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Biomedical subjects

M J Brownstein

Publications and source records attributed to M J Brownstein.

At least 19 recordsLinked to original sources
PubMed1979

Nerve growth factor: effects on D-amphetamine-induced activity and brain monoamines.

Adult male rats were given 6-hydroxydopamine lesions of the nucleus accumbens, followed immediately by injections of saline or nerve growth factor (NGF; 125 B.U.) near the substantia nigra. Such lesions were previously reported to attenuate the locomotor response to D-amphetamine. NGF-treated rats showed an enhanced response to D-amphetamine (1.5 mg/kg) when tested 15 days postoperatively. Levels of dopamine and norepinephrine in the striatum and nucleus accumbens were equivalently depressed in the two lesion groups, indicating that the apparent recovery of the NGF-treated rats was probably not due to catecholaminergic neuronal regrowth. Intracerebral NGF administeration enhanced the response to D-amphetamine 15 days later in rats without lesions, and also appeared to result in increased turnover of brain norepinephrine and serotonin at 3, but not 15, days postadministration. NGF might increase dopamine turnover at 15 days, but the evidence obtained did not convincingly confirm or negate this possibility. The results in brain-damaged and intact rats, and also modify the apparent turnover of brain monoamines.

Animals↗
PubMed1979

alpha-Melanocyte-stimulating hormone: reduction in adult rat brain after monosodium glutamate treatment of neonates.

Intraperitoneal injection of monosodium glutamate in neonatal rates resulted in a 90 percent loss of alpha-melanocyte-stimulating hormone in hypothalamic and extrahypothalamic areas of the brain, whereas the amount of hormone in the pituitary gland did not change. The dramatic reduction of alpha-melanocyte-stimulating hormone in the brain suggests that is primary source there is the neuronal perikarya of the arcuate nucleus.

Animals↗
PubMed1979

Intraventricular carbachol mimics the effects of light on the circadian rhythm in the rat pineal gland.

Environmental lighting regulates numerous circadian rhythms, including the cycle in pineal serotonin N-acetyltransferase activity. Brief exposure of rats to light can shift the phase of this enzyme's circadian rhythm. Light also rapidly reduces nocturnal enzyme activity. Intraventricular injections of carbachol, a cholinergic agonist, can mimic both of these effects. Light and carbachol presumably act on the suprachiasmatic nucleus of the hypothalamus. These experiments demonstrate the feasibility of using a neuropharmacologic approach to the mechanisms underlying mammalian circadian rhythms.

Acetyltransferases↗
PubMed1979

Trypsin liberates an arginine vasopressin-like peptide and neurophysin from a Mr 20,000 putative common precursor.

Although the hypothesis that vasopressin and its associated neurophysin are synthesized together in one macromolecular common precursor was put forward more than a decade ago, direct conformation of this hypothesis has been lacking. A [35S]cysteine-labeled putative precursor for vasopressin-related neurophysin (Mr 20,000, pI 6.1) has been isolated from the supraoptic nuclei of rats. This precursor was subjected to limited proteolysis with trypsin which produced a Mr 10,000 protein and peptide products. The former was identified as neurophysin on the basis of its pH-dependent affinity for vasopressin and its behavior in isoelectric focusing systems (pI 4.6-4.8). The tryptic peptides proved to be vasopressin-like because they: (i) were rich in cysteine, (ii) comigrated with vasopressin on gel filtration columns in 6 M guanidine HCl, (iii) bound to a neurophysin-Sepharose affinity column at pH 5.7, and (iv) were recognized by antibodies against vasopressin. These data on the Mr 20,000, pI 6.1 protein represent direct experimental evidence for a candidate for the common precursor of vasopressin and neurophysin. We propose that this common precursor be called "propressophysin."

Animals↗
PubMed1979

Biosynthesis in vitro of immunoreactive 31,000-dalton corticotropin/beta-endorphin-like material by bovine hypothalamus.

Enzymatically dispersed bovine hypothalamic or cortical tissue was maintained in culture in the presence of (3)H-labeled amino acids. After such incubation, extracts of cells and of media contained (3)H-labeled products that were specifically bound by immobilized affinity-purified antisera to corticotropin (ACTH) and beta-endorphin. The majority of these products eluted in the void volume (V(0)) upon Sephadex G-50 gel filtration; minor (3)H-labeled products eluted in the regions of the ovine beta-lipotropin marker and in fractions having apparent molecular weights of approximately 12,000 and 3800. Sequential use of these immobilized antisera revealed that most of the V(0) material contained both ACTH and beta-endorphin antigenic determinants within the same molecule(s), whereas retarded material contained only one of the determinants. When this V(0) material was rerun on a Sephadex G-75 column, it coeluted with the 31-kilodalton precursor of both ACTH and beta-endorphin obtained from a bovine anterior pituitary extract. Thus, the high molecular weight immunoreactive ACTH/beta-endorphin-like (3)H-labeled product(s) derived from the hypothalamic culture is similar to the pituitary-derived precursor in containing the dual antigenic determinants and in its gel filtration characteristics. In contrast, the cortex-derived cell preparation was devoid of (3)H-labeled products specifically reactive with the antisera employed.

Adrenocorticotropic Hormone↗
PubMed1979

Immunoreactive and biologically active somatostatin-like material in rat retina.

Somatostatin-like activity, as determined by radioimmunoassay and bioassay, is present in HCl extracts of rat retina. The concentrations of immunoreactive somatostatin are 612 +/- 43 (mean +/- SEM)pg per whole retina of 0.621 +/- 0.044 pg/microgram of protein in retinas from rats killed by decapitation, values which are not significantly different from those in retinas from rats killed by ether inhalation. The immunoreactive somatostatin was partially purified and concentrated by immunoaffinity chromatography. Both the crude retinal extracts and the immunoaffinity-purified immunoreactive somatostatin inhibited, in a dose-related manner, the release of rat growth hormone from dispersed rat anterior pituitary cells in culture. When the immunoaffinity-purified immunoreactive somotostatin was subjected to gel filtration chromatography, 96% of the recovered somatostatin eluted as a peak corresponding in position to that of synthetic somatostatin. Retinas from a group of rats with hereditary degeneration of the photoreceptor cells and another group of rats studied 1 year after transection of the optic nerves demonstrated an increased concentration of immunoreactive somatostatin compared to controls.

Animals↗
PubMed1979

Adrenocorticotropin and beta-lipotropin in the hypothalamus. Localization in the same arcuate neurons by sequential immunocytochemical procedures.

Adrenocorticotropin and beta-lipotropin (beta-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-mum sections were immunostained first for either ACTH or beta-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and beta-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and beta-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained beta-LPH, but beta-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. beta-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and beta-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.

Adrenocorticotropic Hormone↗
PubMed1979

Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents.

In view of the potent influences of the central nervous system on glucose metabolism and on its hormonal regulators, and our recent finding of insulin and insulin receptors throughout the central nervous systsem, we have examined extreme conditions of hyperinsulinemia (obese mice) and hypoinsulinemia (streptozotocin-treated rats) with respect to changes in brain insulin and receptor content. Sprague-Dawley rats given streptozotocin (100 mg/kg body wt) developed severe diabetes and by 48 h showed no change in brain insulin. Rats given 65 mg/kg streptozotocin also had severe diabetes, but survived longer. Both at 7 d and at 30 d after streptozotocin treatment there was no significant change in brain insulin or in brain content of insulin receptors, despite the fact that peripheral hepatic receptors were elevated and pancreatic insulin was markedly depleted. The obese mice were studied at 8-10 wk when peripheral plasma insulin concentrations were 50-fold elevated and receptors on peripheral target cells were reduced to congruent with40-50% of normal; brain insulin concentrations and receptor content were indistinguishable from those of thin littermates. Thus, brain insulin, which is typically 10 times higher than plasma insulin concentrations, and brain receptor content, which is equivalent to receptor content on peripheral tissues, appears to be regulated entirely independently of hormone and receptor in the periphery. These findings are consistent with the hypothesis that insulin in the central nervous system is synthesized by the neural elements, and plays a role in the central nervous system which is unrelated to peripheral glucose metabolism.

Animals↗
PubMed1979

Effect of stress, adrenocorticotropin or corticosteroid treatment, adrenalectomy, or hypophysectomy on hypothalamic immunoreactive adrenocorticotropin concentrations.

Despite variations in plasma and/or pituitary ACTH concentrations, no changes in median eminence or medial basal hypothalamic immunoreactive ACTH-like concentrations were seen in rats studied 6 weeks posthypophysectomy, 12 h or 28 days after bilateral adrenalectomy, 6 days after implantation of corticosterone pellets (75 mg), after dexamethasone administration (300 micrograms/100 g BW, ip, twice daily for 4 days), or after chronic immobilization stress. The lack of concordant variation of brain, pituitary, and plasma ACTH concentrations further supports the suggestion of a nonpituitary, central nervous system origin of some portion of brain immunoreactive ACTH-like activity.

Adrenal Cortex Hormones↗
PubMed1978

Successful replantation of two avulsed scalps by microvascular anastomoses.

Two cases of immediate replantation of avulsed scalps by microvascular anastomosis are presented. This method of treatment seems to offer significant economic, social, and psychological advantages over split-skin grafting of the calvarium, or other presently used treatments. The need for secondary reconstructive procedures after a successful replantation is minimal, or nil. The mechanism of scalping is reviewed, and it is related anatomically to the structure of the galea aponeurotica. Specific recommendations are made regarding the immediate care of the avulsed scalp and the denuded calvarium, the value of a team approach in replantation, and various technical aspects of the procedure and postoperative management. The more frequent use of interpositional vein grafts is urged.

Adolescent↗
PubMed1977

On the origin of substance P and glutamic acid decarboxylase (GAD) in the substantia nigra.

Knife cuts in the frontal plane separating the anterior part of the caudate-putamen from the globus pallidus resulted in marked decreases in substances P levels in the reticular part of the substantia nigra. More caudal knife cuts were required in order to effect maximal decreases in nigral glutamic acid decarboxylase levels. Thus, there is a clear anatomical dissociation between the striatal neurons which project to the reticular part of the substantia nigra and which contain SP, and the more caudally located GAD-containing striatal and pallidal neurons, all of which travel through the globus pallidus on their way to the substantia nigra.

Animals↗