Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line.

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.     

X-Ray small-angle scattering from concentrated solutions of normal and sickle cell deoxyhemoglobin

X-ray small-angle scattering of human normal and sickle cell deoxyhemoglobin in aqueous solution was measured at various concentrations, including those approximating the intracellular. The calculated radius of gyration, determination of the overall shape, and Soulé-Porod plots all indicate a concentration-dependent difference in strength of interparticle forces between normal and sickle cell samples at high concentration.     

Anorexic effects of ethanolamine-O-sulfate and muscimol in the rat: Evidence that GABA inhibits ingestive behavior

Intracisternal injections of ethanolamine-O-sulfate (EOS), an irreversible selective inhibitor of GABA-transaminase (GABA-T), resulted in relatively long lasting dose dependent decreases in food consumption and body weight of rats. The anorexic effects of EOS generally corresponded in both time course and magnitude to the elevation of GABA levels and associated decreases in GABA-T activity. Chronic treatment with very high intraperitoneal doses of EOS which were able to cross the blood-brain barrier elevated GABA levels and resulted in weight loss. Muscimol, a GABA receptor agonist also produced anorexia. These findings are consistent with the view that GABA may be involved in mediation of satiety in the rat.     

The isolation of ketocatechols from insect cuticle and their possible rôle in sclerotization

Several catechol-derivatives have been isolated from acid hydrolysates of insect hard cuticle, and the two major compounds were identified as a hydroxy-ketocatechol, 2-hydroxy-3′,4′-dihydroxyacetophenone, and the corresponding aldehyde, 3,4-dihydroxyphenylglyoxal. It is shown that the glyoxal is formed from the former compound during hydrolysis.     

Action of human cathepsin G on the oxidized B chain of insulin.

The specificity of cathepsin G, a serine neutral proteinase from human neutrophil leucotyes, was determine dby its action on the insulin B chain. The most susceptible bonds were Phe-24-Phe-25, Leu-15-Tyr-16 and Tyr-16-Leu-17. Other bonds hydrolysed were Leu-6-Cys(O3H)-7, Leu-11-Val-12, Leu-17-Val-18 and Phe-25-Tyr-26. These results suggest that the specificity of cathespin G is closer to that of pig chymotrypsin C than ox Chymotrypsin A. Tables listing amino acid composition, N-terminal residue, and yields of isolated peptides have been deposited as Supplementary Publication SUP 50 075 (8 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7B2, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1977) 161,1.     

Increased muricide and decreased avoidance and discrimination learning in thiamine deficient rats.

This study assessed the effects of diet-induced thiamine deficiency in rats on two aspects of behavior, aggression and learning. Evidence of enhanced aggression (increased mouse killing) was noted with severe thiamine deficiency, but before the onset of overt neurological signs of thiamine deprivation. This behavioral change was rapidly reversible with thiamine. A similar degree of thiamine deficiency failed to alter learning of two-way shuttle-box avoidance acquisition. Animals with a gross neurological deficit did exhibit a major impairment in shuttle-box performance, but this was probably due to ataxia. However, when such rats were administered thiamine with total reversal of the neurological signs, testing in a three chambered Y-maze avoidance-discrimination apparatus also revealed impaired learning of both responses. These data demonstrate the presence of enhanced aggression during thiamine deprivation and of a persistent learning impairment in rats following reversal of this vitamin deficiency.     

Avian erythrocyte development: microtubules and the formation of the disk shape

The development of avian erythrocytes involves a spheroid to discoid transformation in shape. The disk shape of the young erythroid cells is dependent on the presence of microtubules in a marginal bundle in the early stages of postmitotic maturation. Disassembly of microtubules with colchicine, vincristine, sulfate or cold temperature produces the spheroidal shape. Erythrocytes which have acquired the flattened ellipsoidal shape do not alter their shape with disassembly of the microtubules. The number of microtubules decreases as cell maturation occurs. The correlation coefficient for the number of microtubular profiles in one end of erythrocytes and the concentration of ribosomes (cell age) is 0.88. Microtubules of immature erythrocytes disappear more rapidly at 0°C than do microtubules of mature cells.It is concluded that microtubules play little or no role in the maintenance of mature red cell shape; however, they play an important role in the development of the flat discoid shape of avian erythrocytes during maturation.     

OPTIMIZED PARAMETERS FOR THE MITOTIC CYCLE

A method is described for the maximum likelihood estimation of the six parameters representing the means and standard deviations of the phases G₁, S and G₂ of the mitotic cycle. The likelihood is not explicitly formulated but is computed by the Monte Carlo program which evaluates the percentage of mitotic cells labelled with ³H-thymidine. The method is applied to data obtained from an experiment performed with transplanted Marshall rat mammary tumours.