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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 397 records · Page 22Linked to original sources
PubMed1986

LHRH and catecholamine neuronal systems in the olfactory bulb of the mouse.

The luteinizing-hormone-releasing hormone (LHRH) components of the mouse olfactory system were studied by using the indirect immunohistofluorescence technique. LHRH-positive cell bodies were found in both the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB); two distinct cell groups were found--one located adjacent to the AOB in the dorsal part of the MOB and a second in the superficial ventromedial aspect of the MOB. LHRH-positive fibers were found predominantly in the posterior half of the main olfactory bulb innervating the olfactory nerve layer, the glomerular layer, the external plexiform layer, and the mitral cell layer, and small numbers innervated the AOB. The greatest density of LHRH-immunoreactive fibers was seen adjacent to the AOB where one group of LHRH-positive cells was noted. Sections adjacent to those stained with LHRH antibody were analysed for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). The TH staining was intense for both cells and fibers in the glomerular layer of the MOB. In the AOB lower numbers of cell bodies and fibers were seen in the glomerular layer. The internal granular layer and internal plexiform layers were both stained, the internal granular layer showing more intensely fluorescent fibers with a higher density. Since no overlapping DBH-positive fibers were found here, these TH-positive nerve endings may be dopaminergic. DBH staining was confined to sparse networks of weakly fluorescent fibers with the highest numbers in the internal plexiform layer of the AOB and fewer fibers in the external plexiform, rostral, and granular layers of the MOB. Elution-restaining experiments revealed that the LHRH-positive and TH-positive elements represent different cell populations.

Animals↗
PubMed1986

Preferential vulnerability of A8 dopamine neurons in the primate to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Immunohistochemical examination of the midbrain of vervet monkeys treated with MPTP revealed a marked loss of dopaminergic neurons in the lateral, but not medial, region of the A8 dopamine (DA) cell group. In the same animals, the number of DA neurons in the substantia nigra was only slightly decreased. Biochemical assessment revealed a marked (greater than 85%) depletion of DA in the striatum. However, in the DA cell body regions significant decreases in DA and homovanillic acid were observed only in the lateral A8 region, and not in the medial A8 region or substantia nigra. These data suggest that those A8 DA neurons which project to the striatum are preferentially vulnerable to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists.

The dose response curve for apomorphine reversal of gamma-butyrolactone (GBL)-induced L-DOPA accumulation in rat striatum was shifted almost 6-fold to the right after partial irreversible blockade (83%) of dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ); however, the maximal response was not reduced. In contrast, the major effect of a similar degree of irreversible blockade (86%) on the dose-response curve for the autoreceptor-selective agent EMD 23,448 was a reduction in maximal response (60% of control), indicating that EMD 23,448 is a partial agonist. A large receptor reserve therefore exists at the DA autoreceptor, which may explain in part why many DA agonists are more potent in models pre- than postsynaptic receptor activation.

4-Butyrolactone↗
PubMed1986

Dopamine agonist induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brainstem: possible pharmacological model for Lesch-Nyhan syndrome.

We have investigated the effects of various dopamine (DA) agonists on induction of abnormal involuntary movements (AIM) in a group of monkeys which had denervated nigro-striatal DA neurons for 10-14 years rendered by a unilateral surgical ventromedial tegmental (VMT) lesion of the brainstem. The surgical lesions were placed when the monkeys were 2-4 years old. The administration of mixed DA agonists, such as L-DOPA, apomorphine (Apo) and abeorphine 201-678, elicit a self-mutilative biting behavior (SMB) of the forelimb digits contralateral to the lesion, and spasticity of the contralateral hindlimb. These dysfunctions resemble, in some aspects, the neurological disturbances associated with Lesch-Nyhan syndrome. The SMB behavior was elicited by mixed DA agonists which predominantly stimulate D1, but not D2 DA receptors, and was prevented or abolished by the D1 DA antagonist SCH 23390 or by the D1 and D2 DA antagonist fluphenazine (Flu), but not by the D2 antagonist (+/-)sulpiride. These results suggest that DA agonist-induced SMB behavior is mediated by D1 and/or by both D1 and D2 DA receptor pathways. To study the relationships between HPRT, the defective enzyme in Lesch-Nyhan syndrome, and the DA neuronal systems, we have measured the effects of nigro-striatal DA degeneration and intrastriatal neuronal degeneration on HPRT activity. The unilateral 6-OHDA-induced nigro-striatal DA degeneration does not significantly alter the HPRT activity on the lesioned side of the striatum, while the quinolinic acid-induced intrastriatal neuronal degeneration significantly reduces the enzyme activity. These results suggest that HPRT is localized on intrastriatal neurons which are also known to contain DA receptors. It is postulated that HPRT deficiency in Lesch-Nyhan syndrome results in abnormal guanine nucleotide metabolism which may affect the regulation of DA receptors.

Animals↗
PubMed1986

Analysis of [3H]spiperone binding sites in the rat striatum and frontoparietal cortex by means of quantitative receptor autoradiography after inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: selective protection by sulpiride in the striatum.

By means of quantitative receptor autoradiography in combination with inactivation of dopamine (DA) receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), it was demonstrated in the male rat that [3H]spiperone predominantly labels D2 receptors in the striatum, nucleus accumbens and tuberculum olfactorium, and predominantly non-DA receptors in the frontoparietal cortex, probably mainly serotonin type 2 (5-HT2) receptors in layer IV. Furthermore, the [3H]spiperone-labelled D2 receptors found all over the dorsal and ventral striatum appear to be similarly inactivated by EEDQ and protected by the D2 antagonist (+/-) sulpiride but not the D1 antagonist SCH 23390, indicating a homogeneity of the striatal D2 receptors.

Animals↗
PubMed1986

Activation of the locus coeruleus induced by selective stimulation of the ventral tegmental area.

The effects of selective stimulation of perikarya, but not axons of passage, within the ventral tegmental area (VTA) on the locus coeruleus (LC) noradrenergic system were examined. Anterograde and combined retrograde-immunohistochemical studies indicated both dopaminergic and non-dopaminergic projections to the region of the LC originating from the VTA. Kainic acid (KA) stimulation of the VTA resulted in a dose-dependent increase in the levels of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) in the prefrontal cortex, and also elevated levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenolglycol (MHPG). Prefrontal cortical MHPG levels did not increase in response to vehicle injection or KA infusion into the hippocampus, nor did concentrations of this metabolite increase in the prefrontal cortex in response to intra-VTA KA in animals with neurotoxic lesions of the VTA. KA injection into the VTA resulted in increased MHPG levels in the hippocampus, but not the hypothalamus. Dorsal noradrenergic bundle knife cuts prevented the KA-elicited prefrontal cortical MHPG increase. These data suggest that stimulation of the mesocoeruleo dopaminergic projection arising from the VTA results in selective excitation of the LC-derived dorsal bundle noradrenergic system.

Animals↗
PubMed1986

The pathophysiological functions mediated by D1 dopamine receptors.

The administration of the D1 DA receptor antagonist SCH 23390 produces catalepsy in rat, and this behavior can be abolished by pretreatment with selective D2 DA receptor agonists. The administration of mixed D1/D2 DA agonists, but not of selective D2 DA agonists, produces SMB behavior in monkeys with surgical unilateral VMT lesions of the brain stem. The DA agonist-induced SMB behavior is abolished by pretreatment of the monkeys with either the D1 DA antagonist SCH 23390 or with the mixed D1/D2 antagonist fluphenazine, but not with the selective D2 antagonist (+/-) sulpiride. A hypothetical relationship between abnormal guanine nucleotide metabolism in Lesch-Nyhan syndrome and the development of DA receptor supersensitivity is presented. The possible role of abnormal guanine nucleotide metabolism in some mental disorders associated with DA dysfunctions is discussed.

Animals↗
PubMed1986

Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen. Biochemical and immunohistochemical evidence.

The subcellular distribution of noradrenaline (NA), neuropeptide Y (NPY), Met- and Leu-enkephalin (ENK), substance P (SP), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP) was investigated in homogenates of bovine splenic nerve. The distribution of noradrenergic peptide-containing nerves in the bovine celiac ganglion, splenic nerve and terminal areas in spleen was studied by indirect immunofluorescence histochemistry using antisera to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), NPY, enkephalin peptides, SP, SOM, VIP, and peptide HI (PHI). After density gradient centrifugation, high levels of NPY- and ENK-like immunoreactivity (LI) were found in high-density gradient fractions, coinciding with the main NA peak. SP, SOM and VIP were found in fractions with a lower density, VIP being also enriched in a heavy fraction; the latter three peptides were present in low concentrations. Immunohistochemistry revealed that staining for NPY-LI and ENK-LI partly overlapped that for TH and DBH in celiac ganglia, splenic nerve axons and terminal areas of spleen. Almost all principal ganglion cells were TH- and DBH-immunoreactive. Many were also NPY-immunoreactive, whereas a smaller number were ENK-positive. In the celiac ganglion patches of dense SP-positive networks and some VIP/PHI- and ENK-immunoreactive fibers were seen around cell bodies. The results indicate that NPY and ENK are stored with NA in large dense-cored vesicles in unmyelinated axons of bovine splenic nerve. SP, SOM and VIP appear in different organelles in axon populations separate from sympathetic noradrenergic nerves.

Adrenergic Fibers↗
PubMed1986

Striato-nigral dynorphin and substance P pathways in the rat. I. Biochemical and immunohistochemical studies.

The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Activation of alpha 2-adrenoreceptors enhances haloperidol-induced suppression of operant behavior.

Inhibition of catecholamine synthesis by alpha-methyl paratyrosine (alpha-MT) was previously shown to potentiate the behavioral suppression caused by dopamine-receptor antagonists. This effect of alpha-MT is in all probability due to inhibition of the compensatory increase in dopamine turnover induced by the dopamine receptor antagonists. In the present study we investigated the effect of the alpha 2-adrenoreceptor agonist clonidine on the haloperidol-induced suppression of food-reinforced lever-pressing behavior (fixed ratio 40:1) in rats. Small behaviorally inactive doses of clonidine were found, in analogy with alpha-MT, to enhance the haloperidol-induced suppression of the lever-pressing behavior. The haloperidol-induced increase in dopamine synthesis (measured as the accumulation of DOPA after inhibition of aromatic amino acid decarboxylate) was antagonized by clonidine in the striatum as well as in the dopamine rich limbic regions. Prazosin, a selective alpha 1-adrenoreceptor antagonist had no effect on the clonidine induced behavioral changes. Idazoxane, a selective alpha 2-adrenoreceptor antagonist, counteracted both the behavioral and biochemical effects of clonidine, indicating that these effects of clonidine are mediated via its action on alpha 2-adrenoreceptors. The present findings provide support for the notion that alpha 2-adrenoreceptors may participate in the regulation of nigro-striatal as well as meso-limbic dopaminergic activity. It is suggested that alpha 2-adrenoreceptor agents, especially in combination with classical antipsychotics, might be of therapeutic value in the treatment of disorders associated with abnormal dopaminergic activity.

Animals↗
PubMed1986

Expression and development of phenylethanolamine N-methyltransferase (PNMT) in rat brain stem: studies with glucocorticoids.

To study the differentiation of adrenergic (epinephrine-synthesizing) neurons in brain, the initial appearance and ontogeny of phenylethanolamine N-methyltransferase (PNMT), a specific marker of the adrenergic phenotype, were studied with immunocytochemistry and catalytic assay. The appearance of immunoreactivity to dopamine beta-hydroxylase (DBH-IR), an enzyme common to the noradrenergic and adrenergic phenotypes, was also studied. DBH-IR was initially observed on embryonic Day 13 (E13) in cells located on the ventrolateral floor and wall of the rhombencephalon. A day later (E14), PNMT-IR cells and PNMT catalytic activity were observed in the rhombencephalon suggesting that, as in the adrenal gland, noradrenergic expression precedes adrenergic expression. The PNMT-IR cells were presumed to be precursors of C1 neurons since they were located in the ventrolateral medulla oblongata. Cells located in the wall of the medulla which appeared to be migrating ventrally to the C1 group also contained PNMT-IR. On E15, cells which had PNMT-IR processes coursing through the germinal zone were observed dorsally near the fourth ventricle. Although the location of the C1 cell group was apparent when PNMT was initially expressed, the dorsal C2 and C3 adrenergic cell groups were not evident until late in gestation on E19. Even in the term embryo there appeared to be PNMT-IR cells which had not yet reached their final destination. On E14 and E15, PNMT-IR cells were also observed on the floor of the pons just rostral to the pontine flexure. However, these were not observed in older embryos, suggesting that transient expression of PNMT occurs in brain, as well as in the periphery. To determine whether glucocorticoids regulate brain PNMT, we examined the effects of altered glucocorticoid levels. In contrast to PNMT in the sympathetic nervous system, PNMT activity in medulla oblongata was not affected in neonates or adults by the decrease in glucocorticoids following adrenalectomy or hypophysectomy. Conversely, elevation of glucocorticoids by hormonal treatment did not alter PNMT in neonates. Notably, however, treatment of pregnant rats with dexamethasone on E18-E21, but not earlier, increased PNMT activity in the fetal brain stem. These observations suggest that PNMT expression and development is regulated by different factors in cells derived from neural crest and tube. PNMT is expressed earlier in brain than in adrenal and sympathetic ganglia. Further, the development of PNMT in the periphery, but not in the brain, is dependent on maintenance of physiological levels of glucocorticoids.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1986

'Neuropeptide tyrosine' (NPY) is co-stored with noradrenaline in vascular but not in parenchymal sympathetic nerves of brown adipose tissue.

By using immunohistochemistry it is shown that both the parenchymal and vascular sympathetic innervation in the interscapular depot of brown adipose tissue in the rat contain the catecholamine-synthesizing enzyme tyrosine-hydroxylase (TH). In contrast, 'neuropeptide tyrosine' (NPY) is selectively present in the vascular sympathetic nerves of the tissue--but not in nerves around brown fat cells. This is consistent with the presence of two populations of neurons (containing either TH alone or TH plus NPY) in the stellate ganglion, which is the probable origin of the sympathetic nerves in the interscapular brown adipose tissue. Furthermore, the perivascular NPY-positive nerves in the brown adipose tissue disappeared after 6-hydroxydopamine treatment, demonstrating their noradrenergic nature. Taken together, these findings suggest that sympathetic nerves to blood vessels and brown fat cells represent two separate subpopulations of autonomic neurons.

Adipose Tissue, Brown↗
PubMed1986

Growth of human pheochromocytomas in the anterior eye chamber of the rat. A histochemical study on amine and peptide content of pheochromocytoma tumour cells.

Tissue pieces from seven benign human pheochromocytomas have been successfully transplanted to the anterior eye chamber of cyclosporin-treated rats. In vivo observations showed that 74-99% of the tumour transplants were vascularized within one to two days after transplantation. No increase in the size of the transplants was noted during the observation period (1-4 weeks). Tumour transplants grown in non-immunosuppressed rats were initially vascularized but rejection started to occur one week after transplantation. Histochemical analysis of tumour transplants grown in immunosuppressed rats demonstrated numerous tumour cells with strong catecholamine fluorescence, some of which formed long cell processes on the host iris. Immunocytochemical analysis of tumour transplants demonstrated positively labelled tumour cells after incubation with antisera against neuropeptide Y, enkephalin, vasoactive intestinal polypeptide, somatostatin, substance P, dopamine-beta-hydroxylase, tyrosine hydroxylase and serotonin. A similar histochemical and immunocytochemical pattern was observed in primary tumours but tumour cells sending out cell processes were observed less frequently. Human pheochromocytomas may thus be successfully grown in oculo in cyclosporin-treated rats. This may prove to be a suitable model for the study of storage and release of catecholamines and neuropeptides from pheochromocytoma tumour cells.

Adrenal Gland Neoplasms↗
PubMed1986

Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients.

The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.

Adrenal Gland Neoplasms↗
PubMed1986

Reserpine-induced effects in the adrenergic neuron as studied with cytofluorimetric scanning.

The anterograde axonal transport of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY) and tyrosine hydroxylase (TH) was studied in the rat sciatic nerve after reserpine (10 mg/kg). The histochemical method of Hillarp and Falck was used to study NE and the indirect immunofluorescence technique to study DBH-, NPY- and TH-immunoreactive material (IR), using antisera produced in rabbits. The rats were given reserpine 18 hr, or 1-7 days before sacrifice. Before perfusion fixation one nerve was dissected, frozen and freeze-dried for studies on NE, and the contralateral nerve was then processed for immunofluorescence. The amount of fluorescent material accumulated proximal to a 12 hr crush was quantified in longitudinal sections of the nerve using a cytofluorimetric scanning method. During the early phase after reserpine (18 and 25 hr) the amounts of accumulated NE were undetectable or very low, near control levels at 2 day, and overshooting to 160% of control at 4 d after reserpine. Accumulations of DBH-IR, NPY-IR and TH-IR were also depressed initially to 60-70% of control. DBH-IR and TH-IR thereafter increased to supranormal levels (140% of control) at day 4, while NPY-IR did not exhibit any overshooting but accumulated in the normal range at 2, 4, and 7 days. The results indicate that the amount of material transported distally early after reserpine is depressed. After local vinblastine-treatment of the lumbar sympathetic ganglia the amounts of DBH-IR and TH-IR in the perikarya were markedly lower in reserpine treated rats than in controls, probably due to a decreased perikaryal synthesis of these two enzymes. Rectal temperature in these rats decreased during the initial 10 hr after reserpine by up to 3 degrees C. Thus, the decreased synthesis may be caused by the lowered body temperature, which also may slow down the rate of anterograde axonal transport. The later overshooting in accumulated amounts of NE, DBH-IR an TH-IR gives support to the hypothesis that amine granules containing DBH and NE are produced and transported in supranormal amounts around the 4th day after reserpine. Also, the results indicate that a considerable fraction of TH-IR is transported with organelles, probably amine storage granules, in adrenergic axons. NPY, shown to be localized in amine storage granules, did not overshoot at day 4 after reserpine, in contrast to DBH-IR, TH-IR and NE.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1986

The Apgar score revisited: influence of gestational age.

We tested the hypothesis that Apgar scores are in part related to the newborn infant's level of maturity. Seventy-three pregnant women with normal fetuses of gestational age 22 to 42 weeks were studied. Fetal well-being was documented by a prospectively designed recording of pregnancy history, labor complications, and birth outcome, including cord blood pH and base deficit measurements. The 1- and 5-minute Apgar scores were directly related to gestational age. Respiratory efforts, muscle tone, and reflex were the major determinants for a decreasing Apgar score with declining gestational age. We conclude that the 1- and 5-minute Apgar scores are influenced by the infant's level of maturity and that our data may be useful in evaluating the true value of Apgar scores in assessing the fetal and neonatal condition of low birth weight infants.

Apgar Score↗
PubMed1986

Scrotal temperature reflects intratesticular temperature and is lowered by shaving.

Intratesticular and scrotal skin temperatures were measured in 34 men undergoing scrotal or inguinal surgical procedures under general anesthesia. Scrotal temperatures were measured before and after a dry scrotal shave. Intratesticular temperature was measured under direct vision with a needle thermistor. Linear regression analysis revealed a strong correlation between intratesticular and scrotal skin temperatures. In addition, simple scrotal shaving significantly decreased scrotal skin temperature. These observations suggest that scrotal skin temperature measurements may be useful to detect elevations of intratesticular temperature and scrotal shaving may be a useful adjunct for testicular cooling.

Adult↗