Cursory survey of lymphatic filariasis. An overview.
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Biomedical subjects
Publications and source records attributed to A Dasgupta.
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A host cell protein (host factor) which is required for the in vitro transcription of poliovirus RNA has been purified to near homogeneity from an uninfected HeLa cell ribosomal salt wash. A single protein with an approximate molecular weight of 67,000 is associated with this "host factor" activity. The purified host factor catalyzes the synthesis of genome-length copies of poliovirion RNA in the presence of poliovirus RNA polymerase. Oligo(U) can replace host factor in this reaction. The RNA product synthesized in the presence of host factor is shown to be complementary to virion RNA.
An antibody to a host cell protein (host factor) which inhibited the host factor-dependent transcription of poliovirion RNA was used to characterize the immunoprecipitated proteins from both uninfected and poliovirus-infected HeLa cells. The antibody specifically precipitated a major protein of approximately 67,000 Da and a 40,000-Da minor protein from uninfected HeLa cells. The immune serum also specifically precipitated poliovirus RNA polymerase (P63, NCVP4) from poliovirus-infected HeLa cells indicating an association of the viral RNA polymerase with the host factor in vivo. A physical interaction between purified host factor and P63 could also be demonstrated in vitro. The antibody was further used to determine the distribution of host factor among different subcellular fractions of HeLa cells. Most of the cellular host factor was present in the cytoplasmic fraction (70%). Approximately 30% of the total host factor was found to be associated with the ribosomes.
A synthetic nonapeptide corresponding to the N-terminal sequence of poliovirus genome-linked protein (VPg) was linked to bovine serum albumin and used to raise antibodies in rabbits. The antipeptide antibodies specifically precipitated the nonapeptide, native VPg, and VPg-linked poliovirion RNA. The antipeptide antibodies inhibited host factor-stimulated, poliovirus replicase-catalyzed in vitro synthesis of full-length (35S) RNA in response to virion RNA. Oligouridylic acid-stimulated RNA synthesis was not affected by the antipeptide antibodies. Preincubation of the antibodies with excess nonapeptide reversed the antipeptide antibody-mediated inhibition of host factor-stimulated RNA synthesis by the poliovirus replicase. A role for VPg in the in vitro replication of poliovirus RNA genome is discussed.
Large segments of the aorta and its major branches were found to be diseased in 14 autopsied cases of aortoarteritis. Both renal arteries and the left subclavian artery were frequently affected. Superior vena cava thrombosis and thickening of the inferior vena cava were noted in one case each. Tuberculosis was present as small foci in only 3 of the 14 cases. Angiographic evaluation also revealed thickening and narrowing of diseased segments. The descending thoracic and abdominal aorta and renal arteries were frequently involved. Aneurysmal lesions were infrequent. Antiaorta antibodies were investigated using 4 different parameters. None of our cases showed their presence. The role of tuberculosis and/or autoimmunity appears unlikely in the etiopathogenesis of aortitis.
The ultrastructural changes observed in erythema nodosum leprosum lesions were gross damage to blood vessels, particularly the endothelial cells, and deposition of immune complexes in vessel walls. Infiltrating cells and alteration of the ground substance formed a constant feature of the reaction. These changes are characteristic of an immune complex reaction.
In vitro transcription of poliovirus RNA was catalyzed by the combination of a virus-coded polymerase and a host cell protein (host factor). Antibody to host factor inhibited template-dependent synthesis of complementary RNA where presumably RNA chain initiation occurred. On the contrary, elongation of already initiated RNA chains catalyzed by the replicase-template complex was not inhibited by anti-host factor antibody. These results strongly favored our previous notion that the host factor was needed for the initiation step of viral complementary RNA synthesis.
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Out of 56 thioacetamide (TAA)-fed rats hepatocellular carcinoma were found in four instances after 300, 360, 450 and 495 days in the present experiment. Of the four tumours, two showed lung metastasis. The size of TAA-treated hepatocyte nucleoli increased greatly after several weeks of feeding. Two enzymes, succinate dehydrogenase and glucose-6-phosphatase were found in both cytoplasma and nucleoli of hepatocytes of which nucleolar localizations are quite new. In hepatocellular carcinoma, malignant cells lost glucose-6-phosphatase activity completely in cytoplasm and nucleoli though succinate dehydrogenase activity was present in these organelles.
The Abelson murine leukaemia virus protein (P120) can become phosphorylated in vitro by [gamma-32P]ATP. The protein has been purified from cell membranes to the point that in specific conditions virtually all of the incorporated 32P is in P120. The reaction is stimulated by Mn2+ and Mg2+ but not Ca2+ and is very rapid even at 0 degrees C. The phosphate is linked to P120 at tyrosine, a linkage not previously reported for a phosphorylation reaction. Phosphorylation may be involved in the transforming activity of viruses that cause leukaemia as well as sarcomas.
Two poliovirus-specific RNA polymerase activities have been identified: a poly(U) polymerase that copies poly(A).oligo(U) and a replicase that copies natural heteropolymers with some preference for poliovirus RNA. Both activities purified together until a step of a salt gradient elution from poly(U)-agarose, when poly(U) polymerase but no replicase was recovered. Addition of a salt wash fraction from the ribisomes of uninfected cells to this poly(U) polymerase fraction reconstituted replicase activity, and a host factor was purified 50 fold from the ribosomal salt wash. None of the available initiation factors or elongation factors for protein synthesis were able to reconstitute replicase activity. Host factor activity could be supplied by adding oligo(U), suggesting that the factor acts at the initiation step of RNA replication. With the purified replicase-host factor combination, only poly(A)-containing RNAs were copied, and a preference for poliovirus RNA was shown.
The presence of precipitin antibody and soluble circulating antigen was demonstrated in sera of individuals with clinical filariasis by counterimmunoelectrophoresis. Antigens derived from Litomosoides carinii and antisera raised in rabbits to the adult worm antigens were used for the detection of antibody and antigen in human sera. Of 35 subjects, 2 had microfilariae in the peripheral blood, 9 soluble circulating antigen, 19 antibody in sera, and 6 had both antigen and antibody. It suggests that 5.7% of cases diagnosed as bancroftian filariasis by parasitological examination can be increased to 62.8% by serological means.
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The soluble phase of the cytoplasm of poliovirus-infected cells contains an enzymatic activity able to copy RNA without an added primer. This replicase activity has been purified 60-fold; it is absent from uninfected cells. Poly(U) polymerase activity copurifies with replicase activity. Although less pure replicase fractions copy a variety of RNAs, purer fractions respond better to poliovirus RNA than to other viral RNAs. Even the less pure fractions make a specific copy of the added template, as shown by hybridization of the product to its template RNA but not to other RNAs. Among homopolymers only poly(A)-oligo(U) was copied by the replicase; other primed homopolymer templates were inactive.
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