Search PubMed⌕ Search

Biomedical subjects

F Shanahan

Publications and source records attributed to F Shanahan.

At least 235 records · Page 13Linked to original sources
PubMed1984

The influence of endorphins on peritoneal and mucosal mast cell secretion.

The histamine-releasing effect of certain opiate drugs prompted a survey of endogenous opiates for mast cell-secretagogue activity. Since intestinal mucosal mast cells (MMC) differ from connective tissue mast cells in their response to a variety of secretagogues and anti-allergic compounds, we have examined the influence of several endogenous opiate peptides on histamine secretion from the two mast cell types in the rat. MMC hyperplasia was induced in rats infected with the nematode Nippostrongylus brasiliensis and MMC were isolated by collagenase digestion from the small intestine. Connective tissue mast cells from the peritoneal cavity (PMC) were isolated by peritoneal lavage. Dynorphin, alpha-neoendorphin, and beta-endorphin had a concentration-dependent secretagogue effect (10(-6)M to 10(-4)M) on PMC that was temperature and energy dependent, but MMC from the same animals were unresponsive to these agents. Differences between PMC and MMC did not appear to be attributable to the MMC isolation procedure since PMC treated similarly remained responsive to endorphin. Endorphin-induced histamine secretion from PMC was partially inhibited by the anti-allergic agent disodium cromoglycate. Inhibition with the opiate antagonist naloxone was nonspecific, occurring only at concentrations that also inhibited antigen-induced mediator release. Mast cell secretion induced by certain opiate peptides may therefore be nonreceptor mediated and relate to a direct membrane effect by basic peptides.

Animals↗
PubMed1984

Mast cell heterogeneity.

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell subpopulations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

Animals↗
PubMed1983

Factor V deficiency and its reversal with gluten restriction. In a patient with celiac disease.

Hemorrhagic manifestations in patients with celiac disease are uncommon and, when present, are usually due to a deficiency of the vitamin K-dependent clotting factors. A patient with celiac disease was seen with a severe bleeding diathesis associated with deficiencies of factor V. The deficiencies of vitamin K-dependent clotting factors were rapidly reversed with parenteral administration of phytonadione. Factor V levels returned to normal levels only after gluten restriction.

Adult↗
PubMed1982

Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing.

The clinical features of 24 patients with coeliac disease and insulin-dependent diabetes mellitus were reviewed. The HLA types of 17 of these patients were compared with those of 44 normal subjects, 49 patients with diabetes only and 58 patients with coeliac disease only. The diagnosis of coeliac disease was made after the diagnosis of diabetes in 14 patients, before diabetes in five and simultaneously in five. In established diabetics, coeliac disease was recognized relatively late (mean age 31 years) but the average duration of symptoms attributable to coeliac disease prior to a jejunal biopsy was five months. Gluten restriction was generally followed by a marked improvement in diabetic control. The frequency of HLA-DR3 in patients with coeliac disease and diabetes mellitus (88 per cent), patients with coeliac disease only (88 per cent), and patients with insulin-dependent diabetes mellitus only (69 per cent), was significantly greater than in normal subjects (44 per cent). The subtype of diabetes related to DR4/B15 does not appear to predispose to coeliac disease. The mechanism of the association between coeliac disease and insulin-dependent diabetes is discussed and the importance of coeliac disease in the differential diagnosis of 'diabetic diarrhoea' is emphasized.

Adolescent↗
PubMedDate not supplied

Appropriateness of laboratory tests: requests for atypical pneumonia serology in a teaching hospital.

The cost of providing medical care is ever-increasing but the resources available are at best static. Major savings can be made by reducing inappropriate investigations. Using serological testing for organisms causing atypical pneumonia as an example, we examined the appropriateness of requests and also physicians' understanding of the test. Of 119 patients tested, only 3 had titres indicative of acute infection. Most patients were tested within 2 days of hospital admission, before receipt of results excluding more likely diagnoses. Forty-five patients had no current or recent respiratory symptoms, in whom infection was highly unlikely. Titres were most often requested by the least experienced members of the clinical team. Of 70 patients with an acute illness in whom a definitive diagnosis, bacteriological or otherwise, was not made, in only 9 was a convalescent specimen sent for follow-up titres. Most requests for serology for organisms causing atypical pneumonia were inappropriate. Furthermore, in the majority of cases the test was incorrectly used.

Adolescent↗
PubMedDate not supplied

The prevalence of coeliac disease among female subjects having bone densitometry.

BACKGROUND: Osteoporosis frequently complicates coeliac disease but most studies focus on symptomatic patients at the time of diagnosis. Screening tests have revealed that many individuals with coeliac disease have mild, atypical, or absent symptoms. AIM: To evaluate the relationship between coeliac disease and osteopenia or osteoporosis in female subjects attending for bone densitometry. METHODS: We studied 371 female subjects attending for bone densitometry, without secondary causes of osteoporosis and included those with normal and with reduced bone mineral density. Mineral density was measured by dual energy X-ray absorptiometry. Screening for coeliac disease was by measurement of anti-endomysial antibody by indirect immunofluorescence. RESULTS: Two of 115 (1.7%) female subjects with normal bone density and five of 256 (1.9%) female subjects with sub-normal bone density were positive for endomysial antibody. Five subjects who underwent small bowel biopsy had histological changes suggestive of coeliac disease. CONCLUSIONS: In females referred for bone densitometry, endomysial antibody positivity was not more prevalent among those with reduced bone mineral density. Examining only patients with clinically detected coeliac disease may overestimate the frequency of complications. This study does not support population screening for coeliac disease in an area with a high frequency of the condition.

Absorptiometry, Photon↗
PubMedDate not supplied

Sulfasalazine inhibits the binding of TNF alpha to its receptor.

Sulfasalazine was found to exhibit a dose-dependent inhibition of human mucosal and peripheral blood cytotoxic T-cell function. The drug also inhibited the cytotoxic activity of supernatants from anti-CD3-triggered T-cells against murine L929 fibroblasts. TNF alpha has previously been shown to be primarily responsible for the lytic activity of such supernatants and this was confirmed. Sulfasalazine also inhibited the lytic activity of recombinant TNF alpha. When tested under conditions where TNF alpha was allowed to bind to but not lyse the target cells, the results suggested that the drug inhibits the action of this cytokine by inhibiting its binding to the cell membrane receptor. Additional evidence for an inhibitory effect of sulfasalazine on the membrane binding of TNF alpha was obtained by demonstrating a dose-dependent displacement of 125I-TNF alpha from HL60 cells. Although sulfasalazine is often considered to be a pro-drug for site-specific delivery of its component fragments 5-ASA and sulfapyridine, the results demonstrate an immunopharmacological property of the parent compound that is not shared with its component molecules.

Animals↗
PubMedDate not supplied

Biotinylation of a bombesin/gastrin-releasing peptide analogue for use as a receptor probe.

The development of a biotinylated bombesin/gastrin-releasing peptide (GRP) for use as a receptor probe is reported. The lysine13 of a GRP-27 was substituted by arginine and lysine was added to the amino terminus. Biotinylation of the N-terminal lysine was performed. The biotinylated peptide was purified by HPLC and characterized by mass spectral analysis. Binding studies with murine Swiss 3T3 fibroblasts, cells known to express bombesin/GRP receptors, yielded a dissociation curve for the biotinylated GRP-27 analogue (biotin-Lysyl[Asp12,Arg13]GRP-27) which was nearly identical to that of native GRP. Using studies of gastrin release from isolated canine G cells, equipotent functional activity of the biotinylated probe and unmodified GRP was demonstrated. Measurements of retained 125I-avidin confirmed that the biotin/avidin interaction could occur once the biotin-peptide complex was bound. Applicability of the probe was demonstrated with fluorescent microscopy using avidin-FITC on Swiss 3T3 fibroblasts. In conclusion, a novel biotinylated bombesin/GRP analogue has been developed which retains the functional characteristics of the native peptide and is a useful probe for receptor studies.

Amino Acid Sequence↗