Technology assessment & policy determination.
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Biomedical subjects
Publications and source records attributed to A Desai.
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Haemostasis is the spontaneous arrest of bleeding from damaged blood vessel. Platelet aggregation is the major event in this process. A number of drugs are known to inhibit this process of platelet aggregation. 4,5' 8-trimethyl psoralen a naturally occurring furocoumarin is used as a photochemotherapeutic agent in PUVA therapy. It shows antithrombotic action by preventing platelet aggregation induced by adenosine diphosphate in vitro. It is proposed that a free radical induces a lipid phase transition of the membrane lipids, the platelet membrane undergoes certain biophysical alteration leading to increased membrane fluidity resulting in a loss of aggregating ability.
We report the identification of a new family of proteins, termed the HEM family, which show distinct expression patterns in blood cells and the central nervous system. Through the isolation and characterization of the corresponding brain-specific Drosophila (dhem-2) and rat orthologues (Hem-2), and through the detection of the Caenorhabditis elegans Hem-2 orthologue in the database, we show that this family is conserved throughout evolution. HEM proteins show a conserved length ranging from 1118 to 1126 amino acid residues. Moreover, they are at least 35% identical with each other and harbour several conserved membrane-spanning domains, indicative for their location on the cell surface. One of the members, the Drosophila orthologue dhem-2, was analysed in detail for its spatial expression pattern during development and for its mutant phenotype. dhem-2 is expressed maternally in the oocyte and shows uniform expression during the first half of embryogenesis, but becomes restricted to the brain and the nervous system during late embryogenesis, consistent with the expression of its vertebrate orthologue in the brain. One P-element insertion, located 39 base-pairs downstream from the dhem-2 transcription start site, causes female sterility, due to the fact that developmental processes in the oocyte are disturbed. Of the vertebrate HEM family members, the mammalian Hem-1 gene is expressed only in cells of hematopoietic origin, while Hem-2 is preferentially expressed in brain, heart, liver and testis.
This study reports the pathological findings and the distribution of viral antigen in the brains of 13 confirmed and autopsied cases of Japanese encephalitis (JE) in correlation with other virus-specific immunological parameters measured in the cerebrospinal fluid (CSF) antemortem. Japanese encephalitis virus (JEV)-specific antibodies were detected in the CSF of 10 of 13 patients, JEV antigen was detected in the CSF of 7 of 13 and JEV-specific immune complexes were detected in the CSF of 3 of 11 patients. Viral antigen was localised immunocytochemically in the brain tissue of 11 of 13 cases, indicating, that viral antigen could not be cleared from the tissues by the antibody. The topographic distribution of the tissue-associated antigen in the thalamus, hippocampus, substantia nigra and medulla oblongata explain the evolution of post JE sequelae.
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Cell-mediated immune response to Japanese encephalitis virus (JEV) and its purified envelope (E) protein was measured in 45 laboratory confirmed JE patients using a proliferation assay of peripheral blood mononuclear cells (PBMC). In parallel, JEV-specific IgM antibodies were measured by ELISA. No correlation was observed between the antibody response and results of the lymphocyte proliferation assay. Only 11 of the 42 patients positive in the antibody test were positive in the proliferation assay, and PBMC from 14/45 (31%) patients did not respond to either phytohemagglutinin and to JEV and/or its purified E protein antigen. No correlation was observed between the cell-mediated immune response and the final clinical outcome (fatality vs. recovery).
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In this study, we have evaluated the suitability and ease of performance of seven HIV assays namely: Vironostika anti-HIV Uni-Form; Vironostika HIV MIXT; Elavia MIXT; Genelavia MIXT; Serodia-HIV; Immunocomb Bi-spot; and Test pack HIV-1 and 2 Abbott, for use in Indian laboratories. A panel of 41 blind coded Western blot confirmed sera were used for this purpose. Rapid assays like Immunocomb Bi-Spot, Serodia HIV and Test pack HIV-1/HIV-2 Abbott were found to be more suitable and easy to perform as compared to the ELISAs. Sensitivity of all the assays was excellent (100%). Specificity of Serodia HIV, Immunocomb Bi-spot, Test pack HIV-1 and 2 Abbott and Elavia MIXT were excellent (100%), while that of Vironostika MIXT and Vironostika anti-HIV Uni-Form was poor. Positive predictive value of the assays ranged from 64.5 to 100 per cent. Negative predictive value of six of the assays was 100 per cent and that of Vironostika anti-HIV Uni-Form was very poor.
Pathomorphological features of 10 HIV positive individuals studied at autopsy and biopsy are described. Nine patients had evidence of neuro-AIDS and eight of them succumbed to various opportunistic infections. One surviving patient underwent a diagnostic lymph node biopsy which revealed tuberculous lymphadenopathy. Cryptococcal meningitis was the commonest CNS opportunistic infection, seen in five cases, with disseminated systemic cryptococcosis in two. The other opportunistic infections included toxoplasma encephalitis in two, with acanthamoeba infection in one patient. Pulmonary tuberculosis was noted in three patients while other bacterial infections such as meningococcal meningitis, pseudomonas septicaemia were observed in three and pneumocystis carinii pneumonia in one. One seropositive individual was clinically asymptomatic but succumbed to a road traffic accident. The brain in this case showed features of HIV associated early leucoencephalopathy. Bacterial infections caused by organisms other than Mycobacterium tuberculosis associated with AIDS are often underdiagnosed and should be considered, especially in developing countries. In cases of cryptococcal and tuberculous meningitis or multiple parasitic infections, the patients should be screened for associated HIV infection.
OBJECTIVE: Evaluation of immunogenicity and acceptability of PRP-T vaccine among the Indian children. DESIGN: Multicentric, open, parallel group, comparative study of Haemophilus influenzae type B vaccine, given as single (Group I) or associated (Group II) with DPT vaccine. SETTING: Five different vaccination clinics. SUBJECTS: 125 children between the age group of 18-24 months. PARAMETERS: Measurement of (i) pre and post vaccination antibody titres of Haemophilus influenze type B specific antibody; (ii) Adverse events; and (iii) Tolerance as graded by the physician. RESULTS: Prevaccination antibody levels were > 0.15 mcg/ml in 56.3% in Group I and 35.7% in Group II. Post-seroconversion was seen in 97% in Group II receiving single and all in Group II (P > 0.05). The vaccine was well tolerated. CONCLUSIONS: The probability of subclinical infection or cross immunity is high in India. ACTHIB vaccine has a good immunogenicity and tolerance and association with DPT does not modify the immunogenicity of ACTHIB vaccine.
Two novel casein kinase-1 homologs, cki1+ and cki2+, have been isolated from Schizosaccharomyces pombe and characterized. Both genes reside on chromosome II and encode approximately 50-kDa proteins that are related structurally and enzymatically to the YCK gene products of budding yeast. Subcellular fractionation experiments demonstrate that Cki1 and Cki2 are both cytoplasmic enzymes that do not overlap in subcellular distribution and that probably play distinct roles within the cell. Although gene disruption experiments show that neither cki1+ nor cki2+ is essential for cell viability, overexpression of cki2 leads to a severe growth defect and aberrant morphology. Cells become round or pear shaped and separate poorly following septation. These results suggest that of the four members of the casein kinase-1 family recognized in fission yeast, one member, Cki2, may contribute to the regulation of cell morphology.
This study reports the detection of autoantibodies to myelin basic protein (MBP) and neurofilament proteins (NFP) in serum and cerebrospinal fluid (CSF) of Japanese encephalitis patients. The diagnosis of Japanese encephalitis was confirmed in 72 patients by the presence of virus specific antibodies to JEV in the CSF (28/72), viral antigen in the CSF (19/72) and simultaneous presence of both antigen and JEV antibodies in the CSF in 25/72 patients. Autoantibodies to either purified NFP (10) or MBP (8) or both (17) were detected in the CSF of 35 patients by ELISA in contrast with the control CSF samples. Amongst them 20 had similar antibodies in the serum as well. Correlation of immunological findings with the clinical outcome revealed that the presence of autoantibodies in the CSF especially to NFP was associated with a fatal outcome (P < 0.05).
BACKGROUND: Antigen detection in the CSF is an invaluable tool in the diagnosis of viral infections of the nervous system, especially in the early phase of the illness. Very little information is available on the use of antigen detection in the diagnosis of Japanese encephalitis (JE). OBJECTIVES: Evaluation of two monoclonal antibody-based antigen detection methods in the diagnosis of JE in comparison with the detection of virus-specific IgM antibodies in the CSF. STUDY DESIGN: In this study 115 patients with a clinical diagnosis of JE were investigated. A reverse passive haemagglutination test for the detection of soluble JEV antigens, an immunofluorescent assay for the detection of cell-associated antigen and an IgM capture ELISA for the detection of virus specific IgM antibodies in the CSF were used. RESULTS: Laboratory confirmation of JE was possible in 92/115 patients. Virus-specific IgM was detected in 75/92 and JEV antigen was detected in 52/92 patients. Soluble antigen was detected in 37/52, cell-associated antigen in 30/52. There was no significant difference in the sensitivity of the two antigen detection systems used. CONCLUSIONS: Diagnosis by antigen detection could be done less frequently than by demonstration of virus-specific IgM antibodies in the spinal fluid. However, antigen detection proved useful during the first week of illness when IgM antibodies were not detected in the CSF.