Spontaneous rupture of unscarred uterus in early pregnancy--a rare entity.
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Adult↗
Biomedical subjects
A Singh
Publications and source records attributed to A Singh.
Brainstem nicotinic receptor subtypes that influence intragastric and arterial blood pressures.
The purpose of this study was to investigate the effect of microinjection of nicotine and nicotinic receptor antagonists into the dorsal motor nucleus of the vagus (DMV) or medial subnucleus of the tractus solitarius (mNTS) on intragastric (IGP) and arterial blood pressures (BP) in anesthetized rats. Nicotine microinjected into the DMV (10-300 pmol) produced dose-related increases in IGP (ED(50) = 89 pmol); no significant changes were noted for BP. Ipsilateral vagotomy abolished nicotine-induced increases in IGP. Nicotine microinjected into the mNTS in a dose range of 0.1 to 300 pmol produced dose-related decreases in IGP (ED(50) = 0.6 pmol) and BP (ED(50) = 5.4 pmol). Bilateral vagotomy abolished nicotine-induced decreases in IGP while having no effect on BP. In rats treated with daily s.c. injections of nicotine (0.8 mg/kg of base) for 10 days, microinjections of nicotine into the DMV produced similar increases in IGP. BP responses from the mNTS were not affected by chronic treatment. However, nicotine microinjections into the mNTS no longer produced a decrease in IGP in these chronically treated animals. alpha-Bungarotoxin (100 pmol) significantly blocked nicotine-evoked increases in IGP from the DMV while having no effect on nicotine-induced responses elicited from the mNTS. Hexamethonium (10 and 100 pmol) microinjected into the mNTS dose-dependently blocked nicotine-induced effects but did not interfere with the action of nicotine at the DMV. Our data indicate that nicotine-induced changes in IGP result from nicotine acting at two sites, the DMV and mNTS; and that at least three different nicotinic receptors in the dorsal medulla oblongata can influence gastrointestinal and cardiovascular function.
Animals↗
PCB 128-induced ultrastructural lesions in the rat liver.
PCB 128 (2,2',3,3',4,4'-hexachlorobiphenyl) prepared in 4% corn oil and mixed in diets was given to weanling Sprague-Dawley rats. The animals were placed in eight groups, each comprising 10 males or 10 females; each group received a diet that contained 0.05, 0.5 or 5 ppm PCB. Ten animals of each gender that served as the controls were given diets mixed with only corn oil. Thirteen weeks after the commencement of dosing, animals were euthanized and liver specimens were harvested and prepared for transmission electron microscopy. The architecture of the liver parenchymal cell was indistinguishable in the animals of the lowest concentration group from those in the controls. However, smooth endoplasmic reticulum profiles increased, and abnormal mitochondria were noted in the liver of rats, regardless of gender, from 0.5 and 5 ppm groups. Based on our previous work, PCB 128 is estimated to be equally toxic as PCB 153, another di-ortho substituted PCB congener.
Animals↗
Prevalence of minor injuries among underfives in a Chandigarh slum.
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Age Distribution↗
Stereology of PCB 128-induced ultrastructural alterations in the rat liver.
Hepatocyte cytoplasmic alterations were stereologically determined in male and female Sprague-Dawley rats fed PCB congener 128 (2,2',3,3',4,4'-hexachlorobiphenyl) in concentrations of 0.05, 0.5, 5, 50 ppm, or corn oil in diets daily for 13 weeks. A significant increase (p < 0.05) in the volume-fraction of smooth endoplasmic reticulum (SER) was measured in the female rats fed a diet containing 5 or 50 ppm of the congener and a significant increase was revealed in the male rats at doses of 0.5 and 50 ppm. Because drug metabolizing enzymes are bound to the SER, proliferated profiles may imply heightened enzyme activity necessary to metabolize the PCB. An elevation in volume-fraction of rough endoplasmic reticulum (RER) was measured in the hepatocytes of the male rats fed 5 ppm of the congener and none of the concentrations significantly enhanced the level of RER profiles in the females. The volume-fraction values of mitochondria, peroxisomes or lipid droplets of the hepatocytes in either the males or the females were not significantly different, as were the baseline volume-fraction of parameters studied between the male and the female rats. We determined for PCB 128, when administered in a diet to Sprague-Dawley rats, the no observable adverse effect level (NOAEL) is < 0.5 ppm.
Animals↗
Molecular signaling in pathogenicity and host recognition in smut fungi taking Karnal bunt as a model system.
Karnal bunt of wheat, incited by a phytopathogen Tilletia indica (Syn. Neovossia indica) is a floret infecting disease. In the floral tissues fungus proliferates and produces massive amount of black spores. In smut fungi, belonging to order Ustilaginales, communication between cells is necessary to regulate growth, differentiation and monokaryotic to dikaryotic transition during pathogenic and sexual development. Neighbouring cells are able to communicate with each other by direct cell to cell contact through plasma membrane bound signaling molecules or through formation of gap junctions and alternatively through secretion of chemical signals if cells are some distance away. Current research efforts toward understanding of pathogenic and sexual development in phytopathogenic fungi, offer a number of opportunities. These include the analysis of molecular signal(s) for direct contribution of sexual interactions to ability of smut and bunt pathogens to cause disease. These efforts will provide not only to explore the mechanisms of pathogenesis, but also to enhance knowledge of basic cellular biology of an economically important group of fungi.
Cell Communication↗
Synergistic immunosuppression by candida in HIV infection: a cytokine based analysis.
Candida is a common opportunistic pathogen in HIV infection and is regarded a signal infection for progression to AIDS. Cytokine imbalances between Th1/Th2 groups have been described in both candida and HIV infections. A study was undertaken to assess the role of candida in furthering immunosuppression in HIV infection based on cytokine levels and CD4 cell counts. 30 Indian subjects were enrolled; 10 HIV positive patients with and 10 without mucosal candidiasis and 10 age matched controls. Th1 cytokines; interleukin (IL) 2, IL 12 and interferon (IFN) gamma, Th2 cytokines; IL 4, IL 6, IL 10 and tumor necrosis factor (TNF) alpha with CD 4 cell counts were estimated using ELISA in all subjects. CD4 cell counts were reduced in both patient groups as compared to controls; significantly more in patients with both HIV and candida infections. There was a decrease in Th1 cytokine levels in all patients; lower levels of Th1 cytokines were seen in patients with both infections. Among the Th2 cytokines, there was a significant increase in the levels of IL 6, IL 10 and TNF alpha in both patient groups; IL 10 and TNF alpha values were significantly raised in patients with dual HIV and candida infections as compared to the other patients. There was no difference in IL 4 values across the subject groups. A positive correlation between CD4 cell counts and Th1 cytokine levels and a negative correlation with Th2 cytokines were noted; these were stronger in patients with both HIV and candidiasis. Thus, there was a Th1/Th2 cytokine imbalance with CD4 cell count reduction in all HIV infected patients, which was more pronounced in patients with both infections. It can be concluded that, owing to the depressed CD4 cell count and Th1 response and increased Th2 cytokines in patients with both candidiasis and HIV as compared to patients with only HIV candidiasis may have a synergistic immunosuppressive effect with HIV in patients with dual infections.
AIDS-Related Opportunistic Infections↗
Modulation of antigenicity of mycelial antigens during developmental cycle of Karnal bunt (Tilletia indica) of wheat.
Indirect enzyme linked immunosorbent assays (ELISA) were developed using polyclonal antibodies against soluble cytoplasmic (SCA) and insoluble cell wall antigens (ICWA) for monitoring modulation of mycelial antigens during growth cycle of T. indica. With SCA, continuous decrease in ELISA reactivity was observed in maturing fungus cultures, suggesting that SCA were expressed predominantly during early vegetative phase and their decreasing role was apparent as the fungus matures possibly towards sporogenous mycelium. In case of ICWA, the reaction profile showed an increase up to exponential phase of growth probably due to increase in the cell division and branching of mycelium. But later, ICWA antibody reactivity was decreased which may be due to conversion of mycelial phase to sporogenous phase, a quiescent stage of growth. Characterization of changes in antigenic configuration during developmental cycle of Tilletia indica by these antibodies could prove to be useful in identification of developmentally related and virulence marker(s).
Antigens, Fungal↗
5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content.
AIM: To study the mechanism of antimigraine activity of Tanacetum parthenium (Feverfew), its extracts and parthenolide, a component of Feverfew, by observing their effect on 5-HT storage and release, and stimulation of 5-HT2B and 5-HT2A receptors. Also to standardize a dosage form of Feverfew with respect to its parthenolide content. METHODS: Isometric responses to 5-HT and an indirect acting serotonergic, d-fenfluramine, were obtained on rat fundus and ileum. In one set of experiments the effect of dichloromethane extract of Feverfew and parthenolide was observed on the above. The extract was then thermally degraded upto 10%, 23%, and 33% with respect to its parthenolide content by keeping at 60 degrees C and 75% relative humidity and the experiments were repeated. In another set of experiments rats were fed with 20 mg/kg Feverfew powder (equivalent to a human dose of 500 micrograms parthenolide per day) for 30 d or were i.p. injected with parthenolide (23.4 micrograms/day) for 7 d. In the same set of experiments one group of rats were fed with 15% and 77% degraded Feverfew powder in the same dose as mentioned above. After 30 days the effects of the above were observed on 5-HT and d-fenfluramine. Feverfew was specially formulated and tested for stability under accelerated conditions. RESULTS: Parthenolide (1 x 10(-5) mol/L) non-competitively antagonised the effects of d-fenfluramine but had no significant effect on 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 min which turned significant on increasing the incubation time to 1.5 h, in rat fundus. Parthenolide (5 x 10(-5) mol/L) followed the same trend. However, Feverfew extract (1 x 10(-5) mol/L) potently and directly blocked 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. At 5 x 10(-5) mol/L the extract potently and irreversibly blocked the above. Both parthenolide and Feverfew extract showed a time-dependency in their action. The extract when degraded thermally upto 10% could significantly block the 5-HT receptors and neuronal release of 5-HT, however, on further degradation it lost its inhibitory capacity markedly. Similar results were observed in rats fed orally with undergraded and degraded Feverfew powder and injected i.p. with parthenolide. Feverfew powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feverfew powder is more potent than any of its extract or parthenolide alone in its antiserotonergic activity. Degraded Feverfew extracts show a marked decrease in their antiserotonergic activity. With thermally degraded Feverfew powder containing less contents of parthenolide no built-up antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein its parthenolide content is not degraded to less than 90% of the original content.
Drug Stability↗
Suitability of limited sampling strategy to cyclosporine A oral formulation.
Therapeutic drug monitoring of cyclosporine A in renal transplant patients is normally performed by measuring pre-dose trough levels or doing area under the curve profiles from all possible sampling points. On the basis of good correlation between predicted area under the curve from limited sampling points and actual area under the curve (literature survey), a limited sampling strategy at 1, 3 and 5 hr was used and extended this strategy as a criteria for pilot evaluation of modified cyclosporine A formulations. Hemodialysis patients served as subjects for the study. Panimun Bioral was used as a test formulation while Sandimmun Neoral as standard reference. The study revealed that both formulations had similar restricted AUC0-5h profiles.
Administration, Oral↗
Purification and subunit characterization of the rat liver endocytic hyaluronan receptor.
The endocytic hyaluronan (HA) receptor of liver sinusoidal endothelial cells (LECs) is responsible for the clearance of HA and other glycosaminoglycans from the circulation in mammals. We report here for the first time the purification of this liver HA receptor. Using lectin and immuno-affinity chromatography, two HA receptor species were purified from detergent-solubilized membranes prepared from purified rat LECs. In nonreducing SDS-polyacrylamide gel electrophoresis (PAGE), these two proteins migrated at 175- and approximately 300 kDa corresponding to the two species previously identified by photoaffinity labeling of live cells as the HA receptor (Yannariello-Brown, J., Frost, S. J., and Weigel, P. H. (1992) J. Biol. Chem. 267, 20451-20456). These two proteins co-purify in a molar ratio of 2:1 (175:300), and both proteins are active, able to bind HA after SDS-PAGE, electrotransfer, and renaturation. After reduction, the 175-kDa protein migrates as a approximately 185-kDa protein and is not able to bind HA. The 300-kDa HA receptor is a complex of three disulfide-bonded subunits that migrate in reducing SDS-PAGE at approximately 260, 230, and 97 kDa. These proteins designated, respectively, the alpha, beta, and gamma subunits are present in a molar ratio of 1:1:1 and are also unable to bind HA when reduced. The 175-kDa protein and all three subunits of the 300-kDa species contain N-linked oligosaccharides, as indicated by increased migration in SDS-PAGE after treatment with N-glycosidase F. Both of the deglycosylated, nonreduced HA receptor proteins still bind HA.
Animals↗
PCB congener 126-induced ultrastructural alterations in the rat liver: a stereological study.
Hepatocyte cytoplasmic alterations were morphometrically determined in male and female Sprague-Dawley rats fed PCB congener 126 (3,3',4,4',5-pentachlorobiphenyl) in concentrations of 0.1, 1.0, 10, 100 ppb or corn oil in diets for 13 weeks. A dose-dependent increase (P < 0.05) in the volume fraction of smooth endoplasmic reticulum (SER) and mitochondria was measured in the hepatocytes of the females. However, these cells of the male rats contained a significantly greater baseline volume fraction of SER compared to that in the females. Statistical differences were not detected in the volume fractions of rough endoplasmic reticulum, peroxisomes or lipid droplets of the hepatocytes in either the males or females. We conclude the increase in mitochondrial volume was a necessary cellular adaptation to meet the heightened energy demands by the SER to produce the necessary enzymes to detoxify the PCB. Morphometric analysis rather than a descriptive methodology allowed for a more accurate determination of the liver pathology induced by PCB 126.
Animals↗
Unmasking of a novel potassium current in Drosophila by a mutation and drugs.
The delayed rectifier potassium current plays a critical role in cellular physiology. This current (I(K)) in Drosophila larvae is believed to be a single current. However, a likely null mutation in the Shab K(+) channel gene (Shab(3)) reduces I(K) but does not eliminate it. This raises a question as to whether or not the entire I(K) passes through channels encoded by one gene. Similarly, an incomplete blockade of I(K) by high concentrations of quinidine, a selective I(K) blocker, raises a question as to whether I(K) consists of two components that are differentially sensitive to quinidine. We have addressed these questions by a combined use of genetics, pharmacology, and physiology. The current component removed by the Shab(3) mutation differed from the remaining component in activation kinetics, inactivation kinetics, threshold of activation, and voltage dependence. The two components showed strong differences in sensitivity to quinidine. Physiological properties of the current component removed by the Shab(3) mutation were similar to those of the quinidine-sensitive fraction of I(K). Complementary to this, properties of the current component remaining in the Shab(3) mutant muscles were similar to those of the quinidine-resistant fraction of I(K). These observations strongly suggest that, in contrast to the current belief, I(K) consists of two components in Drosophila, which are genetically, pharmacologically, and physiologically distinct. These components are being called I(KS) and I(KF). I(KS) is carried via Shab-encoded channels. I(KF) defines a new voltage-activated K(+) current in Drosophila.
4-Aminopyridine↗
Quantitative assessment of cervical spondylotic myelopathy by a simple walking test.
BACKGROUND: We developed a 30 m walking test as a quantifiable measure of severity of cervical spondylotic myelopathy (CSM), which will be of use in determining the effects of decompressive surgical treatment. METHODS: Preoperative measurements were made in 41 patients with CSM of 30 m walking times, number of steps taken over this distance, myelopathy disability index (MDI), and Nurick scores. The walking factors were compared with a similar number of age-matched and sex-matched controls. The individuals in the study were patients with CSM and no other relevant pathology consecutively referred for decompressive surgery to the National Hospital for Neurology and Neurosurgery. FINDINGS: Both walking time and the number of steps taken were significantly worse in pre-operative patients than in controls. The walking data were highly reproducible over three trials. Postoperatively, there was a significant improvement in walking time (p=0.0018) and number of steps taken (p=5.87 x 10(-6)). Only two of 41 patients were worse postoperatively. There was also a significant improvement in MDI (two-tailed Wilcoxon, related samples; p<0.0001) and Nurick scores (two-tailed Wilcoxon p<0.0001) postoperatively. The preoperative and postoperative walking scores were significantly and equally correlated with the MDI and Nurick scores. INTERPRETATION: Timed walks are an easily performed, quantitative, and valid means of assessing CSM and the effects of surgery.
Adult↗
Inhibition of tumor necrosis factor alpha-stimulated aromatase activity by microtubule-stabilizing agents, paclitaxel and 2-methoxyestradiol.
The aromatase enzyme, which converts androstenedione to oestrone, regulates the availability of oestrogen to support the growth of hormone-dependent breast tumours. Cytokines, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNFalpha) or prostaglandin E(2) (PGE(2)), can stimulate aromatase activity. These factors may originate from cells of the immune system that infiltrate breast tumours. Paclitaxel, which is used in the treatment of breast cancer, stabilizes microtubules and has previously been shown to rapidly down-regulate TNF-receptors on human macrophages. The endogenous oestrogen metabolite, 2-methoxyestradiol (2-meOE2), also acts to stabilize microtubules. In this study, we have examined the ability of paclitaxel or 2-meOE2 to antagonise TNFalpha-stimulated aromatase activity in stromal fibroblasts derived from normal or malignant breast tissues. Paclitaxel inhibited basal and TNFalpha-stimulated aromatase activities by 88% and 91% respectively. 2-MeOE2 also reduced basal and TNFalpha-stimulated aromatase activities by 46% and 56% respectively. Both paclitaxel and 2-meOE2 also inhibited stimulation of aromatase activity by IL-6 plus its soluble receptor and PGE(2). The 16alpha-hydroxylated derivative of 2-meoE2 and 2-meOE3, which does not bind to microtubules, was less effective at inhibiting TNFalpha-stimulated aromatase activity. Increased 2-hydroxylation of oestrogens, and subsequent formation of their 2-methoxy derivatives, may be associated with a reduced risk of breast cancer. It is possible that the pathway of oestrogen metabolism may influence the ability of stromal cells to respond to cytokine stimulation.
2-Methoxyestradiol↗
A case control study and one year follow-up of registered epilepsy cases in a resettlement colony of North India, a developing tropical country.
A population-based case control study and monthly follow-up of 121 registered epilepsy cases was conducted during 1995-1997 in a resettlement colony of Chandigarh, India. History of various tentative risk factors, e.g. trauma, febrile seizures, family history of seizures, alcohol intake and other possible causes was elicited. An age- and sex-matched control was selected from the neighbouring families for each case. A discordant pair analysis was done for matched case/controls. History of head injury, febrile seizures and developmental delay was observed exclusively in cases (none present in controls). Odds for epilepsy were higher among people who had positive family history (O.R.= 2.1, chi2 = 5.5, C.I. = 1.1-4.3). All cases were followed up and interviewed for history of seizures and drug intake. Fourteen cases could not be followed up completely. Ninety-four (88%) of the remaining 107 cases did not have any seizures during the follow-up. Of them, 70 (75%) patients were not on medication, 13 patients were on phenytoin and 11 patients received phenobarbitone. Thirteen cases reported seizures during the follow-up. Four patients out of the latter had mental retardation and were not on medication. Cumulative incidence of epilepsy was estimated to be 0.6/1000 person-year exposure.
Adolescent↗
Transcription of the mouse RFC-1 gene encoding a folate transporter. Multiplicity and properties of promoters with minimum requirements for their basal activity.
The mouse RFC-1 gene incorporates alternates of exon 1 (exon 1 and 1a) which encode different 5' ends. This finding, and the elucidation of a promoter-like sequence immediately upstream of these alternates of exon 1, suggest that two separate promoters drive transcription of this gene. The regions upstream of either exon 1 or exon 1a inserted in pGL3 will separately promote transcription in NIH3T3 cells of the luciferase reporter gene, with the region upstream of exon 1 having the strongest promoter activity. Tissue-specific expression in the form of RFC-1 mRNA splice variants reflects the separate action of each promoter. In the most upstream portion of the region proximal to exon 1a, elements were revealed that enhance transcription along with a more downstream element that suppresses transcription in NIH3T3 cells. Three Sp1 sites closely proximal to exon 1a within a region spanning 123 nucleotides were shown to be transcriptionally active by site-directed mutagenesis, with the middle SP1 site found to be the most important of the three in maintaining basal promoter activity. A poly (GT) 21 di-nucleotide repetitive element upstream of these Sp1 sites was found in a region which, when deleted, increased transcription. In the region upstream of exon 1, two elements were elucidated which enhanced transcription. Site-directed mutagenesis showed that two adjacent SP1 sites proximal to exon 1 were equally important in sustaining basal promoter activity. The role of each Sp1 site in maintaining basal activity of each promoter was confirmed by DNase I footprinting analysis. In addition, a binding site of unknown significance was identified by this analysis within the upstream promoter sequence between the two Sp1 sites proximal to exon 1a. These data show that both promoters regulating expression of the RFC-1 gene utilize closely spaced Sp1 sites in tandem to sustain basal transcription, at least in NIH3T3 cells, in a manner characteristic of TATA-less promoters.
3T3 Cells↗
Heparin and heparan sulphate protect basic fibroblast growth factor from non-enzymic glycosylation.
Non-enzymic glycosylation of basic fibroblast growth factor (bFGF, FGF-2) has recently been demonstrated to decrease the mitogenic activity of intracellular bFGF. Loss of this bioactivity has been implicated in impaired wound healing and microangiopathies of diabetes mellitus. In addition to intracellular localization, bFGF is also widely distributed in the extracellular matrix, primarily bound to heparan sulphate proteoglycans (HSPGs). Nonetheless, it is not clear if non-enzymic glycosylation similarly inactivates matrix-bound bFGF. To investigate this, we measured the effect of non-enzymic glycosylation on bFGF bound to heparin, heparan sulphate and related compounds. Incubation of bFGF with the glycosylating agents glyceraldehyde 3-phosphate (G3P; 25 mM) or fructose (250 mM) resulted in loss of 90% and 40% of the mitogenic activity of bFGF respectively. Treatment with G3P and fructose also decreased the binding of bFGF to a heparin column. If heparin was added to bFGF prior to non-enzymic glycosylation, the mitogenic activity and heparin affinity of bFGF were nearly completely preserved. A similar protective effect was demonstrated by heparan sulphate, low-molecular-mass heparin and the polysaccharide dextran sulphate, but not by chondroitin sulphate. Whereas non-enzymic glycosylation of bFGF with G3P impaired its ability to stimulate c-myc mRNA expression in fibroblasts, no such impairment was noticeable when bFGF was glycosylated in the presence of heparin. Taken together, these results suggest that HSPG-bound bFGF is resistant to non-enzymic glycosylation-induced loss of activity. Therefore, alteration of this pool probably does not contribute to impaired wound healing seen in diabetes mellitus.
Animals↗