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Biomedical subjects

N Sharma

Publications and source records attributed to N Sharma.

At least 199 records · Page 11Linked to original sources
PubMed1993

The effect of non-mutagenic stress on liquid holding recovery in Escherichia coli AB2463.

Previous work has shown that exposure to many non-mutagenic stresses causes greater UV resistance in Escherichia coli K12 via an error-free, excision repair-dependent process. Induction of the latter should enhance liquid holding recovery in the bacteria. The results in this paper show that this is the case and that the increased UV-resistance is due entirely to an increase in the capacity of the cells for DNA excision repair. The latter arises wholly or in part from an increase in the intracellular level of the key enzyme of the pathway, UvrABC endonuclease.

Caffeine↗
PubMed1993

CSF-1 expression is upregulated in astrocyte cultures by IL-1 and TNF and affects microglial proliferation and morphology in organotypic cultures.

Astrocytes produce factors that control the growth and differentiation of many cell types within the CNS as well as play a role in the generation of the immune response. The extent to which these two functions interact has received less attention. We now report that astrocyte cultures established from rat brain endogenously express mRNA and low levels of secreted biologically active protein for the monocyte growth and differentiation factor colony stimulating factor-1 (CSF-1). Exposure of astrocytes to interleukin-1 (IL-1) and/or tumor necrosis factor (TNF) upregulated the expression of CSF-1 mRNA and protein. Following treatment with 100 U/ml of TNF, IL-1, or TNF+IL-1, maximum CSF-1 mRNA expression was observed at 3 hr. In the presence of IL-1 an increase in biologically active CSF-1 was detected in the astrocyte conditioned medium at 6 hr. These data indicate that the expression of CSF-1 by astrocytes can be modulated by exposure to the cytokines IL-1 and TNF. To determine whether CSF-1 provides a mitogenic signal for microglia during development, mouse spinal cord organotypic cultures were exposed to recombinant mouse CSF-1 (rmCSF-1), resulting in proliferation of microglia by 7 days and an increase in the number of ramified microglia over ameboid microglia by 14 days.

Animals↗
PubMed1993

Nerve growth factor regulates the abundance and distribution of K+ channels in PC12 cells.

We examined the effect of nerve growth factor (NGF) treatment on expression of a neuronal delayed rectifler K+ channel subtype, Kv2.1 (drk1), in PC12 cells. Anti-Kv2.1 antibodies recognized a single polypeptide population of M(r) = 132 kD in PC12 cell membranes, distinct from the more heterogeneous population found in adult rat brain. In response to NGF treatment, levels of Kv2.1 polypeptide in PC12 membranes increased fourfold. This increase in polypeptide levels could be seen within 12 h, and elevated levels were maintained for at least 6 d of continuous NGF treatment. RNase protection assays indicate that this increase in Kv2.1 protein occurs without an increase in steady state levels of Kv2.1 mRNA following NGF treatment. Immunofluorescent localization of the Kv2.1 polypeptide revealed plasma membrane-associated staining of cell bodies in both untreated and NGF-treated PC12 cells. In undifferentiated cells, intense staining is seen at sites of cell-cell and cell-substratum contact. In differentiated cells the most intense Kv2.1 staining is observed in neuritic growth cones. These studies show that in PC12 cells both the abundance and distribution of the Kv2.1 k+ channel are regulated by NGF, and suggest that PC12 cells provide a model for the selective expression of Kv2.1 in neuritic endings.

Animals↗
PubMed1993

Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids.

To determine whether cortisol has an effect on hypothalamic-pituitary-gonadal function, we studied 11 eumenorrheic women in the early follicular phase of consecutive menstrual cycles by performing daytime 10-min blood sampling, one before and one during hydrocortisone administration. Daily blood sampling for gonadotropins and sex steroids was also performed. LH pulsations were determined by modification of a widely used threshold method and compared by paired t-testing. The LH interpulse interval was significantly prolonged (95 +/- 5 to 119 +/- 14 min; p = 0.001), and the mean LH pulse amplitude remained unchanged (1.3 +/- 0.1 and 1.5 +/- 0.2 mIU/ml) with glucocorticoid exposure. Mean estradiol was not altered (46 +/- 5 and 43 +/- 3 pg/ml), but mean LH and FSH from pooled serum aliquots were slightly but significantly reduced (2.6 +/- 0.2 to 2.2 +/- 0.2, 5.5 +/- 0.4 to 4.5 +/- 0.3 mIU/ml; p = 0.004, 0.012, respectively). Mean progesterone levels were also decreased (0.8 +/- 0.3 to 0.5 +/- 0.2 ng/ml; p = 0.011) in the presence of exogenous glucocorticoid. Twenty-four-hour urinary free cortisol levels confirmed a substantial increase in free cortisol excretion (74 +/- 10 to 305 +/- 50 micrograms/day; p = 0.001). These results demonstrate that cortisol can slow LH pulse frequency and, by inference, hypothalamic GnRH secretion, in a manner that appears independent of corticotropin releasing factor. Excess cortisol alone may therefore play a role in the development of stress-associated menstrual disturbances.

Adult↗
PubMed1993

Interactions between the Escherichia coli cyclic AMP receptor protein and RNA polymerase at class II promoters.

The effects of a number of mutations in crp have been measured at different cyclic AMP receptor protein (CRP)-dependent Class II promoters, where the CRP-binding site is centred around 41 1/2 base pairs upstream from the transcription start point. The amino acid substitutions HL159 and TA158 result in reduced CRP-dependent activation, but the reduction varies from one Class II promoter to another. Deletions in the C-terminus of the RNA polymerase alpha subunit suppress the effects of HL159 and TA158. The role of the C-terminus of alpha at these promoters is assessed. Other changes at E58, K52 and E96 affect CRP activity specifically at Class II promoters and their role is discussed.

Amino Acid Sequence↗
PubMed1993

Okadaic acid induces early changes in microtubule-associated protein 2 and tau phosphorylation prior to neurodegeneration in cultured cortical neurons.

Microtubules and their associated proteins play a prominent role in many physiological and morphological aspects of brain function. Abnormal deposition of the microtubule-associated proteins (MAPs), MAP2 and tau, is a prominent aspect of Alzheimer's disease. MAP2 and tau are heat-stable phosphoproteins subject to high rates of phosphorylation/dephosphorylation. The phosphorylation state of these proteins modulates their affinity for tubulin and thereby affects the structure of the neuronal cytoskeleton. The dinoflagellate toxin okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A. In cultured rat cortical neurons and a human neuroblastoma cell line (MSN), okadaic acid induces increased phosphorylation of MAP2 and tau concomitant with early changes in the neuronal cytoskeleton and ultimately leads to cell death. These results suggest that the diminished rate of MAP2 and tau dephosphorylation affects the stability of the neuronal cytoskeleton. The effect of okadaic acid was not restricted to neurons. Astrocytes stained with antibodies to glial fibrillary acidic protein (GFAP) showed increased GFAP staining and changes in astrocyte morphology from a flat shape to a stellate appearance with long processes.

Animals↗
PubMed1993

Magnitude of acute respiratory infections in under five.

A community-based study was carried out in a rural area of Delhi to measure the prevalence and incidence of acute respiratory infections among children below the age of 5 years. The prevalence of 12.1%, was similar in boys and girls and was seen to decline with age. The incidence of acute respiratory infections was 2.5 episodes per child per year; it was not different in boys and girls. There was a statistically significant decline in the incidence with age. Upper respiratory tract infections comprised 87.5% of total acute respiratory infection morbidity while lower respiratory tract infections were 12.5%. Both upper and lower respiratory tract infections declined with increasing age; while the former was similar among boys and girls, the incidence of latter was significantly greater in boys (0.4 episodes per year) as compared to girls (0.2 episodes per year). A total of 87.5% episodes were mild, 10.4% moderate and only 2.1% were severe. The results suggest that acute respiratory infections are a major community health problem and an acute respiratory infection control programme needs to be implemented urgently.

Acute Disease↗
PubMed1992

Esophageal ulcer due to ingestion of melted copper.

We report a patient with esophageal stricture as a result of the accidental swallowing of melted copper by a 49-year-old male. As a result, esophagogastric ulcers developed and left a cicatrical stricture. The patient could only manage to swallow liquid food. Radiology of the upper gastrointestinal tract showed marked stricture of the esophagus from the middle thoracic portion to the esophagogastric junction and shortening of the lesser curvature of the stomach. The patient underwent a single-session total gastrectomy, and excision of the thoracic esophagus and construction of anterior thoracic esophagocolic and duodenocolic anastomoses were performed by right thoracotomy and laparotomy, respectively. Macroscopic findings of the surgical specimens showed extensive circular ulcers at the esophagus, and microscopic findings showed deep ulcers extending to the muscle layer with marked fibrosis. The postoperative course was uneventful.

Accidents, Occupational↗
PubMed1992

A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation.

A new model employing latex of papaya as an inflammagen has been developed for testing anti-inflammatory activity. The latex (exudate) was harvested from the unripe papaya fruit, which had been dried under vacuum. The latex was then suspended in 0.05 M sodium acetate buffer. This suspension when injected in rat hind paw produced concentration-dependent inflammation. Of the 0.25% of this suspension, 0.1 ml was found ideal for evaluating anti-inflammatory activity of test drugs. This concentration produced 70%-100% inflammation lasting for about 5 hr with a maximum effect at h 3. The test drugs employed were prednisolone, aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam, chloroquine, levamisole, and a mixture of boswellic acids. For comparison, these drugs were also tested against carrageenan-induced inflammation. All the test drugs--steroidal, aspirin, and non-aspirin-like--showed anti-inflammatory activity against latex-induced inflammation. The activity of chloroquine, levamisole, and boswellic acids was significantly more against latex as compared with that of the carrageenan model. The inflammation caused by latex may be attributed to both its hydrolytic enzymes--papain and chymopapain--and glutathione, the activator of these enzymes. These enzymes seem to act like lysosomal enzymes that are released in inflammatory disease processes which mediate inflammation by stimulating the synthesis of prostaglandins. The papaya latex-induced inflammation model appears to be a sensitive, broad-based, and relevant one likely to prove useful for discovering new and effective drugs against inflammation and rheumatoid arthritis.

Animals↗
PubMed1992

Giant parotid calculus--an unusual presentation.

We describe a case of a giant sialolith of Stensen's duct in a 48-year-old woman. The patient was investigated and treated with a mistaken diagnosis of chronic inflammation until the clue to the diagnosis was provided by plain radiography. This is an unusual presentation of a salivary calculus and to our knowledge such a huge parotid calculus has not been reported so far in the literature.

Calculi↗
PubMed1992

Biochemical studies on mouse liver following Plasmodium berghei infection.

The lipid composition of mouse liver following infection with P. berghei was investigated. The liver lipid contents of infected animals were greatly increased mainly due to the accumulation of triacylglycerides. There was enhanced lipid concentration (85.29%). Significantly (23.7%) depleted liver cholesterol was also found in the mice. Similarly, phospholipid contents of liver were also decreased by 19.90 per cent. The liver from P. berghei infected mouse produced more lipid peroxide, as compared to control animals (314%). Significant depletion was also observed in carbohydrate, glycogen and glucose (79.1, 86.26 and 78.6% respectively) contents of liver at high parasitaemia. The lower contents of nucleic acid in the infected hosts observed in the study may be partly due to the absorption of nucleic acids by the parasites from the host cells.

Animals↗
PubMed1991

Phorbol-12-myristate-13-acetate (PMA) and inhibitors of protein kinase C alter glial fibrillary acidic protein (GFAP) mRNA levels.

Glial fibrillary acidic protein (GFAP) mRNA levels in the human astrocytoma line U-373MG were examined to explore further the effects of agents that regulate protein kinase C. U-373MG cells exhibit a biphasic change in steady-state GFAP mRNA in the presence of the phorbol ester phorbol-12-myristate-13-acetate (PMA). Short-term treatment with PMA results in increased GFAP mRNA, and long-term treatment results in decreased GFAP mRNA. Nuclear run-off experiments demonstrate that the PMA-induced decrease in GFAP mRNA levels is not at the level of GFAP gene transcription. PMA exerts its effect in the presence of protein synthesis inhibitors, demonstrating that de novo protein synthesis is not required for the PMA-induced changes in GFAP mRNA. Staurosporine, a protein kinase C inhibitor, reduces GFAP mRNA expression in a dose-dependent manner; in the presence of PMA the effect is additive. By contrast HA1004, an inhibitor of cAMP-dependent protein kinase, is not inhibitory to GFAP steady-state mRNA. Total protein kinase C activity was determined to be 2,398.8 +/- 94.3 pmol/min/mg protein, with most of the activity in the cytosol. Short-term PMA treatment results in the translocation of the cytosolic protein kinase C activity to the membrane. Long-term PMA treatment results in a decrease in total protein kinase C activity indicating that downregulation occurs. These studies demonstrate that in the U-373MG cells, protein kinase C inhibitors and long treatment with PMA result in a decrease in steady-state GFAP mRNA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Starvation as an inducer of error-free DNA repair in Escherichia coli.

Previous work in this laboratory has shown that heat shock or vitamin B1 deprivation induces an error-free DNA-repair process in Escherichia coli. The system is absolutely dependent on excision repair, while its induction is delayed in lon- or recA- cells. We have now shown that starvation of E. coli for amino acids, glucose or phosphate, conditions known to induce the stringent response or the glu and pho regulons, respectively, leads to a similar uvrA-dependent increase in UV resistance and decrease in UV-induced mutation frequency. These results support the hypothesis that the effect is a general response to non-mutagenic stress that may play an important role in the survival of cells exposed to harsh environments.

Amino Acids↗
PubMed1991

Insulin reverses haemodynamic changes and pulmonary oedema in children stung by the Indian red scorpion Mesobuthus tamulus concanesis, Pocock.

The efficacy of insulin administration in reversing haemodynamic changes in pulmonary oedema in victims of poisonous scorpion sting is assessed by a study based on animal experiments in which insulin administration reversed metabolic and electrocardiographic changes induced by scorpion envenomation. Six previously healthy children aged 18 months to 11 years were admitted to hospital five to 17 hours after scorpion sting. Frusemide for raised central venous pressure and pulmonary oedema, crystalloid infusion for reduced central venous pressure, and hydrocortisone and dopamine for hypotension were used as standard therapy. Insulin (0.3 units g-1 of glucose) was administered when the standard therapy failed to produce an improvement, and at the earliest sign of haemodynamic instability. Reversal of pulmonary oedema and haemodynamic changes, and attainment or normal respiratory rate, blood pressure and central venous pressure, were observed. It is concluded that insulin administration may be useful in reversing haemodynamic changes and pulmonary oedema in victims of scorpion stings.

Animals↗
PubMed1991

Morphological and functional characterization of a hormonally induced AIMS/GRXII cell line.

The AIMS/GRXII cell line is a product of the line of research our laboratory is pursuing to understand the response of target cells to sustained hormonal stimulation, a situation simulating the one that brings about in vivo tumorigenesis. The cell line was derived from goat ovarian granulosa cells subjected to luteinizing hormone stress (high doses repeated). It was found to be contact-inhibited, nontumorigenic and secreted progesterone. The majority of cells at any given passage showed hypodiploidy. The cell line required hormonal support till passage 8 after which it was hormone-independent. Thus, the system offers a phase-wise development of the cell line which might be useful in cancer research, particularly to understand the mechanisms of cell transformation at the cellular and molecular level and possible hormone (onco)gene nexus in cell proliferation.

Animals↗