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H Weiner

Publications and source records attributed to H Weiner.

At least 163 records · Page 9Linked to original sources
PubMed1986

Effects of induction of rat liver cytosolic aldehyde dehydrogenase on the oxidation of biogenic aldehydes.

Phenobarbital and tetrachlorodibenzo-p-dioxin (TCDD) induce two different forms of aldehyde dehydrogenase (EC 1.2.1.3, ALDH), designated phi and tau respectively, in the rat liver cytosol. The physiological substrates for these enzymes are as yet unknown. In this study we investigated whether the induction of these enzymes forms affected the metabolism of dopamine and norepinephrine in rat liver slices. A 10-fold increase in phi-ALDH produced by phenobarbital treatment resulted in small increases in the formation of 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxymandelic acid from the biogenic amines. The 50- to 100-fold elevation of the tau-isozyme did not alter the rate of formation of the acids. When liver slices were incubated with 40 mM ethanol, the formation of the reduced products of dopamine and norepinephrine, 3,4-dihydroxyphenylethanol and 3,4-dihydroxyphenylglycol, respectively, was favored. Under these conditions, the induction of the phi-isoenzyme again produced only a small increase in the formation of the acid products, whereas the induction of the tau-isoenzyme had no effect on acid production from biogenic amine metabolism. The results suggest that neither the phi- nor the tau-forms of ALDH are involved in the hepatic metabolism of dopamine or norepinephrine and support the conclusion that the oxidation of the aldehyde derived from dopamine occurs in mitochondria [A. W. Tank, H. Weiner and J. Thurman, Biochem. Pharmac. 30, 3265 (1981)].

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Identification and selective precipitation of human aldehyde dehydrogenase isozymes using antibodies raised to horse liver aldehyde dehydrogenase isozymes.

Aldehyde dehydrogenase (ALDH) enzymes from human liver homogenates were recognized in immunoblotting experiments and precipitated in Ouchterlony double diffusion gels by antibodies raised to the horse liver mitochondrial and cytosolic ALDH isozymes. The antibody raised to the cytosolic horse liver ALDH (alpha HC) has been shown to be specific for cytosolic ALDH isozymes, while the antibody raised to the horse liver mitochondrial ALDH (alpha HM) precipitated both mitochondrial and cytosolic ALDH isozymes. It was possible to selectively remove the cytosolic ALDH from a homogenate of a liver sample from a Caucasian by preincubation with alpha HC; the remaining mitochondrial enzyme was then precipitated by alpha HM in double diffusion gels. The experiments were repeated with a liver sample from an Oriental, presumed to have been alcohol sensitive since no active mitochondrial ALDH was found. The precipitation of a relatively inactive mitochondrial enzyme by alpha HM from a cytosolic ALDH-free sample confirmed previous reports of the existence of a mitochondrial ALDH in tissue from an alcohol-sensitive Oriental. The results of immunoblotting experiments confirm the co-migration, in electrophoresis, of the cytosolic and mitochondrial ALDHs from the liver of an alcohol-sensitive Oriental. The results reported here, together with previous observations, indicate that the antibodies raised to horse liver ALDH isozymes can be used to determine the subcellular location of ALDH isozymes in various human tissues, including frozen tissue samples which are not amenable to subcellular fractionation.

Aldehyde Dehydrogenase↗
PubMed1986

Cushing's disease in a young woman with anorexia nervosa: pathophysiological implications.

This report describes a 17-year old student who was found to have Cushing's syndrome two years after she had developed anorexia nervosa (AN). The Cushing's syndrome was treated with bilateral resection of enlarged, hyperplastic, non-tumorous adrenal glands. The diagnosis was further confirmed four years later when, two to three years after new symptoms had appeared, an ACTH secreting pituitary adenoma (that is, Cushing's disease) was found on surgery. The possible mechanism for the development of Cushing's disease in a patient with prior anorexia nervosa, a sequence of events reported once previously, is discussed. It is suggested that increased hypothalamic-pituitary corticotroph stimulation in association with the anorexia nervosa, a now well-established endocrine phenomenon, activated an occult, inactive pituitary basophil adenoma in this patient, eventually resulting in autonomous pituitary overproduction of ACTH by the tumor.

Adenoma, Basophil↗
PubMed1985

Effects of disulfiram on the oxidation of benzaldehyde and acetaldehyde in rat liver.

The in vitro oxidation of benzaldehyde and acetaldehyde was studied in liver samples from disulfiram-treated and control rats. With 25 microM substrate, both cytosol and mitochondria appeared to make a nearly equal contribution to the oxidation of benzaldehyde, whereas ca. 90% of acetaldehyde oxidation occurred in mitochondria. When the Km values for benzaldehyde with aldehyde dehydrogenase (ALDH) were determined, two Km values (3 and 120 microM) were obtained with mitochondria, but only a single Km value (25 microM) was obtained with the cytosolic fraction. The relatively high Km (2.9 mM) found with microsomes makes it unlikely that microsomes are important in the oxidation of benzaldehyde. In intact mitochondria, with 200 microM acetaldehyde or benzaldehyde the matrix space enzyme accounted for 77 and 62%, respectively, of the total ALDH activity. When the activity was determined in a mixture containing both substrates, the activity was found not to be additive, indicating that both substrates are oxidized by the same matrix space enzyme. With subcellular fractions, from livers of disulfiram-treated and control rats, a greater degree of inhibition of ALDH was obtained when acetaldehyde was a substrate compared to that with benzaldehyde in cytosol and mitochondria. Microsomal ALDH was not inhibited by disulfiram. In liver slices from rats given disulfiram, a statistically significant inhibition was found when either 25 or 250 microM acetaldehyde was used (46 and 33%). With benzaldehyde, a significant inhibition (24%) was observed only with the lower substrate concentration. Finding that both mitochondrial fractions and slices were less inhibited at the higher substrate concentration implies that the high Km enzyme is not inhibited. It can be concluded that, in rat, disulfiram inhibiting liver ALDH not only affects oxidation of acetaldehyde, but also that of benzaldehyde.

Acetaldehyde↗
PubMed1985

Enzymatic requirement for cyanamide inactivation of rat liver aldehyde dehydrogenase.

The in vitro inactivation of aldehyde dehydrogenase (ALDH) by cyanamide in rat liver slices, in intact mitochondria, and at various stages of purity was characterized. Low-Km ALDH was more susceptible to cyanamide inactivation than was the high-Km form. In addition, the presence of NAD or NADH was necessary for cyanamide inhibition of the ALDH activity. Cyanamide at low concentrations required enzymatic conversion to a reactive derivative that could inhibit ALDH. The data in this study are consistent with the suggestion of DeMaster et al. [Biochem. biophys. Res. Commun., 122, 358 (1984)] that catalase is the cyanamide-converting enzyme. An inhibitor of catalase activity, malonate, decreased the rate of cyanamide inactivation of ALDH in intact mitochondria. Furthermore, affinity chromatography-purified ALDH, free of catalase activity, was not susceptible to cyanamide inactivation. This affinity-purified ALDH was only inactivated by high concentrations of cyanamide. Thus, an alternative pathway for ALDH inactivation may exist in which enzymatic modification of cyanamide is not necessary. It is more likely, however, that a contaminating enzyme in the ALDH preparation is capable of activating cyanamide.

Aldehyde Dehydrogenase↗
PubMed1985

Aldehyde dehydrogenase activity as the rate-limiting factor for acetaldehyde metabolism in rat liver.

The velocity of acetaldehyde metabolism in rat liver may be governed either by the rate of regeneration of NAD from NADH through the electron transport system or by the activity of aldehyde dehydrogenase (ALDH). Measurements of oxygen consumption revealed that the electron transport system was capable of reoxidizing ALDH-generated NADH much faster than it was produced and hence was not rate-limiting for aldehyde metabolism. To confirm that ALDH activity was the rate-limiting factor, low-Km ALDH in slices or intact mitochondria was partially inhibited by treatment with cyanamide and the rate of acetaldehyde metabolism measured. Any inhibition of low-Km ALDH resulted in a decreased rate of acetaldehyde metabolism, indicating that no excess of low-Km ALDH existed. Approximately 40% of the metabolism of 200 microM acetaldehyde in slices was not catalyzed by low-Km ALDH. Fifteen of this 40% was catalyzed by high-Km ALDH. A possible contribution by aldehyde oxidase was ruled out through the use of a competitive inhibitor, quinacrine. Acetaldehyde binding to cytosolic proteins may account for the remainder. By measuring acetaldehyde accumulation during ethanol metabolism, it was also established that low-Km ALDH activity was rate-limiting for acetaldehyde oxidation during concomitant ethanol oxidation.

Acetaldehyde↗
PubMed1985

Neurobiologic and psychobiologic mechanisms in gastric function and ulceration.

The initiation and termination of feeding behavior are not fully understood. The stomach has been implicated as one source of signals regulating food intake. The sight and smell of food are potent stimuli to gastric acid secretion and contraction. The mouth, upper gastrointestinal tract and liver contain receptors regulating food intake; afferent information passes into the brain stem and into the brain areas. Lateral hypothalamic lesions abolish feeding, raise the body temperature and basal gastric acid secretion and produce gastric erosions. Vagotomy and administering propantheline bromide abolish the increased acid secretion after such lesions; they also alter the mucosal barrier permitting diffusion of protons into mucosal cells. Several of the neuropeptides via the central nervous system stimulate or inhibit gastric acid secretion through modulation of the autonomic nervous system. Most animal models of gastric erosions are associated with a reduced body temperature. Unknown is whether or not this association is the result of increased levels of thyrotropin-releasing hormone-a potent stimulus to gastric acid secretion and erosion formation when injected intracisternally.

Animals↗
PubMed1984

An integrative model of health, illness, and disease.

Health has traditionally been viewed in this country as the opposite of illness, even though what constitutes "health" is usually not clearly defined. This article highlights the complexity of the factors that influence health, probes the relationship between illness and disease, and explores the possibilities of establishing an integrated view of health, illness, and disease.

Attitude to Health↗
PubMed1984

Distribution and properties of aldehyde dehydrogenase in regions of rat brain.

NAD-dependent aldehyde dehydrogenases (EC 1.2.1.3) were isolated from various subcellular organelles as well as from different regions of rat brain. The mitochondrial, microsomal, and cytosolic fractions were found to contain 40%, 28%, and 12%, respectively, of the total aldehyde dehydrogenase (5.28 +/- 0.44 nmol NADH/min/g tissue) found in rat brain homogenate when assayed with 70 muM propionaldehyde at pH 7.5. The total activity increased to 17.3 +/- 2.7 nmol NADH/min/g tissue when assayed with 5 mM propionaldehyde. Under these conditions the three organelles contained 49%, 23%, and 9%, respectively, of the activity. The enzyme isolated from cytosol possessed the lowest Km. The molecular weight of the enzyme isolated from all three subcellular organelles was approximately 100,000. Four activity bands were found by electrophoresis of crude homogenates, isolated mitochondria, or microsomes on cellulose acetate strips. Cytosol possessed just two of the forms. The total activity was essentially the same in homogenates obtained from cortex, subcortex, pons-medulla, or cerebellum. Further, the enzyme had the same molecular distribution and total activity in each of these four brain regions. Disulfiram was found to be an in vivo and in vitro inhibitor of the enzymes obtained from these brain regions. Mercaptoethanol, required for the stability of the enzyme, reversed the inhibition produced by disulfiram. The effect was greater for enzyme isolated from cytosol than from mitochondria. Calculations led to the prediction that aldehydes such as acetaldehyde are oxidized in cytosol.

Aldehyde Dehydrogenase↗
PubMed1984

What the future holds for psychosomatic medicine.

In the recent past, the questions that face a comprehensive psychosomatic medicine have been defined. These questions refer to the context in which disease begins, the timing of the onset of the disease, the role of previous social experience in predisposing to disease, and the choice of the particular disease. It is suggested that a study of bereavement may be paradigmatic in answering these four questions: Bereavement has been cited as a factor in a large variety of disease. However, bereavement may produce discriminated responses of grief; helplessness, hopelessness, and giving-up; and pathological mourning. Pathological mourning in turn may be associated with autoimmune disease. There is evidence that separation and bereavement produces changes in immune function but there is as yet no evidence that it produces distortions of the immune process. There are many factors that affect the timing of disease onset, including maturational ones. Many social experiences have been shown to alter behavior and bodily function and predispose to disease. The question of the choice of disease is determined not only by the effects of bereavement and early experiences, and age, but also by a multiplicity of predisposing ones some of which have been specified.

Animals↗