Search PubMed⌕ Search

Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 307 records · Page 17Linked to original sources
PubMed1995

Obstructed labour: the preventable factors.

Sixty-two cases of obstructed labour were reviewed during 6 months at a district head quarter hospital, Faisalabad to highlight the prevalence of obstructed labour and ascertain how to manage and possibly avoid this complication with special emphasis on preventable factors. There were 1584 deliveries during this period giving an incidence of obstructed labour as one in 25 deliveries. Five patients had rupture of uterus and there was one maternal death.

Bacterial Infections↗
PubMed1995

The effect of exercise conditioning, diet, and drug therapy on glycosylated hemoglobin levels in type 2 (NIDDM) diabetics.

The aim of this study was determine the effect of a 15-week individualized exercise conditioning program on glycosylated hemoglobin (HbAlc) levels on Type 2 diabetes. Thirty-nine participants were sedantary, Type 2 diabetics, on an oral hypo-glycemic drug and no specified diet regimen at study onset. Pre and post 15 weeks subjects underwent: maximal incremental exercise tests, blood analysis, body composition analysis. Twenty-one subjects were prescribed an individualized exercise program for 15 weeks. Significant differences were found in the exercise group after 15 weeks in: total body fat, trunk fat, peak oxygen consumption and MET values. Correlations existed in the exercise group between HbAlc, arm muscle area and leg lean mass. Sixty-two percent of this group showed a reduction in HbAlc values. For this group, dietary intakes of riboflavin and potassium maybe associated with HbAlc levels. Exercise in conjunction with oral drug therapy prescribed for the NIDDM individual did not directly modify HbAlc levels, but did result in favorable effects on blood lipid values, fitness levels, and body composition values.

Adult↗
PubMed1994

Synthesis and antitumor evaluation of bis[(pivaloyloxy)methyl] 2'-deoxy-5-fluorouridine 5'-monophosphate (FdUMP): a strategy to introduce nucleotides into cells.

The bis[(pivaloyloxy)methyl] [PIV2] derivative of 2'-deoxy-5- fluorouridine 5'-monophosphate (FdUMP) was synthesized as a potential membrane-permeable prodrug of FdUMP. The compound was designed to enter cells by passive diffusion and to revert to FdUMP after removal of the PIV groups by hydrolytic enzymes. The most convenient preparation of PIV2FdUMP was by condensation of 2'-deoxy-5-fluorouridine (FUdR) with PIV2 phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV2FdUMP was stable in the pH range 1.0-4.0 (t1/2 > 100 h). It was also fairly stable at pH 7.4 (t1/2 = 40.2 h). In 0.05 M NaOH solution, however, it was rapidly degraded (t1/2 < 2 min). In the presence of hog liver carboxylate esterases, PIV2FdUMP was converted quantitatively to the mono-[(pivaloyloxy)methyl] [PIV1] analogue PIV1FdUMP. After a 24 h incubation, only trace amounts of FdUMP (1-3%) were observed, indicating that PIV1FdUMP is a poor substrate for carboxylate esterases. In mouse plasma, PIV2FdUMP was rapidly metabolized, first to PIV1FdUMP and then to FdUMP. With continued incubation, FUdR was formed, presumably due to further catabolism of FdUMP by plasma phosphatases or 5'-nucleotidases. Since PIV1FdUMP is a poor substrate for carboxylate esterase, the cleavage of the second PIV group is most likely mediated by plasma phosphodiesterases. The rate of degradation of PIV2FdUMP in the presence of acid and alkaline phosphatase, 5'-nucleotidase, or spleen phosphodiesterase was the same as that in buffer controls, indicating that the compound is not a substrate for these nucleotide catabolizing enzymes. The concentration of PIV2FdUMP and its 3'-O-acetyl ester (PIV2 3'-O-Ac-FdUMP) required to inhibit the growth of Chinese hamster ovary (CHO) cells in vitro to less than 50 cells per colony was 5 x 10(-6) M, the same as that required for 5-fluorouracil (FU). Both nucleotide prodrugs showed the same growth-inhibitory potency against a mutant CHO cell line that was 20-fold resistant to FU (CHO/FU). Administered intraperitoneally at optimal dosage for 5 consecutive days, PIV2FdUMP and PIV2 3'-O-Ac-FdUMP were as effective as FU at prolonging the life spans of mice bearing intraperitoneally implanted P388 leukemia. Both prodrugs retained full therapeutic activity against a P388 subline resistant to FU. Collectively, these data indicate that PIV2FdUMP and PIV2 3'-O-Ac-FdUMP are effective membrane-permeable prodrugs of FdUMP.

Animals↗
PubMed1994

Charge interactions in the rod domain drive formation of tetramers during intermediate filament assembly.

The purpose of this study was to test a long standing hypothesis regarding the forces that drive the assembly of intermediate filaments (IFs). The initial step of IF assembly is the formation of dimeric, alpha-helical coiled coils. On the outside of the coiled coils, charged amino acids are distributed periodically such that positively and negatively charged residues are arranged in alternating zones, 9.5/2 residues wide (Parry et al., 1977; McLachlan and Stewart, 1982). This structural feature has given rise to the hypothesis that, if neighboring coiled coils were staggered axially by an odd multiple of a charged zone, electrostatic interactions between them could provide the driving force for the assembly of higher order oligomers or filaments (Fraser et al., 1986; Parry and Steinert, 1992). Using the IF protein vimentin as a model system, we carried out deletion mutagenesis experiments to test this hypothesis. We generated mutant vimentin proteins lacking 14, 21, and 28 residues in Helix 1B of the rod domain, and analyzed their assembly properties by DNA transfection into IF null cells, in vitro assembly, and chemical cross-linking. Results from these experiments are consistent with, and support, the hypothesis that charge complementation plays a key role in the assembly and stabilization of intermediate filaments.

Animals↗
PubMed1994

Different effects of a macrophage cytokine on proliferation in astrocytes and Schwann cells.

The proliferative response in vitro to a novel macrophage inflammatory protein (MIP) 1 alpha has been investigated in astrocytes and Schwann cells. MIP 1 alpha is growth-inhibitory in all cell systems investigated so far and we show here that this cytokine also inhibits the proliferation of astrocytes. This response is seen most clearly when MIP 1 alpha reduces the proliferative response of astrocytes to a potent mitogen. Elevation of intracellular cyclic AMP with forskolin enhances the effects of MIP 1 alpha. In contrast, we show that the proliferation of cultured Schwann cells is stimulated by MIP 1 alpha, and that stimulation is enhanced by simultaneous exposure to forskolin. The possible consequences of these differing responses are discussed in the context of the acute response to injury and potential for regeneration of the peripheral and central nervous systems.

Animals↗
PubMed1994

A conserved region in the tail domain of vimentin is involved in its assembly into intermediate filaments.

Although the head and rod domains of intermediate filament (IF) proteins are known to play significant roles in filament assembly, the role of the tail domain in this function is unclear and the available information supports contradictory conclusions. We examined this question by comparing transfection of the same cDNA constructs, encoding vimentins with modified tail domains, into cell lines that do and do not contain endogenous IF proteins. By this approach, we were able to distinguish between the ability of a mutant IF protein to initiate assembly de novo, from that of incorporating into existing filament networks. Vimentins with modifications at or near a highly conserved tripeptide, arg-asp-gly (RDG), of the tail domain incorporated into existing IF networks in vimentin-expressing (vim+) cells, but were assembly-incompetent in cells that did not express IF proteins (vim-). The failure of the RDG mutant vimentins to assemble into filament arrays in vim- cells was reversible by re-introducing a wild-type vimentin cDNA, whereupon both wild-type and mutant vimentins coassembled into one and the same IF network. We conclude that the function of the tail domain of type III IF proteins, and possibly of keratins K8 and K18, in IF assembly is distinct from those of other domains; a region encompassing the RDG tripeptide appears to be important in the assembly process.

Adrenal Gland Neoplasms↗
PubMed1994

Prevention of cyanide-induced cytotoxicity by nutrients in isolated rat hepatocytes.

The effects of various glycolytic substrates and keto acid metabolites on the cytotoxic effects of cyanide have been studied with isolated rat hepatocytes. The sequence of cytotoxic events with 2 mM cyanide was an immediate inhibition of respiration followed by ATP depletion. Disruption of the plasma membrane occurred when 85-90% of ATP levels had been depleted. Fructose, dihydroxyacetone, glyceraldehyde, pyruvate, and alpha-ketoglutarate prevented cyanide-induced cytotoxicity and ATP depletion. Hepatocyte respiration was also restored by all except fructose. Fructose, unlike the others, also did not prevent cytotoxicity if added 30-60 min after cyanide. Fluoride, an inhibitor of the glycolytic enzyme enolase, prevented protection by fructose but not dihydroxyacetone or glyceraldehyde, suggesting that dihydroxyacetone and glyceraldehyde are cytoprotective by trapping cyanide, thereby restoring cytochrome oxidase activity and cellular ATP levels. Fructose, on the other hand, may be cytoprotective by supplying ATP through glycolysis. Hepatocytes isolated from fasted rats were five- to sevenfold more susceptible to cyanide-induced cytotoxicity. Furthermore, all glycogenic and gluconeogenic amino acids and carbohydrates were cytoprotective against cyanide toxicity toward fasted hepatocytes, suggesting that cellular energy stores determine their resistance to cyanide.

Acetaldehyde↗
PubMed1994

High-performance liquid chromatographic assay for the determination of paracetamol, pseudoephedrine hydrochloride and triprolidine hydrochloride.

The different UV absorption characteristics of paracetamol, pseudoephedrine hydrochloride and triprolidine hydrochloride have been used to facilitate their determination in pharmaceutical preparations by HPLC. The method developed involves isocratic, reversed-phase chromatography. A 'wavelength switching' programme is preferred to the use of a compromise wavelength for all three compounds. This gives reasonable UV responses despite widely different UV characteristics and concentrations of drugs. The limits of quantitation are found to be within 200-700 micrograms ml-1 for paracetamol, 24-84 micrograms ml-1 for pseudoephedrine HCl and 1.0-4.0 micrograms ml-1 for triprolidine HCl. The method performs well in terms of precision and accuracy as indicated by linear regression analysis.

Acetaminophen↗
PubMed1994

Blockade of platelet-mediated relaxation in rat aortic rings exposed to xanthine-xanthine oxidase.

Platelet-induced relaxation of endothelium-intact vascular tissues, mediated via release of endothelium-derived relaxing factor (EDRF), is diminished or lost after ischemia and reperfusion. Release of oxygen free radicals during ischemia-reperfusion may degrade EDRF and influence response of vascular tissues to platelets. To determine platelet modulation of tone of blood vessels treated with oxygen free radicals, rat aortic rings with intact endothelium were exposed to xanthine (X) plus xanthine oxidase (XO) 5 min before contraction with norepinephrine followed by exposure of rings to platelets. Treatment of aortic rings with X+XO caused a modest contraction, potentiated norepinephrine-mediated contraction, and inhibited platelet-mediated vasorelaxation. Exposure of aortic rings to X+XO also decreased ADP- as well as acetylcholine-mediated relaxation. Pretreatment of rings with superoxide dismutase or catalase did not change X+XO-induced inhibition of platelet-mediated relaxation, but it abolished the X+XO-induced contraction of rings as well as subsequent potentiation of norepinephrine-mediated contraction. Pretreatment of rings with hydroxyl radical scavengers dimethyl-2-thiourea, dimethyl sulfoxide, mannitol, or histidine attenuated the X+XO-induced inhibition of platelet-mediated relaxation, although these agents did not affect X+XO-induced contraction of rings. This study indicates that the vasoconstriction on exposure of aortic rings to X+XO is due to generation of superoxide anions, whereas inhibition of platelet-mediated relaxation after exposure of vessels to X+XO is due, at least in part, to release of hydroxyl radicals. Release of superoxide anions and hydroxyl radicals after temporary arterial occlusion may be the basis of subsequent modulation of vascular tone.

Animals↗
PubMed1994

The St. Jude Medical valve. Experience with 1,000 cases.

We analyzed the long-term results of valve replacement with the St. Jude Medical bileaflet valve (St. Jude Medical, Inc., St. Paul, Minn.) in our first 1000 implantations between 1978 and 1992. A total of 399 patients had mitral valve replacement, 471 aortic valve, and 130 double (mitral and aortic) valve replacement. The average patient age was 64 +/- 15 years and the majority of patients (52%) had concomitant coronary disease. With 4328 patient-years of follow-up, 83% of the mitral group, 76% of the aortic group, and 77% of the double valve group were free of thromboembolism at 10 years after operation, and 87% of the mitral group, 82% of the aortic group, and 85% of the double valve group were free of valve-related hemorrhage. At 10 years, 91% of the mitral group, 84% of the aortic group, and 84% of the double valve group were free of valve-related death. However, overall survival at 10 years was only 42% +/- 4% for the mitral group, 43% +/- 4% for the aortic group, and 43% +/- 6% for the double valve group. For all three groups, age was a highly significant factor stratifying survival (p < 0.001), as was the presence of coronary disease (all p < 0.001). The excellent freedom from valve-related death at 10 years of 84% to 91% is in striking contrast to the overall survivals of 42% to 43% at 10 years. This difference suggests that the primary factors limiting long-term survival after valve replacement with the St. Jude Medical valve are not valve-related factors, but other patient factors such as age and concomitant coronary disease.

Aged↗
PubMed1994

Preterm birth--its etiology and outcome.

This is a retrospective case control study. Out of a total of 1238 births occurring over a period of 8 months at the Aga Khan University Medical Centre, Karachi, 9.4% were preterm. Factors found to be associated with preterm labour were age > 35, height < 156 cm, anaemia or urinary tract infection in pregnancy, abruptio placentae, polyhydramnios, preterm rupture of membranes, intrauterine growth retardation, fetal distress and intrauterine death. Previous bad obstetric history was also relevant. A preterm baby was found to be at higher risk of postnatal complications resulting in neonatal death or admission to the Neonatal Intensive Care Unit (NICU) than a full term baby.

Adolescent↗
PubMed1993

Contrasting molecular cytotoxic mechanisms of mitomycin C and its two analogs, BMY 25282 and BMY 25067, in isolated rat hepatocytes.

The molecular cytotoxic mechanisms of mitomycin C (MMC) and its analogs, BMY 25282 and BMY 25067, have been investigated using isolated hepatocytes as a model system for studying toxicity to nondividing tissues. These drugs have quinone and aziridine moieties, and tumor cell cytotoxicity has been attributed to DNA alkylation and cross-linking. By contrast, the following results suggest that these drugs cause oxidative stress in nondividing cells by different mechanisms. Both hepatocytes or hepatic microsomes and NADPH were able to catalyse oxygen activation by all three drugs, suggesting that enzymatic reduction results in the formation of auto-oxidizable species. Their relative effectiveness at activating oxygen was BMY 25282 >> BMY 25067 > MMC. However, their relative cytotoxic effectiveness was BMY 25067 >> BMY 25282 > MMC, and it was increased markedly if hepatocyte glutathione-reductase or catalase was inactivated. Furthermore, ascorbate increased the toxic potencies of both BMY 25282 and MMC in catalase-inactivated hepatocytes by as much as 60- and 40-fold, respectively. Hepatocyte glutathione (GSH) oxidation was also increased. The relative resistance of normal hepatocytes to MMC and BMY 25282 can be attributed therefore, to the high levels of enzymes in hepatocytes involved in hydrogen peroxide detoxification. BMY 25067 cytotoxicity unlike that of BMY 25282 or MMC was prevented by the addition of the thiol reductant dithiothreitol. BMY 25067 also differed in being much more toxic towards GSH-depleted hepatocytes. Furthermore, BMY 25067, unlike MMC and BMY 25282, caused a rapid decrease in hepatocyte ATP levels and inhibited mitochondrial respiration. This could be prevented by the addition of the thiol reductant dithiothreitol, which restored intracellular GSH levels. Its toxic potency to catalase- or glutathione reductase-inactivated hepatocytes also was not increased by ascorbate. Therefore, the cytotoxicity of BMY 25067 can probably be attributed to oxidative stress by the aminodisulfide moiety which causes GSH and mixed disulfide formation, resulting in mitochondrial toxicity.

Adenosine Triphosphate↗
PubMed1993

Anaerobic glycolysis and postanoxic recovery of respiration of rat cortical synaptosomes are reduced by synaptosomal sodium load.

Synaptosomes of rat cerebral cortex were used to study the effect of veratridine-induced Na+ load on postanoxic recovery of respiration and on aerobic and anaerobic ATP turnover, calculated from rates of oxygen consumption and lactate production. Non-stimulated synaptosomes: after onset of anoxia lactate synthesis of synaptosomes rose immediately from 0.8 to 17.7 nmol lactate/min/mg protein indicating an anaerobic ATP turnover of 17.7 nmol ATP/min/mg protein. This value accounts for 80% of ATP synthesized during oxygenated conditions and seems to cover the energetic demand of anoxic synaptosomes. This assumption was supported by linearity of lactate production throughout anoxia (90 min), by unaffected synaptosomal integrity and by complete recovery of postanoxic respiration after 90 min of anoxia. Stimulated synaptosomes: stimulation of oxygenated synaptosomes with 10(-5) mol/l veratridine enhanced ATP turnover 5-fold, due to activation of Na+/K+ ATPase, as a result of veratridine-induced Na+ influx. Consequently, if not limited in capacity, anaerobic ATP synthesis should be enhanced after addition of veratridine during anoxia. However, the opposite effect was observed. Veratridine reduced anaerobic glycolysis in a concentration-dependent manner. This inhibitory effect could be prevented by tetrodotoxin applied 5 min prior to veratridine. Inhibition of anaerobic glycolysis was independent of extrasynaptosomal glucose (1-30 mmol/l) and Ca2+ concentration (Ca(2+)-free and 1.2 mmol/l Ca2+). Veratridine stimulation of anoxic synaptosomes reduced also the recovery of postanoxic respiration. The data indicate that Na+ load inhibits anaerobic ATP synthesis, the only energy source during anaerobic conditions. To our knowledge, inhibition of anaerobic glycolysis due to increased Na+ influx has not been shown so far.

Anaerobiosis↗
PubMed1993

Molecular mechanisms of dibromoalkane cytotoxicity in isolated rat hepatocytes.

The cytotoxicity of dibromoalkanes to isolated hepatocytes was proportional to the dibromoalkane concentration and increasing chain length of the dibromoalkane (C2-C6). The rapid hepatocyte glutathione (GSH) depletion which occurred upon addition of the dibromoalkanes was also dependent on the concentration and chain length of the dibromoalkane. When added to hepatocytes, dibromoalkanes also caused a loss in protein sulfhydryl groups. After a lag period, lipid peroxidation occurred before the onset of cytotoxicity. Antioxidants or removing the oxygen from the medium markedly delayed dibromoalkane cytotoxicity. Bromoaldehydic metabolites formed by cytochrome P450-dependent mixed-function oxidases were probably responsible for lipid peroxidation as deuterated 1,2-dibromoethane (d4-DBE) induced less lipid peroxidation and was less cytotoxic even though GSH was depleted as rapidly and as effectively. Hepatocytes were also more resistant to dibromoalkanes if cytochrome P450 isoenzymes were inactivated with SKF 525A or methyl pyrazole. Furthermore, hepatocyte susceptibility to dibromoalkanes was increased markedly if aldehyde dehydrogenase was inactivated with disulfiram, cyanamide or chloral hydrate. Cytochrome P450-induced hepatocytes isolated from pyrazole-, phenobarbital- or 3-methylcholanthrene-pretreated rats were also more susceptible to dibromoalkanes. These results suggest that dibromoalkane-induced cell lysis is due to lipid peroxidation as well as cytochrome P450-dependent formation of toxic bromoaldehydic metabolites which can bind with cellular macromolecules. Dibromoethane GSH conjugates also contribute to DBE cytotoxicity as depleting hepatocyte GSH beforehand increased hepatocyte resistance to DBE but not other dibromoalkanes.

Acetaldehyde↗