groups, these differences were not statistically significant . Therefore, our investigations do not provide any indications that different etiological factors are responsible for the three subtypes . The individual immune response of the host body is likely to be very much more decisive.

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