Role of the endogenous kallikrein-kinin system in modulating vasopressin-stimulated water flow and urea permeability in the toad urinary bladder.

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Abstract

This study investigates the endogenous kallikrein-kinin system's role as a modulator of vasopressin action in the toad urinary bladder. Kalli-krein inhibition by aprotinin, which results in decreased kinin production, significantly increased both vasopressin and 8-Br-cyclic (c) AMP-stimulated water flow. Kinin potentiation by the kininase II inhibitor captopril (SQ 14225) significantly decreased vasopressin and 8-Br-cAMP-stimulated water flow. In contrast to water flow, vasopressin-stimulated urea permeability was decreased by aprotinin and increased by captopril. We conclude that the endogenous kallikrein-kinin system represents a significant modulator of vasopressin action and it permits separate control of vasopressin-stimulated water flow and solute transport.

Authors

C P Carvounis, G Carvounis, L A Arbeit

Epidermal growth factor receptor number decreases during rat liver regeneration.

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Abstract

The potential role of epidermal growth factor (EGF) in the regulation of rat liver regeneration was examined by assessing the binding of 125I-EGF to hepatic membranes isolated at various times after partial hepatectomy. The results demonstrated a fall in 125I-EGF binding detectable as early as 8 h after partial hepatectomy. The nadir in EGF binding, less than 40% of that observed in sham-operated control rats, was seen 36 and 48 h after partial hepatectomy. Scatchard analysis showed that the decrease in binding capacity was due to a fall in receptor number. The specificity of the observed loss of EGF receptors was substantiated in parallel studies of 125I-insulin and 125I-wheat germ lectin binding; the binding of these ligands did not decrease appreciably during liver regeneration. The data are consistent with the hypothesis that EGF or a similar substance is one component of the complex humoral signal that regulates liver regeneration.

Authors

H S Earp, E J O'Keefe

Human platelet stimulation by acetyl glyceryl ether phosphorylcholine.

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Abstract

Acetyl glyceryl ether phosphorylcholine (AGEPC) induced dose-dependent platelet aggregation and release of [3H]serotonin and platelet factor 4 in citrated human platelet-rich plasma. ADP scavengers or indomethacin prevented irreversible platelet aggregation responses induced by 0.2 microM AGEPC but had no effect upon platelet secretion; prostacyclin inhibited AGEPC-induced aggregation and secretion. EDTA or EGTA inhibited AGEPC-induced aggregation but had no effect on platelet secretion.

Authors

L M McManus, D J Hanahan, R N Pinckard

Disruption of the Purine Nucleotide Cycle: A POTENTIAL EXPLANATION FOR MUSCLE DYSFUNCTION IN MYOADENYLATE DEAMINASE DEFICIENCY

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Abstract

A patient with symptoms of easy fatigability, postexercise myalgias, and delayed recovery of muscle strength after activity is described. Skeletal muscle from this patient had <1.0% normal myoadenylate deaminase activity and NH3 was not released from muscle after ischemic exercise. In association with this enzyme deficiency, exercise led to a >90% reduction in muscle content of adenine nucleotides. No inosine monophosphate accumulated after exercise and total purine content of the muscle fell to 21% of control. Repletion of the adenine nucleotide pool in this patient was delayed compared to controls, and ATP content had only returned to 68% of control at 165 min after exercise. These studies demonstrate that disruption of the purine nucleotide cycle as a consequence of myoadenylate deaminase deficiency results in marked alterations in ATP content of muscle, and potentially, these changes in ATP content could account for muscle dysfunction in this patient.

Authors

Richard L. Sabina, Judith L. Swain, Bernard M. Patten, Tetsuo Ashizawa, William E. O'Brien, Edward W. Holmes

Cellular Mechanisms for Increased Fetal Hemoglobin Production in Culture: EVIDENCE FOR CONTINUOUS COMMITMENT TO FETAL HEMOGLOBIN PRODUCTION DURING BURST FORMATION

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Abstract

Using microscopic immunodiffusion assays and microdensitometric analysis of pericellular immunoprecipitate, the percentage of nucleated erythrocytes containing fetal hemoglobin (FNRBC) and the mean picograms of fetal or adult hemoglobin per nucleated erythrocyte (picograms HbF/NRBC, picograms HbA/NRBC) were assayed in 14-d-old colonies (bursts) derived from peripheral blood erythroid progenitors. In the peripheral blood of 11 normal adults only 2.2±0.5% (mean±SE) erythrocytes contained HbF whereas pooled bursts from the same subjects revealed a 13-fold increase in the percentage of FNRBC (29.6±3.9%). In culture both the picograms HbF/NRBC (5.2±0.4) and the picograms HbA/NRBC (27.7±1.5) are increased ∼20% above the mean in vivo levels in NRBC from normal bone marrow aspirates. Analysis of each of 58 bursts from one subject demonstrated that FNRBC are present in all bursts and range from 5.0 to 95.0% of the total NRBC per burst. The percent FNRBC in each burst was neither correlated with picograms HbF/NRBC per burst nor with picograms HbA/NRBC per burst. Individual subcolonies from one burst in each of two subjects demonstrated between 3 and 81% FNRBC.

Authors

George J. Dover, Makio Ogawa

Antibody to the Rheumatoid Arthritis Nuclear Antigen: ITS RELATIONSHIP TO IN VIVO EPSTEIN-BARR VIRUS INFECTION

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Abstract

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.

Authors

Michael A. Catalano, Dennis A. Carson, James C. Niederman, Paul Feorino, John H. Vaughan

Rapid Thyroxine to 3,5,3′-Triiodothyronine Conversion and Nuclear 3,5,3′-Triiodothyronine Binding in Rat Cerebral Cortex and Cerebellum

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Abstract

Thyroxine (T4) to 3,5,3′-triiodothyronine (T3) conversion was evaluated in vivo in cerebral cortex, cerebellum, and anterior pituitary of male euthyroid Sprague-Dawley rats. Tracer quantities of 125I-T4 and 131I-T3 were injected into controls and iopanoic acid-pretreated rats 3 h before isolation of nuclei from these tissues. Specifically-bound nuclear 131I-T3, denoted T3(T3); 125I-T3, denoted T3(T4); and 125I-T4 were extracted and identified by chromatography. Plasma iodothyronines were similarly quantitated. In control rats, nuclear T3(T3) (percent dose per milligram DNA × 10−4) was 174±31 in cerebral cortex, 50±9 in cerebellum, and 932±158 in pituitary (all values, mean±SEM). Nuclear T3(T4) (percent dose per milligram DNA × 10−4) was 23.3±3.3 in cortex, 3.5±0.6 in cerebellum, and 39.4±6.9 in pituitary. Two-thirds of nuclear T3(T4) derived from local T4 to T3 conversion. Nuclear T3(T4) in all tissues was reduced to less than 15% of its control value by iopanoic acid treatment and all of the residual nuclear T3(T4) could be accounted for by plasma T3(T4). Nuclear T3(T3) binding was not inhibited by iopanoic acid. These results indicate there is rapid local T4 to T3 conversion in rat brain and nuclear binding of the T3 produced. We have previously found that local T3(T4) production is the source of ∼50% of the T3 in rat anterior pituitary. The present observations that the ratio of locally derived nuclear T3(T4) to nuclear T3(T3) is much higher in cerebral cortex (0.1) and cerebellum (0.04) than in anterior pituitary (0.015) suggest that this locally produced T3(T4) is the predominant source of intracellular T3 in these portions of rat brain.

Authors

F. R. Crantz, P. R. Larsen

Sustained Oscillations of Insulin, Glucagon, and Somatostatin from the Isolated Canine Pancreas during Exposure to a Constant Glucose Concentration

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Abstract

Canine pancreata were perfused in vitro to examine whether hormone cycles could be demonstrated without hepatic or central nervous influence. Insulin, glucagon, and somatostatin demonstrated regular sustained cyclic secretion from the in vitro canine pancreas. Oscillations were noted for over 200 min during the infusion of a constant glucose concentration. Insulin demonstrated a 10-min period with a range of 8-12 min/cycle. Somatostatin had a 10-min period with a range of 8-11 min. Glucagon had a period of 8.6 min with range of 6-10 min. These periods do not allow glucagon to be consistently 90° out of phase with insulin and somatostatin.

Authors

John I. Stagner, Ellis Samols, Gordon C. Weir

Dietary Modification of Thyroxine Deiodination in Rat Liver is Not Mediated by Hepatic Sulfhydryls

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Abstract

The enzymatic deiodination of thyroxine (T4) is thiol dependent. Fasting (72 h) depresses hepatic T4 deiodination and lowers the hepatic content of nonprotein sulfhydryls (NP-SH) and reduced glutathione (GSH). It has been proposed that the fasting effect may be mediated through these alterations in hepatic sulfhydryls. To test the importance of tissue (hepatic) thiol content in the modification of T4 deiodination consequent to dietary manipulation, we examined the sequential deiodination of T4 to 3,5,3′-triiodothyronine (T3) (5′-deiodination) and 3,3′,5-triiodothyronine (reverse T3, rT3) (5-deiodination) in liver homogenates without added thiol from groups of rats fed Purina lab chow (P) (a protein-rich diet), glucose alone (G), or glucose plus cysteine (Gc) for 72 h or fasted (F) for the same period. The initial rate of each reaction was compared to the tissue concentrations of NP-SH and GSH.

Authors

Laurence A. Gavin, Francis A. McMahon, M. Moeller

Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification

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Abstract

The pathogenesis of valvar calcification, which complicates the course of cardiac valve disease and also affects tissue valve prostheses, is incompletely understood. The present work explores the possible role of the vitamin K-dependent, calcium-binding amino acid, γ-carboxyglutamic acid (Gla) in valve mineralization. Gla is normally found in the vitamin K-dependent clotting factor proteins, and is also present in unique calcium binding proteins in bone, kidney, and lung. Unique Gla-containing proteins have also been isolated from pathologic calcifications including calcium containing renal stones and calcified atherosclerotic plaque. Calcified valves including specimens with calcific aortic stenosis, calcified porcine xenograft valves, and a calcified aortic homograft valve were analyzed for Gla content, complete amino acid analysis, and tissue calcium and phosphorus levels. Normal porcine valves contained protein-bound Gla (2.0-10.6 Gla/104 amino acids): no Gla was present in normal valve leaflets. Furthermore, Gla levels paralleled tissue calcium content in the calcified valves. In addition, complete amino acid analysis indicated a decline in valvar collagen content plus increased acidic proteins in conjunction with valvar calcification and the presence of Gla-containing proteins. These results suggest that calcific valvar disease may result in part from vitamin K-dependent processes.

Authors

Robert J. Levy, John A. Zenker, Jane B. Lian