Biomedical subjects

H R Morris

Publications and source records attributed to H R Morris.

276 records · Page 16Linked to original sources

PubMedDate not supplied

Neuropeptides and leukotriene biosynthesis: the effect of calcitonin, peptide histidine valine-42, helodermin, neuropeptide Y and galanin.

The effect of five neuropeptides was tested on platelet activating factor (PAF)-stimulated peptidoleukotriene biosynthesis in rat lungs. Calcitonin and peptide histidine valine-42 (PHV-42) were found to inhibit leukotriene C4 (LTC4) and D4 (LTD4) biosynthesis to an extent similar to the previously reported effects of calcitonin gene-related peptide (CGRP) and peptide histidine isoleucine (PHI) respectively. Helodermin potently inhibited the biosynthesis of all three peptidoleukotrienes. Neuropeptide Y and galanin, both present in airways, enhanced the levels of LTD4 and had no effect on LTC4 or leukotriene E4 (LTE4) levels. The theoretical implications of these findings are discussed.

Animals↗

PubMedDate not supplied

Coronary vasodilatation induced by calcitonin gene-related peptide in the anaesthetised pig.

The ability of CGRP to increase blood flow in the coronary circulation of the anaesthetized pig was studied in a constant pressure perfusion model. Human alpha-CGRP, when infused close-arterially into the left anterior descending coronary artery perfused at constant pressure, produced a marked and prolonged dose-related increase in coronary flow, at doses above 10 pmol min-1. The gradient of the flow/pressure curves at each dose increased with an increase in pressure, indicating a drop in the resistance of the coronary bed. No significant change was observed in heart rate, left ventricle pressure, mean arterial pressure or cardiac output.

Animals↗

PubMedDate not supplied

Primary structure of a chloramphenicol acetyltransferase specified by R plasmids.

Naturally occurring isolates of chloramphenicol-resistant bacteria commonly synthesise chloramphenicol acetyltransferase (EC 2.3.28; CAT) in amounts which are sufficient to account for the resistance phenotype and often harbour plasmids which carry the structural gene for CAT. The findings of CAT in such diverse prokaryotes as Proteus mirabilis, Agrobacterium tumefaciens, Streptomyces sp., and a soil Flavobacterium has led to speculation concerning the origin and evolution of the more commonly observed CAT variants specified by plasmids in clinically important bacteria. To provide a more solid basis for studying the evolution and spread of CAT within prokaryotes we chose to determine the complete amino acid sequence of a type I variant of CAT, the variant known to be associated with most F-like plasmids conferring chloramphenicol resistance. The sequence has been determined by combining the results obtained from manual and automated sequential degradation with those obtained by mass spectrometry of peptides generated by enzymatic digestion. The directly determined primary structure is identical with that predicted by the DNA sequence analysis of the chloramphenicol resistance transponson Tn9 known to specify a type I variant of chloramphenicol acetyltransferase.

Acetyltransferases↗

PubMedDate not supplied

Isolation and characterization of human calcitonin gene-related peptide.

The rat calcitonin gene has recently been shown to encode a novel peptide (rat calcitonin gene-related peptide, rCGRP) thought to be produced in nervous tissue after tissue-specific RNA processing. This peptide has so far been identified only in rat tissue, by immunocytochemistry and immunoassay. We now report the isolation of a related (89% homology) peptide from human tissue (hCGRP) which we have sequenced using a novel mass spectrometric approach, fast atom bombardment (FAB) mapping. The human peptide differs significantly from the predicted rCGRP structure in four positions in the amino acid sequence (three effecting charge changes), and the presence of a disulphide bridge and an amide, surmised in the rat work, is proven in the hCGRP molecule. hCGRP was present in plasma from 10 patients with medullary thyroid carcinoma (MTC) and in 6 MTC tumours removed at surgery, suggesting the tissue distribution may differ from that in the rat where the peptide is reported to be absent from thyroid tissue. hCGRP is shown to have biological activity and it is possible that its presence in MTC plasma may be responsible for some of the symptoms in this disease.

Amino Acid Sequence↗

PubMedDate not supplied

Calcitonin gene-related peptide is a potent vasodilator.

A novel peptide, calcitonin gene-related peptide (CGRP), has been predicted to result from alternative processing of the primary RNA transcript of the calcitonin gene in the rat. Several lines of evidence suggest that CGRP is a transmitter in the central and peripheral nervous system. Human CGRP has been isolated and characterized, and shown to have potent effects on the heart. The observations presented here indicate that human and rat CGRP also have potent effects on blood vessels. Intradermal injection of CGRP in femtomole doses induces microvascular dilatation resulting in increased blood flow, which we have detected in the rabbit by using a 133Xe clearance technique. In human skin, CGRP induces persistent local reddening. Microscopic observation of the hamster cheek pouch in vivo revealed that topical application of CGRP induces dilatation of arterioles. Furthermore, CGRP relaxes strips of rat aorta in vitro by an endothelial cell-dependent mechanism. Therefore, we suggest that local extravascular release of CGRP may be involved in the physiological control of blood flow and that circulating CGRP may contribute to hyperaemia in certain pathological conditions.

Amino Acid Sequence↗

PubMedDate not supplied

Chemical structure of the morphogen differentiation inducing factor from Dictyostelium discoideum.

Morphogens are signal molecules presumed to exist in embryos and to be involved in establishing the spatial pattern of cells during development. Differentiation inducing factor (DIF) has the properties of a morphogen required for producing the prestalk/prespore pattern in the aggregate formed by cells of the slime mould Dictyostelium in response to starvation. DIF-1, the major bioactive species after purification, has now been identified using a combined microchemical, spectroscopic and synthetic approach. The structure is defined as 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone, and represents a new class of effector molecule. The availability of relatively large quantities of synthetic and isotopically labelled materials should now allow progress towards a detailed understanding of the pattern-forming processes in Dictyostelium development.

Cell Differentiation↗