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Biomedical subjects

H Weiner

Publications and source records attributed to H Weiner.

At least 199 records · Page 11Linked to original sources
PubMed1981

Possible steady-state concentrations of tetrahydroisoquinolines in brain after the consumption of ethanol.

Dopamine-derived tetrahydroisoquinolines such as salsolinol and tetrahydropapaveroline have been implicated in alcohol-related problems. Though their infusion into the brain can induce a rat to increase its alcohol consumption, it is not known whether the compounds actually form in vivo. Few investigators have been able to extract the compounds or their metabolites from tissue or urine. One notable exception is reported by Collins et al. (Science 206: 1184--1186; 1979), who found that alcoholics excrete 140 micrograms/24 h of O-methyl salsolinol and salsolinol. Using that value as the rate of salsolinol formation in brain, it was possible to estimate the steady-state concentration that could be expected to be found in brain. It was assumed that the rate of synthesis is equal to the rate of removal from tissue. Thus, the concentration is simply vf/kd, where vf is the rate of formation and kd is the rate constant for the disappearance from brain. It is necessary to estimate the concentration of dopamine and aldehyde in brain to determine the rate of formation. The realistic upper limits for salsolinol and tetrahydropapaveroline in brain are ca. 1 ng/g brain tissue. These values are below the level of detection commonly employed.

Alcohol Drinking↗
PubMed1981

Nicotinamide adenine dinucleotide activation of the esterase reaction of horse liver aldehyde dehydrogenase.

The esterase reaction catalyzed by horse liver aldehyde dehydrogenase is activated with NAD(H) by factors of 2 under a Vmax assay and of 6.8 at low ester concentrations (Feldman, R. I., & Weiner, H. (1972) J. Biol. Chem. 247, 267-272). Stopped-flow experiments suggested that an initial burst of 0.4 mol followed by a second burst of 1 mol of nitrophenol per mol of tetrameric enzyme occurred in the absence of NAD, while the magnitudes increased to 2 and 4 mol/mol of enzyme in its presence. If the enzyme was incubated for 1 min with NAD, the burst phase was 4 mol/mol of enzyme. Nonlinear Lineweaver--Burk plots were found in the absence and presence of NAD, but incubation with NAD for 1 min abolished the biphasic response. Mg2+ ions activate the dehydrogenase reaction of horse liver aldehyde dehydrogenase (Takahashi, K., & Weiner, H. (1980) J. Biol. Chem. 255, 8206-8209). The metal neither increased the esterase reaction nor affected the NAD activation. The rate-limiting step for the esterase reaction was thought to be the formation of an acyl intermediate, while that for the dehydrogenase reaction was deacylation (Weiner, H., Hu, J. H. J., & Sanny, C. G. (1976) J. Biol. Chem. 251, 3853-3855). Finding that a full burst exists for the esterase reaction in the presence of NAD shows that the deacylation step or product dissociation can become rate limiting. The major kinetic alteration produced by NAD is to increase the rate of acylation while not affecting deacylation. The presence of NAD appears to activate the attack of the active-site nucleophile on the carbonyl group of the substrate.

Aldehyde Dehydrogenase↗
PubMed1981

Genetic basis for the polymorphism of rat liver cytosolic aldehyde dehydrogenase.

Liver aldehyde dehydrogenase (ALDH), the enzyme involved in the oxidation of aldehydes such as acetaldehyde derived from ethanol, exists in multiple forms in most mammals. Up to five separable forms have been identified from the cytosolic fraction of Wistar rat liver. We investigated genetic basis of a particular set of three enzyme forms by selective breeding and analysis of electrophoretic patterns of liver ALDH by isoelectric focusing. The forms of liver ALDH investigated were at pI 5.8 or 6.2 or a triple form with enzymes at pI 5.8, 6.0, and 6.2. There are two alleles found at the ALDH locus which encode in homozygotes for one of two electrophoretically separable ALDH forms. A rat heterozygous at the locus forms both ALDH types plus a hybrid. The alleles are expressed codominantly, found at an autosomal locus, and remain constant postpartum. The activities associated with the triplet enzyme form were statistically indistinguishable from a 1:2:1 ratio. This suggests that the enzymes hybridize to form a set of dimers or tetramers of the form A2, AB, B2, or A4, A2B2, B4, respectively.

Aldehyde Dehydrogenase↗
PubMed1981

Base-line muscle tensions and motoric responding of schizophrenics.

Schizophrenics with high or low levels of frontalis muscle tensions while at rest (base-line) were instructed to respond (button-press) at different rates, allowed to respond at any rate they preferred, and reinforced for responding under different schedules of reinforcement. Information about response-reinforcement relationships was provided for each reinforcement schedule. High and low levels of base-line muscle tensions were associated with high and low rates of preferred and reinforced responding, respectively. Response rates also varied with different contingencies of reinforcement. Further, the data permit the following tentative conclusions: (a) under certain contingencies, responding may vary more with base-line muscle tensions than with the contingency of reinforcement, and (b) instructed rates of responding may not be correlated consistently with base-line muscle tensions.

Adult↗
PubMed1981

The production rate of cortisol declines during recovery from anorexia nervosa.

The plasma concentration of cortisol is elevated in many patients with anorexia nervosa. It has remained unclear whether this elevation of plasma cortisol level is due only to a slowing of the rate of cortisol metabolism or whether there is, as well, an increase in adrenal secretory activity in anorexia nervosa. We studied adrenocortical activity in 9 female patients and one male patient with anorexia nervosa before and during recovery. The 24-h mean level of plasma cortisol and the rate of urinary free cortisol excretion decreased during recovery, from 11.4 to 7.4 micrograms/dl and from 225 to 116 micrograms/day, respectively (P less than 0.005 and P less than 0.10, paired t test). These changes were associated with a significant decline in the rate of cortisol production from 24.3 to 17.9 mg/day as measured by radioisotope dilution (P less than 0.005). These results suggest that adrenal secretory activity is increased in anorexia nervosa and that the elevation of plasma cortisol level observed in this syndrome reflects not only a slowing of cortisol metabolism but also a rise in cortisol production.

Adolescent↗
PubMed1981

Increasing slowed operant responding of schizophrenics under a fixed-ratio schedule of reinforcement.

Two procedures were evaluated in terms of their ability to modify the slowed responding of schizophrenics under an FR 40 schedule. FR 40 response rates increased when schizophrenics were instructed to earn a minimum number of reinforcements or to imitate the rate of responding of someone shown earning that minimum number of reinforcements. The greater increase in FR 40 responding occurred under the latter procedure.

Conditioning, Operant↗
PubMed1981

Contributions of reinforcement schedule histories to our understanding of drug effects in human subjects.

Like other reinforcing stimuli, drug effects may vary with the reinforcement history of an individual. Data are presented which demonstrate that histories contribute to individual differences in response to reinforcement contingencies and modification of maladaptive behavioral persistence. Possible relevance of these findings to an understanding of drug effects in humans is discussed.

Adult↗
PubMed1980

Increase in S-adenosyl-L-methionine decarboxylase activity during the transformation of chick embroy fibroblasts by Rous sarcoma virus.

The increase in S-adenosyl-L-methionine decarboxylase activity in chick embryo fibroblasts after infection with Rous sarcoma virus has been studied. It has been shown that enzyme levels in transformed cells were two or three times higher than those of the non-infected controls. The activity of this enzyme was not elevated in chick embryo fibroblasts infected with a temperature sensitive mutant of Rous sarcoma virus (RSV-T5) at 42 degrees C, the non-permissive temperature. When the temperature of these infected cultures was shifted from 42 degrees C to 37 degrees C a two- or three-fold increase in decarboxlase activity was detected after 10 to 12 h. The half-live of S-adenosyl-L-methionine decarboxylase was practically identical in normal and RSV-transformed fibroblasts.

Adenosylmethionine Decarboxylase↗
PubMed1980

Vertical transmission of acquired ulcer susceptibility in the rat.

Premature separation of rat pups from their dams greatly increases their susceptibility to restraint-induced gastric erosions. When prematurely separated female rats grow to adulthood and mate with stock males, their normally reared F 1 progeny also have increased susceptibility to restraint-induced erosions. Cross-fostering studies show that prenatal rather than postnatal factors transmit this susceptibility to the F 1 progeny.

Animals↗
PubMed1980

Mechanism of the magnesium ion activation of the catalytic activity of horse liver aldehyde dehydrogenase.

The activity of the pI 5 isozyme of horse liver aldehyde dehydrogenase is markedly enhanced by some divalent metal ions (Ca, Mn, Mg), inhibited by others (Fe, Cu, Cd), totally inhibited by Hg, and not significantly affected by still others (Zn, Ni, Co). Steady-state kinetics show that with 0.5 mM Mg or Mn a 2-fold activation of the velocity measured at pH 7.5 occurs when propionaldehyde is the substrate. In the pre-steady state, the magnitude burst of NADH formulation is increased from 2 moles formed per mole of tetrameric enzyme to 4 moles formed in the presence of Mg. The stoichiometry of coenzyme (NADH, NAD, epsilon-NAD) binding is also increased from essentially 2 moles binding to 4 moles binding per mole enzyme in the presence of Mg. It appears that the enzyme exhibits half of the site reactivity in the absence of metal but has a full complement of catalytic sites in the presence.

Aldehyde Oxidoreductases↗
PubMed1980

Stability of ego defenses and endocrine responses in women prior to breast biopsy and ten years later.

Thirty women with breast masses were evaluated psychologically and endocrinologically ten years ago while they were awaiting breast biopsy (3). Eight of these women proved to have benign fibrocystic disease and 22 had breast cancer. A significant (p < 0.05) positive correlation was found between extent of failure of psychological "defenses" and cortisol metabolite excretion rate in these 30 women. On follow-up, 12 women had died (11 with cancer and one who had had benign disease); 7 women were lost to follow-up. Of the remaining 11, one refused to participate, leaving 10 women for follow-up study (7 who had had mastectomy for breast cancer and 3 with benign breast lesions). They were reevaluated using the same assessment techniques as 10 years before. The psychological parameters and cortisol metabolite excretion rates did not show a significant change over the span of ten years. These data support the hypothesis that these psychological parameters and cortisol metabolite excretion rates reflect relatively abiding characteristics and are not as much affected by a "psychosocial threat" as previous research has suggested.

17-Hydroxycorticosteroids↗
PubMed1980

The effect of alcohol on dopamine metabolism in the caudate nucleus of an unanesthetized monkey.

Previously it was shown that the acute administration of ethanol to the rat significantly alters the metabolism of the dopamine (DA) in liver but not in brain tissue. To extend this finding to the primate, two push-pull perfusion cannulae were implanted in the regions of the left and right caudate nucleus of a Macaca nemistrina. After 14C-DA was injected into the caudate, the site ws perfused with an artificial CSF and the perfusate analyzed for the major metalolites of DA. Ethanol was then administered in a dose of 6 g/kg by the nasopharyngeal route. The results show that very little alteration occurs in the metabolism of DA during or postethanol intoxication.

Animals↗