Over-expression of TATA binding protein (TBP) and p53 and autoantibodies to these antigens are features of systemic sclerosis, systemic lupus erythematosus and overlap syndromes

The aim of this study was to determine the expression levels of p53 and TATA binding protein (TBP) and the presence of autoantibodies to these antigens in Asian Indian patients with systemic sclerosis (SSc), overlap syndromes (OS) and systemic lupus erythematosus (SLE). Fifty patients with SSc, 20 with OS, including mixed connective tissue diseases (MCTD), 20 with SLE, 10 disease controls (DC) and 25 controls (C) were studied. The over-expression of p53 and TBP antigen was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA), varies between four- and sevenfold higher in patients with SSc, OS and SLE, in comparison to DC and C. The expressed protein antigens were not present as free antigens but as immune-complexes. Autoantibodies to p53 were detected by ELISA in 78% subjects with SSc, 100% with OS and 80% with SLE. Autoantibodies to TBP were observed in 28% patients with SSc, 25% with OS and 15% with SLE. In comparison to healthy controls, the titre of antibodies to p53 was significantly higher in patients with SSc (P = 0.00001) than the patients with OS (P = 0.00279) and SLE (P = 0.00289), whereas the titre of antibodies to TBP was higher in patients with OS (P = 0.00185) than the SLE (P = 0.00673) and the SSc (P = 0.00986) patients. Autoantibodies to p53 and TBP were detected in all these patients and the levels of these two autoantibodies showed weak negative correlation with each other. We propose that the over-expression of these antigens might be due to hyperactive regulatory regions in the p53 and TBP gene.     

Sequence Analysis Demonstrates that VP6, NSP1 and NSP4 Genes of Indian Neonatal Rotavirus Strain 116E are of Human Origin

We have sequenced the genes encoding the inner capsid protein VP6 and the nonstructural proteins NSP1 and NSP4 of the Indian neonatal serotype P8[11]G9 human/bovine reassortant candidate vaccine rotavirus strain 116E. These three genes share a high degree of sequence and deduced amino acid homology with human prototype strain Wa. Our results confirm and extend those of previous RNA-RNA hybridization studies which suggested that these genes are of human origin, and will facilitate examination of the host immune response to 116E induced by natural infection and vaccination. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular characterization of a human rotavirus reveals porcine characteristics in most of the genes including VP6 and NSP4

Summary. Long electropherotype with Subgroup I specificity is a common feature of animal rotaviruses. In an epidemic of infantile gastroenteritis in Manipur, India, long but SG I strains predominated in the outbreak in the year 1987–88. One such strain isolated from that region, following the outbreak had G9P [19] specificity. As this is a rare combination, the gene sequences encoding VP4, VP6, VP7, NSP1, NSP2, NSP3, NSP4 and NSP5 of this strain were analyzed. All these genes except VP7 were closely related to porcine rotaviruses (95–99% identity at amino acid level) and clustered with the porcine strains in phylogenetic analysis. In addition, it had subgroup I nature and belonged to NSP4 genotype B which is characteristic of animal rotaviruses. This is the first report of a rotavirus with VP6 and NSP4, two crucial proteins thought to be involved in host range restriction and pathogenicity, were of porcine origin and caused diarrhoea in a human host. Among the genes of this strain sequenced so far, only VP7 had highest identity to human strains at amino acid level. This study suggests reassortment may be occurring between human and other animal strains and some of the reassortant viruses may be virulent to humans.     

Modulation of humoral immune responses by endogenous opioids

The effects of opioid agonists and antagonists were investigated on humoral immune mechanisms in mice and rats. Opioid agonists like morphine, Leu-enkephalin, and Met-enkephalin, enhanced antigen-induced histamine release from mixed peritoneal cells of rats in vitro; this enhancement was effectively antagonized by naloxone, an opioid antagonist. Naloxone, per se, decreased anaphylactic mortality in doses of 10 mg/kg, while it increased mortality in a dose of 1 mg/kg. Reduced IgE antibody titer, measured by passive cutaneous anaphylaxis, decreased hemagglutination titer to sheep red blood cells, blocked histamine release from mixed peritoneal cells of rats in vitro induced by antigen, but had no significant effect when histamine release was induced by compound 48/80. Thus, it appears that endogenous opioids are involved in humoral immune responses.     

Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates.

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.     

The National Football Head and Neck Injury Registry. 14-year report on cervical quadriplegia, 1971 through 1984

Data on cervical spine injuries resulting from participation in football have been compiled by a national registry. Analysis of epidemiologic data and cinematographic documentation clearly demonstrated that the majority of cervical fractures and dislocations were due to axial loading. On the basis of this observation, rule changes banning both deliberate "spearing" and the use of the top of the helmet as the initial point of contact in making a tackle were implemented at the high school and college level. Subsequently, a marked decrease in cervical spine injury rates has occurred. The occurrence of permanent cervical quadriplegia decreased from 34 in 1976 to five in the 1984 season. It is suggested that axial loading of the cervical spine is also responsible for the catastrophic injuries in diving, rugby, ice hockey, and gymnastics. Implementation of appropriate changes in playing techniques and/or equipment modifications could possibly reduce the incidence of cervical spine injuries in these activities.     

ω-123I-Hexadecanoic acid metabolic probe of cardiomypathy

The utility of -¹²³I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40° LAO projection after a standard dose of -¹²³I-hexadecanoic acid. An elimination T_1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients.Of the 16 patients, only 2 had distinctly abnormal -¹²³I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which cartine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, -¹²³I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.Supported by a Canadian Heart Foundation Research FellowshipSupported by an Australian Heart Foundation Travel Grant