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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 523 records · Page 29Linked to original sources
PubMed1983

Characterization of a human anti-hCG antiserum: a proposed standard for laboratories involved with the development of hCG vaccines.

An antiserum (PC-81-1) was obtained from a man who developed antibodies against hCG during treatment for hypogonadism. The antiserum was unique in that its affinity for hCG was high (greater than 10(-10) M(-1] and its cross-reaction with hLH and the hCG-subunits was only 1-12.5% and 0.01%, respectively, of intact hCG. We propose that this human antiserum be used as a laboratory standard by investigators who are developing vaccines directed against hCG. The use of this standard in the proposed protocol will permit comparison of titers between laboratories. Lyophilized samples of antiserum PC-81-1 are available on request from the Population Council.

Antibodies↗
PubMed1983

Development of catecholaminergic phenotypic characters in the mouse locus coeruleus in vivo and in culture.

While abundant studies have begun to elucidate ontogeny of the peripheral nervous system, molecular mechanisms underlying brain development remain obscure. To approach this problem, we initiated parallel in vivo and in vitro studies of the mouse locus coeruleus (l.c.), a brainstem noradrenergic nucleus. The catecholaminergic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) were used to monitor phenotype expression and development. TH catalytic activity and immunocytochemical reactivity were initially detectable on gestational Day 13 (E-13) in vivo, and adult levels of activity were approximately by the third postnatal week. Immunotitration studies indicated that the developmental increase was due to accumulation of enzyme molecules and not enzyme activation. The in vivo developmental profile of DBH approximated that of TH. To begin defining regulatory mechanisms, explants of embryonic brainstem were placed in culture. Explantation on E-12, prior to expression of TH or DBH, resulted in the de novo appearance of these phenotypic characters after 4 days. Explantation on E-18, after the enzymes are already expressed, was followed by a striking sixfold rise in TH activity. Immunotitration studies revealed that the increase in TH activity in E-18 cultures was attributable to increased molecule number, reproducing the in vivo results. Moreover, the E-18 explants, cultured for 3 weeks, attained higher plateau levels of TH activity than E-12 cultures, and this differences was due to increased molecule number. Morphometric analysis indicated that 3-week E-12 cultures actually had more l.c. cells than E-18 cultures, indicating that differences in TH were not due to increased cells in the E-18 l.c. Finally, systemic study revealed that the development of TH activity in culture increased progressively from E-11 to E-12 to E-13, suggesting that critical regulatory events occur at this time. Our studies suggest that the l.c. is an excellent model for the study of brain development in vivo and in vitro. Initial phenotypic expression and dramatic development occur in culture in the absence of normal targets, normal afferent innervation and, presumably, normal humoural milieu.

Animals↗
PubMed1983

Penile replantation.

A case of penile amputation and replantation is presented. Partial amputation may be repaired without microsurgical technique with good results. For complete amputation, specific microneurovascular repair is recommended.

Amputation, Traumatic↗
PubMed1983

Human brainstem catecholamine neuronal anatomy as indicated by immunocytochemistry with antibodies to tyrosine hydroxylase.

Immunocytochemistry based on antibodies to tyrosine hydroxylase is used to identify catecholaminergic neurons in the human brain stem. An atlas is provided and the distribution of structures compared with that in other animals and with biochemical and catecholamine fluorescent data from humans. Broad agreement of results increases the confidence with which tyrosine hydroxylase-like immunoreactivity can be used to trace catecholaminergic pathways in human postmortem material. As compared to most studies of other animals there are striking increases in populations of upper pontine and mesencephalic catecholaminergic neurons in the human. Distinct cytoarchitectonic features, consistent differences in tyrosine hydroxylase immunoreactive staining intensity and regional variations in substance P innervation indicate complexity within the substantia nigra. Human catecholaminergic neurons are prominent in the midline of the ventral tegmentum and the upper parts of the central tegmental tracts. A bundle of tyrosine hydroxylase-immunoreactive axons runs between the latter regions and a cluster of smaller catecholaminergic neurons which lie in the oblique band of axons joining ventrolateral and dorsomedial medullary catecholaminergic groups. There are more catecholaminergic neurons within and closely related to the superior cerebellar peduncles than have been described in other species. Anatomically, the central compact nucleus of the locus coeruleus appears to be related to several nearby catecholaminergic cell groups. The data provided are being used as a basis for neuropathologic studies of human neurological diseases.

Adolescent↗
PubMed1983

Origin of peptide-containing fibers in the inferior mesenteric ganglion of the guinea-pig: immunohistochemical studies with antisera to substance P, enkephalin, vasoactive intestinal polypeptide, cholecystokinin and bombesin.

After different denervation procedures the guinea-pig inferior mesenteric ganglion was analysed by immunohistochemistry using antisera to substance P, enkephalin, vasoactive intestinal polypeptide, cholecystokinin and bombesin. The results demonstrate that each of the nerve trunks connected to the ganglion carries specific peptidergic pathways. Thus, the lumbar nerves contain substance P-immunoreactive primary afferent neurons, which to a large extent traverse the ganglion, and enkephalin-immunoreactive preganglionic neurons; the colonic nerves carry vasoactive intestinal polypeptide-, cholecystokinin- and bombesin-immunoreactive fibers from the distal colon to the ganglion; the hypogastric nerves contain vasoactive intestinal polypeptide-positive fibers from the pelvic plexus; and the intermesenteric nerve contains vasoactive intestinal polypeptide, cholecystokinin, substance P and enkephalin from divergent sources. By studying accumulations of peptides in ligated lumbar splanchnic, intermesenteric, hypogastric and colonic nerves the existence of these major peptidergic pathways was confirmed and evidence was obtained for additional, not so prominent, peptidergic projections. The results arae discussed in view of earlier morphological and physiological studies.

Animals↗
PubMed1983

Influence of solutes in plasma on the total CO2 content determination: implications for clinical disorders.

The purpose of these experiments was to determine the effect of non-aqueous solids on the total CO2 content of plasma. Two major groups of compounds were explored; those which reduced the total CO2 content, such as saline, and those which did not, such as albumin. To assess the former, sufficient sodium chloride was added to a bicarbonate solution gassed with 5% CO2 to increase the total volume by 10%. The total CO2 content fell the predicted 10% from 27.2 to 24.5 mmol/L when sodium chloride was added. In contrast, when the aqueous volume of a bicarbonate solution gassed with 5% CO2 was decreased by isohydric albumin, the total CO2 content was not reduced. We hypothesize that carbamino-compounds were formed with albumin and this raised the volume of CO2 released by an excess of acid. Therefore, the calculated pK' for the bicarbonate buffer system, which is derived from solutions lacking proteins, is not solely determined by the concentrations of bicarbonate, dissolved CO2, carbonate and carbonic acid when albumin is present. The clinical implications of these results will be discussed.

Acid-Base Imbalance↗
PubMed1983

When to use the Chevassu maneuver during exploration of intrascrotal masses.

As many as 50 per cent of explorations for intrascrotal masses result in orchiectomy for benign disease. The most common diagnoses are hydrocele, epididymitis and benign testicular tumors. Many of these diagnoses could be made before orchiectomy if the tunica vaginalis and, occasionally, the tunica albuginea were opened, and the lesion biopsied. However, violation of the testicular tunics traditionally has been considered taboo because of the dangers of tumor seeding. In 1906 Chevassu suggested inguinal exploration and occlusion of the testicular vessels before biopsy of suspicious lesions. We have added scrotal hypothermia, double ligation of the gubernaculum before its division and irrigation with distilled water to provide a procedure that adheres to the principles of good cancer surgery. Its use during inguinal explorations for suspicious intrascrotal masses in 5 patients led to a benign diagnosis and preservation of the testis in 3 instances without subsequent testicular atrophy. Its judicious use can decrease the incidence of orchiectomy for benign disease.

Adolescent↗
PubMed1983

Expression of catecholaminergic characteristics by primary sensory neurons in the normal adult rat in vivo.

Expression of catecholaminergic characteristics by primary sensory neurons was examined in the vagal nodose and glossopharyngeal petrosal ganglia of the normal adult rat in vivo. Catecholaminergic phenotypic expression was documented by immunocytochemical localization of tyrosine hydroxylase (TyrOHase; EC 1.14.16.2), radiochemical assay of specific TyrOHase catalytic activity, and cytochemical localization of formaldehyde-induced catecholamine fluorescence (FIF) within principal ganglion cells. The TyrOHase-containing cells exhibited morphologic features typical of primary sensory neurons, such as an initial axon glomerulus and a single, bifurcating neurite process. These cells were distinguished from TyrOHase- and FIF-positive small intensely fluorescent cells by size, morphology, and staining intensity. TyrOHase-containing neurons appeared to be insensitive to neonatal treatment with 6-hydroxydopamine, thereby distinguishing them from sympathetic neurons. Nodose and petrosal ganglia of adult rats exhibited TyrOHase catalytic activity, linear with respect to tissue concentration over a 10-fold range, indicating that the immunoreactive enzyme was functional. Transection of specific ganglionic nerve roots depleted TyrOHase catalytic activity and neuronal immunoreactivity within the petrosal ganglion, suggesting that target organ innervation regulates enzyme levels within ganglion perikarya. Our study indicates that primary sensory neurons express catecholaminergic transmitter traits in the normal adult rat. Consequently, in the periphery, catecholaminergic characters are not restricted to the sympathoadrenal axis but are expressed by functionally and embryologically diverse populations of autonomic neurons.

Animals↗
PubMed1983

Maximal rate of tachycardia development: sinus tachycardia with sudden exercise vs. spontaneous ventricular tachycardia.

In addition to providing basic physiologic information, knowledge of the maximal rate of sinus tachycardia development may be helpful in developing algorithms permitting new generations of antitachycardia pacemakers to distinguish accurately between sinus and ventricular tachycardia. To determine the maximal rate of sinus tachycardia development, 50 normal subjects rushed up 100 stairs as rapidly as possible, with continuous electrocardiographic monitoring. During the first second of exercise, the mean cardiac cycle length shortened from 709 to 570 ms, equivalent to an increase in heart rate from 85 to 105 beats per minute, or 20 beats per minute per second. Thereafter, a more gradual decrease in cycle length occurred. Differences between men and women, smokers and non-smokers, and sedentary compared to active subjects were all insignificant. Analysis of 50 spontaneous episodes of ventricular tachycardia also revealed a sequential but more abrupt decrease in the cycle length during the first second from 757 to 360 ms, equivalent to a rate increase from 79 to 167 beats per minute, or 88 beats per minute per second. After approximately 1 1/4 seconds, the ventricular tachycardia cycle length remained virtually constant. Baseline cycle lengths were similar in the sinus and ventricular tachycardia groups, but differed in all subsequent beats, although overlap for individual subjects did occur.

Adolescent↗
PubMed1983

Chronic treatment with 1-dopa plus carbidopa in hemitransected rats: preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity.

Chronic i.p. treatment with 1-dopa-carbidopa for 3 weeks in hemitransected male rats leads on one hand to tolerance to 1-dopa induced turning behaviour and on the other hand to behavioural and biochemical signs of dopamine (DA receptor supersensitivity on the intact side. Thus, the apomorphine induced ipsilateral turning behaviour is enhanced and the KD values of the 3H-spiperone binding sites linked to DA receptors of the D2 type on the intact, but not on the denervated side are reduced by 40%. However, the number of 3H-spiperone binding sites is reduced by 20% in striatal membranes on the intact side after this type of treatment. Therefore, chronic treatment with a catecholamine (CA) precursor leads to selective adaptive changes at intact striatal DA synapses with certain signs of the expected development of DA receptor subsensitivity, but above all with signs of paradoxical development of DA receptor supersensitivity. A hypothesis is introduced to explain these results.

Animals↗
PubMed1983

Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.

The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i.p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.

Animals↗
PubMed1983

Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis.

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary PNH3. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, PNH3, and the urine minus blood PCO2 difference (U-B PCO2) were lower during acute hypercapnia. In these experiments, the urine PCO2 was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B PCO2 was 5 +/- 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary PNH3 can modify this relationship.

Acidosis↗
PubMed1983

Further studies with lisuride in Parkinson's disease.

Lisuride was administered to 63 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The group included 40 patients with 'on-off' phenomena. Lisuride alone (13 patients) or combined with levodopa (50 patients) resulted in a 34% decrease in PD disability as assessed in the 'on' period, a 16% decrease in disability as assessed in the 'off' period, and a 96% increase in the numbers of hours in which patients were 'on' (from 5.5 to 10.8 h). All of these changes were significant (p less than or equal to 0.001). 37 of the 63 patients (59%) improved at least one-stage on lisuride. The major adverse effect limiting the use of lisuride was the occurrence of an organic confusional syndrome. This was related, in part, to the presence of an underlying dementia and to the concurrent use of anticholinergic drugs.

Aged↗
PubMed1983

Therapeutic potentials of centrally acting dopamine and alpha 2-adrenoreceptor agonists.

The antiparkinsonian activity of several dopamine agonists was investigated in an animal model and clinically in parkinsonian patients. The semisynthetic ergoline, pergolide, the partial ergoline, LY 141865 and the 8-alpha-aminoergoline, CU 32-085 were found to be effective antitremor agents in monkeys with ventromedial tegmental lesions. The administration of pergolide or LY 141865 results in a relief of tremor with a concomitant occurrence of severe abnormal involuntary movements, while the administration of CU 32-085 results in a relief of tremor with the occurrence of only minor abnormal involuntary movements. Clinical studies have revealed that pergolide is an effective drug in patients with advanced Parkinson's disease, and it reduces the "on-off" phenomena. The possible regulation of dopamine neurotransmission by the norepinephrine neuronal systems was reviewed. Preliminary data suggest that clonidine may interact with presynaptic dopamine receptors.

Adrenergic alpha-Agonists↗