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D Goldman

Publications and source records attributed to D Goldman.

At least 253 records · Page 14Linked to original sources
PubMed1991

Cytochrome P-450 mediated metabolism of progesterone by adrenal microsomes of PCB-treated and untreated barn owl (Tyto alba) and marsh turtle (Mauremys caspica) in comparison with the guinea-pig.

1. Significant differences between species were observed in the profile of steroids produced from progesterone by adrenal microsomes as well as in the effects elicited by Aroclor 1254 on cytochrome P-450-mediated activities. 2. In the guinea-pig, the major metabolites were products of the corticosteroid pathway but products of the androgenic pathway were also detected; in the barn owl products of both pathways were also formed while in the marsh turtle only products of the corticosteroid pathway were detected. 3. The effect of Aroclor 1254 on P-450C21 activity in the turtle and barn owl was inductive in contrast to the inhibitory effect observed in the guinea-pig.

17-alpha-Hydroxyprogesterone↗
PubMed1991

Linkage mapping of human polymorphic proteins identified by two-dimensional electrophoresis.

Nineteen polymorphic lymphocyte proteins were previously detected by two-dimensional protein electrophoresis (2DE). In this report, we describe the genetic linkage mapping of six of these polymorphic proteins (PNIA1-PNIA6), the identification by genetic linkage of a seventh (glyoxalase 1 on 6p21), and support for the mapping of an eighth (plastin or LCP1) to near the ESD locus on Chr 13. PNIA1-PNIA6 were assigned, respectively, to 10q26, 16p13.3, 10q, 11p15, 3q, and 19q13. These genetic linkages were achieved by classical linkage analysis of 2DE protein charge polymorphisms to the panel of RFLPs previously typed in nine pedigrees in the Centre D'Etude du Polymorphisme Humain (CEPH) collection.

Blood Proteins↗
PubMed1991

Induction of adult-type nicotinic acetylcholine receptor gene expression in noninnervated regenerating muscle.

Expression of adult-type nicotinic acetylcholine receptors at the neuromuscular junction is thought to result from selective induction of their genes in endplate-associated nuclei due to local neurotrophic control. However, denervation studies indicate that endplate-specific expression can be maintained in the absence of the nerve. We investigated the role played by the basal lamina in this expression by assaying for the adult-type-specific epsilon RNA in noninnervated regenerating muscle. We found that this RNA is locally expressed beneath the old endplates after 10 days of regeneration. At earlier times epsilon RNA is also found in areas other than the endplate region. These results indicate that in adult muscle the basal lamina contains all the components necessary to direct nicotinic acetylcholine receptor gene expression to the endplate.

Animals↗
PubMed1991

Genetic mapping of the beta 1 GABA receptor gene to human chromosome 4, using a tetranucleotide repeat polymorphism.

As more coding loci for functional human genes are described, there is a growing need to identify DNA polymorphisms in specific genes. By examining DNA sequences within the introns of the beta 1 subunit of the gamma-aminobutyric acid receptor gene, GABARB1, we found a tetranucleotide repeat sequence (GATA). Amplification of this region by using PCR revealed seven alleles and a high degree of polymorphism (PIC = .75) in human populations. DNAs from the CEPH families were typed for the GABARB1 intron polymorphism and were analyzed with respect to 20 linked markers on chromosome 4. The results permit placement of GABARB1 on the linkage map of chromosome 4, between D4S104 and ALB. These results affirm that sequence analysis of noncoding segments included within or adjacent to functional genes has value as a strategy to detect highly informative polymorphisms.

Alleles↗
PubMed1991

Expression of mouse serotonin transporter RNA in Xenopus laevis oocytes.

The serotonin transporter removes serotonin from the synapse, terminating the action of this neurotransmitter. We have taken an initial step towards cloning the serotonin transporter by obtaining its expression in Xenopus oocytes. We found that mouse brainstem is a suitable source of serotonin transporter mRNA and that synthesis of the transporter in injected oocytes occurs steadily over a 3 day period. Uptake of [3H] serotonin was inhibited by 18 nM citalopram, a specific inhibitor of serotonin transport.

Animals↗
PubMed1990

Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism.

Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that the D2/Taq I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls. To assess this association further, we evaluated the D2/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D2 receptor gene. We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. The SADS-L interviews and other data were then used to ascertain diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D2/Taq I or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D2 receptor locus. Several recombinants between the D2/Taq I locus and alcoholism were observed in two white families with an alcoholic parent who possessed the A1 allele. This study does not support a widespread or consistent association between the D2 receptor gene and alcoholism.

Adult↗
PubMed1990

Noradrenergic control of the synthesis of two rat pineal proteins.

Pineal physiology is controlled by norepinephrine released from sympathetic nerves terminating in the gland. In the present study, the effect of norepinephrine on the labelling of specific proteins was investigated by incubating glands with [35S]methionine and then resolving the proteins by two-dimensional polyacrylamide gel electrophoresis; the patterns were analyzed by computer-assisted image analysis. The most prominent effects of norepinephrine were distinct and consistent increases in the labelling of two proteins (37 kDa, pI = 6.0, 50 kDa, pI = 6.0), designated adrenergically induced protein (AIP 37/6 and AIP 50/6). In both cases, norepinephrine was effective at low concentrations (EC50 = 10 nM). Pharmacological studies indicated that the effects of norepinephrine on both proteins involved a beta-adrenergic receptor, and that cyclic AMP was the second messenger. Pulse-chase labelling experiments revealed that these effects of norepinephrine did not involve post-translational modification of previously labelled precursor proteins, but depended upon de novo synthesis of protein. An inhibitor of mRNA synthesis, actinomycin-D, was found to block the effect of norepinephrine on AIP 50/6 but not on AIP 37/6, suggesting that norepinephrine acted on AIP 50/6 via a transcriptional mechanism and on AIP 37/6 via a translational mechanism. These in vitro studies were extended into in vivo investigations by measuring silver-stained AIP 37/6 in the two-dimensional gels. Changes in the amount of AIP 37/6 in pineal glands were studied in response to treatments which block the adrenergic stimulation of the gland, including exposure to constant lighting or removal of the superior cervical ganglia. Both treatments reduced AIP 37/6 by 50-75% in 8 weeks. These observations, together with those from in vitro studies, suggest that the amount of AIP 37/6 in the pineal gland is regulated by norepinephrine; and further, that norepinephrine acts through a beta-adrenergic-cyclic AMP mechanism to control AIP 37/6 synthesis at a translational level.

Adrenergic Fibers↗
PubMed1990

Inhibition by adenosine 3':5'-monophosphate of eicosanoid and platelet-activating factor biosynthesis in the mouse PT-18 mast cell.

A mouse spleen-derived mast cell line (PT-18) was employed to examine the mechanisms of adenosine 3':5'-monophosphate (cAMP)-mediated inhibition of antigen-induced lipid mediator biosynthesis. Specifically, we tested the hypothesis that increasing cAMP in mast cells inhibits lipid mediator biosynthesis by a mechanism independent of effects on histamine release (degranulation) or changes in cytosolic calcium concentration. Forskolin inhibited antigen-induced prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and leukotriene B4 (LTB4) production by 30-50%. In contrast, forskolin had no inhibitory effect on antigen-induced increases in cytosolic calcium concentration, as monitored by the calcium indicator fura-2, or histamine release from the cells. The combination of the phosphodiesterase inhibitor isobutylmethylxanthine with forskolin inhibited the antigen-induced production of PGD2 and LTC4 by 90-100% and histamine release by about 60%. These responses were accompanied by a virtual abolition of the antigen-induced increase in cytosolic calcium. To test further the hypothesis that increasing cAMP can lead to inhibition of lipid mediator biosynthesis in the absence of effects on cytosolic calcium, we employed the calcium ionophores A23187 and ionomycin. Forskolin alone or in combination with isobutylmethylxanthine had no effect on ionophore-induced increases in cytosolic calcium but effectively inhibited leukotriene biosynthesis. In addition, increasing cyclic AMP led to an inhibition of ionophore-induced production of platelet-activating factor and liberation of arachidonic acid. These data suggest that a relatively modest increase in cAMP-dependent protein kinase activity in mast cells leads to inhibition of the lipase-catalyzed cleavage of arachidonic acid from membrane phospholipids in the absence of measurable effects on either histamine release or changes in cytosolic calcium concentration. This effect results in a selective inhibition of the biosynthesis of lipid mediators including LTC4, LTB4, PGD2, and platelet-activating factor.

1-Methyl-3-isobutylxanthine↗
PubMed1990

The interference of aroclor 1254 with progesterone metabolism in guinea pig adrenal and testes microsomes.

The effects of Aroclor 1254 on cytochrome P-450-mediated steroidogenic activities were investigated in adrenal and testis microsomes of male guinea pigs. A significant decrease was recorded in the tissue content of adrenal microsomal cytochrome P-450 as well as a significant reduction in the overall conversion of progesterone to steroid products. The effects of exposure to Aroclor 1254 on activities of cytochrome P450 21-hydroxylase and cytochrome P450 17 alpha-hydroxylase/C17,20-lyase were selective. Cytochrome P-450 21-Hydroxylase activity was inhibited, as reflected by a decrease in production of 11-deoxycortisol and 11-deoxycorticosterone, whereas the cytochrome P-450 17 alpha-hydroxylase/C17,20-lyase activities, represented by the production of 17 alpha-hydroxyprogesterone and androstenedione were elevated. The same and even more pronounced pattern of altered progesterone metabolism elicited by Aroclor 1254 was observed in vitro, when Aroclor 1254 was introduced into incubation mixtures prepared with adrenal microsomes from untreated animals. Under such experimental conditions, a decrease in the overall metabolism of progesterone was observed as well as a decrease in cytochrome P-450 21-hydroxylase activity, while there was significant elevation in the 17 alpha-hydroxylase/C17,20-lyase activities. The effect of Aroclor 1254 on the testes differed largely from its effect on the adrenal cortex. In testis microsomes, pretreatment with Aroclor 1254 resulted in no changes in the cytochrome P-450 content, contrary to the decrease observed in adrenal microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1990

Characterization and chromosomal mapping of a cDNA encoding tryptophan hydroxylase from a mouse mastocytoma cell line.

A cDNA library was constructed from RNA prepared from P815 mouse mastocytoma cells and screened for tryptophan hydroxylase. An essentially full-length clone that recognizes a major mRNA species of 1.9 kb in mastocytoma cell lines and in pineal gland, duodenum, and brainstem of the mouse was obtained. The predicted amino acid sequence of this mouse mastocytoma clone showed 97 and 87% identity, respectively, with tryptophan hydroxylase clones isolated from rat and rabbit pineal glands, but the mouse clone contains an unusual 3-amino-acid duplication near the N-terminus and lacks a phosphorylation site. A fragment of the cDNA produced an enzymatically active protein when expressed in Escherichia coli, thus demonstrating that the catalytic domain is included in the C-terminal 380 amino acids. The mouse tryptophan hydroxylase locus, termed Tph, was mapped by Southern blot analysis of somatic cell hybrids and by an interspecific backcross to a position in the proximal half of chromosome 7. Because TPH has been mapped to human chromosome 11, this assignment further defines regions of homology between these mouse and human chromosomes.

Amino Acid Sequence↗
PubMed1990

Genetic epidemiology of ethanol metabolic enzymes: a role for selection.

Human ethanol consumption has a profound impact on nutritional status, causing major alterations in intermediary metabolism and critical deficiencies of vitamins and trace elements. The major enzyme systems responsible for the principal steps in ethanol metabolism have been characterized and the genes cloned, and significant functional polymorphisms have been identified. An inactive allele of the mitochondrial ALDH is associated with flushing and reduced alcohol intake. This allele may also confer greater sensitivity to some of ethanol's toxic effects. In populations not possessing this variant, twin and adoptive studies have revealed that heritability for alcoholism is greater than 50%. The occurrence of three functional polymorphisms in the ethanol metabolic pathway, including two mutations which are conserved across populations, suggests a role for selection in their maintenance. The two general categories of selective forces to maintain these polymorphisms are food toxins and infectious diseases. Of the infectious agents, amoebi and other anaerobic and microaerophilic organisms of the gut are the most logical candidates.

Alcoholism↗
PubMed1990

Dietary treatment of hypercholesterolemia.

Diet is the first line of treatment for hypercholesterolemia. Patients should be encouraged to make simple and stepwise changes in their diets to lower elevated cholesterol levels. General dietary guidelines from the American Heart Association (AHA) Step-One Diet include limiting the amount of total fat to less than 30% of total calories, decreasing cholesterol intake to less than 300 mg/day, and adjusting caloric intake to levels required to attain or maintain ideal body weight. Diets must be individualized to meet therapeutic needs within the limits of the patient's abilities, knowledge, and motivation.

Cholesterol, Dietary↗
PubMed1990

Profile of bronchospastic disease in Puerto Rican patients in New York City. A possible relationship to alpha 1-antitrypsin variants.

A high prevalence of asthmalike symptoms was noted among patients of Puerto Rican descent attending Beth Israel and North Central Bronx Medical Centers in New York City, as compared with other ethnic groups. An evaluation of family and medical histories, pulmonary function data, and alpha 1-antitrypsin phenotypes was undertaken in such Puerto Rican patients and control subjects without asthma. The patients showed a higher proportion of MS and MV phenotypes. All the patients in both MM and variant phenotype groups, with the exception of four MM patients, had features indicative of asthma, with labile airway obstruction, and elevated serum immunoglobulin E and eosinophil levels. The latter was significantly higher in the patients with variant phenotypes than in MM patients. Patients with alpha 1-antitrypsin variants also had much shorter smoking histories as compared with the MM group, and all reported histories of asthma in first-degree relatives, as compared with 66% among the MM patients. We conclude that there is an increased incidence of asthma among Puerto Ricans in New York City, and that the antitrypsin variant phenotypes (specifically S and V) play a role in this incidence and its expression.

Asthma↗
PubMed1990

Multiple nicotinic acetylcholine receptor genes are expressed in goldfish retina and tectum.

cDNAs encoding a novel nAChR structural subunit (GFn alpha-3) and a ligand-binding subunit (GF alpha-3) have been isolated from a goldfish retina cDNA library. The protein encoded by GFn alpha-3 shares 88% amino acid similarity with that encoded by GFn alpha-2, a structural subunit gene previously identified to be expressed in this system (Cauley et al., 1989). The ligand-binding subunit (GF alpha-3) is likely the goldfish homolog of the rat alpha-3 gene (Boulter et al., 1986). Northern blots and S1 protection experiments show that GFn alpha-3 and GF alpha-3 genes are expressed in retina and brain. GFn alpha-3 identifies multiple RNAs differing in their 3' untranslated regions. In situ hybridization analysis demonstrates GFn alpha-3, GFn alpha-2, and GF alpha-3 expression by cells of the retinal ganglion cell layer. Unlike GFn alpha-2 and GF alpha-3, GFn alpha-3 is expressed at highest levels by cells of the retina's inner nuclear layer. In the optic tectum, both GF alpha-3 and GFn alpha-3 genes are expressed by cells of the periventricular zone, as well as more superficial layers. These results suggest the presence of multiple nAChR systems in retina and tectum. In addition, they indicate that tectal nAChRs may arise from remote (ganglion cell) as well as local (tectal cell) synthesis.

Animals↗