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Biomedical subjects

G McKnight

Publications and source records attributed to G McKnight.

7 recordsLinked to original sources
PubMed1999

Glucose-dependent insulinotropic polypeptide stimulation of lipolysis in differentiated 3T3-L1 cells: wortmannin-sensitive inhibition by insulin.

GIP is an important insulinotropic hormone (incretin) that has also been implicated in fat metabolism. There is controversy regarding the actions of GIP on adipocytes. In the current study, the existence of GIP receptors and effects of GIP on lipolysis were studied in differentiated 3T3-L1 cells. GIP receptor messenger RNA was detected by RT-PCR and RNase protection assay. Receptors were detected in binding studies (IC50 26.7 +/- 0.7 nM). GIP stimulated glycerol release with an EC50 of 3.28 +/- 0.63 nM. GIP (10(-9)-10(-7) M) +/- IBMX increased cAMP production by 1180-2246%. The adenylyl cyclase inhibitor MDL 12330A (10(-4) M) inhibited GIP-induced glycerol production by >90%, and reduced cAMP responses to basal. Preincubation of 3T3-L1 cells with insulin inhibited glycerol responses to GIP, and the inhibitory effect of insulin was blocked by the phosphatidylinositol 3'-kinase inhibitor, wortmannin. It is concluded that GIP stimulates glycerol release in 3T3-L1 cells primarily via stimulation of cAMP production, and that insulin antagonizes GIP-induced lipolysis in a wortmannin-sensitive fashion. It is suggested that effects of GIP on fat metabolism in vivo may depend upon the circulating insulin level, and that meal-released GIP may elevate circulating fatty acids, thus optimizing pancreatic beta-cell responsiveness to stimulation by glucose and GIP.

3T3 Cells↗
PubMed1996

Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease.

BACKGROUND: In subjects on a low nitrate diet, plasma nitrate concentration and urinary nitrate excretion are thought to reflect endogenous nitric oxide (NO) production, and have been reported to increase during infective and inflammatory bowel disease. AIMS: To compare the extent of NO production in patients with infective versus non-infective forms of bowel dysfunction. SUBJECTS: Four groups: 20 healthy, volunteer clerical and laboratory staff, 12 patients with irritable bowel syndrome, 19 patients with inflammatory bowel disease, and 20 patients with infective gastroenteritis. METHODS: The plasma nitrate concentration was determined with a copper coated cadmium column and spectrophotometry. Mean and median plasma nitrate concentrations were calculated and compared within the four groups. Mann-Whitney distribution free rank testing was used to compare the median values. RESULTS: Median plasma nitrate concentrations in the four groups were: controls 32.7 mumol/l; irritable bowel syndrome 35.5 mumol/l; inflammatory bowel disease 35.1 mumol/l; and gastroenteritis 117.9 mumol/l (p < 0.001 gastroenteritis v all other groups). CONCLUSIONS: Plasma nitrate concentration could serve as a discriminant between infective and inflammatory or functional bowel disease in patients presenting with diarrhoea. It is not clear why there is considerable difference in endogenous nitrate synthesis in these two conditions, which are both characterised by severe gut inflammation.

Adolescent↗
PubMed1996

The role of an open-access bleeding unit in the management of colonic haemorrhage. A 2-year prospective study.

BACKGROUND: Major colonic haemorrhage poses difficult diagnostic and therapeutic problems and, in contrast to upper gastrointestinal bleeding, has no generally accepted plan of management. METHODS: We report community-based prospective data accumulated over 2 years (1991-93) on 1602 patients referred to an open-access bleeding unit with suspected gastrointestinal haemorrhage. RESULTS: Of 278 (17%) admissions with suspected lower GI haemorrhage, 252 were confirmed. Forty-eight per cent were defined as "significant' bleeds, with a decrease in haemoglobin and cardiovascular compromise. Of 102 significant bleeds in subjects more than 60 years old, 29% rebled, and 12.6% required emergency surgery. Diverticular disease (24%) was the commonest diagnosis, with tumours, infective colitis, and inflammatory colitis each at 10%. The overall 30-day mortality for colonic bleeding was 5.1% (13 of 252), with only 1 death occurring in the group less than 60 years old. CONCLUSIONS: This study provides a unique database for the natural history of colonic bleeding and its management within the setting of a specialized bleeding unit.

Adult↗
PubMed1995

Ondansetron: perioperative use of a serotonin receptor antagonist for the prevention and treatment of nausea and vomiting.

Postoperative nausea and vomiting (PONV) are common side effects after surgery and have numerous patient factors and etiologies. Although self-limiting, PONV is not without risks and complications. In the past numerous antiemetics have been used successfully in the management of PONV; however, these drugs are associated with adverse effects. Ondansetron is a serotonin receptor antagonist that is effective in preventing and treating PONV. It is believed that ondansetron binds at the serotonin receptor both in the vagal afferents of the gastrointestinal tract and in the chemoreceptor trigger zone. The reported side effects from ondansetron are minor compared with those of the more commonly used antiemetics such as droperidol and metoclopramide and include headache, dizziness, musculoskeletal pain, drowsiness and sedation, and shivers.

Antiemetics↗
PubMed1994

Canine galanin: sequence, expression and pancreatic effects.

To determine if dog galanin is a potent inhibitor of dog insulin secretion we determined its primary structure from its cloned cDNA, evaluated its expression in celiac ganglia and determined its effect on islet hormone secretion. The predicted amino acid sequence differs from the other known species of galanin by three to six amino acids in the C-terminal half of the molecule. In situ hybridization revealed the presence of dog progalanin mRNA in every neuronal cell body in the dog celiac ganglion. The predicted dog galanin peptide was synthesized and infused i.v. at 0.25, 2.5, 25 or 250 pmol/kg/min. It potently inhibited insulin secretion, less potently inhibited pancreatic somatostatin release and stimulated glucagon secretion, similar to the effects of porcine galanin in the dog. In summary, dog galanin is expressed in the neuronal cell bodies that innervate the pancreas and the sequence of the dog galanin preserves the potent insulin inhibitory part of the galanin molecule. These data support the hypothesis that galanin is a sympathetic neurotransmitter in dog pancreas.

Amino Acid Sequence↗
PubMed1980

AUG is the only initiation codon in eukaryotes.

An analysis of mutants of the yeast Saccharomyces cerevisiae indicates that AUG is the sole codon capable of initiating translation of iso-1-cytochrome c. This result with yeast and the sequence results of numerous eukaryotic genes indicate that AUG is the only initiation codon in eukaryotes; in contrast, results with Escherichia coli and bacteriophages indicate that both AUG and GUG are initiation codons in prokaryotes. The difference can be explained by the lack of the t6 A hypermodified nucleoside (N-[9-(beta-D-ribofuranosyl)purin-6-ylcarbamoyl]threonine) in prokaryotic initiator tRNA and its presence in eukaryotic initiator tRNA.

Cells↗