Hepatic blood flow in acute myocardial ischemia

Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.     

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation

Summary L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G₁) and larger (G₂) DNA contents from the dominant S phase peak with intermediate DNA content.This work was supported by grant number 5P01CA13053 awarded by the National Cancer Institute, DHEW USA, and by grant num ber RBI 76-1 from the Queen Wilhelmina Fund, The Netherlands.     

Hh signaling in regeneration of the ischemic heart

Myocardial infarction (MI) is caused by the occlusion of a coronary artery due to underlying atherosclerosis complicated by localized thrombosis. The blockage of blood flow leads to cardiomyocyte (CM) death in the infarcted area. Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury; however, some pathways active during embryogenesis and silent during adult life are recruited in response to tissue injury. One such example is hedgehog (Hh) signaling. Hh is involved in the embryonic development of the heart and coronary vascular system. Pathological conditions including ischemia activate Hh signaling in adult tissues. This review highlights the involvement of Hh signaling in ischemic tissue regeneration with a particular emphasis on heart regeneration and discusses its potential role as a therapeutic agent.     

Influence of common bile duct cannula size on maximal secretory rate of taurocholate in the rat

Summary The common bile duct of male Sprague-Dawley rats was cannulated with either PE 10 or PE 50 tubing. Maximal secretory rate of taurocholate averaged 389±67 (SD) and 657±115 nmoles·min^–1·g liver^–1 in the PE 10 and PE 50 group, respectively (p<0.005). Maximal bile secretory pressure was significantly higher in the PE 10 group (240±28 vs 174±8 mm H20; p<0.005). When the maximal secretory rate was exceeded, bile flow decreased in both groups but this was accompanied with a decrease in maximal bile secretory pressure in the PE 10 group only. Maximal secretory rate of bile salts is markedly influenced by experimental technique. Use of small caliber common bile duct cannulae leads to partial obstruction and decreases the apparent maximal secretory rate for taurocholate.Acknowledgments. J. Reichen was the recipient of a Faculty Development Award in Clinical Pharmacology from The Pharmaceutical Manufacturer's Association Foundation, and is the recipient of a Research Career Development Award (KO4 AM 1189) from the National Institutes of Health. Supported by National Institutes of Health grant RO1 AM 27597.     

Cerebral ischemia is the main cause for the onset of heat stroke syndrome in rabbits

During the onset of heat stroke, rabbits displayed hyperthermia (42.8°C), and decreased cerebral perfusion pressure and decreased cerebral blood flow (as reflected by a prolonged cerebral circulation time) compared to those of normothermic rabbits. On the other hand febrile rabbits, during the fever plateau did not show the above responses, although they had a similar level of hyperthermia (42.4°C). The data support the concept that cerebral ischemia is the main cause for the onset of the heat stroke syndrome.The work reported here was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China).     

Vanadate: Non-selective inhibition of transepithelial transport of Na+, H+ and water

Summary In the isolated urinary bladder of the toad, 10^–5–10^–4M orthovanadate produces inhibition of the active transport of Na⁺ and H⁺ ions as well as of antidiuretic hormone-mediated osmotic flow of water. Since transport of H⁺ ions and osmotic water flow are not inhibited when (Na⁺+K⁺)-ATPase is inhibited by ouabain, biological actions of vanadate are not necessarily related to inhibition of (Na⁺+K⁺)-ATPase.This research was supported by grant AM-14915 from the National Institutes of Helath.     

Novel therapy for myocardial infarction: can HGF/Met be beneficial?

Myocardial infarction (MI) is a leading cause of hospitalization worldwide. A recently developed strategy to improve the management of MI is based on the use of growth factors which are able to enhance the intrinsic capacity of the heart to repair itself or regenerate after damage. Among others, hepatocyte growth factor (HGF) has been proposed as a modulator of cardiac repair of damage due to the pleiotropic effects elicited by Met receptor stimulation. In this review we describe the mechanistic basis for autocrine and paracrine protection of HGF in the injured heart. We also analyse the role of HGF/Met in stem cell maintenance and in stem cell therapies for MI. Finally, we summarize the most significant results on the use of HGF in experimental models of heart injury and discuss the potential of the molecule for treating ischaemic heart disease in humans.     

Labile protein-methyl ester: Comparison between chemically and enzymatically synthesized

Summary The rate of hydrolysis of protein-methyl ester, the enzymatic product of S-adenosylmethionine: proteincarboxyl methyltransferase (EC.2.1.1.24) acting on oxidized ribonuclease, was measured at pH 7.1 and 8.6 at 37°C. The half-life of the hydrolysis of the ester is 25 min at pH 7.1, and 4 min at 8.6. The rate of hydrolysis of the enzymatically formed esters at pH 7.0, in 0.1M phosphate buffer, was about 25 times faster than that of esters formed chemically by reaction with methanol in HCl. The lability of the enzymatically synthesized protein-methyl ester suggests that the esterification is specific to sites such that ionization of neighboring amino acid side chains enhances the rate of the hydrolysis.Acknowledgments. This work was supported by Research Grants AM 09603 from the National Institute of Arthritis and Metabolic Diseases, CA 10439 and CA 12226 from the National Cancer Institute, 1-P01-HD-05874 from the National Institute of Child Health and Human Development, National Institutes of Health, GM 20594-03 from National Institute of General Medical Sciences, USA.     

Ethanol-induced changes in plasma glucose,insulin and glucagon in fed and fasted rats

Summary Orally administered ethanol produced dose-related suppression of IRI levels and elevation of IRG levels in fed and fasting rats. Plasma glucose levels were unaffected in the fasting rats, but a moderate hyperglycemic response accompanied the decline in IRI and the rise in IRG observed in the fed rats.This research was supported in part by a grant from the National Institute on Alcohol Abuse and Alcoholism (AA-3218) and by a supplemental grant from the National Council on Alcoholism.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p<0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p<0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.To whom requests of reprints should be addressed.This work was supported by grants from the National Aeronautics and Space Administration (NSG 2183 and NAG-2-411), a grant from the National Institutes of Health (NIH Grant RR0811) and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR03020).     

Effects of retinoic acid on ascites cells of the TA3 mouse mammary carcinoma

Summary Retinoic acid caused a decrease in adhesiveness but no growth change in the allotransplantable TA3-Ha cell and no change in adhesiveness or growth in the strain specific TA3-St cell. The retinoic acid binding protein was detected in the TA3-Ha, but not the TA3-St, cell.This study was supported in pat by Public Health Service Grants CA-08418 and CA-18600 from the National Cancer Institute, National Institutes of Health. This is publication 955 of the Robert W. Lovett Group for the Study of Diseases Causing Deformities. We gratefully acknowledge the contributions of Drs Luigi M. De Luca and Anton M. Jetten of the Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD, without whose help this study would not have been possible.     

Tissue catecholamines following renal denervation in spontaneously hypertensive rats

Summary The delay in blood pressure increase observed in spontaneously hypertensive rats following bilateral renal denervation appeared to be due to a temporary reduction of the renal catecholamines content.This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (ATP 32-76-64, and AU 79-35) and from the Fonds National Suisse de la Recherche Scientifique (3.033.76)     

Isolation and structural elucidation of 3,6-dioxo-hexahydro-pyrrolo [1,2-a]-pyrazine from the echinodermLuidia clathrata

Zusammenfassung Es wird über die Isolierung und Charakterisierung der Titelverbindung (Gly-l-Pro Lactam, I) aus dem SeesternLuidia clathrata berichtet. Die Kristallstruktur dieses Dioxopiperazinderivats wurde ermittelt. Der Piperazinring liegt in der Wannen-Konformation vor.

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This investigation was supported by contract No. NIH-71-2308 from Chemotherapy, National Cancer Institute, National Institutes of Health and by Public Health Service Research Grant No. CA-11451-03 from the National Cancer Institute. The authors also gratefully acknowledge support from the National Science Foundation which provided the X-ray diffractometer and mass spectrometer. For the previous contribution of this series seeG. R. Pettit, R. H. Ode andT. B. Harvey, III, Lloydia,36 (1973).     

Partial sequence of the tyrosine region of neocarzinostatin

Zusammenfassung Das antitumoraktive Protein-Antibiotikum Neocarzinostatin wurde mit Dithiothreit in flüssigem Ammoniak reduziert und mit Chloressigsäure alkyliert. Tryptische Spaltung des tetra-S-carboxymethylierten Proteins ergab 5 Fragmente. Die Sequenz von 25 Aminosäureresten im tyrosinhaltigen Fragment H₃ wurde durchEdman-Abbau im automatisierten Sequenator ermittelt.

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This work was supported in part by Public Health Service Research Grants No. C-6516 from the National Cancer Institute and No. FR-05526 from the Division of Research Facilities and Resource, National Institutes of Health, to the Children's Cancer Research Foundation and by grants No. AM 04501 and No. AM 11794 from the National Institute of Arthritis and Metabolic Diseases to the Endocrine Unit, Massachusetts General Hospital.     

Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase

Summary The inhibitory activity of 19 flavonoid molecules on cyclic AMP breakdown by a commercial beef heart phosphodiesterase preparation is reported. 7 compounds are active in the micromolar range, 2 of which have a potency equivalent to that of papaverine. Some structure activity relationships are drawn.This investigation was partially supported by grants from the Centre National de la Recherche Scientifique (ATP 2315) and from the Institut National de la Santé et de la Recherche Médicale (CRL 75.1.188.5).     

Chloroperoxidase-catalyzed oxidation of N-methyl-4-chloroaniline

Summary Chloroperoxidase catalyzed the H₂O₂ oxidative conversion of N-methyl-4-chloroaniline to 4-chloronitrosobenzene, 4-chloroaniline and a mixture of complex products.This study was supported by grant No. CA 21992 from the National Cancer Institute, and by Research Career Development Award ES 00038 to M.D.C. from the National Institute of Environmental Health Sciences, DHEW.     

Liver esterase abnormalities in hereditary neurological diseases of mice

Zusammenfassung Alle von uns in Mäusen untersuchten vererblichen neurologischen Erkrankungen stellen entweder primäre oder sekundäre gesamtkörperliche Prozesse dar. Verschiedene allelische Substitutionen produzieren spezifische Leber-Esterase-Isozym-Defekte.

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This work was supported in part by NIH research grant No. NB 06448 from the National Institute of Neurological Diseases nad Stroke, a grant from the National Foundation for Neuromuscular Diseases, Inc., a grant from the Health Research Fund, United Fund of Schenectedy County, Inc., and an allocation from NIH General Research Support Grant No. RR 05545 from the Division of Research Resources to The Jackson Laboratory.

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The principles of laboratory animal care as promulgated by the National Society for Medical Research are observed in this Laboratory.     

Pre- and postreaction pH of two specifically interacting large-molecule systems

Zusammenfassung Diphtherietoxoide und Antitoxin einerseits, gruppen-spezifisches Pflanzenagglutinin und Blutgruppensubstanz anderseits, wurden auf verschiedenes pH gebracht und das erste und das zweite Paar gemischt, ohne dass eine pH-Änderung eintrat. Es wird eine Erklärung versucht.

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The work reported in this paper was made possible by support extended to Boston University by the National Science Foundation (G-1583) and by research grants (H-1076[C4] and RG 4104 M & G) from the National Heart Institute, National Institutes of Health, Public Health Service.     

Norzooanemonin in the hydroidTubularia larynx

Summary The hydrochloride of 1,3-dimethyl imidazole-4-carboxylic acid (norzooanemonin), has been isolated from the hydroidTubularia larynx and its structure determined by X-ray analysis.This investigation was supported by grant No. HD-04543 from the National Institutes of Child Health and Human Development. One of us (RLM) also wishes to thank the National Institutes of Health for a Career Development award No. HD-19931.     

An arachidonic acid-specific lipoxygenase from the gorgonian coralPseudoplexaura porosa

Summary A novel lipoxygenase was partially purified from the gorgonian coralPseudoplexaura porosa and was found to be specific for arachidonic acid. This soluble enzyme catalyzed the formation of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE) from arachidonic acid.This investigation was supported by PHS grant No. CA32395 awarded by the National Cancer Institute and by PHS Research Carreer Development Award No. ES00120 to MDC awarded by the National Institute of Environmental Health Sciences, DHHS. The authors acknowledge Ms M. A. Russell and Dr D. G. Anderson of the University of Miami for assistance in the collection of gorgonian corals. Preliminary work was conducted at the University of Miami School of Marine and Atmospheric Science. This is journal series No. 3638 from the Florida Agricultural Experiment Station.