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Biomedical subjects

S Stafford

Publications and source records attributed to S Stafford.

29 records · Page 2Linked to original sources
PubMed1993

Selective inhibition of the cutaneous late but not immediate allergic response to antigens by misoprostol, a PGE analog. Results of a double-blind, placebo-controlled randomized study.

The objective of this study was to investigate the effect of misoprostol on allergen-induced cutaneous immediate- and late-phase allergic reactions in a double-blind placebo-controlled randomized study. We also studied the mechanism of antiallergic effects of misoprostol. A total of 16 dust mite-allergic patients received misoprostol (200 micrograms) or placebo and then had skin testing on 2 different days. The immediate- and late-phase skin response was monitored for 6 h. Skin biopsy was obtained from 5 selected donors at 5 h. In vitro studies included the effect of misoprostol on eosinophil chemotaxis, eosinophil survival, basophil histamine release, and cytokine production by lymphocytes. All subjects developed an immediate wheal reaction and a late-phase induration in response to dust mite allergens after taking placebo. Misoprostol selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced number of inflammatory cells in the skin dermis after misoprostol treatment. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxis and the production of granulocyte-macrophage colony-stimulating factor by lymphocytes at concentrations > or = 10(-8) M. However, at significantly lower concentrations (> or = 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil survival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation.

Adult↗
PubMed1992

Macrophage inflammatory protein-1 alpha activates basophils and mast cells.

Macrophage inflammatory protein-1 (MIP) is a recently cloned cytokine that causes neutrophilic infiltration and induces an inflammatory response. We studied the effect of MIP-1 alpha on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-1 alpha caused dose-dependent release of histamine from basophils of 14 of 20 allergic donors at concentrations of 10(-9)-10(-7) M, and the mean release was 13.50 +/- 2.9% at the highest concentration. In the same experiments, the mean histamine release by anti-immunoglobulin E and monocyte chemotactic and activating factor (MCAF) (10(-7) M) was 32 +/- 7% and 31 +/- 3%, respectively. The cells from only 2 of 10 normal subjects released histamine in response to MIP-1 alpha. Histamine release by MIP-1 alpha was rapid, and almost complete within the first 3 min. MIP-1 alpha-induced degranulation was a calcium-dependent noncytotoxic process. MIP-1 alpha showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-1 alpha and MCAF at 10(-7) M concentration elicited a chemotactic response that was 40% of the maximal response to C5a (1 microgram/ml). Murine MIP-1 alpha induced histamine release from mouse peritoneal mast cells in a dose-dependent manner. Thus, we have established that MIP-1 alpha is a novel activator of basophils and mast cells.

Animals↗
PubMed1986

Circulating growth hormone forms in type 1 diabetic subjects: comparison with normal subjects and acromegalics.

The molecular forms of growth hormone (GH) in serum from 18 Type 1 diabetic patients with poor metabolic control were analysed using sephadex G-100 chromatography. The profiles obtained were compared with those from normal subjects whose GH secretion was stimulated by exercise and hypoglycaemia and eight acromegalic patients. In the three groups three distinct GH forms were found: little (monomeric), big and big-big-GH. Samples from normal subjects contained 45% little-GH which was less than samples from the diabetics and acromegalics (53% and 65%, respectively, P less than 0.01). Further samples from normal subjects after the onset of hypoglycaemia showed an increase in little-GH. In the three groups, the higher the proportion of little-GH, the lower the proportion of big-big-GH, while the proportion of big-GH remained similar. In the acromegalics the proportion of little-GH was strongly correlated with the log concentration of serum GH. As little-GH is cleared from the circulation quicker than the larger forms these data indicate that the main component of the frequent surges of GH secretion in poorly controlled Type 1 diabetic subjects is little-GH (monomeric forms). The sustained release of GH found in acromegaly is composed largely of monomeric forms.

Acromegaly↗
PubMed1984

Management of patients with polyps containing malignancy removed by colonoscopic polypectomy.

The management of malignant colonic polyps removed colonoscopically has been a controversial subject. A continuing series is reported of 36 patients with 37 malignant polyps removed by colonoscopic polypectomy (CP) between 1976 and 1982. Fourteen polyps contained carcinoma in situ (CIS); 13 were treated by CP alone; one was treated by CP and colectomy. Nineteen polyps contained invasive carcinoma; 13 were treated by CP alone; six were treated by CP and colectomy. Four patients had sessile polyps resected piecemeal, in which accurate staging was impossible. Two were treated with CP alone, and two had CP plus colectomy. All patients were followed with yearly colonoscopy and/or barium enema. Follow-up has been six to 84 months (mean 36 months). Twenty-seven patients whose polyps were treated by CP alone have had no evidence of recurrent tumor at the polypectomy site. Of the nine patients undergoing colectomy, six had residual tumor at the polypectomy resection site. No patients had involved lymph nodes. Our current approach to this problem is based on the degree of invasion and the status of the resection margins. Polyps containing CIS can safely be treated with CP alone. Polyps with invasive carcinoma and clear resection margins should be treated with CP and either colectomy or frequent repeat colonoscopy. This decision is a clinical one and must involve input from both the clinician and the pathologist. Those polyps whose resection margins are involved or where piecemeal excision precludes accurate pathologic assessment should undergo colectomy.

Adenoma↗
PubMedDate not supplied

The interleukin-5/receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak-STAT pathways in eosinophils.

We have shown that the interaction of interleukin (IL)-5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min. IL-5 also stimulates GTP binding to p21ras. The signal is subsequently propagated through the activation of Raf-1, MEK, and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ. Jak2 kinase has been shown to phosphorylate STAT nuclear proteins. The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site (GAS) probe. We found that IL-5 induces two GAS-binding proteins in eosinophils, one of which is STAT1. We conclude that IL-5 induced signals are propagated through two distinct pathways: (1) Lyn-->Ras-->Raf-1-->MEK-->MAP kinase and (2) Jak2-->STAT1.

Calcium-Calmodulin-Dependent Protein Kinases↗