Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.     

Electrophysiologic effects of halothane and quinidine on canine Purkinje fibers: evidence for a synergistic interaction

The authors studied possible interactions between halothane and quinidine on the action potentials of canine Purkinje fibers superfused with Tyrode's solution. Using standard microelectrode techniques and a physiologic pacing rate (2 Hz), halothane in concentrations from 0.5% to 2% decreased the action potential duration to 50% repolarization (ADP50). Total ADP (APD100), in contrast, increased after 1% and 2% halothane. Resting membrane potential (RMP) and action potential amplitude (APamp) increased after 0.5% halothane, but returned to control with higher halothane levels. Conduction time (CT) increased at each halothane level. Pacing at faster (3 Hz) or slower (1 Hz) rates did not markedly alter the effects of halothane. Quinidine 1 X 10(-5)M decreased the phase O upstroke (Vmax) and prolonged APD100 and CT. When halothane was added, RMP and APamp decreased, Vmax decreased further, and APD100 and CT were markedly prolonged. This resulted in conduction block or inexcitability, especially at faster pacing rates (3 Hz). Synergistic interactions between halothane and quinidine were found on RMP, APamp, APD100, and CT. Effects on Vmax, APD50, and action potential duration to 90% repolarization (APD90) were additive. It is concluded that quinidine and halothane act synergistically to decrease action potential amplitude, lower RMP, and prolong conduction. Severe depression of conduction often progressed to conduction block or inexcitability when halothane, 2%, was administered during superfusion with therapeutic concentrations of quinidine.     

Multiple regression analysis of twin data obtained from selected samples

The multiple regression analysis of twin data in which a cotwin's score is predicted from that of a proband (the member of a twin pair selected because of a deviant score) and the coefficient of relationship provides a powerful test of genetic etiology (DeFries and Fulker: Behav Genet 15:467-473, 1985). Moreover, when an augmented model containing an interaction term is fitted to the same data set, direct estimates of heritability (h2) and the proportion of variance owing to shared environmental influences (c2) are also obtained. In the present paper, the expected partial regression coefficients estimated from these models are derived, and the flexibility of the general approach is illustrated. An extended model is formulated for the analysis of data from combined samples of affected and control twin pairs that yields tests for differential h2 and c2 in the two groups as well as pooled estimates of these parameters. The application of these models is illustrated by an analysis of data from reading-disabled and control twin pairs. Because of the ease, flexibility, and utility of the multiple regression analysis of twin data, it is an appealing alternative to more traditional model-fitting approaches.     

Snoring: not funny--not hopeless

Snoring means obstructive breathing during sleep, and its most exaggerated form is obstructive sleep apnea. Mild snoring may respond to simple self-help remedies. Heavy snoring responds well to the surgical removal or reconstruction of obstructive elements in the hypopharynx, nasopharynx or nasal passages.     

Regulation of in vivo IgE biosynthesis in mice with complete Freund's adjuvant

Complete Freund's adjuvant (CFA) administered before sensitization dampened the normal and cyclophosphamide-enhanced response of high and moderate IgE responder phenotype mice (CAF1 and C57B1/6J, respectively). CFA-induced suppression of IgE biosynthesis was effective in reducing anaphylactic histamine release from approximately 2,900 ng histamine per milliliter to background levels (less than 100 ng/ml). CFA-induced ascites fluid was able to reduce the cyclophosphamide-enhanced IgE response of low-responder phenotype SJL mice from 1:320 to less than 1:5 as determined by passive cutaneous anaphylaxis. Muramyl dipeptide, a mycobacterial cell wall component capable of eliciting effects similar to those seen with CFA, was shown to induce suppression of IgE production if incorporated in incomplete Freund's adjuvant. Muramyl dipeptide administered in saline was ineffective, while incomplete Freund's adjuvant alone had some immunoregulatory properties. Ongoing IgE responses were less susceptible to regulation. CFA administered to sensitized C57B1/6J mice was ineffective in inducing IgE suppression when animals were challenged with antigen.