J Immunol Methods, 1992 Jul 31, 152(1), 43 - 8 Chimaeric protein A/protein G and protein G/alkaline phosphatase as reporter molecules; Sun S et al.; The IgG binding domains of staphylococcal protein A and streptococcal protein G were expressed as a chimaera using the pGEX vector which has been advocated because its fusion proteins tend to be soluble and easily isolated on immobilised glutathione . This chimaera was soluble and abundant (yield = 18 mg/l of bacterial culture) and was tested by double diffusion in agarose and by ELISA . It was found to bind IgG of all species that either parent could bind . It was superior to protein A or protein G in binding mouse Ig . A chimaera of protein G and alkaline phosphatase was also constructed and found to be soluble and abundant (yield = 20 mg/l of bacterial culture) . This protein could be used as a secondary reagent in ELISA at 5 micrograms/ml for human, rabbit and mouse and at 25 micrograms/ml for sheep. J Immunol Methods, 1992 Jul 31, 152(1), 49 - 57 Agonistic properties of anti-B cell antibodies purified on staphylococcal protein A may be due to contaminating protein A; Jakobson E et al.; Some antibodies directed to cell surface receptors may mimic the physiological ligands by inducing the transmission of activation or growth signals . Such agonistic antibodies have proven very useful when studying functional properties of various receptor molecules on, e.g., lymphoid cells . However, while investigating the agonistic effects on tonsillar B cells of the anti-CD43 monoclonal antibody (mAb) D4B11 and the anti-CD40 mAb S2C6, we made some observations which emphasize the need for caution when using antibodies purified by protein A affinity chromatography . Both antibody preparations were found to elicit changes in the intracellular free calcium concentration ({Ca2+}i) as well as promoting proliferation of phorbol ester activated cells . However, a closer analysis showed that the increase in {Ca2+}i could be attributed to soluble staphylococcal protein A (SpA) desorbed during antibody purification . By using pure soluble SpA, we were able to show that nanogram amounts were sufficient to increase {Ca2+}i by a mechanism that involved both a mobilization from intracellular stores and an influx across the B cell membrane . A similar effect on cytosolic Ca2+ in B cells was also noted for streptococcal protein G (protein G), another bacterial component used for antibody purification . However, in contrast to SpA, protein G had little effect on cell proliferation . These observations suggest that the presence of trace amounts of SpA or protein G in antibodies purified on these bacterial components may lead to incorrect interpretations of the agonistic properties of such antibodies . When the above findings were taken into account, it was found that the CD43 mAb D4B11, like the CD40 mAb S2C6, stimulated growth of B cells without causing any measurable increase in {Ca2+}i . Both CD40 and CD43 may thus be coupled to signalling pathways which do not involve breakdown of membrane phosphoinositides. Cell, 1992 Jul 24, 70(2), 267 - 81 Sorting of protein A to the staphylococcal cell wall; Schneewind O et al.; The cell wall of gram-positive bacteria can be thought of as representing a unique cell compartment, which contains anchored surface proteins that require specific sorting signals . Some biologically important products are anchored in this way, including protein A and fibronectin binding protein of Staphylococcus aureus and streptococcal M protein . Studies of staphylococcal protein A and Escherichia coli alkaline phosphatase show that the signal both necessary and sufficient for cell wall anchoring consists of an LPXTGX motif, a C-terminal hydrophobic domain, and a charged tail . These sequence elements are conserved in many surface proteins from different gram-positive bacteria . We propose the existence of a hitherto undescribed sorting mechanism that positions proteins on the surface of gram-positive bacteria. Ann Surg, 1992 Jul, 216(1), 44 - 54 A comprehensive multi-institutional study on postoperative adjuvant immunotherapy with oral streptococcal preparation OK-432 for patients after gastric cancer surgery . Kyoto Research Group for Digestive Organ Surgery; Detection of rubella virus-specific polymeric immunoglobulin A by enzyme-linked immunosorbent assay in combination with streptococcal pretreatment of serum; Miyazaki Prefectural Institute for Public Health and Environment, Miyazaki Medical College, JapanAn enzyme-linked immunosorbent assay combined with streptococcal treatment of serum was assessed for its ability to detect serum polymeric immunoglobulin A . This technique detects rubella virus-specific polymeric immunoglobulin A antibody, which appears for only a short time after infection, and it is useful for serodiagnosis of recent rubella virus infection. J Bacteriol, 1992 Jul, 174(13), 4239 - 45 Expression of recombinant proteins on the surface of the coagulase-negative bacterium Staphylococcus xylosus; Hansson M et al.; An expression system to allow targeting of heterologous proteins to the cell surface of Staphylococcus xylosus, a coagulase-negative gram-positive bacterium, is described . The expression of recombinant gene fragments, fused between gene fragments encoding the signal peptide and the cell surface-binding regions of staphylococcal protein A, targets the resulting fusion proteins to the outer bacterial cell surface via the membrane-anchoring region and the highly charged cell wall-spanning region of staphylococcal protein A . The expression system was used to secrete fusion proteins containing sequences from a malaria blood-stage antigen and a streptococcal albumin-binding receptor to the cell surface of S . xylosus . Analysis of the recombinant cells by immunogold staining and immunofluorescence revealed that both the receptor and the malaria peptide were properly processed and exposed on the surface of the host cells . However, only approximately 40 to 50% of the recombinant cells were strongly stained with antiserum reactive with the albumin-binding receptor, while approximately 10 to 15% of the cells were stained with antiserum reactive with the malaria peptide . The incomplete staining of some of the cells suggests steric effects that make the recombinant fusion proteins inaccessible to the reactive antibodies because of variable cell wall structures . However, the results demonstrate for the first time that recombinant techniques can be used to express heterologous receptors and immunogens on the surface of gram-positive cells. Nippon Hinyokika Gakkai Zasshi, 1992 Jul, 83(7), 1110 - 7 {Studies on the production of endogenous cytokines in patients with renal cell carcinoma}; Nakashima J et al.; This study was undertaken to determine the production of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) by biological response modifier (BRM) in patients with renal cell carcinoma (RCC) . Peripheral blood mononuclear cells (PBMC), which were donated from thirteen patients with RCC and five healthy controls, were cultured with streptococcal preparation, OK432, and/or macrophage-colony stimulating factor (M-CSF), and the TNF levels and IFN-gamma levels in the supernatant were evaluated . TNF activities were assayed by cytotoxicity to L929 cells and IFN-gamma activities were measured by inhibition of the cytopathic effects of sindbis virus on FL cells . The highest levels of TNF in the supernatant were 235.4 +/- 96.0 U/ml/1 x 10(4) cells in patients with renal cell carcinoma and 251.6 +/- 71.8 U/ml/1 x 10(4) cells in healthy controls, which were noted at 12 hours of incubation with the concentration of OK432 adjusted to 0.05 KE/ml . There was no statistically significant difference between the TNF activities induced by in vitro culture of PBMC obtained from patients with renal cell carcinoma and those from healthy controls . The production of TNF by in vitro culture of PBMC with OK432 of 0.05 KE/ml was augmented by adding 100 U/ml M-CSF especially at 48 and 72 hours of incubation, whereas M-CSF alone did not stimulated TNF production . The medium levels of IFN-gamma in six different cultures of PBMC with 0.05 KE/ml OK432 at 12, 24 and 48 hours of incubation were 1.15 +/- 0.34 U/ml/l x 10(4) cells, 2.23 +/- 0.93 U/ml/l x 10(4) cells, and 7.83 +/- 4.00 U/ml/l x 10(4) cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Vojnosanit Pregl, 1992 Jul-Aug, 49(4), 335 - 8 {Early treatment of acute nephrotic syndrome in patients with acute post-streptococcal glomerulonephritis}; Jovanovic D et al.; In the period of five years 54 patients with acute poststreptococcal glomerulonephritis were treated . Acute nephritic syndrome was manifested in 45 (almost 4/5 of all) patients . Edema and hematuria were found in all patients, hypertension in 89%, and acute renal failure in 49% of patients with the acute nephritic syndrome . For successful treatment of acute nephritic syndrome of decisive importance have been application of measures intended primarily to correction of positive sodium and water balance by dietetic regimes, diuretics and antihypertensives and rest, while the application of the dialysis has not been necessary even in patients with acute renal failure. Eur Cytokine Netw, 1992 Jul-Aug, 3(4), 391 - 8 Activation of the systemic production of tumor necrosis factor after exposure to acute stress; Yamasu K et al.; Tumor necrosis factor (TNF), which was originally identified as a tumoricidal factor, is now regarded as one of the main regulators of inflammation and various immune systems . Thus it has been considered to be mobilized in case of emergency . However, we assume that TNF and the cytokine network driven by the monokine also function under normal condition for homeostasis of the animal body which is exposed to various kinds of physiological stress . To test this possibility, we exposed C3H/He mice for up to 3 days to five types of acute stress: food deprivation, drinking water deprivation, sleep deprivation, swimming, and physical restraint . After release from the stress, the level of priming for systemic production of TNF was examined using OK-432 (a streptococcal preparation) as a trigger . Priming of TNF production was not observed immediately after 2-day exposure to most of the stressors . Sleep deprivation alone tended to induce a primed state especially when the stress period was lengthened to 3 days . On the other hand, by keeping mice in a normal condition for a 2-day restorative interval after 2-day exposure to the stressors, systemic production of TNF was consistently primed for all the stress examined . The time course of the priming effect was examined in detail for water-deprivation stress . The effect was detected as early as 3 hours after release from stress, was sustained for 2 days, and returned to the basal level by 4 days after the release . Based on these results, we discussed the role of the TNF-driven cytokine circuit in adaptation to stress. Mol Gen Genet, 1992 Jul, 234(1), 105 - 12 In vitro and in vivo analysis of transcription within the replication region of plasmid pIP501; Brantl S et al.; Derivatives of the conjugative streptococcal plasmid pIP501 replicate stably in Bacillus subtilis . The region essential for replication of pIP501 has been narrowed down to a 2.2 kb DNA segment, the sequence of which has been determined . This region comprises two genes, copR and repR, proposed to be involved in copy control and replication . By in vitro and in vivo transcriptional analysis we characterized three active promoters, pI, pII and pIII within this region . A putative fourth promoter (pIV) was neither active in vitro nor in vivo . We showed that copR is transcribed from promoter pI while the repR gene is transcribed from promoter pII located just downstream of copR . The pII transcript encompasses a 329 nucleotide (nt) long leader sequence . A counter transcript that was complementary to a major part of this leader was found to originate from a third promoter pIII . The secondary structure of the counter transcript revealed several stem-loop regions . A regulatory function for this antisense RNA in the control of repR expression is proposed . Comparative analysis of the replication regions of pAM beta 1 and pSM19035 suggested a similar organization of transcriptional units, suggesting that an antisense RNA is produced by these plasmids also. Postgrad Med, 1992 Jul, 92(1), 269 - 72, 277-82 The new macrolide antibiotics . Azithromycin and clarithromycin; Stein GE et al.; Azithromycin (Zithromax) and clarithromycin (Biaxin Filmtabs) are new macrolide antibiotics with several advantages over erythromycin . Azithromycin has an expanded spectrum against gram-negative bacilli . Clarithromycin is more active than erythromycin against gram-positive cocci; combination with its 14-hydroxy metabolite enhances its antimicrobial activity . These new agents penetrate well into tissues and concentrate in macrophages and polymorphonuclear leukocytes . They offer improved bioavailability and an extended half-life . The high tissue-to-serum level and extended elimination half-life of azithromycin allow for once-daily dosing and short-course therapy . Clarithromycin and 14-hydroxyclarithromycin maintain high serum levels and tissue-to-serum concentrations . Both of these new agents have been effective in streptococcal pharyngitis, acute sinusitis, acute lower respiratory tract infections, skin and soft-tissue infections, and sexually transmitted diseases . A single dose of azithromycin is effective for genital chlamydial infections . Adverse reactions to these agents have usually been mild and have not included serious organ toxicity . In clinical trials, the rate of premature discontinuation of therapy has been less than observed with erythromycin . Azithromycin and clarithromycin should be used according to the current guidelines of the Food and Drug Administration; their future role will be determined by ongoing laboratory and clinical evaluations. Pediatr Dent, 1992 Jul-Aug, 14(4), 246 - 50 Antibiotic prophylaxis for patients with hydrocephalus shunts: a survey of pediatric dentistry and neurosurgery program directors; Acs G et al.; A survey of antibiotic prophylaxis recommendations for patients with hydrocephalus shunts was sent to directors of advanced programs in pediatric dentistry and neurosurgery . Recommendations were sought for patients with ventriculoperitoneal (VP) or ventriculoatrial (VA) shunts who were to receive dental care . Most respondents believed that shunt infection (SI) was related infrequently to dental procedures . Pediatric dentists believed that 5.2% of infected VA shunts were related to dental procedures, while neurosurgeons believed the rate to be 3.0% (P < 0.05) . There was no difference in perceived risk for VP shunts . Except for the equal risk associated with extractions, pediatric dentists were significantly more likely than neurosurgeons to recommend chemoprophylaxis for patients with VA shunts undergoing invasive dental procedures (P < 0.05) . They were more likely to agree with neurosurgeons when VP shunts were involved . Except for the equal risk associated with dental prophylaxis, pediatric dentists and neurosurgeons believed VA shunt patients were at greater risk for SI than VP shunt patients (P < 0.05) . Pediatric dentists were significantly more likely to ascribe SI to streptococcal organisms, and recommended penicillin for prophylaxis for both VA and VP shunts (P < 0.01 and 0.025, respectively) . Although neurosurgeons believed that staphylococcal organisms were most likely to be responsible for SI (P < 0.001), 60% still recommended using penicillin for shunt prophylaxis following dental procedures. Roum Arch Microbiol Immunol, 1992 Jul-Sep, 51(3), 157 - 64 Evaluating the minimum active concentrations of penicillin G and V and of retard forms in clinical conditions; Dorobat O et al.; Following several signals indicating the inefficiency of the clinical treatment with various penicillin preparations in some cases, we decided to study the seric penicillin concentrations in the patients hospitalized in the "V . Babes" Hospital of Infectious Diseases, after administration of the various Romanian made forms of penicillin currently used in the therapy of streptococcal infections and in the prophylaxis of the sequelae of these infections . The data obtained on groups exceeding 30 persons by using two methods of determining the penicillin concentrations the dilutions and the diffusimetric methods revealed protective penicillin seric levels satisfactory for penicillin G and Efitard, according to the present treatment schemes . After 5 days from Moldamin administration only 45.4% of children and 43.3% of adults were found to have satisfactory penicillin concentrations . The administration of penicillin V reaches active penicillin concentrations in terms of the dose administered . The paper points out only one of the causes which together with others (such as beta-lactamase production and tolerance), contribute to the unsuccessful treatment with various forms of penicillin. Ann Ital Med Int, 1992 Jul-Sep, 7(3 Suppl), 78S - 85S {The clinical problems of bacterial infections of the upper respiratory tract}; Pallestrini EA et al.; ORL inflammations present particular pathogenetic and clinical characteristics due to the close anatomic and physiological connection among them and to their particular anatomic characteristics . The ear communicates with the rhinopharynx through the Eustachian tube, and this relationship explains how bacterial infections of the upper respiratory tract can cause otitis and how tubal dysfunctions are often responsible for chronic ORL infections, also favoured by the microcavity structure of the middle ear and the mastoid bone . Also the macro- and microcavity anatomic structure of the paranasal sinuses favours chronic infectious diseases, and their adjacency with the endocranial and facial structures justifies the secondary complications of these infections . The palatine tonsil and other structures of the Waldeyer's lymphatic ring play an important immune role in the first respiratory and digestive tract, and infections occurring in these structures (for example, streptococcal infection) can cause pathologies such as rheumatic disease . Other ORL infections are connected to immunodeficiency or atopy. Biochemistry, 1992 Jun 23, 31(24), 5434 - 41 Antigen binding thermodynamics and antiproliferative effects of chimeric and humanized anti-p185HER2 antibody Fab fragments; Kelley RF et al.; The murine monoclonal antibody 4D5 (anti-p185HER2) inhibits the proliferation of human tumor cells overexpressing p185HER2 in vitro and has been "humanized" {Carter, P., Presta, L., Gorman, C . M., Ridgway, J . B . B., Henner, D., Wong, W.-L . T., Rowland, A . M., Kotts, C., Carver, M . E., & Shepard, H . M . (1992) Proc . Natl . Acad . Sci . U.S.A . (in press)} for use in human cancer therapy . We have determined the antigen binding thermodynamics and the antiproliferative activities of chimeric 4D5 Fab (ch4D5 Fab) fragment and a series of eight humanized Fab (hu4D5 Fab) fragments differing by amino acid substitutions in the framework regions of the variable domains . Fab fragments were expressed by secretion from Escherichia coli and purified from fermentation supernatants by using affinity chromatography on immobilized streptococcal protein G or staphylococcal protein A for ch4D5 and hu4D5, respectively . Circular dichroism spectroscopy indicates correct folding of the E . coli produced Fab, and scanning calorimetry shows a greater stability for hu4D5 (Tm = 82 degrees C) as compared with ch4D5 Fab (Tm = 72 degrees C) . KD values for binding to the extracellular domain (ECD) of p185HER2 were determined by using a radioimmunoassay; the delta H and delta Cp for binding were determined by using isothermal titration calorimetry . ch4D5 Fab and one of the humanized variants (hu4D5-8 Fab) bind p185HER2-ECD with comparable affinity (delta G degrees = -13.6 kcal mol-1).(ABSTRACT TRUNCATED AT 250 WORDS) Am J Med, 1992 Jun 22, 92(6A), 74S - 79S Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in an adult population; McCarty J; Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, is a potent anti-bacterial agent . In a double-blind, randomized clinical trial to assess the efficacy and safety of loracarbef in the treatment of streptococcal pharyngitis and tonsillitis, 107 adult patients were treated with loracarbef (200 mg capsules twice a day or 15 mg/kg/day suspension) and 111 patients were treated with penicillin VK (250 mg capsules four times a day or 20 mg/kg/day suspension) for 10 days . In the loracarbef treatment group, 96.6% of the evaluable patients had a favorable clinical response 3-5 days after therapy, a result that compared favorably with the 93.9% response rate achieved in the penicillin group . The clinical failure/relapse rates were 3.4% for loracarbef-treated patients and 6.1% for patients receiving penicillin . Bacteriologic response data approximated the clinical results, with a successful response in 89.9% of the loracarbef-treated patients and 91.5% of the penicillin recipients . Two (1.9%) loracarbef-treated patients with rash and one (0.9%) penicillin-treated patient with diarrhea discontinued the study early because of these adverse events . The incidence of adverse events was comparable in the two treatment groups except for increased cough, which was reported by 3.7% of the loracarbef-treated patients and none of the penicillin recipients . These data support the conclusion that loracarbef is comparable to penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults. J Clin Pharm Ther, 1992 Jun, 17(3), 141 - 6 Advances in paediatric pharmacotherapy; Nahata MC; Marked differences in body composition and organ function development have been demonstrated among neonates, infants, and children versus adults . Specific dosage guidelines for the paediatric population, however, are still not available for the majority of marketed drugs . Much needs to be learned about the pharmacokinetics, pharmacodynamics, comparative efficacy and safety of drugs in infants and children . Recent developments in paediatric therapeutics include the availability of several new antibiotics for the treatment of infections including, streptococcal pharyngitis, otitis media, bacterial meningitis, herpes encephalitis, neonatal herpes, and AIDS . Corticosteroids and intravenous immunoglobulin have become important adjunctive treatments for certain infections . A variety of drugs are available to treat asthma but the mortality due to this disease is still increasing . The identification of a gene defect in patients with cystic fibrosis could lead to more effective treatment in the future . Ondansetron, marketed for use in adults only, shows promise as a more effective and safer antiemetic in children receiving cancer chemotherapy . Numerous drugs are not available in suitable dosage forms for paediatric use and extemporaneous formulations are required . Documentation on the stability of the reformulated drugs is therefore needed . Studies have shown that the methods used for intravenous delivery can influence the serum concentrations of drugs in infants and children . Large numbers of children could be saved worldwide solely with improved vaccination and control of diarrhoea . Despite this, it is encouraging to witness the continued advances being made in paediatric pharmacotherapy. Singapore Med J, 1992 Jun, 33(3), 273 - 5 Inheritance of susceptibility: Lamarckism revisited; Sit KH; The familial nature of susceptibility to rheumatic fever has been known for nearly three quarters of a century but even after massive ascertainments of affected families in 5 major cities, viz Toronto, Belfast, London, Glasgow and New York, a consensus on the exact mode of inheritance could not be reached . Reduced penetrance was suggested 40 years ago and still cited today even though the fit is poor . However with the sampling bias of the observed data resolved in the recently formulated geometric continuum v(affected-1) x P(sibship) (where O less than v----infinity) all those published ascertainments clearly show a unilocal Mendelian recessive mode of inheritance . Since rheumatic fever is clearly associated with streptococcal sore throat, I have therefore demonstrated the inheritance of an acquired trait . This Larmarckian concept is explained using simple numerical examples. FEMS Microbiol Rev, 1992 Jun, 8(3-4), 199 - 209 On the relative importance of specific and non-specific approaches to oral microbial adhesion; Busscher HJ et al.; In this paper, it is suggested that specificity and non-specificity in (oral) microbial adhesion are different expressions for the same phenomena . It is argued that the same basic, physicochemical forces are responsible for so-called 'non-specific' and 'specific' binding and that from a physico-chemical point of view the distinction between the two is an artificial one . Non-specific interactions arise from Van der Waals and electrostatic forces and hydrogen bonding, and originate from the entire cell . A specific bond consists of a combination of the same type of Van der Waals and electrostatic forces and hydrogen bonding, now originating from highly localized chemical groups, which together form a stereochemical combination . The absence or presence of specific receptor sites on microbial cell surfaces must therefore be reflected in the overall, non-specific surface properties of cells as well . This point is illustrated by showing that glucan-binding lectins on mutans streptococcal strains may determine the pH dependence of the zeta potentials of these cells . When studying microbial adhesion, a non-specific approach may be better suited to explain adhesion to inert substrata, whereas a specific approach may be preferred in case of adhesion to adsorbed protein films . Adhesion is, however, not as important in plaque formation in the human oral cavity as is retention, because low shear force periods, during which adhesion presumably occurs, are followed by high shear force periods, during which adhering cells must withstand these detachment forces . Evidence is provided that such detachment will be through cohesive failure in the pellicle mass, the properties of which are conditioned by the overall, non-specific substratum properties . Therefore, in vivo plaque formation may be more readily explained by a non-specific approach. P N G Med J, 1992 Jun, 35(2), 137 - 43 Skin infections in Tanna, Vanuatu in 1989; Harris M et al.; Skin infections are an important health problem in Vanuatu and other Pacific island countries . In this study, 18,223 people, representing 90% of the population of the southern island of Tanna in Vanuatu, were examined . Scabies was found in 16% of those screened, with 24% of children under 10 years affected . Other skin infections were predominantly furuncles, abscesses, impetigo and cellulitis and were found in 12% overall and in 16% of children under 10 years of age . These infections were found to be more common in larger households and in the vicinity of the volcano Yasur . Strategies for prevention and management of skin infections in Vanuatu are discussedPIP: In 1989, the Royal New Zealand Medical Corps and the Health Department augmented their mass treatment program of yaws by also screening the population of Tanna Island in the archipelago nation of vanuatu for other skin infections . Health workers first visited the villages and informed leaders of the program . Radio broadcasts also informed the public . The teams reached about 90% (18,223 people from 288 villages) of the target population . They also treated other diseases and led a health education exchange on vector control, improvements in sanitation and the water supply, and immunization of children with each village . 16.5% of the population had only scabies . They tended to be younger than those with other skin infections (mean age 14.8 vs . 22.6 years; p .05) . Children under 10 years old had the highest prevalence rate (20.6 for 5-9 years olds and 27.5% for 0-4 years olds) . People who lived in the Middle Bush area had the highest prevalence rate of scabies (20.8%) as well as the lowest supply of water for washing . Health workers treated the people with benzoyl benzoate . 11.9% of people had other infections which included furuncles, abscesses, impetigo, and cellulitis . They were most likely staphylococcal and/or streptococcal infections . 9.7% had grade 2 lesions (mean age - 14.1% years) and 2.2% had grade 3 lesions (mean age = 13.5 years) . Grade 2 infections were more common in the north (16.4%) and the southwest (16.8%) while grade 3 infections were most common in White Sands (7.1%) . The high prevalence at White Sands may have been due to the irritating effects of the acidic rain created by the active nearby volcano . Skin infections were more common in crowded households (p .05) . These skin infections were significant because they often transmit hepatitis B virus and have been associated with acute and chronic glomerulonephritis which is common in children in Vanuatu . Tanna Island must develop an extensive strategy to control skin infections . J Pediatr Surg, 1992 Jun, 27(6), 764 - 6 Right-sided diaphragmatic hernia following group B streptococcal pneumonia and sepsis; Handa N et al.; A case of right-sided diaphragmatic hernia following group B streptococcal pneumonia and sepsis is reported herein . The clinical course was characteristic . The position of the right hemidiaphragm was initially normal . After an antecedent group B streptococcal infection, an abnormal shadow indicating either pneumonia or a pleural effusion on the chest x-ray was recognized and an elevation of the bowel and liver into the right hemithorax gradually appeared . Repair of the hernia was indicated and the postoperative result was excellent . The relationship between a delayed-onset diaphragmatic hernia and a group B streptococcal infection is still unknown . Increased intrathoracic pressure caused by mechanical ventilation coupled with an abnormal lung compliance due to inflammation may have resulted in the delayed herniation . Among various methods for diagnosis applied, chest x-ray and ultrasonography were noninvasive and useful. Ann Rheum Dis, 1992 May, 51(5), 686 - 7 Acute aortic insufficiency in a patient with presumed Reiter's syndrome; Misukiewicz P et al.; Cardiac disease is rare in patients with Reiter's syndrome . There have been 15 reported cases of aortic insufficiency in patients with Reiter's syndrome, with the aortic insufficiency developing over several years . This paper reports the case of a black HLA-B27 negative woman who presented with Reiter's syndrome and acute aortic insufficiency . An antecedent streptococcal infection is suggested as the inciting factor . To our knowledge, this is the first report of Reiter's syndrome in a black woman with acute aortic insufficiency. Pneumologie, 1992 May, 46(5), 196 - 202 {Emissions of airborne substances from stalls of domestic animals}; Hartung J; There is concern on recent reports indicating an increase of respiratory affections in humans in areas with high livestock production . A survey is presented on airborne emissions from livestock buildings . About 136 gaseous compounds are analysed in animal house air of which 22 are quantified, only . The most environment-related compounds are ammonia and methane . It is assumed that German animal husbandry emits more than 350,000 t ammonia per year . The content of airborne microorganisms in livestock buildings is between some 100 and several 1000 per liter . The greatest part, more than 80%, are Staphylococcae and Streptococcae . Fungi, moulds and yeasts can form more than 1%, and coli-like bacteria about 0.5% of the total amount . Moulds like Penicillium, Aspergillus, Cladosporium and Alternaria were identified which are known to have allergic properties . The average concentrations of dust in animal barns vary between 0.5 and 20 mg/m3 . The dust contains high amounts of protein and carries endotoxins which both have an allergic potential . Preliminary results show that the germ content of the surrounding air in areas with high animal densities seems to be distinctly higher than in non-livestock regions. Arch Intern Med, 1992 May, 152(5), 1017 - 22 Outbreak of invasive group A streptococcal infections in a nursing home . Lessons on prevention and control; Auerbach SB et al.; OBJECTIVE--Nine outbreaks of group A streptococcal (GAS) infections in nursing homes were reported to the Centers for Disease Control (Atlanta, Ga) during the past two winters . We conducted an intensive epidemiologic and laboratory investigation of one of these outbreaks to determine clinical characteristics, risk factors for transmission and infection, and methods of control and prevention . METHODS--Cases were detected using cultures and serologic tests . Matched case-control and retrospective cohort studies were performed to determine risk factors for infection . RESULTS--Between December 13, 1989, and January 31, 1990, 16 (20%) of 80 residents, and three (7%) of 45 staff, were infected with GAS . Eleven of the residents had invasive disease and four died . Isolates were available from four persons; all were serotype M-1, T-1 . There was strong spatial clustering of cases within the nursing home; having a roommate with prior infection was the most important risk factor . Residents with preexisting decubiti had a reduced risk of infection, perhaps because of stricter infection control practices in their care . No evidence was found for common-source transmission of infection . No further cases occurred after improvement of infection control practices and administration of prophylactic antimicrobials to all residents and staff . CONCLUSIONS--Invasive GAS disease is increasing nationwide, and is a potentially serious problem in the growing and high-risk setting of nursing homes . These data suggest that, in this outbreak, a virulent GAS strain was introduced, with subsequent person-to-person transmission . Adherence to infection control practices can prevent or control GAS outbreaks . Prophylactic antimicrobials may be an effective adjunct to control severe or ongoing outbreaks. Am J Pathol, 1992 May, 140(5), 1205 - 14 Role of Kupffer cells in developing streptococcal cell wall granulomas . Streptococcal cell wall induction of inflammatory cytokines and mediators; Manthey CL et al.; Hepatic granulomas are induced by intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats . Kupffer cells rapidly clear SCW from the blood, and the authors examined Kupffer cells further for a role in SCW-hepatic inflammation . Isolated Kupffer cells cultured with SCW secreted high levels of tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), transforming growth factor beta (TGF beta), and prostaglandin E2 (PGE2) . SCW transiently induced increased steady-state levels of IL-1 beta and TNF alpha mRNA; in contrast, constitutive expression of TGF beta 1 mRNA in Kupffer cells was not affected by SCW . Low concentrations of SCW induced the accumulation of intracellular IL-1 and TGF beta bioactivity, with intracellular IL-1 bioactivity remaining high through at least 72 hours of culture . Kupffer cells isolated 1, 7, and 21 days after SCW injection did not express IL-1 beta or TNF alpha mRNA greater than control levels and exhibited marked hyporesponsiveness to secondary in vitro stimulation with SCW or LPS . SCW transiently induces Kupffer cells to secrete a variety of soluble mediators that contribute to hepatic inflammation by inducing leukocyte recruitment and activation and fibroproliferation . The transient nature of the Kupffer cell response and the hyporesponsiveness to secondary stimulation may be a mechanism by which the hepatic inflammation is negatively regulated. Acad Med, 1992 May, 67(5), 345 - 7 Controlled trial using computerized feedback to improve physicians' diagnostic judgments; Poses RM et al.; The goal of this study was to test an innovative method to improve physicians' diagnostic judgments by integrating the use of a computer program (employing cognitive feedback to teach a clinical rule that predicts the probability of streptococcal pharyngitis), a traditional lecture, and periodic disease-prevalence reports . In a controlled trial using pre- and postintervention measures involving 885 patients, the authors compared the effects of the integrated method on the diagnostic judgments of seven experienced physicians at a university health service (from 1982 to 1985) with the effects of the lecture alone on the judgments of seven experienced physicians at a different university health service (1986 to 1987) . The integrated method significantly improved the quality of the physicians' judgments as measured by calibration curves and Brier scores, and increased the level of agreement between the physicians' judgments and those made by the clinical prediction rule . The lecture alone produced less improvement in the quality of the physicians' judgments, and decreased the level of agreement with the rule . The authors conclude that this method, based on cognitive psychology, is a promising educational tool. Clin Exp Immunol, 1992 May, 88(2), 313 - 7 Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats; van den Broek MF et al.; Streptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis that can be induced in susceptible Lewis rats by one i.p . injection of an aqueous, sterile suspension of SCW . F344 rats are resistant to chronic joint inflammation . Our previous studies showed a correlation between susceptibility to SCW-induced arthritis and the ability to mount SCW-specific T cell responses, suggesting tolerance to SCW as a putative mechanism . Here we prevented the induction of tolerance to bacterial epitopes in F344 rats by using them germ-free and analysed susceptibility to arthritis subsequently . In addition, we conventionalized germ-free F344 rats at different times before induction of arthritis . Our results show that germ-free F344 rats are susceptible to SCW-induced arthritis with a similar severity, chronicity, incidence and onset as Lewis rats . Moreover, T cells isolated from germ-free F344 rats were able to respond to SCW . Conventionalization dramatically moderates arthritis and makes T cells unresponsive to SCW again . Thus, in normal rats (F344) a state of tolerance to arthritogenic epitopes is induced (neonatally) and maintained through life by the bacterial flora, resulting in resistance to bacterium-induced arthritides . In arthritis-prone (Lewis) rats, this tolerance is deficient and/or easily broken. J Infect Dis, 1992 May, 165(5), 879 - 85 Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O; Hackett SP et al.; Previous studies have found that 80% of strains isolated from patients with the streptococcal toxic shock syndrome produce pyrogenic exotoxin A (SPEA) and 100% produced streptolysin O (SLO) . To elucidate the cellular mechanisms contributing to shock, human monocytes were stimulated with SPEA (0.1-10 micrograms/10(6) monocytes) or SLO (0.2-2.5 hemolytic units/10(6) monocytes), and production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta was measured at 24, 48, and 72 h . SPEA and SLO were potent inducers of TNF alpha, with maximum production occurring at 72 h for SPEA and at 48 h for SLO (1067 and 687 pg/ml, respectively) . In contrast, IL-1 beta production was greater for SLO than for SPEA (557 vs . 258 pg/ml) . In addition, the effects of SPEA and SLO together were synergistic in terms of monocyte IL-1 beta production: SPEA, 193 pg/ml; SLO, 452 pg/ml; SPEA plus SLO, 799 pg/ml . These findings suggest TNF alpha and IL-1 beta are important candidates for mediating shock in severe streptococcal infections. J Pharmacobiodyn, 1992 May, 15(5), 255 - 9 Autoimmune kidney disease in MRL/lpr mice inhibited by OK-432; II . Effect of indomethacin; Mihara M et al.; We have reported that OK-432 (a streptococcal preparation) prevents the development of autoimmune kidney disease in MRL/Mp-lpr/lpr (MRL/lpr) mice and prolongs their survival time . In the present study, to clarify the mechanism of this action of OK-432, we examined whether the cyclooxygenase inhibitor indomethacin (IND) affects this inhibition by OK-432 . It was reconfirmed that OK-432 prevented the development of autoimmune kidney disease and prolonged the survival time . This OK-432 effect was counteracted when IND was coadministered . Furthermore, OK-432 produced tumor necrosis factor (TNF)-alpha and prostaglandin (PG) E2 in the peritoneal fluids in this strain of mice . The coadministration of IND suppressed the PGE2 but not the TNF-alpha production . These results suggest the possibility that the inhibition of autoimmune kidney disease by OK-432 might be due to the induction of cyclooxygenase metabolites of arachidonic acid. Antibiot Khimioter, 1992 May, 37(5), 44 - 6 {Use of vilozen and ketotifen combination for increasing the effectiveness and prevention of complications of antibiotic therapy of streptococcal infections}; Frolov VM et al.; The clinical efficacy of a vilozen and ketotifen (zaditen) combination in the treatment of streptococcal infections along with the routine therapy was studied . The use of the combination was shown advisable in the complex therapy and prevention of relapses in patients with streptococcal infections . The combined pharmacotherapy promoted better clinical indices, normalization of the immune status and a reduction in the incidence of allergic reactions to antibiotics and a decrease in sensitization to bacterial allergens. Pediatr Nephrol, 1992 May, 6(3), 231 - 5 Crescentic glomerulonephritis in children; Jardim HM et al.; Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed . Thirty patients (13 male, 17 female) aged 3.7-15.7 years (mean 9.5) were evaluated . Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30) . Henoch-Schonlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic . In 10 patients 50%-79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2) . The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed . Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations . On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m2 . In our experience, 50% progressed to end-stage renal failure . The interval between disease onset and start of treatment was a prognostic factor for outcome . Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P less than 0.05) . Outcome was not, however, related to the percentage of glomeruli affected (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Neuroendocrinology, 1992 May, 55(5), 600 - 8 Neurotransmitter-induced hypothalamic-pituitary-adrenal axis responsiveness is defective in inflammatory disease-susceptible Lewis rats: in vivo and in vitro studies suggesting globally defective hypothalamic secretion of corticotropin-releasing hormone; Calogero AE et al.; The susceptibility of female Lewis (LEW/N) rats to the development of streptococcal cell wall (SCW)-induced arthritis and other autoimmune phenomena is associated with the inability of their hypothalamic-pituitary-adrenal (HPA) axis to adequately respond to inflammatory stimuli . In contrast, resistance to the development of SCW-induced arthritis and other inflammatory autoimmune manifestations in histocompatible female Fischer rats (F344/N) is related to their intact HPA axis response to inflammatory mediators . To evaluate the mechanism and the specificity of the HPA axis defect in LEW/N rats, we examined the ability of three major excitatory neurotransmitter systems to activate the HPA axis in both Lewis and Fisher rats . The responsiveness of plasma ACTH and corticosterone to the cholinergic muscarinic receptor agonist arecoline, the alpha 1-adrenergic receptor agonist methoxamine and the serotonin (5-HT) type 2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane were significantly blunted and/or abolished in LEW/N compared to F344/N rats . To localize the HPA axis defect to the hypothalamic CRH neuron, we evaluated the ability of explanted hypothalami from the two strains to secrete immunoreactive CRH in vitro, in response to acetylcholine (ACh), norepinephrine (NE), 5-HT and the 5-HT agonist quipazine . LEW/N hypothalami released less immunoreactive CRH (iCRH) in response to ACh, NE, 5-HT and quipazine than F344/N hypothalami . The dose-response curves of these compounds in the former were shifted to the right and/or abolished, suggesting decreased sensitivity of LEW/N hypothalami to these neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS) Int J Cancer, 1992 Apr 22, 51(1), 124 - 9 Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line, HCC-M; Saito H et al.; Human neutrophil-mediated oxidative processes against a human hepatoma cell line, HCC-M, was visualized at the cellular level by using a silicon-intensified target camera and subsequently processing with a computer-assisted digital-imaging processor . Neutrophils were activated by a streptococcal preparation, OK-432 . A hydroperoxide-sensitive tracer, dichlorofluorescein diacetate, was loaded in HCC-M and temporal and spatial changes of lipid peroxides in this cell after addition of stimulated neutrophils were analyzed . The luminol-dependent chemiluminescence activity of neutrophils was significantly enhanced and continued for at least 2 hr by stimulation with OK-432, and its activity was shown to be accumulated at the site where a neutrophil attached with HCC-M . The intensity of dichlorofluorescein fluorescence in HCC-M rapidly increased after adding stimulated neutrophils, and their reaction was significantly attenuated by superoxide dismutase . The number of non-viable cells was increased as the dichlorofluorescein fluorescence increase . It is suggested that oxidative stress may play an important role in neutrophil-mediated tumor-cell damage. Biochemistry, 1992 Apr 14, 31(14), 3597 - 603 Thermodynamic analysis of the folding of the streptococcal protein G IgG-binding domains B1 and B2: why small proteins tend to have high denaturation temperatures; Alexander P et al.; We have cloned, expressed, and characterized two naturally occurring variations of the IgG-binding domain of streptococcal protein G . The domain is a stable cooperative folding unit of 56 amino acids, which maintains a unique folded structure without disulfide cross-links or tight ligand binding . We have studied the thermodynamics of the unfolding reaction for the two versions of this domain, designated B1 and B2, which differ by six amino acids . They have denaturation temperatures of 87.5 degrees C and 79.4 degrees C, respectively at pH 5.4, as determined by differential scanning calorimetry . Thermodynamic state functions for the unfolding reaction (delta G, delta H, delta S, and delta Cp) have been determined and reveal several interesting insights into the behavior of very small proteins . First, though the B1 domain has a heat denaturation point close to 90 degrees C, it is not unusually stable at physiologically relevant temperatures (delta G = 25 kJ/mol at 37 degrees C) . This behavior occurs because the stability profile (delta G vs temperature) is flat and shallow due to the small delta S and delta Cp for unfolding . Related to this point is the second observation that small changes in the free energy of unfolding of the B-domain due to mutation or change in solvent conditions lead to large shifts in the heat denaturation temperature . Third, the magnitude and relative contributions of hydrophobic vs nonhydrophobic forces (per amino acid residue) to the total free energy of folding of the B-domain are remarkably typical of other globular proteins of much larger size. Biochemistry, 1992 Apr 14, 31(14), 3604 - 11 Sequence-specific 1H NMR assignments and secondary structure of the streptococcal protein G B2-domain; Orban J et al.; Two-dimensional NMR spectroscopy has been used to obtain sequence-specific 1H NMR assignments for the IgG-binding B2-domain of streptococcal protein G . Secondary structure elements were identified from analysis of characteristic backbone-backbone NOE patterns and amide proton exchange data . The B2-domain contains a four-stranded beta-sheet region in which the two inner strands form a parallel beta-sheet with each other and antiparallel beta-sheets with the outer strands . The outer strands are connected via a 16-residue alpha-helix and short loops on both ends of the helix . The alpha-helix and beta-sheet structures contain well-defined polar and apolar sides, and numerous long-range NOEs from the apolar helix to apolar sheet regions were used to derive a model for the global fold of the B2-domain . While the overall fold is similar to that obtained for B1-type domains, differences in amide proton exchange rates and hydrophobic packing are observed. Schweiz Med Wochenschr, 1992 Apr 11, 122(15), 529 - 37 {Rheumatic fever . Its current status based on 4 cases}; Satz N et al.; We report on 4 patients with rheumatic fever hospitalized and investigated in our clinics within a 12 month period between 1990 and 1991 . In each case a clinically non-severe sore throat preceded the outbreak of rheumatic fever . In three cases diagnosis was according to the revised Jones criteria . Polyarthritis was the only major symptom in these cases . One patient suffered from monarthritis . Minor symptoms were fever, arthralgia, elevated blood sedimentation rates and elevated values for CRP and for antistreptolysin O . The joint symptoms were treated with nonsteroidal drugs and subsided . One of the patients had a recurrence 9 months after the first attack even though correct secondary prophylaxis with a 4-weekly intramuscular regimen of 1.2 million units of benzathine penicillin was carried out . We discuss some epidemiological aspects and diagnostic difficulties resulting from a changing clinical pattern of the disease, and emphasize the need for streptococcal sore throat treatment and continuous secondary prophylaxis to prevent recurrences. Acta Paediatr Jpn, 1992 Apr, 34(2), 169 - 72 Inherited deficiency of the ninth component of complement associated with streptococcal infection; Fujita M et al.; A 7 year old boy, who presented with streptococcal infection, was found to have a low serum complement level (CH50) . The C9 component was undetectable . His CH50 rose to the normal value and remained normal for at least three weeks, but decreased to one-third of the normal level three months later . Family studies were consistent with a familial C9 deficiency, with autosomal co-dominant inheritance. Ther Umsch, 1992 Apr, 49(4), 250 - 6 {Localized bacterial skin infections and dermatologic manifestations of systemic infections}; Zimmerli W et al.; Localized bacterial skin infections are frequent . In furunculosis, a local treatment is usually sufficient . In case of frequent recurrence a possible staphylococcus aureus colonization should be looked for and eliminated . Erysipela is treated by systemic antibiotics in order to avoid complications such as streptococcal gangrena or parainfectious glomerulonephritis . Anaerobic cellulitis and gas gangrena are postoperative or posttraumatic infections of the soft tissues which require a combined surgical and antibiotic treatment . Systemic infections may be recognized by characteristic skin lesions . These skin lesions are the consequence of bacterial emboli, vasculitis, intravascular coagulation or toxins, respectively . Examples for such manifestations are lesions in endocarditis, purpura fulminans, ekthyma gangrenosum, disseminated candidemia and toxic shock syndrome. J Intern Med, 1992 Apr, 231(4), 339 - 47 Prognosis in glomerulonephritis . III . A longitudinal analysis of changes in serum creatinine and proteinuria during the course of disease: effect of immunosuppressive treatment . Report from Copenhagen Study Group of Renal Diseases; Brahm M et al.; A total of 395 consecutive patients with biopsy-proven glomerulonephritis were followed up for 14 years . At the time of entry to the study the patients were classified as having one of nine states of kidney disease according to serum creatinine levels and proteinuria . The transitions of the patients between the nine states were analysed . The influence of 14 independent variables including treatment with cytostatic drugs and prednisolone was estimated by the Cox proportional hazard model . Treatment with immunosuppressive drugs had an influence that emerged within the first month and continued for the next 2 months . Subsequent treatment with cytostatic drugs in combination with prednisolone delayed further improvement . Treatment with prednisolone or cytostatic drugs as single therapy for up to 6 months increased the risk of improvement of the disease, and had no significant effect on deterioration . The beneficial effect of the treatment persisted after withdrawal of the immunosuppressive drugs . The analysis revealed only a slight influence of the histological character of the glomerular changes . Post-streptococcal glomerulonephritis carried an increased tendency for improvement . Arterial hypertension affected the process in several states of kidney disease . Heavy proteinuria increased the risk of increasing serum creatinine levels. Pediatr Infect Dis J, 1992 Apr, 11(4), 295 - 300; discussion 300-3 Group A streptococcal strains in Kuwait: a nine-year prospective study of prevalence and associations; Majeed HA et al.; During a period of 9 years (December, 1980, through November, 1989), 407 Group A streptococcal strains were isolated from 294 children with acute rheumatic fever and 303 of their family contacts, 234 children with acute post-streptococcal glomerulonephritis and 242 of their family contacts and 219 children with uncomplicated Group A streptococcal pharyngitis . Of the 407 strains 216 (53%) were M and/or serum opacity factor typable, 143 (35%) were only T typable and 48 (12%) were nontypable . Throughout the period of study the M12 and M1 were the most prevalent strains; however, important changes among the prevalent strains were observed . Although the study started in 1980 the serotypes M18, M81, M3, M15 and M58 made their first appearance 7 to 9 years later . These findings show the value of long term studies in detecting the changes in the prevalence of streptococcal strains in the community . M18 was isolated from three children with nephritis but not from children with rheumatic fever; this association has not been reported before . M12 was isolated from 26% of the nephritic children and their families vs . 7% from the rheumatic children and their families (P less than 0.05) vs . 17% from children with uncomplicated streptococcal pharyngitis . M49 was isolated from 7% of the nephritic children and their families vs . none from rheumatic children and their families vs . 1.4% from children with uncomplicated streptococcal pharyngitis . These findings support the concept of nephritogenicity of some streptococcal strains.(ABSTRACT TRUNCATED AT 250 WORDS) J Pediatr, 1992 Apr, 120(4 Pt 1), 563 - 4 Prechewing of food by adults and streptococcal pharyngitis in infants; Steinkuller JS et al.; Three infants with group A streptococcal pharyngitis were found to have eaten food prechewed by their parents . One parent had a history of recent pharyngitis and another had frequent episodes of tonsillitis . Prechewing of babies' food, which may be more common in the United States than is generally recognized, may be a mode of transmission of group A streptococcal pharyngitis to infants. Vet Immunol Immunopathol, 1992 Mar, 31(3-4), 205 - 27 Defective in vitro motility of polymorphonuclear leukocytes of homozygote and heterozygote Chediak-Higashi cats; Colgan SP et al.; The in vitro migratory responses of neutrophils of homozygote and heterozygote Chediak-Higashi cats were defective in an under-agarose assay when compared to the behavior of phagocytes of control cats . The linear distances traversed by the leading front of migrating Chediak-Higashi neutrophils toward streptococcal culture supernatant, zymosan-activated serum or buffer were reduced and smaller numbers of Chediak-Higashi phagocytes populated the resulting migration areas than did cells of control animals . The relative migration parameters of the Chediak-Higashi phagocytes, however, did not differ from the corresponding parameters of control neutrophils in the presence of streptococcal culture supernatant . Therefore, phagocytes of homozygote and heterozygote Chediak-Higashi cats recognized and responded equally well to the bacterial stimuli as did cells of control animals but traveled shorter distances primarily because of a reduced inherent motility . Similar results were also obtained when the feline phagocytes were attracted by zymosan-activated serum . In addition the relative migration parameters of the neutrophils of homozygote Chediak-Higashi cats were reduced and the normalized spatial distributions of their migrating cells were significantly different in the presence of 100% and 20% zymosan-activated serum when compared to the corresponding migration parameters of carrier and control animals . Defective recognition or responses to the higher concentrations of these host-derived attractants complicated, therefore, the already reduced inherent motility of the phagocytes of homozygote Chediak-Higashi cats. Semin Dermatol, 1992 Mar, 11(1), 3 - 10 Streptococcal skin diseases in children; Barnett BO et al.; Infections with streptococcal bacteria continue to be a common problem in children . They can produce cutaneous manifestations via three main mechanisms: (1) direct infection of the skin; (2) toxin-mediated disease; and (3) immunologically mediated disease . This review updates a variety of streptococcal diseases involving the skin . The changing bacteriology of impetigo is addressed, as well as the resurgence of rheumatic fever . A new manifestation of invasive streptococcal infection, termed streptococcal toxic shocklike syndrome, is also presented . Many changes in the epidemiology of streptococcal infections during the 1980s can be traced to the reemergence of more virulent strains of the organism . The impact of this natural occurrence is discussed . Therapeutic recommendations are presented for each disease, and the value of rapid streptococcal tests is reviewed. South Med J, 1992 Mar, 85(3), 261 - 5 Resurgence of acute rheumatic fever in west Alabama; Hefelfinger DC; This study was done to ascertain whether there was an increased incidence of acute rheumatic fever (ARF) in west Alabama, similar to that reported elsewhere within the United States . Hospital records for the previous 10 years were reviewed and 5-year intervals were compared (1980 through 1984 vs 1985 through 1989) . A sevenfold increase was noted in the later period . Possible explanations for this increase are discussed . Close surveillance, appropriate testing, and adequate complete treatment must be continued to eradicate streptococcal disease leading to acute rheumatic fever. Infect Immun, 1992 Mar, 60(3), 1202 - 9 Partial characterization and staphylocidal activity of thrombin-induced platelet microbicidal protein; Yeaman MR et al.; Thrombin-induced platelet microbicidal protein (PMP) is considered to play an important role in preventing an important role in preventing streptococcal endocarditis . However, the structural features and functions of PMPs have not been well characterized, and their antibacterial spectra against other common endocarditis pathogens, such as the staphylococci, are not known . Thrombin stimulation of washed rabbit platelets (10(8)/ml) yielded a PMP-rich preparation with a specific activity of approximately 25 U/mg of protein as determined by Bacillus subtilis bioassay . Twenty-eight clinical and laboratory Staphylococcus aureus isolates, exposed to a standardized PMP preparation (100 U/ml for 2 h at 37 degrees C), exhibited a Poisson-distributed heterogeneity to the bactericidal action of PMP, with approximately one-third designated as PMP resistant . Gel filtration chromatography (Sephadex G-50) identified the bioactive moiety within PMP preparations to be in the major protein elution peak; sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) presumptively identified PMP as a low-molecular-weight (MW) (8,500) protein present only in such bioactive protein peaks . Both the bioactivity of PMP preparations and the low-MW protein band were removable by specific anionic membranes (e.g., cellulose-acetate/nitrate), as well as by a variety of anionic resins, further corroborating the suspected cationic charge of PMP . In addition, both PMP bioactivity and the low-MW protein band were recoverable by 1.5 M NaCl elution of the anionic membrane filters post-PMP adsorptive removal . Adsorption of bioactive PMP preparations by highly PMP-susceptible B . subtilis (10(8) CFU/ml, 30 min) resulted in a near-complete loss of residual bioactivity; in contrast, adsorption of bioactive PMP preparations with less PMP-susceptible S . aureus strains failed to reduce bioactivity . Significant lysozyme contamination of PMP-rich preparations was ruled out by determination of differences between bioactive PMP preparations and exogenous lysozyme as regards (i) relative heat stabilities; (ii) differential bactericidal activity versus B . subtilis and Micrococcus luteus; and (iii) SDS-PAGE protein profiles . These data show that the bioactive PMP protein moiety is of low MW, is heat stable, is probably cationic (similar to leukocyte-derived defensins), and possesses potent bactericidal activity against a significant percentage of S . aureus isolates. Exp Eye Res, 1992 Mar, 54(3), 455 - 60 Immunohistochemical localization of hyaluronan synthase in cornea and conjunctive of cynomolgus monkey; Rittig M et al.; Distribution of hyaluronan synthase was investigated in cornea and conjunctiva of Cynomolgus monkeys (Macaca fascicularis) using polyclonal antibodies against the streptococcal enzyme . Strong immunoreaction was found in the cell membranes of the corneal endothelium, corneal epithelium, and most of the conjunctival epithelium . In the corneal epithelium all cells except the basal ones stained . In the conjunctiva all cylindrical cells stained, whereas among the goblet cells one type showed intense membrane staining, the other remained unstained . In the limbal portion of the conjunctival epithelium, which in many other respects differs morphologically and functionally from the remaining conjunctiva, all membranes of the different layers of the stratified epithelium except the most superficial ones, appeared unstained . Staining was also seen in all stromal fibroblasts and capillary endothelial cells. Clin Exp Dermatol, 1992 Mar, 17(2), 87 - 93 Erythema elevatum diutinum: a clinicopathological study; Wilkinson SM et al.; Erythema elevatum diutinum is a syndrome of vasculitis in which lesions, typically over the extensor surfaces, showed a mixed inflammatory infiltrate on biopsy . We describe a series of 13 patients . The most common association in our series was with hypergammaglobulinemia; both mono and polyclonal . Chronic infection, not streptococcal, was a less frequent finding although two of three patients had a positive reaction to the intradermal injection of streptococcal antigen . Dapsone remains the initial treatment of choice. Clin Neuropathol, 1992 Mar-Apr, 11(2), 77 - 86 Immune-mediated neuropathy and myopathy in post-streptococcal disease: electron-microscopical, morphometrical and immunohistochemical studies; Sommer C et al.; A 22-year-old man suffered from a complete flaccid tetraparesis and an immune complex-mediated rapid progressive glomerulonephritis after group A streptococcal infection . Serum creatine kinase was excessively elevated and myoglobinuria occurred . Nerve conduction studies revealed evidence of axonal neuropathy . Recovery was satisfactory within 18 months . Sural nerve and peroneus muscle biopsies were performed in the 4th and 14th week of the disease . Light microscopy of the sural nerve showed an incipient axonal type of neuropathy in the first biopsy . Ultrastructurally, Wallerian degeneration and endoneurial inflammatory cells were present . In the muscle biopsy, few atrophic fibers and altered blood vessels without further anomalies were found . In the second sural nerve biopsy, macrophages were numerous, some of which were immunoreactive for HLA-DR, and only a few myelinated and some unmyelinated nerve fibers remained . Muscle fibers in the second biopsy showed high-grade atrophy and myofibrillar abnormalities . Immunohistochemistry revealed diffuse endoneurial immunoglobulin deposition in the first sample, while in the later biopsy specimen, deposits of IgG, and kappa and lambda light chains were visible in circumscribed endoneurial areas . Immune-mediated neuropathy and myopathy are not well-known complications of streptococcal disease . This is, to our knowledge, the first detailed report on morphological findings in muscle and nerve in such a disorder. Br J Dermatol, 1992 Mar, 126(3), 286 - 9 A case of skin hyperpigmentation due to alpha-MSH hypersecretion; Pears JS et al.; A case is presented of generalized skin hyperpigmentation due to alpha-MSH hypersecretion from the pituitary that was most marked in the light-exposed areas . The patient also had secondary adrenal dysfunction, peripheral lymphadenopathy, streptococcal glomerulonephritis and malabsorption . Analysis of this patient's alpha-MSH using high-pressure liquid chromatography (HPLC) showed a novel acetylation profile compared to normal individuals and to patients with Cushing's disease and Nelson's syndrome . Glucocorticoid replacement therapy resulted in suppression of alpha-MSH hypersecretion and complete resolution of the illness. J Biol Chem, 1992 Feb 25, 267(6), 3832 - 40 Active-site structural comparison of streptococcal NADH peroxidase and NADH oxidase . Reconstitution with artificial flavins; Ahmed SA et al.; The apoproteins of the streptococcal NADH peroxidase (H2O2----2H2O) and NADH oxidase (O2----2H2O) stabilize the neutral forms of 6-hydroxy- and 6-mercapto-FAD, respectively . The redox behavior of the 6-hydroxy-FAD peroxidase closely mimics that of the native enzyme with both dithionite and NADH . Both oxidase and peroxidase preferentially stabilize the N(1)-protonated p-quinonoid species of 8-mercapto-FAD, and the 8-position of the bound flavin is accessible to solvent in both proteins . The 8-mercapto-FAD peroxidase yields an EH2 spectrum on reduction virtually identical to that seen with 8-mercapto-FAD glutathione reductase, but no distinct EH2.NADH form appears . The dramatic decreases in reactivity at the flavin 2- and 4-positions for both the peroxidase and the oxidase, assessed with the reconstituted 2- and 4-thio-FAD enzymes, suggest that these positions are buried by elements of both protein structures . Furthermore, reconstitution of the peroxidase with the higher potential 2- and 4-thioflavins yields enzyme forms which are fully reducible with 1.4 eq of NADH/FAD, giving rise to stable thio-FADH2.NAD+ complexes . This behavior closely mimics that of the native NADH oxidase and provides further evidence supporting the hypothesis that a major functional distinction between the two structurally related proteins is determined by the redox potential and/or NADH reactivity of the bound flavin coenzyme. J Mol Biol, 1992 Feb 20, 223(4), 853 - 6 Localization of bound water in the solution structure of the immunoglobulin binding domain of streptococcal protein G . Evidence for solvent-induced helical distortion in solution; Clore GM et al.; The presence of bound water in the solution structure of the IgG binding domain of streptococcal protein G has been investigated by nuclear magnetic resonance using three-dimensional 1H rotating frame Overhauser 1H-15N multiple quantum coherence spectroscopy . The backbone amide protons of three residues, Ala20, Gln32 and Tyr33, are found to be in close proximity to bound water . Examination of the three-dimensional structure of the IgG binding domain indicates that in the vicinity of these three residues there are no backbone groups that do not already participate in hydrogen bonding and there are no suitably placed side-chain groups available for hydrogen bonding with water . As the lifetime of the bound water detected in this nuclear magnetic resonance experiment is greater than about one nanosecond, it is likely that the two bound water molecules participate in a bifurcating hydrogen bonding network comprising a CO-NH hydrogen bonded pair, such that the water molecule accepts a hydrogen bond from the NH proton and donates one to the carbonyl oxygen with the result that the amide proton is involved in a three center hydrogen bond . On the basis of the structure, one water molecule participates in such an interaction with the Ala20(NH)-Met1(CO) hydrogen bonded pair at the beginning of an anti-parallel beta-sheet, and the other with the Tyr33(NH)-Val29(CO) hydrogen bonded pair in the single alpha-helix . The latter, which is external and solvent accessible, is associated with a distortion in the alpha-helix centered around Tyr33 which consists of a significant increase in the CO(i-4)-N(i) and CO(i-4)-NH(i) distances relative to those in the rest of the helix, as well as a significant departure in the phi, psi angles of Tyr33 relative to regular helical geometry . Such solvent induced distortions in alpha-helices have been previously noticed in crystal structures and were postulated as possible folding intermediates for helical structures . The present observation of this phenomenon in solution indicates, however, that these water molecules are tightly bound and represent an integral part of the protein framework. Vet Rec, 1992 Feb 15, 130(7), 138 - 9 Phenoxymethyl penicillin potassium as an in-feed medication for pigs with streptococcal meningitis; Johnston PI et al.; In two separate studies involving 2500 weaner pigs, strategic infeed medication with phenoxymethyl penicillin potassium significantly reduced the incidence of streptococcal meningitis. Vet Immunol Immunopathol, 1992 Feb 15, 31(1-2), 129 - 40 Streptococcal products and leukocyte activities; Lambot M et al.; Various streptococcal species are directly responsible for udder infections which should normally be countered by polymorphonuclear neutrophils (PMNs) . In order to detect a putative inhibition of streptococcal products on the activities of bovine PMNs, we used a combination of four tests which permits an adequate evaluation of PMNs functions, e.g . PMN adherence on endothelial cells, chemotactic assay, phagocytosis of bacteria labelled with fluorescein isothiocyanate (FITC) and measurement of anion superoxide production . The conclusion is that neither of the two pathogenic streptococcal species isolated from mastitis appeared to produce in vitro factors affecting PMN activities. Biochim Biophys Acta, 1992 Feb 14, 1138(2), 157 - 61 Stimulation of arachidonic acid metabolism by a streptococcal preparation (OK-432) in rat peritoneal macrophages; Watanabe M et al.; A streptococcal preparation OK-432 is reported to be an immunopotentiator and a potent antitumor agent . In order to elucidate the mechanism of biologic action, effects of OK-432 on arachidonic acid metabolism in rat peritoneal macrophages were investigated . Prostaglandin E2 production and release of radioactivity from {3H}arachidonic acid-labeled macrophages were found to be stimulated by OK-432 in a concentration-dependent manner (5 to 80 micrograms/ml) . Heat-treatment of OK-432 further stimulated its effects . These stimulative effects on arachidonic acid metabolism by OK-432 were not observed in MDCK cells that have no phagocytotic activity . Furthermore, cytochalasin B treatment completely suppressed the stimulative effects induced by OK-432 in macrophages . These results strongly indicate that the stimulative effects by OK-432 on arachidonic acid metabolism are dependent on phagocytosis of OK-432 particles . Significance of stimulation of arachidonic acid metabolism in macrophages by OK-432 for its biological effects is discussed. Nucleic Acids Res, 1992 Feb 11, 20(3), 395 - 400 Copy number control of the streptococcal plasmid pIP501 occurs at three levels; Brantl S et al.; Transcriptional analysis of the replication region of plasmid pIP501 has revealed three active promoters . The repR gene which is essential for pIP501 replication was transcribed from promoter pII . A small antisense RNA (136 nt, RNAIII) generated from promoter pIII was complementary to the leader region of the repR mRNA . Introduction of either point mutations or deletions into promoter pIII or RNAIII resulted in a 5-20fold increased plasmid copy number suggesting a negative regulatory function for RNAIII . The copR gene, the complete DNA and amino acid sequence of which is reported, was dispensable for pIP501 replication . However, deletion of the copR promoter pI and/or the copR coding sequence led to a 10-20fold increase in plasmid copy number . This effect was also observed when a -1 frameshift mutation was introduced into the CopR coding region . Mutations in copR and pIII/RNAIII were not additive . It is, therefore, proposed that both components act at the same level of copy number control most likely in a sequential way . A second level of copy number control was found to involve an inverted repeat structure upstream of and overlapping with promoter pII . Destruction of this repeat sequence by deletion caused an increase in copy number 2-3fold higher than that observed for either RNAIII or copR mutations . A working model is proposed how different components of pIP501 interact to regulate its copy number. Biochemistry, 1992 Feb 11, 31(5), 1451 - 7 Localization of the binding site for streptococcal protein G on human serum albumin . Identification of a 5.5-kilodalton protein G binding albumin fragment; Falkenberg C et al.; Protein G is a streptococcal cell wall protein with separate and repetitively arranged binding domains for immunoglobulin G (IgG) and human serum albumin (HSA) . In this work, the binding of protein G to HSA was studied . The results suggest that a single binding site is present on HSA: the apparent size of the HSA-protein G complex (230 kDa) corresponded to two or three HSA molecules bound to one protein G molecule, and Ouchterlony immunodiffusion did not yield any precipitate between protein G and HSA . HSA was cleaved by pepsin and CNBr into several fragments which were identified by SDS-PAGE and N-terminal amino acid sequencing, and the binding of protein G to the fragments was studied in Western blot experiments . The results indicated that the binding area was located in disulfide loops 6-8, involving both the second (loop 6) and the third (loops 7 and 8) domain of HSA . One of the protein G binding pepsin fragments, with an apparent molecular mass of 5.5 kDa, located in loops 7 and 8, was isolated and found to completely inhibit the binding between protein G and the intact HSA, again suggesting a single protein G binding site on serum albumin . Reducing the disulfide bonds of HSA, and subsequent alkylation of the half-cystine residues, significantly decreased the affinity for protein G . Protein G bound to albumin from baboon, cat, guinea pig, hamster, hen, horse, man, mouse, and rat, but not to albumin from cow, dog, goat, pig, rabbit, sheep, snake, or turkey. JAMA, 1992 Feb 5, 267(5), 695 - 7 Insensitivity of rapid antigen detection methods and single blood agar plate culture for diagnosing streptococcal pharyngitis; Wegner DL et al.; OBJECTIVE--To compare the sensitivity of five group A streptococcal antigen detection systems and single blood agar plate culture with a two-plate culture method for diagnosis of streptococcal pharyngitis . DESIGN--Two simultaneous throat swabs were obtained from consecutive patients with suspected streptococcal pharyngitis . One swab was tested for streptococcal antigen by physicians' office nurses and the other was cultured on both aerobic blood agar and anaerobic trimethoprim-sulfamethoxazole blood agar plates . SETTING--Community office practice and community hospital laboratory . PARTICIPANTS--Consecutive outpatients seen by one of four pediatricians or a family practice physician . MAIN OUTCOME MEASURES--Results of rapid streptococcal antigen tests were compared with culture results either on a single aerobic blood agar plate or on the two-plate culture method . RESULTS--On throat swabs from 755 consecutive outpatients, the two-plate culture method detected 261 cases (defined as 100%) of group A streptococcal pharyngitis . The anaerobic trimethoprim-sulfamethoxazole plate alone, read at 1 and 2 days, detected 245 cases (94%) . The blood agar plate used alone detected 189 cases (72%) at 2 days and 151 cases (58%) at 1 day . Antigen detection test results were positive for 106 throat specimens (41%), with individual kit sensitivity ranging from 31% to 50% compared with the two-plate culture method . Antigen detection test sensitivity decreased with decreasing colony counts . Antigen kit false-positivity rates varied from 0 to 28% . CONCLUSIONS--We conclude that the single blood agar plate culture and the antigen detection tests are insensitive, possibly leading the physician toward undertreatment and risking immunologic, local, or distant sequelae . The two-plate culture method should be the standard of practice to rule out streptococcal pharyngitis. Harefuah, 1992 Feb 2, 122(3), 137 - 42 {Inadvertent child health neglect by preference of homeopathy to conventional medicine}; Tsur M; The effectiveness of alternative medicine, especially homeopathy, has not been proven by prospective, double-blind, controlled studies . However, homeopathy has been gaining in popularity in Israel . 4 children of religious parents are presented, who were treated by homeopathic medical practitioners for cervical streptococcal lymphadenitis, acute lymphatic leukemia, bacterial pneumonia and atopic dermatitis, respectively . The parents of the latter 3 children rejected the correct medical diagnoses, as well as any medical treatment offered by other medical practitioners . All of the children had severe, unusual, but preventable complications . "Alternative" medicine, especially homeopathic practice, is dealt with from medical, social and comparative law aspects . The 4 cases are considered examples of a special kind of child neglect, inadvertent child health neglect because of false beliefs or lack of knowledge . The government is called upon to prevent this kind of child neglect by education of the public and the enactment of appropriate laws and their enforcement . This should be done even if the right to choose one's health treatment system and practitioner is preferred to the right not to be offered ineffective treatment. Int J Immunopharmacol, 1992 Feb, 14(2), 205 - 11 Oral administration of a streptococcal agent OK-432 activates alveolar macrophages in mice; Kinoshita A et al.; The effect of orally administered OK-432, a streptococcal preparation, on the functions of alveolar macrophages in mice was examined . The oral administration of OK-432 (1, 2 or 4 KE, four times every 3 days) augmented phagocytic activity, lysosomal enzyme activity and interleukin 1 (IL-1) production of murine alveolar macrophages recovered 5 days after the final administration while it did not augment H2O2 production . The number of alveolar macrophages was not affected by the same treatment . These results suggested that oral administration of OK-432 activates alveolar macrophages qualitatively to protect the lung from the metastasis of cancer cells and infectious diseases by pathogenic micro-organisms. Singapore Med J, 1992 Feb, 33(1), 29 - 30 The toxic strept syndrome: two case reports; Tan HC et al.; We describe two patients with group A beta hemolytic streptococcal septicemia from minor foci in the skin . They developed extreme toxemia, mental obtundation and multi-system organ failure associated with diffuse erythema . They both survived after appropriate antibiotic and intense supportive therapy . These are examples of the "toxic strept syndrome" which is similar to staphylococcal toxic shock. Rev Prat, 1992 Feb 1, 42(3), 293 - 7 {Acute articular rheumatism: physiopathology, clinical aspects}; Longuet P et al.; Acute rheumatic fever is characterized by non suppurative inflammatory lesions involving the heart, joints, subcutaneous tissues and central nervous system . It is a complication of group A streptococcal upper respiratory tract infection . The pathogenic mechanisms remain unknown although there is a general agreement as to an immunological hypothesis . Pharyngitis must be treated, even if streptococcal origin is not proved . Penicillin remains the first choice antibiotic . Epidemiological studies of all group A streptococcal serotypes isolated should be performed. Infect Immun, 1992 Feb, 60(2), 701 - 5 Distinct T-cell receptor V beta gene usage by human T lymphocytes stimulated with the streptococcal pyrogenic exotoxins and pep M5 protein; Tomai MA et al.; A number of streptococcal products, including the streptococcal pyrogenic exotoxin (SPE) types A, B, and C as well as a 22-kDa fragment of M type 5 protein (pep M5), are potent stimulants of human T-lymphocyte blastogenesis and belong to the newly designated family of superantigens . The V beta usage of human T cells stimulated with these toxins was investigated by using the polymerase chain reaction . We demonstrate that SPE A, B, and C as well as pep M5 stimulate the proliferation of T cells in a dose-dependent manner . pep M5 stimulates cells bearing V beta 2, 4, and 8 elements of the T-cell receptor (TCR), whereas SPE A stimulates TCR V beta 2-, 12-, 14-, and 15-bearing cells . SPE B stimulated only cells expressing TCR V beta 8 elements, while SPE C stimulated cells expressing V beta 1, 2, 5.1, and 10 . These studies reveal that the preferential usage of particular V beta elements is distinct for these different superantigens, which may be important in the pathogenesis of various streptococcal diseases. Klin Med (Mosk), 1992 Feb, 70(2), 66 - 71 {Cardiolipin antibodies in acute rheumatic fever}; Dzhuzenova BS et al.; The paper presented the results obtained in studying the patients with acute rheumatic fever for antibodies to cardiolipin (ACL) . The study resulted in the establishment that the development of immunopathies in the presence of acute rheumatic fever combined with the acute streptococcal infection was accompanied by hyperproduction of ACL (more common IgG versus IgM isotypes) . The phenomenon mentioned widened the spectrum of acute infectious diseases associated with an increase in ACL synthesis . It was also stated that increased ACL contents were closely related with the involvement of the cardiac valves . Authentic clinical and echocardiological signs of the heart disease were mainly revealed in the patients with high contents of IgG and IgM isotypes of ACL . A certain relationship between the laboratory activity of the disease and ACL hyperproduction was noted as well . The latter permitted the discussion on the impact of streptococcal infection initiating the development of acute inflammation on the hyperproduction of ACL. Lik Sprava, 1992 Feb, (2), 51 - 3 {Changes in the complement system in acute streptococcal infection}; Bala MA et al.; Results are reported of a study of relationship of complement level, unspecific adaptative reactions, number of circulating immune complexes and some cellular parameters of the immunogram in patients with different forms of streptococcal infection . Different changes were found in acute and chronic forms of the disease . The possible mechanisms of development of these disorders are discussed. Diabetes Res, 1992 Feb, 19(2), 63 - 7 Prediction of insulin dependent diabetes mellitus in non-obese diabetic mice by the endogeneous tumor necrosis factor-alpha level; Setoguchi J et al.; The non-obese diabetic (NOD) mouse is an animal model of human insulin dependent diabetes mellitus (IDDM) . In this strain, the serum concentration of tumor necrosis factor-alpha (TNF alpha) after OK432 (a streptococcal preparation) stimulation is much lower than in any other non-diabetic control strain . Female NOD mice which have a higher incidence of diabetes have significantly lower TNF alpha level (6.5 +/- 4 U/ml, mean +/- SEM) than do male NOD mice (21 +/- 5 U/ml) (P < 0.02) which have lower incidence of diabetes . On the basis of these results, we designed a prospective study to evaluate the relationship between the serum TNF alpha concentration and the incidence of diabetes in individual male NOD mice . Mice were studied until 30 weeks of age . During this period four of eight mice with a low TNF alpha level (TNF alpha < or = 1.1 U/ml) became diabetic, whereas none of eighteen mice with a high TNF alpha level (TNF alpha > 1.1 U/ml) developed overt diabetes . These results indicate that by measuring of endogeneous TNF alpha level after stimulation by OK432, one could predict IDDM in male NOD mice. Brain Res Dev Brain Res, 1992 Jan 17, 65(1), 115 - 8 Arthritis-susceptible Lewis rats fail to emerge from the stress hyporesponsive period; Aksentijevich S et al.; Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion . The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators . In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats . We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats . Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14 . Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period . This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases. Brain Res, 1992 Jan 20, 570(1-2), 54 - 60 Corticotropin releasing hormone related behavioral and neuroendocrine responses to stress in Lewis and Fischer rats; Sternberg EM et al.; We have recently shown that susceptibility to streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats is related to a lack of glucocorticoid restraint of inflammation while the relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats is related to their greater hypothalamic-pituitary-adrenal (HPA) axis response . The difference in pituitary-adrenal responsiveness results from decreased inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion in LEW/N rats . Because CRH not only activates the pituitary-adrenal axis, but also is associated with behavioral responses that are adaptive during stressful situations, we wished to determine if the differential LEW/N and F344/N CRH responsiveness to inflammatory mediators could also be associated with differences in neuroendocrine and behavioral responses to physical and emotional stressors . In this study, LEW/N rats exhibited significant differences compared to F344/N rats, in plasma adrenocorticotropin hormone (ACTH) and corticosterone responses during exposure to an open field, swim stress, restraint or ether . Furthermore, hypothalamic paraventricular CRH mRNA expression was also significantly lower in LEW/N compared to F344/N rats after restraint . These differences in neuroendocrine responses were associated with differences in behavioral responses in LEW/N compared to F344/N rats in the open field . Outbred HSD rats, which have intermediate and overlapping arthritis susceptibility compared to LEW/N and F344/N rats, exhibited intermediate and overlapping plasma corticosterone and behavioral responses to stressful stimuli compared to the two inbred strains . These data suggest that the differences in CRH responses in these strains may contribute to the behavioral and neuroendocrine differences we have observed . Therefore these strains may provide a useful animal model for studying the relationship between behavior, neuroendocrine and inflammatory responses. JAMA, 1992 Jan 8, 267(2), 264 - 7 Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone sodium for 4 weeks . Efficacy and outpatient treatment feasibility; Francioli P et al.; OBJECTIVE--To evaluate the efficacy and safety of ceftriaxone sodium in the treatment of streptococcal endocarditis . DESIGN--An open, multicenter, noncomparative study with a follow-up of patients for 4 months to 5 years . SETTING--Internal medicine wards and outpatient clinics of hospitals of various sizes in three European countries . PATIENTS--Fifty-nine patients with defined criteria for streptococcal endocarditis . INTERVENTION--Ceftriaxone sodium administered at a once-daily dose of 2 g for 4 weeks . MAIN OUTCOME MEASURES--Clinical outcome and microbiological cure rate . RESULTS--Among the 59 patients, 55 completed the treatment and were followed up for 4 months to 5 years . No patients showed evidence of relapse . Treatment was completely uneventful in 42 patients (71%) . A cardiac valve was replaced in four patients (7%) receiving antimicrobial therapy and in six patients (10%) who had completed antimicrobial therapy . One of the 10 valves taken for culture at surgery was positive, but only for microorganisms that were different from the microorganism isolated before the treatment . The treatment had to be interrupted in four patients because of drug allergy . Other side effects were mild except for two cases of reversible neutropenia . The treatment was easy to administer: 27 patients (46%) had no permanent intravenous catheter at any time, seven patients (12%) had such a catheter for less than 4 days . Twenty-three patients (39%) were discharged from the hospital less than 2 weeks after admission . CONCLUSIONS.--Ceftriaxone sodium administered at a once-daily dose of 2 g appears to be an effective and safe treatment of streptococcal endocarditis . In hospitals, this agent may be more convenient to administer than penicillin G with or without aminoglycosides . Some patients may even be treated as outpatients. Int J Syst Bacteriol, 1992 Jan, 42(1), 37 - 43 Analysis of bacteriolytic activity patterns, a novel approach to the taxonomy of enterococci; Pompei R et al.; The bacteriolytic activities of different group D streptococcal species on various media and substrates were studied . Our results showed that all of the enterococcal species which we tested had bacteriolytic activity on at least one of the media used, while the group D nonenterococcal species had no such activity . In addition, using culture media containing different additives and different pH values, we defined seven major groups of bacteriolytic activity (lyogroups), each of which overlapped with one species (four lyogroups), two species (two lyogroups), or four species (one lyogroup) . The detection of enterococcal lyogroups proved to be as reliable for species identification as the conventional methods presently in use. J Cancer Res Clin Oncol, 1992, 118(2), 157 - 62 Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy; Yamasaki S et al.; The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated . OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen . Seventeen (65%) patients responded to the therapy . The median survival time of all patients after treatment was 13 months (range, 2-63 months) . Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01) . The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4 . In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes . The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01) . In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin . These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification. South Med J, 1992 Jan, 85(1), 43 - 4 Group G streptococcal infection in an elderly patient; Daly MP; It is only recently that GGS infections have been reported in the literature . These infections are rare, but they are serious when they occur . The organism is not very virulent, and serious infections occur only in patients who are immunocompromised, have some serious underlying disease such as cancer or intravenous drug abuse, or are at the extremes of age . I have described a fatal case of GGS meningitis and endocarditis in a previously healthy 84-year-old who had obtundation, irritability, and cellulitis . Many of the separately reported characteristics of serious GGS infections were present together in this case. Eur J Immunol, 1992 Jan, 22(1), 57 - 61 Treatment of rats with monoclonal anti-CD4 induces long-term resistance to streptococcal cell wall-induced arthritis; Van den Broek MF et al.; To investigate the role of CD4+ cells in the induction and maintenance of streptococcal cell wall (SCW)-induced arthritis, Lewis rats were treated with a monoclonal antibody against rat CD4 (W3/25) . Injection before onset of the arthritis resulted in resistance to SCW arthritis . Treatment with anti-CD4 during ongoing arthritis induced an amelioration of the arthritis, demonstrating that CD4+ cells are involved in both the induction and effector phases of the chronic arthritis . After return of CD4+ cells to normal levels in the circulation, no arthritis occurred in protected rats, despite the continued presence of SCW in the body . Even reinjection of SCW could not induce arthritis in these rats, suggesting that tolerance to SCW had occurred . In addition, these tolerized rats were refractory to actively induced adjuvant arthritis (AA), but were susceptible to passively transferred AA . Our data imply, that (a) treatment with anti-CD4 plus SCW induces a long-term resistance to SCW-induced arthritis and adjuvant arthritis, (b) SCW and M . tuberculosis may use similar mechanisms of regulation of arthritis and (c) active peripheral suppression is not the mechanism of this nonresponsiveness. J Clin Invest, 1992 Jan, 89(1), 97 - 108 In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis; Sano H et al.; Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo . We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis . Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia . Significantly less or equivocal staining was noted in OA and normal human synovia . Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats . In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis . COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained . Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats . These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids. Clin Immunol Immunopathol, 1992 Jan, 62(1 Pt 2), S87 - 91 Monoclonal antibodies in the therapy of experimental neonatal group B streptococcal disease; Hill HR et al.; Group B streptococcal (GBS) infections continue to be a major cause of morbidity and mortality in human neonates . This has led a number of investigators to explore the role of immunotherapy in the treatment of neonatal GBS disease . In early studies, we showed that intravenous immune globulin (IVIG) offered some protection against less virulent strains of GBS in a neonatal rat model of disease . Against more virulent strains, which produce an excess of sialic acid-containing type-specific antigen, IVIG offered little protection even when given in much higher doses . For this reason, we developed murine monoclonal antibodies (MuMAb) against type III GBS . MuMAb directed against the type III-specific antigen provided excellent protection against virulent (greater than 95%) and less virulent (94-100%) strains of GBS when administered in doses as low as 400 micrograms/kg up to 24 hr after bacterial inoculation . MuMAb IgM antibody was approximately 100-fold more effective than MuMAb IgG2a antibody . Unfortunately, MuMAbs are unlikely to be approved for use in human neonates . For this reason, we have evaluated a human monoclonal antibody (HuMAb) preparation against GBS derived from Epstein-Barr virus-immortalized peripheral blood B lymphocytes . This IgM HuMAb, which appears to be directed against the group B carbohydrate, is extremely active in both opsonic and protective assays against type Ia, II, and III GBS . Optimal immunotherapy of neonatal GBS disease may involve the use of HuMAb preparations, alone or in combination with polyclonal IVIG. Am Fam Physician, 1992 Jan, 45(1), 199 - 205 Culture and antigen detection tests for streptococcal tonsillopharyngitis; Pichichero ME; A throat culture is necessary for accurate diagnosis of group A beta-hemolytic streptococcal tonsillopharyngitis . The use of penicillin therapy in every patient with sore throat results in overtreatment of 85 percent of children and 95 percent of adults presenting to family physicians with the complaint of sore throat . Indiscriminate use of penicillin also increases the risk of drug side effects and subjects some patients to unnecessary alterations of microbial ecology . The signs and symptoms of group A beta-hemolytic streptococcal tonsillopharyngitis are nonspecific, and reliable clinical diagnosis is difficult . Throat culture is cost-effective and, if properly obtained and processed, more than 95 percent accurate . Antigen detection tests (rapid strep tests) are a viable laboratory alternative to throat cultures if these tests are properly performed and if negative test results are confirmed with traditional throat culture. Pediatrics, 1992 Jan, 89(1), 1 - 4 Extracorporeal membrane oxygenation and early-onset group B streptococcal sepsis; Hocker JR et al.; Recently, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy for newborns with overwhelming early-onset group B streptococcal sepsis . To determine which clinical factors best predict mortality and to evaluate the outcome of this therapy, a retrospective examination of the clinical course and outcome of ECMO-eligible newborns with early-onset group B streptococcal sepsis was undertaken . The study period was divided into two phases based on when ECMO was initially used at Kosair Children's Hospital as therapy for septic neonates . Phase 1 (pre-ECMO) was the period from January 1, 1982, through June 15, 1986, and phase 2 (ECMO) from June 16, 1986, through December 31, 1989 . Newborns with gestational age greater than or equal to 34 weeks, birth weight greater than or equal to 2000 g, and evidence of early-onset group B streptococcal sepsis were eligible for study . Only newborns who received mechanical ventilation were evaluated . Sixteen patients from phase 1 met the above criteria . Of those, 10 exhibited no sign of hypotension and all survived . Of the 6 patients with hypotension, 3 died . Forty patients were identified from phase 2 . Seven patients remained normotensive and all survived . Thirty-three patients were hypotensive, of which 15 received ECMO and 13 survived . Of the 18 who did not receive ECMO, 7 died . Regarding all hypotensive newborns, those who did not receive ECMO had a trend toward lower survival (P less than .06) and were more likely to die if they were of lower birth weight, manifested a persistent acidosis (pH less than or equal to 7.25), and had an absolute neutrophil count less than 500 cells/mm3.(ABSTRACT TRUNCATED AT 250 WORDS) Immunogenetics, 1992, 36(5), 319 - 25 Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene; Senju S et al.; The beta chain of the HLA-DQ molecule is shorter by eight amino acid residues than other major histocompatibility complex class II beta chains due to elimination of the fifth exon coding for part of the cytoplasmic domain . This elimination is caused by one base substitution in the splice acceptor site of the exon . We found that two HLA-DQB1 alleles, DQB1*0503 and DQB1*0601, did not have this substitution, and the exon was utilized in these two alleles . However, two forms of HLA-DQB mRNA, with or without exon 5, were generated in Epstein-Barr virus-transformed cell lines homozygous for DQB1*0503 or DQB1*0601, indicating alternative mRNA splicing . The alternative splicing of DQB1*0601 mRNA was also found in peripheral blood lymphocytes and L cell transfectants . To investigate the functional relevance of the allele-specific long cytoplasmic tail of HLA-DQ beta chain, we developed three types of L cell transfectants expressing exclusively the HLA-DQw6 molecules with short cytoplasmic tail, long cytoplasmic tail, or both forms of the beta chain, and used them as antigen presenting cells for streptococcal cell wall antigen-specific T cell lines . These three types of transfectants could function almost equally well as antigen presenting cells . It was thus demonstrated that both forms of HLA-DQ beta chain, with or without eight amino acid residues coded for by the exon 5, can be associated with the HLA-DQ alpha chain, be expressed on the cell surface, and function as restriction molecules in antigen recognition by the CD4+ T cells. Mol Gen Mikrobiol Virusol, 1992, (1-2), 7 - 13 {DNA-protein interactions in chromatin particles differing in electrophoretic mobility}; S'iakste et al.; The chromatin particles from Ehrlich carcinoma differing in the electrophoretic mobility were divided to a transcription active (c-particles) and transcription inactive (a-particles) fractions . Analysis of the DNA-protein interaction strength by the nucleoprotein-celite-chromatography has demonstrated that the majority of DNA-protein relationships in the a-particles is destroyed at NaCl concentrations exceeding 2 M, while in the c-particles at 1 M of NaCl . The study of NPC-chromatographic position of DNA depending on the particle size has shown that in slightly fragmented by streptococcal nuclease preparations of chromatin the DNA-protein relationships are destroyed at 3 M and 1 M of NaCl . Nevertheless, the position of the DNA spike on the chromatogram is not definitely dependent on the particle size. Int Arch Allergy Immunol, 1992, 97(4), 301 - 7 Detection of antibodies against streptococcal peptidoglycan and the peptide subunit (synthetic tetra-D-alanyl-bovine serum albumin complex) in rheumatic-diseases; Todome Y et al.; Serum antibodies reactive with streptococcal cell wall peptidoglycan (PG) and its peptide subunit (synthetic tetra-D-alanine) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), osteoarthritis and acute rheumatic fever (RF) compared with healthy subjects . Using 'checkerboard' titrations, anti-PG antibody in human serum was detected at a concentration of PG antigen at 10 micrograms per well with serum dilutions of 1:1,000 . For measurement of anti-tetra-D-alanine antibody, the antigen, (D-Ala4)31 was used at 0.5 micrograms per well and sera were diluted to 1:200 . When the IgG antibody levels to the PG and the tetra-D-alanine of the sera of patients with RA, JRA and RF were compared with sera from healthy subjects, the sera of the patients had significantly higher levels than did healthy subjects . Antibody that reacted with the PG in serum was absorbed with purified group-specific C-carbohydrate (A-CHO), but A-CHO was not capable of absorbing anti-(D-Ala4)31 antibodies . Therefore, the peptide subunit should be used as antigen in order to measure the specific antibody to PG . Both anti-PG and anti-tetra-D-alanine antibody in human sera primarily belonged to the IgG2 subclass. Clin Ther, 1992 Jan-Feb, 14(1), 30 - 40 Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults; McCarty J et al.; Loracarbef, a member of a unique class of beta-lactam compounds (carbacephems), has excellent chemical and beta-lactamase stability, as well as documented clinical effectiveness against a broad spectrum of bacteria . Ten-day treatment regimens of loracarbef (200-mg capsule BID or 15 mg/kg/day suspension) and penicillin VK (250-mg capsule QID or 20 mg/kg/day suspension) were compared in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis and tonsillitis . Adults (greater than or equal to 12 years of age) were administered loracarbef (n = 58) or penicillin (n = 58) in a double-blind, randomized, parallel study of clinical and bacteriologic response to treatment . Favorable clinical responses among qualified (evaluable) patients in the loracarbef-treated group (46/47; 97.9%) were similar to those for evaluable patients in the penicillin-treated group (43/43; 100%) . Forty-one of 47 (87.2%) of the evaluable loracarbef-treated patients and 100% (43/43) of the evaluable penicillin-treated patients had negative posttherapy throat cultures for GABHS . Thirty-nine evaluable patients in each treatment group were assessed 28 to 35 days after completion of therapy: 2.6% of patients in each group experienced relapse of symptoms; and 7.7% of loracarbef-treated patients had positive cultures, compared to 12.8% of penicillin-treated patients . Two (1.9%) loracarbef-treated patients with rashes and one (0.9%) penicillin-treated patient with diarrhea withdrew from the study due to these adverse events . Diarrhea, the most frequently occurring adverse event during therapy in the loracarbef group, was reported by 8.6% of the loracarbef group and by 5.2% of the penicillin group . These data support the conclusion that loracarbef is comparable in safety and efficacy to penicillin VK for the treatment of streptococcal pharyngitis and tonsillitis in adults. Injury, 1992, 23(2), 134 - 5 Streptococcal gangrene presenting as hip pain: two case reports and review of the literature; Ricketts D et al.; Two cases of streptococcal gangrene are reported . Both patients, with hip pain and no obvious source of infection, presented to the same orthopaedic team within a few days . After initial treatment with NSAIDs the outcome was fatal in the cases described . A review of the literature revealed that the administration of NSAIDs may accelerate the course of the disease . The authors conclude that this very rare cause of arthralgia and malaise should be excluded before the administration of NSAIDs for such complaints. Clin Infect Dis, 1992 Jan, 14(1), 298 - 307 Severe streptococcal infections in historical perspective; Katz AR et al.; The recent unexplained increase in severe streptococcal diseases in the United States and Great Britain is compared to the 1825-1885 pandemic of fatal scarlet fever . Although scarlet fever may not be representative of all severe streptococcal disease, it was the only one reliably identified in the 19th century . The epidemiology of scarlet fever during the 19th century pandemic suggests the following features of the disease;