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D Goldman

Publications and source records attributed to D Goldman.

At least 217 records · Page 12Linked to original sources
PubMed1994

Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat.

The pathogenesis of Cryptococcus neoformans pulmonary infection in the rat was studied after intratracheal inoculation. Lungs were examined at various times following infection for histopathology in conjunction with macrophage markers, proliferating cell nuclear antigen (PCNA), and capsular glucuronoxylomannan (GXM) antigen. Serum GXM, immunoglobulin M (IgM) and IgG titers and organ fungal burden were compared with pathological findings. C. neoformans organisms were in the lung parenchyma 2 h postinoculation, and GXM antigen was present in surrounding tissues shortly thereafter. Extrapulmonary dissemination occurred early in infection. Two phases of host cellular inflammatory response were discernible: early local macrophage recruitment at 2 to 4 days followed by granulomatous inflammation, which reached maximum intensity 14 days after infection. The granulomatous phase was preceded by lymphocyte influx with macrophage proliferation and maturation into epithelioid histiocytes; this was paralleled by a shift of yeasts from extracellular to intracellular spaces. Tissue IgG deposits, serum IgG to GXM, and localization of tissue GXM immunoreactivity to epithelioid cells were noted at 2 to 4 weeks. A 10-fold decrease in lung fungal burden occurred 25 days postinfection and was associated with resolving granulomas, fewer proliferating cells, and decreased tissue GXM. The present study demonstrates that (i) C. neoformans penetrates the lung parenchyma shortly after infection; (ii) immunocompetent rats control pulmonary cryptococcosis efficiently, with minimal extrapulmonary dissemination and low levels of serum GXM; and (iii) macrophage activation is likely to play a crucial role in limiting C. neoformans infection in the rat lung.

Animals↗
PubMed1994

Grandmother dishonored: violence against women by male partners in American Indian communities.

Extensive and scrupulously conducted research during the past decade has established the issue of violence against women by male partners as both an international human rights issue and a public health problem of national concern. This research has rarely been extended into communities of color, and, in particular, to American Indian women. This article presents conceptual and methodological factors involved in conducting research with American Indian women, a comprehensive literature review of available data, assertions regarding abuse of women by male partners in American Indian communities, and directions for future research.

Adult↗
PubMed1994

Detection of mutations and polymorphisms using fluorescence-based dideoxy fingerprinting (F-ddF).

We have adapted the dideoxy finger-printing (ddF) technique for detecting DNA sequence variants to fluorescence detection (F-ddF) using an Applied Biosystems Model 373A DNA Sequencer equipped with GENESCAN 672 software and an external temperature control device. The fingerprints can be precisely aligned using an internal standard run in the same lanes. This facilitates location and characterization of mobility changes resulting from sequence variants. As compared to fluorescence detected single-strand conformation polymorphism analysis (F-SSCP), F-ddF is equally efficient for detection of sequence variants, and it offers additional advantages. These include information regarding location of the sequence variation, greater reliability for distinguishing one sequence variant from another and the capacity to generate large PCR fragments and analyze them in smaller subsegments. Read length and overall quality of data from F-ddF are sequence-dependent when Taq DNA polymerase is used, but reducing terminator concentration can extend read length. The strengths and weakness of F-ddF and F-SSCP are different. Thus F-ddF may work better in a given situation than F-SSCP and vice versa. A strategy for using F-ddF to circumvent limitations of F-SSCP is described.

Animals↗
PubMed1994

Polymorphic admixture typing in human ethnic populations.

A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (delta). The distribution of frequency differences (delta values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high delta values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066-.098), and < 10% of the measured overall molecular genetic diversity in these human samples can be attributed to "racial" differentiation. The median delta values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies.

Alleles↗
PubMed1993

Analysis of the 5-HT1C receptor and the serotonin uptake site in fawn-hooded rat brain.

Both the 5-HT1C receptor and the 5-HT uptake binding sites were measured in Fawn-Hooded, Sprague-Dawley and Wistar rats. Five brain regions were examined: frontal cortex, hippocampus, striatum, hypothalamus, and brainstem. We found significant differences in the Bmax and Kd values in various brain regions comparing Fawn-Hooded rats, with Sprague-Dawley and Wistar animals. The regional differences in receptor number and affinity in both the 5-HT1C receptor and the 5-HT uptake site in the Fawn-Hooded strain, relative to Wistar and Sprague-Dawley animals, provide support for the use of the Fawn-Hooded rat in serotonin dysfunction studies.

Animals↗
PubMed1993

The A1 allele at the D2 dopamine receptor gene and alcoholism. A reappraisal.

OBJECTIVE: An allelic association between the TaqI "A" system A1 allele at the D2 dopamine receptor locus (DRD2) and either alcoholism or severe alcoholism has been proposed. Our purpose was to evaluate whether, based on all of the accumulated evidence, this association could be considered to be proven. DATA SOURCES: We considered data from all published reports of DRD2 allele frequency in alcoholics, controls, or both. STUDY SELECTION: We concentrated on the issue of replication. We therefore considered all data reported (on white samples, because DRD2 allele frequency varies by race and ethnicity) since the first report by Blum et al in 1990. DATA SYNTHESIS: We analyzed the set of data for differences in allele frequencies between alcoholics and controls, and for heterogeneity among samples. We also investigated the influence of the data from the first group to report an association (including a subsequent report from that group) on the findings. Our analysis shows that, when all studies subsequent to the original study are considered, there is no significant difference in DRD2 A1 allele frequency between alcoholics and controls, there is significant heterogeneity among reported alcoholics and reported controls, and there is no significant difference in DRD2 A1 allele frequency between severe and not severe alcoholics. Also, the two reports of Blum et al account for all of the (nonsignificant) differences seen between controls, alcoholics, and severe alcoholics. CONCLUSIONS: In general, heterogeneity among studies (for alcoholics or controls) is considerably greater than differences between alcoholics and controls overall. The findings to date can best be explained by more conservative interpretations than a confirmed physiologically important allelic association between DRD2 alleles and alcoholism. These other possibilities include sampling error and ethnic variation in those studies that individually showed a large effect.

Alcoholism↗
PubMed1993

Coupling muscle electrical activity to gene expression via a cAMP-dependent second messenger system.

Embryonic-type nicotinic acetylcholine receptor (nAChR) gene expression is regulated by muscle activity. The mechanism by which this activity is transduced to the genome is not known. We have addressed this issue by using a rat primary muscle cell culture system that mimics the in vivo effects of muscle activity on nAChR expression. We report here that the suppression of nAChR gene expression by muscle activity can be reversed by increasing intracellular cAMP levels. This effect is specific to the embryonic-type receptor genes. Electrically insensitive genes such as those encoding the adult-type nAChR epsilon-subunit and creatine kinase are not up-regulated by cAMP. In addition, muscle inactivity caused either by tetrodotoxin or denervation increases cAMP levels and protein kinase A activity, consistent with their proposed role in mediating nAChR gene expression. Finally, we report that this same mechanism appears to regulate other genes, such as those encoding the tetrodotoxin-insensitive sodium channel, MyoD, and myogenin which, like the nAChR, are regulated by muscle electrical activity. Based on these results it is proposed that muscle electrical activity is coupled to gene expression via a cAMP-dependent second messenger system.

Animals↗
PubMed1993

Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in rhesus monkeys (Macaca mulatta).

BACKGROUND: To study genetic and environmental contributions to cerebrospinal fluid (CSF) monoamine concentrations, 55 young rhesus monkeys (Macaca mulatta) were reared apart from their 10 fathers to perform a paternal half-sibling analysis. METHODS: To study maternal genetic contributions, 23 infants were reared with their mothers, 23 infants were removed from their mothers at birth and fostered to unrelated lactating female monkeys, and 24 infants were removed from their mothers at birth and reared with age-matched peers. When the monkeys reached age 6 months, CSF samples were obtained via cisternal puncture prior to and during a series of social separations. RESULTS: When the results were statistically pooled according to the biological father, comparisons using analysis of variance indicated that both CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations showed significant heritable (h2) effects (h2 > 0.5) for both sons and daughters, whereas 3-methoxy-4-hydroxyphenylglycol (MHPG) showed a nearly significant paternal genetic effect only for sons (h2 > 0.5). In addition, there were substantial maternal genetic influences on the young monkeys' CSF MHPG and 5-HIAA (h2 > 0.5) levels. Structural equation analyses indicated a maternal genetic contribution without a maternal environmental contribution to CSF 5-HIAA concentration; on the other hand, there was both a maternal genetic and environmental contribution to MHPG. CONCLUSIONS: These findings suggest that a significant portion of the variance in the turnover of the monoamine neurotransmitters is determined by genetic mechanisms.

Animals↗
PubMed1993

Cues intrinsic to the retina induce nAChR gene expression during development.

Recent studies of optic nerve regeneration in goldfish have indicated that the optic tectum plays an important role in modulating the induction of nicotinic acetylcholine receptor (nAChR) gene expression in regenerating retinal ganglion cells (Heiber, Agranoff, and Goldman, 1992, J. Neurochem. 58:1009-1015). These observations suggest that induction of these genes is regulated by brain target regions. The appearance of nAChR mRNA in the developing rat retina coincides with a time when ganglion cells are sending axons to their brain targets (Hoover and Goldman, 1992, Exp. Eye Res. 54:561-571). Might a mechanism similar to that seen during goldfish optic nerve regeneration also mediate induction of nAChR gene expression during development of the mammalian retina? This possibility was tested by either transplanting embryonic rat retina to different brain regions, or explanting it to organ culture and assaying for nAChR gene expression. These studies showed that induction of the nAChR genes in developing rat retina is independent of the environment in which the retina develops. These results indicate that either the retinal microenvironment or a signal intrinsic to the retinal ganglion cell is responsible for this induction.

Animals↗
PubMed1993

Genomic imprinting: implications for behavioral genetics.

In recent years it has become apparent that the parental origin of genetic material has an impact on gene expression and this effect has become known as genomic imprinting. The evidence for the influence of genomic imprinting on behavior and in the etiology of certain neurobehavioral disorders is discussed. The possibilities for a role for genomic imprinting in the inheritance of behaviors related to alcohol abuse and alcoholism and in the paternal alcohol syndrome are also explored.

Alcoholism↗
PubMed1993

Regional analysis of 5-HT1A receptors in two species of Peromyscus.

Two species of deer-mice, Peromyscus maniculatus (P. man) and Peromyscus leucopus (P. leu), were compared for differences in 5-hydroxytryptamine1A (5-HT1A) receptor number and affinity. Both species enter into torpor; however, P. man enters spontaneous torpor with a higher frequency and for a longer duration than P. leu. Further, compared to P. leu a higher percentage of P. man exhibit daily torpor. Deer mice can be induced to enter torpor by a reduction in food supply, shortened photoperiods, and decreasing ambient temperature. Under these conditions, P. man enters into torpor more frequently, for longer durations, and with a higher percentage of individuals as compared to P. leu. [3H]8-OH-DPAT was used to label 5-HT1A brain receptors in three brain regions: the frontal cortex, brainstem, and striatum. In addition, the hypothalamus and hippocampus were examined for 5-HT1A receptor differences; however, no measurable specific binding could be determined in these regions. In the frontal cortex, the Bmax values were significantly lower in P. man compared to P. leu. There were no significant differences in the Bmax values in the striatum and brainstem between P. man and P. leu. Further, there were no significant differences in the Kd values between the two species in any of the brain regions examined. The absence of any difference in receptor number or affinity in any of the brain regions examined, except the cortex, suggests that the 5-HT1A receptor is most likely not involved in a more efficient pathway to torpor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Diurnal rhythms of 5-HT1A and 5-HT2 receptor binding in euthermic and torpor prone deermice, Peromyscus maniculatus.

Deermice display both spontaneous and induced daily torpor bouts, attaining minimum body temperatures of 15-20 degrees C. There is evidence that brain serotonin may be involved in the initiation and/or maintenance of torpor. Inhibition of serotonin [5-hydroxytryptamine (5-HT)] synthesis markedly reduces the duration and depth of torpor. Because a certain percentage of deermice will not enter torpor under any circumstances, we were able to compare 5-HT receptor subtypes in deermice that readily enter into torpor (TP) and in non-torpor prone (NTP) animals. Deermice were trapped in the wild and subjected to food rationing and low ambient temperature and then sacrificed either in a normothermic or torpid state at 11:00 p.m. or 11:00 a.m. Whole brain was assayed for 5-HT1A and 5-HT2 receptor differences using [3H]8-OH-DPAT and [3H]ketanserin, respectively. The Bmax values for 5-HT1A receptors were significantly greater in both TP and NTP animals sacrificed at 11:00 p.m. compared to animals sacrificed at 11:00 a.m. In contrast, the density of 5-HT2 receptors was significantly greater in animals sacrificed at 11:00 a.m. compared to animals sacrificed at 11:00 p.m. This is consistent with the opposing functions of these receptors in the regulation of temperature and sleep. The affinity (Kd) of each receptor was unchanged. A comparison of TP and NTP animals sacrificed at the same time of day revealed no significant differences in either Bmax or in Kd values, indicating that differences in 5-HT1A and 5-HT2 receptors may not explain the heterogeneity of deermice in their ability to enter torpor.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Identification of tryptophan 2,3-dioxygenase RNA in rodent brain.

The gene for tryptophan 2,3-dioxygenase (TDO) heretofore was believed to be expressed only in liver. The data presented here demonstrate that RNA encoding TDO is present in rodent brain. Oligonucleotide primers based on the rat liver TDO cDNA sequence were synthesized and used to amplify RNA derived from mouse whole brain and liver and rat brain regions by the RNA-PCR. Reaction products were purified and subjected to DNA sequencing. Identical sequences were obtained when mouse whole brain and liver RNAs were amplified, and these sequences were shown to be 96% identical to the published rat liver tryptophan TDO cDNA sequence. In addition, TDO sequences were found in RNA derived from rat brainstem, cerebellum, cortex, hypothalamus, and the remainder of the brain.

Animals↗
PubMed1993

DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations.

We defined interpopulation differences in the frequency of the dopamine D2 receptor DRD2/Taq1 A1 allele, which has previously been associated with alcoholism. Frequencies of the A1 allele in unrelated subjects were 0.18 to 0.20 (se = 0.02 to 0.03) in several Caucasian populations previously assessed, 0.38 (+/- 0.05) in American Blacks (n = 44), 0.63 (+/- 0.07) in Jemez Pueblo Indians (n = 23), and 0.80 (+/- 0.04) in Cheyenne Indians (n = 52). The existence of large interpopulation differences in the frequency of the Taq1 alleles suggests that associations to disease status could readily be generated or masked if disease and control groups were uneven in ethnic composition. To address the possibility that the 4-fold higher frequency of the A1 allele in Cheyenne Indians was related to an increased vulnerability to alcoholism in that population, 47 Cheyenne Indians were psychiatrically interviewed and blind-rated. However, there was no significant difference between interviewed controls (0.73 +/- 0.06, n = 24), subjects with alcoholism and/or drug abuse (0.74 +/- 0.06, n = 23) and noninterviewed population controls (0.87 +/- 0.05, n = 20). Legitimate association of the DRD2/Taq1 allele to alcoholism would presumably require it to be in linkage disequilibrium (nonrandom association) with a functional mutation at DRD2 or elsewhere. The level of disequilibrium would vary between populations and could place an upper bound on the strength of an association.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The DRD2 dopamine receptor and the candidate gene approach in alcoholism.

The cloning of the DRD2 dopamine receptor gene and discovery of an associated polymorphism permitted genetic association and linkage studies to alcoholism. Extensive allele frequency differences between populations provide an alternative explanation for explaining a DRD2 association to alcoholism which has been observed in some studies, but more frequently has not been replicated.

Alcoholism↗
PubMed1993

Recent developments in alcoholism:genetic transmission.

This chapter is an overview of developments in the study of genetic factors in vulnerability in alcoholism. The focus is on recent developments, including heritability studies in twins and transmission studies in families, both of which have continued to reveal evidence for a substantial role for genetic factors but also for etiologic complexity and variation in vulnerability across generations and across cultures. Studies are discussed which utilized psychophysiological and neurochemical markers for alcoholism for analysis of genetic association, transmission, and linkage. These markers include the low P300 event-related potential, sensitivity to ethanol's intoxicating and euphoric effects, platelet adenylate cyclase, and neurotransmitter metabolite concentrations. Although it is highly likely that many alcoholism-associated physiologic phenotypes are secondary traits, these approaches have increased the specificity of genetic analyses and genetic analyses are clarifying their relationship to alcoholism. For example, early efforts to study, in families, the co-occurrence of the P300 marker and alcoholism have yielded results indicating that the P300 abnormality precedes significant exposure to alcohol and that relatives of alcoholics are more likely to have this trait. In the area of animal models, two nonhuman primate species, the vervet monkey and the rhesus macaque, were shown to willingly consume alcohol to intoxicating blood levels. Also, linkage studies using the quantitative trait locus (QTL) mapping strategy were attempted for phenotypes relevant for alcoholism. The QTL strategy is theoretically capable of identifying determinant genes which contribute only a small portion of the variance. In human linkage studies, a genetic association was found to the DRD2 dopamine receptor. The DRD2 finding generated controversy, as a number of other groups failed to replicate it, and also focused attention on the advantages and pitfalls of the population association approach for detecting genes influencing behavior. The relationship of the alcohol metabolic gene variants to alcoholism was clarified by the finding that functional variants of alcohol and aldehyde dehydrogenases can act additively to determine vulnerability to alcoholism.

Alcoholism↗