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Biomedical subjects

V S Chadwick

Publications and source records attributed to V S Chadwick.

117 records · Page 7Linked to original sources
PubMed1977

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.

A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.

Adult↗
PubMedDate not supplied

The effect of pirenzepine on gallbladder emptying in humans.

The effect of the selective antimuscarinic agent, pirenzepine, on gallbladder function was studied in six healthy volunteers, using 99mTc HIDA (N-[2,6-diethylthenyl] carbamoylmethyl iminodiacetic acid) hepatobiliary scanning. Pirenzepine, in doses that inhibit gastric acid secretion, did not alter gallbladder emptying responses to sham feeding stimulation or to a test meal.

Adult↗
PubMedDate not supplied

Enzymes degrading bacterial chemotactic F-met peptides in human ileal and colonic mucosa.

Bacterial chemotactic F-met peptides have been identified in culture supernatants of intestinal bacteria and in human faecal dialysates. These potent inflammatory agents could play a role in intestinal inflammatory disorders should they cross the epithelial barrier of the gut. We have identified mucosal peptidases which degrade F-met-leu-phe (FMLP) in ileal and colonic mucosal biopsies obtained at colonoscopy. A carboxypeptidase, inhibited by D-L-benzyl succinate (BzS), accounted for more than 60% of total FMLP-ase activity, other uncharacterized peptidases contributing the rest of the activity against the intact peptide. An F-met deformylase, inactive against di- and tri-peptides, cleaves released F-met completing the degradation. Total FMLP-ase, carboxypeptidase and F-met deformylase activities were measured in serial mucosal biopsies from 15 control patients undergoing colonoscopy for occult bleeding with negative findings and from 15 patients with ulcerative colitis (UC) and 10 with Crohn's disease (CD). Highest activities were found in terminal ileum and lowest in the rectum. Total FMLP-ase and carboxypeptidase activities were similar in controls and UC patients but were substantially reduced in CD, especially in the terminal ileum (controls 493 +/- 146 and 116 +/- 73 nmol/100 micrograms protein per h, respectively and CD 231 +/- 96 and 41 +/- 36 nmol/100 micrograms protein per h, respectively (P = 0.0018 and 0.015). F-met deformylase activities were similar in all groups. There was no correlation between enzyme activity and severity of inflammation. FMLP degrading peptidases probably contribute to the mucosal barrier of the gut in regions of high bacterial colonization, limiting intestinal absorption and inflammatory responses to these potent bacterial products in the intestinal lumen.

Amidohydrolases↗
PubMedDate not supplied

Radio-immunoassay for formyl methionyl leucyl phenylalanine. I. Development and application to assessment of chemotactic peptide production by enteric bacteria.

Bacterial chemotactic peptides are low molecular weight peptides which stimulate a wide range of neutrophil functions following binding to specific leucocyte receptors. Formyl methionyl leucyl phenylalanine (FMLP) is the major chemotactic peptide in Escherichia coli culture supernatants. This paper reports the development and validation of a radio-immunoassay (RIA) for FMLP and its application to the analysis of formyl peptide production by enteric bacteria in vitro. The assay was moderately sensitive (10 nmol/L FMLP) and highly specific showing cross reactivity with F-met-leu-tyr, F-nle-leu-phe and F-met-met-met sequences (ID50 = 200, 100 and 250 nmol/L, respectively) but no significant cross reactivity with non-formylated or other formylated di- and tri-peptides (ID50 = 10(5) nmol/L. Culture supernatants from five species of enteric bacteria were filtered, concentrated and fractionated by reverse phase high performance liquid chromatography before RIA. All five organisms produced immunoreactive F-met peptides. A major peak of immunoreactivity co-chromatographing with authentic FMLP was found in all supernatants, but additional peaks representing more hydrophobic peptides were found in Streptococcus faecalis and Bacteroides fragilis cultures. In E. coli culture supernatants, concentration of immunoreactive FMLP increased in a linear fashion during 3 h of log phase growth reaching 31.2 nmol/L(s.e.m. = 10) with final bacterial concentrations of 3 +/- 0.73 x 10(8)/mL (n = 6). These findings extend earlier work showing production of bioactive formyl oligopeptides by different species of enteric bacteria and suggest that a RIA for FMLP will be a useful tool for investigating the production and metabolic fate of such peptides in man.

Animals↗
PubMedDate not supplied

Radio-immunoassay for formyl methionyl leucyl phenylalanine. II. Demonstration of an enterohepatic circulation of immunoreactive bacterial chemotactic peptides in man.

Bacterial chemotactic peptides (F-met-oligopeptides) are secreted by several species of commensal enteric bacteria and can be assayed by bioassay techniques in human colonic luminal fluid. We have previously demonstrated intestinal absorption and enterohepatic circulation of radiolabelled F-met peptides introduced into rat colon, and an eightfold increase in absorption and biliary excretion in rats with experimental colitis. This paper describes the application of a radio-immunoassay to measurements of formyl oligopeptides in human faecal dialysates, colonic and systemic venous blood and bile. All samples were fractionated by reverse-phase high performance liquid chromatography (HPLC) prior to assay. Immunoreactivity was found in faecal dialysates (5-700 nmol/L F-met-leu-phe equivalents) and bile samples (3-150 nmol/L) from normal subjects. After HPLC fractionation, up to five distinct peaks of immunoreactivity were identified. One of these co-chromatographed with authentic F-met-leu-phe; the others probably represented either closely related peptides or peptides of different chain lengths originating from the same F-met-leu-phe precursor protein. Colonic venous blood from two patients with ulcerative colitis contained immunoreactive peptide (10-30 nmol/L) and substantial immunoreactivity was found in ileostomy fluid and bile from two patients with primary sclerosing cholangitis. These results suggest the presence of an enterohepatic circulation of bacterial F-met oligopeptides in man and provide a basis for studies of the role of such pro-inflammatory peptides in patients with inflammatory bowel disease and associated hepatobiliary disorders.

Animals↗
PubMedDate not supplied

Chronic active hepatitis in a patient presenting with clinical and serological evidence of SLE.

A patient with clinical and serological manifestations of systemic lupus erythematosus (SLE) without renal or neurological manifestations was managed conservatively for 4 1/2 years. At this time she developed ascites and abnormal liver function tests, and was found to have severe chronic active hepatitis (CAH) with cirrhosis and portal hypertension. No clinical or biochemical evidence of liver disease was documented over the first 3 1/2 years of her illness, though no tests were performed in the 12 months before diagnosis. This case emphasizes the value of monitoring liver function tests over extended periods in such patients, since appropriate immunosuppressive therapy may benefit CAH, and as in this case, systemic manifestations of CAH may simulate SLE and precede clinical liver disease.

Adult↗