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C W Richard

Publications and source records attributed to C W Richard.

27 records · Page 2Linked to original sources
PubMed1992

Genetic linkage analysis of bipolar affective disorder in an Old Order Amish pedigree.

We have used genetic linkage analysis in an effort to identify a gene responsible for bipolar affective disorder (BAD) in an Old Order Amish pedigree. The initial study of this pedigree showed strong evidence for linkage of the chromosome 11p15 markers HRAS1 and the insulin gene (INS) to BAD, whereas a second report found no evidence for linkage. We have independently determined the INS and HRAS1 genotypes from 81 individuals in this pedigree. A polymerase chain reaction (PCR) assay was used to score INS alleles that are difficult to distinguish from one another by conventional agarose gel electrophoresis. In addition, we used four separate diagnostic models to score individuals with psychiatric illness as either affected or unaffected. No evidence of significant linkage between BAD and the markers was found with either two-point or multipoint analysis regardless of which diagnostic model was used. However, exclusion of the region of chromosome 11 between INS and RAS1 as a possible location for the BAD gene in this family depended on the diagnostic model. Further genetic linkage studies with additional DNA markers that span the genome are necessary to determine the chromosomal location of the BAD gene in this family.

Base Sequence↗
PubMed1992

Cloning of a candidate gene for ataxia-telangiectasia group D.

Transfection, with a human cosmid clone library, of an ataxia-telangiectasia (AT) cell line (AT5BIVA) from complementation group D previously resulted in the isolation of a cell line (1B3) with partially restored resistance to ionizing radiation. We rescued the integrated cosmid sequences within 1B3 and obtained two cosmid clones that contained overlapping DNA from chromosomal region 11q23, previously shown to be the region containing the AT gene(s) from three complementation groups. Isolation of an apparently full-length 3.0-kb cDNA from a HeLa cell library demonstrated a previously unidentified gene (ATDC) within these cosmid clones. The transfected copy of the ATDC gene in 1B3 is truncated at the 3' end but is a complete transcription unit, because of the presence of SV40 termination sequences within the adjacent cosmid DNA. After further screening of cosmid clones from a chromosome 11 library, we identified contiguous DNA that contained the missing portion of the gene. Southern blot analysis indicated that the ATDC gene is present in a single copy in the human genome; however, RNA blot analysis revealed mRNA of several sizes (1.8, 2.6, 3.0, 4.7, and 5.7 kb) that varied among different cell lines. Because no large rearrangements were detected in AT5BIVA cells by Southern or RNA blot analysis, any alteration in the ATDC gene in this cell line would involve a point mutation or a small rearrangement. Transfection of the AT5BIVA cell line with one of the cosmids partially restored radioresistance. Analysis of 100 X-radiation hybrid cell lines containing various fragments from the chromosomal region 11q23 showed that the ATDC gene is closely linked to THY1. The ATDC gene therefore lies outside the linkage region predicted to contain the AT gene(s) for complementation groups A and C, indicating a separate locus for the AT complementation group D gene.

Ataxia Telangiectasia↗
PubMed1991

A radiation hybrid map of the proximal long arm of human chromosome 11 containing the multiple endocrine neoplasia type 1 (MEN-1) and bcl-1 disease loci.

We describe a high-resolution radiation hybrid map of the proximal long arm of human chromosome 11 containing the bcl-1 and multiple endocrine neoplasia type 1 (MEN-1) disease gene loci. We used X-ray irradiation and cell fusion to generate a panel of 102 hamster-human somatic cell hybrids containing fragments of human chromosome 11. Sixteen human loci in the 11q12-13 region were mapped by statistical analysis of the cosegregation of markers in these radiation hybrids. The most likely order for these loci is C1NH-OSBP-(CD5/CD20)-PGA-FTH1-COX8-PYGM -SEA-KRN1-(MTC/P11EH/HSTF1/INT2)-GST3- PPP1A. Our localization of the human protooncogene SEA between PYGM and INT2, two markers that flank MEN-1, suggests SEA as a potential candidate for the MEN-1 locus. We map two mitogenic fibroblast growth factor genes, HSTF1 and INT2, close to bcl-1, a mapping that is consistent with previously published data. Our map places the human leukocyte antigen genes CD5 and CD20 far from the bcl-1 locus, indicating that CD5 and CD20 expression is unlikely to be altered by bcl-1 rearrangements. PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.

Animals↗
PubMed1988

Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues.

Endogenous opioid peptides have been implicated in stress-induced analgesia and stress-induced feeding behavior. An earlier study from our laboratory showed that rats subjected to cold swim stress consumed significantly more food compared to controls. The present study describes changes in the levels of various opioid peptides in the central nervous system and periphery due to cold swim stress. Male Sprague-Dawley rats were subjected to cold swim stress (1 degree C for 5 min), then sacrificed by decapitation; brain, pituitary, adrenals and plasma were collected. Tissue extracts were assayed for opioid peptides by RIA. Cold swim stress resulted in analgesia which could be blocked by prior administration of naloxone, as observed by a tail-flick latency test. Cold swim stress caused a 42% decrease in pituitary beta-endorphin, but increased the level of this peptide in the hypothalamus and plasma by 36% and 337%, respectively. Dynorphin level decreased by 62% in the hypothalamus, but was not affected in the pituitary. Levels of Leu-enkephalin and Met-enkephalin decreased in the adrenal gland by 37% and 18%, respectively, but were not significantly affected in the CNS. These results indicate that cold swim stress has a differential effect on the level of CNS and peripheral opioid peptides, and that both central and peripheral opioid peptides may be important in stress-induced analgesia and feeding behavior.

Adrenal Glands↗
PubMed1986

Effect of electrolytic and chemical ventromedial hypothalamic lesions on food intake, body weight, analgesia and the CNS opioid peptides in rats and mice.

The hyperphagia and obesity induced by ventromedial hypothalamic (VMH) electrolytic lesions in female rats were associated with a 70-94% decrease in the level of beta-endorphin (beta-E) in the hypothalamus and other regions of brain, but not in the pituitary. Dynorphin (Dyn) and methionine-enkephalin (ME) levels were also decreased. Rats with VMH lesions were less sensitive to the inhibitory effect of naloxone on their food-intake. Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress.

Analgesia↗
PubMed1983

Effect of oral contraceptives on the rat brain and pituitary beta-endorphin.

The purpose of this study was to investigate the effect of oral administration of progesterone (15 micrograms norethindrone, NE) in presence and absence of estradiol (1 microgram ethinyl estradiol, EE2) on the CNS levels of beta-endorphin like immunoreactivity (beta-EI) in female rats. In acute study (5 days), NE alone did not change beta-EI significantly in pituitary. NE and EE2 together decreased beta-EI by 37% (47% at 10X dose). In chronic study (7 weeks), 2NE had no significant effect on pituitary beta-EI, however, NE and EE2 together at 10X dose decreased it by 14%. In the hypothalamus, NE alone or in presence of EE2 had no significant effect on beta-EI, but 10X dose of NE+ EE2 caused 50 and 76% decrease in beta-EI in acute and chronic study. Striatum was the only tissue where NE alone caused a decrease of 82% in beta-EI when given acutely and 52% when given chronically. EE2 had some protective effect on this decrease since when given together (NE+EE2) the decrease in beta-EI was 21% in acute and 43% in chronic study. Thus our results, along with other studies on the regulation of gonadotropin levels by opioids, suggest that oral contraceptives alter the level of beta-EI and in turn may regulate the release of gonadotropins. Morphine and endogenous opioids have been shown to decrease gonadotropin secretion in various species including humans, apparently by suppressing the release of LH-RH from the hypothalamus (1-5). The opiate antagonist naloxone not only causes up to 10-fold increase in the secretion of gonadotropins (1,3, 6-9) but also opposes the negative feedback effect of steroids on the hypothalamic-pituitary-gonadotropin axis (8), suggesting a regulatory interaction between the endogenous opioids, gonadotropins and gonadal steroids. Like ACTH, the secretion of beta-endorphin is inhibited by glucocorticoids (10). Naloxone induced release of LH is facilitated by estradiol in humans (11) suggesting an antagonistic effect of estradiol on the endogenous opioids. beta-endorphin may play a significant role in neurochemical mechanisms of gonadotropin release in the human menstrual cycle. A preovulatory increase of beta-endorphin in serum occurs 2 days prior to LH surge and a postovulatory decrease in beta-endorphin occurs 5 days later.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Interaction of opiate peptide and noradrenalin systems: light microscopic studies.

In this light microscopic immunocytochemical study beta-Endorphin (beta-END), leu-enkephalin and dopamine-beta hydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for beta-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between beta-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.

Animals↗
PubMed1978

Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons.

By means of antiserum (purified by affinity chromatography) directed against adrenocorticotropin (ACTH) 11-24, cell bodies and beaded axons were visualized in rat brain. The ACTH-like immunoreactivity (ACTH-LI) was primarily located in the hypothalamus (cells and axons). Fibers were scattered throughout thalamus, amygdala, periaqueductal gray area, and reticular formation. There was no change in the distribution of ACTH-LI in rats that had been subjected to hypophysectomy. This distribution of ACTH-LI parallels that of beta-lipotropin and is altered by specific lesions in a similar fashion. The presence of ACTH-LI in cells and beaded axons in brain raises the possibility that it is a neuroregulator functioning as a neurotransmitter, neuromodulator, or neurohormone.

Adrenocorticotropic Hormone↗