Search PubMed⌕ Search

Biomedical subjects

M Berman

Publications and source records attributed to M Berman.

At least 145 records · Page 8Linked to original sources
PubMed1972

The use of lithium in the treatment of thyrotoxicosis.

Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed (131)I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of (131)I from the thyroid, led to a fall in serum (131)I levels and diminished urinary (131)I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. NEITHER INHIBITION OF RELEASE NOR OF HORMONE DISAPPEARANCE SEEMED TO BE AFFECTED BY METHIMAZOLE (RELEASE: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: approximately 60% decrease in both). When Li(+) was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li(+) values. When Li(+) is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li(+). The similarity of inhibition of iodine release from the thyroid produced by Li(+) and iodides is discussed.

Adolescent↗
PubMed1971

Regulation of tension in the skinned crayfish muscle fiber. I. Contraction and relaxation in the absence of Ca (pCa is greater than 9).

In isolated skinned crayfish muscle fibers bathed in solutions that were buffered to be virtually free of Ca(2+) (pCa 8-10) the substrate for both contraction and relaxation is the MgNTP complex. Tension increased up to 50% of the maximum capability of the fiber as the substrate MgATP increased to an optimum (pMgATP = 5.5). Relaxation was induced by further increases in MgATP. Similar bell-shaped curves of tension vs. pMgNTP were obtained with UTP and ITP, but optimum pMgUTP was about 4.5 and optimum pMgITP was about 2.6. The relation between equilibrium tension and pMgNTP is described by an equation analogous to that for the kinetics of enzymes regulated by substrate inhibition.

Adenosine Triphosphate↗
PubMed1971

Glycerol-specific revertants of a phosphoenolpyruvate phosphotransferase mutant: suppression by the desensitization of glycerol kinase to feedback inhibition.

Glycerol-specific revertants were isolated from a phosphoenolpyruvate phosphotransferase mutant lacking enzyme I activity. Sixteen of the eighteen separately derived revertants were found to synthesize a fully active glycerol kinase no longer subject to feedback inhibition by fructose 1,6-diphosphate. The suppressor mutation mapped at the known glpK locus. When the fructose, 1,6-diphosphate-insensitive kinase allele was transduced into a strain producing the glp enzymes constitutively, cells of the resultant strain were susceptible to killing by glycerol if this compound was added to a culture growing exponentially in casein hydrolysate. This phenomenon had been previously described for a strain which had a constitutive glycerol kinase refractory to feedback inhibition, but isolated by a different procedure. It is suggested that the suppression of the growth defect on glycerol in the enzyme I(-) mutant by the fructose 1,6-diphosphate-insensitive kinase is achieved by increasing the in vivo catalytic potential of glycerol kinase. This increased activity would allow more rapid conversion of glycerol to l-alpha-glycerophosphate, the true inducer of the glp system. The enzyme I defect in the parental strain impaired the inducibility of the glp system so that the normal basal catalytic activity of the kinase was insufficient to insure induction by glycerol.

Biological Transport, Active↗
PubMed1971

Effects of thyroid disease on glucose oxidative metabolism in man. A compartmental model analysis.

Glucose oxidation to CO(2) in man at the fasted, steady state has been investigated in normal, hypothyroid, patients by monitoring the specific activity of plasma glucose and expired CO(2) after intravenous injection of glucose-1-(14)C, glucose-6-(14)C, and sodium bicarbonate-(24)C in tracer amounts. Making certain stoichiometric assumptions about the oxidation of the C-1 and C-6 carbons of glucose to CO(2), the data are incorporated into a multicompartmental model describing the kinetics of plasma glucose, plasma bicarbonate, and the conversion of glucose to CO(2) by the hexose monophosphate pathway and all other series and parallel pathways which oxidize glucose carbon to CO(2) (EMP-TCA). This formulation separates the distribution kinetics of glucose and bicarbonate from the kinetics of glucose oxidation to CO(2). It allows the calculation of a minimal fraction (varphi(t)) of glucose irreversibly oxidized to CO(2) which is based entirely on the duration of the experimental data. This calculation is independent of the extrapolative implications of the model beyond the experimental interval and of the particular model chosen to fit the data. All modeling and data fitting were performed on a digital computer with the SAAM program. Based on a 300 min experiment the analysis suggests that in hypothyroidism there is a decrease in the rate of glucose metabolized irreversibly (rhoG). There is also a decrease in the minimal fraction (varphi(300)) which is completely oxidized to CO(2) by way of the EMP-TCA. rhoG and varphi(300) are 0.56 and 0.42 mmole/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals. However, the fraction of the C-1 of glucose metabolized irreversibly which undergoes oxidation to CO(2) by the hexose monophosphate pathway (Psi) is not different from normal (0.07 and 0.07 respectively). The hyperthyroid studies suggest that rhoG and varphi(300) are within the normal range (1.01 and 0.46 mmoles/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals). However, Psi is decreased to less than half the normal value (0.03 as compared to 0.07 in normals).

Adolescent↗
PubMed1970

Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets.

Transport of plasma-free fatty acids (FFA) and of fatty acids in triglycerides of plasma very low density lipoproteins (VLDL-TGFA) was studied in two normal subjects, five patients with type IV hyperlipoproteinemia, and two patients with type I hyperlipoproteinemia. After intravenous pulse-labeling with albumin-bound 1-palmitate-(14)C, specific radioactivity of plasma FFA and VLDL-TGFA were determined at intervals up to 24 hr. The results were analyzed using several different multicompartmental models each compatible with the experimental data. Fractional transport of VLDL-TGFA was distinctly lower (no overlap) in the type IV patients than in the control subjects, both on a usual balanced diet (40% of calories from carbohydrate) and on a high-carbohydrate diet (80% of calories). However, net or total transport of VLDL-TGFA in the type IV patients was not clearly distinguishable from that in the control subjects, there being considerable overlap on either diet. The results suggest that in this group of type IV patients the underlying defect leading to the increased pool size of VLDL-TGFA is not overproduction but a relative defect in mechanisms for removal of VLDL-TGFA. Since some of these type IV patients had only a moderate degree of hypertriglyceridemia at the time they were studied, and since it is not established that patients with the type IV phenotype constitute a biochemically homogeneous population, the present results should not be generalized. Four studies were done (in two control subjects and two type IV patients) in which the kinetic parameters in the same individual were determined on the balanced diet and on the high-carbohydrate diet. All subjects showed an increase in VLDL-TGFA pool size. Using two of the models for analysis, all showed an increase in net transport of VLDL-TGFA; using the third model, three of the four studies showed an increase in VLDL-TGFA transport. The results are compatible with the interpretation that the carbohydrate-induced increase in VLDL-TGFA, both in controls and type IV patients, is at least in part due to an increased rate of production of VLDL-TGFA. The magnitude of the increase was approximately the same in controls and patients. Thus, metabolic adjustment to a high-carbohydrate regimen in these type IV patients may not be basically different from that in normal controls; the higher levels of VLDL-TGFA reached may simply be another reflection of a defective removal mechanism. An alternative interpretation, compatible with the data, would involve both a carbohydrate-induced increase in fractional rate of release of VLDL-TGFA from liver to plasma and a decrease in fractional removal of VLDL-TGFA from plasma without increase in net production rate. The simpler hypothesis of a single primary effect on net VLDL-TGFA production from FFA seems more likely.

Adolescent↗
PubMed1970

Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis.

Three different multicompartmental models of free fatty acid (FFA) and very low density lipoprotein triglyceride fatty acid (VLDL-TGFA) transport in man are formulated from plasma FFA and VLDL-TGFA tracee and tracer data collected over a 24 hr interval after the injection of palmitate-(14)C. All modeling and data fitting were performed on a digital computer using the SAAM program. Structural differences in the three models relate to the position of the slowly turning over compartment required to generate the late portion of the plasma VLDL-TGFA tracer data. The positions of this slow compartment are along the hepatic pathway from FFA to VLDL-TGFA (model A) or in the distribution system of VLDL-TGFA (model B) or in the distribution system of FFA (model C). Although all three models are equally consistent with our experimental data and are supported by observations of others, each reveals inconsistency with some data obtained from the literature. Consequently, a combination model of FFA-TGFA transport, incorporating properties of models A, B, and C would be more consistent with all available data. Experiments that would help to determine the quantitative significance of each of the slow compartments in the combination model are suggested. Several other models suggesting recycling of plasma VLDL-TGFA through the plasma FFA pool, kinetic heterogencity of the plasma VLDL-TGFA pool, and contamination of plasma VLDL-TGFA radioactivity with low density lipoprotein (LDL) TGFA radioactivity were tested. The first model does not explain the late portion of the plasma VLDL-TGFA tracer data. The second and third models, while consistent with our tracee and tracer data, have steady-state implications with respect to the extent of kinetic heterogeneity and size of the LDL-TGFA contaminant that make them unlikely. Assumptions underlying other investigator's models of FFA and TGFA transport in man are reviewed within the logical framework of our models. Quantitative differences among the various models are shown by evaluating all of the models with respect to a common set of plasma FFA and VLDL-TGFA data.

Carbon Isotopes↗