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Biomedical subjects

E Mezey

Publications and source records attributed to E Mezey.

285 records · Page 16Linked to original sources

Influence of male hormones on rates of ethanol elimination in man.

The effect of a reduction in androgens on ethanol elimination was determined in man. Bilateral therapeutic orchiectomy in nine patients for prostatic carcinoma decreased mean plasma testosterone levels from 489.8 +/- 31.2 (S.E.) ng per dl to 55.3 +/- 3.8 ng per dl and resulted in an increase in the rate of ethanol elimination in seven patients, no change in one, and a decrease in one. The mean rate of ethanol elimination for all nine patients increased from 83.6 +/- 4.0 to 100.4 +/- 4.2 mg per kg body weight per hr (p less than 0.02). The most likely mechanism for an increase in ethanol elimination after orchiectomy is an increase in liver alcohol dehydrogenase content, which remains to be demonstrated in man.

Aged↗

Enkephalin and neuropeptide Y: two colocalized neuropeptides are independently regulated in primary cultures of bovine chromaffin cells.

We have found that Neuropeptide Y is colocalized with enkephalin in bovine adrenal chromaffin cells. The two peptides can be found in the same granules in those cells where they coexist. These cells correspond to the adrenergic subpopulation of chromaffin cells since they contain the epinephrine synthetic enzyme, phenylethanolamine N-methyltransferase. Despite their coexistence, production of the two peptides is independently regulated. Enkephalin levels are doubled after nicotinic depolarization (which increases enkephalin synthesis) or after treatment with reserpine (which increases enkephalin precursor processing). Neither of these treatments, acting by different mechanisms, has any effect on the levels of Neuropeptide Y.

Adrenal Glands↗

Neuropeptide Y and peptide YY neuronal and endocrine systems.

An extensive system of neuropeptide Y (NPY) containing neurons has recently been identified in the central and peripheral nervous system. In addition, NPY and a structurally related peptide, peptide YY (PYY), containing endocrine cells have been identified in the periphery. The NPY system is of particular interest as the peptide coexists with catecholamines in the central and sympathetic nervous system and adrenal medulla. Evidence has been presented which indicates that NPY may play important roles in regulating autonomic function.

Animals↗

Partial coexistence of growth hormone-releasing hormone and tyrosine hydroxylase in paraventricular neurons in rats.

Immunocytochemistry revealed growth hormone-releasing hormone (GRF)-containing cells (4-10/50 microns thick coronal sections) in the ventral portion of the medial parvicellular subdivision of the paraventricular nucleus (PVN) in the rat. In the same region we also detected about the same number of neurons containing the mRNA that encodes GRF using in situ hybridization histochemistry. Fluorescence double labelling immunohistochemistry showed the presence of GRF and tyrosine hydroxylase (TH) in the same PVN neurons. The overlap between the two populations of cells is only partial: less than half of TH-positive cells contain GRF and vice versa.

Animals↗

Effect of testosterone administration on rates of ethanol elimination in hypogonadal patients.

Rates of ethanol elimination were determined in four hypogonadal subjects at one week and again at eight weeks after the administration of one dose of 200 mg of testosterone cypionate (Depo-testosterone). Ethanol elimination was unchanged in two patients, slightly decreased in one, and markedly increased in one patient at eight weeks as compared to one week after testosterone administration. In the three patients with little or no change in ethanol elimination, initial high levels of plasma-free testosterone, ranging from 445.0 to 3.8 ng/dl did not decrease to abnormally low levels, but ranged between 1.6 and 7.7 ng/dl (normal, 1.20-2.10 ng/dl). In the fourth patient, an increase in ethanol elimination from 86.6 to 107.4 mg/kg body weight/hr was associated with a decrease in plasma-free testosterone from a high level of 4.7 to 0.8 ng/dl. These results indicate that pharmacological plasma concentration of testosterone do not affect the rate of ethanol elimination. A suppressing effect of testosterone on rate of ethanol elimination may occur at levels of plasma-free testosterone which extend from abnormally low up into the normal physiologic range.

Adult↗

Ethanol increases ADP-ribosylation of histones in rat hepatocyte nuclei.

Ethanol was shown previously to increase ADP-ribosylation of hepatocyte proteins. The purpose of this study was to determine the effect of ethanol on ADP-ribosylation of histones in hepatocyte nuclei. Freshly isolated hepatocytes were exposed to 100 mM ethanol for 2 h and ADP-ribosylated histones were separated from nonribosylated histones by phenylboronate agarose chromatography. Both histone factions were then separated into the individual histones by 12% acetic-urea-triton polyacrylamide gel electrophoresis. Ethanol did not change the amounts of outer histone H1 or amounts of core histones (H2A, H2B, H3.1, and H4) but increased the histone variants H3.2 and H3.3. The principal effect of ethanol was to increase the ADP-ribosylation of all the above histones. Exposure of hepatocytes in culture to 100 mM ethanol for 3 days did not increase the synthesis of histones as determined by the incorporation of 14C-L-lysine, but increased the ADP-ribosylation of histones, principally histone H2A, determined from the incorporation of 2, 8, 3H adenosine. These results show that ethanol increases the ADP-ribosylation of histones. This is a potential mechanism for effects of ethanol on the regulation of gene expression and cell differentiation.

Adenosine Diphosphate Ribose↗

Adrenergic projections from the lower brainstem to the hypothalamic paraventricular nucleus, the lateral hypothalamic area and the central nucleus of the amygdala in rats.

Fine networks of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive fibers are found in the hypothalamic paraventricular nucleus--mainly in the anterior, dorsal and dorso-medial parvicellular subdivisions, the lateral hypothalamus (dorsal, lateral and ventral to the fornix) and in the central amygdaloid nucleus. Coronal hemisections of the brainstem through the rostral level of the medulla oblongata show that most hypothalamic and amygdaloid PNMT fibers arise from the medullary adrenergic cell groups. Fourteen, but not 10 days after total hemisections, PNMT fibers disappeared almost completely from the hypothalamus and amygdala, ipsilateral to the knife cuts. A small decrease was also observed in the ventral, lateral hypothalamus on the contralateral side. Partial depletion of PNMT-immunoreactivity in the hypothalamus and the amygdala after medial or lateral brainstem hemisections indicates that ascending PNMT-immunoreactive fibers pass through mainly the lateral portion of the medulla, but some fibers also in its medial portion. Midsagittal transection of the diencephalon slightly reduced PNMT immunostaining in the paraventricular nucleus and the lateral hypothalamus bilaterally. The results show that the ascending PNMT system essentially is ipsilateral, but probably with a small crossing-over component, both at the diencephalic and lower brainstem level.

Adrenergic Fibers↗

Vesicular monoamine transporters in the rat stomach.

Cellular distribution of vesicular monoamine transporters (VMATs), known to regulate vesicular storage and release of biogenic amines (i.e., catecholamines, serotonin, histamine, etc.), have been studied in the rat stomach using in situ hybridization histochemistry (ISHH) and immunohistochemical (IHC) techniques. 35S-UTP labeled riboprobes showed that mRNAs of both VMATs are expressed in the gastric mucosa. A combination of ISHH and IHC verified that most of the parietal cells (among other epithelial cells) express mRNA of the peripheral type transporter (VMAT1) while enterochromaffin-like cells (ECL) of the fundic mucosa express mRNA of the central type (VMAT2). In addition, with double fluorescent IHC we detected VMAT1 protein in serotoninergic enterochromaffin cells (EC) of the stomach and in gastrin producing G cells of the antral mucosa. Similarly to the fundus, VMAT2 protein was present in ECL cells and in the enteric plexus. Surprisingly, serotonin- and/or histamine-containing cells in the connective tissue compartments of the stomach (i.e., lamina propria and submucosa), immunoreactive for a mast cell specific antigen, displayed neither VMATI nor VMAT2 immunoreactivity. Distribution of VMATs in the rat stomach support our previous observations on aminergic properties of two important gastrointestinal (GI) epithelial cell populations primarily known for other specific secretory products, i.e. dopaminergic properties of acid producing parietal cells and histaminergic properties of gastrin producing G cells. These data emphasize the existence of a non-neuronal, intrinsic aminergic system in the GI tract.

Animals↗

Dopaminergic characteristics of isolated parietal cells from rats.

Recently we have identified a dopamine-producing system in the gastric mucosa of rats. All the available morphological data suggest that parietal cells synthesize dopamine. In the present study we investigated the dopaminergic characteristics of isolated parietal cells by different methods. Mixed gastric mucosal cells were isolated and size-fractionated by elutriation. The proportion of neurons, parietal and endocrine cells in the fractions were determined by immunocytochemistry (ICC) using antibodies to neurofilament, proton pump and chromogranin A, respectively. No neurons were found in any of the cell preparations, while 56% parietal cell and 0.0% endocrine cell were achieved in the parietally enriched fraction. By Western blot, a tyrosine hydroxylase (TH, the rate-limiting enzyme of the catecholamine synthesis) immunoreactive protein species was demonstrated in isolated mucosal cells, comigrating with the TH immunoreactivity from PC12 cells. The TH immunoreactivity was colocalized to parietal cells by ICC. Dopamine transporter (DAT), a regulator of extracellular/intracellular dopamine balance in the nervous system, was also demonstrated in parietal cells. A significant amount of dopamine and DOPA were measured by HPLC (13.4 and 9.57 pg/10(6) cell, respectively) in parietally enriched cell fraction. Since this enriched cell fraction was virtually clear of both neurons and endocrine cells, demonstration of TH enzyme, DAT and dopamine in this fraction confirms that the parietal cell population might be a major source of dopamine in the rat stomach, supporting our previous results achieved using whole tissue samples.

Animals↗

A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra.

The amino acid sequence of the opioid peptide Leu-enkephalin is found within several larger peptides, which are generated from the precursors proenkephalin and prodynorphin. Proenkephalin contains four copies of the sequence of Met-enkephalin, a single copy of the sequence of Leu-enkephalin and one copy each of two extended Met-enkephalin sequences. Proenkephalin contains three peptides--alpha-neo-endorphin, dynorphin A and dynorphin B--the N-terminal sequences of which are identical to that of Leu-enkephalin. There is good evidence that the large amounts of Leu-enkephalin found in the adrenal medulla are generated from the precursor proenkephalin, but as yet prodynorphin has not been shown to be processed to yield Leu-enkephalin. We show here that the relatively high levels of Leu-enkephalin found in the rat substantia nigra are supplied by striatonigral axons and generated from the precursor prodynorphin.

Animals↗

Increase of corticotropin-releasing factor staining in rat paraventricular nucleus neurones by depletion of hypothalamic adrenaline.

In response to stress, adrenocorticotropic hormone (ACTH) is released by corticotrophs in the anterior pituitary under the control of several central and peripheral factors including corticotropin-releasing factor (CRF), which was recently isolated from the brain and sequenced. Immunocytochemical studies have shown that most of the CRF-containing cell bodies that project to the median eminence are present in the hypothalamic paraventricular nucleus (PVN). A dense PNMT(phenylethanolamine-N-methyltransferase)-containing fibre network was also observed in the same region--PNMT is the final enzyme in the biosynthesis of adrenaline and has been demonstrated in the brain. In the present study we found an association of adrenergic nerve fibres and CRF neurones by immunohistochemistry using antisera to PNMT and CRF. To examine the functional significance of the adrenergic projection to the PVN, we blocked the synthesis of adrenaline using a specific inhibitor of PNMT. The depletion of adrenaline resulted in an increase in CRF immunoreactivity. The present results suggest that, as well as catecholamines which regulate ACTH release at the anterior pituitary level via a beta 2-adrenergic receptor mechanism, central catecholamines (mainly adrenaline) also affect ACTH release through their action on CRF cells. Peripheral catecholamines seem to have a direct stimulatory effect on the pituitary corticotroph cells, whereas the present findings suggest that central adrenaline-containing neurones have an inhibitory role in the physiological response to stress.

Animals↗

Co-localization of corticotropin-releasing factor and vasopressin in median eminence neurosecretory vesicles.

Vasopressin (VP) potentiates the effect of corticotropin-releasing factor (CRF) on the secretion of adrenocorticotropic hormone (ACTH) from anterior pituitary cells in vitro, and both CRF and VP have been found in portal blood. These data support the hypothesis that VP acts synergistically with CRF to cause the secretion of ACTH in vivo but the origin of the CRF and VP, and the physiology of their release, have not been precisely defined. Parvocellular cell bodies in the paraventricular nucleus (PVN) which project to the external zone of the median eminence can be stained for both CRF and VP after adrenalectomy, and there is light microscopic immunocytochemical evidence that neurophysin (NP) may be located within some of the CRF-containing axons. Electron microscopic immunocytochemical studies have demonstrated the presence of CRF, VP and its 'carrier' protein, VP-associated neurophysin (NP-VP) in 100-nm neurosecretory vesicles (NSVs) in axons terminating near the portal capillary plexus in the external zone of the median eminence. If these peptides are extensively co-localized in the same NSVs in the median eminence, then coordinate secretion of CRF and VP in vivo is obligatory, at least in some physiological circumstances. We demonstrate in this report, using post-embedding electron microscopic immunocytochemistry on serial ultrathin sections, that CRF, VP and NP-VP are contained not only in the same axons and terminals, but in the same 100-nm NSVs in the median eminence of both normal and adrenalectomized rats. In addition, in the normal rat median eminence 44% of the CRF-positive axons and terminals stained strongly for VP and NP-VP, whereas in the adrenalectomized rat virtually all the CRF-positive structures in the median eminence showed strong staining for VP and NP-VP, indicating a transformation of one subpopulation of CRF-positive axons and terminals by adrenalectomy.

Adrenalectomy↗

Erythrocyte aldehyde dehydrogenase activity in alcoholism.

Erythrocyte aldehyde dehydrogenase activity was determined in 44 chronic alcoholic patients within 18-36 hr after discontinuation of chronic alcohol intake and in 20 nonalcoholic controls. The enzyme activity was decreased to 4.98 +/- 0.52 mlU/mg of protein in the alcoholics as compared with a value of 8.25 +/- 1.29 mlU/mg of protein in the controls (p less than 0.05). The level of the enzyme activity did not correlate significantly with the daily quantity of alcohol consumption or the degree of liver injury reflected in elevations of serum aspartate aminotransferase. Repeat determination in 23 of the alcoholics after 2 weeks of supervised abstinence in an inpatient unit resulted in an increase in the enzyme activity to control levels. These findings show that the decreased activity of erythrocyte aldehyde dehydrogenase which occurs in association with alcohol ingestion is not an inherent characteristic of alcoholism.

Acetaldehyde↗

Neurotransmitters and neuropeptides in the baroreceptor reflex arc: connections between the nucleus of the solitary tract and the ventrolateral medulla oblongata in the rat.

The primary baroreceptor area (nucleus of the solitary tract-NTS) is anatomically interconnected with the rostral ("vasomotor area") and the caudal ("vasodepressor area") ventrolateral medulla by a well-defined arc of neuronal pathways. The chemical character and the direction of these pathways have been investigated with immunohistochemical and neurochemical techniques in intact and brainstem-operated rats. The transection of the neuronal arc resulted in an accumulation of tyrosine hydroxylase immunoreactivity in a small group of cells in the NTS adjacent to the area postrema, ipsilateral to the knife cut. Decreased angiotensinogen mRNA and atrial natriuretic peptide concentrations were measured in the ventrolateral medulla after the cut, and an accumulation of angiotensin II-immunoreactivity was found in neuronal perikarya in the ipsilateral NTS. Intracranial vagotomy caused marked depletions in glutamate levels in the subcommissural portion of the NTS and in the caudal ventrolateral medulla but nowhere else in the brainstem investigated including the rostral ventrolateral medulla.

Angiotensin II↗