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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 19 recordsLinked to original sources

Tyrosine hydroxylase immunoreactivity in familial dysautonomia.

Tyrosine hydroxylase antigen was localized immunohistochemically in sympathetic neurons from human autopsy tissue. The reaction persists in paraffin-embedded tissue, and the method is applicable to archival specimens. Increased amounts in this antigen per cell may partially compensate for decreased numbers of sympathetic neurons in familial dysautonomia.

Adolescent

Appearance of tyrosine hydroxylase, aromatic amino-acid decarboxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase during the ontogenesis of the adrenal medulla: an immunohistochemical study in the rat.

The cellular localization of the enzymes tyrosine hydroxylase (TH), aromatic amino-acid decarboxylase (or dopa decarboxylase, DDC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of adult rats and rat fetuses (14th, 17th, 18th, 19th and 21st day) was examined. In the prenatal stages the medullary blastema and an adjacent part of the primitive sympathetic trunk were also investigated. Tissues were fixed in ice-cold 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.2). Cryostat sections (10 micron in thickness) were stained by the indirect immunofluorescence technique. Rabbit antibodies to TH (isolated from human pheochromocytoma), DDC, DBH and PNMT (the latter three isolated from bovine adrenal medulla) were used. Sections incubated with serum of non-immunized rabbits were used as controls. In the adult adrenal medulla, two cell types can be distinguished. One cell type contains only TH, DDC and DBH. The other cell type contains PNMT in addition. It is concluded that these cells correspond to the noradrenaline-(NA-) and adrenaline- (A-)storing cells respectively. In all prenatal stages TH, DDC and DBH are found in the primitive sympathetic trunk, in the medullary blastema, and in the medullary cells which have migrated into the cortical "anlage". PNMT is observed for the first time on the 18th day. Moreover, PNMT could only be demonstrated inside the adrenal gland. From these observations it is concluded that the capacity to synthesize NA is developed even before the "medullary" cells have reached the cortical "anlage". On the contrary, the capacity to synthesize A seems to be acquired only after this contact is established. The hypothesis is put forward that this phenomenon might indicate the induction of PNMT by glucocorticoids secreted by the fetal cortex.

Adrenal Medulla

Dementia in Parkinson Disease.

In 520 patients with parkinsonism seen over eight years, 168 (32%) had moderate to marked dementia. Although the demented patients were older than the nondemented patients (70.4 versus 65.5 years), the incidence of dementia in Parkinson's disease (PD) was tenfold higher than among controls (similarly aged spouses of PD patients), and dementia is held to be related more to the disease than to age. Demented patients, in addition to being older, developed PD later, were more severely involved in a shorter time, and responded less well to levodopa. It is suggested that PD with dementia may represent a different disorder from PD without dementia.

Aged

Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study.

Possible neurotoxic actions of intracerebral injections of ibotenic acid, a conformationally restricted analogue of glutamic acid, have been evaluated in rat brain and compared with those of kainic acid. Light microscopical analysis revealed that ibotenic acid produced a marked disappearance of nerve cells in all areas studied, namely striatum, the hippocampal formation, substantia nigra and piriform cortex. Lesions in areas distant to the injection site were not seen. Axons of passage and nerve terminals of extrinsic origin did not seem to be damaged, since, e.g., no apparent degeneration of the dopaminergic terminals in the neostriatum was observed except for a small area surrounding the cannula. In the neostriatum, enkephalin immunoreactive neuronal cell bodies as well as nerve terminals disappeared after injection of ibotenic acid into this nucleus. After injection into the substantia nigra tyrosine hydroxylase immunoreactive cell bodies in the zona compacta disappeared, whereas no certain effect could be seen on the enkephalin immunoreactive nerve fibers. In vitro experiments, conducted with striatal synaptosomal and membrane preparations, showed that ibotenic acid differed from kainic acid by being devoid of a significant inhibitory effect on high affinity glutamate uptake and by having a low affinity for 3H-kainic acid binding sites. Furthermore, ibotenic acid did not interfere with the binding of a number of radioligands for other transmitter receptors. As compared to kainic acid, ibotenic acid has the advantage of being less toxic to the animals and of producing more discrete lesions, possibly due to faster metabolism and/or other fundamental biochemical differences. Because of these special features, ibotenic acid seems to represent a valuable new tool in the morphological and functional analysis of central neuronal systems.

Animals

Distribution of PNMT and epinephrine in the medulla oblongata of normotensive and spontaneous hypertensive rats.

The distribution of the Epinephrine forming enzyme (PNMT) activity and Epinephrine (E) levels was investigated in the medulla oblongata of spontaneous hypertensive rats (SH-rats) and in two normotensive strains, namely Wistar Kyoto rats (WK-rats) and Wistar rats. The PNMT activity increases progressively from the caudal to rostral parts in the C1 and C2 regions of the medulla oblongata. The enzyme activity and the E levels are in all parts of the C1 and C2 regions higher in Wistar rats than in WK-rats. The PNMT activity in all parts of the C2 region (with the exception of the caudal region), and in the middle part of the C1 region is higher in SH-rats than in WK-rats. The E levels in the SH-rats are higher than in WK-rats in the mediocaudal parts of the C2 and C1 regions.

Animals

Catecholamine turnover changes in hypothalamus and dorsal midline area of the caudal medulla oblongata of spontaneously hypertensive rats.

The central noradrenaline (NA) and adrenaline (A) turnover in 15--16-week-old stroke prone, spontaneously hypertensive (sp-SH) female rats in an advanced stage of hypertension was found to differ from that of normotensive Wistar-Kyoto (WKy) control rats. The catecholamine (CA) levels were measured after inhibition of dopamine-beta-hydroxylase (DBH) or phenylethanolamine-N-methyltransferase (PNMT). in the hypertensive rats the dopamine (DA) and NA levels and the NA turnover were reduced in the hypothalamus, while in the dorsal part of the caudal medulla oblongata NA levels and A turnover were reduced. Changes in hypothalamic DA and NA mechanisms and in A mechanisms in medulla oblongata may therefore be of importance in the blood pressure regulation of sp-SH rats.

Animals

Enkephalin- and somatostatin-like immunoreactivities in human adrenal medulla and pheochromocytoma.

By using the Coons indirect immunofluorescence technique, enkephalin-like immunoreactivity with a granular localization was observed in human adrenal medullary gland cells and pheochromocytomas. In two of the tumors and in a few adrenal gland cells, a somatostatin-like peptide could also be identified. Catecholamine cell types were visualized on adjacent sections with antisera to the synthesizing enzymes dopamine-beta-hydroxylase [DBH; dopamine beta-monooxygenase; 3,4-dihydroxyphenylethylamine, ascorbate: oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1] and phenylethanolamine-N-methyltransferase (PNMT; noradrenalin N-methyltransferase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28). In the normal adrenal medulla more DBH- than PNMT-immunoreactive gland cells were observed. In the adrenal pheochromocytoma both DBH- and PNMT-positive cells were seen, whereas the two extra-adrenal tumors contained only DBH. These findings correlated well with plasma catecholamine measurements. Finally, enkephalin immunoreactive fibers and somatostatin immunoreactive cells were observed in a sympathetic ganglion extirpated together with one of the tumors.

Adrenal Gland Neoplasms

Selective loss of noradrenergic phenotypic characters in neuroblasts of the rat embryo.

To define the fate of embryonic neuroblasts in rat gut, which transiently express several noradrenergic traits, we investigated the high-affinity uptake of norepinephrine. At 12.5 days of gestation, these cells exhibited immunoreactivity to tyrosine hydroxylase [tyrosine 3-monoxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and endogenous catecholamine fluorescence. However, by 13.5 days these noradrenergic neurotransmitter phenotypic characters essentially disappeared. In contrast, norepinephrine uptake, which was also apparent at 12.5 days, persisted at least through 17.5 days. These observations indicate that norepinephrine uptake develops as an additional noradrenergic characteristic in these cells and persists after the disappearance of other noradrenergic traits. Consequently, neurotransmitter phenotypic characters may be transiently displayed during normal development in vivo.

Adrenergic Fibers