Search PubMed⌕ Search

Biomedical subjects

N Aronin

Publications and source records attributed to N Aronin.

At least 73 records · Page 4Linked to original sources

Immunoreactive leu-enkephalin in the monkey hypothalamus including observations on its ultrastructural localization in the paraventricular nucleus.

The distribution of immunoreactive leu-enkephalin neurons and fibers in the monkey hypothalamus, including ultrastructural localization in the paraventricular nucleus (PVN), was examined with the peroxidase-antiperoxidase immunocytochemical method. Immunoreactive leu-enkephalin cell bodies and fibers were present in the PVN, the region of the dorsal nucleus and nucleus of the anterior commissure, the dorsomedial nucleus, ventromedial nucleus, and lateral hypothalamus. Within the PVN labeled cells were found mostly in the medial parvocellular region, and a smaller proportion including some large cells was present in the lateral, and dorsolateral zones. Immunoreactive neurons contained numerous large granular vesicles (LGV) which ranged from 63 to 235 nm in size, suggesting that at least some enkephalin-containing neurons belong to the population of neurosecretory cells. Positive neurons were postsynaptic to four types of unlabeled axon terminals. Leu-enkephalin-containing fibers (some of which were myelinated) and boutons contained small clear vesicles and numerous LGV. Axon terminals made synaptic contacts with the cell bodies, primary and distal dendrites of unlabeled neurons. The findings show that enkephalin-containing neurons in the PVN integrate a variety of neuronal inputs and provide morphological evidence for the inhibiting influence of enkephalins on the firing rate of PVN neurons. It may be speculated that the effects of opioids on the release of vasopressin and other substances possibly originating from PVN neurons may be regulated in part within the nucleus by locally synapsing axons belonging to enkephalin-containing neurons.

Animals↗

Ultrastructural localization of immunoreactive neurotensin in the monkey superficial dorsal horn.

Neurotensin, a tridecapeptide, has been proposed to have a role in sensory systems, especially those mediating pain. The light microscopic and ultrastructural localization of neurotensin immunoreactivity in neurons of the monkey spinal cord was studied with the aim of examining their synaptic interactions. At the light microscopic level, neurotensin-containing cells were located in laminae II and III and immunoreactive axons and terminals were found in laminae I, II, and III. Neurotensin-positive axons were mostly thin and unmyelinated and their boutons contained both clear and large granular vesicles. Boutons varied considerably in size (1-3 micron) and in their relative content of large granular vesicles, which appeared occasionally in presynaptic locations. In lamina I neurotensin-immunoreactive terminals formed synapses with cell bodies which varied both in size and subcellular features. Some large dendrites in lamina I were contacted by numerous neurotensin-positive axons and also unlabeled terminals. In lamina II boutons with neurotensin immunoreactivity formed synapses mostly with small unlabeled dendrites some of which contained vesicles. The present results together with recent anatomical and physiological findings suggest that spinal cord neurons which contain neurotensin synapse with cells in the superficial dorsal horn that receive either input from primary afferents conveying nociceptive information or form part of the spinothalamic tract, or both. The diversity observed both in the morphology of neurotensin-positive terminals and in their synaptic patterns may indicate that they arise from more than one type of dorsal horn cell.

Animals↗

Regulation by thyroid hormone of the concentration of substance P in the rat anterior pituitary.

The content of immunoreactive substance P (iSP) in the male rat anterior pituitary was measured after thyroidectomy and excess T4 administration. Baseline values for iSP content (mean +/- SE, 400 +/- 37 fmol/mg protein) increased progressively after thyroidectomy (4 days, 893 +/- 100; 6 days, 1321 +/- 242; 14 days, 1897 +/- 509). Administration of pharmacological doses of T4 (50 micrograms daily) for 2 and 14 days significantly decreased anterior pituitary iSP content (2 days, 196 +/- 30; 14 days 138 +/- 12). Thyroid status did not affect iSP content in the hypothalamus, caudate nucleus, amygdala, or brainstem. Partial chemical characterization of SP immunoreactivity in the anterior pituitary was obtained by gel permeation chromatography on Sephadex G-25, high pressure liquid chromatography, and the use of two antisera in RIAs, one directed against the amino-terminus and one directed against the carboxyl-terminus of the peptide. SP in the anterior pituitary was readily releasable in vitro by 44 mM potassium chloride in a calcium-dependent manner. The present study demonstrates that the concentration of iSP in the rat anterior pituitary is affected by the thyroid status of the animal and supports the probability that thyroid hormones participate in the regulation of the synthesis and/or release of iSP from the anterior pituitary.

Animals↗

The effects of gonadal steroids on the content of substance P in the rat anterior pituitary.

The effects of gonadectomy and of the administration of gonadal steroids on the content of substance P in the anterior pituitary (AP-SP) were studied in adult rats. The effect of gonadal status on the AP-SP content of thyroidectomized (TX) rats was also studied. We have confirmed that the AP-SP content in adult males is higher than that in adult females. Ovariectomy (OVX) caused an increase in AP-SP content which was apparent 6 days after surgery. Estradiol (E2; 2 micrograms/rat daily) administered for 13 days beginning the day after OVX prevented the increase in AP-SP content induced by OVX. Orchiectomy of adult rats had no effect on AP-SP content 14 and 45 days after surgery. E2 administered to adult female rats for 13 days caused a reduction in the AP-SP content, whereas dihydrotestosterone (0.2 mg/rat daily for 13 days) caused an increase that was even more pronounced in TX rats. E2 administration to TX adult female rats caused a significant decrease in the AP-SP content both when treatment was begun on the day after surgery or 2 weeks later. Administration of T4 (1.5 and 25 micrograms/100 g BW daily for 7 days) to rats made hypothyroid by thyroidectomy 2 weeks earlier abolished the increase in AP-SP content seen in TX animals. Neither E2 nor dihydrotestosterone had an effect on the substance P content of any of the brain regions examined. The AP-SP content of pregnant or lactating rats was not different from that of age-matched controls. The content of substance P in the AP and median eminence did not vary significantly throughout the estrous cycle. The data indicate that AP-SP content is dependent on the gonadal status of the animal and that gonadal steroids interact with thyroid hormones in the regulation of substance P turnover in the AP.

Animals↗

Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy.

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Adult↗

The distribution of substance P-containing neurons in the cat Edinger-Westphal nucleus: relationship to efferent projection systems.

The light microscopic localization of substance P-like immunoreactivity (SPLI) was examined in the cat Edinger--Westphal complex using the peroxidase--antiperoxidase method. A high density of cell bodies and processes staining for SPLI were found in the caudal part of the Edinger--Westphal complex (EWc) capping the somatic divisions of the oculomotor nucleus. This distribution continued rostrally into the anteromedian nucleus (AM). Cells labeled with SPLI were also found arranged in a thin layer dorsally capping the oculomotor nucleus, and scattered cells were found in the periaqueductal gray region at the same level. This distribution of SPLI-positive cells was then compared with the distribution of cells in EWc and AM that are retrogradely labeled by horseradish peroxidase or Nuclear Yellow injections into spinal cord, cerebellum, or ciliary ganglion. Injections of horseradish peroxidase into both cervical and lumbar cord labeled a large number of cells throughout the length of EWc and the more rostral AM. A similar pattern of labeling was seen following injections of Nuclear Yellow into the deep cerebellar nuclei. In contrast, cells innervating the ciliary ganglion were found predominantly outside of the Edinger--Westphal complex in AM, the rostral periaqueductal region, and the tegmentum ventral to the oculomotor complex. The distribution of cells projecting to spinal cord or cerebellum and the pattern of SPLI staining was found to closely overlap, evidence that substance P may be contained in cells that give rise to the central projections of the Edinger--Westphal complex.

Animals↗

Somatostatin is increased in the basal ganglia in Huntington disease.

Huntington disease (HD) is an autosomal dominant hereditary disorder characterized by premature cell death, predominantly in the neostriatum. Decreased concentrations of several neurotransmitters and neuropeptides have been reported in the basal ganglia in Huntington disease. We now report that concentrations of radioimmunoassayable somatostatin are increased in extracts of the caudate (mean +/- standard error of the mean, ng/gm net weight; 247 +/- 24 versus 85 +/- 11), putamen (275 +/- 48 versus 74 +/- 11), external globus pallidus (100 +/- 10 versus 27 +/- 6), and internal globus pallidus (108 +/- 21 versus 21 +/- 8) in the disease. The concentrations of immunoreactive substance P measured in the same extracts were markedly reduced in caudate (mean +/- standard error of the mean, pmol/gm wet weight; 25 +/- 3 versus 109 +/- 20), putamen (28 +/- 7 versus 88 +/- 28), external globus pallidus (39 +/- 9 versus 196 +/- 62), and internal globus pallidus (60 +/- 17 versus 263 +/- 39), as well as in both subdivisions of the substantia nigra. Gel permeation chromatography and high-performance liquid chromatography showed radioimmunoassayable somatostatin to include peptides with physicochemical properties of the tetradecapeptide somatostatin and larger substances, including somatostatin-28-like material. A single peak of immunoreactive substance P corresponding to synthetic substance P was found by high performance liquid chromatography. These results suggest that immunoassayable somatostatin-containing neuronal elements in the neostriatum and globus pallidus in Huntington disease are affected differentially by the disease process from neurons that contain immunoreactive substance P.

Adolescent↗

Plasma immunoreactive beta-endorphin is elevated in uraemia.

Plasma immunoreactive-(IR) beta-endorphin (beta-EP) and beta-lipotrophin (beta-LPH) levels were measured in 15 adult uraemic patients on chronic haemodialysis. The presence of immunoreactivity eluting in the position of beta-EP was demonstrated following submission of pooled extracts of uraemic plasma to gel permeation chromatography on Sephadex G-50. To separate beta-EP from beta-LPH, pre-dialysis plasma extracts from six individual patients, and three pools of three patients each, were submitted to sequential immune-affinity chromatography and levels were measured by radioimmunoassay. In all cases, plasma IR beta-EP concentrations were markedly increased compared with normal subjects (m +/- SEM fmol/ml; 64.4 +/- 13.7 vs. 2.3 +/- 0.2). IR beta-LPH concentrations were also increased (m +/- SEM fmol/ml; 55.7 +/- 13.2 vs. normal 6.1 +/- 0.8). In addition, post-dialysis concentrations of plasma IR beta-EP and beta-LPH were lower than pre-dialysis levels (n = 4).

Adult↗

Light microscopic and ultrastructural localization of immunoreactive substance P in the dorsal horn of monkey spinal cord.

Light- and electron-microscopic localization of substance P in the monkey spinal cord was studied by the peroxidase anti-peroxidase technique with the particular aim of examining types of interactions made by substance P-positive boutons with other neuronal elements in the dorsal horn. By light-microscopy dense labeling for immunoreactive substance P was found in laminae I, II (outer zone) and V (lateral region), consistent with findings in other mammalian species. By electron-microscopy, substance P-positive staining was mostly in unmyelinated and in some thinly myelinated small diameter fibers. Substance P-positive terminals contained both large granular vesicles (80-120 nm diameter), which were filled with reaction product, and clear round vesicles (40-60 nm). Substance P-positive large granular vesicles were sometimes observed near presynaptic sites and in contact with dense projection there. Immunoreactive substance P boutons were small to large in size (1-4 micron), formed synapses with somata and large dendrites and were the central axons of synaptic glomeruli where they were in synaptic contact with numerous small dendrites and spines. Substance P-labeled axons frequently formed synapses with dorsal horn neurons which were also postsynaptic to other types of axons. Substance P-positive profiles participated in numerous puncta adhaerentia with unlabeled cell bodies, dendrites and axons. Only rarely, some suggestive evidence was obtained indicating that axons might synapse onto substance P-containing boutons. Biochemical analysis of monkey spinal cord tissue extracts, undertaken to characterize more precisely the immunoreactive substances, indicated that only substance P and its oxide derivative were detected with the antiserum used in the immunocytochemistry. These morphological findings show that substance P is contained within a class of axon terminals, many of which have been shown previously in the monkey to originate from the dorsal root. The results suggest that modulation of substance P primary afferents terminating in the outer dorsal laminae of the monkey spinal cord occurs in part via axonal inputs onto dorsal horn neurons postsynaptic to the primary afferent.

Animals↗

Failure of bromocriptine to lower plasma catecholamines in normal men and women.

A plasma catecholamine-lowering effect of bromocriptine has previously been reported in normals, but not in patients with PRL- or GH-secreting pituitary tumors, and has been used as evidence to support the concept of disordered central nervous system dopaminergic tone in patients with such tumors and as a test to distinguish them from normals. In the present study of 16 normal subjects (9 women and 7 men), we found no significant change in plasma norepinephrine or epinephrine after bromocriptine. Similarly, no change occurred in plasma catecholamines in 8 patients with PRL-secreting tumors or 6 patients with ACTH hypersecretion. Our data, therefore, do not provide confirmatory evidence for an effect of bromocriptine on plasma catecholamines in normal subjects and do not support the proposed use of bromocriptine as a test for defective central dopaminergic regulation.

Adrenocorticotropic Hormone↗

Impaired clearance of beta-lipotropin in uremia.

Immunoreactive ACTH and beta-lipotropin (beta-LPH) plasma concentrations are elevated in clinically stable chronic renal failure patients on hemodialysis (LPH: patients, 271.8 +/- 35.7 fmol ml-1; normal subjects; 6.6 +/- 0.5; ACTH: patients, 56.4 +/- 15.3; normal subjects, 19.4 +/- 1.7). To begin to study the etiology of such elevated levels, the MCR, apparent volume of distribution, and fractional rate of disappearance of synthetic human ACTH and highly purified human beta-LPH were determined in two clinically stable chronic renal failure patients on hemodialysis, after bolus simultaneous injection of both peptides. Biphasic disappearance curves were obtained for beta-LPH; triphasic for ACTH. The MCR of ACTH was within the range seen in normal subjects, whereas the MCR of beta-LPH was less than one half the normal rate. The data indicate that a decrease in MCR (rather than an increase in pituitary secretory rate) may account for the higher plasma levels of beta-LPH in uremic patients.

Adolescent↗

Ultrastructural localization and biochemical features of immunoreactive LEU-enkephalin in monkey dorsal horn.

Leu-enkephalin is an opioid peptide that has been found to modulate nociception in the spinal cord. Both pre- and postsynaptic interactions by enkephalins have been proposed. By the peroxidase . anti-peroxidase immunocytochemical method, we studied the distribution and ultrastructure of neuronal elements in the monkey dorsal horn to elucidate possible morphological substrates for postulated opioid actions. Biochemical analysis of immunoreactive Leu-enkephalin-like peptides in the cord was performed to characterize the forms present in labeled neurons and terminals. At the light microscopic level, fiber immunostaining was found in most areas of gray matter, especially in laminae I to V, and in the dorsolateral funiculus. Cell bodies were located in laminae I, II, III, and V. At the ultrastructural level, in the superficial dorsal horn, we found that neurons with Leu-enkephalin receive numerous types of axon inputs, some of which have been identified previously as originating from the dorsal root. Leu-enkephalin terminals formed primarily axosomatic and axodendritic synapses and less frequently synapsed with other axons. With the same Leu-enkephalin antiserum as used in the immunocytochemistry, a peptide physicochemically similar to intact Leu-enkephalin and two larger Leu-enkephalin-like peptides were identified in monkey spinal cord extracts. It is likely that a family of Leu-enkephalin-like peptides is present in monkey spinal cord and that the labeled elements may contain any or all of these substances. It is concluded that both pre- and postsynaptic physiologic effects of Leu-enkephalin are possible, although the preponderance of axodendritic synapses favors a principal postsynaptic site of action. The anatomical results suggest that neurons containing immunoreactive Leu-enkephalin in the dorsal horn, some of which may receive input from primary afferents, modulate nociception by directly synapsing with cells of origin of the spinothalamic tract and also by interacting with primary afferent terminals.

Animals↗