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Biomedical subjects

F Ahmad

Publications and source records attributed to F Ahmad.

At least 55 records · Page 3Linked to original sources
PubMed2000

A comparative study of omega-3-fatty acids obtained from marine fish and bezafibrate alone and in combination as hypolipidemic agents.

The fish oil and its constituents have been studied in detail with special reference to ailments. The discovery of omega-3 fatty acids led to a detailed investigation about its effect and role as anti-cholesterolemic agents. The effect of fish oil alone and in combination with acid derivatives was found to be a potent cholesterol and triglycerides lowering agent. Comparative studies of fish oils and bezafibrate led to the formulation of new therapeutic combination having lesser side effects and toxicity.

Journal Article↗
PubMed1999

Prevalence of self-reported cervical cancer screening and impact on cervical cancer mortality in Austria.

Pap smear screening was introduced in Austria in the late 1960's and was recommended annually for all women older than 20 years ever since. This is an opportunistic screening. The evaluation has to rely on population based data (mortality, stage distribution, screening prevalence). In a representative cross-sectional study (women aged 20-69 years, n = 933, conducted in 1995), 76% reported at least one Pap screening during their life; the highest prevalence (88%) was reported by women aged 50-59 years, the lowest prevalence (65%) by women aged 60-69 years. Forty-eight per cent of all women reported that they had undergone screening at least 4 times (40-49 years: 57%, 20-29 years: 34%). Between 1980 and 1996, mortality due to cancer of the uterus, part unspecified (ICD-9: 179), decreased by 54% (P = 0.0001) and that of cancer of the cervix (ICD-9: 180) by 44% (P = 0.0001). Since 1980, age-specific incidence rates of invasive disease decreased (P = 0.0001) in all 10-year age groups (20-29 years: -59%, 30-39 years: -48%, 40-49 years: -34%, 50-59 years: -62%, 60-69 years: -59%). The incidence of preinvasive disease increased significantly (P = 0.001) in the age groups 20-29 years by 30% and 30-39 years by 45%, respectively. No significant changes are observed in other age groups. Opportunistic screening has reduced mortality from cervical cancer and particularly limited the increase among younger women, but the high proportion of cancer deaths from uterine cancer, in part unspecified, obscures the actual trend. We estimate that the true mortality from cervical cancer has been nearly halved between 1980 and 1996. Most of this reduction must be attributed to the screening activities in the 1970's and we expect a further decrease as a result of the expanded screening activities in the 1980's.

Adult↗
PubMed1999

IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells.

In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with phosphatidylinositol 3-kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase inhibitor), and wortmannin (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS-2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation of PDE4 by IL-3. These results suggested that IL-4-induced activation of PDE3 and PDE4 was downstream of IRS-2/PI3-K, not STAT6, and that inhibition of tyrosine phosphorylation of IRS molecules might be one mechnism whereby TNF-alpha could selectively regulate activities of cytokines that utilized IRS proteins as signal transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen-activated protein (MAP) kinase and protein kinase B via PI3-K signals; PMA activated only MAP kinase via PKC signals. The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL-3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced activation of PDE3. In FDCP2 cells transfected with constitutively activated MEK, MAP kinase and PDE4, not PDE3, were activated. Thus, in FDCP2 cells, PDE4 can be activated by overlapping MAP kinase-dependent pathways involving PI3-K (IL-4, IL-3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-2/PI3-K dependent).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Protein stability: functional dependence of denaturational Gibbs energy on urea concentration.

Determination of protein stability (DeltaGD0) from the conformational transition curve induced by a chemical denaturant is problematic; for different values of DeltaGD0, the value of the Gibbs energy change on denaturation (DeltaGD) in the absence of the denaturant are obtained when different extrapolation methods are used to analyze the same set of (DeltaGD, denaturant concentration) data [Pace, C. N. (1986) Methods Enzymol. 131, 266-280]. We propose a practical solution to this problem and use it to test the dependence of DeltaGD of lysozyme, ribonuclease-A, and cytochrome-c on [urea], the molar urea concentration. This method employs (i) measurements of the urea-induced denaturation in the presence of different guanidine hydrochloride (GdnHCl) concentrations which by themselves disrupt the native state of the protein at the same temperature and pH at which denaturations by urea and GdnHCl have been measured; (ii) estimation of DeltaGDcor, the value of DeltaGD corrected for the effect of GdnHCl on the urea-induced denaturation using the relation (DeltaGDcor = DeltaGD + mg [GdnHCl] = DeltaGD0 - mu [urea], where mg and mu are the dependencies of DeltaGD on [GdnHCl] and [urea], respectively) whose parameters are all determined from experimental denaturation data; and (iii) mapping of DeltaGDcor onto the DeltaGD versus [urea] plot obtained in the absence of GdnHCl. Our results convincingly show that (i) [urea] dependence of DeltaGD of each protein is linear over the full concentration range; (ii) the effect of urea and GdnHCl on protein denaturation is additive; and (iii) KCl affects the urea-induced denaturation if the native protein contains charge-charge interaction and/or anion binding site, in a manner which is consistent with the crystal structure data.

Animals↗
PubMed1999

The burden of cancer in Austria.

The aim of this study was to assess the overall progress against cancer in Austria by analysing changes in age-adjusted mortality rates from 1970 to 1996. For the years 1970 to 1996, age-adjusted rates for all malignant neoplasms and for selected sites were calculated for men and women, according to year, age and sex. The number of cancer deaths were obtained from the Austrian Central Statistical Office--age-adjusted mortality rates of all malignant neoplasms decreased in men between 1971 and 1996 by 13% (from 289.1 to 251.4 deaths per 100,000), and in women between 1970 and 1996 by 19.1% (from 276.6 to 223.7 deaths per 100,000). Among older people (> or = 55 years) the mortality decreased by 13% in men and by 17% in women; among younger people (< 55 years) by 12% and 30%, respectively. The decrease in total cancer mortality is promoted by three tumour sites (the leading causes of cancer deaths in 1970). In both sexes, the decrease of stomach cancer mortality had the major impact, followed by colorectal cancer in women and by lung cancer in men. The observed changes in mortality are primarily related to changing incidence and early detection, rather than improvements in treatment. Unfortunately, there is evidence that prevention is losing ground in Austria. The implementation of the well-established knowledge of cancer prevention and the strengthening of preventative research is urgently needed.

Adolescent↗
PubMed1998

Role of non-compatible osmolytes in the stabilization of proteins during heat stress.

This study is a systematic attempt to understand the roles of non-compatible osmolytes, i.e. solutes that have inhibitory effects on enzymes, in the stabilization of proteins against denaturing stress. Thermal denaturation of RNase A, holo-alpha-lactalbumin, apo-alpha-lactalbumin, lysozyme and metmyoglobin in the absence and presence of various concentrations of free basic amino acids was studied by observing changes in the absorption coefficients of these proteins. It has been observed that arginine and histidine destabilize all proteins in terms of the midpoint of the transition curve and Gibbs energy change on denaturation. Study of the heat-induced denaturation of the proteins in the presence of various concentrations of arginine at different pH values demonstrated that arginine binds to the denatured molecules. In contrast with the effect of arginine and histidine on protein stability, it was observed that the effect of lysine on proteins stability is unpredictable, i.e. it may have a stabilizing effect, no effect or a destabilizing effect on proteins during denaturing stress. The results of this study are considered from an evolutionary perspective.

Amino Acids↗
PubMed1998

Phosphorylation and activation of hormone-sensitive adipocyte phosphodiesterase type 3B.

Phosphodiesterases (PDEs) include a large group of structurally related enzymes that belong to at least seven related gene families (PDEs 1-7) that differ in their primary structure, affinity for cAMP and cGMP, response to specific effectors, sensitivity to specific inhibitors, and regulatory mechanism. One characteristic of PDE3s involves their phosphorylation and activation in response to insulin as well as to agents that increase cAMP in adipocytes, hepatocytes, and platelets and in response to insulin-like growth factor 1 in pancreatic beta cells. In adipocytes, activation of the membrane-associated PDE3B is the major mechanism whereby insulin antagonizes catecholamine-induced lipolysis. PDE3B activation results in increased degradation of cAMP and, thereby, a lowering of the activity of cAMP-dependent protein kinase (PKA). The reduced activity of PKA leads to a net dephosphorylation and decreased activity of hormone-sensitive lipase and reduced hydrolysis of triglycerides. Activation of the rat adipocyte PDE3B by insulin is associated with phosphorylation of serine-302. The mechanism whereby insulin stimulation leads to phosphorylation/activation of PDE3B is only partly understood. In rat adipocytes, lipolytic hormones and other agents that increase cAMP, including isoproterenol, also induce rapid phosphorylation, presumably catalyzed by PKA, of serine-302 of PDE3B. The phosphorylation is associated with activation of the enzyme, most likely representing "feedback" regulation of cAMP, presumably allowing close coupling of the regulation of steady-state concentrations of both cAMP and PKA and, thereby, control of lipolysis. In the review we describe methods and strategies used in the authors' laboratories to study phosphorylation and activation of PDE3B in adipocytes and in vitro.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Hepatic encephalopathy and role of antibenzodiazepines.

The majority of pharmacological agents are designed to accomplish a specific effect based on the established mechanisms of a disease. However, there are a few examples in which investigation of a pharmacological action has led to a previously unknown mechanism, i. e. the drug effect was observed initially before its mechanism became known. For example, the opiates had been in use for their analgesic effect for centuries before the question of endogenous substances that might explain the presence of opiate binding sites in the central nervous system (CNS) was raised, leading to the discovery of the opioids. A somewhat analogous development has occurred in another investigative arena, the observation that the administration of the benzodiazepine antagonist, flumazenil, has reversed the encephalopathy of hepatic failure. This has refocused research to discover whether one or more endogenous substances that bind to the benzodiazepine receptor in the CNS are responsible for the inhibition of CNS function of advanced liver failure. The investigative impetus was initiated by observations that patients with liver failure were highly vulnerable to benzodiazepines; therapeutic dosages precipitated coma or near-coma, and this effect was prolonged. The question was raised whether any given patient presenting with a coma-like state associated with advanced liver dysfunction might have received a benzodiazepine in the recent past, under circumstances overlooked or not recorded, that might be a contributing factor to the patient's condition. This led to testing the effects of the antagonist, with transitory success in arousing patients or improving their level of stupor. Further inquiry revealed that this improvement in mental function occurred in the absence of prior exposure to benzodiazepines. There followed a search for endogenous substances capable of binding to the benzodiazepine receptor, with CNS inhibitory effects. These investigations have resulted in the identification of several substances that may play a role in encephalopathy and can be displaced from the CNS receptor by properly designed antagonists-an ongoing investigative effort.

Flumazenil↗
PubMed1998

Energy provision from glycogen, glucose, and fatty acids on adrenergic stimulation of isolated working rat hearts.

We postulated that glycogen is a significant energy substrate compared with fatty acids and glucose in response to adrenergic stimulation of working rat hearts. Oxidation rates were determined at 1-min intervals by release of 3H2O from [9,10-(3)H]oleate (0.4 mM, 1% albumin) and 14CO2 from exogenous [U-14C]glucose (5 mM) or, by a pulse-chase method, from [14C]glycogen. We estimated the 14C enrichment of glycogen metabolized at each time point to determine true rates of glycogen use. Based on the pattern of glycogen enrichment over time, glycogenolysis did not exhibit a high degree of preference for newly synthesized glycogen. Epinephrine (1 microM) increased contractile performance 86% but did not stimulate oleate oxidation. The increased energy demand was supplied by carbohydrates, initially by a burst of glycogenolysis (contributing 35% to total ATP synthesis for 5 min) and followed by delayed increase in the use of exogenous glucose (eventually contributing 29% to ATP synthesis). On the basis of the release of 14CO2 and [14C]lactate specifically from glucose or glycogen, we found that a larger portion of glycogen was oxidized compared with exogenous glucose, augmenting the yield of ATP from glycogen. Thus the heart responds to an acute increase in energy demand by selective oxidation of glycogen.

Adenosine Triphosphate↗
PubMed1998

Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases.

Protein-tyrosine phosphatases (PTPases) have been implicated in the physiological regulation of the insulin signalling pathway. In cellular and molecular studies, the transmembrane, receptor-type PTPase LAR and the intracellular, non-receptor enzyme PTP1B have been shown to have a direct impact on insulin action in intact cell models. Since insulin signalling can be enhanced by reducing the abundance or activity of specific PTPases, pharmaceutical agents directed at blocking the interaction between individual PTPases and the insulin receptor may have potential clinical relevance to the treatment of insulin-resistant states such as obesity and Type II diabetes mellitus.

Animals↗
PubMed1998

Electrophoretic analysis of polypeptides and glycopeptides of erythrocyte membrane sampled from rats simulating mild insulin dependent diabetes mellitus.

In order to understand the molecular mechanism of reduced life span of diabetic erythrocyte, polypeptides and glycopeptides were analyzed by disc gel preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis. An additional glycopeptide (244.5 kDa) and two additional polypeptides (39.81 and 144.5 kDa) were observed on glycopeptide and polypeptide gel profiles of mild insulin dependent diabetes mellitus (mIDDM) sample as compared to control. On the basis of molecular weight, their position on gel profile and their widely accepted nomenclature they were termed as glycosylated-ankyrin, membrane accreted glyceraldehyde-3-phosphate dehydrogenease (G 3-PD) and stress induced band 2.3 peptide. Earlier we have reported an increase in heterogeneity associated with increase in the population of aged fragile cells having altered membrane bound cation dependent ATPases, cytosolic dehydrogenase and hexokinase activities of mIDDM simulating rat erythrocyte sample. Significance of above observation in view of our earlier observation is discussed to explain the molecular mechanism of reduced life span of diabetic erythrocytes.

Animals↗
PubMed1997

Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes.

Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase activity in the skeletal muscle particulate fraction and cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, and obese individuals with non-insulin-dependent diabetes. PTPase activities in subcellular fractions from the nondiabetic obese subjects were increased to 140-170% of the level in lean controls (P < 0.05). In contrast, PTPase activity in both fractions from the obese subjects with non-insulin-dependent diabetes was significantly decreased to 39% of the level in controls (P < 0.05). By immunoblot analysis, leukocyte antigen related (LAR) and protein-tyrosine phosphatase 1B had the greatest increase (threefold) in the particulate fraction from obese, nondiabetic subjects, and immunodepletion of this fraction using an affinity-purified antibody directed at the cytoplasmic domain of leukocyte antigen related normalized the PTPase activity when compared to the activity from control subjects. These findings provide further support for negative regulation of insulin action by specific PTPases in the pathogenesis of insulin resistance in human obesity, while other regulatory mechanisms may be operative in the diabetic state.

Adult↗
PubMed1997

Functional association between the insulin receptor and the transmembrane protein-tyrosine phosphatase LAR in intact cells.

The receptor-type protein-tyrosine phosphatase LAR (for leukocyte common antigen-related) has been implicated as a physiological regulator of the insulin receptor. To demonstrate a functional interaction between LAR and the insulin receptor, we incubated CHO cells overexpressing the human insulin receptor with an antibody to the extracellular domain of LAR and found a 47% decrease in insulin receptor autophosphorylation and kinase activity. A physical association between LAR and the insulin receptor was then shown by immunoprecipitation of LAR from cell lysates and immunoblotting with antibody to the insulin receptor, or vice versa. Up to 11.8% of the LAR protein in the lysates of CHO cells overexpressing both the insulin receptor and LAR co-immunoprecipitated with the insulin receptor. The LAR/insulin receptor association was related to the level of LAR or insulin receptor overexpression and was increased 6.5-fold by chemical cross-linking and 3.9-fold by treatment with insulin, suggesting that receptor activation influences the affinity of LAR for the insulin receptor. In insulin-stimulated rat liver, LAR was temporally enriched in endosomes with the insulin receptor, and incubation of endosomes with neutralizing LAR antibodies decreased insulin receptor dephosphorylation in situ by 28% (p = 0.01 versus control). These data provide more direct evidence of a role for LAR in the physiological regulation of insulin action at the receptor level.

Animals↗
PubMed1997

Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein-tyrosine phosphatases in adipose tissue.

Insulin resistance in adipose tissue in human obesity is associated with increased protein-tyrosine phosphatase (PTPase) activity and elevated levels of the PTPases leukocyte common antigen-related PTPase (LAR) and PTP1B. To determine whether the improved insulin sensitivity associated with weight loss in obese subjects is accompanied by reversible changes in PTPases, we obtained subcutaneous adipose tissue from seven obese subjects (mean body mass index [BMI], 40.4 kg/m2) before and after a loss of 10% of body weight and again after a 4-week maintenance period. Weight loss was accompanied by an 18.5% decrease in overall adipose tissue PTPase activity (P = .015) that was further reduced to 22.3% of the control value (P = .005) at the end of the maintenance period. By immunoblot analysis, the abundance of LAR was decreased by 21% (P = .04) and abundance of PTP1B was decreased by 40% (P < .004) after the initial weight loss, and the decreases persisted during the maintenance period. Enhanced insulin sensitivity following weight loss, evident from a 26% decrease in fasting insulin levels (P < .05), was also closely correlated with the reduction in the abundance of both LAR (R2 = .80, P < .01) and PTP1B (R2 = .64, P = .03). These results support the hypothesis that LAR and PTP1B may be reversibly involved in the pathogenesis of insulin resistance, and may be therapeutic targets in insulin-resistant states.

Adipocytes↗
PubMed1997

Sensitivity of Helicobacter pylori to metronidazole.

Gastric antral forceps biopsies taken at gastroscopy were cultured for Helicobacter pylori and tested for anti-microbial sensitivity. Using micro-aerophilic culture, and disc testing or E-testing, there was 98-100% sensitivity to amoxycillin, tetracycline, clarithromycin and erythromycin. However, there was apparent resistance to metronidazole in 19 of 102 samples (19%). When sensitivity by E-testing was performed with preliminary anaerobic culture for 24 h only two of 94 samples (2%) showed resistance. In 37 cultures both micro-aerophilic disc testing and anaerobic then micro-aerophilic E-testing were conducted. Eight cultures showed resistance upon disc testing (MIC > 5 mg/l) but all of these organisms were sensitive on E-testing (MIC 0.003-0.5 mg/l). Metronidazole may be used with confidence in eradication regimes.

Drug Resistance, Microbial↗
PubMed1997

Helicobacter pylori infection and upper gastrointestinal patholgy in a British immigrant Indian community.

OBJECTIVES: To assess the pattern of upper gastrointestinal pathology and the prevalence of Helicobacter pylori infection in the Southall Indian community. DESIGN: A prospective study of endoscopic findings in 124 Indian and 107 whites from the Southall area. In a separate study blood samples were taken from 100 Indian subjects presenting to a single general practitioner in Southall. METHODS: The presence of gastritis and H. pylori infection was assessed histologically in Indian and white patients undergoing endoscopy. Serum samples were analysed using a specific enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G. RESULTS: In the endoscopic study, Indian and white patients had the same rate of H. pylori infection (52% vs. 43%, respectively) (P= NS). The pattern of upper gastrointestinal pathology was similar in whites and Indians. In the general practice based study 41 subjects were H. pylori seropositive. Seropositivity increased with age (P<0.05). CONCLUSION: There is no excess of H. pylori-related pathology in Southall immigrant Indians. The similarity of upper gastrointestinal pathology in UK Indian and white patients presenting for endoscopy suggests that the high rates of duodenal ulceration, gastritis and H. pylori infection in India are environmentally rather than racially determined.

Adult↗