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Biomedical subjects

E Herbert

Publications and source records attributed to E Herbert.

At least 37 records · Page 2Linked to original sources
PubMed1987

Patient response to sigmoidoscopy. A randomized, controlled trial of rigid and flexible sigmoidoscopy.

Sigmoidoscopy could aid in the control of large bowel cancer by early detection of the 55% of colorectal cancers that develop in the rectosigmoid and by the identification and eradication of significant rectosigmoid adenomas. Rigid sigmoidoscopy has had poor patient acceptance and therefore has not been successful. The present study is a prospective randomized trial to evaluate patient response to flexible as compared with rigid sigmoidoscopy. Patients reported significantly less discomfort (10.1% versus 29.7%), anxiety (9.8% versus 27.6%) and embarrassment (5.2% versus 12.8%) during flexible as compared with rigid sigmoidoscopy. Flexible sigmoidoscopy appears to have better patient acceptance than rigid sigmoidoscopy (P less than 0.01). This could enhance its value as a cancer-control instrument. This article addresses the feasibility of sigmoidoscopy. Its validity also needs to be addressed within the framework of a long-term trial, evaluating mortality for rectosigmoid cancer.

Clinical Trials as Topic↗
PubMed1987

Two mammalian genes transcribed from opposite strands of the same DNA locus.

This report describes the characterization of a genomic locus in the rat that encodes overlapping genes occupying both strands of the same piece of DNA. One gene (strand) encodes gonadotropin-releasing hormone (GnRH). A second gene, SH, is transcribed from the other DNA strand to produce RNA of undefined function. The RNAs transcribed from each DNA strand are spliced and polyadenylated, and share significant exon domains. GnRH is expressed in the central nervous system while SH transcripts are present in the heart. Thus, the genome of a mammalian organism encodes two distinct genes by using both strands of the same DNA.

Animals↗
PubMed1987

A solution hybridization assay for the quantitation of prodynorphin mRNA.

We have developed a RNA-RNA solution hybridization assay to quantitate the mRNA coding for prodynorphin precursor. This assay is extremely sensitive and highly specific. Using this assay we have measured the prodynorphin mRNA in various brain regions and reproductive tissues of rat. When we compared the distribution of prodynorphin mRNA with the dynorphin related peptides in these tissues, we found a general parallelism and a few noteworthy exceptions.

Animals↗
PubMed1987

The rat corticotropin-releasing hormone gene.

In this paper we have described the isolation and characterization of the rat corticotropin releasing hormone gene. Nucleotide sequence comparisons with the human CRH gene have demonstrated several interesting regions of homology and suggest that the gene was highly conserved through evolution. Additionally we have demonstrated the tissue-specific expression of the rat CRH gene. The regional distribution of expression parallels previously documented immunocytochemical demonstrations and supports the hypothesis that CRH peptides have multiple roles in different tissues. In the peripheral tissues that express CRH mRNA it will be very interesting to document the specific cell type of synthesis by using combined immunocytochemical and in situ histochemical techniques. Additionally we have described initial studies using gene transfer techniques to examine the cAMP responsiveness of the rat CRH gene. We are presently constructing other fusion genes (CRHCAT plasmids) in order to more carefully localize the DNA sequence in the rat CRH gene which mediates this effect, and compare it to the previously reported cAMP-responsive "consensus sequence." Similarly, we also plan to utilize the CRHCAT constructs to examine regulation of the rat CRH gene by glucocorticoids and several other hormone-mediated regulatory pathways. Through these CAT fusion studies we hope to gain a better understanding of the role of certain conserved sequences in the 5' flanking DNA for transcriptional control of the rat (and human) CRH genes.

Animals↗
PubMed1987

Immunohistochemical demonstration of proGnRH and GnRH in the preoptic-basal hypothalamus of the primate.

An antiserum (ARK-1) specific to the gonadotropin-releasing hormone precursor (proGnRH) was produced by immunizing with a synthetic peptide (proGnRH 6-16; Gly-Leu-Arg-Pro-Gly-Gly-Lys-Arg-Asp-Ala-Glu) which bridges the proteolytic cleavage site of proGnRH. When used in the radioimmunoassay, ARK-1 bound 25% of the iodinated 5-16 fragment at a 1:30,000 dilution with a sensitivity of 1 pg/tube. Using immunohistochemical techniques, we observed that in serial and the same sections through the preoptic-basal hypothalamus (POA-BH), the precursor molecule was primarily present in the cell soma, whereas GnRH was found in the cell soma, nerve fibers, and terminals of the same neurons. These data indicate that the processing of proGnRH to biologically active peptides (e.g., GnRH) in the rhesus macaque and the baboon POA-BH primarily occurs in the cell soma.

Animals↗
PubMed1987

Expression of the prodynorphin gene in male and female mammalian reproductive tissues.

Recent studies suggest that opioid peptides may be involved in modulating the hypothalamus-pituitary-gonadal axis at a variety of levels in both males and females. We report here the presence of mRNA coding for the opioid peptide precursor prodynorphin in rat ovary, uterus, and testis. Expression of this opioid peptide precursor gene is compared to expression of two other opioid peptide precursor genes, proenkephalin and proopiomelanocortin, in mammalian reproductive tissues. Immunohistochemical analysis reveals that in the rat testis, prodynorphin-derived peptides are present in Leydig cells. The distribution of dynorphin immunoreactivity in various reproductive tissues was determined. Male reproductive tissues of the rat, rabbit, and guinea pig as well as rat ovary and uterus all contain detectable levels of dynorphin immunoreactivity. These observations suggest that prodynorphin-derived peptides may exert paracrine and/or autocrine effects in mammalian reproductive tissues.

Animals↗
PubMed1987

Rat corticotropin-releasing hormone gene: sequence and tissue-specific expression.

The rat corticotropin releasing hormone (CRH) gene has been isolated and characterized by DNA sequence analysis. The gene exhibits a structural organization similar to that of the human CRH gene. The nucleotide sequence encoding the entire rat CRH precursor is located on the second exon, while exon I encodes the 5'-untranslated region of the mRNA. Analysis of the nucleotide sequence homology between the human and rat CRH genes reveals several highly conserved regions including the CRH peptide-encoding sequence and the 5'-flanking sequence. RNA blot analysis demonstrates that CRH mRNA can be observed in numerous regions of the rat brain as well as the spinal cord, adrenal gland, pituitary, and testis.

Amino Acid Sequence↗
PubMed1986

Expression and cell type--specific processing of human preproenkephalin with a vaccinia recombinant.

The posttranslational maturation of a complex precursor polyprotein, human proenkephalin, was assessed by infection of a wide spectrum of cell types with a recombinant vaccinia virus that expressed human proenkephalin. The infected cells rapidly produced both cellular and secreted Met-enkephalin immunoreactivity. Although each cell line could secrete intact proenkephalin, only a mouse pituitary line was capable of processing proenkephalin to mature enkephalin peptides. The quantity of intact proenkephalin secreted from BSC-40 cells (derived from African Green monkey kidney) was sufficient to establish the value of vaccinia virus as a mammalian cell expression vector.

Animals↗
PubMed1986

Coordinate expression of hypothalamic pro-dynorphin and pro-vasopressin mRNAs with osmotic stimulation.

Peptides derived from pro-dynorphin and pro-vasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons in the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated using physiological manipulations known to increase plasma vasopressin levels, such as dehydration and salt-loading. With chronic osmotic challenge, the mRNAs for both pro-dynorphin and pro-vasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, but not within the nonmagnocellular suprachiasmatic nucleus cell groups projecting elsewhere than the neural lobe. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain.

Animals↗
PubMed1986

Pro-dynorphin is endogenous to the anterior pituitary and is co-localized with LH and FSH in the gonadotrophs.

Pro-dynorphin peptides have been shown to exist in the anterior lobe of the pituitary gland. The dynorphin in the anterior lobe is distinct from that which is co-localized with vasopressin in the magnocellular system in both post-translational processing and regulation of release. Here, we report on the existence of pro-dynorphin mRNA, approximately 2400 nucleotides in length, in the anterior lobe. Furthermore, we present immunocytochemical evidence for the co-existence of dynorphin, LH and FSH in a subset of gonadotrophs. These findings suggest a possible role of pro-dynorphin products in the regulation of the hypothalamic-pituitary-gonadal axis.

Animals↗
PubMed1986

Hypothalamic dynorphin and vasopressin mRNA expression in normal and Brattleboro rats.

Peptides derived from prodynorphin and provasopressin precursors coexist within neurosecretory vesicles of magnocellular neurons of the rat hypothalamus projecting to the posterior pituitary. The secretory activity of these neurons can be stimulated with physiological manipulations that elevate plasma levels of vasopressin (VP), such as dehydration and salt-loading. Evidence indicates that both VP- and prodynorphin-derived peptides are secreted under such conditions. With chronic osmotic challenge, the mRNAs for both prodynorphin and provasopressin increase in parallel in the supraoptic and paraventricular nuclei of the hypothalamus, and not within nonmagnocellular cell groups projecting elsewhere in the brain. The results indicate an example of coordinate regulation of mRNA expression for coexisting peptides within the brain. These results from microdissected tissues have been coupled with the more anatomically precise method of in situ hybridization histochemistry. Using 35S-radiolabeled synthetic oligonucleotides complementary to VP and dynorphin mRNAs, these mRNAs have been autoradiographically localized to magnocellular parikarya in the rat hypothalamus. Results also indicate that this technology can be used for regulatory studies, as evidenced by the increased hybridization of VP oligonucleotide to hypothalamic nuclei from salt-loaded rats.

Animals↗
PubMed1986

Modulation of beta-endorphin secretion from mouse pituitary tumor cells by calmodulin inhibitor W7.

The involvement of calmodulin in the secretion of beta-endorphin from the mouse anterior pituitary tumor cell line, AtT-20, was investigated. The calmodulin inhibitor W7 potentiated secretion produced by 8-BrcAMP, and induced a secretory response to arginine vasopressin, which did not elevate beta-endorphin levels when added alone. Release of hormone in response to CRF was not affected. Calmodulin phosphodiesterase inhibitor 8-MeOMeMIX produced a dose-dependent increase in 8-BrcAMP stimulation, suggesting that inhibition of cAMP degradation is the mechanism of enhancement of 8-BrcAMP-induced secretion in the presence of W7.

Animals↗