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Biomedical subjects

M Fodor

Publications and source records attributed to M Fodor.

At least 55 records · Page 3Linked to original sources

Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain.

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.

Adult↗

Distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches.

The distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches of the cat was demonstrated by immunocytochemical techniques. A large number of immunoreactive nerve fibres was observed in the tela submucosa very close to the Peyer's patches. Some immunoreactive nerve cell bodies were also found in this layer. The immunoreactive nerve terminals ran around the margin of the follicles and only a few nerve fibres were observed in the centre of follicles. Electron-microscopic investigation showed that these immunoreactive nerve terminals were in very close contact with lymphocytes and plasma cells, where no Schwann cell sheath was interposed. The gap between the nerve processes and the lymphocytes and plasma cells was about 20-200 nm, and occasionally less. These results provide morphological evidence consistent with the view that somatostatin has a neuroimmunomodulatory action.

Animals↗

Alterations in brain atrial natriuretic polypeptide levels in hypophysectomized rats.

Twelve days after hypophysectomy depleted atrial natriuretic polypeptide (ANP) concentrations were measured in the plasma and in 8 of 18 microdissected brain nuclei of rats. Reduced ANP levels were found in brain structures (subfornical organ, organum vasculosum laminae terminalis, preoptic and hypothalamic periventricular nuclei, paraventricular nucleus, lateral hypothalamic area), which are directly involved in the central regulations of salt and fluid homeostasis, as well as in the medial amygdaloid nucleus and the locus ceruleus. ANP concentrations in the median eminence, medial preoptic and arcuate nuclei did not alter by hypophysectomy. Elevated ANP concentrations were measured only in the supraoptic nucleus of hypophysectomized rats.

Amygdala↗

Corticotropin-releasing factor induces differential behavioral and cardiovascular effects after intracerebroventricular and lateral hypothalamic/perifornical injections in rats.

The contribution of the lateral hypothalamic/perifornical (LH/PFx) area in mediating central effects of corticotropin-releasing factor (CRF) on cardiovascular and behavioral activity was assessed by monitoring blood pressure, heart rate and behavioral responses for a 45-min period after injections of various doses of CRF into the LH/PFx region or the lateral cerebral ventricle (intracerebroventricular, i.c.v.) in conscious, unrestrained rats in a familiar environment. After LH/PFx injection, CRF (3 and 30 ng) dose-dependently induced behavioral activation, predominantly consisting of grooming, eating and locomotor activity. Concomitantly, dose-related increases in mean arterial pressure (delta MAP) and heart rate (delta HR) were observed. Increases in MAP and HR following injection of 3 ng CRF were associated with the paroxysmal occurrence of behavioral activation and as such superimposed on CRF-induced elevation of baseline MAP and HR. Thirty nanograms CRF given i.c.v. produced grooming behavior similar to that observed after the same dose injected into the LH/PFx region, but failed to induce significant changes in cardiovascular concomitants. Rats receiving 100 ng CRF i.c.v., showed a significant increase in behavioral activity, respective to rats treated with 30 ng CRF in the LH/PFx, the tachycardiac responses, however, being similar in these groups. Both doses of CRF i.c.v. failed to induce significant delta MAP. The effects of CRF on cardiovascular and behavioral activity were more marked when the peptide was injected into the caudal part of the LH than those measured after administration into the rostral LH. Similarly, injections of CRF around or dorsal to the fornix (PFx) were more effective than those located ventrally to it. This site specificity of CRF-evoked responses was reflected in differential time response relations of the various effects. In summary, when i.c.v. is the route of administration, a higher dose of CRF is required to induce autonomic and behavioral responses similar to those elicited by CRF injected into the LH/PFx. The cardiovascular and behavioral effects of LH/PFx-CRF indicate that this region may be an important site for central CRF to produce stress-related autonomic and behavioral responses. In addition, the CRF-induced effects, both in magnitude and onset, show site specificity, the caudal LH and perifornical area being more responsive to the peptide than the rostral LH and the area ventral to the Fx. As CRF-evoked behavioral activation does not necessarily coincide with changes in MAP and HR, our data suggest a dissociation of the peptide's central actions to influence behavioral and autonomic responses.

Animals↗

Neuropeptide Y-containing neuronal pathway from the spinal trigeminal nucleus to the pontine peribrachial region in the rat.

The existence of ascending medullary neuropeptide Y (NPY)-containing projection from the spinal trigeminal nucleus to the pontine peribrachial area has been demonstrated by a combination of immunohistochemical methods with surgical transections in the lower brainstem. An NPY immunopositive cluster of varicose fibers was detected in the spinal trigeminal and in the paratrigeminal nuclei. Numerous immunoreactive perikarya could also be visualized here after colchicine treatment. Transections destroying the lateral region of the medulla oblongata resulted in an accumulation of NPY immunoreactivity in several trigeminal neurons ipsilateral to the knife cut, but no such retrograde accumulation was seen in any neuronal perikarya anywhere else in the medulla oblongata.

Animals↗

A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies.

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.

Adult↗

Immunohistochemical distribution of neuropeptide Y and catecholamine-synthesizing enzymes in nerve fibers of the human liver.

The course and distribution of neuropeptide Y (NPY)-immunoreactive (ir) nerves in the human liver was studied using immunohistochemistry. The distribution and density of NPY-ir fibers was compared with tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) immunoreactivity, two enzymes which are markers for dopamine- and noradrenaline-synthetizing neurones. NPY-immunopositive nerve fibers were densely distributed in the perivascular plexus of the portal trials, along the vena centralis, as well as close to the sinusoids and hepatocytes. The distribution of perivascular TH-ir and DBH-ir nerve fibers was similar to that of NPY-ir nerves, with the exception of intralobular nerves, where close topographical relations to individual hepatocytes and sinusoids were rarely observed. These results suggest that NPY is present in noradrenergic perivascular nerve fibers; probably of sympathetic origin and also in other parasympathetic, presumably cholinergic nerve fibers around the sinusoids.

Dopamine beta-Hydroxylase↗

Neuropeptides in atrial subepicardial ganglia of rats.

The distribution of several neuropeptides in subepicardial atrial ganglia was examined in the rat heart by using immunohistochemical techniques. Some of the ganglion cells in the right atrium exhibited neuropeptide Y-immunoreactivity while no immunostaining was found with antisera against atrial natriuretic polypeptide (ANF), substance P, vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP). Nerve fibers in and around the ganglia showed neuropeptide Y, calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivities. Some of these immunoreactive fibers (substance P, calcitonin gene-related peptide, neuropeptide Y) formed relatively dense networks around blood vessels and capillaries. Atrial natriuretic polypeptide-like immunoreactivity which was present in atrial myocytes failed to show up in any neuronal elements in the rat heart.

Animals↗

Ethanol elimination in man under influence of hepatoprotective silibinin.

The effect of a single dose of hepatoprotective silibinin on blood alcohol elimination was investigated. Neither influence on the blood alcohol curve, nor detectable increase in the beta 60 value was found, although biochemical considerations suggest such an effect. Though silibinin has a protective effect on chronic alcohol liver injury, it does not influence acute alcohol elimination, and is therefore not suitable for use as a "sobering-up" agent.

Adult↗

[Immunoscintigraphy in stomach neoplasms with anti-CEA BW 431/26 monoclonal antibodies marked with Tc 99 m].

A 57 year old female had a tubular gastric adenocarcinoma confirmed by endoscopy and radiologic studies. Echotomography of the abdomen revealed multiple adenopathies. Immunoscintigraphy with 99mTc labeled anti-CEA BW 431/26 monoclonal antibody was performed. Images obtained at 6 and 24 h showed a significant uptake at the primary lesion and at periaortic adenopathies both in conventional gamma-camera and single emission photon tomography. This immuno-scintigraphic technique may be helpful in the management of patients with gastric cancer.

Adenocarcinoma↗

Neuropeptides in atrial subepicardial ganglia of rats.

The distribution of several neuropeptides in subepicardial atrial ganglia was examined in the rat heart by using immunohistochemical techniques. Some of the ganglion cells in the right atrium exhibited neuropeptide Y-immunoreactivity while no immunostaining was found with antisera against atrial natriuretic polypeptide (ANF), substance P, vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP). Nerve fibers in and around the ganglia showed neuropeptide Y, calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivities. Some of these immunoreactive fibers (substance P, calcitonin gene-related peptide, neuropeptide Y) formed relatively dense networks around blood vessels and capillaries. Atrial natriuretic polypeptide-like immunoreactivity which was present in atrial myocytes failed to show up in any neuronal elements in the rat heart.

Animals↗

[Medical oncology: notions for a new specialty].

The higher incidence and mortality rates of cancer require an increasing concern of the medical community regarding this disease. In the last decade the management of advanced stages of the disease has progressed significantly. The contributions of basic research, and improvements in diagnostic methods, chemotherapy, hormonal therapy and bio-therapy has made this possible. The internist is the most competent specialist to take over the diagnosis and management of this disease; therefore he should be trained in the different disciplines which will enable him to become a medical oncologist. The training program for this new specialty should be designed by post-graduate schools with the support of the universities, the Ministry of Health and even private institutions. In Chile, as in other developed countries, there are training programs which have been suited to satisfy the growing needs of different specialties.

Chile↗

Dynorphin A-containing neural elements in the nucleus of the solitary tract of the rat. Light and electron microscopic immunohistochemistry.

Distribution of dynorphin A (DyA) immunoreactivity in the nucleus of the solitary tract (NTS) was examined in rats after various surgical transections by light and electron microscopic immunohistochemistry. In colchicine-treated animals DyA immunostained perikarya were seen in each subdivision of the NTS. In intact rats, dense network of immunopositive nerve fibers was localized light microscopically, and synaptic contacts were found between DyA immunopositive structures (axo-axonic, axo-dendritic synapses), electron microscopically. Surgical transections medial, caudal or rostral to the nucleus did not alter the distribution pattern of DyA in the NTS. Lesion immediately lateral to the nucleus resulted in an ipsilateral appearance of immunostained cell bodies. Vagal and glossopharyngeal afferents (including baroreceptor fibers) terminate in the medial and commissural subnucleus of the NTS. Two days after extracranial vagotomy, synaptic contacts between degenerated presynaptic boutons and DyA immunopositive postsynaptic elements were observed in both medial and commissural part of the NTS. These observations provide morphological evidence suggesting that (1) axons of dynorphin A-containing cell bodies form an intrinsic network inside the nucleus; (2) these DyA cells receive direct peripheral inputs through the vagus nerve, and (3) projecting DyA neurons may exist in the NTS, they may innervate medullary, rather than forebrain, higher brainstem or spinal cord neurons.

Animals↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Concentrations of atrial natriuretic factor (ANF) were measured in discrete brain nuclei by radioimmunoassay in rats. Alterations in the salt and fluid homeostasis and aldosterone treatment resulted in marked changes of ANF levels in the preoptic-hypothalamic periventricular structures including the organum vasculosum laminae terminalis, in the subfornical organ and the perifornical nucleus. Furthermore, marked changes were observed in ANF levels of these nuclei in various types of renal hypertensions. Altered ANF levels were found in several brain nuclei (locus coeruleus, dorsal raphe nucleus, tegmentum pontis, nucleus of the solitary tract) of animals with diabetes insipidus or spontaneous hypertension.

Animals↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Atrial natriuretic factor (ANF) is widely distributed in the preoptic area and the hypothalamus, it is present there both in cell bodies and nerve terminals. Effect of experimental alterations in the salt and water balance was examined on preoptic-hypothalamic ANF levels measured in ten microdissected nuclei. Immunohistochemical analysis was also performed to confirm radioimmunological results. Following interventions were performed in adult male rats: adrenalectomy (5 days), daily 0.9% NaCl, aldosterone (5 micrograms/100 g) and dexamethasone (2 micrograms/ml drinking water) treatments in both intact and adrenalectomized groups, and in rats with diabetes insipidus (Brattleboro rats) and DOC-salt hypertension. Although no appreciable alterations were observed in the intensity of ANF-like immunoreactivity in sections of the preoptic-hypothalamic region, ANF levels altered markedly in the periventricular structures (organum vasculosum laminae terminalis, preoptic and periventricular nuclei). Little or no changes were measured in ANF levels of other hypothalamic nuclei (except the perifornical nucleus). Adrenalectomy depleted ANF levels which were restored by NaCl drinking. Aldosterone elevated ANF concentrations both in intact and adrenalectomized animals while dexamethasone treatment was without any significant effect on ANF levels in the periventricular preoptic nucleus. Diabetes insipidus or DOC-salt hypertension had little or no effect on ANF levels in this brain area. Unchanged ANF concentrations were also measured in the vasopressin-containing supraoptic nucleus following adrenalectomy or in diabetes insipidus rats.

Animals↗

[Variabilities of kinetics of alcohol catabolism].

The resorption, distribution and elimination of ethanol vary individually. The differences in the resorption deficit and elimination coefficient can be of great extent. Though the generally accepted average of resorption deficit is 20%, which is calculated with in forensic practice, this value can occasionally be a lot higher. The elimination coefficient (beta value) depends on the blood alcohol level. Beta value was found higher than 0.15%o/h, the generally accepted one, even below 1.5% blood alcohol content, above 2.5% the beta value was found to be as high as 0.33%o h. This faster rate of ethanol clearance is due to induction of alcohol elimination systems. The ethanol metabolism at higher blood alcohol levels is characterized by Michaelis-Menten kinetics.

Alcohol Drinking↗

[Cutaneous metastasis in gastric cancer].

We report 3 patients operated on for gastric cancer who developed skin metastasis proven by biopsy. Within a year of this complication 2 patients had died, confirming the bad prognosis associated to this finding. No estimates of the frequency of this complication are available in Chile.

Adult↗