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Biomedical subjects

H Gregory

Publications and source records attributed to H Gregory.

At least 73 records · Page 4Linked to original sources
PubMed1979

The identification of urogastrone in serum, saliva, and gastric juice.

Urogastrone, a peptide isolated from human urine, is known to cause inhibition of gastric acid secretion and proliferation of fibroblasts in culture; furthermore immunofluorescent localization techniques show it to be present in submandibular and Brunner's glands. Serum, saliva, and gastric juice samples have now been fractionated upon Sephadex G-200 and G-50 and the immunoreactive urogastrone located using a specific radioimmunoassay. Biologic activity was shown by mitogenic studies with 3T6 fibroblasts. In serum, the major immunoreactive component was ca. 1-2 X 10(5) daltons, but trypsin treatment then gave a smaller biologically active species in the same position as pure urogastrone on Sephadex G-50. Both saliva and gastric juice showed major components at the position defined by urogastrone, and these also stimulated the uptake of [H]thymidine into the fibroblasts. It is concluded that a urogastrone-like molecule can be released enzymically from a high molecular weight serum precursor and that the small biologically active peptide is also a normal component of saliva and gastric juice.

Autoradiography↗
PubMed1978

Immunohistochemical localisation of urogastrone to human duodenal and submandibular glands.

Urogastrone has been localised by immunostaining to granules of the cells of human duodenal (Brunner's) glands and their ducts and of acinar cells in the human submandibular gland. The immunoreactive peptide is present in large quantities in duodenal glands and their secretory ducts. Urogastrone or human epidermal growth factor promotes cellular proliferation in vivo as well as in vitro and inhibits gastric acid secretion and may, therefore, be one of the duodenal factors inhibiting gastric activity. Thus it may have an important regulatory and protective function for the intestinal mucosa and may possibly become a useful therapeutic agent.

Brunner Glands↗
PubMed1977

Topographical localization of the receptors for luteinizing hormone-releasing hormone on the surface of dissociated pituitary cells.

A derivative of the hypothalamic peptide luteinizing hormone-releasing hormone (LHRH) has been coupled to ferritin and the conjugate purified by gel chromatography. In its ability to stimulate the secretion of luteinizing hormone from pituitary cells in vitro, the conjugate has the same potency and specificity as the native peptide. When dissociated pituitary cells maintained in short-term culture are lightly fixed with formaldehyde and then incubated with the conjugate, examination in the electron microscope shows an even distribution of ferritin particles over the free cell surface of the gonadotrophin cells. This binding appears to be specific for the LHRH receptor since it is prevented by a 10-fold excess of native peptide. In addition to the gonadotrophin cells, some somatotrophin and thyrotrophin cells bind conjugate on their free surfaces under similar conditions. If living cells are incubated with the conjugate for 15 min, the bound conjugate becomes aggregated and then concentrated in one localized area of the cell surface. In this area, which lies immediately above the juxtanuclear Golgi complex, the plasma membrane is frequently invaginated in a manner which suggests that the bound, aggregated conjugate is internalized by endocytosis.

Animals↗
PubMed1977

The primary structure of human urogastrone.

Urogastrone is a potent inhibitor of gastric acid secretion which is present in human urine. Its existence has been known for over 30 years but it has only recently been isolated in a sufficiently pure form for detailed structural studies to be undertaken. Two separate polypeptides beta- and gamma-urogastrone were isolated. The structures were established by carrying out enzymic degradations of S-carboxymethyl and S-carboxamidomethyl derivatives with trypsin, chymotrypsin, thermolysin and a protease derived from the fungus Armillaria mellea. Sequences of the smaller peptides thus obtained were determined by the dansyl Edman method. Partial acid hydrolysis of urogastrone itself gave fragments containing single intact disulphide bonds, and oxidation then allowed the direction of individual bonds to be established. Beta-Urogastrone was shown to be a 53-amino acid residue polypeptide containing three disulphide bonds, and gamma-urogastrone had an identical sequence but lacked the C-terminal arginine residue. Urogastrone was subsequently found to be structurally related to mouse epidermal growth factor in that 37 of the 53 residues were commonly located in each polypeptide. Furthermore, as both peptides has similar effects upon gastric acid secretion and upon epidermal growth, urogastrone was also a human epidermal growth factor. The 16 variable residues were spread across the molecule, all apart from two were compatible with single base changes in the triplet condons, and the overall effect was to make uorgastrone more acidic than EGF. The smallest biologically active unit has not been defined but at least six residues can be removed from the C-terminus without causing a reduction in potency.

Amino Acid Sequence↗
PubMed1977

Urogastrone levels in the urine of normal adult humans.

Urogastrone is a potent inhibitor of gastric acid secretion isolated from human urine and it is structurally related to and shares the properties of a potent mitogen-mouse epidermal growth factor. The amounts of urogastrone in 24 h normal human urine samples were measured using a specific and sensitive radioimmunoassay. Values varied from 120--1360 ng/kg/24 h but a significant difference (2P less than 0.005) was observed between urine samples from men (602 +/- 41 SE, n = 39) and women (782 +/- 44 SE, n = 33). A series of 24 h urine collections from male and female volunteers showed that wide variations could occur over a 4 week period in the individual output of urogastrone. Levels from women did not show variations that could be related to the stage of the menstrual cycle.

Adolescent↗
PubMed1975

Effect of urogastrone in the Zollinger-Ellison syndrome.

The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.

Adult↗
PubMed1975

Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects.

Purified human urogastrone was given by intravenous infusion to 12 normal volunteer subjects and measurements made of gastric acid, pepsin and intrinsic factor secretion, and of plasma gastrin concentration. Clinical, haematological, and biochemical screening tests were made throughout the period of study. Urogastrone inhibited acid and intrinsic factor secretion whether stimulated by pentagastrin, histamine, or insulin, but had a much less marked effect on gastric pepsin output. Plasma gastrin levels did not alter significantly. Limited dose-response studies showed that 0-25 mug urogastrone kg--1 hr--1 resulted in inhibition of acid output of 80% and was not associated with clinical side-effects. No significant alteration in any of the haematological or biochemical measurements was observed in any of the subjects.

Adult↗
PubMed1975

The isolation of the urogastrones - inhibitors of gastric acid secretion - from human urine.

It has been known for over thirty years that extracts of human urine could cause inhibition of gastric acid secretion. The active principle was called urogastrone and this has now been isolated using a series of twelve simple stages of partition, gel and ion-exchange chromatography. In fact two products were obtained, each in a yeild of less than 1 mg per 1 000 l urine, which represented an overall recovery of 3 - 5%. These materials were biologically indistinguishable, causing inhibition of gastric acid secretion in a variety of circumstances at doses of less than 1 mug/kg. The purified urogastrones were found to be acidic polypeptides composed of 53 and 52 amino acid residues with three internal disulphide bonds, and they differed by only one arginine residue. Neither threonine nor phenylalanine residues were present in the urogastrones.

Amino Acids↗