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Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 289 records · Page 16Linked to original sources
PubMed1989

Evidence for the occurrence of an enkephalin-like peptide in adrenaline and noradrenaline neurons of the rat medulla oblongata.

The indirect immunofluorescence technique was used to analyze the catecholaminergic neurons in the medulla oblongata of the rat for the presence of enkephalin (ENK)- and neuropeptide Y (NPY)-like immunoreactivity (LI). In colchicine pretreated animals, using a double staining technique with mouse and rabbit antibodies against ENK and tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT), it was demonstrated that both TH- and ENK-LI occurred in the same neurons, particularly in many neurons of the A1 noradrenaline cell group. In the transition zone to the C1 adrenaline cell group, a proportion of PNMT-positive cells also contained ENK-LI. In the rostral and mid portion of the C1 group only few TH/PNMT-positive cells were found to be ENK-positive. In the noradrenergic A2 region, a moderate number of cell bodies also contained TH- plus ENK-LI, whereas only a few of the adrenaline cells of the C2 and C3 groups showed ENK-LI. In addition, with an elution restaining technique it was possible to demonstrate that several of the cells containing TH- and ENK-LI were also positive for NPY-LI. The present findings demonstrate that a subpopulation of the catecholaminergic neurons in the medulla oblongata of the rat is ENK-positive, thereby indicating a possible co-release of the two compounds in their projection areas, for example the paraventricular nucleus and the spinal cord.

Adrenergic Fibers↗
PubMed1989

Probabilistic models of genome shuffling.

The comparison of entire genomes in evolutionary studies gives rise to alignments characterized by many intersections, or inversions in the order of two fragments in different genomes. To model this, we suggest a random migration process for fragments, and discuss its equilibrium distribution in the case of linear and circular genomes. Simulations are carried out to explore "cut-off" behavior as the process approaches equilibrium. We define a new process to take into account the indistinguishability of two fragments which are adjacent in both genomes being compared. Questions of applicability of these models are discussed.

Biological Evolution↗
PubMed1989

Prolonged hyperinsulinemia reduces plasma fatty acid levels in the major lipid groups in fetal sheep.

The offspring of women with poorly controlled diabetes have increased total body fat. Experimental fetal hyperinsulinemia has previously been associated with increased fat accumulation in rhesus monkey fetuses and increased lipid content and lipogenesis in rat fetuses. We hypothesized that prolonged fetal hyperinsulinemia would alter plasma total fatty acids and the individual fatty acids in each major lipid group. Fatty acids determined by gas-liquid chromatography were measured in the arterial blood of 12 chronically catheterized fetal sheep after 10 to 12 days of insulin (n = 7) or placebo (n = 5) infusion. Plasma concentrations of insulin were 412 +/- 63 microU/ml and 9 +/- 3 microU/ml (mean +/- SE) in the insulin- and placebo-treated fetal sheep, respectively. Prolonged fetal hyperinsulinemia was associated with lower circulating total fatty acid levels in each lipid class except cholesterol esters. Although the precursor of arachidonic acid, 18:2 (linoleic acid), was not decreased in any lipid class, insulin infusion was associated with reduced arachidonic acid in each lipid class. We conclude that prolonged fetal hyperinsulinemia decreases circulating total fatty acid and the individual fatty acids in each of the major lipid classes, except for the cholesterol esters. We speculate that these reductions in circulating fatty acids represent an insulin-mediated increase in tissue deposition.

Animals↗
PubMed1989

Effects of chronic fetal hyperinsulinemia on plasma arachidonic acid and prostaglandin concentrations.

In adult diabetic subjects and infants of diabetic mothers, hyperglycemia has been associated with increased intravascular thromboxane and decreased prostacyclin production. Because of the association between states of altered insulin concentration and prostaglandin metabolism, we hypothesized that chronic experimentally induced fetal hyperinsulinemia results in perturbations in fetal arachidonic acid and prostaglandin metabolism. Arachidonic acid, thromboxane B2 (the stable breakdown product of thromboxane A2), and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin) were determined in the arterial blood of chronically catheterized fetal sheep after 9 to 12 days of continuous insulin (15 U.day-1, n = 7) or placebo (n = 5) infusion. Fetal insulin infusion resulted in fetal hypoglycemia and a reduction in fetal arterial plasma arachidonic acid concentration (p less than 0.01). In addition, the concentration of thromboxane B2 relative to 6-keto-prostaglandin F1 alpha was significantly reduced in the insulin-treated group compared with the placebo-treated group (p less than 0.03). We conclude that fetal hyperinsulinemia in sheep produces perturbations in prostaglandin metabolism with reductions in the plasma arachidonic acid concentration and in the plasma concentration of thromboxane A2 relative to prostacyclin. The hyperinsulinemic-hypoglycemic state in the fetus influences the relative proportion of the vasoconstricting to the vasodilating prostaglandins, thereby potentially modulating fetal vasomotor tone.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system: an animal model of olivopontocerebellar atrophy-associated parkinsonism.

The effects of 3-acetylpyridine (3-AP) administration to rats on the mesotelencephalic dopamine system were assessed. A single 3-AP injection resulted in biochemical and immunohistochemical evidence of degeneration of the nigrostriatal dopamine system. Six weeks after 3-AP treatment decreases in both striatal dopamine content and the activity of the catecholamine biosynthetic enzyme tyrosine hydroxylase were observed. Immunohistochemical examination suggested a decreased density of striatal tyrosine hydroxylase-immunoreactive fibers and revealed the emergence of a distinctly patchy organization of the dopamine innervation to the dorsolateral striatum. While 3-AP administration resulted in biochemical and anatomical data consistent with the degeneration of nigrostriatal dopamine fibers, no significant changes in dopamine content or the density or pattern of tyrosine hydroxylase-immunoreactive fibers in the anteromedial prefrontal cortex or nucleus accumbens were seen. These data suggest that 3-AP administration may result in a relatively specific degeneration of the nigrostriatal dopamine system. Since 3-AP causes both a profound loss of the climbing fiber input to the cerebellum derived from the inferior olivary nucleus, and the degeneration of nigrostriatal dopamine neurons, 3-AP administration may provide a useful model of olivopontocerebellar atrophy-associated parkinsonism. Moreover, the differences in the neurotoxicity caused by 3-AP and that elicited by another pyridine which causes striatal dopamine depletion (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) may offer important insights into the mechanisms of both species- and site-specific pyridine neurotoxins.

Animals↗
PubMed1989

Accelerated idioventricular rhythm complicating atrioventricular junction ablation for automatic atrial tachycardia.

A 13-year-old male with histologic evidence of cardiomyopathy, drug-refractory primary atrial tachycardias, and deteriorating left ventricular function underwent transcatheter His bundle ablation to control ventricular rate. Following an initial successful ablation at the level of the atrioventricular node, the patient exhibited an accelerated escape rhythm of apparent junctional origin (ventricular cycle length = 470 msec, HV = 100 msec) with complete heart block. A second ablation procedure was undertaken, following which an accelerated idioventricular rhythm (cycle length = 500 msec) became apparent and has persisted (follow-up 15 months). Thus, findings in this patient suggest that attempts to control refractory rapid ventricular responses in cardiomyopathy patients with primary atrial tachycardias may be complicated by the potential for junctional and idioventricular sites to exhibit similar abnormally accelerated subsidiary pacemaker function.

Adolescent↗
PubMed1989

Monkeys with unilateral ventromedial tegmental lesions of the brain stem: models for Parkinson's disease and Lesch-Nyhan syndrome.

1. Monkeys with surgical unilateral ventromedial tegmental lesions of the brain stem served as models for investigating abnormalities in Parkinson's disease and Lesch-Nyhan syndrome. 2. The animals exhibited some neurological deficits which are similar to those observed in Parkinson's disease or Lesch-Nyhan syndrome. 3. In monkeys with unilateral ventrolateral tegmental lesions, the levels of dopamine and the activities of catecholamine-synthesizing enzymes were reduced on the lesion side of the striatum, and hypokinesia and tremor developed on the contralateral extremities. 4. Dopa or dopamine agonists relieve tremor and evoke abnormal involuntary movements which are similar to the responses observed in patients with Parkinson's disease. 5. The antitremor effect of Dopa is potentiated by catechol-O-methyltransferase inhibition, suggesting a therapeutic potential for these types of agents. 6. Evidence was obtained that stimulation of D2 dopamine receptors by selective dopamine agonists exerts antitremor activity and evokes abnormal involuntary movements. 7. Combined administration of D1 and D2 dopamine agonists seems to enhance the antitremor activity. 8. Partial dopamine agonists exert antitremor activity and produce less severe abnormal involuntary movements than full dopamine agonists. 9. In a group of monkeys with unilateral ventromedial tegmental lesions of the brain stem the administration of mixed D1/D2 dopamine agonists results in the occurrence of self-biting behavior of the forelimb digits and spasticity of the hindlimbs and these symptoms are similar to those observed in patients with Lesch-Nyhan syndrome. 10. The self-biting behavior seems to be associated with the stimulation of central D1 dopamine receptors and therefore the possible involvement of dopamine neuronal abnormalities in Lesch-Nyhan syndrome deserves further investigation.

Animals↗
PubMed1989

Calcitonin gene-related peptide and chromogranin A: presence and intra-axonal transport in lumbar motor neurons in the rat, a comparison with synaptic vesicle antigens in immunohistochemical studies.

The presence and intra-axonal transport of calcitonin gene-related peptide and chromogranin A were investigated in motor neurons belonging to the rat sciatic nerve. Their co-localization with markers of cholinergic organelles (SV2, p38, and synapsin I) was also investigated, using immunofluorescence techniques, including double labelling experiments. It was found that motor perikarya in the lumbar spinal cord contained calcitonin gene-related peptide-like immunoreactivity and chromogranin A-like immunoreactivity, and probably also caligulin-like immunoreactivity, located in the Nissl substance of the cytoplasm. Also, some SV2 (detected by the monoclonal antibody 10H) was present in some motor neuron perikarya, but most often these were devoid of SV2 and p38, as well as of synapsin I-like immunoreactivity. These three antigens were, on the other hand, concentrated in nerve terminals in the entire gray substance of the spinal cord. In the ventral root, after crushing, calcitonin gene-related peptide, chromogranin A, synapsin I, SV2, p38 and caligulin-like immunoreactivity accumulated in thick and medium-sized axons proximal to the crush, while only antisera against SV2 and p38 labelled accumulated material distal to the crush. In the sciatic nerve, the same essential picture was observed as in the ventral root, but here two other nervous components were also present in the normal sciatic nerve, i.e. peripheral branches of the sensory system and axons of the sympathetic system. By various denervation procedures, it was demonstrated that most calcitonin gene-related peptide-like immunoreactivity and almost all chromogranin A-like immunoreactivity, accumulating in thick axons proximally, emanated from the ventral root. Thin and medium-sized axons originated from the sensory and sympathetic systems and contributed to accumulations both proximally and distally to the crush. Synapsin I-like immunoreactive material accumulated only proximal to the crush, while SV2 and p38-like material accumulated bidirectionally in axons of all sizes. In motor endplates of the rat diaphragm and gastrocnemic muscle, no calcitonin gene-related peptide-like material was observed. However, some chromogranin A-like immunoreactivity was present, in addition to large amounts of synapsin I-like, p38-like and SV2-like material, which had a finely granular appearance and was concentrated near the presynaptic membrane of the nerve terminal endfeet, where synaptic vesicles are known to be located.

Animals↗
PubMed1989

Correlation of sperm-bound immunoglobulins with impaired semen analysis in infertile men with varicoceles.

Sperm-bound immunoglobulins were found in 27 (32%) of 84 infertile men with palpable varicoceles. These men were divided into two groups based on the presence (group I; 32%) or absence (group II; 68%) of sperm-bound immunoglobulins, as measured by an enzyme-linked immunosorbent assay. Circulating antisperm antibodies were identified in 52% of patients with sperm-bound immunoglobulins and 14% of group II patients. The presence of sperm-bound immunoglobulins was associated with a small but significant decrease in both sperm concentration and motility. Sperm-bound immunoglobulins are present in a greater percentage of infertile men with varicoceles than infertile men without varicoceles. Their presence may be a marker for damage to the seminiferous epithelia in men with varicoceles and may also contribute to varicocele-associated infertility.

Adult↗
PubMed1989

Elevation of intratesticular and scrotal skin surface temperature in men with varicocele.

A possible mechanism of varicocele-induced infertility is believed to be elevation of testicular temperature. Sensitive needle thermistors were used to measure directly intratesticular and bilateral scrotal surface temperatures simultaneously in anesthetized infertile men with varicocele and control subjects. We found that intratesticular temperature is elevated significantly in humans with varicocele. In addition, we have shown that scrotal skin surface temperature is elevated in men with varicocele. Furthermore, we demonstrate that unilateral varicocele is associated with bilateral elevation of scrotal surface temperature. These findings confirm the results of animal studies revealing elevation of intratesticular temperature associated with varicocele and suggest bilateral elevation in unilateral varicocele.

Adult↗
PubMed1989

Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat.

The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease.

Animals↗
PubMed1989

Rapid increase in enzyme and peptide mRNA in sympathetic ganglia after electrical stimulation in humans.

Thoracic ganglia in humans were studied after electrical, preganglionic stimulation using in situ hybridization with synthetic oligonucleotide probes against the catecholamine-synthesizing enzymes tyrosine hydroxylase (EC 1.14.16.2) and dopamine beta-hydroxylase (EC 1.14.17.1) and neuropeptide tyrosine. Immunohistochemical analysis was also performed. Following short peroperative stimulation a severalfold increase in all three mRNAs was found in principal ganglion cells, whereas no definite changes could be detected in enzyme or peptide levels with immunohistochemistry. The results suggest a very rapid and sensitive regulation of genes involved in signal transmission in the sympathetic nervous system of humans. Moreover, they indicate that electrical stimulation of neurons and/or pathways combined with in situ hybridization may be used as a method to define neuronal projections by visualizing increases in mRNAs for transmitter enzymes and/or peptide in target cells.

Autoradiography↗
PubMed1989

Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress.

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine and of immobilization stress, subcutaneous injection of capsaicin, and intraperitoneal injection of hypertonic salt solution on expression of c-Fos-like immunoreactivity was studied in the rat brain with immunohistochemistry. All the procedures induced c-Fos immunoreactivity in parvocellular neurons of the paraventricular nucleus, and many of these neurons also contained corticotropin-releasing factor immunoreactivity. c-Fos immunoreactivity was also observed, for example, in subpopulations of neurons in the locus coeruleus, the ventrolateral medulla oblongata, and the nucleus tractus solitarii. Many of these cells also expressed catecholamine-synthesizing enzymes. The results suggest that intraventricular injection of colchicine is a stressful stimulus and support the view that several catecholamine cell groups in the lower brainstem are part of the brain circuitry mediating stress reactions, as are the hypothalamic neurons that contain corticotropin-releasing factor.

Animals↗
PubMed1989

Greater calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in chronic Doca-salt hypertension.

The present study was carried out to investigate the role of calmodulin in the adrenergic transmission of deoxycorticosterone acetate (DOCA)-salt hypertension. In perfused mesenteric vasculatures prepared from DOCA-salt hypertensive rats (seven to eight weeks after operation) and age-matched normotensive control rats, the effects of a specific calmodulin antagonist (W-7: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) on the norepinephrine release and vascular responsiveness were examined. Endogenous norepinephrine overflow during electrical nerve stimulation was significantly greater in the mesenteric vasculatures of DOCA-salt hypertensive rats both at low (5 Hz) and high (15 Hz) frequencies than in those of the normotensive controls. Vasoconstrictor responses to electrical nerve stimulation or exogenous norepinephrine were also enhanced in the DOCA-salt hypertension compared to those in the controls. The calmodulin antagonist (W-7) inhibited the stimulation-evoked norepinephrine overflow and pressor responses in a dose-dependent manner. The suppressive magnitudes in these responses by W-7 were significantly greater in the mesenteric vasculatures of the DOCA-salt hypertension than in those of the control rats. These results demonstrate that the vascular adrenergic neurotransmission might be enhanced in the mesenteric vasculatures of the DOCA-salt hypertensive rats. Further, it is suggested that the marked reduction in stimulation-evoked norepinephrine overflow and vasoconstrictor responses by W-7 showed the greater calmodulin-dependent regulation in the vascular adrenergic activity of DOCA-salt hypertension.

Animals↗
PubMed1989

Antibodies to a synthetic peptide corresponding to a Ser-40-containing segment of tyrosine hydroxylase: activation and immunohistochemical localization of tyrosine hydroxylase.

A peptide corresponding to position 32-47 in tyrosine hydroxylase was synthesized (TH-16) and polyclonal antibodies against this peptide were raised in rabbits (anti-TH-16). The effects of anti-TH-16 on modulation of tyrosine hydroxylase activity were investigated. Anti-TH-16 enhanced the enzymatic activity in a concentration-dependent manner, and the antigen TH-16 inhibited the stimulatory activity of the antiserum in a concentration-dependent manner. The activated enzyme had a lower Km app for the cofactor 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropterin and a higher Vmax app than the nonactivated enzyme. Anti-TH-16 was characterized further by its ability to immunoprecipitate the enzyme activity by labeling tyrosine hydroxylase after Western blotting and by immunohistochemical labeling of catecholaminergic neurons. Anti-TH-16 did not block activation of tyrosine hydroxylase by phosphorylation catalyzed by cyclic AMP-dependent protein kinase. Exposure of the enzyme to anti-TH-16 and subsequent phosphorylation of the enzyme resulted in a greater activation of the enzyme than the sum of activation produced by these two treatments separately. However, the activation was less than additive when the enzyme was first phosphorylated and subsequently exposed to anti-TH-16. The present study demonstrates the utility of anti-TH-16 in investigating the molecular aspects of the enzyme activation.

Adrenal Gland Neoplasms↗
PubMed1989

Adrenal medullary transplants as a treatment for advanced Parkinson's disease.

Open autologous adrenal medullary to caudate nucleus transplantation was performed in 12 patients with advanced Parkinson's disease (PD). Ten of these patients had diurnal response fluctuations including "wearing off" and "on/off" phenomena. All of the patients were no longer satisfactorily responding to levodopa/carbidopa and dopamine agonists. The mean age of the patients was 55.1 years (range 37-65 yrs); mean duration of PD was 11.7 years (range 4-40 yrs); mean stage "on" was 3.3 (range 2-4); mean stage "off" was 4.8 (range 4-5). Mean duration of follow up from surgery was 10.4 months (range 2-17 months). Three patients improved dramatically with major changes in their lifestyle. The course of improvement in these 3 patients was different in each, implying that different mechanisms were responsible for the improvement. One of the patients died unexpectedly. In this patient, there were no surviving adrenal cells. Three patients improved moderately. Patients reported that they were "on" longer and had to take medication less often and were less dependent on individual doses of levodopa/carbidopa. The improvement has been sustained in two patients. However, in one of these patients there had to be frequent changes in scheduling to maintain the improvement. Two patients after technically successful implants did not improve. One of these patients subsequently died. In this patient there were a few surviving adrenal medullary cells. Four patients suffered major complications. One patient had a cerebral infarction and two had cerebral hemorrhages. One of these patients has shown a good recovery. One patient with autonomic insufficiency had a cardiac arrest with cerebral anoxia one week after surgery. This patient has shown a partial recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗