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Biomedical subjects

M Ali

Publications and source records attributed to M Ali.

At least 289 records · Page 16Linked to original sources
PubMed1989

Glucocorticoid regulation of chloroquine nonsensitive insulin degradation in cultured fetal rat hepatocytes.

The influence of cortisol and other culture conditions on insulin degradation by the chloroquine-sensitive pathway and the chloroquine-nonsensitive pathway (CNP) was investigated in fetal rat hepatocytes during 3 days of culture. The proportions of the chloroquine nonsensitive release of 125I-insulin degradation products into the conditioned medium/h increased from the 1st to the 3rd day of culture, i.e. from 19 to 50% by cells grown in the presence of cortisol and from 17 to 82% by those grown in the absence of cortisol. Replacement of the conditioned medium with the respective fresh medium dramatically enhanced cellular insulin degradation by CNP, i.e. from 22 to 58%, and 19 to 85% in cells grown for 2 days in the presence and absence of cortisol, respectively. Thus, the conditioned medium contained some factor(s) that inhibited CNP. Therefore, we used the inhibited insulin and alpha-casein degradation by papain in vitro as an assay to investigate the nature of the putative anti-(insulin) protease. Cycloheximide completely prevented the appearance of anti-papain activity in the medium. Conditioned medium obtained from cells grown in the presence of cortisol contained about 2-fold more anti-papain activity than the medium that was obtained in the absence of the steroid. The release of anti-papain activity also declined with time from 1 to 3 days of culture and showed an inverse relationship with the magnitude of cellular insulin degradation by CNP. The inhibition of papain-mediated insulin degradation by the anti-(insulin) protease was noncompetitive. The anti-(insulin) protease was nondialyzable (up to the 10-kDa exclusion limit) and inactivated by heat treatment at 50 degrees C for 30 min. These results suggest that fetal hepatocytes synthesize and secrete a glucocorticoid-regulated heat-labile low molecular mass (less than 25 kDa) anti-(insulin) protease, which may contribute to the suppression of insulin degradation caused by the enzymes involved in CNP.

Animals↗
PubMed1989

Regulation of glucocorticoid receptor protein and mRNA levels.

The level of steroid receptors in target cells affects the responsiveness of the cell to the hormone. In mouse AtT-20 cells, it has been shown that chronic glucocorticoid treatment causes a down-regulation of glucocorticoid receptor (GR) levels (F. Svec and M. Rudis, J. Biol. Chem., 256:5984-5987, 1981). The current study shows that chronic hormone treatment reduces the amount of GR mRNA to about 50% of that in untreated cells. A combined treatment of the cells with an inhibitor of RNA transcription and the glucocorticoid hormone causes a more rapid decrease in steady-state GR mRNA levels than either agent alone. This suggests that glucocorticoids regulate the expression of the GR gene posttranscriptionally, perhaps via destabilization of the GR mRNA. An additional transcriptional regulation by the steroid hormone is not ruled out by this observation. It was also found that heat shocking a variety of cell types at 42 degrees C not only causes an induction of heat shock proteins but also results in a dramatic decrease in the level of glucocorticoid-binding activity. GR labeled with a covalent ligand (dexamethasone 21-mesylate) was also reduced by heat shock, implying that heat shock caused an increased degradation in the GR protein itself. Finally, in vitro studies show that the GR is degraded in an ATP- and tRNA-dependent fashion in rabbit reticulocyte lysate. It therefore seems likely that the GR is degraded by the ubiquitin-dependent proteolytic pathway. Because ubiquitin is itself a heat shock protein, this may be the reason that the GR is rapidly degraded in heat-shocked cells. These studies point to possible mechanisms whereby the responsiveness of the cell to steroid hormones is altered by the regulation of the steroid receptor protein and mRNA levels.

Animals↗
PubMed1989

Effect of consumption of green and black tea on the level of various enzymes in rats.

Drinking of both green and black tea as the only liquid ingested resulted in significant decreases in the activity of transketolase in whole blood of rats both before and after the in vitro addition of thiamin diphosphate. Liver transketolase activity was decreased only by green tea. Mucosal transketolase activity was not affected by either type of tea. The activity of lactate dehydrogenase (LDH) was not affected by either type of tea, while whole blood LDH was decreased by both green and black tea. Neither tea had any affect on mucosal alkaline phosphatase, but thiamin diphosphatase activity was decreased by both teas. An increase in liver total thiamin resulted from the drinking of both types of tea.

Alkaline Phosphatase↗
PubMed1989

Histopathological observations on organs from rabbits injected with the skin toxin of the Arabian Gulf catfish (Arius bilineatus, Valenciennes).

Toxicity of soluble protein extracts (skin toxin) from epidermal skin secretions of the catfish, Arius bilineatus (previously identified as Arius thalassinus), was examined in rabbits. Intravenous injections containing doses as low as 2 mg protein/kg body weight caused mortality in most animals tested. Histopathological examination of lung, heart, liver and kidney tissues of rabbits injected with skin toxin indicated that the lungs and livers of treated animals were adversely affected, while heart and kidney tissues appeared to be normal. Lethality of skin toxin was prevented by pretreatment of the rabbits with indomethacin. Histopathological examination of lung and liver tissues of indomethacin pretreated animals showed a significant reduction in the damage observed after injection of skin toxin.

Animals↗
PubMed1989

Domain structure of herpes simplex virus 1 glycoprotein B: neutralizing epitopes map in regions of continuous and discontinuous residues.

Herpes simplex virus 1 (HSV-1) glycoprotein B (gB) is a multifunctional glycoprotein required for infectivity; it is thought to promote fusion of the viral envelope with the cell membrane and entry of virions into cells. To map the antigenic and functional domains on gB, we constructed amino terminal derivatives lacking the entire carboxyl terminus and internal deletion mutants lacking defined regions of the extracellular and transmembrane domains. Transient expression of the mutants in COS-1 cells revealed that the amino terminal derivatives were released into the medium whereas those with deletions in the extracellular domain were mostly retained within the transfected cells. Analysis of intact gB and the amino terminal derivatives showed that the intact molecule formed dimers whereas the mutant derivatives did not. Reactions of the derivatives with a panel of well-characterized monoclonal antibodies to gB showed that the neutralizing epitopes cluster in two domains. The first maps in the amino terminal 190 residues and contains seven continuous epitopes, five of which are HSV-1-specific. Reactions of antibodies with a set of oligopeptides fine-mapped the epitopes between residues 1 and 47. The second domain is composed of discontinuous epitopes and was expressed by amino terminal derivatives that were at least 457 residues in length or longer. Eleven epitopes map in this region, including those of four potent neutralizing antibodies whose cognitive sites mapped between residues 273 and 298 in mapping studies using antibody-resistant mutants. Results of the present study indicate that the cognitive sites of these antibodies are assembled into the discontinuous domain by juxtaposing residues from the amino-terminal half of gB monomers.

Amino Acid Sequence↗
PubMed1989

Effect of paraquat administered intraperitoneally on the nonpolar lipids of rabbits.

Rabbits were injected intraperitoneally with 3, 6, or 12 mg of paraquat/kg/day for a period of 3, 7, or 14 days. Rabbits receiving 3 or 6 mg of paraquat/kg/day showed a significant loss of body weight at 7 days of the treatment. Liver, kidney, heart, and lungs demonstrated a significant decrease in their weights in the first 3 days of paraquat treatment. A decrease in total lipids, total triglycerides, and total cholesterol of both liver and kidney was observed. This decrease was accompanied by a significant increase in plasma total triglycerides and total cholesterol at 7 days of paraquat treatment. The ratio of cholesterol to cholesterol esters in liver decreased after 3 days of paraquat treatment after which it showed a consistent increase until the 14th day of the paraquat treatment. In kidney, this ratio increased for up to 7 days of paraquat treatment followed by a decrease at the 14th day. These results indicate, contrary to earlier reports, that rabbits are susceptible to paraquat toxicity.

Animals↗
PubMed1989

Comparative biochemical and pharmacological properties of epidermal secretions from Ariid catfish of the Arabian Gulf.

1. Comparative biochemical and pharmacological studies on epidermal secretions from three species of Ariid catfish were carried out to determine whether they share common properties. 2. Protein compositions are generally similar, but show some differences in size and numbers of proteins. 3. Lipids also differ. However, seasonal and dietary changes in lipid compositions exceed the differences among species. 4. Enzymes in the secretions appear common to each fish species, though some differences are noted in relative activities. 5. Toxicity responses of rabbits to injections with secretions from each of the catfish species indicated that two were lethal, with similar lethal dose levels when injected intravenously. 6. Secretions from all three catfish induced changes in plasma enzyme levels indicative of heart and liver damage, and also induced changes in blood glucose and cholesterol levels.

Animals↗
PubMed1989

Toxicity of echinulin from Aspergillus chevalieri in rabbits.

Rabbits were injected intraperitoneally with purified echinulin, a product of Aspergillus chevalieri. After 2 h, the rabbits were bled and enzyme analyses were carried out on the supernates of liver homogenates and citrated plasma. Elevated levels of total plasma lactate dehydrogenase, cardiac derived isozyme, glutamic-oxaloacetic and glutamic-pyruvic transaminase activities in animals receiving toxin were observed. These levels were statistically significant compared to the vehicle control. A significant increase in liver lactate dehydrogenase of toxin-treated rabbits was also observed. Light-microscopic examination of lung and liver showed a significant degree of damage. The increase in plasma enzyme levels is indicative of damage to these organs.

Alkaloids↗
PubMed1989

Acute and chronic Legionnaires' disease and co-existent tuberculosis: a trial of erythromycin.

To assess the prevalence of Legionnaires' disease, 115 patients with 'difficult-to-treat' chest infections were screened for Legionnella pneumophila. The results were positive in 10 (37%) of 27 patients with pulmonary tuberculosis, 15 (22%) of 68 with a recent onset acute respiratory infection, and 7 (35%) of 20 patients with history of a chronic respiratory infection. These 32 patients were enrolled in an open therapeutic trial of erythromycin. Less severe cases (17 of 32) received erythromycin stearate orally (500 mg 4-times daily) for up to 28 days, while severe cases were treated for the first few days with intravenous erythromycin lactobionate (4 g/day). Weekly chest X-ray examinations revealed prompt resolution. Most patients had no signs and symptoms detectable after 7 days, and none persisted up to 28 days. There were no therapeutic failures and microbiological tests on Day 28 were negative for Legionella pneumophila. It is suggested that the possibility of co-existing legionellosis should be considered in all patients with difficult to treat acute and chronic chest infections, particularly in developing countries where tuberculosis is very common, and treatment instituted or supplemented with erythromycin as the drug of choice.

Acute Disease↗
PubMed1989

Legionella pneumophila: laboratory diagnosis in developing countries like Pakistan.

Three hundred random sputum samples were collected for analysis from cases of mild to severe respiratory infections and screened for Legionella pneumophila by both the culture method and also the direct fluorescent antigen test. In one third of the cases, blood specimen was also collected and screened for Legionella serum antibodies. With the direct fluorescent test it was possible to identify Legionella in 9% of the samples while the culture gave positive results in 4.3% of cases. Diagnostic antibody titers (1:256) were obtained in 12% of the samples while another 12% cases showed serum antibody titers of 1:64 to 1:128. In Pakistan where antibiotics are used extensively, the direct fluorescent examination of sputum samples gives more accurate diagnosis of Legionella cases than the culture method.

Colony Count, Microbial↗
PubMed1989

Glycogenolytic responsiveness to glucagon, epinephrine, vasopressin and angiotensin II in the liver of developing hypothyroid rats. A comparative study of in vitro hormonal binding and in vivo biological response.

Both dose-response curves and time-courses of plasma glucose levels after single maximal doses showed that in vivo glycogenolytic responsiveness to glucagon and epinephrine was significantly higher in developing hypothyroid rats, whereas it remained unchanged after vasopressin and angiotensin II injections. In contrast with the decreased basal activity of phosphorylase(a), the glucagon-stimulated activity increased in hypothyroid rats, whereas it was only slightly modified under vasopressin stimulation. Daily thyroxine treatment abolished these abnormalities. Thus, there is a close correlation between glucose output and enzyme activation. The maximal binding capacity of [3H]vasopressin and [125I]glucagon was significantly decreased in hypothyroid rats, without changes in the apparent dissociation constant of hormone from its specific receptor. Daily thyroxine treatment also abolished this deficit, which moreover appeared to be independent of possible changes in plasma hormone levels. With respect to glucagon action, neither basal nor Gpp(NH)p-stimulated adenylate cyclase activities were affected in hypothyroid rats. Glucagon-sensitive adenylate cyclase activity and the apparent activation constant appeared to be unaffected. The apparent discrepancy between the results obtained from in vivo and in vitro experiments is discussed on the basis of different membrane transducing phenomena and related intracellular mechanisms underlying the biological response to hormonal stimulation.

Adenylyl Cyclases↗
PubMed1988

Impact of B subunit killed whole-cell and killed whole-cell-only oral vaccines against cholera upon treated diarrhoeal illness and mortality in an area endemic for cholera.

The impact of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind trial in rural Bangladesh. 62,285 children aged 2-15 years and women aged over 15 ingested three doses of one of the vaccines or placebo. During the first year of follow-up there was a 26% reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22% reduction in the WC group. The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48% in the BS-WC group and 33% in the WC group. Overall mortality rates were 26% lower in the BS-WC group and 23% lower in the WC group during the first year, and reductions of mortality were observed only in women vaccinated at ages over 15 years. However, no differences in cumulative mortality were evident at the end of the second year of surveillance.

Administration, Oral↗
PubMed1988

Discontinuation of breast-feeding during episodes of diarrhoea in rural Bangladeshi children.

Discontinuation of breast-feeding during an episode of childhood diarrhoea is widely regarded as a common, high-risk practice in the developing world. We studied cessation of breast-feeding in a rural Bangladeshi population under comprehensive surveillance for medically treated diarrhoeal episodes. Among 2129 episodes in children aged under 36 months and breast-fed before the onset of diarrhoea, there were only 33 (2%) in whom breast-feeding had stopped before presentation for care. Children in whom breast-feeding had stopped (cases) differed little from those in whom it had not (controls) in respect to exclusive vs partial breast-feeding, age, gender, or several maternal characteristics (maternal age, education, and recent maternal diarrhoeal illness). In contrast, cases were more likely to have presented with clinically severe illness or to have died within 30 d of presentation (odds ratio = 2.20, P less than 0.05). We conclude that discontinuation of breast-feeding during diarrhoea is an infrequent phenomenon in this population. However, the association of cessation of breast-feeding with severe clinical outcomes may be of considerable importance, particularly in countries where discontinuation of breast-feeding is more common.

Bangladesh↗