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Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 379 records · Page 21Linked to original sources

Ion selectivity of the Vibrio alginolyticus flagellar motor.

The marine bacterium, Vibrio alginolyticus, normally requires sodium for motility. We found that lithium will substitute for sodium. In neutral pH buffers, the membrane potential and swimming speed of glycolyzing bacteria reached maximal values as sodium or lithium concentration was increased. While the maximal potentials obtained in the two cations were comparable, the maximal swimming speed was substantially lower in lithium. Over a wide range of sodium concentration, the bacteria maintained an invariant sodium electrochemical potential as determined by membrane potential and intracellular sodium measurements. Over this range the increase of swimming speed took Michaelis-Menten form. Artificial energization of swimming motility required imposition of a voltage difference in concert with a sodium pulse. The cation selectivity and concentration dependence exhibited by the motile apparatus depended on the viscosity of the medium. In high-viscosity media, swimming speeds were relatively independent of either ion type or concentration. These facts parallel and extend observations of the swimming behavior of bacteria propelled by proton-powered flagella. In particular, they show that ion transfers limit unloaded motor speed in this bacterium and imply that the coupling between ion transfers and force generation must be fairly tight.

Cell Movement↗

Discrepancies between Doppler and catheter gradients in aortic prosthetic valves in vitro. A manifestation of localized gradients and pressure recovery.

To evaluate possible causes of discrepancy between Doppler and catheter gradients across prosthetic valves, five sizes (19-27 mm) of St. Jude and Hancock valves were studied in an aortic pulsatile flow model. Catheter gradients at multiple sites distal to the valve were compared with simultaneously obtained Doppler gradients. In the St. Jude valve, significant differences between Doppler and catheter gradients measured 30 mm downstream from the valve were found: Doppler gradients exceeded peak catheter gradients of 10 mm Hg or more by 81 +/- 35% (15 +/- 3.6 mm Hg), and mean catheter gradients by 71 +/- 11% (10.3 +/- 2.5 mm Hg). When the catheter was pulled back through the tunnel-like central orifice of the valve, high localized gradients at the valve plane and significant early pressure recovery were found. When the catheter was pulled back through the large side orifices, gradients at the same level were only 46 +/- 6% of the central orifice gradients (mean difference, 7.6 +/- 4.5 mm Hg). Doppler peak and mean gradients showed excellent agreement with the highest central orifice catheter gradients (mean difference, 1.0 +/- 3.1 and 0.9 +/- 1.5 mm Hg, respectively). A significantly better agreement between Doppler and catheter gradients at 30 mm was found for the Hancock valve, although Doppler peak and mean gradients were still slightly greater than catheter gradients. Doppler gradients exceeded catheter gradients by 18 +/- 10% (3.4 +/- 1.9 mm Hg) and 13 +/- 11% (2.1 +/- 0.9 mm Hg), respectively. When the catheter was pulled back through the valve, the highest gradients were found approximately 20 mm distal to the valve ring.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Malignant transformation in a laryngeal hemangioma.

Laryngeal angiosarcoma is uncommon, with only 19 previously reported cases. Malignant transformation in nonirradiated hemangiomas is extremely rare, with only five equivocal cases reported, all of which occurred in the skin. We report the first documented case of malignant transformation in a laryngeal hemangioma, and review the literature.

Adult↗

Molecular mechanisms for bromotrichloromethane cytotoxicity in isolated rat hepatocytes.

1. Bromotrichloromethane added to isolated rat hepatocytes resulted in increased cell death as determined by trypan blue uptake. Toxicity increased in a concentration-dependent fashion between 2.0-5.0 M bromotrichloromethane. 2. Lipid peroxidation (malondialdehyde) increased in a time-dependent fashion but in contrast to toxicity reached a maximum level at 2.0 mM bromotrichloromethane. 3. Hypoxia increased the toxicity of bromotrichloromethane three-fold but only decreased the amount of lipid peroxidation to a small degree. 4. In spite of this poor correlation between toxicity and lipid peroxidation, the antioxidant butylated hydroxyanisole and the iron chelator desferal protected the cells from toxicity under both aerobic and hypoxic conditions and prevented lipid peroxidation. 5. During treatment with bromotrichloromethane, cellular glutathione levels slowly decreased and oxidized glutathione appeared in the media. The addition of cystine to the incubation media prevented the formation of extracellular oxidized glutathione, indicating that cellular glutathione had leaked from the cell during treatment and was oxidized in the incubation media. Although this suggested that glutathione does not play a protective role against bromotrichloromethane toxicity, diethyl maleate-pretreatment of the cells to decrease glutathione levels markedly increased bromotrichloromethane toxicity. 6. The addition of ascorbic acid to the incubation media increased bromotrichloromethane toxicity. This was attributed to the reductive activation of bromotrichloromethane in an iron and oxygen-dependent reaction. 7. It was concluded that peroxidation of essential phospholipids contributes to bromotrichloromethane-induced hepatocyte cytotoxicity.

Aerobiosis↗

Toxicity of nitrobenzene compounds towards isolated hepatocytes: dependence on reduction potential.

1. The cytotoxicity of p-substituted nitrobenzenes towards isolated hepatocytes under aerobic or hypoxic conditions has been determined. The nitrobenzene concentration required to cause 50% cytoxicity in 2 h was a function of the one-electron reduction potential of the nitrobenzene, with the more cytotoxic compounds having the strongest electron-withdrawing substituents. 2. The effectiveness of the nitrobenzenes at causing cytotoxicity under aerobic but not hypoxic conditions was markedly increased if hepatocyte catalase was inhibited with azide. 3. Nitrobenzenes at cytotoxic concentrations induced cyanide-resistant respiration in isolated hepatocytes. Their effectiveness correlated with their cytotoxicity. 4. The rate of oxygen activation of these nitrobenzenes by ascorbate was also a function of the one-electron reduction potential. The nitro compounds with the strongest electron-withdrawing substituents were the most rapidly reduced. 5. Most nitrobenzenes were more cytotoxic under aerobic than hypoxic conditions. Ascorbate enhanced hypoxic, but not aerobic, cytotoxicity. 6. It was concluded that the cytotoxicity of different nitrobenzenes is related to their ease of reduction to nitro radical anions and nitrosobenzenes. Aerobic cytotoxicity is probably initiated by redox cycling and oxygen activation by the nitro radical anions whereas hypoxic cytotoxicity is probably initiated by the alkylation of macromolecules by nitrosobenzene metabolites.

Alkylation↗

Relationship of prolactin and gonadotrophic hormones in regulation of the ovarian function.

Circulating concentration of the LH, FSH, prolactin (PRL), oestradiol-17 beta (E2) and progesterone (P) in serum were investigated in women with normal cycles and proven fertility, with irregular cycles and infertility and with primary or secondary amenorrhea in order to understand the relationship of the prolactin and gonadotrophic hormens in regulation of the ovarian function. The results indicate that hyperprolactinemia inhibits the pituitary to release the midcycle LH surge in response to the positive feedback action of the elevated oestrogen at the midcycle. The elevated LH and FSH levels found in the cases of the secondary amenorrhea is the indication of the absence of the steroid negative feedback due to the ovarian failure. Prolactin does not seem to play a role on the manifestation of either primary or secondary amenorrhea.

Adult↗

Hemodynamic comparison of Hancock and Carpentier-Edwards mitral bioprosthetic valves.

Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow-dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis↗

Modulation of benzene toxicity by polyinosinic-polycytidilic acid, an interferon inducer.

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt.) for 3 days produced leucopenia, lymphocytopenia and significantly decreased body wt. (P less than 0.001) and organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Low molecular weight (LMW) bleomycin detectable iron content was accumulated in bone marrow, whereas hepatic LMW iron was not detectable after benzene intoxication to rats. Prior administration of single dose (250 micrograms/100 g body wt.) of Poly IC, an interferon inducer with immunomodulating potential was found to be ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content (bone marrow) were normalised. Pretreatment of animals with Poly IC was able to enhance the SRBC antibody titre in benzene-treated animals. This study suggests that the beneficial effects of Poly IC in the amelioration of the acute toxicity of benzene has clinical significance.

Animals↗

Perturbation of liver microsomal calcium homeostasis by ochratoxin A.

The effect of ochratoxin A on hepatic microsomal calcium sequestration was studied both in vivo and in vitro. The rate of ATP-dependent calcium uptake was inhibited by 42-45% in ochratoxin A intoxicated rats as compared to controls. In the presence of NADPH, addition of ochratoxin A (2.5 to 100 microM) caused a concentration-dependent inhibition of calcium uptake (28-94%) by untreated rat liver microsomes. The rate of NADPH-dependent lipid peroxidation, measured as malondialdehyde formed, was also greatly enhanced by ochratoxin A. Various agents that inhibited ochratoxin A enhanced lipid peroxidation were also able to block the destruction of calcium uptake activity. Lipid peroxidation enhanced by ochratoxin A was also accompanied by leakage of calcium from calcium-loaded microsomes. These results suggest that ochratoxin A disrupts microsomal calcium homeostasis by an impairment of the endoplasmic reticulum membrane probably via enhanced lipid peroxidation.

Animals↗

Effect of different dietary brans on lipid metabolism in male albino rats.

Male albino rats were fed different dietary brans at 20% level for two months to study their effect on lipid metabolism. Wheat and corn brans significantly (P less than 0.05) decreased the serum cholesterol level while chickpea bran significantly (P less than 0.05) lowered the liver and heart cholesterol concentrations. Significant (P less than 0.05) reduction was observed in liver and heart triglyceride with all brans. Wheat, corn and chickpea brans fed at 20% level had no significant effect on serum triglyceride concentration.

Animal Feed↗

Effect of roasting and autoclaving on phytic acid content of chickpea.

Chickpea cultivars CM-68, C-44, Kabuli, CM-72 and 6153 were analysed for phytic acid, phytate phosphorus and total phosphorus. The effect of roasting and autoclaving on these constituents of whole seed and cotyledons was determined. The data revealed that roasting and autoclaving significantly decreased (P less than 0.05) the phytic acid of chickpea cultivars. Phytic acid of whole seed was reduced to a range value of 16-60% and 16-64% by roasting and autoclaving respectively depending upon the cultivar. In the cotyledon, the phytic acid was reduced to a range value of 32-68% and 18-68% during roasting and autoclaving respectively. Similar effect of these treatments was observed in phytate phosphorus however, total phosphorus was little affected.

Cooking↗

Differentiation between androgen and estrogen receptor mediated effects of testosterone on FSH using androgen receptor deficient (Tfm) and normal mice.

The comparison of normal and androgen receptor (AR) deficient Tfm-mice allows distinction between AR mediated and estrogen receptor (ER) mediated effects of testosterone (T)--the latter after aromatization of T to estrogens--on serum and pituitary FSH. Normal male and female as well as Tfm mice were gonadectomized after 8 days and treated for 11 days with either T, estradiol (E2) or vehicle. Serum and pituitary FSH was determined by RIA for rat FSH. In Tfm mice T caused a suppression of serum FSH, indicating an ER mediated effect. Lower serum FSH levels after T in normal mice than Tfm mice indicate an additional AR mediated suppression. Lower serum FSH values in E2 treated Tfm than in T treated Tfm mice--where T acts only through ER--suggest two classes of estrophilic cells: one which aromatizes, thus being susceptible for both T and E2, and the other which does not aromatize. Only AR but not ER mediated T effects on pituitary FSH could be demonstrated.

Animals↗

Effect of a Prudhoe Bay crude oil on hepatic and renal peroxisomal beta-oxidation and mixed-function oxidase activities in rats.

The effect of oral administration of a Prudhoe Bay crude oil (PBCO) to male rats (PBCO, 2.6 g/kg body weight, daily) for 5-12 days on hepatic and renal microsomal monooxygenase activities and peroxisomal beta-oxidation has been investigated. PBCO administration leads to liver enlargement. This is associated with induction of microsomal cytochrome P-450 levels (1.6- to 2.0-fold) and dependent mixed-function oxidase activities (7-ethoxyresorufin-O-deethylase and 7-pentoxyresorufin-O-depentylase, representing cytochrome P-450I and cytochrome P-450IIB isoenzymes respectively, 9- to 15-fold; omega-oxidation of lauric acid representing the cytochrome P-450IVA1 isoenzyme, 1.4- to 1.5-fold) along with peroxisomal beta-oxidation (palmitoyl CoA oxidation, 2- to 5-fold). It was observed that rats exposed to PBCO showed an increase in renal microsomal cytochrome P-450 content (1.6- to 2.3-fold), cytochrome P-450I activity (5- to 8-fold) and omega-oxidation activity (1.3- to 1.4-fold). However, renal peroxisomal beta-oxidation was unaltered. Serum total triglycerides were lowered by 41-46% after PBCO exposure. These results suggest that induction of peroxisomal beta-oxidation and possibly mono-oxygenases may be related to the carcinogenic/tumorigenic potential of crude oil.

Animals↗

Differential effects of follicle-stimulating hormone and luteinizing hormone on Leydig cell function and restoration of spermatogenesis in hypophysectomized and photoinhibited Djungarian hamsters (Phodopus sungorus).

Effects of pure human follicle-stimulating hormone (hFSH) and ovine luteinizing hormone (oLH) on testicular function were investigated in long-term hypophysectomized or photoinhibited Djungarian hamsters. hFSH (5 IU) or oLH (5 micrograms) or a combination of FSH and LH (5 IU and 5 micrograms, respectively) were injected s.c. twice daily for 7 days to hypophysectomized and photoinhibited hamsters. Other photoinhibited hamsters were treated for 14 and 21 days with FSH and LH (3 IU and 3 micrograms, respectively) in a similar way. LH alone had little, if any, effect on testicular weights; FSH, when injected alone or in combination with LH (FSH/LH), caused a significant increase in testes weights at each time point. On the other hand, LH or FSH/LH, but not FSH alone, caused a significant increase in the accessory organ weights. FSH had no effect on intratesticular testosterone (T) or on 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity but enhanced the in vitro response of interstitial cells to hCG. LH and FSH/LH had pronounced effects on intratesticular T, 3 beta-HSD activity, and in vitro response of interstitial cells to human chorionic gonadotropin. Treatment with FSH or FSH/LH caused regrowth of the testis and restoration of tubular lumen and tubular diameter and restored complete spermatogenesis. However, LH had little effect on spermatogenesis in spite of increased intratesticular and peripheral T levels. These results indicate that although LH can cause a full redifferentiation of Leydig cells in photoinhibited hamsters, it has only minor effects on tubular function. On the other hand, FSH alone induces full restoration of tubular function in these animals and has no direct effect on Leydig cell steroidogenesis, but may enhance the Leydig cell responsiveness to LH.

3-Hydroxysteroid Dehydrogenases↗

Appendicectomy stumps: 'to bury or not to bury'.

A prospective randomized trial of 130 patients was carried out to compare simple ligature with invagination of the appendix stump. There were 64 and 66 patients, respectively, in the two groups and they were well matched for age, sex, weight and severity of appendicitis. One patient in the invagination group developed wound infection but there was no infection in the other group. This difference was not statistically significant (P greater than 0.5) and there was no evidence of adhesive ileus in either group after a mean follow-up period of nine months. We recommend simple ligature of the appendix stump as a safe procedure.

Appendectomy↗

Effects of mot gene expression on the structure of the flagellar motor.

Direct freezing procedures have enabled us to visualize distinctive intramembrane particle ring structures in the cytoplasmic membranes of peritrichously flagellated bacteria by means of freeze-fracture electron microscopy. These structures were identified as flagellar motor components because their distribution matched that of flagella, and because they were absent in non-flagellated mutants of Escherichia coli. Particle rings were present in both the Gram-positive Streptococcus and the Gram-negative E. coli. In E. coli, a non-functional mocha operon produced flagellated but immotile cells lacking the particle rings. Simultaneous introduction of the motA and motB genes, led to recovery of both motility and the ring structures but neither gene alone was sufficient. The concomitant loss of the rings and motility is consistent with the ring particles having a central role in the flagellar motor.

Escherichia coli↗