Acute rheumatic fever and streptococci: the quintessential pathogenic trigger of autoimmunity.

Acute rheumatic fever (ARF) is a non-suppurative complication of pharyngeal infection with group A streptococcus. Signs and symptoms of ARF develop 2 to 3 weeks following pharyngitis and include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. In developing areas of the world, ARF and rheumatic heart disease are estimated to affect nearly 20 million people and remain leading causes of cardiovascular death during the first five decades of life.

Characterization of recombinant Streptococcus mitis-derived human platelet aggregation factor.

We previously purified Streptococcus mitis-derived human platelet aggregation factor (Sm-hPAF) from the culture supernatant of S. mitis strain Nm-65, isolated from the tooth surface of a patient with Kawasaki disease. Here we produced recombinant Sm-hPAF protein (rSm-hPAF) in Escherichia coli, to determine whether rSm-hPAF conserves its platelet aggregation activity.

Presence of a D8/17 B lymphocyte marker and HLA-DR subgroups in patients with rheumatic heart disease.

Objective: The aim of our study was to investigate the association of HLA antigens and a non-HLA protein D8/17 with rheumatic heart disease and its pattern of cardiac involvement.

Methods: This cross- sectional observational study included 35 children and 12 adult patients who have rheumatic heart disease and 35 healthy children and 12 healthy adult controls. After physical examination, all patients and control group members were evaluated with 2D and color-coded echocardiography.

Atherosclerosis in survivors of Kawasaki disease.

Objectives: To test the hypothesis that long-term survivors of low-risk Kawasaki disease (KD) have ongoing vascular inflammation and dysfunction and a higher risk of accelerated atherosclerosis than healthy control subjects.

Study Design: Twenty-eight patients with KD (7-20 years after acute illness) and 27 age-matched healthy control subjects were examined for medical and dietary history, serum markers of atherosclerotic risk and inflammation, carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning and arterial stiffness with applanation tonometry.

Results: Patients and control subjects were similar in age, sex, body mass index, waist-to-hip ratio, blood pressure, cigarette smoking, family history, diet, high-density lipoprotein cholesterol level, lipoprotein (a) level, homocysteine level, glucose level, insulin level, CIMT, arterial stiffness, C-reactive protein level, and inflammatory cytokine level.

Dose profile modeling of Idaho National Laboratory's active neutron interrogation laboratory.

A new laboratory has been commissioned at Idaho National Laboratory for performing active neutron interrogation research and development. The facility is designed to provide radiation shielding for deuterium-tritium (DT) fusion (14.1 MeV) neutron generators (2 x 10(8) n/s), deuterium-deuterium (DD) fusion (2.

Comprehensive analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever.

Acute rheumatic fever (ARF) is an autoimmune disease occurring in individuals following untreated group A streptococcal infection believed to be triggered by antibodies to bacterial components that cross-react with human tissues. We developed a multiplexed immunoassay for the simultaneous quantitation of antibodies to nine streptococcal-related antigens including streptolysin O (SLO), DNase B, collagen I and IV, fibronectin, myosin, group A carbohydrate, M6 protein and streptococcal C5a peptidase. Utilizing this method, we examined serum from 49 ARF, 58 pharyngitis patients and age- and sex-matched controls in samples collected at initial disease onset, and at 4 weeks, 6 months and 1 year after diagnosis.

Presence of D8/17 B-cell marker in patients with poststreptococcal reactive arthritis.

An elevated expression of the alloantigen D8/17 on B lymphocytes has been previously proposed as a susceptibility marker in rheumatic fever. The aim of the study was to investigate the presence of the D8/17 marker on B lymphocytes in poststreptococcal reactive arthritis (PSRA). The study sample included 19 patients (15 boys, 4 girls; mean age 11.

Identification of pyruvate kinase as an antigen associated with Tourette syndrome.

Immune responses to beta-hemolytic streptococcal infections are hypothesized to trigger tic disorders and early-onset obsessive-compulsive disorder (OCD) in some pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme, pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated disorders. Antibodies to PK reacted strongly with surface antigens of infectious strains of streptococcus, and antibodies to streptococcal M proteins reacted with PK.

Group A streptococcus (GAS) carbohydrate as an immunogen for protection against GAS infection.

Previous studies have shown that human serum containing anti-group A streptococcus carbohydrate (GAS CHO) antibodies were opsonic for different M protein-carrying serotypes. To investigate the role that anti-GAS CHO antibodies play in passive and active protection, mice were immunized subcutaneously or intranasally with GAS CHO conjugated to tetanus toxoid, and mortality and oral colonization were monitored after challenge with live GAS. Compared with control mice, immunized mice were significantly protected against systemic or nasal challenge with GAS.

A randomized clinical trial of valacyclovir in multiple sclerosis.

Objective: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).

Beta-haemolytic streptococci in school children 5-15 years of age with an emphasis on rheumatic fever, in the tri-island state of Grenada.

The objective of this study is to determine the prevalence of beta-haemolytic streptococci in the pharynx and antibodies to beta-haemolytic streptococci in school children 5-15 years of age in the tri-island state of Grenada Blood samples and throat swabs were obtained from 1388 school children, aged 5-15 years old attending randomly selected schools in each parish of the tri-island state of Grenada. Serum samples were subjected to antistreptolysin o testing (ASOT) while throat swabs were cultured on sheep blood agar plates. The prevalence of positive throat swab was 15.

Co-localization of human herpes virus 6 and tissue plasminogen activator in multiple sclerosis brain tissue.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of unknown etiology. Several viruses have been suggested as playing a role in the pathogenesis of MS. The aim of this study was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen activation at the cellular level in MS plaques.

Studies of recombinant streptococcal pyrogenic exotoxin B/cysteine protease (rSPE B/SCP) in the skin of guinea pigs & the release of histamine from cultured mast cells & basophilic leukocytes.

Background & Objectives: Streptococcal pyrogenic exotoxin B/streptococcal cysteine protease (SPE B/SCP) is considered to be one of the virulence factors of Streptococcus pyogenes (S. pyogenes) which causes serious diseases such as severe invasive infections and streptococcal toxic shock syndrome (STSS). There are no reports on the histamine releasing activity of SPE B/SCP from mast cells, although several biological activities have been studied.

Antibodies to highly conserved peptide sequence of staphylococcal and streptococcal superantigens in Kawasaki disease.

Superantigen-mediated disease such as toxic shock syndrome is seen in patients who have a weak antibody response to the antigen toxic shock syndrome toxin 1 (TSST-1). We hypothesized that there may be deficiency in antibody production to staphylococcal and streptococcal toxins in Kawasaki disease (KD) children. A peptide was constructed from the homologous portion of the staphylococcal enterotoxins (SE) and streptococcal pyrogenic enterotoxins (SPE), and antibodies to the peptide were made.

Decreased levels of cystatin C, an inhibitor of the elastolytic enzyme cysteine protease, in acute and subacute phases of kawasaki disease.

Elevation of tissue-destructive proteases has been reported in acute Kawasaki disease. Cystatin C is a naturally occurring inhibitor of elastolytic cysteine protease in humans. Serum cystatin C deficiency in human beings has been linked to atherosclerosis and aortic aneurysms.

Staphylococcus aureus express unique superantigens depending on the tissue source.

A comprehensive analysis of Staphylococcus aureus superantigen (SAG) genes was undertaken in isolates from a major hospital and compared with isolates from patients with toxic shock syndrome (TSS). Polymerase chain reaction (PCR) analysis included recently discovered SAGs. Staphylococcal enterotoxin (SE) G and SEI were uniquely expressed in genital isolates.

D8/17 expression on B lymphocytes in anorexia nervosa.

Objective: The authors' goal was to determine whether D8/17, a rheumatic fever susceptibility trait marker, identifies a possible type of anorexia nervosa: pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) anorexia nervosa.

Method: Using immunofluorescence, the authors measured the percentage of D8/17-positive B lymphocytes in the peripheral blood of 16 subjects 7-21 years old who had not had rheumatic fever but who had possible PANDAS anorexia nervosa. The comparison subjects were 17 psychiatric patients with no eating disorder and no PANDAS characteristics.

Cysteine protease activity and histamine release from the human mast cell line HMC-1 stimulated by recombinant streptococcal pyrogenic exotoxin B/streptococcal cysteine protease.

We constructed the expression vector pSK-SCP containing the streptococcal exotoxin B gene (spe b) which expressed protease activity. We showed that the recombinant streptococcal pyogenic exotoxin B/streptococcal cysteine protease (rSPE B/SCP) was secreted into the culture supernatant of the transformant and retained its SCP activity, which was equivalent to or greater than that of the naturally occurring molecule. The secreted rSPE B/SCP induced histamine release and degranulation of the human mast cell line HMC-1.

Presence of the d8/17 B-cell marker in children with rheumatic fever in Israel.

A genetic predisoposition to rheumatic fever (RF) has been suspected by several researchers. Ten years ago, using monoclonal antibodies, the B-cell alloantigen D8/17 was identified in 90-100% of patients with RF. The aim of the present study was to evaluate whether the marker is found in patients with RF in Israel, where the population is made up of diverse ethnic groups.

The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder.

Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17.

Inhibition of bacterial superantigens by peptides and antibodies.

The pyrogenic exotoxins of group A streptococci and staphylococcal enterotoxins are a family of structurally related superantigens with similar biological activity. Two distinct areas have been identified which have a highly conserved amino acid homology in all of the toxin families. A number of peptides were constructed from these regions, some of which were concatenated and polymerized to enhance their immunogenicity in animals.