Glia maturation factor influences recovery from injury in neonatal rat brains

Newborn rats were injured with a puncture wound in one cerebral hemisphere. Experimental animals were treated with three i.p. injections of Glia Maturation Factor (GMF) at daily intervals starting from the time of injury, whereas control littermates were treated with equivalent amounts of bovine serum albumin. At 25 days old the size of the cerebral cortex at the plane of injury was measured on representative brain sections. In control rats the injured side was 18% smaller than the normal side whereas in GMF-treated animals the difference was only 1%. The results suggest a possible regulatory role of GMF in promoting tissue recovery from brain damage.     

Altered brain cholinergic enzymes activity in the genetically obese rat

Summary Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals and a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system.This work was supported by a grant from the National Aeronautics and Space Administration (NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811), and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR 03020).     

Intercellular junctions of hyperplastic retinal pigment epithelium

Summary In rats with retinopathies induced by excess fluorescent light or injections of urethane, the retinal pigment epithelium (RPE) undergoes focal hyperplasia. Neither intravascularly injected horseradish peroxidase or lanthanum nitrate penetrated the sensory retina at these hyperplastic sites. Electron microscopy revealed that this was due to the persistence of intact, tight junctions among a single layer of hyperplastic cells facing the sensory retina. These junctions prevented intraocularly injected microperoxidase from passing as well. Cells within the hyperplastic foci were connected only by adherent junctions that presented no permeability barrier.Supported by a grant from the National Eye Institute to Dr R. Bellhorn, whose support is greatly appreciated, and an unrestricted grant and a Research Manpower Award from Research to Prevent Blindness, Inc.     

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.     

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).     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Epstein-barr virus and inflammatory bowel disease

Zusammenfassung Die Häufigkeit und der Antikörpertiter gegen Epstein-Barr-Virus (EBV) wurde in Patienten mit Ulkus-Colitis und Crohn's Krankheit, eine granulomatische Abnormalität ähnlich zur Sarkoidose untersucht und normale Häufigkeit und Antikörpertiter gegen EBV bei ihnen gefunden.

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Supported by Research Contract No. NIH-69-2078 within the Special Virus Cancer Program of the National Cancer Institute, National Institutes of Health, USPHS, National Institutes of Health Grant No. AM 05126 and the National Foundation for Ileitis and Colitis, Inc., New York, New York.

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Dr.Grotsky is a recipient of a National Institutes of Health Graduate Training Grant in Gastroenterology, No. Am 05126.

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Dr.Hirshaut is a recipient of a National Cancer Institute Grant No. CA 08748 an a grant from the New York Cancer Research Institute.

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Dr.Glade is a recipient of a Research Career Development Award No. A1-46371 of the USPHS.     

Pituitary response to gonadotropin-releasing hormone in diabetic male rats

Summary The rise in serum luteinizing hormone concentration after treatment with gonadotropin-releasing hormone was less in diabetic castrated male rats than control castrates. In intact male rats, gonadotropin-releasing hormone treatment resulted in higher serum luteinizing hormone concentrations in diabetic than in control rats.Acknowledgments. This work was supported in part by a grant from the Medical Research Council of Canada. The authors are grateful to Dr G.D. Niswender, Dr L.E. Reichert, Jr. and the National Institute of Arthritis, Metabolism and Digestive Diseases, Rat Pituitary Hormone Program for providing radioimmunoassay materials. The streptozotocin was kindly provided by Dr W.E. Dulin, The Upjohn Company. D.B. Beaton and J. Brunka provided excellent technical assistance.     

The mitigating effect of dietary antioxidants on chemically-induced carcinogenesis

Summary The effect of a dietary antioxidant mixture on 3-methylcholanthrene mediated carcinogenesis in hairless mice was investigated. The antioxidant mixture significantly reduced the frequency of premalignant lesions and their subsequent development into tumors. The similarities in response of chemical and UV light-carcinogenesis to these antioxidants suggest some congruity in the mechanisms of the carcinogenic process.This investigation was supported by National Research Service Award 1 F32 CA05062, awarded by the National Cancer Institute, DHEW and USPH grant CA13464 from the NCI, DHEW. We thank Dr John I. Thornby for statistical analysis of the data.     

Effect of diabetes on the vertebral column of rats and its modification by estradiol

Summary In vertebrae of genetically selected sucrose-fed diabetic rats a statistically significant bone deficit was found after diabetes had been present for about 8 months. No osteopenia was observed in diabetic rats following treatment with estrogenic hormone for 5–7 months. The development of osseous centers in the end plates of the vertebrae was retarded in diabetic rats, but was about normal in diabetic rats given estrogen.—No differences were noted in the growth zones or in the tendency to develop articular lesions in rats of the various groups. Possible differences in the amount of GAG in intervertebral discs of diabetic and non-diabetic rats respectively await further confirmation.These investigations were aided by grant No. 2 RO1 EYO 1837-03, of the Institute of Arthritis and Metabolic Disease, National Institutes of Health, Bethesda, Maryland, USA.We are indebted to Professor Dr J. Rüttner, Institute of Pathology, University of Zürich, for his permission to use the calculator.     

Effect of starvation and refeeding on catalase and superoxide dismutase activities in skeletal and cardiac muscles from 12-month-old rats

Summary Catalase and superoxide dismutase (SOD) activities were determined in muscles from 12-month-old rats after severe starvation and after subsequent refeeding. Catalase increased in most muscles after starvation and decreased after refeeding, while SOD remained unchanged.This research was supported by the Science and Education Administration of the U.S. Department of Agriculture under grant No. 5901-0410-8-0014-0 from the Competitive Grants Office. We thank Dr Craig Frisk for advice in the care of the animals.Scientific Journal Series No. 11, 191, Minnesota Agricultural Experiment Station.     

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.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

Summary The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

The effect of postnatal undernourishment on epileptiform kindling of dorsal hippocampus

Summary Rats were undernourished postnatally from birth through 20 days of age. They were subsequently tested for susceptibility to motor seizures kindled in hippocampus in adulthood. Compared to littermate control animals the postnatally undernourished rats were more susceptible to the kindling treatment. We conclude that early postnatal undernourishment has a permanent effect on susceptibility of the hippocampus to electrically-induced seizures.This work was supported by Public Health Service grant NS 13799, National Science Foundation grant GB 35532, and by Hoffman-LaRoche, Inc.     

Methadone and brain development

Summary The effect of maternally administered methadone hydrochloride (5 mg/kg) on brain development of off-spring treated during gestation and/or lactation was studied in 21-day-old rats. Animals treated during gestation or lactation were the most severely affected, with reductions in brain weights (12% and 30%,respectively), and DNA values (50% and 34%, respectively) observed.The assistance of Eileen J. Zagon is gratefully acknowledged. This research was supported in part by American Cancer Society grant PDT-27B and NIDP grant DA01618-01.     

The generality of the nitroso-glyoxylate reaction: Conversion ofp-nitronitrosobenzene to the hydroxamic acid

Summary The reaction of glyoxylic acid withp-nitronitrosobenzene (1b) in dilute aqueous solution gave the hydroxamic acid (2b) as the major detectable product. The significance of this observation with respect to the title reaction is discussed.This study was supported by grant No. CA 32395 from the National Cancer Institute, and by Research Career Development Award ES 00120 from the National Institute of Environmental Health Sciences, DHHS.     

Influence of 2-methyl-2-(p-1,2,3,4-tetrahydro-1-naphthylphenoxy)propionic acid on the oxidation of cholesterol by rat liver mitochondria

Zusammenfassung Es wird gezeigt, dass bei männlichen Wistar-Ratten im 3-Wochen-Diätexperiment mit Zusatz von 0,3% 2-Methyl-2-(p-1,2,3,4-Tetrahydro-1-naphthylphenoxy)-Propionsäure (Su-13437) die Oxydation von 26-¹⁴C-Cholesterin zu¹⁴CO₂ durch Lebermitochondrien (bezogen auf mg/N) ähnlich wie bei den Kontrollen war. Bei den Versuchstieren war jedoch bei Abwesenheit von Cytosol im System die Oxydation durch Lebermitochondrien erhöht.

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Acknowledgment. This work was supported, in part, by a grant No. HE-03299 and a Research Career Award No. 4-K6-HE-0734 from the National Heart Institute, N.I.H. We are indebted to Dr. W. I.Taylor, CIBA Pharmaceutical Co., Summit, N.J., for the generous gift of Su-13,437.     

Freeze tolerance in the frog,Rana sylvatica

Summary Wood frogs survive extracellular freezing at moderate subzero temperatures (–4°C) for at least 11 days. Freezing survival is aided by the accumulation of high concentrations of glucose as a cryoprotectant in blood and tissues. Glucose production was accompanied by a rapid decline in liver, but not muscle, glycogen levels suggesting that liver is the organ controlling cryoprotectant synthesis.Acknowledgments. This study was supported by grants to L.M.G. from the Kroc Foundation (Santa Ynez, California) and from the National Institute of Dental Research (Grant No. DE-03987). The authors wish to thank K. Yorko, M. Shakin, J. Finan and Mrs N. Manivannan for their technical and secretarial assistance.Acknowledgments. I thank Dr J. Ballantyne, Dr F. Schueler and I. McMurray for help with frog collections and Dr. W. Schmid, Dr J. Bogart and Dr F. Cook for helpful discussions. Supported by an N.S.E.R.C. operating grant and by a grant from the Atkinson Charitable Foundation.     

Effect of pectin and cellulose on formation and regression of gallstones in hamsters

Summary Male Syrian hamsters were fed a lithogenic diet containing 7% cellulose or 4.2% pectin. After 50 days, pectin was 76% and cellulose 64% less lithogenic than the control diet. Hamsters fed the control diet for 50 days were maintained on that diet for another 50 days or fed diets containing cellulose or pectin. These was a 52% increase in gallstone incidence in hamsters continued on the control diet and a 9% increase in those on cellulose. Pectin promoted regression of gallstones (by 52%).Acknowledgments. This work was supported, in part, by a grant (HL-03299) and a Research Career Award (HL-00734) from the National Institutes of Health, and by funds from Mary L. Smith and the Commonwealth of Pennsylvania.     

Hematocrit as an index of changes in plasma volume in conscious dogs

Summary Hematocrit (HCT) measurements were made in intact and splenectomized conscious dogs to determine if observed decreases in HCT were produced by plasma volume expansion or splenic sequestration of erythrocytes. We found that in conscious dogs HCT is a poor indicator of changes in plasma volume.Supported by National Institutes of Health grant No. HL 13427.I.Z. ist the recipient of an Established Investigator Award from the American Heart Association.Acknowledgment. The authors wish to thank Mary Anne Richards for her technical assistance.