HBV antigens in peripheral blood mononuclear cells (PBMC) during the course of viral infection.
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Hepatitis Antigens↗
Biomedical subjects
K Nagaraju
Publications and source records attributed to K Nagaraju.
High prevalence of HBV infectivity in blood donors detected by the dot blot hybridisation assay.
Hepatitis B virus (HBV) continues to be a significant cause for post-transfusion hepatitis in India, in spite of the introduction of compulsory hepatitis B surface antigen (HBsAg) screening. To understand the true HBV-infective pool in the blood donor population, HBV DNA was detected by a 32P-labelled dot blot hybridisation assay in 605 donor units that were negative for HBsAg by a third-generation Elisa. Serum alanine aminotransferase (ALT) was estimated in all these samples and correlated with DNA positivity. The frequency of HBV DNA positivity in HBsAg-negative units was very high (9.91%) and correlated well with the elevation in ALT (p < 0.00005). However, the frequency of elevated ALT was high (11.9%), using the locally determined upper limit of normal, and half of the DNA-positive samples had a normal ALT. Thus, ALT is a poor surrogate marker for HBV infectivity and efforts should be made to apply DNA detection systems in blood banks.
Adult↗
Enzyme replacement therapy in the mouse model of Pompe disease.
Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal muscle cells took up little enzyme compared to liver and heart. Glycogen reduction was less than 50%, and some fibers showed little or no glycogen clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable levels at either dose. Skeletal muscle fibers with residual glycogen showed immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained in proliferating lysosomes. Glycogen clearance was more pronounced in type 1 fibers, and histochemical analysis suggested an increased mannose-6-phosphate receptor immunoreactivity in these fibers. Differential transport of enzyme into lysosomes may explain the strikingly uneven pattern of glycogen removal. Autophagic vacuoles, a feature of both the mouse model and the human disease, persisted despite glycogen clearance. In some groups a modest glycogen reduction was accompanied by improved muscle strength. These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle.
Animals↗
Chronic hepatitis B virus carriers have low lymphoproliferative responses to HBsAg and reduced interleukin-2 synthesis.
BACKGROUND: Chronic carriers of hepatitis B virus (HBV) have impairment of lymphoproliferative responses. Recently HBV infection of peripheral blood mononuclear cells (PBMC) has been reported. The defect in the proliferative capacity of carrier PBMC has not been correlated to the presence of HBV in these cells. METHODS: PBMC of fourteen HBV carriers and 14 healthy individuals were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM) or anti-CD3 for 3 days and with HBsAg and purified protein derivative (PPD) for 6 days. The supernatants of unstimulated and PHA-stimulated PBMC cultures were bioassayed for interleukin-2 (IL-2); the supernatants of unstimulated and lipopolysaccharide (LPS)-stimulated cultures were bioassayed for IL-1. DNA extracted from PBMC was hybridized with a 32P-labeled HBV probe to look for HBV DNA. RESULTS: HBV carriers' PBMC showed impaired responses to PHA, PWM and anti-CD3. No carrier demonstrated lymphoproliferative response to hepatitis B surface antigen (HBsAg). Seven of eight carriers with impaired HBsAg-specific proliferative responses who were tested for their response to an unrelated antigen showed a positive response to PPD. PBMC from HBV carriers produced similar amounts of IL-1 as normal PBMC on LPS stimulation; however, they produced significantly lower amounts of IL-2 as compared to normal PBMC under both spontaneous and PHA-stimulated conditions. HBV DNA was demonstrable in the PBMC of all fourteen carriers. CONCLUSIONS: The abnormal immune function found in chronic HBV carriers may be a consequence of replicative viral infection of the mononuclear cells.
Adult↗