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Biomedical subjects

H R Morris

Publications and source records attributed to H R Morris.

At least 217 records · Page 12Linked to original sources
PubMed1985

Glutamyl-taurine is the predominant synaptic taurine peptide.

Several taurine-containing peptides have been identified from trichloracetic acid extracts of synaptosomes and their subcellular vesicles prepared from calf brain. These peptides contain aspartic and glutamic acids, serine and taurine, and are often present in an N-acetylated form. The peptides were isolated as single spots by TLC. Glutamyl-taurine was found to be the predominant structure when analyzed by fast atom bombardment (FAB) mass spectrometry.

Animals↗
PubMed1984

Leukotriene biosynthesis and metabolism detected by the combined use of HPLC and radioimmunoassay.

A radioimmunoassay for leukotriene D4 (LTD4) has been developed which exhibits sufficiently high sensitivity to be useful in conjunction with RP-HPLC in the detection of LTC4, LTD4 and LTE4 in physiological samples. The detection limit of the assay was approximately 240 amoles, using antiserum TG1 at a dilution of 6 X 10(3), with 50% displacement at 70 fmoles. Antiserum NW1, also at a dilution of 6 X 10(3), displayed a detection limit of 9 fmoles with 50% displacement at 100 fmoles. The two antisera have similiar crossreactivities, both manifesting useful affinities for LTE4 and LTC4, and low or negligible affinities for other arachidonic acid metabolites, or their derivatives. The radioimmunoassay was used to detect 1) LTC4, LTD4 and LTE4 released from perfused rat lung in response to platelet-activating factor (PAF) stimulation, 2) conversion of exogenous LTD4 to LTE4 in human blood, and 3) endogenous leukotrienes in human blood samples.

Animals↗
PubMed1984

The biological activities of phthalate esters on rat gastric muscle.

Monoethylhexyl phthalate, at concentrations that can occur in blood stored in plastic bags (0.1-0.5 mg/ml), reduced contractions of rat isolated gastric fundus to PGE2 and acetylcholine; the diethyl compound was less effective. In contrast, dibutyl phthalate (1 and 10 micrograms/ml) and, to a lesser extent di-isobutyl phthalate, increased the muscle tone. These results are discussed in relation to blood transfusion, and to structural similarities between phthalates and prostaglandins.

Animals↗
PubMed1984

The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP).

Human and rat calcitonin gene-related peptides cause a dose-related contraction of guinea pig ileum, which is antagonised by an anti-histamine, mepyramine, and an anticholinergic compound, hyoscine. Both peptides also cause a positive inotropic and a positive chronotropic effect in the rat isolated auricle and these responses are antagonised by propranolol, a B adrenoceptor blocker. Further, the peptides lower plasma calcium levels in both rats and rabbits in a dose-related manner resembling calcitonin; in the rabbit, but not in the rat, the initial calcium lowering effect is succeeded by hypercalcaemia at higher doses, while in the chick, only the parathyroid hormone-like calcium-raising effect is seen.

Animals↗
PubMed1984

Amino acid sequence and post-translational modification of human interleukin 2.

Human interleukin 2 was separated into multiple molecular forms by selective immunoaffinity chromatography and chromatofocusing. For the most part, this heterogeneity was attributed to variations in glycosylation of the threonine residue in position 3 of the polypeptide chain. The various molecular forms of interleukin 2 had nearly identical specific activities in the in vitro proliferation assay, indicating that the glycosylation had no significant effect on this response. The entire primary sequence of interleukin 2, including the location of the intramolecular disulfide bridge, was determined by a combination of peptide mapping and protein sequencing. This information should aid in the determination of the active site(s) of the molecule.

Amino Acid Sequence↗
PubMed1983

FAB-mapping of recombinant-DNA protein products.

A new method is described for screening and establishing the primary structure of proteins. The procedure is both rapid and sensitive and allows study of the C-terminus of the protein with equal facility to the N-terminus. This new strategy which is illustrated here for the polypeptide hormone Insulin, has obvious applications in recombinant DNA biotechnology research, in post-translational modification and site-directed mutagenesis studies, or any other aspect of modern protein chemistry requiring accurate definition of primary structure.

Amino Acid Sequence↗
PubMed1983

Beta-cell tropin: synthesis and biological activity.

The structure of beta-cell tropin, an insulin secretagogue released by the neuro-intermediate lobe of the obese (ob/ob) mouse, has recently been determined as the 22-39 moiety of ACTH. A method for the preparation of this octadecapeptide using mild solid-phase procedures followed by preparative high pressure liquid chromatography is described. The molecular weight of the synthetic peptide has been confirmed by Fast Atom Bombardment mass spectrometry. Synthetic beta-cell tropin is indistinguishable in its chromatographic, antigenic and biological properties from natural beta-cell tropin.

Adrenocorticotropic Hormone↗
PubMed1983

Evidence that the insulin secretagogue, beta-cell-tropin, is ACTH22-39.

The pituitary neurointermediate lobe of genetically obese (ob/ob) mice contains a hormone which stimulates insulin release and which cross-reacts with a -COOH-terminal ACTH antiserum, suggesting that it is related to corticotropin-like intermediate lobe peptide (CLIP), the 18-39 fragment of ACTH. The hormone, which we have called beta-cell-tropin, has been shown to be present in the plasma of the ob/ob mouse and to potentiate glucose induced insulin secretion. We have now shown that ACTH22-39 prepared by tryptic digestion of human synthetic CLIP behaves similarly on Biogel chromatography and on reverse-phase HPLC to the naturally occurring beta-cell-tropin. Furthermore, beta-cell-tropin and ACTH22-39 have indistinguishable antigenic and insulin releasing properties.

Adrenocorticotropic Hormone↗
PubMed1982

Preparation, purification, and structure elucidation of slow-reacting substance of anaphylaxis from guinea pig lung.

The work that we have described had originally three main aims: (a) to design a new purification system for SRS-A from which we would obtain pure material for the structural analysis: (b) to define the functional groups in the pure material by spectrophotometric, chemical, and enzymic inactivation methods; and (c) to deduce the complete covalent structure by an accepted spectroscopic method capable of defining structure in atomic detail. These aims have been achieved. The structure of SRS-A, the physiologically more relevant example of the SRSs that were studied, because it was derived immunologically from an animal model of an acute hypersensitivity reaction, has been rigorously defined. Of paramount importance in the determination of this structure was the mass spectrometric analysis of the intact molecule. Degradative and comparative studies are not capable of unequivocally defining structure. For example, the mass spectrum clearly showed the absence of an amide or similar C-terminal blocking groups or, as has been suggested, a sulfone in the molecule; such conclusions could not be drawn from comparative chromatographic data even on multiple systems. Mass spectrometric analysis of the intact molecule could overcome these problems by allowing the complete covalent structure to be collated from the information obtained from each fragmentation. The use of stable isotopes and accurate mass measurement removed possible ambiguities in the interpretation, and the sensitivity and specificity of mass spectrometry made it the method of choice for the structural analysis.

Animals↗
PubMed1982

Slow reacting substances (leukotrienes): enzymes involved in their biosynthesis.

Slow reacting substances (leukotrienes C4, D4, E4) are synthesized in vivo by a combination of two previously unrelated pathways: lipoxygenase oxygenation of arachidonic acid and the glutathione detoxification pathway. Enzymes involved in the latter pathway (glutathione transferase [RX: glutathione R-transferase, EC 2.5.1.18]; gamma-glutamyltransferase [(5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2] ) have been investigated in guinea pig lung and rat basophilic leukemia (RBL-1) cells. We report data on levels of enzymic activity both before and during the release of slow reacting substances. Both glutathione transferase and gamma-glutamyltransferase are present in significant quantities in guinea pig lung and RBL-1 cells. A model for the changes in gamma-glutamyltransferase during leukotriene release is proposed for the cell line, and differences from the guinea pig lung system are reported. Leukotriene C4 is converted to the more potent leukotriene D4 by the action of gamma-glutamyltransferase on guinea pig ileum during bioassay. gamma-Glutamyltransferase may represent a control feature in the biosynthesis of leukotriene D4, and thus be involved in leukotriene-induced bronchoconstriction in the lung.

Animals↗
PubMed1982

Identification of leukotrienes in the sputum of patients with cystic fibrosis.

Sputum extracts from 16 of 25 adult patients with CF produced a slow, sustained contraction of isolated guinea pig ileum which was partially inhibitable by the SRS-A antagonist FPL 55712. Following progressive purification and HPLC, the major ileum-contracting substance was identified as LTD4. LTC4 was also present but in smaller amounts. The sputum contained other SRS-A-like activity which was not inhibited by FPL 55712; this substance was of a smaller molecular size than LTD4. The presence of LTB4 was also established using HPLC and an assay of neutrophil chemotaxis. These studies raise the possibility that leukotrienes and other lipoxygenase products may contribute to the progressive lung disease characteristics of CF.

Adolescent↗