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Biomedical subjects

R V Bhat

Publications and source records attributed to R V Bhat.

At least 37 records · Page 2Linked to original sources
PubMed1998

Region-specific targets of p42/p44MAPK signaling in rat brain.

In vitro studies indicate that p42/p44MAPK phosphorylate both nuclear and cytoplasmic proteins. However, the functional targets of p42/p44MAPK activation in vivo remain unclear. To address this question, we localized activated p42/p44MAPK in hippocampus and cortex and determined their signaling effects after electroconvulsive shock treatment (ECT) in rats. Phosphorylated p42/p44MAPK content increased in the cytoplasm of hippocampal neurons in response to ECT. Consistent with this cytoplasmic localization, inhibition of ECT-induced p42/p44MAPK activation by the extracellular signal-regulated kinase kinase inhibitor PD098059 blocked phosphorylation of the cytoplasmic protein microtubule-associated protein 2c (MAP2c), but failed to inhibit the induction of the nuclear protein c-Fos in response to ECT. In contrast to hippocampal neurons, cortical neurons exhibited an increase in amount of phosphorylated p42/p44MAPK in both the nucleus and cytoplasm after ECT. Accordingly, PD098059 blocked the induction of Fos-like immunoreactivity in the nuclei of cortical neurons as well as MAP2c phosphorylation in the cytoplasm. Our data indicate that both nuclear and cytoplasmic substrates can be activated by p42/p44MAPK in vivo. However, the functional targets of p42/p44MAPK signaling depend on the precise location of p42/p44MAPK within different subcellular compartments of brain regions. These results indicate unique functional pathways of p42/p44MAPK-mediated signal transduction within different brain regions in vivo.

Animals↗
PubMed1998

Activation of p38MAPK in microglia after ischemia.

p38MAPK has been implicated in the regulation of proinflammatory cytokines and apoptosis in vitro. To understand its role in neurodegeneration, we determined the time course and localization of the dually phosphorylated active form of p38MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38MAPK and mitogen-activated protein kinase-activated protein 2 activity increased over 4 days after ischemia. Phosphorylated p38MAPK immunoreactivity was observed in microglia in regions adjacent to, but not in, the dying CA1 neurons. In contrast, neither c-Jun N-terminal kinase 1 nor p42/p44MAPK activity was altered after ischemia. These results provide the first evidence for localization of activated p38MAPK in the CNS and support a role for p38MAPK in the microglial response to stress.

Animals↗
PubMed1998

Mycotoxins in foods--occurrence, health & economic significance & food control measures.

Mycotoxins of importance in India include aflatoxin, fumonisins, trichothecenes, ergot alkaloids and ochratoxins. The ICMR multicentric study on the occurrence of aflatoxin contamination in risk commodities namely, maize and groundnut showed that 21 per cent of groundnut samples and 26 per cent of maize samples analysed exceeded Indian tolerance limits of 30 micrograms/kg. A study on the aflatoxin intake from maize-based diets in a rural region of Andhra Pradesh showed the intakes to be in the range of 4-100 ng/kg body wt/day. Studies on the occurrence of aflatoxin M1 in milk in the southern and western regions of India indicated levels in the range of 0.05-3.0 micrograms/l. Analysis of feed samples indicated high incidence of aflatoxin B1 contamination in the groundnut cake component. Fumonisins have been shown to occur in Indian maize and sorghum. Studies showed high levels of fumonisins in rain-affected maize and sorghum consumption of which resulted in an outbreak of fumonisin mycotoxicosis in rural regions of the Deccan Plateau. A similar disease outbreak occurred in poultry due to consumption of fumonisin contaminated feed containing rain damaged maize. Biomarkers have been developed for assessing the risk of exposure for two mycotoxins viz., aflatoxin by measurement by ELISA of aflatoxin B1 N7-guanine adduct which has a detection limit of 15.6 pmol aflatoxin B1 N7 guanine; and fumonisin B1 by measurement in urine using HPLC with a detection limit of 8 ng/ml urine. Assessment of the economic implications of aflatoxin contamination showed economic losses resulting in rejection of export consignment of hand-picked-selected (HPS) groundnut and losses in the poultry industry. Approaches for prevention and control of mycotoxin contamination in foods have shown that methods involving the segregation of contaminated or mouldy grains by hand picking and density segregation resulted in a reduction of 70-90 per cent of aflatoxin and fumonisin present in the grains. While harmonization of international regulatory limits, the requirements of food producing countries needs to be recognized and realistic but not idealistic safe limits, need to be proposed.

Animal Diseases↗
PubMed1997

Disease outbreak in laying hens arising from the consumption of fumonisin-contaminated food.

1. During the last quarter of 1995 an unusual disease outbreak characterised by black sticky diarrhoea, severe reduction in food intake, egg production and body weight follow by lameness and death was observed in 2 layer farms in Andhra Pradesh. A total of 6700 hens of 64 weeks age and 3000 hens of 36 weeks age were affected. 2. Around 10% mortality and a 20% reduction in egg production was observed. Postmortem examinations showed pale yellow coloured livers with peripheral congestion, mild haemorrhage in the proventriculus and watery accumulations in the intestine. 3. The disease was traced to a new batch of food and its withdrawal improved the health status of the flocks. 4. Analysis of the diet indicated contamination with fumonisin B1 up to 8.5 mg/kg and aflatoxin B1 up to 0.1 mg/kg. 5. Diarrhoea was induced in day old cockerels by feeding the suspect diet containing 8.5 mg/kg fumonisin B1, and in laying hens by feeding a normal diet with fumonisin B1 additions of 8 and 16 mg/kg.

Animal Feed↗
PubMed1997

A foodborne disease outbreak due to the consumption of moldy sorghum and maize containing fumonisin mycotoxins.

BACKGROUND: Unseasonal rains beginning in 1995 damaged the maize and sorghum crops harvested in a few villages of the Deccan plateau in India. Human consumption of those grains resulted in a foodborne disease outbreak characterized by abdominal pain, borborygmi and diarrhea. METHODS: A rapid epidemiological survey was conducted in the affected villages and a detailed house to house survey in selected villages. RESULTS: People in 27 out of 50 villages surveyed were affected and disease was seen only in households and subjects consuming the rain damaged moldy sorghum or maize. The disease was self limiting. Diarrhea was reproduced in day old cockerels fed contaminated grains from affected households. All 20 sorghum and 12 maize samples collected from affected households had Fusarium sp. as the dominant mycoflora and contained fumonisin B1 in the range of 0.14-7.8 mg/kg and 0.25-64.7 mg/kg, respectively. In contrast, samples collected from unaffected households had fumonisin B1 in low levels ranging from 0.07-0.36 mg/kg and 0.05-0.24 mg/kg, respectively. CONCLUSION: The higher water activity in the grains left in the field following harvest led to the production of high levels of fumonisin B1 and consumption of such grains by humans resulted in the disease.

Abdominal Pain↗
PubMed1997

Identification of insulin-like growth factor binding protein-2 as a biochemical surrogate marker for the in vivo effects of recombinant human insulin-like growth factor-1 in mice.

Recent studies indicate that a daily s.c. injection of 1 mg/kg of recombinant human insulin-like growth factor-1 (rhIGF-1) for 17 days is efficacious in enhancing the functional recovery of injured sciatic nerves in CD-1 mice. To identify and characterize surrogate marker(s) that are altered in association with the administration of an efficacious dose of rhIGF-1, dose-response curves (0.1, 1 and 10 mg/kg) and time course effects (0, 0.5, 3, 6 and 24 hr) were determined after acute (single) and chronic (once daily for 17 days) injections of rhIGF-1 in CD-1 mice. Plasma glucose levels decreased in a dose-dependent fashion after either acute or chronic injections of rhIGF-1 with maximal effects at 0.5 to 1 hr after administration of rhIGF-1. Among the three insulin-like growth factor binding proteins (IGFBPs) evaluated in the study, only IGFBP2 levels were consistently increased in a dose-dependent fashion with maximal effects 3 hr after the last of a series of injections of rhIGF-1. Furthermore, IGFBP2 levels increased at a dose of rhIGF-1 (1 mg/kg) that enhances the regeneration of injured sciatic nerves in mice. Chronic administration of insulin at doses that cause comparable decreases in plasma glucose to that of rhIGF-1 did not alter IGFBP2 levels or enhance hindlimb function suggesting that the beneficial effects of rhIGF-1 occur via activation of the type-I IGF receptor rather than the insulin receptor. Based on these criteria, IGFBP2 appears to be useful as a surrogate marker for determining the in vivo effects of rhIGF-1.

Animals↗
PubMed1996

Increased expression of IL-1beta converting enzyme in hippocampus after ischemia: selective localization in microglia.

Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the in vivo expression of one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neurons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity was not altered in these neurons. ICE-like immunoreactivity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of ischemic brains. These results provide the first evidence for the localization and induction of ICE expression in vivo after ischemia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.

Animals↗
PubMed1996

Expression of the APC tumor suppressor protein in oligodendroglia.

Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been linked to familial polyposis, an inherited predisposition to colon cancer, and a high percentage of sporadic colon adenomas. Although this gene is best known for its role in development of bowel neoplasms, in recent studies we have found that APC mRNA levels are greatly enriched in brain compared with peripheral tissues. To help define its role in the nervous system, in this study we have determined its cellular localization immunohistochemically in adult rat brain sections and have detected intense APC immunoreactivity in oligodendrocytes. Since prominent APC immunostaining is detected in cell bodies of mature oligodendrocytes, these antibodies may provide a useful addition to available oligodendrocyte markers. Although the cellular function of APC remains undefined, previous biochemical studies have demonstrated that APC is associated with catenins, cytoplasmic proteins involved in regulating cell-cell adhesion. We propose that, in addition to its critical role in ensuring normal maturation of colonic epithelial cells, the APC tumor suppressor protein also regulates the adhesive properties of oligodendrocytes.

Adenomatous Polyposis Coli↗
PubMed1996

Aflatoxin B1 contamination in groundnut samples collected from different geographical regions of India: a multicentre study.

Under a multicentre study conducted by the Indian Council of Medical Research, 2062 samples of groundnut were collected from rural and urban areas of 11 states representing different geographical regions of the country. These samples were analysed for aflatoxin B1 using the AOAC method. Analytical quality assurance between various participating laboratories was ensured through analysis of check-samples. Twenty-one per cent of groundnut samples collected from 11 states exceeded the permissible Indian regulatory limit of 30 micrograms/kg. No statistically significant difference in percentage of samples contaminated (> 30 micrograms/kg) were observed between pooled rural (22.9%) and urban (19.9%) data. Amongst the 11 states, the minimum and maximum per cent contamination respectively (> 30 micrograms/kg) was observed to be 15.2 in the state of Andhra Pradesh and 28.3 in the state of Haryana. The maximum level of contamination of 833 micrograms/kg was observed in the state of Gujarat. The median level of < 5 micrograms/kg was observed in the states of Gujarat, Haryana, Punjab, Andhra Pradesh and Karnataka. In all other states studied, the median level was found to vary between 10 and 20 micrograms/kg. The 90th percentile values were high in Andhra Pradesh (125 micrograms/kg), Gujarat (111 micrograms/kg) and Haryana (110 micrograms/kg). In the remaining states the 90th percentile value ranged from 60 to 93 micrograms/kg. Analysis of pooled data showed the percentages of samples exceeding the level of contamination of 5 micrograms/kg and 15 micrograms/kg, respectively were 44.9% and 37.4% which therefore, showed a marked increase when compared with the per cent of samples exceeding 30 micrograms/kg in the overall data.

Aflatoxin B1↗
PubMed1996

A comparative clinico-pathological study of oral submucous fibrosis in habitual chewers of pan masala and betelquid.

BACKGROUND: Oral submucous fibrosis associated with chewing of betel nut products has an estimated prevalence of 0.2-1.2% in India. The increasing use of pan masala/gutkha, a mix of tobacco and a less moist form of betelquid lacking the betel leaf, seems associated with an earlier age of onset of oral submucous fibrosis. METHOD: A prospective study examined the in vivo effects of pan masala/gutkha and betelquid chewing on buccal mucosal cytology in 50 patients with oral submucous fibrosis and 40 controls. RESULTS: The percentage of nucleolated intermediate cells or proliferative fraction of buccal mucosa cells was significantly higher in all habitual chewers than controls. Pan masala/gutkha chewers presented with oral submucous fibrosis after 2.7 +/- 0.6 y of use whereas the betelquid users presented with oral submucous fibrosis reported 8.6 +/- 2.3 y of use (p < 0.05). CONCLUSIONS: Habitual chewing of pan masala/gutkha is associated with earlier presentation of oral submucous fibrosis than betelquid use. Factors which may be responsible for these differences are the tobacco content, the absence of the betel leaf and its carotenes and the much higher dry weight of pan masala/gutkha.

Adult↗
PubMed1995

Activation of arc, a putative "effector" immediate early gene, by cocaine in rat brain.

As immediate early genes (IEGs) are thought to play a critical role in mediating stimulus-induced neuronal plasticity, several laboratories have characterized the IEG response induced by cocaine to help define the changes in gene expression that may underlie its long-lasting behavioral effects. Although activation of several transcription factor IEGs has been described, little is known about which "effector" IEGs, if any, are also induced. In the present study, we have examined whether cocaine administration affects expression of a recently identified "effector" IEG, referred to as arc (activity-regulated, cytoskeleton-associated). This IEG encodes a protein with homology to spectrin that appears to be associated with the actin cytoskeleton. Using in situ hybridization, we have found that systemic cocaine administration elicits a robust, transient rise in arc mRNA levels in striatum, which is suppressed by D1 dopamine receptor blockade, reserpine treatment, or striatal 6-hydroxydopamine lesions. D2 receptor antagonist triggered arc expression when administered alone. Immunohistochemical studies indicated that Arc protein induced by cocaine is expressed in neuronal cell bodies and dendrites. As Arc appears to be component of the neuronal cytoskeleton, it may be involved in structural alterations underlying neuronal plasticity triggered by cocaine.

Animals↗
PubMed1995

Accidental acute fatal sodium nitrite poisoning.

An accidental food poisoning outbreak occurred resulting in the death of 14 of the 22 affected persons. Chemical analysis of food materials revealed the presence of sodium nitrite and potassium arsenate. Analysis of urine, gastric contents, liver and kidney, collected at the time of autopsy, confirmed the presence of these chemical substances in high concentrations. Epidemiological data indicated that the food poisoning occurred due to the accidental use of sodium nitrite and potassium arsenate instead of table salt in the preparation of tamarind (Tamarindus indica) soup.

Adolescent↗
PubMed1995

Foodborne disease outbreak due to consumption of rancid biscuits.

A foodborne disease outbreak characterized by vomiting, abdominal pain and diarrhea, involving mostly children was investigated. Epidemiological, hospital and laboratory investigations indicated that the disease outbreak was associated with consumption of rancid biscuits abandoned in the street corner in a crowded locality of old city Hyderabad. The offensive flavors of rancidity were masked by the strong pineapple flavor used in the biscuits. Rancidity of the biscuits was confirmed by high peroxide value and acidity of extracted fat. Bacterial contamination was excluded by the total aerobic plate counts and negative tests for Staphylococcus and Salmonella.

Adolescent↗
PubMed1995

Parasitic contamination of stored water used for drinking/cooking in Hyderabad.

A study was undertaken to investigate the parasitic contamination of water in Hyderabad city, India. A total of 232 samples of water were collected from different places; social welfare hostels, small restaurants, different households, public places like railway stations, bus depots, street food vendors, hand washings from the food handlers, and vegetable washings from vegetable vendors. Of these 232 samples 61 samples indicated the presence of pathogenic parasites which include protozoans (cysts of Giardia lamblia, Entamoeba histolytica, adult stages of G. lamblia, Balantidium coli) and nematode eggs, (Enterobius vermicularis, Ascaris lumbricoides, Trichuris trichiura), rhabditiform and filariform larvae and adult stages of Strongyloides stercoralis and Enterobius vermicularis. The source of the samples in all places was the water stored in overhead tanks and various other containers. Hand washings from food handlers also showed the presence of pathogenic parasites although the original water used for such washings were free from contamination.

Animals↗
PubMed1994

Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.

The aquaporins transport water through membranes of numerous tissues, but the molecular mechanisms for sensing changes in extracellular osmolality and regulating water balance in brain are unknown. We have isolated a brain aquaporin by homology cloning. Like aquaporin 1 (AQP1, also known as CHIP, channel-forming integral membrane protein of 28 kDa), the deduced polypeptide has six putative transmembrane domains but lacks cysteines at the known mercury-sensitive sites. Two initiation sites were identified encoding polypeptides of 301 and 323 amino acids; expression of each in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability not blocked by 1 mM HgCl2, even after substitution of cysteine at the predicted mercury-sensitive site. Northern analysis and RNase protection demonstrated the mRNA to be abundant in mature rat brain but only weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of brain localized the mRNA to ependymal cells lining the aqueduct, glial cells forming the edge of the cerebral cortex and brainstem, vasopressin-secretory neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje cells of cerebellum. Its distinctive expression pattern implicates this fourth mammalian member of the aquaporin water channel family (designated gene symbol, AQP4) as the osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.

Amino Acid Sequence↗
PubMed1994

Genetic and activity-dependent regulation of zif268 expression: association with spatial learning.

We have reported that C57BL/6 and DBA/2 mice differ in spatial learning performance and associated hippocampal protein kinase C (PKC) activity (Upchurch and Wehner, 1989, Behav Neurosci 103:1251-1258; Wehner et al., 1990, Brain Res 523:181-187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) (Fordyce and Wehner, 1993b, Brain Res 619:111-119). To assess whether physical activity induces alterations in gene expression that may underlie these changes in PKC and learning performance, we examined the effect of physical activity on expression of zif268, a transcription regulatory factor linked to stimulus-induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chronic (8 weeks) physical activity. The mice were then tested on the Morris water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocampal-specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523-181-187; Fordyce and Wehner, 1993b, Brain Res 619:111-119; Paylor et al., 1993, Psychobiology 27:11-26), displayed lower basal levels of zif268 mRNA (P < .05). As observed previously, chronic physical activity produced an enhancement in spatial learning performance accompanied by alterations in hippocampal PKC activity in both strains of mice (P < .05). In addition, the present investigation demonstrated that acute physical activity increased mRNA levels of zif268 in hippocampal regions CA1, CA3 and overlying cortex (P < .005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity-dependent regulation of zif268 may influence learning performance.

Animals↗
PubMed1994

Effects of chronic nicotine infusion on kinetics of high-affinity nicotine binding.

It is well established that chronic nicotine treatment produces a dose-dependent increase in high-affinity L-[3H]nicotine binding. This increase may be due to chronic desensitization of the receptor. Sophisticated kinetic analyses of high-affinity nicotine binding to rat brain have demonstrated that the association rate is biphasic; the fast phase may represent binding to a high-affinity predesensitized state and the slow phase may represent binding to a lower affinity ground state that then isomerizes to form the high-affinity binding site. This isomerization presumably leads to receptor desensitization. The studies reported here assessed whether binding to mouse brain nicotinic receptors shows these same properties and whether chronic intravenous infusion of nicotine results in changes in these kinetic properties. The results obtained indicate that mouse brain nicotine binding also shows biphasic association kinetics and uniphasic dissociation kinetics, which supports the assertion that the receptor exists in two interconvertible states. However, unlike other results obtained with rat brain, the rate of the slow association process did not change with ligand concentration. Chronic infusion resulted in a dose-dependent increase in L-[3H]nicotine binding, but the ratio of fast/slow phases of binding was not changed by these treatments. These results suggest that chronic infusion does not alter measurably the kinetics of nicotinic receptor binding when measured in vitro.

Animals↗