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Biomedical subjects

P Chew

Publications and source records attributed to P Chew.

49 records · Page 3Linked to original sources

Some aspects of breast cancer in Singapore--a review of 306 cases.

A retrospective study of 306 cases of carcinoma breast in Singaporean patients managed at the University Department of Surgery, Singapore General Hospital was made, based on all available case notes, pathology report forms, operation record books, Cancer Registry Notification Forms, and data obtained from the Registry of Births and Deaths. These cases had their initial histological diagnosis made between 1970 to 1978. Basic data like age distribution, sex distribution and racial distribution of our cases are presented. Aspects of breast cancer like stage at time of diagnosis and 5- and 10-year survival figures are also presented. The crude five-year survival for all 306 cases was 56% and the crude 10-year survival for 223 cases was 22%. Survival for small lesions (T1, or less than 2 cm) was 90% at five years and 68% at ten years, a rate comparable with most centres in the world.

Adult↗

Effect of parietal cell vagotomy on acid secretory responsiveness to circulating gastrin in humans. Relationship to postprandial serum gastrin concentration.

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.

Duodenal Ulcer↗

Potency of natural and synthetic canine gastrin-releasing decapeptide on canine antral muscle.

The carboxyl terminal decapeptide of gastrin-releasing peptide (GRP-10), a small, naturally occurring bombesin-like peptide, has been isolated from canine antral muscle, synthesized, and its bioactivity compared with other synthetic and natural gastrin-releasing peptides on stimulation of spontaneously occurring contractions of canine circular antral muscle in vitro. Concentrations of peptides were verified by amino acid analysis and radioimmunoassay. In this system three forms of natural canine GRP, synthetic GRP-10, synthetic porcine gastrin-releasing heptacosapeptide (GRP-27), [Gln3]GRP-10, and [Arg3]GRP-10 all were similar in potency to synthetic amphibian bombesin. These results differ from the low activity of GRP-10 previously reported in rat brain. The full biological potency on canine antral motility and the presence of GRP-10 in nerve fibers in the gut and in the spinal cord suggest a possible role for this peptide as a neurotransmitter or neuromodulator in regulation of smooth muscle contraction.

Amino Acids↗

Gastric emptying and pancreatic polypeptide response to carbohydrate meals.

This study examined pancreatic polypeptide responses to isocaloric meals of radioactively labeled glucose or starch in six normal and seven vagotomized subjects. Liquid glucose meals were ingested with the subject both erect and supine and starch meals were ingested in the upright posture as a solution and as solid balls. In normal subjects, each meal left the stomach at a similar rate and the resultant pancreatic polypeptide responses were not significantly different from one another. Emptying rates varied markedly in vagotomized subjects depending upon the physical consistency of the carbohydrate ingested and the patient's posture. Despite these differences, pancreatic polypeptide responses to each meal were almost identical. These studies demonstrate that the pancreatic polypeptide response to carbohydrate meals is still present several years after vagotomy and is unaffected by alterations in the rate of gastric emptying after vagotomy and by the physical consistency and chemical nature of the carbohydrate ingested.

Adult↗

Amino acid sequences of three bombesin-like peptides from canine intestine extracts.

Amino acid sequences of three canine bombesin-like peptides were determined after sequential purification of an extract obtained from 820 g of intestinal muscle. These three peptides contained 27, 23, and 10 amino acid residues. The sequences of the two shorter forms were identical to the corresponding carboxyl-terminal sequence of the heptacosapeptide. The sequence of the largest peptide is H2N-Ala-Pro-Val-Pro-Gly-Gly-Gln-Gly-Thr-Val-Leu-Asp-Lys-Met-Tyr-Pro-Arg-Gly-Asn - His(Trp-Ala-Val-Gly-His-Leu-Met-CONH2). The sequence of the 23-residue peptide is H2N-Gly-Gly-Gln-Gly-Thr-Val-Leu-Asp-Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala- Val-Gly(His-Leu-Met-CONH2). The sequence of the decapeptide is: H2N-Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-CONH2. Comparison of the 27-residue peptide with the known structure of porcine gastrin-releasing peptide, another bombesin-like heptacosapeptide, reveals four amino acid substitutions: canine bombesin-like peptide had Pro 4, Gly 5, Gln 7, Asp 12, whereas porcine gastrin-releasing peptide had Ser 4, Val 5, Gly 7, Ala 12. Radioimmunoassay of brain extracts after similar purification revealed the presence of similar large and small forms of immunoreactive bombesin peptides, but with apparent tissue concentrations of about 4% of those present in intestinal muscle. Canine bombesin-like peptides represent another example of mammalian neuropeptides existing in more than one biologically active molecular form.

Amino Acid Sequence↗

The concentrations of four neuropeptides in various brain areas of summer active and hibernating Spermophilus lateralis.

1. Twenty-six female golden-mantled ground squirrels were divided into four physiological stages; low weight summer, medium weight summer, high weight summer, and early hibernation period. 2. Sections of six brain regions from each animal were analyzed by radioimmunoassay for bombesin, cholecystokinin, neurotensin and somatostatin-like immunoreactivity. 3. Significant (P less than 0.05) between-stage differences were detected in thalamic bombesin, thalamic and hypothalamic neurotensin, and cerebellum somatostatin concentrations. 4. Significant (P less than 0.05) peptide concentration versus physiological stage correlations were found in cerebral cortex and hypothalamic cholecystokinin and hypothalamic somatostatin concentrations.

Animals↗

Rapid high-yield purification of neuropeptides from canine intestinal muscle.

A simplified method for purification of gastrointestinal neuropeptides from relatively small amounts of tissue is described. Sequential adsorption, gel filtration, ion-exchange chromatography, and high-performance liquid chromatography without lyophilization produced good yields of somatostatin, bombesin, and vasoactive intestinal polypeptide immunoreactivity. The method is suitable for simultaneous purification of several small, basic peptides from limited amounts of starting material.

Animals↗

Pancreatic polypeptide responses to hypoglycemia in chronic autonomic failure.

Pancreatic polypeptide (PP) and catecholamine responses to insulin-induced hypoglycemia have been measured in 15 patients with neurogenic orthostatic hypotension. Eight of the patients had idiopathic orthostatic hypotension, and 7 had multiple system atrophy, a condition characterized by the presence of central nervous system lesions in addition to the orthostatic hypotension common to both diseases. Eleven healthy subjects exhibited rapid and substantial elevations in plasma epinephrine, norepinephrine, and PP concentrations in response to insulin hypoglycemia. In contrast, patients with neurogenic orthostatic hypotension exhibited impaired catecholamine and PP responses to insulin hypoglycemia. There was no correlation between the catecholamine and PP responses in either the normal subjects or the patients, suggesting that PP release during hypoglycemia is independent of the sympathoadrenal medullary response. As PP release in response to insulin hypoglycemia is abolished by truncal vagotomy and unaffected by splanchnic nerve section, our results suggest that patients with chronic autonomic failure may have a diffuse autonomic dysfunction involving the parasympathetic as well as the sympathetic nervous system.

Adult↗

Unique amino terminal structure of rat little gastrin.

The heptadecapeptide form of rat gastrin was purified by a combination of DEAE cellulose, Sephadex G50 affinity, and high performance liquid chromatography. An amino terminal pyroglutamyl blocking group was removed by incubation with PCA peptidase. Amino acid analysis before and after the unblocking reaction revealed the presence of one additional residue of arginine and proline compared with porcine gastrin. Microsequencing analysis of the unblocked peptide revealed that the sequence of the remaining hexadecapeptide was RPPMEEEEEAYGWMDF. The corresponding sequence of porcine gastrin is GPWMEEEEEAYGWMDF amide. The presence of carboxyl-terminal amide group in rat gastrin is strongly supported by complete immunoreactivity with antibodies specific for amidated C-terminal sequences of mammalian gastrins. The Arg and Pro substitutions in the amino terminal region can explain poor crossreactivity of rat gastrin with antibodies specific for the amino-terminal portion of porcine or human gastrin and its more basic chromatography pattern on ion exchange resins.

Amino Acid Sequence↗

Role of the small intestine and gastric antrum in pancreatic polypeptide release.

Gastrointestinal peptides have been proposed to play an important role in the pancreatic polypeptide response to a meal. These studies examine the role of the small intestine and gastric antrum in pancreatic polypeptide release in unanesthetized dogs. Intestinal perfusion with 5% liver extract in seven dogs resulted in a significant increase (P less than 0.05) in serum pancreatic polypeptide concentration (mean delta PP = 35.0 +/- 10.5 pM). Antrectomy without truncal vagotomy in four of these dogs significantly inhibited (P less than 0.05) this response. In five other dogs, antrectomy inhibited the pancreatic polypeptide response to an ingested meat meal by 81.9 +/- 4.5% (P less than 0.01). To further delineate the mechanism by which antrectomy inhibits pancreatic polypeptide release, the pancreatic polypeptide response to a meal was measured in four dogs before and after selective antral denervation. Antral denervation inhibited pancreatic polypeptide release to a degree similar (81.5 +/- 13.4%) to that previously observed after antrectomy. These studies have demonstrated an intestinal phase of pancreatic polypeptide release. They also suggest that antrectomy exerts its inhibitory effect on pancreatic polypeptide release by partially denervating the pancreas.

Animals↗

Isolation and characterization of rabbit gastrin.

The heptadecapeptide form the rabbit gastrin was extracted from 16 rabbit antra and purified by a combination of DEAE Sephadex, C-18 SEP PAK cartridges, fast performance liquid chromatography (FPLC) and reverse phase high pressure liquid chromatography (HPLC) steps. After the HPLC purification, a sharp, single peak of gastrin-like immunoreactivity was detected that had the same absorption to immunoreactivity ratio as human gastrin. An amino terminal pyrrolidone carboxylic acid blocking group was removed by incubation with pyrrolidone carboxylic peptidase. The amino acid analysis, microsequence analysis and mass spectrometry all confirmed the structure of rabbit gastrin being pQGPWLQEEEEAYGWMDFamide. This sequence is identical to human gastrin-17 except for glutamine in position 6 which replaces glutamate in human gastrin. Both sulfated and unsulfated rabbit gastrin-17 were characterized by mass spectrometry.

Amino Acid Sequence↗