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Biomedical subjects

R J Polinsky

Publications and source records attributed to R J Polinsky.

At least 73 records · Page 4Linked to original sources
PubMed1983

Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol.

Concentrations of free 3-methoxy-4-hydroxyphenylglycol in the plasma and cerebrospinal fluid are highly correlated, but concentrations in the cerebrospinal fluid are always higher than those in plasma, even when large amounts of the catecholamine metabolite are derived from a tumor of the adrenal medulla. This is explained by considering the plasma and cerebrospinal fluid as a two-compartment system in which the rate constants for entry into and exit from the cerebrospinal fluid compartment are similar. 3-Methoxy-4-hydroxyphenylglycol that is synthesized, but not catabolized, in the central nervous system maintains cerebrospinal fluid levels at an increment over those in plasma. This increment can be used to provide the best available index of formation of 3-methoxy-4-hydroxyphenylglycol in the central nervous system.

Adrenal Gland Neoplasms↗
PubMed1983

A family with histologically confirmed Alzheimer's disease.

A Canadian family comprising 51 members affected with Alzheimer's disease was evaluated clinically, histologically, and genetically. Ancestors were traced through eight generations, and 51 members were examined at the National Institute of Mental Health, Bethesda, Md. The pedigree is consistent with autosomal dominant inheritance. The effect of interrelatedness among some parents of affected individuals is unknown. In contrast to other studies, there was not an increased incidence of Down's syndrome, hematologic malignancy, or preponderance of affected females.

Alzheimer Disease↗
PubMed1983

Evidence that lack of deoxyribonucleic acid repair causes death of neurons in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder with hypersensitivity to the lethal effects of ultraviolet radiation caused by inherited defects in deoxyribonucleic acid (DNA) repair processes. Some patients with XP develop a primary neuronal degeneration which has been thought to result from unrepaired damage in neuronal DNA. Five years ago we reported that cultured skin fibroblasts from a 12-year-old girl with XP, who then had only one major neurological abnormality of the disease, had a sensitivity to ultraviolet radiation intermediate between that of XP patients with numerous neurological abnormalities and those with none. Recent neurological studies reveal that she has a slowly but progressively developing sensorineural deafness as well as cerebellar and motor dysfunction typical of XP. The results support the postulate that defective DNA repair is associated with premature neuron death.

Adolescent↗
PubMed1983

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.

Adult↗
PubMed1983

Urinary catecholamine metabolites distinguish different types of sympathetic neuronal dysfunction in patients with orthostatic hypotension.

Urinary excretion rates of the major norepinephrine metabolites, 3-methoxy-4-hydroxymandelic acid, 3-methoxy-4-hydroxy-phenylglycol and normetanephrine, were determined in 12 normal subjects and 23 patients with neurogenic orthostatic hypotension due to either multiple system atrophy [Shy-Drager Dyndrome (MSA)] or idiopathic orthostatic hypotension (IOH). There were striking and parallel decreases in all catecholamine metabolites in IOH consistent with loss of peripheral sympathetic nerves. Patients with MSA excreted greater amounts of the deaminated metabolites than did the patients with IOH, but most excreted equally low amounts of normetanephrine. The disproportionate decrease in excretion of normetanephrine by patients with MSA is consistent with observations in experimental animals that O-methylation is the primary metabolic route for active released norepinephrine, whereas deamination is the predominant metabolic route for intraneuronal degradation of the catecholamine. The similar proportional decreases in all catecholamine metabolites in patients with IOH (who have no central nervous system deficit) indicates that brain norepinephrine is a source of only a small fraction of urinary norepinephrine metabolites, including 3-methoxy-4-hydroxy-phenylglycol.

Humans↗
PubMed1983

Alzheimer disease: evidence for susceptibility loci on chromosomes 6 and 14.

We report the transmission of HLA haplotypes and Gm allotypes in 97 members of a single kindred containing 257 individuals, 45 of whom were determined by clinical examination, autopsy, or historical data to have had Alzheimer disease (AD). Extensive inbreeding suggests that more than one gene may contribute to susceptibility to AD in this family, despite the apparent vertical transmission of illness. The distribution of HLA haplotypes and of Gm allotypes to affected and unaffected siblings is consistent with the possibility that genes in the HLA region of chromosome 6 and perhaps also in the Gm region of chromosome 14 are determinants of susceptibility. Further studies are needed to investigate whether susceptibility to AD may result from an interaction between (immune response?) genes on these two chromosomes.

Adult↗
PubMed1982

Pancreatic polypeptide responses to hypoglycemia in chronic autonomic failure.

Pancreatic polypeptide (PP) and catecholamine responses to insulin-induced hypoglycemia have been measured in 15 patients with neurogenic orthostatic hypotension. Eight of the patients had idiopathic orthostatic hypotension, and 7 had multiple system atrophy, a condition characterized by the presence of central nervous system lesions in addition to the orthostatic hypotension common to both diseases. Eleven healthy subjects exhibited rapid and substantial elevations in plasma epinephrine, norepinephrine, and PP concentrations in response to insulin hypoglycemia. In contrast, patients with neurogenic orthostatic hypotension exhibited impaired catecholamine and PP responses to insulin hypoglycemia. There was no correlation between the catecholamine and PP responses in either the normal subjects or the patients, suggesting that PP release during hypoglycemia is independent of the sympathoadrenal medullary response. As PP release in response to insulin hypoglycemia is abolished by truncal vagotomy and unaffected by splanchnic nerve section, our results suggest that patients with chronic autonomic failure may have a diffuse autonomic dysfunction involving the parasympathetic as well as the sympathetic nervous system.

Adult↗
PubMed1982

Lymphocyte proteins in Huntington's disease: quantitative analysis by use of two-dimensional electrophoresis and computerized densitometry.

We used quantitative two-dimensional electrophoresis to study lymphocyte proteins in Hungtington's disease. Three hundred and six polypeptides from 14C-labeled, phytohemagglutinin-stimulated lymphocytes were measured for variation in relative spot density and 186 for variation in spot position by use of a computer program requiring operator interaction. Each polypeptide was measured in a total of 30 electrophoretograms from 28 individuals, including 13 with Huntington's disease, 2 at risk for it, and 13 controls. The study included two sets of identical twins and, as neurological controls, individuals with neurofibromatosis, Alzheimer's disease, or Shy-Drager syndrome. Seven protein polymorphisms were identified among the 186 most dense polypeptides of each gel, corresponding to a minimum average heterozygosity of 1.4%. Stringent criteria were used to define polymorphic proteins, including observation of at least one individual with each of two homozygous phenotypes and one with the heterozygous phenotype, demonstration of the expected gene dosage relationship by quantitative densitometry, consistency with genetic relationships, and reproducibility. One polymorphic protein showed three electrophoretically variant alleles. Our identification of seven polymorphisms among the 186 proteins measured on a single electrophoretogram illustrates the potential of this technique for performing linkage analysis in diseases of genetic origin. However, we observed no quantitative or positional protein variations that were characteristic of (i.e. specific for) Huntington's disease.

Blood Proteins↗
PubMed1981

Essential hypertension: central and peripheral norepinephrine.

The concentration of norepinephrine in cerebrospinal fluid from patients with essential hypertension is higher than that from healthy normal volunteers, but the concentrations of norepinephrine in plasma from these groups are similar. This finding indicates that central nervous system noradrenergic hyperactivity occurs in essential hypertension but apparently is not reflected in abnormal function of the peripheral sympathetic nervous system in these patients.

Adult↗
PubMed1981

Urinary 6-hydroxymelatonin excretion in patients with orthostatic hypotension.

The rates of melatonin formation and its diurnal fluctuations have been examined in patients with three types of orthostatic hypotension by measuring the urinary excretion rates of 6-hydroxymelatonin, the major metabolite of the pineal gland hormone. Deficiencies in the peripheral autonomic nervous system resulted in markedly diminished daily excretion (2.5 +/- 1.3 micrograms) relative to control (12.2 +/- 1.2). Patients with impaired central nervous system function exhibited low and/or abnormal excretion patterns. Two patients with sympathotonic orthostatic hypotension excreted greater amounts of 6-hydroxymelatonin than any of the control subjects. Melatonin secretion by the pineal gland can be used as an index of sympathetic nerve function. The study of patients with altered function may reveal the role of the pineal gland in human physiology.

Adolescent↗
PubMed1981

Pharmacologic distinction of different orthostatic hypotension syndromes.

We studied the pressor responses to vasoactive agents in patients with orthostatic hypotension. Greater-than-normal slopes of the stimulus-response curves in patients with multiple system atrophy (Shy-drager syndrome) and idiopathic orthostatic hypotension (IOH) were consistent with deficient reflex modulation. Patients with IOH also had a shift to the left of the plasma norepinephrine-blood pressure curves, suggesting "denervation supersensitivity." This was consistent with the deficient plasma norepinephrine response to tyramine in these patients. Patients in whom orthostatic hypotension is attended by tachycardia are subsensitive to administered catecholamines, and may suffer from deficient effector organ responsivity.

Adult↗