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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 505 records · Page 28Linked to original sources
PubMed1984

Combined use of benserazide and carbidopa in Parkinson's disease.

The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. Although many patients respond better to one drug than the other, we sought to exploit the differences in pharmacokinetics by giving both drugs to the same patient. Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, including 22 patients with diurnal oscillations in performance, "wearing off" or on-off phenomena. Previous attempts to change the dose, sequence, or ratio of levodopa to carbidopa in these patients had been unrewarding. Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. The mean dose of levodopa:carbidopa before benserazide was 910:100 (9 to 1 ratio); the mean dose of levodopa:benserazide was 355:90 (4 to 1 ratio). The mean dose of levodopa:carbidopa + benserazide was 925:155 (6 to 1 ratio). The combination of carbidopa with benserazide is useful in some parkinsonian patients.

Adult↗
PubMed1984

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗
PubMed1984

[Aneurysm ruptures of the abdominal aorta].

Rupture of an abdominal aortic aneurysm remains a dramatic complication and its operative mortality is still about 50%. The authors reviewed 41 cases of ruptured abdominal aortic aneurysms which were operated from 1978 to 1983. On arrival at the hospital and after clinical diagnosis, the patients were rapidly brought to the theatre without specialized complementary examinations. Coated Dacron prostheses were used in all cases. The operated patients were brought to the intensive care unit where special attention was given to central venous pressure, arterial pressure and capillary wedge pressure (Swan-Ganz-catheter). The authors tried to determine the influence of shock, preoperative delay, blood loss, age and associated diseases on the mortality rate. In this series the perioperative mortality (30 days) could be reduced to 39%.

Aged↗
PubMed1984

Further studies on the effects of the GM1 ganglioside on the degenerative and regenerative features of mesostriatal dopamine neurons.

By means of computer assisted morphometry and microdensitometry the effects of chronic GM-1 ganglioside treatment have been further evaluated on the degenerative and regenerative features of mesostriatal DA neurons in the rat brain. In this study mainly a rostrocaudal morphometrical analysis was performed in the substantia nigra of the lesioned side. The specificity of the action of the GM-1 ganglioside on the substantia nigra DA cells was evaluated by a comparison with antiinflammatory drugs such as betametazon and acetylsalicylic acid. In the rostrocaudal analysis it was demonstrated that chronic GM-1 treatment preferentially protected the caudally located dopamine nerve cells from degeneration after partial hemitransection, while instead this chronic GM-1 treatment increased tyrosine hydroxylase immunoreactivity mainly within the rostrally located DA nerve cells present close to the site of the lesion. Furthermore, the specificity of the GM-1 action was demonstrated by the absence of protective effects of chronic treatment with betametazon and acetylsalicylic acid on the dopamine nerve cells of the lesioned side. These results open up the possibility that chronic GM-1 treatment, by exerting a stimulatory metabolic action on the DA nerve cells located close to the lesion, can enhance the production of neurotrophic factors in these cells, which in turn can diffuse out to increase the survival of the less severely lesioned DA nerve cells located in the caudal part of the substantia nigra. These results indicate that chronic GM-1 treatment may be beneficial in the treatment of neurons undergoing degeneration, which takes place e.g. in Parkinson's disease and after mechanical injury to the brain due to accidents or neurosurgical operations.

Animals↗
PubMed1984

Pergolide and lisuride in advanced Parkinson's disease.

In a retrospective study, treatment with lisuride was compared to pergolide in 25 patients with advanced PD in whom the response to levodopa had diminished. Sixteen patients had wearing off and/or ON-OFF phenomena. Lisuride or pergolide, when added to levodopa, resulted in comparable and significant decreases in disability in both ON and OFF periods; pergolide resulted in a greater increase in the number of hours in which patients were ON. Adverse reactions were comparable on both drugs. However, patients who developed an adverse reaction on one drug did not necessarily develop the same reaction on the other drug. Both lisuride and pergolide are effective anti-Parkinson drugs.

Aged↗
PubMed1983

Morphometrical analysis of the distribution of luteinizing hormone-releasing hormone and tyrosine hydroxylase-immunoreactive nerve terminals within the lateral palisade zone of the median eminence of the male rat.

By means of a semiautomatic image analyzer coupled to an Apple II computer with suitable computer programs it has been possible to demonstrate in a quantitative way the morphological interaction between luteinizing hormone-releasing hormone (LH-RH) and tyrosine hydroxylase (TH)-immunoreactive nerve terminals in the lateral palisade zone (LPZ) at various rostrocaudal levels of the median eminence. The overlap area represented about 50% of the TH- or the LH-RH-immunoreactive area. The dopamine nerve terminals showed a more medial and ventral position than the LH-RH-immunoreactive nerve terminals. The transmitter-identified nerve terminals in the LPZ may be organized in strips extending in the rostrocaudal direction and may have a differential regulation.

Animals↗
PubMed1983

High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man.

Using a highly specific radioimmunoassay for neuropeptide Y (NPY), levels in the peripheral nervous system of guinea-pig, cat, pig and man were measured. In all species very high levels (up to 800 pmol X g-1) were found in sympathetic ganglia and in tissues which receive a dense sympathetic innervation, such as vas deferens, heart atrium, blood vessels and spleen. By immunocytochemistry, NPY-immunoreactive (-IR) principal ganglion cells in sympathetic ganglia and the pelvic plexus were also found to contain dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), strongly suggesting that the NPY-IR cells are noradrenergic. NPY- and DBH-IR nerves had a roughly parallel occurrence in the heart, spleen, kidney, respiratory and urogenitary tracts, around blood vessels and within visceral smooth muscle. Considerably more NPY-IR than DBH-IR nerve fibres were seen in the gastrointestinal tract from the oesophagus to the anal sphincter. In addition, NPY-IR local ganglion cells were observed in the submucous and myentric plexuses. NPY-like immunoreactivity was also observed in the adrenal medulla of guinea-pig and cat. NPY thus seems to be a major peptide in the sympathetic nervous system, supporting its proposed role in sympathetic neurotransmission.

Animals↗
PubMed1983

NADPH-diaphorase: a selective histochemical marker for striatal neurons containing both somatostatin- and avian pancreatic polypeptide (APP)-like immunoreactivities.

Certain neurons in the brain are specifically and intensely stained by a histochemical method which demonstrates nicotinamide adenine dinucleotide phosphate NADPH-diaphorase activity. The cell types containing this enzyme in certain areas of the rat forebrain were examined by combining NADPH-diaphorase histochemistry with the indirect immunofluorescence technique. Neurons containing somatostatin- or avian pancreatic polypeptide (APP)-like immunoreactivities were found throughout the forebrain including the striatum and neocortex. These two neuropeptides were also found to coexist in many telencephalic neurons. After photography, the sections processed for immunohistochemistry were stained for NADPH-diaphorase activity by a histochemical method. It was found that within the striatum all of the neurons that were selectively stained by this technique also contained both somatostatin- and APP-like immunoreactivities. Also in the neocortex NADPH-diaphorase was found only in those neurons displaying somatostatin- or APP-like immunoreactivity. In other brain regions such as the nucleus laterodorsalis tegmenti, NADPH-diaphorase-containing cells did not contain these neuropeptides. The results indicate that NADPH-diaphorase histochemistry provides a simple, reliable, histochemical method to demonstrate those striatal neurons in which somatostatin- and APP-like immunoreactivities coexist. The selective occurrence of this enzyme within these neurons may provide a useful target for pharmacological studies of these neuropeptide-containing cells.

Animals↗
PubMed1983

Regulation of the multiple forms of dopamine beta-hydroxylase by nerve growth factor, dexamethasone, and dibutyryl cyclic AMP in the PC12 pheochromocytoma cell line.

Treatment with nerve growth factor was found to influence the subunit forms of dopamine beta-hydroxylase in PC12 pheochromocytoma cells. In untreated cells, near equal amounts of two subunit forms were observed (apparent Mr = 77,000 and 73,000) by labeling with [35S]methionine. Upon treatment of PC12 cells with nerve growth factor for several days, the Mr = 73,000 subunit form of dopamine beta-hydroxylase was almost exclusively observed. The shift in subunit forms became apparent only after a day of treatment and was maximal with 3 days or more of exposure to nerve growth factor. The dose-response curve was similar to most other nerve growth factor-induced responses in PC12 cells. Neurite outgrowth, however, was not essential for the shift in predominance of the Mr = 73,000 subunit form. This effect of nerve growth factor also occurred in suspension cultures or in the presence of low concentrations of inhibitors of transcription sufficient to prevent neurite outgrowth. Pulse-chase experiments with nerve growth factor-treated cells indicated that the Mr = 77,000 form is initially synthesized (5 min) and is then converted to the Mr = 73,000 form by 30-60 min. Insulin (100 ng/ml) and epidermal growth factor (1 ng/ml) had no effect on the subunit forms of dopamine beta-hydroxylase. However, treatment of PC12 cells for several days with dexamethasone (10(-5)M) or dibutyryl cyclic AMP (1 mM) leads to predominance of the Mr = 73,000 form of the enzyme. These experiments suggest that the proportions of the subunit forms of dopamine beta-hydroxylase can be regulated in cells by external signals and this may reflect alterations in post-translational processing enzymes and may serve as a potential mechanism to regulate catecholamine metabolism.

Adrenal Gland Neoplasms↗
PubMed1983

Mechanism of biosynthesis of soluble and membrane-bound forms of dopamine beta-hydroxylase in PC12 pheochromocytoma cells.

Dopamine beta-hydroxylase was present as 2 subunit forms (apparent Mr = 77,000 and 73,000) in the PC12 pheochromocytoma cell line as detected by immunoprecipitation from [35S]methionine-labeled cultures, and analyzed by sodium dodecyl sulfate gel electrophoresis and fluorography. The Mr = 77,000 form was present in a crude membrane fraction, while the Mr = 73,000 form was soluble. Both forms appeared to be present in approximately equal amounts, and both were glycosylated. Treatment of PC12 cells with tunicamycin, a potent inhibitor of core glycosylation in the endoplasmic reticulum, completely inhibited the appearance of the Mr = 77,000 and Mr = 73,000 forms, and 2 new immunoreactive polypeptides were obtained (apparent Mr = 67,000 and 63,000). Pulse-chase experiments suggested that the Mr = 77,000 form is initially synthesized (by 5 min) and a portion is converted in 15-90 min to the Mr = 73,000 form. Thereafter, the ratio between forms remains relatively constant, at least for several hours. Translation of mRNA from bovine and rat adrenals, and immunoprecipitation, indicated that dopamine beta-hydroxylase is initially synthesized as a single polypeptide (apparent Mr = 67,000). The subcellular site of biosynthesis of dopamine beta-hydroxylase was determined by isolation of mRNA from free and membrane-bound polysomes from bovine adrenal medulla. Translation in a cell free system and immunoprecipitation localized the synthesis of dopamine beta-hydroxylase on membrane-bound polysomes. These experiments suggest that both soluble and membrane-bound forms of dopamine beta-hydroxylase are synthesized and core glycosylated in the endoplasmic reticulum, and that there probably is a precursor-product relationship between the Mr = 77,000 and the Mr = 73,000 subunit forms of dopamine beta-hydroxylase.

Adrenal Gland Neoplasms↗
PubMed1983

Immunohistochemical evidence for a new group of catecholamine-containing neurons in the basal forebrain of the monkey.

Using a specific antibody to the catecholamine (CA) synthesizing enzyme, tyrosine hydroxylase (TH), in combination with the avidin-biotin-peroxidase complex method, we have found evidence for the existence of a new CA-containing cell group extending from the orbitofrontal cortex through the olfactory and pyriform cortices in the brain of two species of monkey. The TH-positive perikarya, which are 4000-5000 in number, are situated within the outer layers of these cortices and also within the olfactory tubercle and horizontal limbs of the diagonal band of Broca. They have small (10-20 microns) somata of round or oval shape. A majority are bipolar with long, slender dendrites but some are small, multipolar with widely branching dendrites. The shape and laminar distribution of these TH-positive neurons suggest that they may serve functions as cortical interneurons.

Animals↗
PubMed1983

Effect of GABA and benzodiazepine antagonists on [3H]flunitrazepam binding to cerebral cortical membrane.

The effects of GABA on the binding of [3H]flunitrazepam to bovine cerebral cortical membranes was investigated in presence and in absence of benzodiazepine antagonists. The percentage stimulation of [3H]flunitrazepam binding by GABA is higher when approximately 50% of the binding is displaced by benzodiazepine antagonists. The observed increase in percent stimulation of [3H]flunitrazepam binding by GABA might reflect the preferential displacement of the ligand by benzodiazepine antagonists from a GABA-insensitive conformational state or site of the receptor.

Animals↗
PubMed1983

Effect of insulin on central catecholamines.

The effects of insulin on levels and turnover of catecholamines in the hypothalamus and medulla oblongata were investigated. Systemic or intraventricular administration of insulin had no effect on catecholamine levels, but increased the turnover rate of norepinephrine and epinephrine. Insulin induced a dose-related increased release of norepinephrine, epinephrine and dopamine from hypothalamic slices. These results indicate that the effects of insulin on central catecholamines are elicited by its action in the brain.

Animals↗
PubMed1983

Abnormal unloading reflex in a patient with infarction of the medial lemniscus.

The unloading reflex was measured in the intrinsic muscles of the hand. By removing various fractions of the load on the muscles, we determined the size of the electromyographic response as a function of the change in the external force. This technique was applied to both hands of a patient with a pontine lesion who had impaired position sense in the left hand. The response to fractional unloading was significantly smaller in the left hand, an asymmetry not found in control subjects. The results suggest (1) that the unloading reflex is mediated, at least in part, by suprasegmental pathways, and (2) that the fractional unloading technique can reveal abnormalities not found by conventional methods.

Adult↗