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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 181 records · Page 10Linked to original sources
PubMed1990

Characterization of functional nerve growth factor-receptors in a CNS glial cell line: monoclonal antibody 217c recognizes the nerve growth factor-receptor on C6 glioma cells.

The biological effects of nerve growth factor (NGF) have been shown to be mediated by the high-affinity form of the nerve growth factor receptor (NGF-R) in sympathetic and sensory neurons, and in PC12 cells. We report here that the central nervous system C6 rat glioma cell line likewise expresses functional high-affinity NGF-Rs. The expression of NGF-R mRNA in C6 cells can be up-regulated by cycloheximide and its own ligand, NGF; and it can be rapidly down-regulated by epidermal growth factor (EGF). Furthermore, C6 cells display NGF responsiveness by expressing c-fos mRNA within 30 minutes of treatment with NGF; and after 4-5 days of NGF exposure, C6 cells cease dividing as measured by [3H]-thymidine uptake, change shape, and reveal neurite-like processes. Scatchard analysis of [125I]-labelled NGF bound to solubilized C6 cells confirms the presence of both high- and low-affinity receptor protein. Crosslinking radiolabeled NGF to its receptor in the presence or absence of excess unlabeled NGF, followed by immunoprecipitation with monoclonal antibody (mAb) 192-IgG (a known anti-NGF-R antibody) and SDS-PAGE reveals a 100 kD band corresponding to the NGF/NGF-R complex. An identical band is observed when the immunoprecipitation is carried out with mAb 217c, suggesting that the 217c epitope is related to NGF-R. The 217c antibody was generated against C6 cells and shown to be a cell surface antibody (Peng et al., Science 215:1102-4, 1982); several investigators have used it subsequently as an immunocytochemical marker for Schwann cells. The significance of NGF-Rs in a CNS glial cell line is unclear, but association of NGF with the control of proliferation and/or differentiation of primitive glial cells is suggested.

Animals↗
PubMed1990

Developmental regulation of myelin-associated genes in the normal and the myelin deficient mutant rat.

Oligodendrocyte development and myelinogenesis, both in vivo and in vitro, are characterized by the sequential and coordinate expression of markers which participate in the differentiation of oligodendrocytes as a prerequisite for myelination. The myelin deficient (md) rat shows greatly reduced mRNA expression for several oligodendrocyte markers: glycerol phosphate dehydrogenase (GPDH), myelin basic protein (MBP) and proteolipid protein (PLP). Brain GPDH mRNA levels are initially equivalent in md and unaffected littermates, but the mutant rats fail to display the normal developmental increase in gene expression. Immunostaining of brain tissue sections also reveals decreased expression of these oligodendrocyte markers. The number of oligodendrocytes containing GPDH-like immunoreactivity is reduced in mutant rats, and in general these cells appear morphologically less complex with shorter processes. However, the intensity of staining in many oligodendrocytes appears equivalent to that observed in unaffected rats. Expression of the neuronal marker, glutamic acid decarboxylase, and the astrocyte markers, glutamine synthetase and glial fibrillary acidic protein, are largely unaffected at either the mRNA or protein level. Mixed glial cultures prepared from the brains of neonatal male md rats possess fewer oligodendrocytes compared to cultures derived from unaffected littermates, and the temporal sequence of marker development is delayed. Although an abnormality in the PLP gene is suspected in the md rat, these findings document profound deficits in many oligodendrocyte gene products.

Animals↗
PubMed1990

Corpus callosum lipoma with frontal encephalocele.

Computed tomographic and plain X-ray observations in a patient with corpus callosum lipoma associated with frontal encephalocele are reported. The rarity of the lesion and the specific diagnostic criteria on CT are emphasised.

Brain Neoplasms↗
PubMed1990

Focal cerebral infarction in cats in the presence of hyperglycemia and increased insulin.

Although it has been well established that hyperglycemia increases cerebral damage following transient cerebral ischemia, its effect on permanent focal ischemia is controversial. We hypothesized that other factors associated with hyperglycemia, such as plasma insulin, may alter the brain's response to hyperglycemia. The objective of this study was to determine if hyperglycemia changes infarction size following 8 hr of middle cerebral artery occlusion in the anesthetized cat and to examine if changes in plasma insulin levels alter hyperglycemia's effects. Infarct size in hyperglycemic cats with increased plasma insulin (38.3 +/- 8.4, mean +/- SE) or in hyperglycemic cats without increased plasma insulin (30.5 +/- 7.6%) was not significantly different from that of ischemic controls (33.8 +/- 2.8%). However, the variability in infarct size tended to be greater (P = 0.0647) among all hyperglycemic cats compared to control animals. The source of the variability is unknown, but this observation is dependent on the exact nature of the focal ischemic insult (i.e., degree of collateral blood supply) and that this effect may vary greatly from individual to individual within a population.

Analysis of Variance↗
PubMed1990

Activity of a fowlpox virus late gene promoter in vaccinia and fowlpox virus recombinants.

Characterization of a late promoter of fowlpox virus (FPV) and a study of its activity in FPV and vaccinia virus (VV) was carried out. The 5'-mRNA start site of the FPV late gene mapped to a TAAAT sequence near the translation start site (ATG). A cloned DNA fragment of FPV genome (PFL1) comprising of the 5'-end of the late gene was used to express the LacZ gene of E. coli in FPV and VV recombinants. A comparative analysis of beta-galactosidase (BG) expression from the LacZ gene under the control of the FPV promoter and a VV late promoter (PL11) was performed. Like FPV-PL11-LacZ and VV-PL11-LacZ constructs, FPV-PFL1-LacZ and VV-PFL1-LacZ virus recombinants expressed BG indicating that essential features of transcription were conserved in the two viruses. Furthermore, the LacZ transcripts originating from PFL1 in FPV and VV recombinants mapped to the expected TAAAT sequence. Time course analysis of BG expressed by VV and FPV recombinants suggested that although the transcription machinery in the two viruses was essentially conserved, subtle differences in the efficiency of transcription or translation may exist.

Animals↗
PubMed1990

Contraceptive vaginal ring--a rising star on the contraceptive horizon.

Two studies were carried out at AIIMS to judge efficacy, side-effects and acceptability of the contraceptive vaginal ring, a Silastic ring with an inner core containing 6.0 mg levonorgestrel mixed with Silastic and an outer core of Silastic only. It releases levonorgestrel at a constant rate of 20 micrograms/day and remains effective for 90 days. The first study of 50 women lasted for 12 months and the second study of 46 women lasted 24 months. Menstrual irregularity in 36% of women was the commonest reason for discontinuation. The majority of women experienced menorrhagia or irregular spotting per vaginum. Vaginal irritation or increased vaginal discharge was the second commonest reason for discontinuation and was noted in 23% of subjects. Repeated spontaneous expulsions accounted for discontinuation in 6% of subjects. No method-related failure was noted in the study. Follow-up study revealed users to be happier with the ring than with any other method and no spouse complained of feeling the ring during coitus. With its ease of administration, absence of gastrointestinal side-effects and a high success rate, the contraceptive vaginal ring is a promising contraceptive method for the last decade of the 20th century.

Adolescent↗
PubMed1990

Spontaneous gallbladder perforation--an unusual presentation of carcinoma of the pancreas.

A 50 year old man with a two month history of upper abdominal pain and a one month history of anorexia and weight loss, presented with icterus and evidence of peritonitis. Laparotomy revealed biliary peritonitis which had been caused by a rupture of the fundus of the gallbladder. The common bile duct was dilated and there was a large growth in the head of the pancreas with multiple hepatic metastases. A cholecystojejunostomy and gastrojejunostomy were done and the patient had an uneventful recovery.

Adenocarcinoma↗
PubMed1990

Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive with hLH.

Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups. These were, however, unrelated to prevailing anti-hCG antibody titres or to cross-reactivity of antibodies with hLH.

Chorionic Gonadotropin↗
PubMed1990

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine.

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.

Adult↗
PubMed1990

A poxvirus bidirectional promoter element with early/late and late functions.

A novel bidirectional promoter element of fowlpox virus (FPV) was characterized by transcription analysis, transient expression assays, and recombinant virus construction. This promoter element contained an early/late and a late function in opposite orientation, all within 42 bp of the DNA sequence. The 42-bp sequence was sufficient to express two reporter genes simultaneously in a temporally regulated manner. Both early and late mRNA from the early/late promoter originated at the same TAAAT motif and lacked a long 5'poly(A) leader sequence. Late mRNA, initiated from a TAAAT motif of the oppositely oriented late promoter strand, had a leader sequence of approximately 26 bases. Sequence alignment of two strands of the bidirectional element showed that 28 of 42 bases matched. Because of its small and defined size as well as unique structure, this bidirectional promoter should prove to be an important tool in defining the sequences required for the temporal regulation of poxvirus genes.

Animals↗
PubMed1990

Mutagenicity of dibenz[a,c]anthracene and its derivatives in Salmonella typhimurium TA100.

The mutagenic activities of dibenz[a,c]anthracene (DB[a,c]A), and its 11 derivatives, including 3 diols, 6 phenols and 2 oxepines, were studied in the TA100 strain of Salmonella typhimurium at doses varying from 0 to 20 micrograms/plate in the presence of a rat-liver S9 (9000 x g) preparation. Among the diols of DB[a,c]A tested DB[a,c]A-10,11-diol was the most mutagenic compound. However, it was consistently less mutagenic than the parent hydrocarbon. Oxepine-1 and oxepine-2 which are believed to be the photoisomerized products of DB[a,c]A-1,2 oxide and DB[a,c]A-3,4-oxide, respectively, were also less mutagenic than DB[a,c]A. In contrast to these results, 4-hydroxyDB[a,c]A was almost twice as active as DB[a,c]A, and 2-hydroxy- and 3-hydroxyDB[a,c]A were even more (4-6-fold) mutagenic than DB[a,c]A. The remaining phenols were relatively inactive or weakly active in this mutagenicity assay. These results provide initial evidence that the bay-region theory may not be applicable to the mutagenesis of DB[a,c]A, and that the angular ring substituted phenols of DB[a,c]A may be involved in the metabolic activation of this highly mutagenic hydrocarbon.

Animals↗
PubMed1990

Cellular mechanisms in immunity to blood stage infection.

We studied mechanisms of immunity to blood stage infection in the mouse malarias Plasmodium vinckei and Plasmodium yoelii 17X. Infection with P. vinckei was uniformly lethal, whereas P. yoelii 17X caused a self-limited, nonlethal infection. Transfer of immune CD4+ T cells conferred protection against P. yoelii in nude mice. Previous studies by others had suggested that immunity to P. yoelii may be related to MHC class I expression on reticulocytes and found that CD8+ T cells alone transferred protection in immunodeficient mice. However, in our experiments, immune CD8+ T cells failed to transfer protection. In the P. vinckei system, both B cell-deficient and immunologically intact mice developed immunity to P. vinckei after parasite infection and drug cure. In vivo depletion of CD4+ T cells abrogated immunity in these immune mice. Adoptive transfer of CD4+ T cells failed to protect nude or normal mice from P. vinckei infection, but the transfer of immune CD4+ T cells reconstituted immunity in CD4-depleted immune mice. Splenectomy of immune mice resulted in the complete loss of immunity. Despite the fact that immunity to P. vinckei could be achieved with live parasite infection and drug cure, immunization of mice with killed P. vinckei with various adjuvants failed to protect mice from live challenge. In contrast, immunization with killed P. vinckei antigens in combination with attenuated Salmonella typhimurium SL3235 induced a high degree of protective immunity. These results suggest that induction of immunity against virulent malarias requires both induction of CD4+ T cells and certain splenic alterations caused by parasite infection or S. typhimurium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mapping of a major early/late gene of fowlpox virus.

Identification, cloning and mapping of a major gene expressed during the early and late stages of infection with fowlpox virus is described. The gene is located within a 17.3 kb PstI fragment of the fowlpox virus genome and has an open reading frame of 501 bp. Analysis of the 5'-ends of mRNA transcribed from this gene showed that the start sites of both early and late transcripts map to the sequence TAAAT near the translation start site (ATG). This is the first poxvirus early/late gene described in which both early and late transcription start sites map to same DNA sequence. From northern hybridization analysis it was shown that the early function of this gene gives rise to the most abundant early mRNA coded by 17% of the fowlpox virus genome. The strong early function of this gene promoter will be useful in the construction of recombinant fowlpox viruses.

Base Sequence↗
PubMed1990

Comparative analysis of vaccinia virus promoter activity in fowlpox and vaccinia virus recombinants.

A quantitative and qualitative comparison of vaccinia virus (VV) promoter activity in fowlpox virus (FPV) and VV recombinants was performed. The VV PL11 late promoter was used to express beta-galactosidase from the E. coli LacZ gene in FPV (FPV-LacZ) and VV (VV-LacZ) recombinants. Time courses of FPV-LacZ beta-galactosidase expression in chicken embryo skin (CES) cells demonstrated temporal regulation of the PL11 promoter with maximum enzyme activity nine- and four-fold lower than those obtained in VV-LacZ infected 143B and CES cells, respectively. The level of beta-galactosidase activity per LacZ DNA gene copy was determined for each recombinant and found to be greater for VV-LacZ than FPV-LacZ. The VV P7.5 early/late promoter was used to express the E. coli xanthine-guanine phosphoribosyl transferase (Ecogpt) gene in FPV and VV recombinants. Northern blot analysis showed early Ecogpt RNA transcripts to be of defined lengths. Transcript size estimations mapped the termination sites to regions containing sequences associated with VV early transcript termination, providing supportive evidence for a common poxvirus early transcript termination signal. Late LacZ and Ecogpt transcripts were heterogeneous in length. S1 nuclease mapping of the 5'-ends of early and late Ecogpt RNA transcripts produced by FPV and VV recombinants showed transcription initiation occurred at the same sites in both poxviruses and corresponded to the regions previously identified as the early and late start sites of the P7.5 promoter. These results would indicate a high level of conservation in the expression and regulation of genes by poxviruses.

Animals↗
PubMed1990

Expression of bovine leukaemia virus envelope gene by recombinant vaccinia viruses.

Recombinant vaccinia viruses (VV) containing the envelope gene of bovine leukaemia virus (BLV) were constructed. Three virus constructs were designed: VV-BLV1 which contained the open reading frame for envelope glycoprotein gp51 alone, under control of VVP7.5 promoter; VV-BLV2 and VV-BLV3 contained the entire gene (gp51 + gp30) coding sequence downstream of VP7.5 and the fowlpox virus early/late promoter (PFE/L) respectively. All three VV recombinants expressed envelope glycoproteins as determined by the agar gel diffusion assay. By immunofluorescence techniques it was shown that while VV-BLV2 and VV-BLV3 expressed envelope glycoprotein on the surface of virus-infected cells, VV-BLV1 failed to do so. Rabbits inoculated with VV-BLV1 failed to show an anti envelope glycoprotein antibody response, however, significant levels of antibodies against envelope glycoprotein were detected in sera from rabbits inoculated with VV-BLV2 and VV-BLV3.

Animals↗
PubMed1990

Formation and persistence of DNA adducts in the liver of brown bullheads exposed to benzo[a]pyrene.

The formation and persistence of benzo[a]pyrene (BP)-DNA adducts in the liver of brown bullheads (Ictalurus nebulosus) treated with the hydrocarbon (20 mg/kg body wt, i.p.) was investigated using the 32P-postlabeling assay. The highest level of covalent binding of BP to liver DNA (188 fmol BP adducts/mg DNA) was observed 25-30 days following treatment. After 70 days, the adduct level in liver DNA had declined to approximately 26% of the maximum adduct level. One major BP-DNA adduct and several minor ones were detected in the liver. The major adduct co-chromatographed with anti-BP-7,8-diol-9,10-epoxide-deoxyguanosine (anti-BPDE-dGuo) adduct. The data suggest that brown bullheads metabolically activate BP by the same mechanism as the mammalian systems susceptible to carcinogenic effects of the hydrocarbon.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1990

Carcinogenic activity of a carbamate fungicide, mancozeb on mouse skin.

Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas.

Administration, Topical↗