Prolonged inhibition of acid secretion causes hypergastrinaemia without altering pH inhibition of gastrin release in humans

Hypergastrinaemia induced by potent inhibitors of acid secretion is thought to occur as a result of the elimination of the inhibitory effects of intragastric acid on gastrin release. The present study was designed to determine if the mechanisms responsible for feedback inhibition of gastrin release and acid secretion by intragastric acid are preserved during four weeks of varying degrees of drug-induced acid inhibition. Forty-eight healthy male volunteers were randomly assigned to one of four treatments for four weeks: 10 mg omeprazole o.m., 20 mg omeprazole o.m., 40 mg omeprazole o.m. or 150 mg ranitidine b.d. Gastrin release and acid secretion in response to peptone meals maintained at pH 2.5 and pH 5.5 by intragastric titration, and 24-hour gastrin profiles in response to standard meals were determined before treatment, at the fourth week of treatment and two weeks after discontinuing treatment. As expected, omeprazole produced dose-related effects on acid secretion and gastrin concentrations that were largely reversed after treatment was discontinued. Gastrin release in response to pH 5.5 peptone meals remained significantly greater than gastrin release in response to pH 2.5 meals during treatment with all doses of omeprazole. The ratio of pH 5.5/pH 2.5 peptone meal-stimulated gastrin release was approximately 1.5, and remained constant for all treatment groups throughout the study period. These data indicate that four weeks of drug induced hypochlorhydria causes an apparent increase in overall G-cell function, but it does not interfere with normal feedback inhibition of gastrin release and acid secretion mediated by intragastric acidity.     

Spontaneous Neoplasms in Control Wistar Rats

Neoplastic data on 1370 control Wistar rats from 10 carcinogenicitybioassays done between 1980 and 1990 were reviewed. Mean percentagesurvival at 104 weeks was 58% for males and 59% for females.A total of 1857 neoplasms were diagnosed in 466 (68%) male and582 (85%) female rats; 1390 were benign and 467 were malignant(12% with metastasis). Seventy-four percent of all neoplasmswere in endocrine and reproductive systems. Most common neoplasms(affecting more than 7% of either sex) were pituitary adenoma(27.7% males; 55.0% females), mammary fibroadenoma (1.0% males;25.3% females), mammary adenocarcinoma (1.0% males; 13.1% females),adrenal cortical adenoma (8.3% males; 9.3% females), and endometrial stromal polyp (9.6% females). Fourteen neoplasms affecting2 to 6% of either sex included adrenal pheochromocytoma, thyroidC cell adenoma, thyroid follicular adenoma, pancreatic isletcell adenoma, lymphoma, histiocytic sarcoma, thymoma, hepaticadenoma, pancreatic acinar adenoma, mammary adenoma, dermalfibroma, astrocytoma, testicular interstitial cell tumor, andovarian granulosa cell tumor. Remaining neoplasms were seenin less than 2% of animals.     

Recombinant interleukin-2 in lepromatous leprosy lesions: immunological and microbiological consequences*

Seven patients with lepromatous leprosy (LL) were inoculated with recombinant interleukin-2 (rIL-2) at 5 lesional sites on the back, four sites receiving one dose of 10μg and biopsy specimens being obtained on 4 consecutive days after the injection. At the 5th site, rIL-2 was instead administered over several days, three patients receiving a total dose of 40 μg and 4 patients 150μg, while biopsy specimens from this site were obtained 7, 14 and 21 days after the first injection. Most injection sites developed features of a delayed-type hypersensitivity reaction, namely erythema and induration at the injection site, infiltrates rich in T helper cells, monocytes, and Langerhans cells, and at sites receiving higher doses, multinucleated Langhans giant cells and epithelioid granulomas. In some patients, there were favourable shifts in histological classification or small changes in bacterial load. Lew doses of rIL-2 injected into LL lesions rapidly enhance cellular immunity and may alter the histological classification or bacterial load at the injection site.     

Regulation of smooth muscle actin—myosin interaction and force by calponin

Smooth muscle contraction is regulated primarily by the reversible phosphorylation of myosin triggered by an increase in sarcoplasmic free Ca²⁺ concentration ([Ca²⁺]_i). Contraction can, however, be modulated by other signal transduction pathways, one of which involves the thin filament-associated protein calponin. The h1 (basic) isoform of calponin binds to actin with high affinity and is expressed specifically in smooth muscle at a molar ratio to actin of 1: 7. Calponin inhibits (i) the actin-activated MgATPase activity of smooth muscle myosin (the cross-bridge cycling rate) via its interaction with actin, (ii) the movement of actin filaments over immobilized myosin in the in vitro motility assay, and (iii) force development or shortening velocity in permeabilized smooth muscle strips and single cells. These inhibitory effects of calponin can be alleviated by protein kinase C (PKC)-catalysed phosphorylation and restored following dephosphorylation by a type 2A phosphatase. Three physiological roles of calponin can be considered based on its in vitro functional properties: (i) maintenance of relaxation at resting [Ca²⁺]_i, (ii) energy conservation during prolonged contractions, and (iii) Ca²⁺-independent contraction mediated by phosphorylation of calponin by PKCε, a Ca²⁺-independent isoenzyme of PKC.     

Skin test and RAST responses to wheat and common allergens and respiratory disease in bakers

Interrelationships between skin and humoral tests for immediate hypersensitivity to wheat and indicators of respiratory disease were examined in 176 male bakers. Skin tests were assessed by measuring the diameter of the weal resulting from prick innoculation of allergen extract and circulating allergen-specific IgE by radioallergosorbent test (RAST). Fifteen per cent of subjects showed positive skin-prick test responses to wheat extracts. These subjects demonstrated an increased prevalence of respiratory symptoms and of measurable bronchial responsiveness to methacholine. Thirty per cent of subjects had positive skin test responses to common allergens but negative responses to whole wheat. Compared to subjects with no positive skin test responses they had an increased prevalence of bronchial responsiveness to methacholine but a similar prevalence of respiratory symptoms. There was a significant association between skin test responses to whole wheat and skin test responses to common allergens suggesting that bakers with pre-existing sensitivity to common allergens are at increased risk of developing wheat flour sensitization. There was no significant difference between skin-prick test and RAST responses to wheat, water-soluble wheat protein and common allergens. Both tests showed similar relationships with indices of respiratory disease. The associations between skin test and RAST responses to wheat extracts and indices of respiratory disease was stronger for the water-soluble wheat proteins than for other wheat grain extracts. These results suggest that immediate hypersensitivity to wheat flour is important in the development of non-specific bronchial hyperreactivity in bakers and that the water-soluble fractions of wheat flour are the most important allergenic components. It agrees with in vitro results showing that water-soluble wheat proteins bind IgE in sensitive bakers more closely than other grain extracts.     

COGNITIVE IMPAIRMENT AND AUTOANTLBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS

Nervous system involvement in systemic lupus erythematosus (SLE)includes a wide array of manifestations some of which have beenassociated with specific autoantibodies. These include reactivityto surface neuronal and lymphocyte antigens, ribosomal P andcardiolipin. The aim of the present study was to examine theassociation between cognitive abnormalities and these autoantibodiesin an unselected female population of SLE patients. Using abattery of standardized neuropsychological tests, cognitiveimpairment was identified in 15/70 (21%) SLE patients comparedto 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%)healthy subjects (P=0.04). Circulating antineuronal antibodieswere measured by indirect immunofluorescence using human neuroblastomacell lines IMR-6 and SK-N-SH. Lyrnphocytotoxic antibodies weremeasured by microcytotoxicity. Antibodies to ribosomal P andcardiolipin were measured by ELISA. Antineuronal antibodieswere detected in 34%, lymphocytotoxic antibodies in 47%, anti-Pantibodies in 17% and anticardiolipin antibodies in 24% of patients.In the cognitively impaired and unimpaired SLE patients therewas no significant difference in the prevalence of antineuronalantibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%),anti-P antibodies (20 vs 17%) or anticardiolipin antibodies(7 vs 29%). The titre and isotype of autoantibodies were alsosimilar in both groups. These results suggest that autoantibodieswhich have previously been associated with nervous system manifestationsof SLE are not likely to be directly involved in the pathogenesisof cognitive dysfunction. KEY WORDS: Cognitive impairment, Autoantibodies, Lupus     

Technique and Results of Cardiac Transplantation Using "Domino-Donor" Hearts

Heart-lung transplantation is now well established for treatment of patients with terminal cardiopulmonary disease. More than 50% of heart-lung transplant recipients have normal or near normal hearts, with the majority having some degree of right ventricular hypertrophy. This potential source of "prepared" cardiac allografts remained untapped until the introduction of the "domino-donor" operation, a procedure in which the heart-lung recipient serves as a cardiac donor. The implantation of these available allografts contributes to the alleviation of the short supply of donor organs for cardiac transplantation. Aspects of the surgical technique, results, and potential benefits of this procedure are presented.