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M Berman

Publications and source records attributed to M Berman.

At least 127 records · Page 7Linked to original sources

Effects of estrogen on thyroxine-binding globulin metabolism in rhesus monkeys.

To investigate the effects of estrogen on thyroxine-binding globulin (TBG) metabolism, 4 female Rhesus monkeys were studied before and 3-4 weeks after implantation of beta-estradiol (E2)-containing capsules. In addition, 2 of the animals were also studied for the first 7 days after the start of E2. Serum E2 increased 10-fold from 20 +/- 7 to 212 +/- 41 pg/ml. Serum TBG, initially 20.2 +/- 6 mug/ml, was elevated by 24 h after E2 implantation, and reached a steady level of 46.8 +/- 5.0 mug/ml by 7-10 days. For the turnover studies, highly purified [125I]iodo-TBG was injected iv and serum [125I]PBI and urinary 125I excretion were measured daily. TBG kinetics were evaluated by use of a compartmental model. Although a 2-compartment model was sufficient to fit the control and late E2 data, a 3-compartment model was developed in order to account for the modifications observed during the early E2 period. The final decay rate (k) of TBG was 0.26 +/- 0.01/day during the control period and was slightly lower after E2 (0.23 +/- 0.01/day). In the 2 monkeys studied during the early E2 period, the major effect of E2 was a stimulation of the TBG production rate. This was simulated in the model by a stepwise increase occurring in the last quarter of the first day after E2. There was also an abrupt redistribution of TBG in the compartments defined by the model. The total distribution or serum equivalent volume of TBG after 3-4 weeks of E2 increased 1.4-fold, from 338 +/- 37 ml to 458 +/- 22 ml, and the metabolic clearance rate increased 1.3-fold, from 90 +/- 10 ml/d to 113 +/- 12 ml/d. The increase in the final TBG production rate (2.9-fold) was only slightly greater than the rate calculated for the early E2 period, and was similar to the increase we have recently found in monkey hepatocytes studied in vitro after isolation from E2-treated animals. It appears that stimulation of hepatic synthesis of TBG accounts for the elevated serum levels of TBG observed after estrogen.

Animals

The turnover and conversion to glucose of alanine in newborn and grown dogs.

The extent of transfer of carbon atoms from alanine to glucose was examined in pups and grown dogs. [U-14C]Alanine and [2-3H]glucose were injected intravenously and by using the SAAM-26 program a compartmental model was formulated from the tracer data to quantify the kinetics of the alanine- and glucose-carbon system. A 3-compartment model was necessary to describe the alanine-carbon kinetics. Strict identification of these compartments with physiological counterparts was not possible. The overall transport (turnover) rate of alanine-C was found not to change significantly with age when calculated on the basis of body weight. Carbon atoms from alanine reach glucose by three identifiable pathways of different speed. The kinetics suggest that the different pathways are at least in part due to differences in the metabolism of the three carbon atoms of alanine. In pups less than 11 days of age 45-49% of the carbon atoms leaving the alanine subsystem enter glucose; in adults it was 70%. In young pups 18-19% of glucose-C utilized was derived from alanine-C, whereas in adults, 62%. Accordingly a smaller percentage of carbon atoms utilized as alanine appears in glucose and a smaller percentage of glucose-C is derived from alanine in pups than in grown dogs.

Age Factors

Pertechnetate distribution in man after intravenous infusion: a compartmental model.

Using a primed infusion technique, distribution of pertechnetate was monitored in normal volunteer subjects over an 8-hr period. Two groups of subjects were studied, during hours 0-4 (n = 8) and hours 4-8 (n = 7), respectively, of the infusion. At 6.5 hr a large dose of NaI (1000 mg) was administered intravenously to the second group. Plasma, salivary, and urinary radioactivities were assayed, and external counts were made of radioactivities over the neck, thigh, and right upper abdomen. A kinetic model was developed for pertechnetate based upon the distribution data, the iodide perturbation, and known physiology for pertechnetate and iodide. The model has three major subsystems: (1) the thyroid trap; (2) a whole-body distribution, containing plasma and two extravascular compartments; and (3) the gastrointestinal tract, including the salivary, stomach (including upper small intestine), and two lower intestinal compartments. One of the latter, which turns over very slowly, is believed to represent bowel wall. The large NaI dose markedly reduced transport into compartments of the thyroid trap, the saliva, and the stomach and small intestine. This study shows that, in most respects, pertechnetate is distributed qualitatively but not quantitatively like iodide but that, unlike iodide, large bowel distribution plays an important role, especially in long-term studies.

Adult

Evidence for a new intermediate state in the mechanism of (Na+ + K+)-adenosine triphosphatase.

A rapid mixing technique was used to follow the intermediate formation of phosphorylated enzyme and liberation of inorganic phosphate by a microsomal preparation of (Na+ + K+)-ATPase. In the presence of 100 mM Na+,but without added K+, phosphorylation reaches a constant level at a rate which is dependent on ATP concentration. Inorganic phosphate production lags during the inital phase of phosphorylation and then accumulates at a constant rate. These observations favor a scheme in which Pi is liberated as the result of turnover of the phosphorylated enzyme. In the presence of 100 mM Na+ and 2.5 mM K+ phosphate production was resolved into two phases consisting of an initial 'burst' and late steady state phase...

Adenosine Triphosphatases

Cerebral dominance for consciousness.

In a prospective study we evaluated the relationship of level of consciousness to hemispheric side of lesion following acute cerebrovascular injury. Fifty-seven percent of patients with left hemispheric lesions had initial impairment of consciousness, in contrast to 25% with right-sided damage.

Cerebrovascular Disorders

Effects of age and fasting on gluconeogenesis from glycerol in dogs.

The extent of gluconeogenesis from glycerol was examined in pups and adult dogs. With use of the SAAM-26 program, a four compartment model was formulated from tracer data to calculate the kinetics of the glycerol:glucose system. In the postabsorptive state gluconeogenesis from glycerol declines with age: 13.8% of glucose carbon originated from glycerol in 0- to 4-day-old pups, 6% in adults. Approximately 50% of glycerol carbon is converted to glucose carbon independent of age. During fasting, a) the percentage of glucose carbon arising from glycerol carbon increased to 13.3% and 10.3% in adult dogs and pups 5-19 days old, respectively, in younger pups it declined to 3.4%; b) glycerol production increased in adults, but decreased in the youngest pups; c) glucose production and utilization decreased at all ages, and a smaller percentage of glycerol carbon was converted to glucose carbon, especially in the youngest pups. Thus in neonates fasting decreases gluconeogenesis from glycerol.

Aging

Effects of arterial versus venous sampling on analysis of glucose kinetics in man.

A compartmental model is presented to account for transient and steady-state changes in blood glucose concentration which result from transit through the forearm and hand in man. This model permits the inter-conversion of arterial and venous data and the derivation of arterial equivalent total body glucose models from venous data. Data were obtained from subjects in the basal state following a pulse injection of [1-14C]glucose tracer. An artery, an antecubital vein, and a dorsal vein of a heated hand (68 degrees C environment) were sampled. Blood transit time is shorter 0.3 vs. 1.0 min) and irreversible glucose loss is reduced (1.9 vs. 2.9%) in the heated hand preparation when compared to the antecubital vein preparation. Because of the smaller correction required and the smaller variation among individuals when heated hand rather than antecubital vein data are obtained, we suggest that for analysis of whole-body kinetics such data should be used along with the compartmental model correction when arterial data cannot be obtained.

Adult

Directional forces.

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Extraoral Traction Appliances

The hepatic adenylate cyclase system. III. A mathematical model for the steady state kinetics of catalysis and nucleotide regulation.

This paper presents a steady state kinetic model for hepatic adenylate cyclase. The activity of the enzyme has been assayed in the presence of a range of concentrations of magnesium, adenylylimidodiphosphate (App(NH)p), 5'-guanylylimidodiphosphate (Gpp(NH)p), and in the presence and absence of saturating concentrations of glucagon. The data were tested against proposed models using an iterative least squares curve fitting program (SAAM25) and confidence estimates for the model parameters were obtained. Hepatic adenylate cyclase is viewed as an enzyme having three characteristic states of catalytic function (E, E', E''). Each state has its own intrinsic activity in carrying out the catalysis of MgApp(NH)p-3 minus to form cyclic adenosine 3':5'-monophosphate. It is shown, in agreement with a proposal by de Haën, that unchelated substrate can inhibit adenylate cyclase activity. It is further concluded that this inhibition is principally due to App(NH)pH-3 minus. The three catalytic states differ markedly in their susceptibility to inhibition as well as in their Vmax, but the Km for MgApp(NH)p-2 minus is essentially the same for all states. The state transitions induced by Gpp(NH)p and by hormone are considered. Gpp(NH)p binding to state E causes transformation to state E'. State E' undergoes spontaneous transformation to state E''. Glucagon augments the transition from E' to E''. We conclude that the activating species of Gpp(NH)p is an unchelated form, most probably Gpp(NH)p-4 minus. Our results indicate that state E' is significantly more susceptible to inhibition by App(NH)pH-3 minus than the other two states. Certain phenomena occurring in fat cell adenylate cyclase are discussed in light of our findings in hepatic adenylate cyclase.

Adenine Nucleotides

Preliminary model for human lipoprotein metabolism in hyperlipoproteinemia.

A model is proposed for the metabolism of plasma lipoprotein apoproteins based on studies of a hyperlipoproteinemic subject who received 2.5 mCi[3H]leucine intravenously. Measurements included apoprotein specific activities (apo-B and apo-C) of very low density lipoprotein (VLDL) and of three low density lipoprotein (LDL) subspecies, Sf 17 LDL, Sf 10 LDL, and Sf 4 LDL. Activities of plasma albumin were also determined. The data were analyzed using a compartmental model and the SAAM computer program. A chain-like series of compartments were necessary to simulate plasma VLDL kinetics, suggesting a multistep delipidation process. The data are consistent with the notion that VLDL is the dominant LDL precursor. Two modes of conversion from VLDL to LDL are required. After partial delipidation some VLDL is converted to the Sf 17 LDL, while the remainder undergoes further delipidation before being converted to Sf 4 LDL, the major plasma LDL component. Some direct release of LDL into plasma had to be introduced to fit the data, about 24% of total LDL production. The three LDL subspecies follow a precursor-product relationship (Sf 17 leads to Sf 10 leads to Sf 4). The analysis also indicates that in using labeled leucine as a tracer, the slow exchange of leucine with the total body protein pool must be considered in trying to resolve the LDL subsystem and in the estimation of steady-state apoprotein levels. In view of the fact that the proposed model is based predominantly on the data from a single patient, no generalizations can be made about parameter values. The study is most valuable, however, in pointing out metabolic pathways not considered before and in calling attention to variables that must be considered in the design of experiments to study lipoprotein kinetics.

Apoproteins

A model of the kinetics of insulin in man.

The design of the present study of the kinetics of insulin in man combines experimental features which obviate two of the major problems in previous insulin studies. (a) The use of radioiodinated insulin as a tracer has been shown to be inappropriate since its metabolism differs markedly from that of the native hormone. Therefore porcine insulin was administered by procedures which raised insulin levels in arterial plasma into the upper physiologic range. Hypoglycemia was prevented by adjusting the rate of an intravenous infusion of glucose in order to control the blood glucose concentration (the glucose-clamp technique). (b) Estimation of a single biological half-time of insulin after pulse injection of the hormone has been shown to be inappropriate since plasma insulin disappearance curves are multiexponential. Therefore the SAAM 25 computer program was used in order to define the parameters of a three compartment insulin model. The combined insulin mass of the three compartments (expressed as plasma equivalent volume) is equal to inulin space (15.7% body wt). Compartment 1 is apparently the plasma space (4.5%). The other two compartments are extra-vascular; compartment 2 is small (1.7%) and equilibrates rapidly with plasma, and compartment 3 is large (9.5%) and equilibrates slowly with plasma. The SAAM 25 program can simulate the buildup and decay of insulin in compartments 2 and 3 which cannot be assayed directly. Insulin in compartment 3 was found to correlate remarkably with the time-course of the servo-controlled glucose infusion. Under conditions of a steady-state arterial glucose level, glucose infusion is a measure of glucose utilization. We conclude that compartment 3 insulin (rather than plasma insulin) is a more direct determinant of glucose utilization. We suggest that the combined use of glucose-clamp and kinetic-modeling techniques should aid in the delineation of pathophysiologic states affecting glucose and insulin metabolism.

Adolescent

Interrelations in the oxidative metabolism of free fatty acids, glucose, and glycerol in normal and hyperlipemic patients. A compartmental model.

Palmitate, glucose, and glycerol oxidation to CO(2) have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-(14)C]palmitate, [1-(14)C]glucose, or [1-(14)C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO(2) were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO(2). A bicarbonate subsystem was also included in the model to account for its role in shaping the CO(2) curves. All the CO(2) activity following a palmitate injection could be accounted for by a direct oxidative pathway from plasm FFA with the addition of a 20-min delay compartment. The same also applied to glucose, except that the delay compartment had a mean time of about 150 min. Only about a third of the injected glycerol was directly oxidized to CO(2) from plasma; the delay time was about 4 min. Most of the remainder was converted to glucose. In normals about 45% of the FFA is oxidized to CO(2) directly. This constitutes about 30% of the total CO(2) output. In hyperlipemia the CO(2) output is nearly unchanged and the contribution from FFA is nearly the same. There is a considerable increase (factor of 2), however, in FFA mobilization, most of which is probably diverted to triglyceride synthesis. The glucose and glycerol subsystems are roughly the same in normals and hyperlipemics. About 50% of glucose is oxidized by the direct pathways which accounts for about 35% of the CO(2) output. Glycerol accounts for only 1.5% of the CO(2) produced. Major changes occurred in the glycerol and glucose subsystems in glycogenosis. The changes are consistent with the known deficiency in glucose-6-phosphatase in this disorder. There is a considerable reduction (factor of 2 or more) in the release of glucose to plasma (gluconeogenesis) and in the conversion of glycerol to glucose. Despite the integration of the kinetics of the glucose, glycerol, and FFA subsystems over a 24-h period, 36% of the CO(2) production was still unaccounted for in normals and 50% in hyperlipemics. Thus, some of the carbon must wind up in very slowly turning-over pools which supply CO(2) through subsystems not covered in these studies (triglycerides, glycogen, amino acids, etc.). All the modeling was carried out with the aid of the SAAM25 computer program.

Adolescent