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Biomedical subjects

F Ismail-Beigi

Publications and source records attributed to F Ismail-Beigi.

At least 73 records · Page 4Linked to original sources
PubMed1988

Thyroidal regulation of rat renal and hepatic Na,K-ATPase gene expression.

Na,K-ATPase activity, Na,K-ATPase alpha- and beta-subunit mRNA abundance (mRNA alpha and mRNA beta), and gene transcription rates were determined in kidney cortex and liver of hypothyroid and triiodothyronine (T3)-treated rats. In hypothyroid rats, Na,K-ATPase activity (expressed per unit of DNA) was 3.6-fold greater in kidney cortex than liver, and the abundance of mRNA alpha and mRNA beta in kidney cortex exceeded that of liver by 2.8- and 5.2-fold, respectively. In vitro nuclear run-on analysis revealed similar rates of Na,K-ATPase alpha and beta gene transcription in nuclei isolated from either kidney cortex or liver. Administration of T3 for 72 h elicited a 2.3-fold stimulation of renal Na,K-ATPase activity that was associated with a 3.1- and 2.6-fold increase of mRNA alpha and mRNA beta content, respectively. In contrast, T3 induced a 1.3-fold stimulation of liver Na,K-ATPase activity accompanied by a 7.3-fold increase in mRNA alpha and no change in mRNA beta abundance. Transcription rates of alpha and beta genes (assayed by nuclear run-on) in renal cortex were both stimulated 1.8-fold in response to T3 injection. Similarly in liver nuclei, T3 treatment produced a 1.4- and 1.3-fold stimulation in the rate of alpha and beta gene transcription, respectively. These results indicate that significant discrepancies exist in the quantitative relationships between control and T3-induced changes in renal and hepatic enzyme activity, mRNA abundance and rate of gene transcription, and imply that the T3-induced increase in Na,K-ATPase abundance is mediated at both transcriptional and post-transcriptional steps.

Actins↗
PubMed1988

Kinetic analysis of Na,K-activated adenosine triphosphatase induced by low external K+ in a rat liver cell line.

Exposure of ARL 15 cells to medium containing reduced concentrations of K+ (0.65 mM) elicited a 50-100% increase in Na,K-ATPase activity. The inhibition by ouabain of both the basal and the induced enzyme conformed to a single-site model (KI = 1 x 10(-4) M). The low K+-induced increment in Na,K-ATPase activity was accompanied by an equivalent increase in the abundance of Na,K-pump sites estimated by ouabain-stabilized ("back-door") phosphorylation, such that the calculated catalytic turnover number of approximately 8000/min was minimally changed. Comparison of the dependence of ouabain-inhibitable K+ uptake on intracellular Na+ and on extracellular K+ concentrations in control and low K+-treated cells revealed no change in the respective half-maximal stimulatory concentrations for these cations, whereas the maximal rate of active K+ uptake in cells exposed to low external K+ increased by nearly 100%. The derived Hill coefficients for active K+ transport rate were also unchanged by the low K+ treatment (i.e. approximately 1.4 for extracellular K+ and 2.6 for intracellular Na+). Na,K-ATPase activity of basal and low K+-induced cells calculated from the measured maximal Na,K transport rate closely approximated the Na,K-ATPase activity measured enzymatically in unfractionated cell lysates under Vmax conditions, suggesting that all or most of the Na,K-ATPase enzymatic units present in both basal and stimulated states are functionally active. Northern blot analysis of RNA isolated from control cells indicated the presence of the Na,K-ATPase alpha-I isoform of the enzyme which increased by nearly 200% following incubation of the cells in low-K+ medium. By contrast, the alpha-II and alpha-III mRNAs were undetectable in either the basal or low K+-stimulated state. These results indicate that the Na,K-ATPase induced by incubation of ARL 15 cells in low-K+ medium is kinetically and functionally indistinguishable from the basal enzyme, and that only the alpha-I isoform is expressed under control and low-K+ conditions.

Animals↗
PubMed1988

Increased abundance of Na+-K+-ATPase mRNAs in response to low external K+.

Exposure of ARL 15 cells, an established line from adult rat liver, to external K+ concentrations less than 1 mM for 24 h increases Na+-K+ pump abundance (Na+-K+-ATPase) (J. Gen. Physiol. 87:591-606, 1986). We found that treatment of confluent monolayers of ARL 15 cells with low-K+ medium (0.65 mM) caused a 100% increase in total RNA content per plate after 24 h, as well as a 25% increase in DNA and protein content per plate. Concomitant with this growth effect, low-K+ exposure for 6 h elicited 60% increases in mRNA alpha and mRNA beta, the mRNAs that encode the constituent subunits of the Na+-K+-ATPase, in a polyadenylated RNA fraction. At 24 h, however, the abundance of mRNA alpha increased by 290%, whereas mRNA beta increased by only 70%. Moreover, in both control and low-K+-treated cells, mRNA alpha was 30-fold or more greater in abundance than mRNA beta. This discrepancy in abundance was also present in rat liver, but not in cultured MDCK cells. The differences in abundance of mRNA alpha and mRNA beta suggest that the liver may have an unusual subunit composition or biosynthetic mechanism. Nevertheless, the increases in the abundance of mRNA alpha and mRNA beta are sufficient to account for the observed 70-100% increase in Na+-K+-ATPase activity in response to low external K+.

Animals↗
PubMed1988

Time course of Na,K transport and other metabolic responses to thyroid hormone in clone 9 cells.

To elucidate the relationship between the stimulation of Na+ and K+ fluxes by thyroid hormone and the induction of the Na,K-ATPase, we performed a detailed comparison of the time courses of these hormonal effects in a rat liver cell line, clone 9. Stimulations of passive K+ efflux, passive Na+ influx, and ouabain-inhibitable K+ uptake were all evident within 6-12 h of exposure of cells to T3 (10(-7) M). The time course of the induction of Na,K-ATPase activity closely paralleled that of the increase in the rate of Na+ and K+ fluxes. The maximal stimulatory effects of T3 on ouabain-inhibitable K+ uptake and Na,K-ATPase activity at 72 h were +49% and +36%, respectively. Intracellular Na+ and K+ contents were virtually unchanged during these increases in ion fluxes and Na,K-ATPase activity, suggesting an efficient homeostatic adaptation to the augmented passive "leak" of Na+ and K+ down their transmembrane concentration gradients. T3 treatment for 72 h was also shown to stimulate both lactate production (+62%) and [3H]2-deoxyglucose uptake (+82%) in these cells. The onset of these effects appeared to precede that of the stimulation of Na+ and K+ fluxes, being detectable at 4 h. Neither these latter effects of T3 nor the stimulation of ouabain-inhibitable K+ uptake could be demonstrated when RNA or protein synthesis was inhibited by actinomycin D or cycloheximide, respectively. It is concluded that in clone 9 cells thyroid hormone causes increases in passive Na+ influx, passive K+ efflux, active Na,K transport, and Na,K-ATPase activity whose time courses are closely parallel.

Animals↗
PubMed1987

Ionic dependence of active Na-K transport: "clamping" of cellular Na+ with monensin.

The Na+ ionophore monensin was used to study the Na+- and K+-dependence of ouabain-inhibitable 86Rb+ uptake in ARL 15 cells, a rat liver cell line. Graded concentrations of monensin rapidly induced incremental elevations of cellular Na+ that were stable for up to 2 h. In experiments in which cellular Na+ was thus "clamped" at various levels, the activation curve for ouabain-inhibitable 86Rb+ uptake as a function of intracellular Na+ was found to be steepest near basal Na+ levels (Hill coefficient approximately equal to 2.4), indicating that these cells can respond to relatively large changes in passive Na+ entry by increasing the race of Na-K pump function with only minimal increases in cellular Na+. Exposure of cells to monensin also permitted examination of the extracellular-K+ dependence of ouabain-inhibitable 86Rb+ uptake in the presence of saturating intracellular Na+ and yielded a Hill coefficient of approximately 1.5. The rate of ATP hydrolysis calculated from measurements of the maximal rate of ouabain-inhibitable 86Rb+ uptake in intact cells was similar to the enzymatic Vmax of the Na+-K+-ATPase in cell lysates, suggesting that the Na+-K+-ATPase activity in these broken-cell preparations closely reflects the functional transport capacity of the Na-K pump.

Animals↗
PubMed1987

Effect of thyroid hormone on the abundance of Na,K-adenosine triphosphatase alpha-subunit messenger ribonucleic acid.

The effects of thyroid hormone on Na,K-ATPase alpha-subunit mRNA (mRNA alpha) content and Na,K-ATPase activity were measured in renal cortex, heart, and cerebrum of hypothyroid rats 24 and 72 h after injection of diluent or T3. Use of a cDNA probe complementary to rat brain mRNA alpha in Northern blot analysis revealed a single 26-27 S band in RNA isolated from these three tissues regardless of thyroid status. Tissue mRNA alpha content was estimated by dot blot analysis of whole cell extracts and isolated total RNA. Injection of T3 augmented mRNA alpha content by 2.1- to 2.5-fold in kidney cortex and myocardium at 24 h. After three daily injections of T3, the increases in mRNA alpha were evident despite a global increase in RNA content associated with hypertrophy of these target tissues. Furthermore, the increases in abundance of mRNA alpha after 72 h of T3 treatment correlated with enhancement of Na,K-ATPase activity. In contrast, both mRNA alpha and enzyme activity were invariant in the cerebrum. These data suggest that T3-induced augmentation of Na,K-ATPase activity is mediated, at least in part, by increased mRNA alpha content in target tissues.

Animals↗
PubMed1986

Stimulation of Na,K-activated adenosine triphosphatase and active transport by low external K+ in a rat liver cell line.

Exposure of ARL 15 cells, an established line from adult rat liver, to concentrations of external K+ below 1 mM caused a rapid fall in intracellular K+ and a corresponding rise in intracellular Na+ that became maximal within 12 h. Upon continued exposure to low external K+, these initial changes were followed by a striking recovery such that, by 24 h, intracellular Na+ and K+ concentrations approached their control values. Concomitant with this recovery, there was a substantial increase in Na,K-ATPase specific activity that was detectable at 12 h and maximal at 24 h. After restoration of the external K+ concentration, the elevated level of enzyme activity showed little change for at least 24 h. In contrast, restoration of external K+ resulted in a rapid rise in intracellular K+ and a fall in Na+ such that within 30 min the Na+/K+ ratio was lower than in control cells. This overshoot, together with a demonstrated increase in active 86Rb+ uptake under "Vmax" conditions, confirms that the enhancement in Na,K-ATPase specific activity in response to low external K+ represents an increase in functional Na,K pumping capacity.

Animals↗
PubMed1986

Stimulation of active Na+ and K+ transport by thyroid hormone in a rat liver cell line: role of enhanced Na+ entry.

A continuous cell line derived from rat liver (ARL 15) has been identified that responds to thyroid hormone with a stimulation of active Na,K transport. Stimulation of ouabain-inhibitable K+ uptake, which is half-maximal at a T3 concentration of 1.4 X 10(-10) M, is accompanied by corresponding increases in passive Na+ influx and in passive K+ efflux. The enhancement of Na+ and K+ fluxes by T3 is shown to be accompanied by smaller and equivalent increases both in enzymatically measured Na,K-ATPase activity and in maximal ouabain-sensitive Na,K transport in the presence of the Na+ ionophore monensin. The demonstration that both passive Na+ influx and passive fractional K+ efflux are simultaneously increased by T3 supports the earlier suggestion that the stimulation of active Na,K transport by thyroid hormone is attributable, at least in part, to an enhancement of rate-limiting passive Na+ and K+ fluxes by an increase in membrane permeability.

Animals↗
PubMed1982

Hemobilia detected by Tc-99m labeled red blood cells.

Tc-99m labeled red blood cells were successfully used to determine the site of hemorrhage in a 67-year-old man with hemobilia. A false hepatic artery aneurysm was confirmed at angiography and ultimately successfully embolized. The relative merits of using Tc-99m labeled red blood cells for detecting sources of upper gastrointestinal bleeding are discussed.

Aged↗
PubMed1981

Nuclear binding of T3 and effects of QO2, Na-K-ATPase, and alpha-GPDH in liver and kidney.

Thyroid status was altered by use of a low-iodine-perchlorate (PC) regimen and either reversal with NaI or injections of L-3,5,3'-triiodothyronine (T3). The PC regimen decreased renal and hepatic oxygen consumption (QO2), alpha-glycerophosphate dehydrogenase (alpha-GPDH), and Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) to comparable extents (25 vs. 23%, 26 vs. 39%, and 41 vs. 51%, respectively). Administration of T3 to hypothyroid rats elicited dose-dependent increases in hepatic and renal cortical QO2, ouabain-sensitive oxygen consumption (QO2(t)), alpha-GPDH, and Na-K-ATPase activities. The half-maximal increases in all of the response parameters in both kidney and liver were obtained at dosages of 6-32 micrograms T3/100 g body wt. The equivalences in the renal cortical vs. hepatic responses were indicated by correlation coefficients of approximately 0.97. Kidney and liver nuclei also showed similar high-affinity binding of 125I-T3-K1/2 = 29 vs. 18 micrograms T3/100 g body wt, and Nmax = 1.8 vs. 2.1 ng T3/mg DNA. The patterns of the responses plotted as a function of T3 occupancy of the high-affinity nuclear binding sites were indistinguishable in kidney and liver. These results imply similar modes of action of T3, probably initiated at the nuclear level, in both kidney and liver.

Animals↗
PubMed1979

Thyroid thermogenesis in adult rat hepatocytes in primary monolayer culture: direct action of thyroid hormone in vitro.

We have studied the effect of 3,5,3'-triiodothyronine (T3) on the respiration of adult rat hepatocytes in primary monolayer culture prepared from hypothyroid rat liver. After addition of T3 to the culture medium at a concentration of 2 x 10(-7) M, oxygen consumption of the cultured cells increased detectably at 24 h and was maximal at 72--96 h, relative to control cultures (38.0 +/- 1.8 vs. 25.0 +/- 1.5 microliter/h.mg protein). The thyroid-responsive enzymes, Na+ + K+-activated adenosine triphosphatase (NaK-ATPase) and alpha-glycerophosphate dehydrogenase (GPD), each exhibited increased activity in response to T3, in parallel with the change in oxygen consumption, whereas the activity of Mg-dependent ATPase was unaffected. These responses to T3 were dose dependent over similar concentration ranges, the half-maximal response for each occurring at ca 8 x 10(-10) M. In thyroid-treated cells, the observed increase in respiration was almost completely (90%) inhibited after addition of ouabain (10(-3) M) to the culture medium. It was found also that a 4-h exposure of the cultured hepatocytes to T3 was sufficient to elicit a significant thermogenic response, measured at a time (48 h later) when T3 was no longer present in the medium. The response to T3 occurred in fully defined culture medium and was independent of the presence or absence of hypothyroid rat serum, corticosterone, or insulin, and cellular ATP was unaffected by T3 in concentrations up to 2 x 10(-7) M. The findings document that adult rat hepatocytes in primary monolayer culture respond directly to thyroid hormone; the increases in respiration and NaK-ATPase activity elicited by T3 were cotemporal and apparently coordinate.

Animals↗
PubMed1977

Role of bacterial overgrowth in the malabsorption syndrome of primary small intestinal lymphoma in Iran.

Malabsorption studies were performed on five Iranian patients with primary small intestinal lymphoma. The effect of oral tetracycline (1.0 g daily) was also studied in three of the above subjects. The results of breath tests (utilizing glycine-1-14C-cholic acid) were abnormal in all five subjects before the antibiotic treatment. Oral tetracycline had a striking effect towards normalizing the results of breath tests. Schilling tests (with intrinsic factor) improve in two patients and steatorrhea improved in all and there was significant weight gain. The antibiotic had no apparent effect on D-xylose or folate absorption tests. It is concluded that bacterial overgrowth in the small intestinal lumen is an important contributory factor to the malabsorption syndrome of this disease.

Adult↗
PubMed1977

Binding of zinc and iron to wheat bread, wheat bran, and their components.

Wholemeal wheat bread decreases the availability and intestinal absorption of divalent metals. To define this action further, binding of zinc in vitro to a wheat wholemeal bread (Tanok), dephytinized Tanok, and cellulose was determined at pH 5.0 to 7.5. Zinc binding by each was highly pH-dependent and reached a maximum at pH 6.5 to 7.5. Removal of phytate from Tanok did not reduce its binding capability. Wheat bran at pH 6.5 and 6.8 bound 72% of iron (0.5 microgram/ml of solution) and 82.5% of zinc (1.43 microgram/ml solution), respectively. Lignin and two of the hemicellulose fractions of wheat bran and high binding capabilities for zinc (85.6, 87.1, and 82.1%, respectively) whereas a third had a lower zinc-binding capability (38.7%). Binding of zinc to various celluloses and dextrans is also demonstrated. Formation of complexes of these metals with wheat fiber can explain, at least in part, the decreased availability of dietary iron and zinc in wholemeal wheat bread.

Bread↗
PubMed1977

Effects of cellulose added to diets of low and high fiber content upon the metabolism of calcium, magnesium, zinc and phosphorus by man.

Addition of 10 g of cellulose dispersed in 150 g of apple compote to the daily diet with a low fiber content for a 20-day period caused the fecal excretion of calcium and zinc of three men to increase significantly. Balances of both metals became negative and their concentrations in plasma decreased. Magnesium balances became negative in two subjects while phosphorus balance changed to negative in one. In a similar experiment in which the cellulose was added to a fiber-rich diet, fecal excretions of calcium and zinc increased significantly in each of two men and excretion of magnesium in one. Previously negative balances became more negative, and calcium and zinc concentrations decreased in plasma. The dependence of fecal dry weight upon fecal fiber content measured by the acid-detergent method was confirmed. However, increments of dry matter per g of fiber were less fecal fiber concentrations were high. Fecal calcium content correlated significantly with fecal fiber in two subjects, and fecal fiber and zinc in one. No correlations were demonstrated in the subject who apparently digested fiber most effectively. Our findings indicate that high intakes of fiber can explain to a considerable extent the impaired utilization of zinc, calcium, and magnesium among villagers in rural Iran.

Adult↗
PubMed1977

Mild sickle-cell anaemia in Iran associated with high levels of fetal haemoglobin.

Sixteen subjects, with sickle-cell anaemia, all Iranians (ages 3 to 56 years), with very mild symptomatology are reported. Some of the subjects had been totally asymptomatic. Splenomegaly was noted in 9 cases. There was an increase in the mean level of fetal haemoglobin (18%); this is the probable explanation for the mild phenotype. In 29 subjects with sickle-cell trait, the level of HbF was also significantly raised as compared with normal (1-6% vs. 0-6%). The mechanism of increased synthesis of HbF is unknown. The findings are similar to those reported in the Shiite Moslems of Saudi Arabia suggesting that in these populations there is a genetically-determined ability to produce high levels of Hb F in the presence of the sickle-cell gene.

Adolescent↗