Streptococci

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; cocirculation of both virulent and less-virulent streptococcal strains eliciting cross-immunity; circulation of hyperendemic prevalent strains in urban centers of developed nations, with periodic spillovers to rural areas and developing nations; and protection of infants from infection (but not from fatal disease once infection occurred) by the transfer of maternal antibodies via the placenta, breast milk, or both . The 19th century data suggest that efforts to prevent severe streptococcal diseases should begin with better characterization of the epidemiology of streptococcal disease, a task entailing identification of streptococcal virulence factors and measurement of their distribution among isolates from individuals with streptococcal diseases and in open populations.

Clin Infect Dis, 1992 Jan, 14(1), 29 - 37
Group A streptococcal bacteremia in a community teaching hospital--1980-1989; Burkert T et al.; This report reviews 45 episodes of group A streptococcal bacteremia during 1980-1989 in a large hospital; 24 episodes occurred in the first 5 years of study (1980-1984) and 21 in the last 5 years (1985-1989) . Four episodes were nosocomial . The remaining 41 episodes were community acquired; of these episodes, 12 occurred in patients who were transferred from nursing homes . There was a definite seasonal predominance (84%) during November-June . All but three patients had chronic underlying conditions . The major portals of entry were the skin and lungs, and the main types of infection were primary septicemia, cellulitis and soft-tissue infection, pneumonia, and infective endocarditis . The overall mortality rate was 24%; 20% of the deaths were due to infection . Factors that adversely influenced mortality were septic shock (P less than .02), less than 10,000/mm3 leukocytes (P less than .05); less than 80% segmented polymorphonuclear leukocytes and band forms (P less than .02), and hyperbilirubinemia (P less than .01) . Neither prevalence nor severity of group A streptococcal bacteremia increased during the last 5 years of study.

Nephron, 1992, 61(1), 58 - 63
Glomerular localization of platelet factor 4 in streptococcal nephritis; Mezzano S et al.; Since platelet factor 4 (PF4), a cationic (pI 7.6) platelet secretory protein, binds avidly to glomerular polyanions both in vitro and in vivo, and is implicated in neutrophil chemotaxis, we studied by indirect immunofluorescence microscopy the presence of PF4 deposits in glomeruli of patients with poststreptococcal nephritis (APSGN) . Goat antihuman PF4 serum was used as primary antibody and fluorescein-conjugated IgG fraction of rabbit antigoat IgG as second antibody . Controls consisted of nonimmune goat serum or anti-PF4 serum preabsorbed with human PF4, as primary antibodies . Glomerular deposits of PF4 were demonstrated in renal tissues obtained by biopsy in 14 of 20 patients studied; the deposits were particularly intense in 9 patients . PF4 was bound to the mesangium and to the capillary walls . There was a significant positive correlation between intraglomerular deposits of PF4 and the levels of proteinuria (p = 0.024) . These findings provide further evidence for a role of platelets in the pathogenesis of APSGN and suggest that PF4 may contribute to alter the glomerular permeability in this disease.

Chemotherapy, 1992, 38 Suppl 2, 33 - 7
Comparative study of cefetamet pivoxil and penicillin V in the treatment of group A beta-hemolytic streptococcal pharyngitis; Ramet J et al.; The efficacy of cefetamet pivoxil (20 mg/kg and 10 mg/kg b.i.d.) was investigated in an open, prospective, randomized, comparative multicenter trial involving 148 children suffering from group A beta-hemolytic streptococcal (GABHS) pharyngo-tonsillitis . Phenoxymethylpenicillin given for 10 days was used as the reference drug and resulted in 15% treatment failures . After treatment with cefetamet pivoxil 20 mg/kg b.i.d., 2 failures (5.8%) were observed in 34 patients treated for 7 days and 2 (6%) in 33 patients after 10 days treatment . In 8 children treated with cefetamet pivoxil 10 mg/kg b.i.d . for 10 days, 7 were cured and 1 relapsed in the late follow-up . Recruitment for this dosage group is being continued . No serious adverse events occurred . Cefetamet pivoxil, given b.i.d., can be considered an alternative to phenoxymethylpenicillin in the treatment of GABHS pharyngo-tonsillitis.

Pediatr Radiol, 1992, 22(2), 123 - 7
Deep cerebral venous thrombosis in thalamo-ventricular hemorrhage of the term newborn; Govaert P et al.; Unilateral thalamic bleeding with associated intraventricular hemorrhage is reported in three full-term neonates . The first presented within 48 hours from birth with early onset streptococcal meningitis, persistent pulmonary hypertension, tonic seizures and a tense fontanelle . The second presented 6 days after birth with irritability, opisthotonus, a tense fontanelle and tonic seizures . The third was admitted three days after birth with seizures and a tense fontanelle . In the latter two infants NMR and CT imaging documented thrombosed superficial and deep cerebral veins . The etiopathogenesis of intracranial venous thrombosis in the neonate is diverse: asphyxia, dehydration, polycythemia, sepsis-meningitis and difficult delivery are the main causes . In one of our patients jugular vein compression by the collar of a negative-pressure ventilation chamber probably initiated the intracranial events . More than half of the survivors sustain severe neurological impairment.

Zh Mikrobiol Epidemiol Immunobiol, 1992, (9-10), 31 - 4
{The rapid diagnosis of acute streptococcal infection in children}; Grevnina GS et al.; The present work deals with trials of the method of rapid diagnosis of streptococcal infection, carried out in children's infectious hospital, with the use of a new diagnostic kit . The proposed diagnosticum has proved to be highly sensitive and specific in scarlet fever and tonsillitis . The sensitivity and specificity of the diagnosticum depend on the duration of the disease, prehospital treatment and the quality of the bacteriological analysis.

Intensive Care Med, 1992, 18(6), 373 - 4
Treatment of neonatal hyperbilirubinaemia by plasmapheresis; South M et al.; A term baby developed severe hyperbilirubinaemia in association with group-B streptococcal sepsis . Haemodynamic instability deterred us from performing exchange transfusion, and so plasmapheresis was used to lower the bilirubin level . The procedure was very effective and well tolerated.

Scand J Infect Dis, 1992, 24(5), 599 - 605
Outbreaks of group A beta-hemolytic streptococcal pharyngitis in children: correlation of serotype T4 with scarlet fever; Ohga S et al.; We evaluated the clinical features of 121 children who had group A beta-hemolytic streptococcal (GABHS) pharyngitis during 2 outbreaks in the Chikuhou district, Fukuoka, Japan, with respect to T types . During the first outbreak (November 1989-February 1990), T12 (50%) and T22 (27%) were the dominant T types isolated . During the second outbreak (January-April 1991), 64% of the typable strains were T4 . Pus on the tonsils was less common and strawberry tongue more common in patients with eruptions than in those without . Skin eruptions were much more common in the patients infected with T4 than with other T types (p < 0.001) . Despite a 10-day regimen of amoxicillin, 12/69 patients (17.4%) had evidence of GABHS on repeat cultures . The results suggest that T4 may be associated with a high incidence of scarlet fever . Serotyping should be performed to identify disease carriers and patterns of GABHS infection.

Ren Fail, 1992, 14(4), 533 - 9
IgA nephropathy: acute renal failure, acute tubular necrosis, and features of postinfectious acute glomerulonephritis; Mazzarolo-Cruz HM et al.; From 1976 to 1987 on our Nephrological Unit, 57 patients with IgA nephropathy (IgAN) proven by renal biopsies were found . Three of those presented with acute tubular necrosis (ATN) and glomerulitis, without extrarenal predisposing cause in two; and showed, as prominent manifestation, a severe acute renal failure syndrome (ARFS), needing dialytic treatment . All three had hematuria, which was macroscopic in two and microscopic in one . Thus the prevalence of the association of glomerulitis and ATN was about 5.2% . There was complete recovery of renal functions in all three patients, but the usual symptomatology of IgAN . Two patients presented polymorphonuclear neutrophils infiltration of glomerular capillaries and in one of them, electron-dense deposits on the epithelial side of glomerular basement membrane ("humps") were observed, as well as those identified in the mesangial area . The glomerular polymorphonuclear neutrophils infiltration and endothelial cells proliferation (cases 1 and 3), the presence of "humps" (case 1), high antistreptolysin O (ASO) titers (cases 1 and 2), and low serum complement levels (case 1), suggest the possibility that antigens able to cause postinfectious glomerulonephritis (streptococcal or not) could induce in some individuals, by another immunopathogenetic route, mixed histopathological and clinical features of IgAN and postinfectious glomerulonephritis.

Ter Arkh, 1992, 64(6), 54 - 6
{Streptococcal infection and chronic glomerulonephritis in children}; Naumova VI et al.; Microbiological, immunological and immunohistochemical studies were carried out in 78 children with different clinicomorphological forms of chronic glomerulonephritis (GN) . According to the data obtained, the role of streptococcal infection (SI) is inconclusive in certain clinicomorphological forms of chronic GN, suggesting different approaches to the treatment of these patients . The etiological role of SI is most probable in mesangioproliferative and mesangiocapillary GN, manifesting by hematuric and mixed forms of chronic GN . Antibacterial therapy is indicated to patients with a rise of the level of ASL-O and with the clinical signs of acute SI or exacerbation of chronic tonsillitis in the same patients, especially during immunosuppressive therapy.

Ter Arkh, 1992, 64(4), 58 - 62
{Acute rheumocarditis in young men}; Dzhuzenova BS et al.; A study was made of the characteristic features of rheumocarditis in 200 young recruits . Rheumocarditis developed within the first 2-3 days since the onset of migrating polyarthritis and high fever . In many cases, it was accompanied by rhythm and conduction disorders as well as by a moderate increase of the left heart in combination with intracardiac hemodynamic disturbances . In 42 patients (21%), myocardial injury was coupled with mitral valve lesion . Injury to the pericardium was recorded in 20 patients (10%); fibrinous pericarditis was diagnosed in 15 patients, exudative pericarditis in 5 patients . Injury to all 3 heart membranes was ascertained in 5 patients (2.5%) (according to echocardiography) . Thus, the clinical and instrumental manifestations of rheumocarditis made it possible to diagnose marked carditis symptoms almost in all the patients (in 96%) . Unmarked carditis was only discovered in 7 patients . The above-mentioned characteristics of rheumocarditis in young men may be due to the intensity of the action of streptococcal infection on the heart structures within the first days of the disease as well as due to the action of immunopathological processes . Besides, a definite role may be played by the foregoing physical load.

Med Microbiol Immunol (Berl), 1992, 181(4), 209 - 13
The group A streptococcal M-type 3 protein gene exhibits a C terminus typical for class I M proteins; Podbielski A et al.; The M protein gene (emm gene) from a reference group A streptococcal strain of serotype M3 was amplified by the polymerase chain reaction and partially sequenced . Hybridization assays using an oligonucleotide probe derived from the N-terminal sequence revealed that this gene segment is highly homologous among M-type 3 isolates . Of note, analysis of the nucleotide sequence data from the C terminus of the gene confirmed that the emm 3 gene exhibited all the features characteristic for group A streptococcal M-class I molecules . Recently published sequence data that were assigned to emm 3 resulted from a strain confusion and were shown to be the first one derived from an emm gene of an M-untypable isolate.

Biotherapy, 1992, 5(1), 83 - 93
Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432; Yamaue H et al.; We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro . NK and LAK activity against K562 cells was not enhanced by their treatment with OK432 . In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced . Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells . Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

Biotherapy, 1992, 5(1), 63 - 9
Effective in vivo induction of lymphokine-activated killer (LAK) cells by pretreatment with a streptococcal preparation, OK-432; Shimoda K et al.; Effects of a streptococcal preparation, OK-432, on precursors of lymphokine-activated killer (LAK) cells were observed in vivo . Total number of splenocytes and the ratio of asGM1+ cells increased gradually after i.v . administration of OK-432, reaching their peaks at 3 to 4 days . It was found that asGM1+ cells were nonadherent and large in size . There were little differences in the ratios of Thy-1+, Lyt-2+, and L3T4+ cells before and after OK-432 treatment . Mice were injected i.p . with recombinant interleukin 2 (rIL-2) at a dose of 5 x 10(4) U per mouse 4 days after OK-432 administration and LAK activity in their splenocytes was examined using natural killer (NK) resistant EL-4 target cells . Splenocytes in mice treated with both OK-432 and rIL-2 showed higher LAK activity than those in mice treated with rIL-2 alone . In vivo treatment with anti asGM1 antibody prior to rIL-2 injection abolished completely such augmentation of LAK activity in OK-432 treated mice . These results demonstrated that asGM1+ LAK precursor cells induced by OK-432 were effectively differentiated into LAK cells by rIL-2.

Biotherapy, 1992, 5(1), 21 - 9
Therapeutic and life-prolonging effect of intrapleural injection with a streptococcal preparation, OK-432, and IL2-cultured effusion lymphocytes to breast cancer patients with malignant pleural effusion; Hori T et al.; We developed a local AIT using PEL cultured with TCGF combined with preadministration of OK-432 . Twenty-six patients of breast cancer with pleural effusion have been treated with this therapy since 1983 . PEL expanded and tumor cells collapsed by day 9 in culture with TCGF . Cultured PEL possessed significantly higher cytotoxic activity against autologous tumor cells than PBL cultured in the same condition (p less than 0.05), but there was no difference between their cytotoxic activities against K562 . The proliferation rate of PEL obtained after intrapleural administration of OK-432 was higher than that obtained before OK-432 (p less than 0.01) . Moreover, the cytotoxic activities against both autologous tumor and K562 of cultured PEL obtained after OK-432 administration was significantly (p less than 0.05) higher than those cultured PEL obtained before . Cultured PEL (1 x 10(8)-6 x 10(9)) were transferred into the pleural cavity after the intrapleural administration of OK-432 (1-5 KE) . The volume of pleural effusion increased temporarily after the administration of OK-432 but significantly (p less than 0.01) decreased after AIT . Tumor cells disappeared cytologically in 22 patients at the last puncture of pleural effusion . Pleural effusion disappeared completely in 19 of 26 patients and decreased by more than 50% in volume in 6 patients . Performance status improved in 22 patients . The response rate for OK-432-combined AIT in the present study was 96% . The survival period of the patients treated by OK-432-combined AIT in this trial was significantly (p less than 0.002) prolonged compared to that of the patients receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Surg Suppl, 1992, (567), 9 - 13
Teicoplanin in the treatment of bone and joint infections . Teicoplanin Bone and Joint Cooperative Study Group, USA; LeFrock JL et al.; Teicoplanin is a new glycopeptide antibiotic with activity against Gram-positive bacteria, including methicillin-resistant organisms . Teicoplanin is administered once daily, either intravenously or intramuscularly . Teicoplanin was given once daily, intravenously or intramuscularly, in the treatment of hospitalized or ambulatory patients with Gram-positive bone or joint infections . A total of 90/98 patients were evaluated for efficacy; 41 had acute osteomyelitis, 41 had chronic osteomyelitis, and 8 had septic arthritis . At the end of therapy, 37 acute osteomyelitis patients were cured/improved with a 90% cure rate at 6-month follow-up; 2 relapsed and 1 failed . At the end of therapy 30 chronic osteomyelitis patients were cured/improved with an 88% cure rate at 6-month follow-up; 2 relapsed and 1 failed . 100% of the septic arthritis patients were cured at the end of therapy and at 1-month follow-up . The most common bacterial isolates cultured from bone were S . aureus (39 isolates), S . epidermidis (11 isolates), other coagulase-negative staphylococci (20 isolates), enterococci (6 isolates), and other streptococcal species (20 isolates) . The most common bacterial isolates cultured from joint fluid were S . aureus (6 isolates) and S . epidermidis (2 isolates) . All patients tolerated the intramuscular or intravenous routes of administration well . Adverse reactions were mild and most cases did not require discontinuation of therapy . The majority of therapy was administered on an outpatient basis . Teicoplanin was safe, effective, convenient and relatively well tolerated in patients with acute or chronic osteomyelitis or septic arthritis.

Cancer Immunol Immunother, 1992, 35(2), 92 - 6
Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy; Misaki T et al.; To elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation . Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method . The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls . Among these T cells, the CD4+ subset was more numerous than the CD8+ population . In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells . In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage . Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine . The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.

Biotherapy, 1992, 5(4), 241 - 50
Establishment of cytotoxic CD4+ T cell clones from cancer patients treated by local immunotherapy; Nagaoka H et al.; We have previously reported that the antitumor effect of OK-432, a Streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (Cancer, 69: 636-642, 1992) . In order to elucidate the mechanism of the antitumor effects, we established T cell clones from regional lymph nodes of colorectal cancer patients who received this local immunotherapy . By culture of lymph node lymphocytes, in the presence of IL-2 and OK-432, 4 clones of T cells were established from 4 patients treated by local immunotherapy . These clones had a helper T cell phenotype (CD3+, CD4+, CD8-, CD56-, WT31+) and were successfully maintained for several months . The cells strongly expressed CD25 when stimulated with OK-432 and exhibited a high level of cytotoxic activity in part explained by the increased expression of ICAM-1 and LFA-1, and the release of TNF beta . These results suggest that the CD4+ T cells play a role in the antitumor mechanism of local immunotherapy.

J Clin Lab Immunol, 1992, 38(2), 73 - 82
Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis; Yamashiki M et al.; We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines . Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium . OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days . Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits . Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers . The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05) . Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good . When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy . However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon . Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients . From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.

Pediatrie, 1992, 47(1), 47 - 53
{Results and complications of induction treatment of acute leukemia in children . A personal series of 79 cases (1988-1989)}; Regaieg R et al.; In 1988 and 1989, 79 children have been treated for induction of acute leukemia . 68 presented an acute lymphoblastic leukemia (ALL) and 11 an acute non-lymphoblastic leukemia (ANLL) . The complete remission rate was 92% (96% in ALL, 73% in ANLL) . Fever occurred in 50% of the children, with positive blood cultures in 11 of them . One child died from streptococcal sepsis . No metabolic disorder was noted . Four patients were transferred into the intensive care unit . After 8 days, the treatment of ALL was continued in the outpatient clinic in more than 50% of the cases . The treatment of ANLL is frequently complicated by hemorrhages and sepsis and needs adapted supportive care in a specialized unit.

Growth Factors, 1992, 7(1), 73 - 83
Kupffer cells express type I TGF-beta receptors, migrate to TGF-beta and participate in streptococcal cell wall induced hepatic granuloma formation; Kossmann T et al.; Intraperitoneal injection of Group A streptococcal cell wall (SCW) fragments into female Lewis rats results in the induction of an acute hepatic inflammation that progresses to granulomatous lesions . Kupffer cells have been shown to rapidly clear circulating SCW which triggers production of TGF-beta . In this study, we examined Kupffer cells for the expression of TGF-beta receptors to determine if these cells might be modulated in an autocrine/paracrine fashion by TGF-beta during SCW-hepatic inflammation . By receptor crosslinking and subsequent SDS-PAGE analysis we demonstrate that Kupffer cells express Type I TGF-beta receptors, but not Types II and III . Scatchard analysis indicated a receptor density of approximately 1100 receptors per cell . Functionally, TGF-beta was found to be chemotactic for Kupffer cells in vitro and this chemotactic response was higher in cells isolated from rats 1-21 days post SCW-injection . Although TGF-beta 1 mRNA is constitutively expressed by Kupffer cells, in vitro stimulation of the cultures with purified TGF-beta augments the expression of TGF-beta 1 mRNA and protein synthesis suggesting autocrine/paracrine regulation . These results indicate that TGF beta secreted by Kupffer cells during SCW-induced hepatic inflammation may amplify its own expression and regulate Kupffer cell functions relevant to the formation of granulomatous lesions within the liver.

Acta Ophthalmol Suppl, 1992, (202), 42 - 6
Surface-associated activation of plasminogen on gram-positive bacteria . Effect of plasmin on the adherence of Staphylococcus aureus; Kuusela P et al.; In this article we review a novel type of plasminogen activation on staphylococcal and streptococcal cells . The activation mechanism implies a specific binding of glu-plasminogen to bacterial surface via the lysine-binding sites of plasminogen . Association of plasminogen with bacterial surfaces greatly enhances the t-PA mediated activation which takes place only poorly in solution . The end product, surface-associated plasmin, is enzymatically active, protected against high molecular weight plasmin inhibitors and capable of converting itself from glu-plasmin to the lys-form . The modification is associated with an increased affinity of the bound lys-plasmin towards the binding molecules on bacterial surface . This novel way of retaining plasmin on the surface may be important for the bacteria to invade and penetrate surrounding tissues . Our data on the effect of plasmin on staphylococcal adherence indicate that plasmin is not very effective in cleaning bacteria from surfaces coated with extracellular matrix components, fibronectin and fibrinogen.

Cancer Immunol Immunother, 1992, 35(2), 75 - 82
Enhancement of rat hepatic macrophages by treatment with interleukin-2 and streptococcal preparation OK432, with reference to antitumor activity, soluble factor production and Ia expression; Sasaoki T et al.; The effect of biological response modifiers, such as interleukin-2 (IL-2) and streptococcal preparation OK432, on the functions of hepatic macrophages was investigated . The macrophages, even with no exogenous stimulation, produced superoxide anion (O2-) and tumor necrosis factor (TNF), displayed cytotoxicity against K562 cells and cytostasis against P815 cells and expressed immune-region-associated antigen (Ia) . IL-2 administered in vitro or in vivo enhanced O2- production by hepatic macrophages and the intravenous injection of OK432 also enhanced O2 production . Furthermore, IL-2 added to the culture medium of hepatic macrophages isolated from OK432-injected rats augmented O2- production even more . The TNF production and Ia expression of the macrophages were also increased by the intravenous injection of OK432 . As with O2- production, the cytotoxicity of the cells was enhanced by OK432 injection or by IL-2 added to the culture medium and the combination of OK432 and IL-2 augmented their cytotoxicity even more . Thus, the present study suggested that IL-2 and OK432 induce the augmentation of the antitumor activity of hepatic macrophages, partly as a result of the increase in production of O2- and TNF and Ia expression.

Postgrad Med J, 1992, 68 Suppl 3, S43 - 6; discussion S46-8
Cefaclor AF in the treatment of streptococcal pharyngitis/tonsillitis; Derriennic M et al.; Two double-blind, double-dummy, randomized multicentre studies compared the safety and efficacy of 10-day regimens of cefaclor advanced formulation (cefaclor AF) (375 mg twice daily) with cefaclor (250 mg three times daily) in the treatment of proven group A beta-haemolytic streptococcal pharyngitis/tonsillitis . Of the 1,138 patients enrolled, 764 (cefaclor AF:392; cefaclor: 372) were evaluated for efficacy . All patients enrolled in the studies (570 treated with cefaclor AF and 568 treated with cefaclor) were evaluated for safety . Clinical and bacteriological evaluations were performed on treatment days 4-6, and after completion of treatment within 3-5 days and 2-3 weeks . In evaluable patients, the post-therapy clinical success and bacteriological cure rates for cefaclor AF were 96.7% and 93.6%, respectively; the rates were 98.1% and 94.1% for cefaclor . Sixteen cefaclor AF-treated patients and 14 cefaclor-treated patients withdrew early from the trial because of adverse events . There were no significant differences between treatment groups in the overall number of adverse events reported . Diarrhoea was the most frequently reported adverse event (5.6%) in cefaclor AF-treated patients, and headache/migraine was the most frequently reported adverse event (5.6%) in the cefaclor-treated patients . Cefaclor AF (375 mg twice daily) is as effective and safe as cefaclor capsules (250 mg three times daily) in the treatment of streptococcal pharyngitis/tonsillitis.

Ugeskr Laeger, 1991 Dec 30, 154(1), 27 - 8
{Manchincel poisoning complicated by streptococcal pharyngitis and impetigo}; Bygbjerg IC et al.; A Danish tourist to Antigua in the West Indies, ate a fruit of Hippomane mancinella and developed acute poisoning with blistering of the oral mucosa and diarrhoea and a streptococcal superinfection . Ignorant tourists and their travel advisers are warned against this potentially deadly apple-tree-like plant and its tempting fruits.

Clin Immunol Immunopathol, 1991 Dec, 61(3), 353 - 64
Influence of IgG1 and IgG2 antibodies to streptococcal group A carbohydrate on neutrophil chemiluminescence; Ruefenacht R et al.; IgG antibodies to streptococcal group A carbohydrate (A-CHO) were isolated from normal human serum and from pooled Cohn fraction II using N-acetyl-D-glucosamine affinity chromatography columns . They consisted of the subclasses IgG1 and IgG2 in variable proportions depending on the pH of the elution buffer and on the subclass composition of anti-A-CHO in the starting material . Streptococcal group A particles exposing the antigen A-CHO were opsonized with various concentrations of these antibodies and incubated with normal human polymorphonuclear leukocytes (PMN) . The luminol-enhanced chemiluminescence (CL) elicited with these particles was recorded over a 60-min period . With 12 of the 14 antibody preparations tested, the observed CL signal was dose-dependent . When used at comparable concentrations for opsonization, the antibodies enriched in IgG1 induced markedly stronger CL signals than those consisting predominantly of IgG2 . It was concluded that the observed CL differences reflect mainly the preferential recognition of IgG1 molecules by Fc gamma receptors of PMN.

Zentralbl Bakteriol, 1991 Dec, 276(1), 94 - 106
Scarlet fever and types of erythrogenic toxins produced by the infecting streptococcal strains; Knoll H et al.; Group A streptococcal strains were isolated from the throats of 46 children suffering from scarlet fever . For detection of erythrogenic toxins (ETs), the culture supernatants were concentrated 100 times by ethanol precipitation and solubilisation in acetate buffer . ELISA was used to identify ETA and double immunodiffusion to identify ETB and ETC . The presence of the ETA gene was detected by a specific DNA probe . ETA (alone or in combination with ETB and/or ETC) was found in 51.9% of the strains, ETB (alone or in combination with ETA and/or ETC) in 76.9% and ETC (in combination with ETA and ETB) in 28.9% . Only 5.8% of strains did not produce any detectable ET . In SDS-PAGE, supernatants of ETB-producing strains showed a pronounced band in either the region of the proteinase zymogen or the active proteinase . There was no correlation between the type of erythrogenic toxin and the serological M or T type of the producing strain . The mitogenic potency of culture supernatants did not differ significantly irrespective of the toxin type(s) present . Culture supernatants of strains without a detectable amount of the known ETs were highly mitogenic, indicating the production of other streptococcal mitogens . A correlation with clinical symptoms was determined with regard to exanthema and fever . Strains producing two or three toxins caused a more intense exanthema . Patient temperature was higher (greater than or equal to 38 degrees C) when the infecting strain produced ETB . The toxin-producing patterns of the strains of this study were compared with those isolated during the last epidemic outbreak of scarlet fever in East Germany.

J Clin Microbiol, 1991 Dec, 29(12), 2809 - 16
Use of monoclonal antibodies with neutralizing effects on toxic antigens from human bacterial plaque to detect specific bacteria by colony blotting; Levine M et al.; Inflammatory periodontal diseases are provoked by bacteria which adhere to teeth at the gingival margin and form plaques containing toxins detectable by their effect on mammalian cells in culture . The aim of this study was to make toxin-neutralizing monoclonal antibodies and determine whether they detect antigen in specific oral bacteria . Bacterial plaque was collected from teeth and homogenized, and the fluid phase (plaque extract) was boiled or first fractionated over Sephacryl S-300 . Hybridomas from immunized mice secreted immunoglobulin M (IgM) antibodies which reacted to plaque antigens . Neutralization was detected by an increase in the growth of HL60 cells which were exposed to plaque toxins in the presence of IgM from hybridoma culture or ascitic fluids . However, the neutralization was obvious only when the plaque toxins reduced growth by 50% or less . Plaque toxin preparations were found to contain proteases which hydrolyzed all of the IgM in ascitic fluids within 24 h . Replenishing the IgM daily preserved protection compared with protection from IgM from other hybridomas or saline only . The decrease in the specific activity of plaque proteins caused by replenishing one such antibody (3hE5) was 2.5-fold compared with activity with unreplenished 3hE5, 3.8-fold compared with activity with saline only, and 10.7-fold compared with activity with replenished, unrelated antibody . The neutralizing IgM detected an array of 14,000- to 22,000-molecular-weight antigens . The native toxins may be aggregates of these antigens, or the array may indicate fragments of an undetected, larger antigen or a common, nonpeptide adduct . Only 0.5 to 0.8% of the bacteria from sites with periodontitis and grown on blood agar contained antigen . One group of reactive bacteria was identified as Actinomyces odontolyticus serotype I . Other isolates were identified as Staphylococcus epidermidis, but antigen disappeared from the these isolates within 6 weeks of subculture . Epitope-containing antigens were also found in streptococcal and Eikenella isolates, and it is likely that the antigens from only some of these bacteria are toxic.

Clin Exp Immunol, 1991 Dec, 86(3), 413 - 8
Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice; Seino H et al.; We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-alpha), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM . In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice . Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-gamma) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P less than 0.01) and in mice treated with control serum (P less than 0.02) . This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody . In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P less than 0.01) and surface-Ig+ (S-Ig+) cells increased (P less than 0.05), whereas the proliferative response of spleen cells to concanavalin A (P less than 0.01) and lipopolysaccharide (P less than 0.05) increased . The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF.

Infect Immun, 1991 Dec, 59(12), 4324 - 31
Mapping T-cell epitopes in group A streptococcal type 5 M protein; Robinson JH et al.; Group A streptococcal cell surface M proteins elicit highly protective, serotype-specific opsonic antibodies and many serotypes also elicit host cross-reactive antibodies, which may contribute to the pathogenesis of poststreptococcal autoimmune disease . To date, studies aimed at designing safe (non-host-cross-reactive, defined-epitope) M vaccines have focused almost exclusively on antibody epitopes . Here we identify T-cell epitopes recognized by T cells from BALB/c, C57BL/6, and CBA/Ca mice immunized with purified, recombinant serotype 5 M protein (rM5) . The responses of rM5-specific, major histocompatibility complex class II-restricted, T-cell clones to synthetic peptides representing most of the M5 sequence identified at least 13 distinct T-cell recognition sites, including sites recognized by more than one major histocompatibility complex haplotype of mice . Although none of these sites appeared to be strongly immunodominant, an N-terminal peptide, sM5{1-35}, was recognized by lymph node T cells of rM5-immunized mice and by a larger proportion of rM5-specific T-cell clones than any other individual peptide . The fine specificity of these clones was mapped with subpeptides to a single site at or overlapping the sequence ELENHDL at residues 21 to 27, which is in close proximity to previously mapped protective antibody epitopes . Other T-cell recognition sites are distributed throughout the M protein and include several in the highly conserved C-terminal region of the molecule . One of these C-terminal sites, located within residues 300 to 319, was recognized by a significant proportion of T-cell clones from two strains of mice . Helper T-cell epitopes located in the C-terminal region of M5 are likely to be widely conserved between different M serotypes and could be particularly useful in designing multivalent, defined-epitope M vaccines.

Cesk Oftalmol, 1991 Dec, 47(5-6), 384 - 7
{Evaluation of the long-term therapeutic effect of bacterial vaccines administered 1960-1968 to patients with recurrent anterior uveitis}; Stara J et al.; The authors evaluate after an interval of many years the effectiveness of treatment of relapsing anterior uveitis by streptococcal vaccines administered in the sixties by L . Klenka, I . Hana, M . Koleckarova . The evaluation is based on a survey conducted by means of questionnaires . After 21 years 91% of the respondents do not report relapses . The authors discuss possible reasons why this desensitization treatment is successful.

Rev Prat, 1991 Nov 15, 41(24), 2431 - 6
{Glomerulonephritis of infectious origin}; Kleinknecht D et al.; Glomerulonephritis may complicate infections due to various microorganisms . These microorganisms are bacterial, fungal, viral or parasitic . Considerable clinical and experimental evidence has accumulated to indicate that glomerular injury is due to in situ immune complex deposition . In France, renal lesions are more often due to focal skin infection and sinus or visceral abscesses, with or without endocarditis, rather than to pharyngeal streptococcal infection . Staphylococcal infections are a frequent cause, especially in intravenous illicit drug users . Recovery requires suppression of the infective agent . However, in severe forms, after initial acute glomerular damage the evolution may be characterized by the development of chronic glomerulonephritis.

South Med J, 1991 Nov, 84(11), 1313 - 5
Soft tissue infections in the emergency department: the case for the use of 'simple' antibiotics; Powers RD; Cellulitis, infected wounds, abscesses, and other bacterial infections of skin and soft tissue are commonly seen in the practice of emergency medicine . Informal observations in a teaching hospital suggest that newer agents having a broader antibiotic spectrum are frequently used for empiric outpatient treatment of mild to moderate soft tissue infections, so information from a prospective study was analyzed to determine whether this practice is appropriate . Healthy adult volunteers were enrolled in a study of the aerobic bacteriology and response to treatment of skin and soft tissue infections . Patients were randomized to receive a 10-day regimen of cephalexin (500 mg bid or qid) or ofloxacin (300 or 400 mg bid) . Clinical response was assessed on two follow-up visits . Of 72 patients enrolled, 45 (63%) had cultures positive for pathogens . Cultures in 31 patients (43%) were positive for Staphylococcus aureus, five (7%) grew gram-negative rods, and five (7%) grew streptococcal species . Clinical response rates exceeded 95% in both the cephalexin- and ofloxacin-treated patients . Pathogens isolated from skin and soft tissue infections treated in the emergency department are not exotic or multiply resistant . The bacteriologic profile and clinical course of uncomplicated soft tissue infections indicate that treatment with a "simple" antibiotic, such as cephalexin, will result in resolution of the infection in nearly all cases . Broader spectrum antibiotics are not required for initial treatment of soft tissue infections in the emergency department.

Obstet Gynecol, 1991 Nov, 78(5 Pt 1), 774 - 7
Cord blood gas patterns identifying newborns at increased risk of group B streptococcal sepsis; Montgomery DM et al.; The effect of group B streptococcal sepsis acquired in utero on umbilical cord gas values is not known . Hypothesizing that fetal acid-base balance may be affected, we sought to identify a pattern of cord gas values that might detect newborns at increased risk of group B streptococcal sepsis . This review encompassed all newborns from January 1, 1986 to March 31, 1990 who manifested group B streptococcal sepsis as confirmed by a positive blood culture . An increased-risk cord gas profile was identified as an arterial pH less than 7.18 with either an arterial carbon dioxide pressure less than 59 mmHg or bicarbonate level less than 19 mEq/L . This pattern was found in four of 11 newborns with group B streptococcal disease but in only 43 of 4290 controls, yielding a relative risk of 51.7 (95% confidence interval 13.1-224.9) . Our results suggest that a mild metabolic acidosis characterized by these indices may serve as an indicator of increased risk of early-onset group B streptococcal disease.

Minerva Stomatol, 1991 Nov, 40(11), 689 - 94
{Focal infection in dentistry: the in vitro specific lymphocyte blast test}; Marini R et al.; The authors used an "in vitro" test of specific blastogenic response to streptococcal antigens, to evidence a sensitivity status in chronic odontogenic infections . The authors didn't find always a direct correlation between specific lymphoproliferative response and haematologic tests but found a good correlation with clinics . They conclude an increased value of specific lymphoproliferative response as predictive meaning of metafocal diseases.

Nippon Jinzo Gakkai Shi, 1991 Nov, 33(11), 1045 - 54
{The role of sulfatides in autoimmunity in children with various glomerular disease}; Tamaoki A et al.; Previous studies have suggested that autoimmunity to a number of kidney antigens may exist in glomerular disease . Our own work suggested that sulfatide which is one of the major acidic glycolipids of human kidney may be antigenic . Glycolipids were isolated from lipid extract of human kidney using thin-layer chromatography (TLC) . As the major acidic glycolipids, sulfatide, CDH-sulfate, GM3, GD3 were identified . Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining . Sera from patients with IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) contained antibody to the sulfatide of human kidney as determined by the direct binding of antibody to TLC . In addition, we measured the presence of sulfatide antibodies by enzyme linked immunosorbent assay (ELISA) in sera of patients with various glomerular disease: IgAN, HSPN, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), focal and segmental glomeruosclerosis (FSGS), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), acute post streptococcal glomerulonephritis (PSAGN), and lupus nephritis (LN) . IgM class sulfatide antibody were demonstrated in many cases of them . The incidence of IgA class sulfatide antibody in HSPN and IgAN was significantly high, and also the high incidence of IgG class sulfatide antibody occurred in IgAN . On the other hand, we evaluated cellular hypersensitivity to sulfatide in IgAN, HSPN, and FSGS using an active E-rosette assay . Positive results occurred in IgAN and HSPN . It was suggested that delayed hypersensitivity to sulfatide may generate an autoimmune inflammatory process . It has been reported that laminin binds specifically to sulfatide . Autoimmunity to sulfatide may disturb the laminin binding and consequently interfere with renal function . These results suggested sulfatide antigen may play important role in occurrence and aggravation of glomerular disease.

Am J Vet Res, 1991 Nov, 52(11), 1883 - 90
Detection of anti-equine neutrophil antibody by use of flow cytometry; Jain NC et al.; Flow cytometric and conventional fluorescence microscopic methods were compared to detect heterologous (rabbit) neutrophil antibody bound to equine neutrophils . Unfixed and paraformaldehyde-fixed neutrophils were treated with normal rabbit serum or various dilutions of an antineutrophil serum . The cells were then reacted with fluorescein conjugates of goat anti-rabbit IgG, staphylococcal protein A, and streptococcal protein G . Antibody binding was evaluated by use of fluorescence microscopy and flow cytometry . Unfixed neutrophils treated with normal rabbit serum did not fluoresce, whereas many of the fixed neutrophils had distinct cytoplasmic and some membranous (nonspecific) fluorescence . Unfixed cells treated with the antiserum had localized areas (capping) of intense membrane fluorescence, whereas fixed cells had bright uniform membranous fluorescence . The intensity of specific fluorescence varied with the antiserum dilution and the conjugate . On flow cytometry, over 80% of unfixed cells treated with antiserum dilutions up to 1:1,024, 1:2,048, and 1:256 fluoresced, respectively, with anti-IgG, protein-G, and protein-A conjugates . Fixed cells generally had similar percentages of fluorescent cells, but at a higher (1-step) antiserum dilution . It was concluded that flow cytometry is more sensitive than conventional fluorescence microscopy to detect antibodies associated with equine neutrophils.

Postgrad Med J, 1991 Nov, 67(793), 1013 - 4
Staphylococcal enterotoxins in scarlet fever complicating chickenpox; Brook MG et al.; Two cases of scarlet fever are described, both following super-infection of chickenpox . Enterotoxin B and C producing staphylococci were the only pathogens identified . The role of staphylococcal and streptococcal toxins in the pathogenesis of scarlet fever and toxic shock syndrome is discussed.

Ann Rheum Dis, 1991 Nov, 50(11), 752 - 4
Human heart sarcolemmal sheath antibodies in children with non-suppurative sequelae of group A streptococcal infections: a follow up study; Majeed HA et al.; The kinetics of the human heart sarcolemmal sheath antibody were studied in children with acute rheumatic fever who had no carditis, children with acute rheumatic fever who had carditis and developed rheumatic heart disease, and in children with acute poststreptococcal glomerulonephritis . The children with rheumatic fever and those who developed valvular heart disease were given continuous secondary antistreptococcal prophylaxis . The titre of antibody at onset was significantly higher than that of the controls in children with acute rheumatic fever and carditis and in children with acute poststreptococcal nephritis . The difference in the antibody titre between children with rheumatic fever who had no carditis and controls was not statistically significant . After a mean follow up of three years, however, a high titre was only maintained in children with rheumatic fever who developed valvular heart disease.

Clin Exp Rheumatol, 1991 Nov-Dec, 9(6), 611 - 5
Correlation of antiperinuclear factor with antibodies to streptococcal cell-wall peptidoglycan-polysaccharide polymers and rheumatoid factor; Nesher G et al.; Antiperinuclear factor (APF) has been noted in most seropositive rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) patients . The nature of the antigen is unknown; however, there are some suggestions that it might be a glycoprotein or proteoglycan . We studied the correlation of APF with antiproteoglycan antibodies and the reactivity of IgM-rheumatoid factor (RF) with the perinuclear antigen . Ten serum samples were separated to IgG, IgM, and IgM-RF enriched fractions . In seven samples, APF was found in the IgG fraction . Only 4 had APF in their IgM rheumatoid factor (RF)-containing fraction . In two of these, APF activity was present solely in the IgM RF fraction and was inhibited by pre-incubation with IgG . Fifty-five JRA patients' sera were also tested for the presence of antibodies to Streptococcal cell wall peptidoglycan-polysaccharide polymers (PG-PSP) . 76% of the APF-positive sera were anti-PG-PSP positive and 59% of the APF-negative sera were also anti-PG-PSP negative . Furthermore, 75% of the APF-positive sera lost their APF activity following adsorption to Streptococcal cell wall PG-PSP . Our results show that in JRA sera APF are polyclonal antibodies of both the IgG and IgM classes . Although the presence of APF correlates with RF positivity, and they sometimes may cross-react, many IgM RF-containing fractions do not show APF activity . However, the presence of APF does correlate with anti-PG-PSP positivity and the data suggest cross-reactivity between these two antibodies . This implies antigenic similarity between Streptococcal cell wall PG-PSP and the perinuclear antigen.

Vaccine, 1991 Nov, 9(11), 797 - 806
Group A streptococcal antigens and vaccine potential; Kehoe MA; Attempts over the past seventy years to produce an effective vaccine to protect humans against group A streptococcal infections and their immunologically mediated sequelae (acute rheumatic fever and post-streptococcal glomerulonephritis) have been frustrated by two basic problems, first, the ability of the highly protective cell-surface M proteins to elicit potentially harmful host reactions and second, the existence of a large number of distinct serovars of M proteins and the fact that human immunity to group A streptococcal infections is predominantly M serovar-specific . In recent years, progress towards overcoming these problems has been greatly facilitated by an increased understanding of the structural and immunological properties of protective group A streptococcal antigens, which has emerged from molecular biology studies . This article reviews these studies and discusses the potential for developing an effective group A streptococcal vaccine.

Zhonghua Yi Xue Za Zhi (Taipei), 1991 Nov, 48(5), 351 - 8
Overview of viridans streptococcal endocarditis: clinical analysis of 99 cases; Chao CH et al.; A total of 99 cases of viridans streptococcal endocarditis encountered during the period of 1973 and 1990 at the Veterans General Hospital-Taipei were reviewed to evaluate its prognostic factors . Applying strict clinical and laboratory criteria, 24 cases were categorized as definite, 44 probable, 23 possible and 8 likely . The symptoms were frequently subtle and atypical but initial laboratory tests gave useful indications: 69.1% with leukocytosis, 78% with anemia, 58.5% with elevation of LDH level, 88.9% with elevation of ESR value and 100% with elevation of CRP level . Furthermore, 32.4% of the cases demonstrated proteinuria and 67.4% microscopic hematuria . Seventy-three of the subjects had a history of underlying heart disease, predominantly rheumatic heart disease . Histological examination and echocardiography revealed that 51 patients suffered from vegetative endocarditis, 7 (13.7%) of whom were found to have anatomically confirmed vegetations without initial echocardiographic evidence, Vascular events were seen in 61 cases (61.6%): peripheral stigmata (32 cases), cerebral vascular accidents (17 cases), pulmonary embolism (10 cases) and others (2 cases) . The overall mortality rate was 18.2% . Congestive heart failure with embolization was the most common cause of death in this group . The presence of vegetation was not well correlated with embolic events . There was no statistically significant association between the mortality and the following characteristics: age, sex, underlying heart disease, evidence of echocardiographically detected vegetations, major surgical intervention and recurrent cases except for embolic events (p less than 0.01) . In conclusion, viridans streptococcal endocarditis complicated embolic events usually presented with a fulminant course and a grave outcome.

N Z Med J, 1991 Oct 23, 104(922), 446 - 7
Neonatal septicaemia: a changing picture?
Maxwell FC, Bourchier D.
The incidence, aetiologic organism and mortality associated with neonatal septicaemia were retrospectively reviewed over a seven year period (June 1983 to July 1990) . Trends with time were evaluated by dividing the study period in half . Although there was no significant change in the incidence of septicaemia during the study period (3.59 vs 3.40 per 1000 livebirths), there was a marked increase in the numbers of very low birthweight infants developing early onset group B streptococcal sepsis and an associated increase in mortality.

J Immunol, 1991 Oct 15, 147(8), 2559 - 64
Inhibitors of reactive oxygen intermediates suppress bacterial cell wall-induced arthritis; Skaleric U et al.; Peritoneal and peripheral blood monocyte-macrophages from inbred Lewis (LEW) rats generate higher levels of reactive oxygen intermediates (ROI) in response to group A streptococcal cell walls (SCW) than do similar populations of cells from histocompatible Fischer rats . This differential sensitivity of the phagocytes to SCW is reflected in differences in susceptibility of the two strains to the development of arthritis in response to SCW . After systemic administration of the SCW, LEW rats develop acute and chronic erosive polyarthritis, whereas the Fischer rats are arthritis resistant . Inasmuch as these data suggested that the SCW-induced release of inflammatory cell products such as ROI might be an important contributory factor in the pathogenesis of arthritis in the LEW rats, the animals were injected with SCW and treated with ROI inhibitors . A single intraarticular injection of superoxide dismutase or catalase significantly reduced the SCW-induced inflammatory response and evolution of erosive arthritis in the treated animals (articular index 3.6 +/- 0.36 for SCW only vs 1.4 +/- 0.3 for SCW + SOD; p less than 0.001; n = 6) . These data indicate that ROI play a pivotal role in synovitis and, furthermore, that suppression of these inflammatory mediators modulates both acute and chronic SCW-induced inflammation of the joint.

Ethiop Med J, 1991 Oct, 29(4), 167 - 73
Neonatal sepsis; Ghiorgis B; A two year retrospective study of 242 neonates with a clinical diagnosis of neonatal sepsis was undertaken . The neonates on whom blood culture results were available for analysis were categorized into "proven" or "presumptive" sepsis . A changing pattern in aetiological pathogens is identified . The conspicuous absence of Group B Streptococcal (GBS) sepsis is discussed . The overall mortality rate was 37% but the mortality rate in the bacteraemic patients was only 22.6% . This discrepancy is discussed in detail and further prospective study suggested.

Mol Immunol, 1991 Oct, 28(10), 1055 - 61
Structural and functional analysis of the human IgG-Fab receptor activity of streptococcal protein G; Eliasson M et al.; Streptococcal protein G (SPG) shows specific binding activity to IgGs and serum albumins from various species . In order to investigate the structural domains of SPG responsible for the specific interaction with human IgG-Fab, the binding characteristics of a collection of recombinant receptors were analysed . The study includes receptors comprising different parts of the SPG molecule as well as chimeric receptors containing IgG-binding domains of staphylococcal protein A (SPA) fused to the N-terminal AB-region of SPG, which has been claimed to interact with human IgG-Fab . Purified defined gene products were allowed to compete for the binding to human IgG, human IgG-F(ab')2 fragments and human serum albumin (HSA) in several sets of competitive binding experiments . The results demonstrate that the C-terminal C domains have both IgG-Fc- and IgG-Fab-binding capacities, whereas the N-terminal AB region is responsible for the HSA-binding only . These results, which are in conflict with previous work, demonstrate that the binding to both the IgG-Fc and the IgG-Fab region is mediated by the same structurally distinct receptor region of SPG.

J Med Assoc Thai, 1991 Oct, 74(10), 475 - 7
Group B streptococcal infection in children beyond neonatal period: report of 3 patients; Thisyakorn U et al.; Three patients beyond the neonatal period with group B streptococcal infection were presented, including acute osteomyelitis and septic arthritis, bacteremia and septicemia . Serotyping was done in two patients . One was type Ia and the other was type III . All patients recovered from the disease.

Thorac Cardiovasc Surg, 1991 Oct, 39(5), 273 - 80
Identification of abscess formation in native-valve infective endocarditis using transesophageal echocardiography: implications for surgical treatment; Rohmann S et al.; The object of the study was to follow patients with endocarditis-associated abscesses in order to evaluate the clinical outcome with and without surgical intervention . Transesophageal echocardiography successfully displayed the location and extent of abscess cavities in 14 patients (group A) with aortic valve endocarditis . The infective process was limited to the perivalvular tissue in two, extended into the ascending aorta in six, and included the interventricular septum, the right ventricular outflow tract, interatrial septum, and/or mitral valve annulus in six patients . The complication rate was significantly higher in group A than in group B, which consisted of 27 patients with proven signs of endocarditis but without endocarditis-associated abscesses . The complication rates were embolic events 64.3% in group A vs 29.6% in group B, need for surgery in 64.3% vs 18.5%, and death in 50.0% vs 3.7%, respectively . The duration of fever--as a marker of an active infective process--before diagnosis and the onset of adequate treatment was significantly higher in group A than in group B (46.7 +/- 8.4 days vs 7.7 +/- 2.6 days) . Organisms were isolated in 71.4% in group A and in all patients of group B . Streptococcal infections were noted in A in 54.5% vs 44.4% in B., staphylococcal in 27.3% vs 40.7% . Initial surgical repair in 9 of 14 patients in A (64.3%) included nine aortic valve and one mitral valve prosthesis implantations, two aortic valve-annulus reconstructive procedures, one dacron patch closure, and three partial resections of the aorta ascendens with end-to-end anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

An Esp Pediatr, 1991 Oct, 35(4), 239 - 42
{Rheumatic fever and post-streptococcal arthritis . Clinical review}; Merino Munoz R et al.; We report 11 patients diagnosed of Acute Rheumatic Fever (ARF), and 7 of Poststreptococcal Reactive Arthritis (PSRA): patients with group A beta hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria . All patients with ARF were treated with monthly prophylaxis (with penicillin G benzathine) . Carditis was seen in five patients, but only one of them has developed a mitral valve insufficiency . The prophylaxis in patients with PSRA was individualized . None of these patients had clinical evidence of carditis during the acute disease, but one of them developed a mitral and aortic stenosis two years after the initial episode . The possible indication of penicillin prophylaxis in these patients with PSRA in suggested.

Recenti Prog Med, 1991 Oct, 82(10), 541 - 6
{Rheumatic fever, the idea of progress and the circularity of time}; Taranta A; Rheumatic fever, once virtually "gone" from the western world, has made a come-back in the mid nineteen-eighties . This is disturbing because the control of rheumatic fever was a source of pride to the medical community . Changes in medical practice, such as a less compulsive attitude vis-a-vis streptococcal infections, and social changes, such as "house starvation", probably conspired to bring about the come-back . It's likely that the emergence of more virulent and more rheumatogenic streptococcal strains was facilitated by these changes . Physicians should once again be alert to the streptococcal threat, and accurately diagnose and effectively treat streptococcal pharyngitis.

Acta Paediatr Scand, 1991 Oct, 80(10), 911 - 6
Ampicillin-aminoglycoside combinations as initial treatment for neonatal septicaemia or meningitis . A retrospective evaluation of 12 years' experience; Tessin I et al.; In a retrospective study covering the years 1975-1986, 341 episodes of invasive infections in 338 newborn infants were evaluated . Of the 365 pathogens isolated from blood and/or cerebrospinal fluid, 91% were sensitive to either ampicillin or aminoglycosides or both . Ampicillin resistance was mainly found in very low and low birthweight infants with late-onset infections, in which aerobic Gram-negative rods were common pathogens . In contrast, aminoglycoside resistance was common in early-onset infections, due to the dominance of group B streptococcal infections . The ampicillin-aminoglycoside combination had been given as initial treatment in 189 cases of septicaemia or meningitis . Treatment failed in 36 infections (20%), although all organisms were sensitive to one or both antibiotics . Treatment failed in 6 of 34 patients with meningitis but the failure was not related to ampicillin or aminoglycoside resistance . In conclusion, both in vitro and clinical results show that the ampicillin-aminoglycoside combination can be used as initial treatment of invasive infections in neonates.

Jpn J Clin Oncol, 1991 Oct, 21(5), 330 - 3
In vitro induction of perforin mRNA and cytotoxic activities in human splenocytes by the streptococcal preparation, OK-432; Kataoka K et al.; Mononuclear cells were isolated from a spleen excised during surgery and cultured with 0.05 KE (Klinische Einheit)/ml of the streptococcal preparation, OK-432, or 700 JRU (Japan Reference Units)/ml of recombinant interleukin-2 (rIL-2) . When the cytotoxicity against K562 and Daudi cells was measured by four-hour 51Cr release assay, OK-432 induced about the same killing activity as that of rIL-2 . The peak activity was observed on day 2 . When the expression of human perforin messenger RNA (mRNA) was investigated by Northern blot analysis, a low-grade expression was seen in the splenocytes shortly after isolation (day 0) . An expression 2.7-fold stronger than that seen on day 0 was produced after one day of culturing with OK-432 . This enhanced expression decreased only slightly after the first day . The increases in expression of perforin mRNA on day 2 were similar for OK-432 and rIL-2 . The results indicate the multicytokine inducer, OK-432, to induce perforin to about the same degree as rIL-2 does, and perforin to act as one of the effector molecules in the killing activity induced by OK-432.

Immunology, 1991 Oct, 74(2), 333 - 7
Lack of IgG4 antibody response to carbohydrate antigens in patients with lymphatic filariasis; Lal RB et al.; It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens . To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein {streptolysin-O (SO), deoxyribonuclease B (DB)} and carbohydrate {group A carbohydrate (GAC)} antigens . Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P less than 0.01), and the subclass composition of these antibodies proved heterogenous . Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P less than 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group . These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin.

Bone Marrow Transplant, 1991 Oct, 8(4), 275 - 82
Serum concentrations of immunoglobulins and of antibody isotypes in bone marrow transplant recipients treated with high doses of polyspecific immunoglobulin or with cytomegalovirus hyperimmune globulin; Gratwohl A et al.; The kinetics of immunoglobulins (Ig) and antibodies were followed in 10 bone marrow transplant recipients who received either high doses (0.5 g/kg body weight) of polyspecific intravenous Ig (HD-IVIG) weekly or cytomegalovirus hyper-Ig (CMV-IVIG, 0.1 g/kg body weight) every 3 weeks . In the HD-IVIG group, the mean total IgG concentration more than tripled and similar significant increases were seen for IgG1 and IgG2 . IgG antibodies to CMV showed a marked increase in the HD-IVIG and a less pronounced rise in the CMV-IVIG group . IgM antibodies to CMV were present initially or became detectable in five patients, unrelated to the IVIG preparation . HD-IVIG induced a significant increase of IgG antibodies to streptococcal group A carbohydrate (A-CHO) and to smooth strain lipopolysaccharides (LPS) but not of antibodies against lipid-A . When the Ig treatment was discontinued, levels of total IgG and of IgG antibody to CMV decreased with an apparent half-life of 30 days . Both IVIG preparations were well tolerated and had no negative feedback on total Ig and on specific antibody production or other antimicrobial defence mechanisms . In patient nos . 4 and 10 who developed severe graft-versus-host-disease, transient serum Ig peaks including several Ig isotypes appeared after day 14 . In patient no . 10 this peak contained an IgG antibody to H . influenzae type b (Hib), and IgM antibodies to CMV, Hib, A-CHO and LPS . This study clearly shows that serum concentrations of Ig isotypes, subtypes and specific antibodies, depend on at least four factors: total amount and composition of Ig infused, consumption, catabolism and endogenous production.

J Immunol Methods, 1991 Sep 20, 143(1), 111 - 7
Protein A-streptokinase fusion protein for immunodetection of specific IgG antibodies; Schmidt KH et al.; The streptococcal streptokinase gene truncated at its 5' end was fused to regions of the staphylococcal protein A gene encoding the Fc-binding domains A and B . The resultant fusion gene, when expressed in the Escherichia coli lacPO system or under the speA expression/secretion signals in S . sanguis, specified a bifunctional hybrid protein, SPA-SKC, capable of Fc binding and plasminogen activation . When used in immunoassays designed to titrate antisera raised against bovine chymosin, human serum albumin and fibrinogen, the assay using SPA-SKC compared well with that using a commercial SPA-enzyme conjugate . The simple preparative method together with its efficacy and ease of use, make SPA-SKC a potentially valuable detector reagent in quantitative immunology.

Rev Infect Dis, 1991 Sep-Oct, 13(5), 783 - 8
Multisystem group A beta-hemolytic streptococcal disease in children; Jackson MA et al.; Eight children (median age, 8 years; range, 3-11 years) with severe streptococcal infection and multisystem dysfunction are described . All were febrile and in a toxic condition at presentation, and five (62%) of eight required fluid resuscitation . Encephalopathic symptoms were prominent, and two of three examinations of cerebrospinal fluid revealed mild pleocytosis . Severe hyperesthesia with or without an erythematous rash occurred in four (50%) of eight patients . Hyponatremia had occurred in all patients . Musculoskeletal complaints were noted in seven (87%) of eight patients . Three had synovitis and three had soft tissue infection . Renal involvement was noted in all patients, and hepatopathy characterized by mild hyperbilirubinemia and elevated levels of liver transaminase was found in four of five patients . Prolonged fever was noted in children with occult infection and debridement or drainage procedures of the foci were required in three of five affected children . Given the diversity of clinical manifestations, a high index of suspicion is necessary if these patients are to be recognized and appropriate therapy initiated.

Eur J Pediatr, 1991 Sep, 150(11), 782 - 3
Fatal ureaplasmal pneumonia and sepsis in a newborn infant; Brus F et al.; Ureaplasma urealyticum was isolated in pure culture from blood tracheal aspirate and lung tissue in a newborn infant, who died of a severe pneumonia within 48 h after birth . The clinical course was characterized by persistent pulmonary hypertension of the newborn (PPHN) . Post-mortem examination revealed extensive hyaline membrane formation combined with signs of inflammation in both lungs . The clinical and histopathological picture resembled that of early onset group B haemolytic streptococcal pneumonia/sepsis.

J Bacteriol, 1991 Sep, 173(17), 5280 - 9
Characterization and comparative sequence analysis of replication origins from three large Bacillus thuringiensis plasmids; Baum JA et al.; The replication origins of three large Bacillus thuringiensis plasmids, derived from B . thuringiensis HD263 subsp . kurstaki, have been cloned in Escherichia coli and sequenced . The replication origins, designated ori 43, ori 44, and ori 60, were isolated from plasmids of 43, 44, and 60 MDa, respectively . Each cloned replication origin exhibits incompatibility with the resident B . thuringiensis plasmid from which it was derived . Recombinant plasmids containing the three replication origins varied in their ability to transform strains of B . thuringiensis, Bacillus megaterium, and Bacillus subtilis . Analysis of the derived nucleotide and amino acid sequences indicates that the replication origins are nonhomologous, implying independent derivations . No significant homology was found to published sequences of replication origins derived from the single-stranded DNA plasmids of gram-positive bacteria, and shuttle vectors containing the three replication origins do not appear to generate single-stranded DNA intermediates in B . thuringiensis . The replication origin regions of the large plasmids are each characterized by a single open reading frame whose product is essential for replication in B . thuringiensis . The putative replication protein of ori 60 exhibits partial homology to the RepA protein of the Bacillus stearothermophilus plasmid pTB19 . The putative replication protein of ori 43 exhibits weak but extensive homology to the replication proteins of several streptococcal plasmids, including the open reading frame E replication protein of the conjugative plasmid pAM beta 1 . The nucleotide sequence of ori 44 and the amino acid sequence of its putative replication protein appear to be nonhomologous to other published replication origin sequences.

Cell Immunol, 1991 Sep, 136(2), 278 - 90
Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras; van Bruggen MC et al.; Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis . Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant . In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease . In this communication we describe our studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras . By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction . F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection . For AA comparable results were obtained . These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.

Int J Cardiol, 1991 Sep, 32(3), 361 - 4
Anti-streptokinase levels in Indian patients; Alexander T et al.; Levels of anti-streptokinase antibodies were measured in 75 Indian patients who were divided into three groups . The first group consisted of 25 healthy blood donors; the second group of 25 patients with ischaemic heart disease with stable angina; and the third group of 25 patients with acute myocardial infarction . The mean level of anti-streptokinase for the entire group was 0.37 SD 0.20 million international units (IU) (range 0.09 to 1.15 million IU) . There was no significant difference in the anti-streptokinase levels among the three groups . In order to neutralise the anti-streptokinase levels in 90% of the study population, 0.57 million IU of streptokinase was necessary . These levels are more than twice the current Western levels . In the light of this study, it may be necessary to reconsider the adequacy of the conventional dosage of streptokinase while treating acute infarctions in India and, possibly, other tropical countries where prevalence of prior streptococcal infection is high.

Pediatr Med Chir, 1991 Sep-Oct, 13(5), 479 - 80
{Prevention of acute hypertensive encephalopathy in the course of acute post-streptococcal glomerulonephritis in children: considerations in 31 cases}; Di Pietro A et al.; The authors analysed 31 cases of an acute hypertensive glomerulonephritis . The antihypertensive efficacy of two medicines: a vasodilator (dihidralazine) and a diuretic (Furosemide) was underlibed an these patients . Their efficacy was evident not only in the stabilization of P.A . around normal values on three days, but also on the disappearance of signs of on hypertensive encephalopathy whereas these ones were present.

Bol Med Hosp Infant Mex, 1991 Sep, 48(9), 627 - 36
{Diagnosis of streptococcal pharyngo-tonsillitis: clinical criteria or coagglutination?}; Reyes H et al.; With the purpose of evaluating the usefulness of clinical data and a coagglutination test for the diagnosis of streptococcal pharyngeal tonsillitis, a study was carried out comparing both methods with the standard pharynx culture (gold standard) . One hundred and forty-one patients clinically diagnosed with pharyngeal tonsillitis were analyzed . 80 other patients diagnosed with rhino-pharyngitis were used as control groups as well as a group of 66 healthy patients . It was found that the presence of pus in the tonsils and the absence of rhinorrhea and/or a productive cough were isolated clinical variables which showed a significant difference when comparing those cases with a positive or a negative culture (P less than 0.01) . These clinical data had a sensitivity and adequate negative predictive values (68 to 83% and 90 to 92%, respectively); specificity was 44 to 74% and the positive predictive value from 24 to 36% . The gathering of combined clinical indexes with different symptoms and signs, were not greater than isolated data . The coagglutination test in those cases of pharyngeal tonsillitis showed greater better specificity (98%) and positive predictive value (93%), but saw no improvement in sensitivity (72%) nor in the negative predictive value (91%), which is why when faced with a negative coagglutination test, it is still necessary to perform a throat culture due to the risk which the patient may be exposed to when no treatment is given . The analysis of the advantages and disadvantages in the routine use of coagglutination and cultures in their particular cases, allows us to conclude that in daily clinical practice the use of clinical criteria is of greater usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Vrach Delo, 1991 Sep, (9), 76 - 9
{The pathogenetic and prognostic significance of the level of class-E immunoglobulins in erysipelas}; Ambalov IuM et al.; The authors determined the content of total immunoglobulins of the E class in the blood plasma: native (IgE) and exhausted by a streptococcal allergen in the dynamics of the disease in 145 patients with erysipelas . The level of antistreptococcal reagins was evaluated . It was established that at the onset of erysipelas the concentration of IgE and a-IgE showed a short-term increase in 52 +/- 4% and 87 +/- 3% of patients correspondingly . During convalescence the level of these antibodies did not differ from that of the normal excluding high risk patients for recurrence . The participation of IgE-mediated type of allergic reactions in the pathogenesis of erysipelas is suggested . It is recommended to use the content of IgE and a-IgE for the prognosis of immediate and remote recurrences of erysipelas.

Eur J Obstet Gynecol Reprod Biol, 1991 Aug 20, 41(1), 64 - 9
Treatment with biologic response modifiers in patients with ovarian cancer; Koelbl H et al.; The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions . OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly . Five women were treated intracavitary with rIFN-gamma twice a week . The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks . With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients . The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively) . In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients . Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM . With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented . In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity . rIFN-gamma augmented natural killer activity in 2 of 3 patients.

Can J Ophthalmol, 1991 Aug, 26(5), 283 - 7
Anterior segment necrosis associated with endogenous endophthalmitis secondary to group C streptococcal septicemia; Moffett DG Jr et al.; Anterior segment necrosis following ocular infections and endophthalmitis secondary to group C streptococcal infection are both rare . We report a case of unilateral anterior segment necrosis associated with bilateral metastatic group C streptococcal endophthalmitis in a 68-year-old black man with multiple systemic disorders complicated by culture-confirmed group C streptococcal septicemia and endocarditis . Pathological examination of the left eye at autopsy demonstrated necrosis of the anterior segment involving the cornea, iris, lens and ciliary body . The right eye showed signs of mild residual inflammation . To our knowledge anterior segment necrosis has not previously been described in association with group C streptococcal endophthalmitis.

J Rheumatol Suppl, 1991 Aug, 30, 6 - 13
Host-parasite interaction in the pathogenesis of rheumatic fever; Ayoub EM et al.; Recent investigation has delineated some of the bacterial and host factors that may play a role in the pathogenesis of rheumatic fever . Continuing studies support the role of antibodies to crossreactive antigens in human tissues and the group A streptococcal cell in inducing tissue damage associated with this disease . Several specific epitopes have now been defined that are common to the crossreactive antigens . Data from recent outbreaks of rheumatic fever in the USA suggest that mucoid group A streptococcal strains, belonging to serotypes M1, M3, M5, M6 and M18 may have accounted for these outbreaks . While these strains are thought to be rheumatogenic, the exact characteristic(s) that renders them so is yet to be determined.

J Rheumatol Suppl, 1991 Aug, 30, 1 - 5
The genetics of rheumatic fever: relationship to streptococcal infection and autoimmune disease; Gibofsky A et al.; A large body of evidence suggests that patients with rheumatic fever immunologically respond abnormally both at a humoral and cellular level to streptococcal antigens cross-reactive with mammalian tissues . Implicit in this concept is that this abnormal immune response is genetically programmed . Using a monoclonal antibody called D8/17, a B cell marker has now been identified in 90-100% of all patients with rheumatic fever tested in 5 different geographical and ethnic populations . This trait appears to be inherited in an autosomal recessive fashion . This recognition of a B cell marker unique to individuals with rheumatic fever has important public health implications with respect to identification of individuals susceptible to rheumatic fever, possible prevention of disease and the recognition of prime candidates for future streptococcal vaccines.

Kansenshogaku Zasshi, 1991 Aug, 65(8), 913 - 8
{A study on the incidences of streptococcal infectious diseases in the regional surveillance informations of infectious diseases in Japan (2nd report)}; Morita M et al.; The incidences of streptococcal infectious diseases in the regional surveillance informations of infectious diseases of 47 prefectures were compared with each other by the ratios of number of patients with streptococcal infectious diseases, exanthema subitum and varicella to the populations of surveyed age groups, respectively . It was estimated that although there were almost no regional differences in the ratios of exanthema subitum and varicella, the ratios of streptococcal infectious diseases were high in Hokkaido, Akita, Yamanashi, Shiga and Ehime Prefectures, respectively, and was low in Okinawa Prefecture . The corrected incidences of number of patients with streptococcal infectious diseases, calculated on the basis of the ratios of exanthema subitum and/or varicella, were also high in the regions of Hokkaido, Akita, Iwate, Nagano, Yamanashi, Gifu, Shiga, Okayama and Ehime Prefectures, respectively, and were low in the regions along the Pacific from the southern Tohoku (northern Japan) through a part of the Shikoku Island and the Sea of Japan from the Hokuriku (central Japan) through the Kyushu Island, and the regions of Nara and Okinawa Prefectures, respectively . The climate in the regions with high corrected incidence belonged to the Tohoku-Hokkaido, the Central Highlands and the Seto Inland Sea types, respectively . On the other hand, the regions with low corrected incidence belonged to the Tokai-Kanto, the Nankai (southern sea of Japan), the Hokuriku-Sanin, the Kyushu and the Okinawa climate types, respectively.

Jpn Circ J, 1991 Aug, 55(8), 799 - 803
Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditis--timing of operation; Soma Y et al.; Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed . There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE) . In the NVE group there were 175 clinically active patients and 10 non-active patients . The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively . Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage . Patients with embolism showed significantly higher mortality . Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis . In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died . Indications for operation were intractable cardiac failure, uncontrollable infection and angina . In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively . The only survivor was a patient operated early under stable hemodynamics . These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection.

Chest, 1991 Aug, 100(2), 569 - 71
Group B streptococcal endocarditis of tricuspid valve; Watanakunakorn C et al.; We report three cases of group B streptococcal endocarditis of the tricuspid valve . Two patients were intravenous drug abusers . In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve . Half of the patients were intravenous drug abusers . Four of the other patients had underlying conditions . All patients were treated with a penicillin with or without an aminoglycoside . Three patients underwent tricuspid valve surgery . The overall mortality was 20 percent . Both patients who died received medical therapy only.

J Histochem Cytochem, 1991 Aug, 39(8), 1057 - 65
Protein AG-gold complex: an alternative probe in immunocytochemistry; Ghitescu L et al.; The purpose of this study was to evaluate the use of protein AG tagged with colloidal gold as a reliable immunocytochemical reagent . Protein AG is a recombinant of 47.3 KD molecular weight and pI = 4.3, which displays immunoglobulin Fc binding sites for both staphylococcal protein A and streptococcal protein G . It adsorbs to 10-nm colloidal gold particles with a lower affinity than does protein A, and is saturable . A maximal number of 12 protein AG molecules could be accommodated on the gold particle surface . Protein AG-gold conjugates yielded positive signals in post-embedding immunocytochemical assays when used as a secondary reagent in conjunction with several species and classes of polyclonal (rabbit, goat, sheep, guinea pig) and mouse monoclonal immunoglobulins (IgG1, IgG2, and IgG3) . In addition, protein AG-gold was found to be a useful reagent in immunoblot analysis because of its ability to bind and identify nitrocellulose-immobilized IgGs (rabbit, mouse, goat, sheep, rat, and cow) . Its spectrum of specificity towards various types of antibodies combines those of the parental protein A and protein G molecules . The protein AG-gold complex therefore appears to be a highly versatile and convenient alternative probe for immunochemical and immunocytochemical studies.

Zhonghua Nei Ke Za Zhi, 1991 Aug, 30(8), 489 - 91, 521
{Clinical evaluation of anti-DNAse B test in rheumatic fever and rheumatic heart disease}; Wang SH et al.; Anti-DNAse B test was performed with microtechnique in 160 subjects including patients with acute streptococcal pharyngitis, rheumatic fever and rheumatic heart disease as well as normal controls . It was shown that the antibody titer varied with age, stage of rheumatic fever and rheumatic heart disease as well as the frequency of benthazine penicillin injections . It was also shown in this study that the school children group had considerably higher geometric mean antibody titer than the adult group . The upper normal limit of anti-DNAse B titer was 240 units in the school children group and 160 units in the adult group . The anti-DNAse B test shows a higher positive detection rate for streptococcal infection than ASO, especially when these two tests are used in combination . In patients with manifestations of acute rheumatic fever without elevation of ASO titer, anti-DNAse B test will be of great diagnostic value.

Zentralbl Bakteriol, 1991 Aug, 275(3), 327 - 34
Isolation and characterization of group B streptococcal type antigens X and R; Wibawan IW et al.; The group B streptococcal surface antigens X and R were isolated from culture supernatant by ammonium sulphate precipitation and subsequent high performance gel filtration (HPLC) . The type antigens appeared in numerous protein bands . Type antigen X was in the range of 180 kD, type antigen R, in the range of 116 kD . The protein antigens reacted specifically with their homologous antisera in Western blot analysis and in immunoelectrophoresis, indicating that there was no immunological relationship between both proteins . Preparative isoelectric focusing of the X and R antigens revealed for both proteins isoelectric points at acid pH . Specific antibodies produced against the purified proteins could be used for routine serotyping without further absorption.

Hepatology, 1991 Jul, 14(1), 91 - 8
Aztreonam vs . cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients; Ariza J et al.; Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis . Patients were randomized into two therapeutic groups of similar characteristics . Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period . Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms . Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group . In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure . Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment . The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS) . Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment . Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group . We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection . Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population.

Int J Hyperthermia, 1991 Jul-Aug, 7(4), 653 - 65
Augmentation of mouse natural killer cell activity by combined hyperthermia and streptococcal preparation, OK-432 (Picibanil) treatment; Taradi M et al.; It has previously been demonstrated that the local administration of OK-432 (Picibanil) enhances the response of a murine tumour and normal tissue to elevated temperatures . The experimental animals were C3Hf/Sed mice and the tumours were the fourth generation isotransplants of a spontaneous non-immunogenic fibrosarcoma, FSa-II . The thermal enhancement ratio was greater for the tumour than for normal tissue, resulting in a favourable differential effect between normal and malignant tissues . Further studies were conducted to disclose the mechanism of OK-432 induced thermal enhancement . Although OK-432 showed a slight direct cytotoxic activity against tumour cells in vitro, the in vivo antitumour effect of combined OK-432 and hyperthermia treatments was greater than the effect expected from in vitro cytotoxicity, indicating the involvement of the host-mediated mechanisms . Whole body irradiation (WBI), which suppressed the host's immune reaction, did not affect the thermal enhancement mediated by OK-432, suggesting that radiosensitive cells (sensitive to WBI) were not involved in this process . As expected, the i.v . injections of the anti-mouse T-cell serum did not have any effect on the thermal enhancement of OK-432 . The administration of blockers of the reticuloendothelium system, i.e . silica or trypan blue, did not inhibit the OK-432 induced thermal enhancement . Moreover, local intratumoural injections of normal or OK-432 induced macrophages showed no effect on tumour growth . The thermal enhancement by OK-432 was eliminated following treatments with anti-(asialo GM1) globulin . Despite the fact that the cytotoxic effect of anti-(asialo GM1) globulin was not selective to natural killer (NK) cells, all the experimental results indicated that NK cells were probably attributable to thermal enhancement by OK-432 in vivo . The NK cell activity was stimulated when the OK-432 was locally administered with hyperthermia.

Stomatologiia (Mosk), 1991 Jul-Aug, (4), 21 - 5
{The development of the maxillodental system in the fetus and the newborn animal in intrauterine streptococcal infection}; Gemonov VV et al.; Effects of an intrauterine streptococcal infection induced at different stages of pregnancy on the developing fetus and newborn were studied in non-inbred white rats . The course of denture development was found changed in both fetuses and newborns . A number of functional shifts in the central nervous system and physical status, presenting in the postnatal period, were detected in the experimental animals.

Cesk Pediatr, 1991 Jul, 46(6-7), 327 - 31
{Serologic diagnosis of infectious mononucleosis in children}; Votava M et al.; In 116 children admitted to hospital with tonsillitis of varying types and suspected infectious mononucleosis resp., antibodies, of the IgM class against the EB virus VCA were detected in 27%, a quadruple increase of IgG antibodies in 20% and a negative finding of IgG antibodies also in a second serum sample in 24% . In another group of 51 children admitted with suspected infectious mononucleosis IgM antibodies were found in 47%, a fourfold increase of IgG in 53% and a negative finding of IgG in 10% . In sub-groups of 25 and 30 children resp . from the above groups it was possible to compare the results of specific serology of the EB virus with tests for heterophil antibodies in two serum samples . IgM antibodies were detected in 40% and 50% of children resp., a fourfold rise of IgG in 20% and 67% of children resp., the absence of IgG in 20% and 7% of children resp . Paul-Bunnell reaction was positive in 64% and 60% resp., the OCH-test in 60% and 70% resp., Tomcsik reaction in 16% in the first sub-group and the IM-test in 60% in the second sub-group . In younger children (1-5 years) positive Paul-Bunnell and Tomcsik reactions were less frequent . The IM-test was not positive in any of the children in this age group . An EB-virus aetiology was proved in all types of tonsillitis, least frequently in angina streptococcia (11%), most frequently in angina pseudomembranosa (46%) and mononucleosis infectiosa susp . (54%).

Eur J Biochem, 1991 Jul 1, 199(1), 41 - 6
Differential degradation of a recombinant albumin-binding receptor in Escherichia coli; Murby M et al.; The degradation in Escherichia coli of the recombinant serum-albumin-binding receptor derived from streptococcal protein G was investigated using a dual-affinity fusion approach . The proteolytic degradation of the receptor was characterized when fused to human proinsulin and human secretin . Several cleavages occurred at sequences not normally regarded as proteolytically sensitive, such as the dipeptide sequences Ile-Gly, Val-Ser and Ser-Ala . Depending on the fusion partner, large differences in the degradation of the albumin-binding domain were observed . Thus, susceptibility to proteolysis of a recombinant protein can be affected by a neighbouring domain.

J Immunol, 1991 Jun 15, 146(12), 4187 - 9
Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta; Yoshino S et al.; Rats treated with an mAb (R73) against the TCR-alpha beta failed to develop chronic persistent arthritis after injection of streptococcal cell walls . Histologically, R73 mAb-treated rats had mild hyperplasia of synovial lining cells and minimal destruction of cartilage . In contrast, control-treated animals developed marked pannus formation, with pronounced infiltration of mononuclear cells and severe destruction of cartilage and subchondral bone . The preventive effect of R73 mAb on streptococcal cell wall-induced arthritis was associated with the marked depletion of alpha beta + T cells by R73 mAb . These results indicate that T cells play a crucial role in chronic erosive streptococcal cell wall-induced arthritis.

Curr Opin Rheumatol, 1991 Jun, 3(3), 407 - 20
Animal models of rheumatoid arthritis; Wooley PH; Experimental animal models of arthritis, including type II collagen-induced arthritis, proteoglycan-induced arthritis, adjuvant arthritis, pristane-induced arthritis, and streptococcal cell wall-induced arthritis have contributed to recent advances in the understanding of the immunopathology of arthritis . The dissection of the T-cell populations regulating the autoimmune response is currently the most active area of investigation . Research into the mechanism underlying the association of specific class II major histocompatibility complex antigens with arthritis has focused attention on the interaction of particular V beta T-cell subsets with antigens presented in context of permissive major histocompatibility complex antigens . Several models indicate that both the structure of the major histocompatibility complex antigen and the T-cell receptor may be critical in the development of autoimmunity, while the MIs antigen system appears to regulate the availability of T cells with self-reactivity specificities . Studies on the role of heat-shock proteins in experimental arthritis have prompted research into the role of gamma/delta T cells in joint disease, while the availability of recombinant cytokines has permitted the direct analysis of soluble factors . In addition to providing basic insights into autoimmune disease, animal models continue to provide the means to test novel experimental approaches to the treatment of rheumatoid arthritis.

J Immunol, 1991 Jun 1, 146(11), 3747 - 50
Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B; Abe J et al.; Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever . Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins . In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B . SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8 . Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells . The T cell response to these toxins, however, was not MHC-restricted . Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset . Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.

J Perinatol, 1991 Jun, 11(2), 144 - 6
Purpura fulminans in three cases of early-onset neonatal group B streptococcal meningitis; Lynn NJ et al.; The diagnosis of purpura fulminans was associated with three cases of early-onset group B beta-hemolytic streptococcal (GBS) disease . All three infants had confirmed bacterial disease, extensive purpuric lesions involving the extremities, and laboratory evidence of a consumptive coagulopathy . All three children survived but had markedly compromised neurologic outcomes . Purpura fulminans has not been previously reported with early-onset GBS disease.

J Perinatol, 1991 Jun, 11(2), 126 - 9
Early-onset Hemophilus influenzae sepsis in the neonate; Mendoza JC et al.; Hemophilus influenzae sepsis has been increasingly reported in recent years . Thirteen neonates have been treated in our institution in the past 8 years, 12 of whom were admitted within the last 4 years . H influenzae is responsible for 8% of neonatal sepsis occurring during the first 3 days of life . It is usually transmitted before or at the time of birth and is more frequently encountered in premature and low birthweight infants . It is strongly associated with maternal obstetric complications particularly genitourinary tract infections and prolonged rupture of membranes before delivery . Most cases are caused by non-type-b strains and are susceptible to ampicillin . Neonatal H influenzae sepsis presents clinically like early-onset group B streptococcal disease and is especially fulminant in neonates born prematurely.

Cardioscience, 1991 Jun, 2(2), 93 - 7
NADPH oxidase activity in the monocytes and neutrophils of patients with rheumatic fever; Kumar V et al.; The enzyme NADPH oxidase is involved in the production of oxygen free radicals . We measured its activity in neutrophils and monocytes obtained from patients with acute rheumatic fever, chronic rheumatic heart disease, acute streptococcal pharyngitis and normal controls . Follow up studies were made at 15 days, 3 months and 6 months . Streptococcal membrane antigen, carbohydrate antigens and latex were used to stimulate the oxidative activity in the neutrophils and monocytes . These three agents caused a significant increase in the enzyme activity of the phagocytes of patients with acute rheumatic fever and chronic rheumatic heart disease (p less than 0.001) but not in acute pharyngitis . Maximal NADPH oxidase enzyme activity was observed in patients with acute rheumatic fever . During the follow-up, there was a significant decline in the enzymatic activity in patients with acute rheumatic fever but not in those with chronic rheumatic heart disease . Enzymatic activity was greater when the phagocytic cells were triggered with membrane as compared to carbohydrate antigen and latex in all the groups and at all intervals . The enzymatic response of neutrophils and monocytes was similar although the magnitude of the NADPH oxidase activity was significantly higher in neutrophils than in monocytes.

Mol Immunol, 1991 Jun, 28(6), 661 - 71
Isolation and partial characterization of a type IV bacterial immunoglobulin binding protein; Raeder R et al.; A series of bovine G streptococcal isolates were screened for expression of type IV Fc binding proteins . An isolate expressing high levels of type IV binding proteins was selected and expanded by use of a colony selection technique . A variety of different extraction procedures were compared and the optimal solubilization procedure was found to be hot acid extraction of the bacteria . The extracted protein could be affinity purified on a column of immobilized rabbit IgG . The type IV Fc binding protein was found to be antigenically unrelated to the type I, II or III bacterial Fc binding proteins and displayed the lowest affinity and most limited range of species and subclass reactivity of any bacterial Fc binding protein thus far characterized.

J Trop Pediatr, 1991 Jun, 37(3), 127 - 30
Henoch-Schönlein syndrome in Saudi Arabia; al Rasheed SA et al.; A retrospective study was carried out on 40 children from Saudi Arabia with Henoch-Schonlein syndrome to delineate its clinical pattern . More than 50 per cent of the cases occurred in winter . There was no apparent causal relationship with B-haemolytic streptococcal infection . All patients had skin rash . Fifty-eight per cent had gastrointestinal manifestations, 58 per cent had joint manifestations and 38 per cent had renal manifestations . The main clinical features of Henoch-Schonlein syndrome in Saudi children are comparable to those reported elsewhere.

Nippon Sanka Fujinka Gakkai Zasshi, 1991 Jun, 43(6), 611 - 8
{Effect of malignant ascitic fluids and OK-432 on the induction of LAK activity in peripheral blood mononuclear cells of gynecological cancer patients}; Kanaoka Y et al.; Recently, successful treatment of peritonitis carcinomatosa by intraperitoneal administration of lymphokine-activated killer (LAK) cells followed by intraperitoneal recombinant interleukin 2 (rIL-2) has been reported by several authors, in spite of the well documented results of the immunosuppressive activity of malignant ascitic fluid . We investigated the effect of malignant ascitic fluid on in vitro induction of LAK cells obtained from patients' peripheral blood mononuclear cells . We also examined whether Streptococcal preparation OK-432, which has been instilled into the peritoneal cavity to treat malignant ascites, is able to synergize with rIL-2 to induce LAK activity, and the following results were obtained; 1 . A little augmentation of LAK activity was observed at a lower concentration of malignant ascitic fluid, while the results were diversified at a concentration higher than 10% . In two cases out of six, a severe suppressive effect was observed at a concentration higher than 40% . At the higher concentration, fewer cells were recovered after a 5 day culture in all cases . 2 . No augmentation of LAK activity following the combination of OK-432 with rIL-2 was observed . At a lower concentration of OK-432 (ranging from 0.01-0.04KE/ml), the number of cells increased in comparison with rIL-2 alone . These results suggest that the potential of adoptively transferred LAK cells followed by rIL-2 was not effectively suppressed by malignant ascitic fluid in vivo and that the administration of OK-432 followed by rIL-2 could induce a larger number of various killer cells than rIL-2 alone.

Semin Respir Infect, 1991 Jun, 6(2), 69 - 76
Antibiotic treatment of pharyngitis; Kind AC et al.; Pharyngitis is one of the most common medical problems and ranges in severity from minor to fatal . The treatment regimens presented have been standardized for the various pathogens on the basis of clinical response and pathogen eradication . The current major challenge is the rapid recognition and diagnosis of streptococcal infection and clarification of the etiologic role of several nonstreptococcal pathogens.

J Med Assoc Thai, 1991 Jun, 74(6), 340 - 3
Group A beta-hemolytic streptococcal type M11 sepsis and empyema: a case report; Likitnukul S et al.; A case of serious suppurative disease caused by GABHS in a previously well 2-month-old Thai female presenting with clinical features of sepsis and right pleural effusion was reported . Treatment was initially with cloxacillin and a right side intercostal drainage . When subsequent cultures of blood and pleural fluid grew GABHS; intravenous penicillin was substituted . She made an uneventful recovery . Typing of the GABHS revealed non typable T-antigen and M-protein 11 GABHS, although very sensitive to penicillin, can cause severe and rapidly progressive disease in a very young infant . This is the first case of GABHS type M11 causing pleural effusion and sepsis in an infant ever reported in Thailand . Epidemiologic study might be indicated if an epidemic should occur.

J Clin Lab Immunol, 1991 Jun, 35(2), 65 - 9
Antibodies to N-acetylglucosamine and heparin in acute and remission phases of rheumatic fever; Shastry P et al.; The etiology of acute rheumatic fever (ARF) is believed to involve an immunological response to group A streptococcal antigens . Antibodies to group A carbohydrate (A-CHO) have been reported in ARF and rheumatic heart disease patients . As N-acetylglucosamine (GlcNAc) units form the major immunodominant regions in A-CHO antigens, we investigated levels of antibodies to GlcNAc and heparin (with repeated sequences of GlcNAC) in rheumatic fever (RF) patients . Serum samples from 26 acute cases (ARF), 18 remission cases and 17 normal healthy subjects were analyzed for IgG and IgM levels of antibodies to GlcNAc and heparin . High titres of IgG antibodies to heparin and GlcNAc were observed in the ARF group in comparison with controls (p less than 0.0025 and 0.0125 respectively) . There was no difference in the levels of IgM antibodies . Remission group demonstrated low titres of IgG to heparin and GlcNAc (p less than 0.01 and 0.0125 respectively) in comparison with ARF group . Heparin antibodies of IgM class was comparatively lower in remission group (p less than 0.005) . While the role of these antibodies in different phases of RF needs to be investigated, we conclude that GlcNAc antibodies do not play any role in the pathogenesis of RF or rheumatic heart disease.

Rev Prat, 1991 May 21, 41(15), 1350 - 3
{Epidemiology and prevention of perinatal group B streptococcal infections}; Lejeune C et al.; Neonatal group B streptococcal infection is frequent and may be responsible for lethal neonatal septicaemia . Its preventive treatment is still hotly debated . Digestive and genital tracts colonization is frequent in mother (15-20% of the cases) but it is unstable . About one out of two infants born of a colonized woman becomes colonized or infected . Neonates can also be colonized during their stay in maternity hospitals . Colonization is much more frequent than infection which strikes 0.2 to 0.6 per cent of neonates (at a very early period in two-thirds of the cases), but it jeopardizes their prognosis for life and later their functional prognosis . Prematurity and chorioamnionitis are the two main infection facilitating factors . Some of the various measures proposed to prevent infection in neonates, such as antibiotic therapy of colonized mothers during pregnancy and of symptomatic colonized neonates, do not seem to be effective, but others are interesting, including administration of antibiotics to mothers during delivery in high-risk situations, combined with early detection and immediate bactericidal treatment of neonatal infections.

J Infect, 1991 May, 22(3), 225 - 31
Neonatal group B streptococcal infections in Indian (Asian) babies in South Africa; Haffejee IE et al.; In this, the first report of group B streptococcal (GBS) infections in Asian neonates in South Africa, the incidence was 2.65/1000 live births over a period of 3.5 years . Early onset disease (EOD), defined as arising less than or equal to 5 days after birth, was present in 79% cases; in most of these, the onset was before the age of 24 h . One baby presented with two episodes of late onset GBS infection . The incidence of culture-proven neonatal septicaemia during the same period was 12.3/1000 live births, GBS being commonest organism isolated . It was also the most frequent cause of bacterial meningitis in the newborn, accounting for 89% cases . Although neurological signs were present in 40% patients with EOD, only 13.3% had CSF-culture-positive meningitis . Radiographic features of hyaline membrane disease were found in half of the babies with EOD and for whom a chest radiograph was performed, while one had a pneumothorax . The overall mortality was 13.2% which is much lower than that reported in other series.

J Am Board Fam Pract, 1991 May-Jun, 4(3), 139 - 43
The effects of the rapid strep test on physician management of streptococcal pharyngitis; Bryars CH 3rd et al.; Management of pharyngitis remains an important and controversial subject . A retrospective chart review at the University of South Alabama Family Practice Center was undertaken to assess changes in physician prescribing and testing patterns since the advent of rapid testing of streptococcal pharyngitis (rapid strep tests {RST}) . Charts for study were identified by encounter form coding of a diagnosis of streptococcal pharyngitis or pharyngitis not otherwise specified . Control and test groups were formed based on the availability of the RST, and a stratified sample was drawn from each group . In the group of patients studied after the RST became available, data analysis showed a significantly increased likelihood that patients received antibiotics with a positive RST (odds ratio {OR} = 6.42), whereas those patients with a negative or no RST were significantly less likely to receive antibiotics (OR = 2.50 and 2.48, respectively) . Group assignment was a significant predictor of test-ordering behavior (P less than 0.05) . A higher than expected rate of streptococcal pharyngitis was noted in the group of patients who had the RST available to them . The RST plays an important though not fully defined role in the current management of pharyngitis.

Ann Rheum Dis, 1991 May, 50(5), 328 - 9
Multisystem disease in post-streptococcal arthritis; Livneh A et al.; The case presented is of a patient with migratory polyarthritis and serological evidence of a recent streptococcal infection, consistent with the diagnosis of acute rheumatic fever, who in addition had multisystem disease manifestations . This case supports the concept that the sequelae of streptococcal infection can encompass a broader clinical spectrum than is suggested by the Jones criteria for the diagnosis of acute rheumatic fever.

J Pediatr, 1991 May, 118(5), 680 - 6
Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease . United States Multicenter Kawasaki Disease Study Group; Burns JC et al.; STUDY OBJECTIVES: (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States . (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD . (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established . DESIGN: Case comparison study . SETTING: Seven pediatric tertiary care centers . PATIENTS: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever . MEASUREMENTS AND MAIN RESULTS: (1) Infectious diseases, particularly measles and group A beta-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group . (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established . (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash . The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count less than 10 X 10(3)/mm3 and platelet count less than 200 X 10(3)/mm3 were significantly less prevalent in patients with KD . (4) Residence within 200 yards of a body of water was more common among KD patients . CONCLUSIONS: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD . (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erythrocyte sedimentation rate, and serum alanine aminotransferase activity . (3) Residence near a body of water may be a risk factor for the development of KD.

J Immunol, 1991 May 1, 146(9), 3132 - 7
Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium; Baird RW et al.; Rabbit antisera evoked by purified pepsin-extracted group A streptococcal M proteins were screened for the presence of joint cross-reactive antibodies by indirect immunofluorescence using thin sections of mouse knee joints . Pep M1, M5, and M18 antisera contained antibodies that cross-reacted with chondrocytes, cartilage, and synovium . Immunofluorescence inhibition assays showed that some of the joint cross-reactive epitopes were shared among the three heterologous serotypes of M protein . The pep M5 joint cross-reactive epitopes were localized to three different synthetic peptides of the C-terminal region of pep M5 . Immunoblot analyses showed that the M5 joint cross-reactive antibodies recognized two proteins of human synovium and cartilage of molecular mass 56 and 58 kDa . The cross-reactive antibodies binding to the 56-kDa protein were inhibited by purified vimentin in immunoblot inhibition experiments . M protein-specific antibodies from patients with acute rheumatic fever were also shown to cross-react with joint tissue in a pattern similar to the rabbit antisera . Rabbit and human M protein-specific antibodies that were bound to articular cartilage activated significant levels of complement when compared to control serum, suggesting that M protein joint cross-reactive antibodies could potentially be involved in the pathogenesis of ARF and arthritis.

Jpn Heart J, 1991 May, 32(3), 413 - 8
Native valve bacterial endocarditis due to Staphylococcus epidermidis . A community acquired infection following an acute course; Rudniki C et al.; Staphylococcus epidermidis (SE) is the leading pathogen of prosthetic valve endocarditis . At the same time it is a very rare cause of native valve endocarditis and it follows a clinical course and outcome similar to Streptococcal viridans endocarditis . We report here the case of a 41-year-old man with a community acquired SE endocarditis of a native aortic valve . Despite early surgical intervention, the case followed an acute and fatal course.

Am J Med, 1991 May, 90(5), 639 - 45
Hemorrhagic disorder due to an isoniazid-associated acquired factor XIII inhibitor in a patient with Waldenström's macroglobulinemia; Krumdieck R et al.; A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenstrom's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid . The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter . Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity . Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor . A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption . The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein . The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody . The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein . Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal . Isoniazid was discontinued after the patient was admitted to the hospital . Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50% . Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further . Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity . Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer . This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid.

Z Gesamte Inn Med, 1991 May, 46(7), 234 - 6
{Behçet's syndrome . Possible differential diagnosis in multi-system symptoms}; Weimann C et al.; Behcet's syndrome was described as a triad with recurrent ulcers of the mouth, aphthae of the genitals as well as changes of the eyes . A fourth later added main criterion comprises multifarious dermatological symptoms . Facultative signs of a disease, which, however, occasionally may stand also in the centre of the clinical picture are vascular, gastrointestinal and central-nervous participations, arthritic pains and swellings as well as an epididymitis . On account of the infrequency of the disease outside the endemic regions and the development of the individual manifestations over larger periods it is often recognized very late . Out of the six casuistics described three of them fulfilled the criteria of a complete Behcet's syndrome with evidence of all four main criteria, in the remaining casuistics the incomplete clinical picture was present with three main and one to four side criteria . In all cases the course was relatively benign . Recently, streptococcal antigens were considered to be etiological factors; correlations with the HLA-system are ascertained for patients from endemic regions . In phases of clinical activity the combination of immunosuppressive agents with cortisonoids is the therapy of choice.

Pediatr Res, 1991 May, 29(5), 504 - 9
Modulation of neonatal myelopoiesis in newborn rats after 7 days' administration of either granulocyte-monocyte colony stimulating factor or interleukin-3; Cairo MS et al.; Single-pulse administration of either recombinant human granulocyte-monocyte colony stimulating factor or recombinant human granulocyte colony stimulating factor to newborn rats has previously been demonstrated to increase the peripheral neutrophil count and modulate bone marrow (BM) neutrophil pools . In our present study, we investigated the effects of 7 d of either recombinant murine granulocyte-monocyte colony stimulating factor (rmGM-CSF) (75 micrograms/kg/d) or recombinant murine IL-3 (rm IL-3) (10 micrograms/kg/d) on newborn rat myelopoiesis . Sprague Dawley newborn rats (greater than or equal to 24 h) were injected (intraperitoneally) daily for 7 d with either rmGM-CSF, rmIL-3, or PBS/BSA . rmGM-CSF induced a significant increase in the peripheral neutrophil count on d 3 (p less than 0.03) and d 7 (p less than 0.001) (75% increase) . Additionally, rmGM-CSF induced a 50% increase in the BM neutrophil storage pool (p less than 0.025) . rmIL-3 increased the BM colony forming unit-granulocyte monocyte pool (p less than 0.001); however, it failed to increase the peripheral neutrophil count or BM neutrophil storage pool . Neither CSF increased the BM neutrophil proliferative pool or BM colony forming unit-granulocyte monocyte proliferative rate . Additionally, 7 d of rmGM-CSF with or without antibiotics did not synergistically alter the mortality rate after group B streptococcol inoculation . This study suggests that rmIL-3 appears to stimulate more neonatal myeloid committed progenitor cell activity compared with rmGM-CSF . Optimal modulation of neonatal myelopoiesis may require the use of a sequential combination of hematopoietic CSF, namely an early-acting CSF followed by a more lineage myeloid-specific CSF.

Anticancer Res, 1991 May-Jun, 11(3), 1269 - 74
Splenectomy abolishes antitumor effect of immunotherapy with streptococcal preparation, OK-432, on mouse liver tumors; Imai S et al.; In the present study, we investigated the therapeutic effects of oral and subcutaneous administration of OK-432 prior to or following the transplantation of murine liver tumors . In addition, the effect of splenectomy on the antitumor activity of OK-432 was investigated . Mice which received OK-432 orally prior to tumor transplantation exhibited significantly lower tumor weight and significantly improved survival, when compared to the control mice . Prior subcutaneous injection of OK-432 did not show any antitumor activity . On the other hand, both oral and subcutaneous administration of OK-432, subsequent to tumor transplantation, led to a significant improvement of survival and a decrease in the number of lung metastases, although tumor weight was not affected . The anti-tumor effect of OK-432 required the presence of the spleen, since the survival of the mice with liver tumors was not improved by OK-432 if splenectomy and tumor transplantation were performed simultaneously . These results suggest that immunotherapy with OK-432 may beneficial in the treatment of liver tumors and that these effects are dependent on the presence of the spleen.

Nippon Hinyokika Gakkai Zasshi, 1991 May, 82(5), 716 - 25
{Effect of biological response modifiers on a spontaneous murine renal cell carcinoma regression of metastases caused by the streptococcal preparation OK-432}; Tanji S; The effect of the streptococcal preparation OK-432, which is one of the biological response modifiers, was examined in BALB/c mice using a transplantable murine renal cell carcinoma (Renca) of spontaneous origin, and an analysis of effector cells was performed . The tumor grew progressively and metastasized consistently to the abdominal lymph nodes and then to distant organs following the inoculation of Renca cells in the left renal subcapsular site in BALB/c mice, and the survival time of the mice was under 42 days . In this tumor model, i.p . administration of OK-432 after tumor inoculation significantly extended the survival time and significantly inhibited the formation of the inoculated tumor itself . Removal of the left kidney on the 7th day after tumor inoculation neither extended the survival time nor augmented the effect of OK-432 . Splenic cells obtained on the 7th day after tumor inoculation from Renca-bearing mice treated with OK-432 were capable of lysing syngeneic Renca cells, NK-sensitive allogenic YAC-1 cells, and LAK-sensitive EL-4 cells in a 4-hour 51Cr-release assay in vitro . Those obtained from healthy mice treated with OK-432 also showed cytotoxic activity against Renca cells . The cytotoxicity of splenic cells from Renca-bearing mice treated with OK-432 was lost almost completely for both Renca and YAC-1 cells after in vitro treatment with anti-asialo GM1 antibody, and was partially lost after in vitro treatment with anti-Thy-1,2 antibody . Additionally, in vivo i.p . administration of anti-asialo GM1 antibody significantly counteracted the effect of OK-432 on survival . These findings demonstrated that Renca cells were NK-sensitive and that the i.p . administration of OK-432 was beneficial for the prevention of the spontaneous metastasis of Renca carcinoma . As the effectors, NK cells played a dominant role and activated T cells were also involved.

Vrach Delo, 1991 May, (5), 77 - 80
{The clinical significance of the morphofunctional status of the neutrophilic granulocytes in the palatine tonsils of angina patients}; Lobzin IuV et al.; The morphofunctional state of neutrophils of the palatine tonsils and peripheral blood was studied by means of the lysosomal-cationic test (LCT) in 73 patients with primary streptococcal angina . It is concluded that the LCT test may be used for objective evaluation of the severity of angina and its treatment efficacy.

Minn Med, 1991 May, 74(5), 27 - 9
Group G streptococcal purulent pericarditis . A case report; Halverson KC et al.; We report one of the first two cases of group G streptococcal purulent pericarditis in the medical literature . Our experience illustrates that outcome for patients with this serious group G streptococcal infection may be poor . Failure of single-drug antibiotic therapy can occur, and we conclude that aggressive drainage and combination antibiotics are the most appropriate response to this potentially fatal infection.

Jpn J Surg, 1991 May, 21(3), 297 - 303
Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients; Yanagawa E et al.; The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients . Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432 . Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432 . Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432 . Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432 . An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432 . Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.

Clin Exp Immunol, 1991 May, 84(2), 232 - 7
Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitides and infections; Gallicchio MC et al.; Autoantibodies that produce a perinuclear pattern on indirect immunofluorescent examination of ethanol-fixed neutrophils (pANCA) are found in about half of all cases of microscopic polyarteritis . These antibodies are often directed against myeloperoxidase or elastase and we have developed sensitive reproducible ELISAs for their detection and study . Seven sera from 19 patients with microscopic polyarteritis or segmental necrotizing glomerulonephritis contained anti-myeloperoxidase or anti-elastase antibodies or both . In contrast, only one of 18 sera from patients with Wegener's granulomatosis, where the pattern of immunofluorescence is predominantly cytoplasmic, had anti-myeloperoxidase antibodies and no anti-elastase antibodies were detected . Using sera from patients with microscopic polyarteritis, both anti-myeloperoxidase and anti-elastase antibodies were demonstrated to be of high affinity . There was no immunoglobulin class, subclass or light chain restriction noted . Anti-myeloperoxidase and anti-elastase antibodies were also found occasionally in anti-glomerular basement membrane disease, mixed connective tissue disease, systemic lupus erythematosus, post-streptococcal glomerulonephritis and atypical pneumonia . In further studies these antibodies were not associated with other lung infections, although anti-elastase antibodies were noted in one of 14 sera positive for ASOT that were tested . Anti-myeloperoxidase antibodies were found more frequently than anti-elastase antibodies and these antibodies were occasionally present together . In addition some sera with pANCA had neither anti-myeloperoxidase nor anti-elastase antibodies . The target molecules in these cases remain unclear.

J Immunol, 1991 Apr 15, 146(8), 2588 - 95
The mitogenic activity of type III bacterial Ig binding proteins (protein G) for human peripheral blood lymphocytes is not related to their ability to react with human serum albumin or IgG; Otten RA et al.; The mitogenic potential of bacterial IgG Fc binding proteins for human PBL is controversial . Wild type and recombinant type III IgG Fc binding proteins induce a wide spectrum of proliferative responses ranging from non-mitogenic to potent responses . To understand the reason for these differences, three recombinant forms of a type III IgG Fc binding protein derived from a single human group C streptococcal strain, 26RP66, were generated . Form I bound human IgG and human serum albumin, form II bound IgG alone and form III bound human serum albumin alone . These functionally distinct forms were compared with the corresponding wild type preparation from the same strain for mitogenic potential . A mitogenic response was induced only with the form I recombinant or the native wild type protein . These proteins shared the functional characteristics of binding human serum albumin and IgG . Mixtures of the IgG binding (form II) and human serum albumin binding fragments (form III) failed to reconstitute the mitogenic potential of the full length proteins . These results demonstrate that the type III IgG Fc binding protein has mitogenic potential for human PBL that is not related to its ability to react with human serum albumin or IgG.

Ann Intern Med, 1991 Apr 15, 114(8), 635 - 40
Emboli in infective endocarditis: the prognostic value of echocardiography; Steckelberg JM et al.; OBJECTIVE: To determine whether vegetations visualized on two-dimensional echocardiography are an independent risk factor for the development of subsequent emboli in patients with infective endocarditis and to assess the timing of emboli relative to the initiation of antimicrobial therapy . DESIGN: Investigator-blinded, retrospective incidence cohort study . SETTING: Tertiary referral center . PATIENTS: Patients with left-sided native valve infective endocarditis who had two-dimensional echocardiography within 72 hours of beginning antimicrobial therapy . MEASUREMENTS AND MAIN RESULTS: The crude incidence rate of first embolic events in patients receiving antimicrobial therapy was 6.2 per 1000 patient-days (95% CI, 4.2 to 9.2) . The rates in patients with and without vegetations were 7.1 and 4.9 per 1000 patient-days, respectively (incidence rate ratio, 1.4; 95% CI, 0.6 to 3.3) . The relation between vegetations and risk for emboli was microorganism-dependent: Stratified incidence rate ratios were 6.9 (95% CI, 1.1 to 42.5; P less than 0.05) and 1.0 (95% CI, 0.2 to 3.9) for viridans streptococcal and Staphylococcus aureus endocarditis, respectively . The rate of first embolic events diminished over time (P less than 0.001), falling from 13 per 1000 patient-days during the first week of therapy to less than 1.2 per 1000 patient-days after completion of the second week of therapy . CONCLUSIONS: Overall, the presence of vegetations on echocardiography was not associated with a significantly higher risk for embolus in patients with left-sided native valve infective endocarditis . The relative risk for embolic events associated with echocardiographically visualized vegetations may be microorganism-dependent, with a significantly increased risk seen only in patients with viridans streptococcal infection . The rate of embolic events declines with time after initiation of antimicrobial treatment.

J Immunol, 1991 Apr 15, 146(8), 2560 - 7
HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders; Kamikawaji N et al.; We have found that the low immune response to streptococcal cell wall Ag (SCW) was inherited as a dominant trait and was linked to HLA, as deduced from family analysis . In the present report, HLA class II alleles of healthy donors were determined by serology and DNA typing to identify the HLA alleles controlling low or high immune responses to SCW . HLA-DR2-DQA1*0102-DQB1*0602(DQw6)-Dw2 haplotype or HLA-DR2-DQA1*0103-DQB1*0601(DQw6)-DW12 haplotype was increased in frequency in the low responders and the frequency of HLA-DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15 haplotype or HLA-DR9-DRw53-DQA1*0301-DQB1*0303(DQw3)-Dw23 haplotype was increased in the high responders to SCW . Homozygotes of either DQA1*0102 or DQA1*0103 exhibited a low responsiveness to SCW and those of DQA1*0301 were high responders . The heterozygotes of DQA1*0102 or 0103 and DQA1*0301 showed a low response to SCW, thereby confirming that the HLA-linked gene controls the low response to SCW, as a dominant trait . Using mouse L cell transfectants expressing a single class II molecule as the APC, we found that DQw6(DQA1*0103 DQB1*0601) from the low responder haplotype (DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12) activated SCW-specific T cell lines whereas DQw4(DQA1*0301 DQB1*0401) from the high responder haplotype (DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15) did not activate T cell lines specific to SCW . However, DR4 and DR2 presented SCW to CD4+ T cells in both the high and low responders to SCW, hence the DR molecule even from the low responder haplotype functions as an restriction molecule in the low responders . Putative mechanisms linked to the association between the existence of DQ-restricted CD4+ T cells specific to SCW, and low responsiveness to SCW are discussed.

Vrach Delo, 1991 Apr, (4), 74 - 6
{Immunological indices in the differential diagnosis of rheumatic and nonrheumatic carditis}; Glebova LP et al.; The cellular and humoral immunity was studied in 32 children with primary rheumocarditis and 34 children with nonrheumatic carditis . It is shown that there are no distinct diagnostic criteria of rheumatism form with a paucity of symptoms . This gave an impetus to develop a new method of diagnosis of the rheumatic process by means of preincubation of blood lymphocytes of the patient with a standard streptococcal allergen (dose: 0.1 ml, 30-40 mcg of protein) within 30 min . with subsequent realization of E-rosette formation reaction . Of diagnostic value was an increase of the relative content of E-rosette formation by 10% as compared with the control . The positive effect of this method as compared with determination of the antistreptolysin titer--79% . This allows to recommend wide introduction of the method in practical medicine.

Isr J Med Sci, 1991 Apr, 27(4), 192 - 5
Evaluation of a rapid method for diagnosing streptococcal pharyngitis in a rural community clinic; Hermoni D et al.; Group A beta-hemolytic streptococcal pharyngitis is a common ailment whose accurate diagnosis is dependent on laboratory testing . Transport problems common to rural practices, for laboratory testing, could be resolved by a reliable rapid test . Laboratory evaluations of rapid streptococcal tests, performed mostly in research settings, indicate that the tests have acceptable specificity and sensitivity . This paper describes a comparison study of 248 consecutive throat swab specimens using a commercially available agglutination test with routine throat culturing . All agglutination testing was done by the office staff under actual working conditions, in a rural primary care clinic . The cultures were processed in the main regional microbiology laboratory . As a result of transportation delay, swabs were plated either within 6 h from collection or after 6 h . The test sensitivity (72%) and specificity (88%) compared well with that reported in the literature from microbiology laboratories, especially for swabs plated within six hours (80% and 93% respectively) . The rapid test is an acceptable alternative to the standard culture technique in the family practice office under normal working conditions, provided that patients with negative results follow up with throat cultures.

Clin Orthop, 1991 Apr, (265), 42 - 53
Animal models of rheumatoid arthritis . Clues to etiology and treatment; Brahn E; Animal models of rheumatoid arthritis (RA) provide useful systems for the characterization of the immunopathogenic mechanisms of chronic inflammatory synovitis . Although at least eight models have been described, the adjuvant arthritis, streptococcal cell wall-induced arthritis, and collagen-induced arthritis models have provided the most useful insights . Each of these three models has contributed clues to our understanding of RA and have yielded promising new approaches to treatment . These include combination pharmacotherapy, antigen-specific therapy, cell-specific therapy, and monoclonal antibody therapy . All of these immunotherapeutic interventions have been shown to be beneficial in one or more animal systems . This suggests that future therapies for RA and other human autoimmune diseases may be more immunoselective and, potentially, less toxic.

Clin Orthop, 1991 Apr, (265), 36 - 41
Do infectious agents cause rheumatoid arthritis?
Wilder RL, Crofford LJ.
Although rheumatoid arthritis (RA) has been widely suspected to have an infectious etiology, this hypothesis has remained difficult to prove . Epstein-Barr virus, parvoviruses, and retroviruses are considered by some investigators to be the primary candidates . An increasing body of data, on the other hand, appears to implicate bacteria or their products in the syndrome . Important evidence has surfaced in support of this view . Lyme arthritis, a disease caused by a bacterium, can mimic RA . Bacteria and their products have been conclusively linked to many forms of inflammatory "reactive" arthropathies . RA-like diseases can be induced in certain inbred strains of rats with bacterial cell-wall fragments, e.g., streptococcal and other bacterial peptidoglycans . Immunologic relationships between host and bacterial peptidoglycans, relevant to RA, have been well documented, e.g., heat shock proteins, bacterial IgG Fc binding proteins, and rheumatoid factors . These data not only support the hypothesis that bacteria may play an important role in RA but also indicate that current concepts of infection and autoimmune disease are broadening and overlapping.

Med Decis Making, 1991 Apr-Jun, 11(2), 119 - 24
The impact of a rapid screen for streptococcal pharyngitis on clinical decision making in the emergency department; Hedges JR et al.; The impact of a rapid streptococcal screening test (RSS) on clinical decision making in the management of patients with acute pharyngitis was evaluated . Physicians managing 95 ambulatory patients with the complaint of sore throat were asked to estimate the probability of group A beta-hemolytic streptococcal pharyngitis (GRABS) in each patient and whether they intended to treat with antibiotics both before and after the results of the RSS were known . Simultaneous throat cultures were obtained for 80 patients at the discretion of the treating physicians . Regression analysis revealed that the RSS result was an important independent predictor for the posttest decision to treat with antibiotics and for the estimated probability of disease . The mean absolute log-likelihood ratio was used to quantify the effect of the RSS on diagnostic certainty; a greater contribution to diagnostic certainty occurred when the RSS was positive . Physicians would have prescribed an antibiotic 49 times without the benefit of the RSS and prescribed an antibiotic 48 times given the RSS result . Without the RSS, the treatment decision contradicted the throat culture result in 25 cases . With the RSS, this occurred in 26 cases . The RSS, while influencing decision making, especially when positive, did not decrease the use of antibiotics.

Scott Med J, 1991 Apr, 36(2), 42 - 4
Group G streptococcal bacteraemia--a review of thirteen cases in Grampian; Packe GE et al.; Thirteen cases of group G streptococcal bacteraemia are described . All subjects were hospital in-patients between 1980-1988, and were either middle-aged or elderly . A primary site of infection was identified in 11, of whom nine had soft tissue infection and two had infections derived from the gut/biliary tree . Seven patients had underlying disease, two of whom had malignancy . One patient died of septicaemia . In the majority of patients early institution of treatment led to prompt recovery.

Pediatr Infect Dis J, 1991 Apr, 10(4), 275 - 81
A comparison of cephalosporins and penicillins in the treatment of group A beta-hemolytic streptococcal pharyngitis: a meta-analysis supporting the concept of microbial copathogenicity; Pichichero ME et al.; Although penicillin has been the antibiotic of choice for therapy of Group A beta-hemolytic streptococcal pharyngitis for more than four decades, reports of bacteriologic and clinical treatment failures with penicillin have increased in recent years . We conducted a meta-analysis of 19 studies to examine whether oral cephalosporins were associated with lower failure rates than oral penicillin in the treatment of Group A beta-hemolytic streptococcal pharyngitis . The overall bacteriologic cure rate for penicillin was 84% (95% confidence interval (CI), 82%, 86%) compared with 92% (95% CI, 91%, 94%) among patients treated with cephalosporins (P less than 0.0001) . The overall clinical cure rate in the penicillin groups was 89% (95% CI, 87%, 91%) compared with 95% (95% CI, 94%, 96%) in the cephalosporin group (P less than 0.001) . There was no significant difference between the cephalosporins and the penicillins with respect to adverse events . There may be clinical circumstances in which treatment of Group A beta-hemolytic streptococcal pharyngitis with cephalosporins is indicated.

Mol Biol Med, 1991 Apr, 8(2), 207 - 18
Considerations affecting selection of thrombolytic agents; Smitherman TC; The data reviewed above show that the ideal thrombolytic or thrombolytic plus anticoagulant regimen does not exist . Nor is it clear to me that one regimen is unequivocally better than another in regards to clinical outcome . Publication of the full results of the ISIS-3 study and completion of the TAPS study, the GUSTO study, the TIMI-4 study plus others only now in the planning phases, should help . This review will not stay current very long . These data do, however, give some guides to certain circumstances in which one regimen might be preferred over others . If economics is a compelling issue, as it may be in public hospitals on a fixed budget or in the developing world, streptokinase may be the best choice . For early application of thrombolytic therapy, such as at the site of infarct occurrence and in automotive and aerial ambulances, anistreplase may be preferred because of its ease of administration . Previous administration of streptokinase or anistreplase (within the period of 48 h to 6 months after prior use) militate against their use as does a recent streptococcal infection . Heightened concerns about bleeding risk, except intracranially, in the absence of absolute contraindication of fibrinolytic therapy, e.g . remote gastrointestinal hemorrhage or the expected imminent need for an invasive procedure, may lead to preference for alteplase over streptokinase or anistreplase . On the other hand, heightened concerns about intracranial hemorrhage may lead to preference for streptokinase over alteplase or anistreplase . Alteplase may be preferred over non-fibrin-selective agents in the treatment of patients when administration is begun more than three hours after the presumed onset of infarction . These considerations notwithstanding, it is crucial that debates over the best choice of a regimen must not be allowed to prolong the time before administration of an effective thrombolytic agent to a patient with evolving Q-wave infarction who is a good candidate for this therapy . This review may also become dated in the not-too-distant future because of expected further advances in thrombolytic regimen . Application of new antithrombotic regimens was noted above . Future thrombolytic and antithrombotic regimens may be "cocktails" of one or more thrombolytic agents plus more powerful antithrombotic and antiplatelet agents . New generations of thrombolytic agents may replace the current first and second generation agents now used . Combination thrombolytic and anti-fibrin antibody agents and mutant tissue-type plasminogen activators with lower affinity for plasminogen activator inhibitor and longer half-lives are being developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Eur J Biochem, 1991 Mar 14, 196(2), 363 - 8
Characterization of a murine beta 1-4 galactosyltransferase expressed in COS-1 cells; Nakazawa K et al.; We inserted a full-length murine cDNA, which had been isolated from F9 embryonal carcinoma cells by using a bovine lactose synthetase A protein cDNA as a probe, in a mammalian expression vector (pCMGT1) and expressed it in COS-1 cells to characterize the pCMGT1-directed enzyme . The galactosyltransferase activity toward asialo-agalacto-transferrin (AsAg-Tf) in the pCMGT1-transfected cells was approximately eightfold higher than that in mock- or non-transfected cells . In contrast, no difference was observed in the specific activity of galactose transfer between pCMGT1-transfected cells and mock- or non-transfected cells when asialo-ovine submaxillary mucin were used as an acceptor . Since almost all {3H}galactose incorporated into the AsAg-Tf was released by digestion with streptococcal beta-galactosidase, most of the linkage created by this enzyme was in the Gal beta 1-4GlcNAc group . The acceptor specificity of the pCMGT1-directed enzyme was changed from N-acetylglucosamine to glucose by adding alpha-lactalbumin in the reaction mixture . Alpha-Lactalbumin also partially inhibited the galactose transfer to AsAg-Tf . The kinetic study revealed that the apparent Km values of the pCMGT1-directed enzyme for N-acetylglucosamine, AsAg-Tf and UDP-Gal are 2 mM, 60 microM and 24 microM, respectively . These results indicated that the murine cDNA isolated from F9 cells encodes an active enzyme which catalyzes not only the lactose synthesis but also the transfer of galactose to N-acetylglucosamine residues of Asn-linked sugar chains of glycoproteins in a beta 1-4 linkage.

Biochem J, 1991 Mar 1, 274 ( Pt 2), 503 - 7
The secondary structure of protein G', a robust molecule; Goward CR et al.; The secondary structure of recombinant streptococcal Protein G' was predicted and compared with spectropolarimetric data . The predicted secondary structure consisted of 37 +/- 4% alpha-helix and 30 +/- 5% beta-sheet, whereas the values obtained from c.d . data were 29 +/- 2% alpha-helix and 41 +/- 3% beta-sheet . An alpha-helix-beta-sheet/turn-alpha-helix motif is conjectured to comprise the Fc-binding unit . The c.d . spectra in the near u.v . and far u.v . show that the Protein G' molecule is stable to heating at 100 degrees C and to extremes of pH (pH 1.5 to 11.0) . The protein retained biological activity at these extremes . The molecule uncoils above pH 11.5 in a time-dependent fashion . Unfolding of the molecule in guanidinium chloride was monitored by c.d . and fluorescence emission; 3 M-guanidinium chloride was required to unfold the protein by 50% . The protein was completely unfolded in 5.5 M-guanidinium chloride and fully refolded with restoration of activity after removal of guanidinium chloride.

J Clin Invest, 1991 Mar, 87(3), 1108 - 13
Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals; Brandes ME et al.; Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats . TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs . 11; P less than 0.025) and the chronic phase (AI = 0 vs . 12.5) of the disease . Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease . Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion . Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis . Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment . These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent.

Infect Immun, 1991 Mar, 59(3), 1210 - 4
Cell and receptor requirements for streptococcal pyrogenic exotoxin T-cell mitogenicity; Leonard BA et al.; Streptococcal pyrogenic exotoxins (SPEs) A, B, and C, like other members of the pyrogenic toxin family, are able to cause toxic shock-like syndromes . One of the major properties of these toxins is the ability to induce T-cell proliferation . Characterization of T cell mitogenicity associated with SPEs A, B, and C was undertaken . SPEs A, B, and C were mitogenic for C57BL10/SnJ and BALB/cWAT T cells, with activities differing in intensity depending on the mouse strain and toxin employed . SPE-induced, T-cell-proliferative activity was dependent on class II major histocompatibility complex molecules expressed on antigen-presenting cells . The abilities of SPEs A, B, and C to preferentially stimulate murine cells with certain T-cell receptor V beta s were investigated by fluorescence-activated cell sorter analysis . SPE A preferentially activated T cells expressing V beta 8 but not V beta 3, 6, or 11, while SPEs B and C preferentially stimulated T cells which did not express any of the tested V beta s.

Cytokine, 1991 Mar, 3(2), 98 - 106
Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon; Allen JB et al.; Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats . Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions . Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01) . Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN . Histopathologic evaluation of the joints demonstrated that gamma IFN-treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls . gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects . These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis.

Vrach Delo, 1991 Mar, (3), 90 - 1
{The characteristics of a streptococcal-etiology angina in an industrial center}; Bala MA et al.; Results are presented of a study of the clinical picture of angina of streptococcal etiology in conditions of a large industrial center . The authors analyzed the state of unspecific adaptative reactions of the body at different periods of the disease . Conclusions on the characteristic aspects of sanogenesis in this type of pathology are made.

Equine Vet J, 1991 Mar, 23(2), 111 - 5
The raising of equine colostrum-deprived foals; maintenance and assessment of specific pathogen (EHV-1/4) free status; Chong YC et al.; Over a period of two years, a total of 22 full term foals from Welsh Mountain pony mares were raised in conditions that were free from infection by Equid herpesvirus (EHV-1/4) . Parturition dates were predicted by monitoring colostrum electrolytes, and the mares allowed to foal naturally under supervision or following induction with intravenous oxytocin . Immediately following birth, foals were separated from their dams and transferred to a specially built, positive pressure isolation unit . They were given antibiotic prophylaxis and fed bovine colostrum during the first 24 h, and then mare's milk replacer until weaned . Out of 22 specific pathogen free (SPF) foals one that had not been given antibiotic prophylaxis died of an E . coli septicaemia aged eight days . Two foals developed a streptococcal upper respiratory tract infection, which responded to antibiotic therapy and did not spread to the rest of the herd . A self limiting upper respiratory tract infection was seen in a fourth foal and mild diarrhoea was observed in six foals . Physical development in all SPF foals appeared normal and behavioural patterns resembled those of conventional handreared foals . Newborn foals were held in a separate quarantine area, within the isolation unit, and checked extensively for evidence of EHV-1/4 infection, before being transferred to the main holding unit . Periodic checks were then made for EHV-1/4 over a period ranging from 2 to 4 months; none of the SPF foals showed evidence of infection with EHV-1/4 in terms of clinical disease, virus isolation, sero-conversion or specific lymphocyte transformation.

Enzyme Microb Technol, 1991 Mar, 13(3), 204 - 9
Partitioning of beta-galactosidase fusion proteins in PEG/potassium phosphate aqueous two-phase systems; Kohler K et al.; Four different beta-galactosidase fusion proteins have been partitioned in poly(ethylene glycol) (PEG) 4000/potassium phosphate aqueous two-phase systems . The partition coefficients (K) of staphylococcal protein A-beta-galactosidase (SpA beta gal) (K = 3.5) and staphylococcal protein A-streptococcal protein G-beta-galactosidase (AG beta gal) (K = 2.8) were compared with the partition coefficients of their constituent molecules, beta-galactosidase, SpA, and protein AG . It was found that by fusing beta-galactosidase to the smaller proteins SpA and protein AG, their partition coefficients were increased four to five times . Experimental data were fitted into, and found to agree with, the Albertsson partition model of interacting molecules . The compatibility with PEG and potassium phosphate of beta-galactosidase, SpA, and two different versions of the SpA beta gal protein, displayed as precipitation curves, showed a relationship to the protein partition coefficients in PEG/potassium phosphate systems . High solubility in one phase component was accompanied by preferential partitioning to the phase rich in the same component in the PEG/potassium phosphate system . Also, a changed linker region in SpA beta gal resulted in a more soluble protein . This, together with the improved K values of the target proteins by fusion, shows that it is possible to use beta-galactosidase as an affinity handle.

J Immunol Methods, 1991 Feb 15, 136(2), 279 - 86
Optimization of binding capacity and specificity of protein G on various solid matrices for immunoglobulins; Pilcher JB et al.; Streptococcal protein G is a more versatile and efficient alternative to staphylococcal protein A in purifying immunoglobin G (IgG) isotypes from various animal species . Optimizations are most dramatic with goat IgG, which binds protein G 55 times better than protein A . Using GammaBind G (a recombinant form of protein G (Genex Corp.)), we optimized binding capacity and specificity for IgG . Protein G was covalently coupled to three different matrices (CNBr-Sepharose, Tresyl-Sepharose, and Affigel-10) and compared with protein A-CNBr-Sepharose . Equal volumes of human, mouse, and goat serum samples were equilibrated into Hepes/NaOH buffers with various ionic strengths (i.e., concentrations of NaCl) and pH values and allowed to bind to affinity columns of proteins G and A . Bound ligands were eluted with 8.0 M urea, 0.05-M Tris/HCl, pH 8.00 . Bound fractions were assayed for protein concentration and analyzed by sodium dodecyl sulfate polyacrylamide electrophoresis . The optimal conditions for binding IgG to protein G are 1.0 M NaCl and pH 8.0 for human, mouse, and goat.

Fam Med, 1991 Feb, 23(2), 117 - 21
The prevalence of Mycoplasma pneumoniae in ambulatory patients with nonstreptococcal sore throat; Williams WC et al.; Several studies have implicated Mycoplasma pneumoniae as an important cause of nonstreptococcal pharyngitis in certain clinical settings . This study was performed to determine the prevalence of M . pneumoniae infection in family practice patients with sore throats and to identify patient characteristics predictive of this infection . M . pneumoniae throat cultures were obtained from 419 patients aged five years or older who were seen in one of four family practice offices with a complaint of sore throat . The overall prevalence of M . pneumoniae infection was 13% . It was characterized by more frequent hoarseness and less frequent complaint of postnasal drip when compared with other nonstreptococcal infections . Compared to patients with streptococcal pharyngitis, M . pneumoniae patients revealed a strikingly dissimilar clinical presentation . In particular, while pharyngitis is predictive of streptococcal infections, its presence did not predict M . pneumoniae infection . Recently developed rapid office-based tests for M . pneumoniae may allow timely diagnosis of this common and formerly elusive pathogen . Further study is required to validate the utility of such methods and to evaluate the efficacy of treatment.

J Antimicrob Chemother, 1991 Feb, 27 Suppl A, 75 - 82
A comparative study of clarithromycin and penicillin VK in the treatment of outpatients with streptococcal pharyngitis; Bachand RT Jr; This double-blind, randomized 17-centre clinical trial compared the safety and efficacy of clarithromycin (2 x 125 mg capsules) 12-hourly and penicillin VK (2 x 125 mg tablets in capsules) 6-hourly in the treatment of proven Group A, beta-haemolytic streptococcal pharyngitis . One hundred and twenty-eight patients (clarithromycin: 65, penicillin VK: 63) were enrolled in the study and included in the safety analysis . Clinical and bacteriological evaluations were performed on treatment days 5-7, and within two to ten and 15 to 56 days post-treatment . The post-treatment clinical success and bacteriological cure rates for clarithromycin were 95% (41/43) and 88% (38/43), respectively, with both rates 91% (43/47) for penicillin VK . Three clarithromycin patients withdrew because of adverse events, but only one of these events was possibly drug related . More clarithromycin patients (19/65) reported digestive system related adverse events than did penicillin VK patients (8/63); however, there was no significant difference between treatment groups in the overall number of patients reporting adverse events . Clarithromycin (250 mg, 12-hourly) is a safe and effective as penicillin VK (250 mg, 6-hourly) in the treatment of streptococcal pharyngitis.

Med Clin (Barc), 1991 Feb 9, 96(5), 169 - 72
{Erythema nodosum: a study of 160 cases}; Atanes A et al.; We have evaluated 160 patients diagnosed of erythema nodosum (EN) on the basis of clinical and/or histopathological criteria to assess their etiology and their major epidemiological, clinical and laboratory features in our area . Mean age was 37.5 years and 86% of patients were females . The etiology could be determined in 67.5% of cases: sarcoidosis (20.6%), drugs (18%), streptococcal infection (16.3%), tuberculosis (6.3%), pregnancy (1.9%), Crohn's disease (1.3%), Behcet's disease (1.3%), lymphoma (0.6%), adenocarcinoma (0.6%), and toxoplasmosis (0.6%) . 32.5% of cases were idiopathic . We found significant differences between the different etiological factors regarding mean age, fever, joint disease, ESR, leukocytosis and serum proteins . We compare our results with those from other series and we emphasize the need for a systematic workup in all patients with EN to facilitate their etiological diagnosis.

J Cell Biochem, 1991 Feb, 45(2), 162 - 6
Endothelial cells and the pathogenesis of rheumatoid arthritis in humans and streptococcal cell wall arthritis in Lewis rats; Wilder RL et al.; Endothelial cells play a fundamental role in the pathogenesis of chronic inflammatory arthritis in humans such as rheumatoid arthritis (RA), as well as experimental animal models such as streptococcal cell wall (SCW) arthritis in Lewis (LEW/N) rats . This review summarizes data in support of this concept . The earliest apparent abnormalities in synovial tissues of patients with RA and Lewis rats with SCW arthritis appear to reflect microvascular endothelial cell activation or injury . At the molecular level, the abnormalities include enhanced expression by endothelial cells of activation markers such as class II major histocompatibility complex antigens, phosphotyrosine, leukocyte adhesion molecules, oncoproteins such as c-Fos and c-Myc, and metalloproteinases such as collagenase and transin/stromelysin . The development of severe, chronic, destructive arthritis is dependent upon thymic-derived lymphocytes and is accompanied by tumorlike proliferation of cells in the synovial connective tissue stroma (blood vessels and fibroblastlike cells), which results in resorptive destruction of bone and cartilage . Multiple criteria support the analogy to a neoplastic process . Paracrine and autocrine factors such as interleukin-1 (IL-1), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and heparin-binding fibroblast growth factors (HBGF, FGF) appear to play important roles in the generation of these lesions . Finally, in addition to the autocrine and paracrine regulatory factors, neuroendocrine factors, particularly the hypothalamic-pituitary-adrenal axis, appear to be involved in the counterregulation of the inflammatory process . The counterregulatory effects are mediated, in part, by inhibition of endothelial cell activation by corticosteroids.

Am J Med Sci, 1991 Feb, 301(2), 138 - 49
The role of infections in the rheumatic diseases: molecular mimicry between bacterial and human stress proteins?
Smiley JD, Hoffman WL.
Infections can cause or exacerbate the rheumatic diseases in several ways, including immune cross-reactivity between bacterial heat shock proteins and similar proteins in normal human tissues . This may lead to autoimmunity in rheumatoid arthritis and systemic lupus . In addition, increased activation of the gene regulating the synthesis of a heat shock protein has been found in scleroderma fibroblasts . As an infection-induced model for other rheumatic diseases, rheumatic fever (RF), with its well-established link to prior group A streptococcal infection, will be revisited . The lessons learned from RF and other rheumatic diseases directly linked to infection will be applied to ankylosing spondylitis, rheumatoid arthritis, Sjogren's syndrome and polymyositis, for which a mounting body of circumstantial evidence suggests a probable infectious cause . The interplay of genetic susceptibility and infection with particular organisms and the implications of this new information for present and future therapy of the rheumatic diseases will also be presented.

W V Med J, 1991 Feb, 87(2), 61 - 5
Acute post-streptococcal glomerulonephritis; Richards J; Acute glomerulonephritis is characterized by the presence of hematuria, proteinuria and edema, and often hypertension and acute renal failure . Acute post-streptococcal glomerulonephritis is the prototypic disease of acute glomerulonephritis . It is seen after both streptococcal pharyngeal and skin infections with a latency period from infection to presentation of 7-14 days and 14-21 days respectively . Approximately 90 percent of post-streptococcal glomerulonephritis occurs in young children . The diagnosis is made by supporting evidence of recent streptococcal infection, a positive ASO-titer or Anti-DNAase B titer, with associated hypocomplementemia . The disease is self-limited and generally requires only supportive therapy with resolution occurring over a period of weeks to months . There are generally no permanent sequelae in children . Adults may have a higher incidence of hypertension and chronic renal failure as a result of post-streptococcal glomerulonephritis.

Am J Kidney Dis, 1991 Feb, 17(2), 228 - 30
Recurrent acute glomerulonephritis; Glotz D et al.; Biopsy-proven recurrent acute glomerulonephritis (AGN) is extremely rare and is usually seen in children with acute, well-defined streptococcal infections . We present here a patient with recurrent AGN in the absence of chronic bacterial infection . The subject, an 80-year-old man, had eight episodes of acute nephritic syndrome following upper respiratory tract infection . No abnormalities were detected during remissions . Renal biopsies during two of those episodes showed typical postinfectious acute exsudative endocapillary glomerulonephritis, while results of another biopsy performed during remission were normal.

South Med J, 1991 Feb, 84(2), 205 - 8
Adenotonsillectomy in children with sickle cell disease; Derkay CS et al.; The pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia . With proper patient selection and appropriate perioperative management, adenotonsillectomy can be accomplished safely in children with sickle cell disease . We review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy . Indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children . No complications resulted from any of these procedures, and the mean length of postoperative hospitalization was 2.4 days . The principal feature of preoperative management was the transfusion of red blood cells to suppress the patient's endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30% . Though a prospective, multi-institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease, balancing the risks of transfusion-related complications against anesthesia-related complications, our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease.

J Fam Pract, 1991 Feb, 32(2), 138 - 44
Treatment of beta-hemolytic streptococcal pharyngitis with cefaclor or penicillin . Efficacy and interaction with beta-lactamase-producing organisms in the pharynx; Reed BD et al.; The recommended treatment for group A beta-hemolytic streptococcal pharyngitis has continued to be penicillin given in parenteral or oral form . Treatment failures, as determined by the continued presence of the streptococcal organism in the pharynx, however, do occur in 6% to 25% of patients treated with penicillin . Furthermore, beta-lactamase produced by other bacteria in the pharynx could potentially inactivate the penicillin, resulting in increased treatment failures or infection relapses . A study was undertaken to compare the efficacy of cefaclor, which is relatively resistant to inactivation by beta-lactamase, with penicillin for eradicating the group A beta-hemolytic streptococcal organism from the throats of 93 patients with pharyngitis . Additionally, extensive cultures for potential beta-lactamase-producing organisms were conducted on 37 patients; 27% of these had one or more pharyngeal organisms that were producing beta-lactamase . No statistically significant difference was found between the clinical responses or the bacteriological cure rates of those treated with cefaclor and those treated with penicillin when stratified by the presence or absence of beta-lactamase-producing organisms . The prevalence of beta-lactamase-producing organisms in the pharynx, however, was increased after treatment with penicillin, whereas no change was noted following treatment with cefaclor.

Obstet Gynecol, 1991 Feb, 77(2), 322 - 6
Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients; Skoll MA et al.; Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery . Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures . The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay . Overall, 105 patients (9.9%) had at least one positive culture . The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate . Specificities were 99.3 and 98.7%, respectively . Sensitivity was minimally increased in the setting of ruptured membranes for both tests . Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test . In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units . We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.

Pediatr Infect Dis J, 1991 Feb, 10(2), 126 - 30
Immediate vs . delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V; el-Daher NT et al.; Three hundred six children with probable Group A beta-hemolytic streptococcal pharyngitis were enrolled in a randomized double blind trial to compare the effects of immediate vs . delayed treatment with oral penicillin V . Among the 229 culture-positive patients, 111 were randomly assigned to receive penicillin V immediately and 118 to receive a placebo for 48 to 52 hours followed by penicillin V . Patients were evaluated clinically for 48 to 52 hours following initiation of treatment . The Streptozyme test was used to measure acute to convalescent antibody titer . Both regimens resulted in a greater than 92% cure rate . Early treatment was associated with significantly fewer and milder signs and symptoms on Day 3 and a significantly lower rise in the antibody titer . On the other hand we found 8 (7%) relapses and 18 (16%) early and 14 (13%) late recurrences in this group; all were significantly higher than the corresponding numbers of 2 (2%), 6 (5%) and 4 (3%), respectively, in the late treatment group . This study shows the beneficial effect of early treatment with penicillin V on the clinical course of Group A beta-hemolytic streptococcal pharyngitis . This study also shows that delayed penicillin treatment may be associated with a lower incidence of subsequent Group A beta-hemolytic streptococcal pharyngitis.

Aten Primaria, 1991 Feb, 8(2), 92, 94, 96 - 8
{Evaluation of clinical data and a technique of rapid detection (TestPack Strep A) in the diagnosis of acute streptococcal pharyngo-tonsillitis}; Blade J et al.; We have evaluated the validity of the clinical data, the clinical impression (CI) of the physician and a rapid antigenic technique (RAT) for the diagnosis of acute streptococcal pharyngitis and tonsillitis (SPT) . We evaluated 126 patients aged 7-60 years (October 1988-March 1989) . The incidence of SPT was 19% . SPTs had a significantly higher frequency of lack of cough and sudden onset as isolated findings, and of the associations fever greater than 38 degrees C + exudate + lack of cough, and sudden onset + fever greater than 38 degrees C + exudate + lack of cough . CI had a sensibility (S) of 56%, a specificity (Sp) of 72%, a positive predictive value (PPV) of 32%, a negative predictive value (NPV) of 88% and an overall valve (OV) of 69% . The RAT had a S of 79.2%, a Sp 93%, a PPV of 73%, a NPV of 95%, and an OV of 90.5% . Only some clinical data are useful to diagnose SPT . The CI of the physician has a low predictive value, whereas TestPack Strep A is useful and has a similar value as pharyngeal culture.

J Immunol, 1991 Jan 15, 146(2), 708 - 14
Modulation of monocyte chemotactic function in inflammatory lesions . Role of inflammatory mediators; Katona IM et al.; Monocyte recruitment and accumulation in the synovial tissue is pivotal in the evolution of rheumatoid arthritis (RA) . In the present study we examined the chemotactic potential of monocytes obtained from synovial fluid (SF) of patients with RA . Functionally, SF monocytes exhibited greatly diminished chemotactic activity to C5a compared with monocytes from the peripheral blood . In contrast, their chemotactic responsiveness to the synthetic peptide, FMLP, was nearly normal . To define a mechanism for this differential chemotactic dysfunction, cell-surface receptors for C5a (C5aR) and FMLP (FMLP-R) were evaluated . Whereas FMLP-R expression was similar on both blood and inflammatory monocytes, C5aR expression was markedly reduced on SF cells . Because decreased C5a binding in certain RA SF samples could not be attributed to free C5a, known or suspected components of inflammatory SF were evaluated for their ability to modulate chemotactic ligand receptors . Bacterial products including LPS and streptococcal cell walls, which are potent monocyte activators, down-regulated C5aR without affecting FMLP-R . Moreover, the cytokines IFN-gamma and granulocyte-macrophage-CSF selectively decreased C5aR in parallel with decreased in vitro chemotactic activity to C5a . Thus, these data indicate that 1) synovial effusions may contain C5a and/or inflammatory mediators that modulate phenotypic and functional changes in monocytes, 2) chemotactic ligand receptors are independently regulated in inflammatory lesions, and 3) decreased C5aR expression and chemotactic potential likely provide a mechanism whereby monocyte-macrophages persist within the inflamed synovium.

Int J Immunopharmacol, 1991, 13(2-3), 147 - 54
Oral administration of a streptococcal agent OK-432 activates peritoneal macrophages in mice; Suzuki I et al.; The effect of orally administered OK-432, a streptococcal preparation, on the function of peritoneal macrophages in mice was examined . The administration of OK-432 orally (1 KE or 2 KE, four times every three days) did not affect the numbers of both total peritoneal cells and macrophages recovered five days after the final administration . However, the macrophages exhibited an increase in their spreading ability . Other functions of the peritoneal macrophages including lysosomal enzyme activity, phagocytic activity and interleukin 1 (IL-1) production were also enhanced significantly by the oral administration of OK-432 (1 KE or 2 KE) . The production of H2O2, however, was not affected by the same treatment with OK-432 . The activation of peritoneal macrophages by orally administered OK-432 reported here may contribute to expansion of the clinical application of this drug.

Int J Hyperthermia, 1991 Jan-Feb, 7(1), 113 - 23
Enhancement of the thermal response of murine tumour and normal tissues by a streptococcal preparation, OK-432 (Picibanil); Urano M et al.; We have studied the effect of a streptococcal preparation, OK-432, given alone or in combination with hyperthermia on murine tumour and normal tissues . The experimental tumour was a spontaneous non-immunogenic fibrosarcoma FSa-II transplanted in the foot of C3Hf/Sed mice . Local hyperthermia was achieved by immersing the mouse foot into a constant temperature water bath (42-45 degrees C) for various lengths of time . Tumour response was studied by analysing the tumour growth (TG) time . Various doses of OK-432 (1-5 KE/mouse) were injected locally into the tumour . Local administration of OK-432 alone (without hyperthermia) had no effect on the TG time . Thermal enhancement ratio (TER) for combined treatment was independent of drug dose greater than or equal to 2 KE, and the mean TER was 1.48 +/- 0.27 (95% CL) . The TER was greater for 6 mm tumours than for 4 mm tumours, and it was greatest if the time interval between hyperthermia and drug administration was 3 h or less . There was no effect if the drug was administrated 4 days before hyperthermia, but its application 9 days prior to hyperthermia caused a slight prolongation of the TG time of non-heated tumours, and a reduction in the TG time of heated tumours . Normal-tissue response was studied by scoring the peak foot reaction and RD50 (the treatment time to induce a specified response in one-half of the treated animals) . The effect of OK-432 on the thermal response of the foot was also studied at various temperatures . The mean TER was 1.11 +/- 0.07 . Local administration of OK-432 failed to modify significantly the kinetics of thermotolerance . Present experiments demonstrated that OK-432 after local administration enhanced the thermal response of murine tumour and normal tissues . This enhancement was greater for the tumour than for the normal tissue, resulting in a favourable differential effect between normal and malignant tissues (the average therapeutic gain was 1.33 +/- 0.19).

Eur J Clin Pharmacol, 1991, 40(4), 427 - 8
Pharmacokinetics of ibuprofen in febrile children; Nahata MC et al.; Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients . We studied 17 patients (age 3-10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media . Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients) . Multiple blood samples were collected over 8 hours and analyzed by HPLC . The maximum observed serum concentrations of ibuprofen ranged from 17-42 micrograms.ml-1 at 5 mg.kg-1 and 25-53 micrograms.ml-1 at 10 mg.kg-1 doses . Pharmacokinetics did not appear to be affected by ibuprofen dose . Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml.min-1.kg-1, and 1.6 h, respectively in patients at 5 mg.kg-1 doses; the corresponding values were 1.2 h, 1.4 ml.min-1.kg-1, and 1.6 h in those receiving 10 mg.kg-1 doses . There was no relationship between age and ibuprofen kinetics . No adverse effects occurred in any patients . These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.

J Emerg Med, 1991 Jan-Apr, 9(1-2), 33 - 5
Arcanobacterium hemolyticum infection: confused with scarlet fever and diphtheria; Kain KC et al.; Arcanobacterium hemolyticum infections are a common cause of pharyngitis and rash in the 10- to 30-year-old age group . Despite its prevalence, many emergency and primary care physicians may not be aware of the pathogenic potential of this organism . We present a case that illustrates the distinctive clinical spectrum of A . hemolyticum infections that may be confused with drug allergy, group A streptococcal scarlet fever, diphtheria, and even toxic shock syndrome . Recognition of this syndrome will reduce misdiagnoses and facilitate appropriate treatment.

Refract Corneal Surg, 1991 Jan-Feb, 7(1), 62 - 6
Complications of penetrating keratoplasty: graft infections; Varley GA et al.; Microbial infection of a corneal transplant is a complication that is a bane to all corneal surgeons, the sequelae of which can be devastating . Identified risk factors include exposed, loose, or broken sutures; persistent epithelial defects or severe punctate keratopathy; soft contact lens wear including therapeutic lenses; graft hypoesthesia; kerato-conjunctivitis sicca; previous herpetic eye disease; graft failure; ocular adnexa and lid abnormalities; and ongoing external and corneal infections . Management includes preventive measures, microbiologic diagnostic procedures, and antibiotic therapy . Infectious crystalline keratopathy is a unique corneal infection that predominantly occurs in corneal transplants . It is characterized by the slowly progressive development of needle-like opacities in the corneal stroma and is most commonly caused by streptococcal species . Another group of infections that occur in grafts is recurrence of an infectious process for which the patient was originally grafted . Two notable pathogens in this group include Acanthamoeba and herpes simplex.

Rev Infect Dis, 1991 Jan-Feb, 13(1), 8 - 11
Characteristics of group A streptococcal bacteremia in patients at the San Bernardino County Medical Center; Braunstein H; On the basis of a 12-year study of 58 patients at our medical center who had group A streptococcal bacteremia, we found that this disease is not uncommon when compared with other varieties of bacteremia . It occurs with about one-half of the frequency of bacteremias due to Klebsiella species and one-eighth of that of bacteremias due to Staphylococcus aureus . The infection is infrequently nosocomial (3.5% of cases) and the predominant causes are cutaneous or subcutaneous infections (72% of cases) . While many patients are chronically ill, debilitated, or elderly, in our institution, as in some other public hospitals, the most important underlying condition is a history of iv drug abuse (28% of cases) . Our data and those of some other recent publications suggest that the occurrence of cases related to iv drug abuse may be increasing . Intravenous drug abusers tend to be young adults, while other sources of infection are found more frequently in older patients . The frequent presence (10.3% of cases) of other organisms (especially S . aureus) in the blood of patients with group A streptococcal bacteremia has not been sufficiently emphasized in previous studies.

Pediatr Pulmonol, 1991, 10(1), 18 - 24
The paradox of adult respiratory distress syndrome in neonates; Pfenninger J et al.; Six full-term newborn infants are described who suffered from severe adult respiratory distress syndrome (ARDS) . The triggering event was intrauterine/perinatal asphyxia in five, and group B streptococcal (GBS) septicemia in three . All had severe respiratory distress/failure and were ventilated mechanically with high concentrations of inspired oxygen and positive end-expiratory pressure . Radiography of the chest showed dense bilateral consolidation with air bronchograms and reduced lung volume . Persistent pulmonary hypertension (PPH) was documented in all cases . The coincidence of ARDS and PPH rendered respiratory management extremely difficult . For this reason high-frequency ventilation was instituted in all patients in order to improve CO2 elimination and induce respiratory alkalosis . Acute complications of respiratory therapy were encountered in five patients (pneumothorax, pulmonary interstitial emphysema, pneumopericardium) . Three infants died (irreversible septic shock, progressive severe hypoxemia, and sudden cardiac arrest) after 17, 80, and 175 h of life . Histologic examination of the lungs was possible in all fatal cases and revealed typical changes of acute to subacute stages of ARDS . Three infants survived, the mean time of mechanical respiratory support being 703 h . Two patients were still dependent on oxygen after 1 month of life, and all survivors had increased interstitial markings and increased lung volumes on their chest roentgenograms at this time.

Arch Intern Med, 1991 Jan, 151(1), 133 - 6
Acute rheumatic fever in West Virginia . Not just a disease of children; Mason T et al.; Rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community . We describe a recent increase in the number of observed cases of acute rheumatic fever (ARF) in West Virginia . This is the fifth report of a recent increase in the incidence of ARF in the Ohio Valley area in the last 4 years . In contrast to the other reports, nearly two thirds of our cases of ARF were in adults, more than half of whom had suffered previous bouts of ARF . In these adults with recurrences, none was taking prophylactic penicillin at the time of presentation . Carditis was present in seven adults, two without a history of carditis . Arthritis was present in all adult patients . These data indicate a possible geographic phenomenon related to the increased number of observed cases of ARF and document that ARF is not simply a disease of childhood . Furthermore, our findings highlight the need for extended penicillin prophylaxis for secondary prevention of ARF, especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection.

Zentralbl Bakteriol, 1991 Jan, 274(4), 475 - 80
Immuno-electronmicroscopic demonstration of alpha and beta components of group B streptococcal protein antigen c; Wibawan IW et al.; Affinity purified and absorbed monospecific antibodies against the protein type antigen c components c alpha and c beta were used in immuno-electronmicroscopic studies . As demonstrated with protein A gold particles the c alpha specific antibodies reacted with the c alpha antigen, the c beta specific antibodies with the c beta antigen . The respective antigens were distributed over the whole surface of the bacterial cells, mainly at the outermost layer of the cell wall.

Int J Immunopharmacol, 1991, 13(2-3), 205 - 15
Analysis of antitumor effects of OK-432 against syngeneic mouse fibrosarcoma: combination effect of OK-432 and recombinant lymphokines; Nanjo M et al.; OK-432, a streptococcal preparation with potent biological response modifying activities, had the ability to cure mice bearing BAMC-1 (fibrosarcoma) ascites when it was injected intraperitoneally five times, 2, 4, 6, 8, and 10 days after the tumor inoculation . Previously, it was shown that the OK-432 injection on day 2 was indispensable since only a minimal antitumor effect was obtained when an inflammation-inducing agent such as thioglycolate instead of OK-432 was injected on day 2, followed by four OK-432 injections on days 4, 6, 8 and 10 . In the present study, the injection of OK-432 on day 2 and a subsequent injection of either IL-2 or IFN-gamma on day 4 or 6 showed a significant antitumor effect, achieving a complete cure in approximately 50% of mice treated, although none of the mice could be cured by a single injection of either OK-432, IL-2, or IFN-gamma on day 2 . Interestingly, however, the mice treated with an injection of a lymphokine (IL-2 or IFN-gamma) on day 2 followed by OK-432 on day 4 were not cured either . Peritoneal cells on day 12 in mice treated with OK-432 and either of the lymphokines contained pantropic killer cells, which were Thy-1+ and asialo GM1+ (AsGM1+) . Moreover, the antitumor effect of the combined treatment was abolished when mice were pre-treated with anti-AsGM1 . No significant antitumor effect was observed in athymic nu/nu mice . Together with our previous findings, these results indicate that lymphokines induced by OK-432 administration may account for some of its therapeutic effects and that these lymphokines may also facilitate the subsequent induction of specific killer cells . These results warrant further investigation on possible effective therapeutic protocols with the combined use of OK-432 and lymphokines.

J Immunol, 1991 Jan 1, 146(1), 95 - 100
IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis; Wahl SM et al.; Localization of streptococcal cell wall Ag (SCW) in the synovial tissue of treated rats induces an influx of leukocytes and a cell-mediated immune response leading to arthritis and joint destruction . Systemic administration of the T cell product, IFN-gamma (10(6) U/kg/day), suppresses the recruitment of leukocytes into the synovium and effectively inhibits the inflammation and pathology characteristic of SCW-induced arthritis (articular index 10.4 +/- 0.6 for SCW vs 2.0 +/- 0.7 for SCW with IFN-gamma, p less than 0.005) . Monocyte-macrophages from animals treated with IFN-gamma exhibited defective chemotactic responses when tested in vitro and furthermore, monocytes cultured with IFN-gamma (25 to 500 U/ml) in vitro had significantly suppressed chemotactic responses to the complement fragment C5a (p less than 0.005) . The decreased ability to migrate to C5a was associated with decreased binding of fluorochrome-conjugated C5a indicative of reduced expression of C5a receptors . Based on these data, IFN-gamma that induces monocyte maturation as reflected by increased Ia expression conversely inhibits C5a receptor expression . Although locally elevated IFN-gamma levels may serve to inhibit recruitment away from an inflammatory site, systemic exposure to IFN-gamma appears to inhibit leukocyte recruitment to the inflammatory site by its ability to induce premature maturation and concomitant inability to respond to certain chemotactic ligands . Inasmuch as monocyte recruitment to the synovium is pivotal in the development of SCW-induced polyarthritis, the ability of IFN-gamma to inhibit this event effectively inhibits the synovial pathology.

Ethn Dis, 1991 Fall, 1(4), 368 - 78
Is serious research possible in the Caribbean?
Figueroa JP.
This essay describes the rich tradition of research in the English-speaking Caribbean and the possibilities for meaningful collaboration between Caribbean researchers and scientists from developed countries . Significant contributions include work related to the human T-lymphotropic virus type I (HTLV-I), Jamaican vomiting sickness, veno-occlusive disease of the liver, J-type diabetes, and the role of skin sepsis and streptococcal infection in the etiology of glomerulonephritis . In the fields of malnutrition, human metabolism, child development, and sickle cell anemia, the Caribbean has been at the forefront of medical research internationally . Many characteristics of the Caribbean population, including the disease profile, offer advantages and unique opportunities for significant research, despite difficulties related to the "brain drain" and weaknesses of the infrastructure.

Australas J Dermatol, 1991, 32(3), 133 - 6
Linear IgA dermatosis with severe arthralgia; Hepburn DJ et al.; Linear IgA dermatosis with severe arthralgia is a rare clinical syndrome . Streptococcal infection may be important in its pathogenesis . The rash and arthralgia respond to dapsone although additional treatment with non-steroidal anti-inflammatory drugs and/or corticosteroids may be necessary . A case is presented which illustrates these features.

Reumatizam, 1991, 38(1-4), 13 - 6
{Epidemiologic characteristics of rheumatic fever throughout the world}; Adanja B et al.; In this article we discuss the epidemiologic changes in rheumatic fever leading up to the recent resurgence . The multifocal outbreaks occurred within the same time period, 1984 to 1988, in different sections of the United States and in Italy and Chile . The clinical manifestations in the current outbreaks were strikingly different than in the recent past--carditis was frequently present and very severe . One of the most unsual demographic features was that the majority of the patients lived in suburban or rural communities and were mostly white and middle class . However the average size of the families in which the index cases occurred was higher than in the corresponding populations, pointing out to the importance of crowding for spreading of streptococcal infectious and rheumatic fever occurrence . Still another contrast to prior outbreaks was that the recent ones did not follow clinically apparent epidemics of streptococcal infections . It is clear from the resurgence of acute rheumatic fever in the mid--1980s in developed countries among people with good living conditions, that rheumatic fever is worldwide problem . Intesified efforts to understand the pathogenesis of rheumatic fever should undertaken, but in the meantime, the preventive methods that are available should be vigorously applied.

Otolaryngol Pol, 1991, 45(6), 455 - 8
{Phlegmon of the mouth floor with extremely severe course}; Gryczynski M et al.; A case of the 38-years old patient with a severe streptococcal phlegmon fundi oris and secondary deficiency of gamma-globulins was reported . The patient was successfully treated by surgery, proper antibiotico-therapy and immunoregulation.

Biotherapy, 1991, 3(4), 373 - 9
A possible clinical application of multicytokine-producing cytotoxic mononuclear cell (MCCM) therapy; Katano M et al.; When peripheral blood mononuclear cells (PBMC) were incubated with a streptococcal preparation, OK-432, for 24 h, PBMC acquired cytolytic activity against cultured and fresh human tumor cells . Such PBMC were called OK-432-activated mononuclear cells (OK-MC) . OK-MC produce several kinds of cytokines such as interferon alpha (IFN alpha), IFN gamma, and tumor growth inhibitory factor (TGIF) both in vitro and in vivo . OK-MC-produced cytokines also inhibited the growth of cultured and fresh human tumor cells . The growth inhibition was examined by human tumor clonogenic assay using a double-layer agar technique . The results indicate that two pathways of anti-tumor activity are induced in OK-MC, i.e., cell-mediated and cytokine-mediated.

Biotherapy, 1991, 3(4), 359 - 64
The augmentative effect of a protein-bound polysaccharide (PSK) on tumoricidal activity of the soluble factor produced by a streptococcal preparation (OK-432)-activated macrophages; Baba N et al.; The enhancement of antitumor activities of the tumoricidal soluble factor (SF) from a streptococcal preparation (OK-432)-activated macrophages by the pretreatment with a protein-bound polysaccharide (PSK) was investigated in tumor-bearing mice . Two-step stimulations with OK-432 at in vivo priming and in vitro eliciting were required for the production of the tumoricidal SF by macrophages, and the tumoricidal activity of the SF apparently correlated with the uptake of OK-432 by macrophages at priming phase . Tumoricidal activity of the SF from OK-432-activated macrophages in proteose-peptone (P-P)-pretreated mice significantly decreased with the development of the tumor, whereas in PSK-pretreated mice did not . Pretreatment of tumor-bearing mice with PSK saved a decrease in the macrophages carrying Iak or asialo GM1 antigens and an increase in wheat germ agglutinin (WGA) receptors . Furthermore, the uptake of OK-432 by macrophages at priming phase was enhanced . The tumoricidal activity of the SF from OK-432-activated macrophages was augmented . Thus, PSK may restore the depressed functions of macrophages, and the combination therapy with PSK and OK-432 may be effective to enhance the production of tumoricidal SF in tumor-bearing mice.

Biotherapy, 1991, 3(4), 337 - 44
In vivo effects of human recombinant tumor necrosis factor alone and in combination with other biological response modifiers on human digestive organ cancer xenografts transplanted in nude mice; Nio Y et al.; The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers . Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 10(3), 5 x 10(3), or 10(4)U/head directly into the tumor 3 times a week for 2 weeks . EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 10(3) U/head caused tumor regression . PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 x 10(3) U/head, however, the tumors regrew after treatment . Li-7 and BDC-SN were resistant to rTNF . The effects of rTNF in combination with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN . All combinations of rTNF at 5 x 10(3) U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-gamma or rTNF and OK-432 . However in all cases, the combination of rTNF at 10(3) U/head and any other BRM did not improve the effect . Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone . TNF may still be a useful cytokine, because it can induce the regression of tumors . However, for its clinical application, a method should be developed to reduce its side effects.

Autoimmunity, 1991, 10(2), 115 - 24
Hybridomas to specific streptococcal antigen induce tissue pathology in vivo; autoimmune mechanisms for post-streptococcal sequelae; Fitzsimons EJ et al.; A gross examination of organs from approximately 100 mice which were producing ascites fluids toward a series of streptococcal reactive monoclonal hybridomas showed, in some animals, what appeared to be autoimmune-like findings . A pattern of major lung pathology was associated with specific clones . These specific hybridomas led to the development of an experimental autoimmune animal model mimicking a Goodpasture's syndrome . Tissue injury was induced in mice, on a dose dependent basis, by the injection of monoclonal antibody generated against streptococcal cell membrane (SCM) antigens . A more severe onset of the pathology, also on a dose dependent bases, was induced by placement of the anti-SCM mAb secreting hybridoma cells into the peritoneal cavity of the host . Severity of observed lesions was dependent upon the number of cells injected (10(5), 5 x 10(5), 10(6) or 10(7}, as well as the animals' sex . Severe and total hemorrhagic lungs were seen in animals challenged with 1 x 10(6) hybridomas cells when sacrificed on the tenth day . In all cases the lesions were greater in the female litter mate than the male . Gross and histologic observations were confirmed by lung/body weight ratios . Pulmonary hemorrhage ranged from slight, when mAb was injected at a low dose of 24 micrograms/g, to severe when 96 micrograms/g was injected . Reported findings were based on the review of approximately 300 mice . Immunochemical evaluations and ELISAs confirmed the ability of these anti-SCM mAb to react with glomerular basement membrane (GBM) antigens as well as lung basement membrane (LBM) . Mitogenic experiments indicated that the parent immunogen (SCM) used to generate immunocytes was non-stimulatory to lymphocytes.

Bull Pan Am Health Organ, 1991, 25(3), 201 - 6
IgA testing for diagnosis of retroviral infections in the Caribbean; Ridel PR et al.; In Guadeloupe, a Caribbean island with a high prevalence of HTLV-I infected subjects, the percentage of false positive results for HIV IgG is high, requiring additional time and expense for confirmatory tests . This article describes a simple way of overcoming this problem . First, all IgG and IgG immune complexes are removed by protein G treatment, and then IgA enzyme-linked immunosorbent assay (ELISA) and the Western blot test are performed with minor modification of commercially available kitsPIP: Researchers wanted to determine whether they could do a more specific ELISA HIV test directed at IgA rather than IgG antibodies . So they 1st used streptococcal protein G to remove IgG from serum samples of 10 follow up patients from Guadeloupe who previously tested positive via ELISA for HIV-1/2 IgG and HTLV-I IgG . They did this to test sera for IgA . The protein G treatment resulted in a 99.9% reduction in the IgG concentration (12.21.7 mg/ml to .007-.017 mg/ml) . After IgG depletion, the researchers noted no ELISA positive samples for HIV-1/2 or HTLV-I IgG . In fact, all the values were well below the cutoff levels . This result indicated that streptococcal protein G treatment followed by IgA ELISA is more specific than testing for IgG . The sera of 8 patients tested negative for HIV-1/2 IgA, but all tested positive for HTLV-1 IgA . This result showed that IgA may be more useful than IgG for also confirming retroviral infections . The sera of 2 patients were 44% and 27% above the cutoff level indicating that these patients had HIV-1/2 IgA antibodies . The researchers observed that protein G treatment suppressed all HIV-1/2 and HTLV-I IgG Western blot reactivity which confirmed the effectiveness of protein G treatment . Further the HIV IgG bands in the 8 false positive sera did not materialize at all suggesting that the IgG reactivity observed was most likely nonspecific . These results indicated that nonspecific HIV-1/2 IgG caused the false positive HIV-1/2 IgG ELISA results . In conclusion, in Caribbean countries where HTLV-1 infection can be as high as 13%, the more specific HIV IgA ELISA test should be used since its use saves time and money . Further it can do generalized testing for HTLV antibodies .

Ann Chir Plast Esthet, 1991, 36(6), 520 - 6
{Necrotizing fasciitis of the upper limb . Apropos of a case}; Hubault-Marcade P et al.; Necrotizing fasciitis is a rare infection, serious because of its risk of functional sequelae and mortality . The first clinical and histological descriptions of acute Streptococcal infection of the fascia were published in 1924 by Meleney, who referred to this condition as "Streptococcal haemolytic gangrene" . However, since Meleney, numerous authors have reported cases of necrotizing fasciitis due to a wide range of bacteria . The authors report a case of necrotizing fasciitis of the upper limb in a 45 year old man following a superficial lesion of the dorsum of the hand . Despite the use of antibiotics, the morbidity and mortality of this disease are still high . Treatment is surgical and must be performed urgently . A review of the literature groups together the published cases and analyses the various aetiologies and risk factors.

Ann Chir Main Memb Super, 1991, 10(4), 286 - 96
{Necrotizing fasciitis of the upper limb . 12 cases}; Bleton R et al.; Twelve cases of necrotizing fasciitis or streptococcal cellulitis of the upper limb are reported . Four cases presented with a low grade aggressive for and one case was chronic . Seven fulminating cases resulted in two deaths . These different presentations are in fact different stages of the same disease which is a group A beta-hemolytic streptococcal necrotizing infection of the subcutaneous tissue . It is a medical emergency in which surgery is the main treatment . In cases seen early, surgery helps by making an early diagnosis by showing the typical appearance of the subcutaneous tissue and by isolating organisms in wound culture . In fulminant cases, only extensive surgical debridement can control infection . Delayed or incomplete radical excision may lead to disseminated infection . Infection spreading beyond one upper limb worsens the vital prognosis.

Ann Trop Paediatr, 1991, 11(3), 225 - 31
Acute rheumatic fever during childhood in Saudi Arabia; al-Eissa YA; During a 5-year period ending in December 1989, 73 episodes of acute rheumatic fever in 67 children aged 4-14 years were prospectively studied to ascertain the clinical profile of the disease in initial attacks and recurrences, and to compare the findings with those from other countries . Among 51 children with a first episode of acute rheumatic fever, 76% had arthritis and 43% had carditis . In 22 children with recurrences, arthritis was present in 45% and carditis in 91% . Carditis was more severe among the cases with recurrences . Mitral insufficiency was the most common valvular lesion, but no case of mitral stenosis was detected . Chorea, subcutaneous nodules, and Erythema marginatum were relatively rare . The demographic, clinical and laboratory findings of this study resemble those from Western countries, in contrast with data from tropical countries . Efforts aimed at prompt recognition and adequate treatment of streptococcal pharyngitis and maintenance of anti-streptococcal chemoprophylaxis would be rewarding in reducing the incidence of this disease and its sequelae.

Ann Trop Paediatr, 1991, 11(2), 119 - 21
Acute renal failure related to infectious disease in infancy and childhood; Gokalp AS et al.; In this prospective study done between 1983 and 1989, of 109 children with acute renal failure in Sivas, Turkey, infectious disease was found in 94 . This was related mainly to preventable disease such as acute gastro-enteritis, sepsis and post-streptococcal acute glomerulonephritis . Within this infectious disease group, the highest incidence rate was found in sepsis.

Ann Chir Plast Esthet, 1991, 36(1), 75 - 8
{Beta-hemolytic streptococcal periorbital necrotizing fasciitis in a child}; Pannier M et al.; The authors report a case of beta-haemolytic streptococcal periorbital necrosing fasciitis in a two old girl . Extensive cutaneous necrosis of the four eyelids developed after the installation of a major septic syndrome . Excision of the necrotic tissues required removal of the palpebral part of the orbicularis muscle and opening of the orbital septum . A graft was performed on the 23rd day . Active palpebral occlusion was retained by means of the orbital portion of the orbicularis muscle . Two complementary grafts had to be performed to ensure satisfactory palpebral occlusion . The periorbital localization, exceptional in children, must not be confused with periorbital cellulitis, a common disease, which never progresses towards necrosis . The authors stress the necessity of an early diagnosis in view of the importance of medical treatment and surgical drainage with opening of the septum, which is the only way of decompressing the oedema and preventing palpebral necrosis due to tissue ischaemia.

Padiatr Padol, 1991, 26(1), 53 - 6
{Panarteritis nodosa with secondary hyperaldosteronism involving renal arterioles}; Bart G et al.; A case of a 6 year old girl with angiographically and bioptically verified systemic polyarteritis nodosa is reported . Secondary hyperaldosteronism due to involvement of small and medium-sized renal arteries caused severe hypertension and left ventricular hypertrophy, and together with abdominal complaints, loss of weight, livedo reticularis and elevated titers of streptococcal antibodies formed the clinical pattern of the disease . It may be assumed, that there is a correlation between the recurrent streptococcal infections and the development of systemic polyarteritis nodosa by hypersensitivity or disordered immunologic reactivity . Therapy and short time follow up is reported . For treatment of hypertension an angiotensin converting encyme inhibitor was used, which immediately slowed down the maximal stimulated plasmarenin-angiotensin system.

J Immunol, 1991 Jan 1, 146(1), 11 - 7
An evolutionary conserved mechanism of T cell activation by microbial toxins . Evidence for different affinities of T cell receptor-toxin interaction; Fleischer B et al.; The enterotoxins produced by Staphylococcus aureus are the most potent mitogens known . They belong to a group of distantly related mitogenic toxins that differ in other biologic activities . In this study we have compared the molecular mechanisms by which these mitogens activate human T lymphocytes . We used the staphylococcal enterotoxins A to E, the staphylococcal toxic shock syndrome toxin, the streptococcal erythrogenic toxins A and C (scarlet fever toxins, erythrogenic toxins (ET)A, ETC), and the soluble mitogen produced by Mycoplasma arthritidis . We found that all these toxins can activate both CD4+ and CD8+ T cells and require MHC class II expression on accessory and target cells . However, T cells could be activated in the absence of class II molecules if the toxins ETA or SEB were co-cross-linked on beads together with anti-CD8 or anti-CD2 antibodies . Enterotoxins, toxic shock syndrome toxin and scarlet toxins stimulate a major fraction of human T cells, and show preferential, but not exclusive, stimulation of T cells carrying certain TCR V beta . In contrast, the mitogen of M . arthritidis, a pathogen for rodents stimulates only a minority of human T cells but activates a major fraction of murine T cells . Analysis of human T cell clones expressing V beta 5 or V beta 8 TCR showed that these clones responded also to those toxins that did not stimulate V beta 5+ and V beta 8+ T cells in bulk cultures . These results indicate that different TCR bind to these toxins with different affinities and that the specificity of the TCR-V beta-toxin interaction is quantitative rather than qualitative in nature . Taken together our findings suggest that these toxins use a common mechanism of T cell activation . They are functionally bivalent proteins crosslinking MHC class II molecules with variable parts of the TCR . Besides V beta, other parts of the TCR must be involved in this binding . The finding that murine T cells responded more weakly to the toxins produced by the human-pathogenic bacteria than to the Mycoplasma mitogen could indicate that the toxins have been adapted to the host's immune system in evolution.

Acta Clin Belg, 1991, 46(2), 82 - 8
Streptococcal myositis . A report of two cases; Demey HE et al.; Two patients are described with acute streptococcal myositis . One of them died after a brief duration of illness in multiple organ failure; the other survived extensive muscular damage complicated by diffuse intravascular coagulation, acute renal failure, adult respiratory distress syndrome, bronchopneumonia, Pseudomonas septicaemia and probably streptococcal toxic shock syndrome . Both patients received nonsteroidal antiphlogistics, purportedly involved in the pathogenesis of this syndrome . Based on a mouse model, clindamycin would seem to be the antibiotic of choice.

Klin Wochenschr, 1990 Dec 4, 68(23), 1198 - 201
Poststreptococcal glomerulonephritis flare-up in a patient with varicella infection; Fuhrer JA et al.; A 15-year-old boy with poststreptococcal glomerulonephritis is described . During his recovery from nephritis he acquired varicella, which led to a flare-up of the glomerulonephritis with a transitory increase in blood pressure, body weight, and serum creatinine . We can only speculate on the pathogenetic mechanism of the flare-up . The glomerulonephritis may have been reactivated by immune complexes containing varicella antigens, or the varicella infection may have provoked immunologic changes leading to a new burst of immune complexes containing streptococcal antigensPublication Types:

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