Intracellular restraint: a new basis for the limitation in response to oxidative stress in human erythrocytes containing low-activity variants of glucose-6-phosphate dehydrogenase. Several mechanisms recently proposed for regulation of the hexose monophosphate shunt require the concentration of NADP to be low or that of NADPH to be high. The present study indicates that the first enzyme of the hexose monophosphate shunt of human erythrocytes is under severe restraint even when these conditions do not exist. In human erythrocytes containing low-activity variants of this enzyme, glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP(+) 1-oxidoreductase; EC 1.1.1.49), measurements of the rate of oxidation of C-1 labeled glucose show that the enzyme is operating at a rate much closer to its maximum than in normal cells. This requires that the ratio of inhibitory NADPH to NADP be much lower in the variant cells than in normal cells. A small increase in oxidative rate, induced by naphthol, then causes a disappearance in reduced glutathione in the variant cells, presumably because a significant further decrease in NADPH occurs in these cells, whereas the same oxidative stress in normal cells would not lower the NADPH level appreciably. A low NADPH/NADP ratio in unstressed cells deficient in glucose-6-phosphate dehydrogenase is confirmed by direct measurement. The maximum activity of the variant enzyme in the cell, as measured with methylene blue to keep most of the NADP in the oxidized form, is only about 1/60 of that found in hemolysates, thus accounting for the failure to compensate for a relatively small oxidative stress in vivo in spite of an apparent sufficiency of enzyme. The reason for the limitation on maximum intracellular activity is unknown. A similar limitation is seen with normal cells incubated with methylene blue, where the maximum intracellular rate is also only about 1/60 of that found in hemolysates.


Studies on bile secretion with the aid of the isolated perfused rat liver. I. Inhibitory action of sporidesmin and icterogenin.


Nutrition of algal-invertebrate symbiosis. I. Utilization of soluble organic nutrients by symbiont-free hosts.


The sphincter pupillae of the guinea-pig: structure of muscle cells, intercellular relations and density of innervation.


Dimorphism of ureides. alpha-Bromisovalerylurea (bromisoval) and alpha-bromdiaethylacetylcarbamide (carbromal).


Orchidectomy and the immune response. III. The effect of orchidectomy on tumour induction and transplantation in mice.


Mechanisms and evolutionary origins of variable X-chromosome activity in mammals.


Rates of dispersal of Drosophila pseudoobscura and its relatives.


Evidence that ATP is hydrolysed in a one-step reaction of the sodium pump.


Hormonal modulation of circadian neural activity in Carcinus maenas (L.).


On the structure and innervation of the muscle bands of Doliolum (Tunicata: Cyclomyaria).


Suppression of contact sensitivity by T cells in the mouse. I. Demonstration that suppressor cells act on the effector stage of contact sensitivity; and their induction following in vitro exposure to antigen.


Tapeta lucida in the eyes of goatsuckers (Caprimulgidae).


The internal structure of the chromaffin granule.


Electrogenic sodium pump in mouse liver parenchymal cells.


Alopecia areata, vitiligo, scleroderma and ulcerative colitis.


On the functional morphology of the family Verticortiidae (Bivalvia) with descriptions of new species from the abyssal Atlantic.


Further observations on the spasmogenic activity of caerulein on the rat pylorus.


On the reversal by (plus) and (minus)-propranolol of irreversible alpha-adrenoceptor blockade in rabbit aorta.


Modes of activation of motoneurons controlling ventilatory movements of the locust abdomen.


The organization of inputs to motoneurons of the locust metathoracic leg.


Synapses upon motoneurons of locusts during retrograde degeneration.


Implantation, foetal membranes and early placentation of the African elephant, Loxodonta africana.


Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment.


Proceedings: Dose effects of stimulants in hyperkinetic children.


Proceedings: The nature of the interaction between melanin and drugs.


Proceedings: Drugs, neurotransmitters, and psychosis.


Proceedings: Drug toxicity as related to ocular melanin.


Proceedings: Phenothiazine drugs and melanin synthesis.


Proceedings: Metabolic adaptation to antidepressant drugs--a neurochemical paradox.


Proceedings: Neuroendocrine transducers: brain monoamines and the control of hypothalamo-pituitary function.


Proceedings: Putative neurotransmitters involved in discharging gonadotropin releasing factors and the action of these neurohormones on the central nervous system.


Identifying future alcoholics with MMPI alcoholism scales.


Differences in the modulation of cardiac activity between psychopaths and normal controls.


Competitive radioprotection and radiosensitization in chemical systems.


Free fatty acid mobilization during suggestion of exercise and stress using hypnosis and sodium amytal.


Production of glutamine synthetase by Proteus mirabilis in short time periods.


The experimental imperative: laboratory analyses of aggressive behaviors.


The effect of mesuprine HC1 on selected smooth muscles.


Microsomal (muS) chemiluminescence (CL) induced by NADPH and its relation to aryl-hydroxylations.


Regulation of thiols in the brain. 3. Glucose metabolism in the cytoplasmic fraction of rat brain during stimulation of the hexose monophosphate shunt in vitro.


Interaction of cholinergic function with mg2 plus-na plus-k plus-dependent ATP-ase system of cells in the human fundic gastric mucosa.


Beta-adrenergic receptor: stereospecific interaction of iodinated beta-blocking agent with high affinity site. An iodine-labeled beta-adrenergic inhibitor ((125)l-hydroxybenzylpindolol) binds specifically to a site on turkey erythrocyte membranes. A series of beta-adrenergic agonists and inhibitors compete for this binding site, with apparent affinities paralleling biological effectiveness as activators or inhibitors of catecholaminestimulated adenylate cyclase. The activity of d-(+) agonists or inhibitors was 1 percent (or less) than that of the corresponding l-(-) isomers in competing for binding of the iodinated blocker as well as in affecting catecholamine-stimulated adenylate cyclase. 1-(-)-Norepinephrine was about one-tenth as active as l-(-)-isoproterenol in competing for the beta-blocking agent site. The stereospecificity of the interaction with the iodinated beta-blocking agent and the correspondence between affinity for site and biological potency of analogs suggested that this interaction is involved in function of the beta-adrenergic receptor.


The transplantation milieu, St. Luke's Episcopal Hospital, 1968-1969.


The living, genetically unrelated, kidney donor.


Psychiatric side effects of nonpsychiatric drugs.


Depressions following reserpine: a reevaluation.


Uses and toxicity of belladonna alkaloids and synthetic anticholinergics.


Population changes in antigen-binding and antibody-secreting cells in the course of the immune response.


Genetic fine structure of the H-2 gene complex.


Purulent pericarditis in South Vietnam: report of 16 cases.


Rapid identification of pills, capsules, and other forms of drugs.


Japanese encephalitis vectors: isolation of virus from culicine mosquitoes in the Saigon area.


Lankesteria, a gregarine protozoan, previously unreported in mosquitoes of Malaysia.


Does regenerative capacity decrease with age?


Pharmacology and toxicology of metiamide, a histamine H2-receptor antagonist.


Influence of pharmacological agents on the growth of processes of spinal ganglion nerve cells in culture.


Acquired immunologic deficiencies after trauma and surgical procedures.


Fetal thymus glands obtained from prostaglandin-induced abortions. Cellular immune function in vitro and evidence of in vivo thymocyte activity following transplantation.


Cystometry.

Cystometry.


Cryptorchidism. A pediatric review.

Cryptorchidism. A pediatric review.


Management of testicular tumors in children.


Biochemical and biophysical properties of two strains of mosquito iridescent virus.


Metabolic interconversions and binding of imipramine, imipramine-N-oxide, and desmethylimipramine in rat liver slices.


Editorial: An open letter to a committee searching for a chairman of a department of medicine.


The enzymic formation of methylenedioxyphenyl derivative exhibiting an isocyanide-like spectrum with reduced cytochrome P-450 in hepatic microsomes.


Metabolism of prolintane in rats and the effect of prolintane metabolites on general activities in mice.


An improved coupled test procedure for glutathione peroxidase (EC 1-11-1-9-) in blood.


The application of the serum gamma-glutamyl transpeptidase and the 5'-nucleotidase assay in cancer patients: a comparative study.


The effect of temperature on enzyme activity and on the affinity of enzymes to their substrates.


Autochthonous grafts of spontaneous mammary tumors implanted together with allogeneic tissues.


The determinants of microbial pathogenicity.


A role for cell-mediated immunity in the pathogenesis of periodontal disease.


The non-operative removal of retained common duct stones after biliary surgery.


Methoxyflurane and lipid and carbohydrate metabolism in rats.


Neuro-humoral concepts of bronchial asthma.


Effects of some drugs applied topically to the nasal mucosa before nasal provocation tests with allergen.


Graft-versus-host reactions mediated by a thymus-bone marrow combination, spleen cells, and lymph node cells from amyloidotic and nonamyloidotic mice.


Effects of prolonged treatment with adrenergic beta-receptor antagonists on blood pressure, cardiovascular design and reactivity in spontaneously hypertensive rats (SHR).


The functional pattern of the cadaveric kidney in the early posttransplant period.


The relationship of social and personality characteristics to hallucinogen use among college females.


Postflight analysis of Bacillus thuringiensis organisms exposed to spaceflight conditions on Apollo 16.


Basic concepts of psychopharmacological research as applied to the psychopharmacological analysis of the amygdala. Since the neural impulses in the brain are transmitted from one neuron to the next by various chemical mediators such as noradrenaline, dopamine, serotonin, acetylcholine, etc., the use of drugs acting specifically on one or more of these mediators should illucidate the chemical substrates of behavior. However, recent data indicating an extensive interaction between the various neurotransmitters on a cellular and even synaptic level, suggests that interpreting the behavioral effects of drugs in term of only one neurotransmitter is a potentially misleading oversimplification. Perhaps, rather than the action of a single neurotransmitter, it is the balance between neurotransmitter systems that determines behavior. Because of its rich innervation by noradrenaline, dopamine, serotonin and acetylcholine synapses, the amygdala is ideally suited for monitoring the balance between these neurotransmitters and altering maladaptive behavior based on fluctuations in neurotransmitter balance.


Dental development and trauma.

Dental development and trauma.


Three cases of pneumococcal bacteriuria.


Rational use of psychotropic drugs II. Antianxiety agents.


Histamine H2 receptor antagonists.

Histamine H2 receptor antagonists.


The effect of scopolamine on fetal heart rate baseline variability.


Cyclic nucleotides.

Cyclic nucleotides.


Metabolic studies on heart of unweaned rabbits infected with foot-and mouth disease virus.


Physician's assistants and clinical algorithms in health care delivery. A case study.


Interaction of Na, K-ATPase with chlorpromazine free radical and related compounds.


Red cell glucose-6-phosphate dehydrogenase deficiency in Finland. Further biochemical characterization of G-6-PD Helsinki.


Histochemistry of primate laryngeal muscles.


Localization of the reaction site of cytochrome 552 in chloroplasts from Euglena gracilis. Cytochrome content and photooxidation in different chloroplast preparations.


Controlled emergence from anesthesia using the closed-circle system.


Fluroxene toxicity in dogs: possible mechanisms.


Localization of the reaction site of cytochrome 552 in chloroplasts from Euglena gracilis. Effects of a specific antibody on endogenous, external and reincorporated cytochrome 552 in chloroplast membranes.


Irreversible inactivation of rat liver tyrosine aminotransferase.


Induction of tyrosine aminotransferase by Sepharose-insulin.


Mechanism of allylisopropylacetamide-induced increase of delta-aminolevulinate synthetase in liver mitochondria. Effects of administration of glucose, cyclic AMP, and some hormones related to glucose metabolism.


Health care delivery in Cummins Engine Company.


Detection of bacteremia by an automated radiometric method and a tubed broth method.


Isoenzymes of creatine kinase; separation by acrylamide gel electrophoresis.


Effects of diazepam on cell division rates and productivity of Scenedesmus obliquus in Synchronous cultures.


Biochemical abnormalities in Reye's syndrome.


Higher education in nursing.

Higher education in nursing.


Beta-adrenergic blocking drugs.

Beta-adrenergic blocking drugs.


Effect of acute exposure to carbon disulfide vapour upon some components of the hepatic-microsomal enzyme system in rats.


Seizure inhibition and REM sleep: a possible neurohumoral relationship.


Subjective ratings of credibility following brief exposure to desensitization and pseudotherapy.


Metabolic adaptations during lactogenesis. Fatty acid synthesis in rabbit mammary tissue during pregnancy and lactation. 1. Mammary tissue was obtained from rabbits at various stages of pregnancy and lactation and used for tissue-slice incubations (to measure the rate of fatty acid synthesis and CO(2) production) and to determine relevant enzymic activities. A biphasic adaptation in fatty acid synthetic capacity during lactogenesis was noted. 2. The first lactogenic response occurred between day 15 and 24 of pregnancy. Over this period fatty acid synthesis (from acetate) increased 14-fold and the proportions of fatty acids synthesized changed to those characteristic of milk fat (77-86% as C(8:0)+C(10:0) acids). 3. The second lactogenic response occurred post partum as indicated by increased rates of fatty acid synthesis and CO(2) production (from acetate and glucose) and increased enzymic activities. 4. Major increases in enzymic activities between mid-pregnancy and lactation were noted for ATP citrate lyase (EC 4.1.3.8), acetyl-CoA synthetase (EC 6.2.1.1), acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthetase, glucose 6-phosphate dehydrogenase (EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (EC 1.1.1.44). Smaller increases in activity occurred with glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) and NADP(+)-isocitrate dehydrogenase (EC 1.1.1.42) and the activity of NADP(+)-malate dehydrogenase (EC 1.1.1.40) was negligible at all periods tested. 5. During pregnancy and lactation there was a close temporal relationship between fatty acid synthetic capacity and the activities of ATP citrate lyase (r=0.94) and acetyl-CoA carboxylase (r=0.90).


Regulation of the pentose phosphate cycle. 1. A search was made for mechanisms which may exert a ;fine' control of the glucose 6-phosphate dehydrogenase reaction in rat liver, the rate-limiting step of the oxidative pentose phosphate cycle. 2. The glucose 6-phosphate dehydrogenase reaction is expected to go virtually to completion because the primary product (6-phosphogluconate lactone) is rapidly hydrolysed and the equilibrium of the joint dehydrogenase and lactonase reactions is in favour of virtually complete formation of phosphogluconate. However, the reaction does not go to completion, because glucose 6-phosphate dehydrogenase is inhibited by NADPH (Neglein & Haas, 1935). 3. Measurements of the inhibition (which is competitive with NADP(+)) show that at physiological concentrations of free NADP(+) and free NADPH the enzyme is almost completely inhibited. This indicates that the regulation of the enzyme activity is a matter of de-inhibition. 4. Among over 100 cell constituents tested only GSSG and AMP counteracted the inhibition by NADPH; only GSSG was highly effective at concentrations that may be taken to occur physiologically. 5. The effect of GSSG was not due to the GSSG reductase activity of liver extracts, because under the test conditions the activity of this enzyme was very weak, and complete inhibition of the reductase by Zn(2+) did not abolish the GSSG effect. 6. Preincubation of the enzyme preparation with GSSG in the presence of Mg(2+) and NADP(+) before the addition of glucose 6-phosphate and NADPH much increased the GSSG effect. 7. Dialysis of liver extracts and purification of glucose 6-phosphate dehydrogenase abolished the GSSG effect, indicating the participation of a cofactor in the action of GSSG. 8. The cofactor removed by dialysis or purification is very unstable. The cofactor could be separated from glucose 6-phosphate dehydrogenase by ultrafiltration of liver homogenates. Some properties of the cofactor are described. 9. The hypothesis that GSSG exerts a fine control of the pentose phosphate cycle by counteracting the NADPH inhibition of glucose 6-phosphate dehydrogenase is discussed.


Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride. 1. The time-course of the changes in the concentrations of hepatic metabolites in response to a non-toxic load of NH(4)Cl were measured in fed and starved rats. 2. There was a rapid increase (after 2min) in [alanine] and [aspartate] which remained high for 10-15min; the absolute increase in [alanine] was smaller in starved rats. 3. These changes were accompanied by a decrease in [oxoglutarate] and in the [3-hydroxybutyrate]/[acetoacetate] ratio. 4. Prior administration of l-arginine to fed rats resulted in smaller increases in [alanine] and [aspartate] after the ammonia load. This is presumably due to stimulation of the urea cycle. 5. Increased formation of alanine in starved rats occurred after prior administration of dihydroxyacetone to increase the availability of pyruvate. 6. Administration of l-cycloserine, an inhibitor of glutamate-alanine aminotransferase, completely prevented the increase in [alanine] after the ammonia load; in this case the absolute increase in [aspartate] was higher. 7. [Oxoglutarate], [citrate] and [isocitrate] at 25min after the ammonia load were higher than the initial concentrations, but returned to normal by 50min. It is suggested that this ;overshoot' may be due to temporary compartmentation of oxoglutarate. 8. The mechanisms and physiological significance of alanine and aspartate formation in these experiments are discussed.


Clinical experience with pipothiazine palmitate (19552 R.P.) in hospitalized and open ward patients with functional psychoses.


The partial characterization of purified nitrite reductase and hydroxylamine oxidase from Nitrosomonas europaea. Nitrite reductase has been separated from cell-free extracts of Nitrosomonas and partially purified from hydroxylamine oxidase by polyacrylamide-gel electrophoresis. In its oxidized state the enzyme, which did not contain haem, had an extinction maximum at 590nm, which was abolished on reduction. Sodium diethyldithiocarbamate was a potent inhibitor of nitrite reductase. Enzyme activity was stimulated 2.5-fold when remixed with hydroxylamine oxidase, but was unaffected by mammalian cytochrome c. The enzyme also exhibited a low hydroxylamine-dependent nitrite reductase activity. The results suggest that this enzyme is similar to the copper-containing ;denitrifying enzyme' of Pseudomonas denitrificans. A dithionite-reduced, 465nm-absorbing haemoprotein was associated with homogeneous preparations of hydroxylamine oxidase. The band at 465nm maximum was not reduced during the oxidation of hydroxylamine although the extinction was abolished on addition of hydroxylamine, NO(2) (-) or CO. These last-named compounds when added to the oxidized enzyme precluded the appearance of the 465nm-absorption band on addition of dithionite. Several properties of 465nm-absorbing haemoprotein are described.


Pyridine nucleotide transhydrogenase activity of soluble cardiac NADH dehydrogenase and particulate NADH-ubiquinone reductase.


The superoxide anion and singlet molecular oxygen: their role in the microbicidal activity of the polymorphonuclear leukocyte.


Simulation of the pentose cycle in lactating rat mammary gland. A computer model representing the pentose cycle, the tricarboxylic acid cycle and glycolysis in slices of lactating rat mammary glands has been constructed. This model is based primarily on the studies, with radioactive chemicals, of Abraham & Chaikoff (1959) [although some of the discrepant data of Katz & Wals (1972) could be accommodated by changing one enzyme activity]. Data obtained by using [1-(14)C]-, [6-(14)C]- and [3,4-(14)C]-glucose were simulated, as well as data obtained by using unlabelled glucose (for which some new experimental data are presented). Much past work on the pentose cycle has been mainly concerned with the division of glucose flow between the pentose cycle and glycolysis, and has relied on the assumption that the system is in steady state (both labelled and unlabelled). This assumption may not apply to lactating rat mammary glands, since the model shows that the percentage flow through the shunt progressively decreased for the first 2h of a 3h experiment, and we were unable to construct a completely steady-state model. The model allows examination of many quantitative features of the system, especially the amount of material passing through key enzymes, some of which appear to be regulated by NADP(+) concentrations as proposed by McLean (1960). Supplementary information for this paper has been deposited as Supplementary Publication SUP 50023 at the British Museum (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.


Human erythrocyte glucose 6-phosphate dehydrogenase. Interaction with oxidized and reduced coenzyme.


Abuse of psychopharmacological drugs--experiences in Norway.


Interactions of alpha-methylfluorene-2-acetic acid with adenylate cyclase.


Pharmacological inhibition of hormonal tyrosine amino transferase induction.


Relationship between reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation and drug hydroxylation in rat liver microsomes.


Protective effect of adenosine and nicotinamide against audiogenic seizure.


Effect of phenobarbital on the incorporation of 3H or 14C labeled precursors into fatty acids.


Effect of the convulsive agent 3-mercaptopropionic acid on the levels of GABA, other amino acids and glutamate decarboxylase in different regions of the rat brain.


The synthesis and pharmacology of a novel benzodiazepine derivative, 1-methyl-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one(ID-540).


Central actions of some beta-adrenoceptor blocking agents.


Periosteal new bone formation in polyarteritis nodosa: a syndrome involving the lower extremities.


Comparison of beta-adrenergic blocking activities of propranolol, isopropylmethoxamine, sotalol, practolol, alprenolol, pindolol, oxprenolol and D-32 in the atria and trachea of the guinea-pig.


Determination of dl-fencamine in rat and human urine.


Vasculitis of the breast: an unusual manifestation of polyarteritis.


Workshop on the use of acupuncture in the rheumatic diseases. Summary of proceedings. National Institutes of Health, Bethesda, Maryland, September 17-18, 1973.


Effects of Kö 1366 on the distribution of intrarenal blood flow in normal canine kidneys.


Tetracycline for the treatment of pityriasis lichenoides.


Effect of propranolol on morphine metabolism.


The estimation of enzyme activity in living epidermal cells.


Genetic heterogeneity and pathophysiology of G6PD deficiency.


Nuclear magnetic resonance studies of the binding of substrate analogs and coenzyme to dihydrofolate reductase from Lactobacillus casei.


The biochemical pharmacology of abused drugs. III. Cannabis, opiates, and synthetic narcotics.


The formation and characterization of the nicotine analog of triphosphopyridine nucleotide.


Testosterone metabolism in rooster comb.


The structure of ceramide aminoethylphosphonate from the sea anemone, Metridium senile.


Effect of alpha-tocopherol on reconstitution of photosystem I in heptane-extracted spinach chloroplasts.


Malate dehydrogenase in Zea mays: properties and inhibition by sulfite.


Trypsin inhibition of photosynthetic pyridine nucleotide reduction.


Spectroscopic probes of Escherichia coli glutamine synthetase. Rare earth ions by difference absorption.


Comparison of gastric and pancreatic inhibitory properties of metiamide and atropine.


Splenic transplantation in Gaucher disease.


Alteration of hepatic microsomal metabolism of male mice by certain anticholinesterase insecticides.


Psychometric prediction of institutional adjustment: a validation study.


Effect of dietary amino acids on hepatic drug metabolism in the rat.


Metabolism of 3,4-benzpyrene in rainbow trout (Salmo gairdneri).


Effect of catecholamines, serotonin, and some amino acids, injected into the amygdala, on the conditioned avoidance reflex and motor activity of rats.


Pseudomonas osteomyelitis following puncture wounds in children.


Blood and neoplastic diseases. Acute myeloblastic leukaemia.


Optic and cochleovestibular degenerations in the hereditary ataxias. I. Clinico-pathological and genetic aspects.


Familial oculocranioskeletal neuromuscular disease with abnormal muscle mitochondria.


The effect of barbiturates on (3H)GABA transport in rat cerebral cortex slices.


Reserpine selectively increases tyrosine hydroxylase and dopamine-beta-hydroxylase enzyme protein in central noradrenergic neurons.


Alterations in brain norepinephrine and tyrosine hydroxylase activity during experimental hypothyroidism in rats.


Gamma-aminobutyrate transaminase activity in rat cerebellar cortex: a histochemical study.


Differential effects of neuroleptic drugs on amphetamine-induced stimulation of locomotor activity in 11-day-old and adult rats.


A description of the embryology, larval development, and feeding of the sea anemones Anthopleura elegantissima and A. xanthogrammica.


Prescription drugs and the patient's health.


Total and regional coronary blood flow during acute right ventricular pressure overload.


Correlation between azo reduction and formation in vitro of DNA-bound DAB metabolites in liver microsomes from rats fed on carcinogenic or normal diets.


A kinetic determination of ammonia in plasma.


Preservation of gamma-glutamyl transpeptidase activity in human urine.


A fluorometric method for the measurement of butaperazine in human plasma.


A 3-year study among Yugoslavian schoolchildren on caries reduction after topical application of 4% NaF-PO4.


Studies on the effect of dentifrices with low fluoride content.


A longitudinal study of caries experience and extraction of permanent first molars in English children.


Oral health in the republic of Paraguay.


Effect of methionine sulfoximine on glutamine synthetase activity and blood metabolite levels in the chicken (Gallus domesticus).


Respiratory enzymes of the silkmoth Antheraea pernyi in relation to metamorphosis and pupal diapause.


A comparison of the distribution and electron acceptor specificities of xanthine oxidase and aldehyde oxidase.


The antispastic effects of Ba 34647 (B-4-p-chlorophenyl-gamma-amino-butyric acid) a GABA derivative.


Comparative in vitro activity of amoxicillin and ampicillin against bacteria isolated from ill children.


Effect of tolamolol versus propranolol on systolic time intervals in angina.


Baclofen: a preliminary report of its pharmacological properties and therapeutic efficacy in spasticity.


The clinical use of psychotherapeutic drugs in the elderly.


Use of beta-adrenergic receptor blocking drugs in psychiatry.


Anaesthesia in the hypertensive patient.


A practical approach to the management of angina.


An investigation into the enzyme histochemistry of adenocarcinomas of human large intestine and of the transitional epithelium immediately adjacent to them. Histochemical enzymatic studies were performed on 30 freshly resected large bowel carcinomas, 30 samples of normal colonic epithelium, and six samples of the histologically normal epithelium (so-called transitional epithelium) immediately adjacent to a carcinoma. Five enzymes were studied: nicotine adenine dinucleotide tetrazolium reductase (NADH-TR), glucose-6-phosphate dehydrogenase, succinate dehydrogenase, monoamine oxidase, and acid phosphatase. QUANTITATIVE AND QUALITATIVE DIFFERENCES IN ENZYME ACTIVITY WERE OBSERVED BETWEEN NORMAL, TRANSITIONAL, AND CARCINOMATOUS MUCOSA AS FOLLOWS: monoamine oxidase activity was moderate in normal mucosa, high in transitional mucosa, and low in carcinoma. Succinate dehydrogenase activity was high in transitional mucosa and low or moderate in normal and carcinomatous mucosa. Glucose-6-phosphate dehydrogenase activity showed a gradation from low in normal mucosa to high in carcinoma while acid phosphatase showed the reverse of this pattern. The tetrazolium reductase activity was low or moderate in normal and transitional mucosa and high in carcinoma. These differences in enzyme activity and their possible clinical and metabolic significance are discussed.


Enzyme histochemical study of fat absorption in human duodenal mucosa. In seven healthy subjects the activities of various intestinal enzymes were studied using a fasting control peroral biopsy and two other biopsies 15 minutes and 30 minutes after an intestinal infusion of emulsified corn oil. Specific histochemical methods permitted the comparison of the enzymatic activities of the absorptive cells at the top of the villi before and during fat absorption which was demonstrated with a Sudan black stain. FOUR OXYDATIVE ENZYMES WERE MODIFIED AFTER THE CORN OIL INFUSION: NADH2-tetrazolium reductase, NADPH2-tetrazolium reductase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase. In six cases, the activity of NADH2-tetrazolium reductase was increased. Two of these subjects presented a simultaneous increase of NADPH2-tetrazolium reductase and glucose-6-phosphate dehydrogenase. Two other subjects presented a decrease in lactate dehydrogenase activity.


An immunological approach to ferredoxin specificity and activity.


Reduction of adenosine 5'-phosphosulfate to cysteine in extracts from Chlorella and mutants blocked for sulfate reduction.


Studies with ubiquinone-depleted submitochondrial particles. Quantitative incorporation of small amounts of ubiquinone and its effects on the NADH and succinate oxidase activities.


Cell envelope composition of Escherichia coli K12: a comparison of the cell poles and the lateral wall.


Possible role of cerebral amino acids in acute neurotoxic effects of DDT in mice.


Effect of mianserin, a potent anti-serotonin agent, on the isolated rat stomach fundus preparation.


Influence of autonomic blockade on the reduction in myocardial performance produced by clonidine.


Beta-adrenoceptor studies. III. On the beta-adrenoceptors in rat adipose tissue.


The nucleus amygdaloideus centralis and neuroleptic activity in the rat.


Long lasting stimulation of locomotor activity produced by the intraventricular injection of a cyclic analogue of dopamine into conscious mice.


The beta-blocking potency and cardioselectivity of tolamolol and its isomers in rodents.


The effect of epinephrine following practolol on the pulmonary circulation of dogs.


Blockade by prostaglandins E2 and F1 alpha of the response of the rabbit ileum to stimulation of sympathetic nerve and its reversal by some antihistamines, dexamphetamine and methylphenidate.


A thermodynamic approach to problems of drug antagonism. Measurements of the parameters of affinity (pA2) of antihistaminics and a beta-haloalkylamine under varying experimental conditions.


Assessment of effects of beta-blocking drugs on blood glucose levels and insulin hypoglycaemia in rats.


Anticonvulsant activity of some beta-adrenoceptor blocking agents in mice.


A vasodepressor action of histamine mediated by H2-receptor activation.


Studies on the action and mechanism of action of oxyfedrine on isolated tracheal chains.


Comparative effects of apomorphine, piribedil and other neurotropic agents on central analgesic-induced catatonia in the rat.


Structure-selectivity relationships of beta-adrenoceptor antagonists in cats.


Inhibition of in vitro stimulated gastric acid secretion by a histamine H2-receptor antagonist, metiamide.


Nitrilophenoxypropanolamines: influence of ring substitution on beta-receptor blockade.


Microspectrofluorometric evaluation of the oxygen probe 1-pyrene butyric acid in single living cells.


Histochemical demonstration of gamma-glutamyltranspeptidase in rat liver after portacaval anastomosis.


Activity of some juvenoids in chironomid larvae.


Local alpha-adrenoceptor mediated feed-back inhibition of catecholamine release from the adrenal medulla?


Selectivity of beta-adrenergic compounds. III - Classification of beta-receptors.


Subcellular distribution of catecholamines and enzymes in human neuroblastoma.


Sequence of the reaction of heme catabolism catalyzed by the microsomal heme oxygenase system.


Inhibition of steroid inducible tyrosine aminotransferase by mouse and rat interferon in hepatoma tissue culture cells.


Kinetics of binding of oxidized coenzymes in ternary complexes with glutarate by L-glutamate dehydrogenase.


An investigation into the influence of a graft-versus-host reaction, induced by parent line cells, on the growth of lymphoma transplants in F1 hybrid mice.


Blood lymphocyte nucleoli in ontogenesis and allograft reaction in normal and neonatally thymectomized mice.


Possible role of serum factors in non-H-2 allograft response in mice.


Analysis of some in vitro activities of rabbit and duck anti-chicken anti-brain sera.


Popliteal lymph node activation in graft-versus-host and host-versus-graft reaction in mice.


Effect of phytohaemagglutinin on graft-versus-host reaction in F1 hybrid mice.


Effect of hepatocarcinogenic azo dyes on glutathione and related enzymes in rat liver.


Congenital and hereditary abnormalities in the elderly.


Effect of calcitonin on the formation, composition, and enzymatic activity of the hepatic bile in guinea pgs. Porcine calcitonin given to guinea pigs in doses causing hypocalcaemia and hypophosphataemia decreased the bilirubin concentration and increased the activity of gamma glutamyl transpeptidase (GGTP) in the hepatic bile. Calcitonin had no effect on bile flow, its pH, electrolyte composition including calcium, or on the concentration of protein, glucose, cholesterol, nonprotein nitrogen (NPN), and bile acids. It also did not affect the activities of alanine aminotransferase (AIAT) and alkaline phosphatase (AP) in the hepatic bile. Calcitonin increased the calcium content in the liver.


Atopic dermatitis anxiety and conditioned scratch responses.


Verbal desensitisation in bronchial asthma.


Hydroperoxide metabolism in hemoglobin-free perfused rat liver.


2-alkenal reductase isolation, properties and specificities.


Mitochondrial nicotinamide nucleotide systems: ammonium chloride responses and associated metabolic transitions in hemoglobin-free perfused rat liver.


Enzymatic ribonucleotide reduction in wheat.


Measurement of the ATP/ADP ratio in mitochondria and in the extramitochondrial compartment by fractionation of freeze-stopped liver tissue in non-aqueous media.


NADP-specific glutamate dehydrogenase from Plasmodium chabaudi.


Invertebrate collagens: qualitative and quantitative studies on their carbohydrate moieties.


Phospholipids as cinchocain action site during inhibition of lipoperoxidative reactions in rat liver microsomes.


Manpower:  How five nations respond to the issues.


Editorials: Intestinal shunting for morbid obesity.


Medical malpractice: viewpoint of a plaintiff's attorney.


A children's hospital in Chicago, 1882-1904.


Angiomatous lymphoid hamartoma of the mediastinum.


The importance of vehicles in topical applications.


Surgical grand rounds. Carcinoma of lip.


Experience with the halo and body cast in the ambulatory treatment of cervical spine fractures.


Hyponatremia and central nervous system disease.


Neurology--epilepsy and learning disorders.


Effect of inhibition of the Hill reaction on polyribosomes level and on induced synthesis of nitrate and nitrite reductases in rice seedlings.


Isolation and cofactor requirements of benzoic acid-4-hydroxylase from Aspergillus niger.


Isocitrate dehydrogenase of soybeans.

Isocitrate dehydrogenase of soybeans.


Metabolism of glucose in cerebral cortex of rat in leptazol-induced convulsions and effect of gamma-aminobutyric acid on the same.


Antihistaminic effect of a new piperazine derivative, 1-phenoxy-2-(N-methyl-piperazino)-3-ephedrinopropane monohydrochloride.


Casein-induced experimental amyloidosis. III. Response to mitogens, allogeneic cells, and graft-versus-host reactions in the murine model.


Vitamin E protects mice against Diplococcus pneumoniae type I infection. Vitamin E protects nonimmunized and immunized mice against fatal Diplococcus pneumoniae type I (DpI) infection. A dietary supplementation of 180 mg of dl-alpha-tocopheryl acetate per kg of diet increased survival of nonimmunized mice from 20 to 80% when challenged with 20 organisms, and of mice immunized with 0.5 ng of DpI polysaccharide from 15 to 70% when challenged with 20,000 organisms. The phagocytic index of immunized mice was four times higher in the 180-mg vitamin E group than in the control group. Both the survival and phagocytic index revealed a biphasic dose response, indicating a cause-effect relationship between phagocytosis and survival. Vitamin E also significantly increased the rate of carbon clearance from blood, indicating a general increase in phagocytic activity. The data indicated that increased macrophage activity probably aided by increased antibody production was the principal reason for increased protection.


Lipid peroxidation in the killing of phagocytized pneumococci. To directly examine the role of hydrogen peroxide in the killing of bacteria after ingestion by granulocytes, we have studied some of the events of phagocytosis of a mutant strain of pneumococci which is relatively deficient in peroxide production. The hydrogen peroxide-deficient pneumococci and the otherwise identical wild type were grown with [(14)C]arachidonic and [(3)H]palmitic acid labels to label their lipids with unsaturated and saturated fatty acids, respectively. They were then incubated with both normal and chronic granulomatous disease granulocytes. The rates of ingestion and bacterial killing and the stability of fatty acids in the cell-bacteria complex were followed. Radioactive carbon dioxide released from glucose was also independently followed to measure glucose oxidation. Ingestion was similar for all cell-bacteria combinations. Chronic granulomatous disease cells killed the peroxide-positive wild pneumococci much more effectively (20-fold) than the peroxide-deficient mutant. Normal cells killed both peroxide-positive and -negative strains effectively. A considerable loss of [(14)C]arachidonic acid ( approximately 40%) consistent with lipid peroxidation of this unsaturated fatty acid was observed in all normal cells and in chronic granulomatous disease cells with peroxide-positive pneumococci. However, no loss of [(14)C]arachidonic acid occurred in chronic granulomatous disease cells with the peroxide-deficient pneumococci. No loss tritiated palmitic acid occurred in any cell-bacteria combination. Glucose oxidation was impaired in the chronic granulomatous disease cells in comparison to normal cells at rest and was especially impaired in chronic granulomatous disease cells ingesting the peroxide-deficient mutant pneumococci. This defect was partially corrected after phagocytosis of the peroxide-positive strain. These data directly support the hypothesis that bacterial killing is partially dependent upon an intact peroxide-generating system in the leukocyte-bacteria complex. Moreover, they indicate that bacterial lipid peroxidation is associated with the generation of peroxide during phagocytosis. Finally, they suggest that such peroxidation may contribute to effective phagocytic bacterial killing.


Effect of progesterone on Neisseria gonorrhoeae. The effects of progesterone on the growth of pathogenic and nonpathogenic species of Neisseria were studied in liquid cultures. Only strains of N. gonorrhoeae and N. meningitidis were highly sensitive to growth inhibition by progesterone. This inhibitory effect was either bacteriostatic or bactericidal, depending upon the ratio of progesterone concentration to cell mass. The site of progesterone inhibition appeared to be located in the cell membrane; >86% of [4-(14)C]progesterone was recovered in the lipid-containing cell fractions. Membrane preparations from N. gonorrhoeae bound progesterone more efficiently than those from progesterone-insensitive cells. In addition, progesterone significantly inhibited the activity of the membrane-associated enzymes reduced nicotinamide adenine dinucleotide oxidase and (cytochrome b) l-lactate dehydrogenase.


A university system drug profile.

A university system drug profile.


Influence of some psychoactive drugs on mineral metabolism in man.


Letter: Interaction between piperazine and some phenothiazine derivatives.


A simplified guide to the rational use of psychotropic drugs.


Proteins of two strains of mosquito iridescent virus.


A medical classification system for ambulatory-care manpower planning.


A microspectrofluorometric approach for the study of benzo(a)pyrene and dibenzo(a, h)anthracene metabolization in single living cells.


Microspectrofluorometric study of benzo(a)pyrene metabolization in benzo(a)pyrene-grown single living cells.


Purification and characterization of the two 6-phosphogluconate dehydrogenase species from Pseudomonas multivorans. The two species of 6-phosphogluconate dehydrogenase (EC 1.1.1.43) from Pseudomonas multivorans were resolved from extracts of gluconate-grown bacteria and purified to homogeneity. Each enzyme comprised between 0.1 and 0.2% of the total cellular protein. Separation of the two enzymes, one which is specific for nicotinamide adenine dinucleotide phosphate and the other which is active with nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate was facilitated by the marked difference in their respective isoelectric points, which were at pH 5.0 and 6.9. Comparison of the subunit compositions of the two enzymes indicated that they do not share common peptide chains. The enzyme active with nicotinamide adenine dinucleotide was composed of two subunits of about 40,000 molecular weight, and the nicotinamide adenine dinucleotide phosphate-specific enzyme was composed of two subunits of about 60,000 molecular weight. Immunological studies indicated that the two enzymes do not share common antigenic determinants. Reduced nicotinamide adenine dinucleotide phosphate strongly inhibited the 6-phosphogluconate dehydrogenase active with nicotinamide adenine dinucleotide by decreasing its affinity for 6-phosphogluconate. Guanosine-5'-triphosphate had a similar influence on the nicotinamide adenine dinucleotide phosphate-specific 6-phosphogluconate dehydrogenase. These results in conjunction with other data indicating that reduced nicotinamide adenine dinucleotide phosphate stimulates the conversion of 6-phosphogluconate to pyruvate by crude bacterial extracts suggest that in P. multivorans, the relative distribution of 6-phosphogluconate into the pentose phosphate and Entner-Doudoroff pathways might be determined by the intracellular concentrations of reduced nicotinamide adenine dinucleotide phosphate and purine nucleotides.


Sporulation properties of cytochrome a-deficient mutants of Bacillus subtilis. Three classes of cytochrome a-deficient mutants of Bacillus subtilis have been found to be asporogenic or oligosporogenic. All three classes showed declines in adenosine 5'-triphosphate (ATP) concentrations during early sporulation, at a time when ATP levels in wild-type strains are constant. Class III mutants were found to be deficient in aconitase and isocitric dehydrogenase, and showed reduced maximum growth in nutrient sporulation medium. These mutants also suffered the most rapid decline in ATP concentration in early sporulation, and exhibited neither the biphasic oxygen consumption curve nor the increase in pH normally observed at the end of logarithmic growth in nutrient sporulation medium. Nicotinamide adenine dinucleotide oxidase activities of purified membrane preparations were approximately normal for mutants in all classes, except for two of the class II mutants and one class III mutant. Neither cytochrome a nor cytochrome c appears to be an obligatory intermediate in cyanide-sensitive nicotinamide adenine dinucleotide oxidation in B. subtilis.


Involvement of threonine dehydratase in biosynthesis of the alpha-ketobutyrate prosthetic group of urocanase. Seventeen mutants of Pseudomonas putida that were unable to grow on threonine as nitrogen source owing to a lack of threonine dehydratase were isolated, and all were found to be unable to synthesize active urocanase. Spontaneous revertants selected for urocanase production concomitantly regained threonine dehydratase. Mutants that were unable to utilize urocanate as carbon source were also isolated, and these were defective in urocanase formation but were normal in threonine dehydratase levels. Since alpha-ketobutyrate is the prosthetic group for urocanase, these results are consistent with the proposal that threonine dehydratase is necessary for urocanase prosthetic group biosynthesis. However, the lack of urocanase activity in threonine dehydratase-negative mutants was shown not to be the result of reduced levels of endogenous free alpha-ketobutyrate, nor to the participation of threonine dehydratase in the initiation of urocanase biosynthesis through the conversion of threonyl-tRNA(Thr) to alpha-ketobutyryl-tRNA(Thr). Other alternatives for the participation of threonine dehydratase in urocanase biosynthesis are discussed.


Purification and characterization of the Pseudomonas multivorans glucose-6-phosphate dehydrogenase active with nicotinamide adenine dinucleotide. The Pseudomonas multivorans glucose-6-phosphate dehydrogenase (EC 1.1.1.49) active with nicotinamide adenine dinucleotide, which is inhibitable by adenosine-5'-triphosphate, was purified approximately 1,000-fold from extracts of glucose-grown bacteria, and characterized with respect to subunit composition, response to different inhibitory ligands, and certain other properties. The enzyme was found to be an oligomer composed of four subunits of about 60,000 molecular weight. Reduced nicotinamide adenine dinucleotide phosphate, but not reduced nicotinamide adenine dinucleotide, was found to be a potent inhibitor of its activity. The range of concentrations of reduced nicotinamide adenine dinucleotide phosphate over which inhibition occurred was about 100-fold lower than that for adenosine-5'-triphosphate. The data suggest that reduced nicotinamide adenine dinucleotide phosphate may play an important role in regulation of hexose phosphate metabolism in P. multivorans. Antisera prepared against the purified enzyme strongly inhibited its activity, but failed to inhibit the activity of the nicotinamide adenine dinucleotide phosphate-specific glucose-6-phosphate dehydrogenase which is also present in extracts of this bacterium. Immunodiffusion experiments confirmed the results of the enzyme inhibition studies, and failed to support the idea that the two glucose-6-phosphate dehydrogenase species from P. multivorans represent different oligomeric forms of the same protein.


Inhibition of induction of competence in Pneumococcus by isologous teichoic acid. Pneumococcal teichoic acid inhibits induction of competence in incompetent cells of Pneumococcus. The inhibitory effect is very similar to that observed in the presence of d-glucosamine and d-galactosamine.


Structure and function of D-amino acid oxidase. VIII. Circular dichroism study in the ultraviolet region.


The redox reactions in propionic acid fermentation. IV. Participation of menaquinone in the electron transfer system in Propionibacterium arabinosum.


Pleuropulmonary manifestations of collagen diseases.


Cellular senescence in yeast caused by carbon-source starvation. II. Induction and subcellular location of lipid peroxidation activity.


Is cytochrome oxidase a constituent of nuclear membranes?


Ornithine cyclase (deaminating). III. Mechanism of the conversion of ornithine to proline.


Purification and properties of the Neurospora crassa assimilatory nitrite reductase.


Monovalent cation effects on lysine-sensitive aspartokinase catalytic activity and allosteric regulation.


Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione.


The biosynthesis and turnover of nicotinamide adenine dinucleotide in enucleated culture cells.


The alpha-glycerophosphate cycle in Drosophila melanogaster. IV. Metabolic, ultrastructural, and adaptive consequences of alphaGpdh-l "null" mutations. "Null" mutations previously isolated at the alphaGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing alpha-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, alphaGpdh-1(BO-1-4), and alphaGpdh-1(BO-1-5,) when made hemizygous with a deficiency of the alphaGpdh-1 locus, Df(2L)GdhA, were rendered homozygous by recombination with and selective elimination of the Df(2L)GdhA chromosome. After over 25 generations, a homozygous alphaGpdh-1(BO-1-4) stock regained the ability to fly despite the continued absence of measurable alphaGPDH activity. Inter se heterozygotes of three noncomplementing alphaGpdh-1 "null" alleles and the "adapted" alphaGpdh-1(BO-1-4) homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the alpha-glycerophosphate cycle in Drosophila. The enzyme functions tested included glyceraldehyde-3-phosphate dehydrogenase, cytoplasmic and soluble malate dehydrogenase, lactate dehydrogenase, mitochondrial NADH oxidation, oxidative phosphorylation, and respiratory control with the substrates alpha-glycerophosphate, succinate, and pyruvate. These activities in any of the mutant genotypes in early adult life were indistinguishable from those in the wild type. There was, however, a premature deterioration and atrophy of the ultrastructural integrity of flight muscle sarcosomes observed by electron microscopy in the "null" mutants. These observations were correlated with a decrease in state 3 mitochondrial oxidation with alpha-glycerophosphate, succinate, and pyruvate, as well as with loss of respiratory control in adults as early as 2 wk after eclosion. Such observations, which normally are seen in aged dipterans, were accompanied by premature mortality of the mutant heterozygotes. The adapted alphaGpdh-1(BO-1-4) was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation.


The distribution of pyridine nucleotides between nucleus and cytoplasm.


An apparatus for the detection and quantitation of volatile human effluents.


Gas chromatographic analysis of medazepam and its metabolites using an electrolytic conductivity detector.


An initial investigation of the psychedelic drug flashback phenomena.


The structure of word storage in the permanent memory of nonpsychotic schizophrenics.


Use of sensory deprivation in facilitating the reduction of cigarette smoking.


Comparison of the effects on renin release of beta adrenergic antagonists with differing properties. Continuous 6-h infusions of the beta adrenergic blockers d,l-propranolol or oxprenolol significantly reduced plasma renin activity (PRA) and mean blood pressure in the resting rabbit and prevented the stimulatory effects of isoproterenol on renin release and heart rate. These actions were due to blockade of beta receptors, for the inactive isomer, d-propranolol, had no effect. Despite sustained high plasma concentrations of d,l-propranolol (0.2 mug/ml) in the unstimulated animal, PRA did not fall below 36% of control values, suggesting that basal renin secretion is maintained partly by factors other than beta adrenergic mechanisms.Prindolol, another beta blocker, also abolished the effects of isoproterenol on renin and on the heart, and reduced blood pressure in the resting animal. However, prindolol increased resting PRA and heart rate, and in animals already receiving d,l-propranolol, it raised PRA and heart rate without further altering blood pressure. This suggests that the effect on PRA of prindolol was due to its intrinsic sympathomimetic activity and not hypotension-mediated mechanisms. The observation that the blood pressure-lowering effect of prindolol was associated with a rise in PRA, while another beta antagonist, H 35/25, lowered PRA but had no effect on blood pressure, indicates that the hypotensive action of beta blockers is unrelated to their effects on renin release. In both unstimulated and isoproterenol-challenged animals, only blockers possessing beta-1 receptor affinity (d,l-propranolol, oxprenolol, prindolol, practolol, and metoprolol) affected heart rate, while effects on PRA were more prominent with agents possessing beta-2 activity (d,l-propranolol, oxprenolol, prindolol, and H 35/25). Thus, the changes in PRA caused by the beta adrenergic blockers appear to be dependent upon the summation of their direct effects, antagonistic or sympathomimetic, on beta-2 adrenergic receptors regulating renin release.


Reactions of internal and external test-anxious students to counseling and behavior therapies.


The use of liquid and gel isoelectric focusing as a means of further evaluating the degree of restriction of rabbit antibodies.


Piperacetazine study in state hospital patients.


Physician's assistants and rural health care: a study of physician's attitudes.


Physiological studies of conducting systems in the colonial hydroid Hydractinia echinata 1. Polyp specialization.


Cardiac function in patients treated with phenothiazines. Comparison with quinidine.


Morphological substrates of conduction in the colonial hydroid Hydractinia echinata. 1. An ectodermal nerve net.


Intracellular actions of 5-hydroxytryptamine on the bivalve myocardium. 1. Adenylate and guanylate cyclases.


Nitrite and ammonia assimilation by anaerobic continuous cultures of Escherichia coli.


The regulation of glutamine metabolism in Candida utilis: mechanisms of control of glutamine synthetase.


A comparative study of cells and mitochondria of Saccharomyces cerevisiae and of a hydrocarbon-utilizing yeast, Candida lipolytica.


The enzymes of ammonia assimilation in Schizosaccharomyces spp. and in Saccharomycodes ludwigii.


The pentobarbital test dose for depressant drug dependence.


Acid-etched resin splint for temporarily stabilizing anterior teeth.


Utility of three abbreviated MMPIs with psychiatric outpatients.


Regional changes in amino acid content in developing rat brain.


Free amino acids in the photoreceptor cells of the frog retina.


Evidence for specific synaptosomal localization of exogenous accumulated taurine.


Sodium-dependent efflux and exchange of GABA in synaptosomes.


Effect of riboflavin and riboflavin 2',3',4',5'-tetrabutyrate on rat liver microsomal lipid peroxidation.


The occurrence and properties of methylenetetrahydrofolate dehydrogenase in pea seedlings, and intracellular distribution of some folate-linked enzymes in the plant.


The relation between urinary excretion of tryptophan and niacin metabolites and pyridine nucleotides in the liver in rats fed a tryptophan-deficient diet.


Studies on D-tetrose metabolism. V. Identification of protecting factor against cold inactivation of D-erythrulose reductase from beef liver.


Mosquito transmission of Plasmodium (Giovannolaia) circumflexum Kikuth, 1931, to waterfowl in the Tantramar Marshes, New Brunswick.


Spectrophotometric determination of ampicillin sodium in the presence of its degradation and polymerization products.


An observation of an unusual repair of an osseous defect.


Detection, isolation and characterization of normorphine and norcodeine as morphine metabolites in man.


A quantitative gas-liquid chromatographic method for phorbol and related diterpenes as their acetates.


A polarographic method for the determination of the N-oxide, N-oxide-sulphoxide and sulphoxide metabolites of chlorpromazine.


The cannabinoid content of Cannabis sativa L grown in England.


The influence of porosity upon the distribution of reserpine in calcium sulphate granules.


The response of isolated cardiac muscle to acute anoxia: protective effect of adenosine triphosphate and creatine phosphate.


Histamine, 5-hydroxytryptamine, kinins and the anti-inflammatory activity of human plasma fraction in carrageenan-induced paw oedema in the rat.


Effect of a sea snake (Enhydrina schistosa) venom on the ganglionic nicotinic actions of acetylcholine.


Inhibition by non-steroidal anti-inflammatory agents of the release of rabbit aorta contracting substance and prostaglandins from chopped guinea-pig lungs.


Long-lasting anti-tremor induced by 2-Br-alpha-ergocryptine in monkeys.


Further evidence for the stimulation of rat brain dopamine receptors by ergometrine.


The effect of beta-phenethylamine on noradrenaline and dopamine turnover in rat brain.


The effect of amphetamine on glucose uptake into the rat isolated hemidiaphragm.


Further observations on the relaxant effect of caerulein on the guinea-pig ileum.


Effect of muscarinic agonists on the release of (3H)noradrenaline from the guinea-pig perfused heart.


Influence of different anions on tyramine and amphetamine uptake by cow adrenal medulla chromaffin vesicles.


The role of solvent interaction in quantum pharmacological studies.


Characteristics of the mass spectra of some aliphatic amine N-oxides.


Structure of an acidic metabolite of delta1-tetrahydrocannabinol isolated from rabbit urine.


Plasma and urine concentrations of a new adamantane derivative.


Isosalsolinol formation: a secondary reaction in the Pictet-Spengler condensation.


The effect of particle size reduction on digoxin crystal properties.


Effect of maleic acid in compendial UV absorption assays for antihistamine maleate salts.


Caries-experience of preschool children in selected day-care centers.


Rats, flies and mosquitos of Lebanon: pests, reservoirs and vectors of disease.


Carotid reconstruction for Takayasu's (pulseless) disease using open thromboendarterectomy at aortocarotid junction.


Influence of the beta-adrenergic blocking drug Kö 1366 on haemodynamics in healthy volunteers and patients with ischaemic heart disease.


Portacaval shunt in the pig 1. Effect on survival, behavior, nutrition, and liver function.


Optometrists as ancillary personnel.

Optometrists as ancillary personnel.


Characteristics of physician's assistants: a focus on specialty.


Manpower in obstetrics--gynecology in a period of declining birth rate.


Pancreatic tumors and the first hormones.


Lipid peroxidation in chronic ethanol treated rats: in vitro uncoupling of peroxidation from reduced nicotine adenosine dinucleotide phosphate oxidation.


Factors in oxygen delivery to tissue.

Factors in oxygen delivery to tissue.


Determination of the activity of succinate, NADH, choline, and alpha-glycerophosphate dehydrogenases.


MMTP: a patient-oriented view.

MMTP: a patient-oriented view.


Tyrosine-dependent increase of tyrosine hydroxylase in neuroblastoma cells.


Detection of the use of methaqualone and benzodiazepines in urine screening programs.


Effects of an antispastic drug (beta-(4-chlorophenyl)-gamma-aminobutyric acid) on Renshaw cell activity.


Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration. Comparison with copper sulfate and factors governing the deportment of fluids injected into brain.


Inhibitory and disinhibitory effects of nitrazepam, diazepam and flurazepam hydrochloride on delayed matching behaviour in monkeys (Macaca mulatta).


Effects of phenoxybenzamine on the narcotic withdrawal syndrome in the rat.


The blockade of bulbospinal inhibition by imipramine, desipramine and pargyline.


Inhibition of the catalytic site of adenylate cyclase in the central nervous system by phenothiazine derivatives.


Renal transplant recipients. Significance of bacterial infections.


Acute iron poisoning in infancy. Guide to treatment.


Fluorosis and dental caries in the Ellice Islands.


Second messenger system in neoplasia.

Second messenger system in neoplasia.


Tyrosine hydroxylase: activation by nerve stimulation. The synthesis of the sympathetic neurotransmitter, norepinephrine, is accelerated by electrical stimulation of the guinea pig vas deferens. The molecular mechanism responsible for this enhanced formation of transmitter is unknown but has been attributed to an increase in the activity of tyrosine hydroxylase (EC 1.14.16.2; tyrosine 3-monooxygenase) during nerve stimulation. In the present experiments, we found that crude preparations of tyrosine hydroxylase isolated from guinea pig vasa deferentia that were electrically stimulated or depolarized by potassium show an increase in activity compared with enzyme obtained from untreated paired control tissues. This increase in activity is partially antagonized by addition of the Ca(++) chelator, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA), to the assay medium, and can be completely blocked if Ca(++) is removed from the potassium-rich medium used to depolarize the intact tissue, before preparation of the enzyme. A similar increase in enzyme activity occurs when Ca(++) ions are added directly to enzyme prepared from untreated vasa deferentia. In this instance, the activation is completely reversed by EGTA. The increase in activity produced by addition of Ca(++) to the isolated enzyme or by electrical stimulation or potassium depolarization of the tissue before isolation of the enzyme appears to be mediated by changes in the kinetic properties of tyrosine hydroxylase. All treatments appear to activate tyrosine hydroxylase by causing an increase in its affinity for substrate and pteridine cofactor and by decreasing its affinity for the end-product inhibitor, norepinephrine. These results provide direct evidence that the enhanced formation of norepinephrine seen during stimulation of sympathetically innervated tissues arises from an activation of tyrosine hydroxylase. The fact that the activation produced by nerve stimulation is mimicked by Ca(++) ions raises the intriguing possibility that the influx or mobilization of Ca(++) that accompanies nerve stimulation and that is intimately involved in release of transmitter may also participate in the activation of tyrosine hydroxylase.


Amino-acid sequence of NADP-specific glutamate dehydrogenase of neurospora crassa. A tentative primary structure of the NADP-specific glutamate dehydrogenase [L-glutamate: NADP oxidoreductase (deaminating), EC 1.4.1.4] from Neurospora crassa has been determined. The proposed sequence contains 452 amino-acid residues in each of the identical subunits of the hexameric enzyme. Comparison of the sequence with that of the bovine liver enzyme reveals considerable homology in the amino-terminal portion of the chain, including the vicinity of the reactive lysine, with only shorter stretches of homology within the carboxyl-terminal regions. The significance of this distribution of homologous regions is discussed.


Dental needs of Minnesota's head start children.


Phosphoprotein phosphatase activity associated with estrogen-induced protein in rat uterus. Estrogen-induced protein was purified from rat uteri and assayed for several enzymatic activities involved in the metabolism and action of cyclic nucleotides. No adenylate and guanylate cyclase (EC 4.6.1.1 and 4.6.1.2, respectively), protein kinase (EC 2.7.1.33), and cyclic nucleotide binding activities could be demonstrated in three independent preparations of the protein. However, all three preparations exhibited significant phosphoprotein phosphatase activity (EC 3.1.3.16) on phosphorylated protamine and histones F1. This activity is optimal at neutral pH, inhibited by Zn(++), and unaffected by cyclic AMP or cyclic GMP.


Biosynthesis of tyrosine hydroxylase in rat adrenal medulla after exposure to cold. Exposure of rats to cold increases the content of tyrosine hydroxylase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla, causing a long-lasting enhancement of the enzymatic activity. We have used an antibody specific to tyrosine hydroxylase to study the molecular mechanisms involved in the trans-synaptic induction of adrenal tyrosine hydroxylase. The rate of [(3)H]-leucine incorporation into adrenal tyrosine hydroxylase was measured by specific immunoprecipitation at various times after exposure to cold (4 hr). This enhanced rate of incorporation was evident between 11 and 30 hr after the beginning of exposure to cold, but not at 7 and 50 hr. The increase of (3)H incorporation preceded the maximal enhancement of adrenal tyrosine hydroxylase activity, which occurred about 30 hr after stimulation. Neither the activity of tyrosine hydroxylase nor the rate of (3)H incorporation into tyrosine hydroxylase in cervical sympathetic ganglia was changed by 4 hr of exposure to cold. The rate of degradation of tyrosine hydroxylase was estimated at 26 and 50 hr after the beginning of cold stress, as determined by the technique of double-isotope labeling. The data indicate that the tyrosine hydroxylase degradation rate was not reduced by exposure to cold. Thus, the induction of adrenal tyrosine hydroxylase appears to be due to an increased rate of its synthesis.


Glucose inhibition of epinephrine stimulation of hepatic gluconeogenesis by blockade of the alpha-receptor function. For isolated rat hepatocytes, glucagon, 3':5'-cyclic AMP, 3':5'-cyclic GMP, and epinephrine stimulate the rate of gluconeogenesis from substrates not involving pathways of mitochondrial metabolism. From estimation of the rates of glucose formation, fructose 6-phosphate phosphorylation, and lactate and pyruvate formation it is concluded that epinephrine and 3':5'-cyclic GMP stimulate gluconeogenesis from either galactose or fructose by influencing the rate of reactions involving fructose 6-phosphate in a manner similar to that already reported for glucagon and 3':5'-cyclic AMP. Each agent acts to inhibit flux through phosphofructokinase (EC 2.7.1.11) and enhance flux through fructose diphosphatase (EC 3.1.3.11), resulting in the re-direction of carbon from lactate and pyruvate formation to glucose synthesis. In addition to 3':5'-cyclic GMP, dibutyryl 3':5'-cyclic GMP, 8-bromo 3':5'-cyclic GMP, 8-benzyl-thio 3':5'-cyclic GMP and 8-(4-chlorophenyl)thio 3':5'-cyclic GMP stimulate glucose formation and inhibit lactate and pyruvate formation from galactose. Guanosine monophosphate and 2':3'-cyclic GMP are inactive. As the stimulatory effect of epinephrine is inhibited by phenoxybenzamine and not by propranolol, and is not simulated by isoproterenol, it is concluded that catecholamine activity is expressed through the alpha-receptor. Increased extracellular glucose concentration (>10 mM) decreases the stimulatory effect of epinephrine, 3':5'-cyclic GMP, and partially that of 3':5'-cyclic AMP but does not alter the efficacy of glucagon.


Heterogeneity of membrane vesicles from Escherichia coli and their subfractionation with antibody to ATPase. The energy-transducing, Mg-Ca activated ATPase (ATP phosphohydrolase, EC 3.6.1.3) of E. coli is located on the inner surface of the cytoplasmic membrane. Antibody to purified ATPase has now been used to demonstrate that membrane vesicles as ordinarily prepared by the lysozyme-EDTA method consist of two distinct populations. About half the vesicles are everted, and thus readily agglutinated by antibody to ATPase, while half are right-side out. NADH oxidase (reduced NAD:O(2) oxidoreductase EC 1.6.99.3) activity is associated almost entirely with everted vesicles, while the ability to concentrate proline is a property of the right-side out vesicles. The results explain the failure of previous workers to observe the energization of membrane vesicles by oxidation of NADH.


Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. [(3)H]Gamma-aminobutyric acid (GABA) binds to synaptic membrane fractions of rat brain in a selective fashion representing an interaction with postsynaptic GABA receptors. Inhibition of [(3)H]GABA binding by a variety of amino acids closely parallels their ability to mimic the synaptic inhibitory actions of GABA and does not correlate with their relative affinity for the presynaptic synaptosomal GABA uptake system. [(3)H]GABA binding is saturable with an affinity constant of about 0.1 muM. The GABA antagonist bicuculline inhibits [(3)H]GABA binding with half maximal effects at 5 muM, whereas it requires a concentration of 0.5 mM to reduce synaptosomal GABA uptake by 50%. In subcellular fractionation experiments [(3)H]GABA binding is most enriched in crude synaptic membranes. [(3)H]GABA binding is greatest in the cerebellum, least in the spinal cord and medulla oblongatapons, with intermediate values in the thalamus, hippocampus, hypothalamus, cerebral cortex, midbrain, and corpus striatum.


Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress- and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low K(m) phosphodiesterase (3':5'-cAMP 5' nucleotidohydrolase, EC 3.1.4.17). Increases in intracellular cGMP levels were associated with elevated guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity. Furthermore, adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was less sensitive to stimulation by the beta-adrenergic stimulant isoproterenol in both the aortas and the hearts of the hypertensive animals. These changes could provide the biochemical basis for the (a) increased vascular smooth muscle tone and peripheral resistance observed in these animals, (b) increased reactivity to norepinephrine, and (c) decreased ability of aortas from hypertensive rats to relax. The presence of these same effects in different etiologic types of hypertension indicates that this aberration in cyclic nucleotide metabolism may represent a common metabolic defect basic to the hypertensive syndrome irrespective of etiology.


Synthesis of acetyl coenzyme A holocarboxylase in vitro by a cytosolic preparation from chicken liver.


Indirect evidence for superoxide anion and singlet oxygen generated by NADPH--NADPH-dependent cytochrome c reductase and by L-alpha-hydroxyacid--L-amino acid oxidase at high pH.


Effect of heparin treatment on GVH disease.


Effect of microsomal enzyme inducers on the liver changes produced by common bile-duct ligature.


Effect of barbiturates and isoniazid on cerebral hemisphere gamma-aminobutyric acid content in pp' DDT treated mice.


Influence of adrenergic drugs on prostaglandin E release from the dog kidney,.


Problems in immunology.

Problems in immunology.


Present controversies in the treatment of schizophrenia.


One-step isolation and characterization of nuclear membranes.


Complex envelope system. Membrane systems of plant cells.


Structural studies relating to the distribution of molecular components in erythrocyte membranes.


The ultrastructure and chemistry of the luminal plasma membrane of the mammalian urinary bladder: a structure with low permeability to water and ions.


Membranes. Freeze-etching techniques applied to biological membranes.


Membranes and membrane surfaces. Dynamics of cytoplasmic membranes in pancreatic acinar cells.


Form and function of the glycocalyx on free cell surfaces.


Nuclear envelopes. Structure and biochemistry of the nuclear envelope.


Nuclear pores at prophase of meiosis in plants.


Varieties of depression in one patient.

Varieties of depression in one patient.


Bibliography on behavioral approaches to modification of smoking: January 1964 through December 1973.


Covert reinforcement and self-control procedures in systematic desensitization of gagging behavior.


Need for establishing desensitization programs on university campuses.


Personality characteristics of female narcotic addicts on the MMPI.


Social introversion-extraversion and Rorschach human responses in adult psychiatric patients.


Lethality of suicidal behavior and the MMPI.


Immunologic activation of oncogenic viruses.


Animal response to meteorological stress as a function of age.


The use of pins in the restoration of mutilated teeth.


Subfractions obtained from inner mitochondrial membranes incubated with cysteine. II. Distribution of enzymes and respiratory chain components.


Implications of catecholamine systems of the brain in schizophrenia.


An enzymatic basis for a blood-brain barrier? The gamma-glutamyl cycle-background and considerations relating to amino acid transport in the brain.


Bronchoconstriction tests in epidemiology. Discussion.


Response of the bronchial tree to chemical stimuli.


Bronchoconstriction tests in epidemiology. Summary and conclusions of the meeting.


Oral metiamide as an effective inhibitor of gastric acid secretion in man.


Fetal laryngeal and tracheal transplants in rats.


Assessment of immunocompetency by DNCB sensitization prior to human renal allotransplantation.


Effect of heparin, dextran and dipyridamole on the immunogenicity of renal allografts.


Immunological responses in transplantation of canine small intestine.


Tumor growth and lymphatic vasculature of free grafts and skin pedicles.


Effects of metiamide, a histamine H2-receptor antagonist, on vagally induced gastric secretion in dogs.


Selective gondal angiography for testicular localization in patients with cryptorchism.


Degradation of red cell membrane phospholipids by sea anemone nematocyst venom.


Actions of Chironex fleckeri toxins on cardiac transmembrane potentials.


Toxicological evaluation of palytoxin in several animal species.


The low molecular weight fraction of sea wasp (Chironex fleckeri) venom.


Different ways of using graft-versus-host reactivities to achieve acceptance of rat spleen allografts in the same donor-recipient pairing.


Bone marrow transplantation: introduction.


Bone-marrow transplantation in France, 1958-1973.


Allogeneic marrow grafts in man using cyclophosphamide.


Bone-marrow transplantation following combination chemotherapy immunosuppression (B.A.C.T.) in patients with acute leukemia.


Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors.


Strategy of clinical bone-marrow transplantations with emphasis on treatment of combined immune deficiency.


Fatal graft-vs.-host reaction following transfusion of allogeneic blood and plasma in infants with combined immunodeficiency disease.


Proposal for a world bank of reactive cells from bone marrow.


Infectious complications of marrow transplantation.


Use of ionizing radiation in transplantation.


Allogeneic marrow transplantation using matched sibling donors.


Histopathology in clinical renal transplantation.


Caveat myxoma.

Caveat myxoma.


Pharmacokinetic criteria for the evaluation of retard formulations.


Chromosomes of golden hamster tumors obtained by tumoral polypassage of the RS 1 rat tumor.


[Biological variants of the tick-borne encephalitis virus isolated in various foci of the disease].


About the hazard of obtaining false information as to oxygen supply to tissues by the hitherto used method of monitoring patients during extracorporeal circulation.


New substrates for measuring gamma-glutamyl transpeptidase activity.


Studies on glutathione reductase in serum.


Molar extinction coefficients of NADH and NADPH at Hg spectral lines.


On the quality of reduced pyridine coenzymes.


A simple method for the determination of enzyme activities in turbid plasma of patients with hyperlipoproteinemia.


Normal values of enzyme activities during pregnancy.


A glucose-determination on mechanized analyzers using glucose-dehydrogenase.


Report on a lethal antazoline intoxication.


Toxicology of some autopsy cases involving tricyclic antidepressant drugs.


Haemagglutination-inhibiting antibodies to arboviruses in a human population in Greece.


Evaluation of the immunofluorescent reagents in the identification of Salmonella bacteria.


A modified microslide gel double diffusion test.


A rapid method of identifying Escherichia coli H antigens.


Isolation of two strains of Klebsiella pneumoniae with transferable resistance determinants against ten antimicrobial drugs from clinical material.


Notes on the age and sex distribution of attack rates of clinical cholera in endemic urban area.


Future trends in antihypertensive therapy.


The mode of action of the gaba derivative baclofen in human spasticy.


Abnormal involuntary movements induced by anticholinergic therapy.


Frequency of hypodontia in relation to tooth size and dental arch width.


A histochemical study on the activity of gamma-glutamyl transpeptidase in liver disease.


Pharmacological modification of glutathione and NADP+ reduction.


Fetal outcome from prolonged versus acute drug administration in the pregnant rat.


The function of alpha- and beta-adrenergic receptors and a cholinergic receptor in the secretory cell of rat parotid gland.


The soluble acidic lipoproteins (SALPS) of storage granules. Matrix constituents which may bind stored molecules.


Remarks on the organization of axon terminals in relation to secretory processes at synapses.


Delayed increase of tyrosine hydroxylase activity induced by transsynaptic stimulation in chromaffin cells: role of cyclic nucleotides as second messengers.


Disinhibition as an organizing principle in the nervous system. The role of gamma-aminobutyric acid.


Some neuroactive compounds in the substantia nigra.


Evidence for descending pallido-nigral GABA-containing neurons.


Effects of iron and copper deficiencies on monoamine metabolism.


A new biosynthetic pathway to catecholamines via m-tyrosine.


The "on-off" effect.

The "on-off" effect.


The clinical physiology of side effects in long-term L-DOPA therapy.


Some aspects of dopamine in the central nervous system.


In vivo spontaneous and evoked release of newly synthesized dopamine in the cat caudate nucleus.


The effect of L-DOPA on brain polysomes and protein synthesis: probable mediation by intracellular dopamine.


On the use of membrane feeding to study the development of Trypanosoma brucei in Glossina.


Comparison of specific and relative alanine and aspartate aminotransferases of Trypanosoma brucei subgroup trypanosomes.


Letter: Serum gonadotropins in cryptorchidism.


Necrotizing arteritis.

Necrotizing arteritis.


ASMT position paper on physician extenders.


Sympathetic nervous system and renin release from submaxillary glands and kidneys.


Infection-induced hyperglucagonemia and altered hepatic response to glucagon in the rat.


Effects of altitude and semistarvation on heart mitochondrial function.


Evidence for presence of adrenergic receptors in the 6-day-old chick embryo.


Directions for statutory change: The physician extender..


Prolactin and human breast cancer.

Prolactin and human breast cancer.


Therapeutic effects of luteinizing hormone releasing hormone (LH-RH) in cryptorchidism.


Mechanism of action of some bronchodilators. Cyclic nucleotide metabolism in tracheal preparations.


Autonomic drugs in ophthalmology: some problems and promises. Section III: Sympathomimetic drugs.


Virulence of Venezuelan equine encephalomyelitis virus subtypes for various laboratory hosts. Mice, guinea pigs, and duck embryo cell cultures were inoculated with known subtypes of Venezuelan equine encephalomyelitis (VEE) virus and the attenuated (TC-83) strain of VEE. With the exception of TC-83, all strains were highly pathogenic for suckling mice by either intracranial or intraperitoneal routes of inoculation used. Virulence for older mice and guinea pigs provided a means to distinguish strains. In addition, virulence or lack of virulence for adult mice or guinea pigs provides a rapid method for separating epizootic subtype IB from TC-83 VEE virus isolates.


Glucose 6-phosphate dehydrogenase from brewers' yeast (Zwischenferment). Further observations on the ligand-induced macromolecular association phenomenon: kinetic properties of the two-chain protein species; and studies on the enzyme-substrate interactions.


Properties of leaf NAD malic enzyme from plants with C4 pathway photosynthesis.


The mechanism of cytochrome b5 reduction by NADPH-cytochrome c reductase.


Action of diethylstilbestrol on the NADH-dehydrogenase region of the respiratory chain.


Different effects of 2-n-heptyl-4-hydroxyquinoline-N-oxide on oxygen and nitrate respiration in Klebsiella aerogenes.


Chorismate synthase of Neurospora crassa: a flavoprotein.


Effect of andrenalectomy on cyclic 3',5'-guanosine monophosphate metabolism of rat liver and other tissues.


Substrate specificity of uptake of diamines in mouse brain slices.


Proceedings: Antagonism of the histamine response in the synovial microcirculation.


New and emerging roles in nursing.

New and emerging roles in nursing.


New evidence for the beta-adrenergic receptor blocking activity of dihydroergotamine.


Pharmacology of sympathomimetic amines with beta-adrenoreceptor agonist and alpha-adrenoreceptor antagonist properties.


Effects of diphenylaminoethanol (DPAE) on GABA and synaptic inhibitions in the cerebral and cerebellar cortices.


Effect of small doses of clonazepam upon soman-induced seizure activity and convulsions.


The antiarrhythmic effects of quaternary salts of beta-adrenergic blocking agents.


Antagonism of acute lethality of narcotic analgesics in aggregated and isolated mice by the central cholinomimetic action of pilocarpine.


The role of carotid sinus reflex, cardiac distention and catecholamines in the vagal escape mechanism.


Purulent pericarditis in the antibiotic era.


Beta-adrenergic receptor blocking drugs in psychiatry.


Neuropsychological assessment of undergraduate marihuana and LSD users.


Folic acid metabolism in vitamin B12-deficient sheep. Effects of injected methionine on liver constituents associated with folate metabolism. 1. The effects of injected l-methionine (2g every second day for 28 days) on liver folates and other constituents of liver associated with folate metabolism were studied in vitamin B(12)-deficient ewes and their pair-fed controls receiving vitamin B(12). The dose rate of methionine used was sufficient to restore almost to normal the elevated excretion in the urine of formiminoglutamate in the deficient animals. 2. Liver folates active for Lactobacillus casei, Streptococcus faecalis R and Pediococcus cerevisiae were severely depressed in deficient livers and were partly restored by methionine. Analysis of the folates after ion-exchange chromatography showed that the major effect of methionine was to increase the concentrations of tetrahydrofolates and formyltetrahydrofolates. Methyltetrahydrofolates were also increased, but there was no effect of methionine on the small amounts of incompletely reduced folates present in deficient livers. The folates present were predominantly penta-, hexa- and hepta-glutamates whether or not animals received vitamin B(12) or methionine. 3. Concentrations of ATP, NAD(+), NADH and NADPH were lower in freeze-clamped liver from vitamin B(12)-deficient sheep than in liver from pair-fed, vitamin B(12)-treated sheep. These changes were not affected by methionine which was also without effect on the elevated K(+)/Na(+) ratios found in deficient livers. 4. The livers of vitamin B(12)-deficient animals contained lower concentrations of choline and higher concentrations of lipid than their pair-fed controls. These effects were reversed by methionine.


Progesterone-induced lysis of rat kidney lysosomes as studied by changes in light-absorbance. 1. A rat kidney lysosomal fraction was prepared by the method of Maunsbach (1966) and characterized by its content of representative marker enzymes for lysosomes, mitochondria, peroxisomes and endoplasmic reticulum. 2. It was shown that both pH-dependent and progesterone-induced lysis lead to a decrease in the E(520) of suspensions of this preparation. This decrease parallels quantitatively and temporally the release of soluble acid phosphatase. 3. It is suggested that E(520) measurements are a valid method for the continuous measurement of changes in lysosomal integrity. 4. As an example, results are included which demonstrate the ability of Zn(2+) to stabilize lysosomes against spontaneous and progesterone-induced lysis.


Folic acid metabolism in vitamin B12-deficient sheep. Effects of injected methionine on methotrexate transport and the activity of enzymes associated with folate metabolism in liver. 1. A study was made of the effects of injected l-methionine on the activity of several enzymes of folate metabolism, and on the transport of methotrexate in liver preparations from vitamin B(12)-deficient ewes and their pair-fed controls receiving vitamin B(12). 2. The activities of dihydrofolate reductase (EC 1.5.1.3) and 5-methyltetrahydrofolate-homocysteine transmethylase were significantly decreased in the liver of vitamin B(12)-deficient animals, but were unaffected by l-methionine. 3. The concentration of S-adenosyl-l-methionine in the liver of deficient animals was about one-half of that in normal animals, and was restored to normal by either vitamin B(12) or l-methionine. 4. Methylenetetrahydrofolate reductase (EC 1.1.1.68) from sheep liver was inhibited by S-adenosyl-l-methionine in vitro, but not by concentrations of S-adenosyl-l-methionine found in the liver of vitamin B(12)-deficient animals after injection of physiological amounts of l-methionine. 5. Pteroylpolyglutamate synthetase activity was significantly increased in the liver of vitamin B(12)-deficient animals, and was decreased by intravenous injections of l-methionine. 6. l-Methionine injections increased the initial rate of uptake of methotrexate in liver slices from deficient animals and acted synergistically with vitamin B(12) to increase the quantity taken up in 40min. The failure of folate metabolism in vitamin B(12) deficiency can be satisfactorily explained if l-methionine similarly affects the membrane transport of naturally occurring folates. 7. Further details of the results have been deposited as Supplementary Publication SUP 50028 (4 pages) at the British Library (Lending Division), (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5.


Effect of glucagon on phenylalanine metabolism and phenylalanine-degrading enzymes in the rat. Glucagon administered subcutaneously to rats for 10 days had no significant effect on liver phenylalanine hydroxylase activity, but induced liver dihydropteridine reductase more than twofold. In rats administered a phenylalanine load orally, glucagon treatment stimulated oxidation and depressed urinary phenylalanine excretion. These responses could not be related to an effect of glucagon on hepatic tyrosine-alpha-oxoglutarate aminotransferase activity. Even in rats with phenylalanine hydroxylase activity depressed to 50% of control values by p-chlorophenylalanine administration, glucagon treatment increased the phenylalanine-oxidation rate substantially. Although hepatic phenylalanine-pyruvate aminotransferase was increased tenfold in glucagon-treated rats, glucagon treatment did not increase urinary excretion of phenylalanine transamination products by rats given a phenylalanine load. Glucagon treatment did not affect phenylalanine uptake by the gut or liver, or the liver content of phenylalanine hydroxylase cofactor. It is suggested that dihydropteridine reductase is the rate-limiting enzyme in phenylalanine degradation in the rat, and that glucagon may regulate the rate of oxidative phenylalanine metabolism in vivo by promoting indirectly the maintenance of the phenylalanine hydroxylase cofactor in its active, reduced state.


The effect of lysine on gluconeogenesis from lactate in rat hepatocytes. 1. In freshly prepared isolated rat liver cells there is a lag in gluconeogenesis from lactate. The magnitude of the lag increases with increasing lactate concentration. 2. The lag is virtually abolished by lysine. 3. A few other amino acids (tyrosine, arginine, asparagine, ornithine) and NH(4)Cl had effects similar to, but less pronounced than, lysine during the early stage of incubation. Lysine was unique in accelerating gluconeogenesis beyond the lag period. 4. The effects of the accelerators are not additive. 5. Glycine, serine, threonine, cysteine, tryptophan and histidine at 2mm markedly inhibit (>20%) gluconeogenesis from lactate. 6. Oleate, which promotes gluconeogenesis from lactate by supplying acetyl-CoA required for the pyruvate carboxylase reaction, had no effect on the lag, yet oleate oxidation showed no lag. 7. Preincubation of cells decreased the lag and decreased the magnitude of the lysine effect. 8. Pyruvate (added at 1mm to give an initial [lactate]/[pyruvate] ratio of 10) also abolished the lag and decreased the lysine effect by about 50%. 9. Lysine reversed the inhibition by ethanol of gluconeogenesis from lactate. 10. All accelerators increased the rate of re-oxidation of cytosolic NADH as shown by a rapid re-adjustment of the [lactate]/[pyruvate] ratio on addition of 10mm-lactate. 11. The accelerated rates of gluconeogenesis are associated with an increased formation of aspartate and glutamate and especially alanine. 12. The existence of the lag period can be explained on the basis of the fact that the accumulation of pyruvate during the lag diverts oxaloacetate from gluconeogenesis to malate formation, i.e. that the re-oxidation of cytosolic NADH takes precedence over gluconeogenesis. This means that much oxaloacetate formed by the pyruvate carboxylase reaction has to be transferred twice from the mitochondria to the cytosol by the aspartate shuttle. Under these conditions the operation of the shuttle limits the rate of gluconeogenesis from lactate. Lysine and other accelerators may increase the effectiveness of the shuttle by providing components of the aspartate aminotransferases involved. The question of why lysine specifically accelerates gluconeogenesis beyond the lag period is discussed.


Hormonal regulation of adipose-tissue acetyl-Coenzyme A carboxylase by changes in the polymeric state of the enzyme. The role of long-chain fatty acyl-Coenzyme A thioesters and citrate. 1. Acetyl-CoA carboxylase activity was measured in extracts of rat epididymal fat-pads either on preparation of the extracts (initial activity) or after incubation of the extracts with citrate (total activity). In the presence of glucose or fructose, brief exposure of pads to insulin increased the initial activity of acetyl-CoA carboxylase; no increase occurred in the absence of substrate. Adrenaline in the presence of glucose and insulin decreased the initial activity. None of these treatments led to a substantial change in the total activity of acetyl-CoA carboxylase. A large decrease in the initial activity of acetyl-CoA carboxylase also occurred with fat-pads obtained from rats that had been starved for 36h although the total activity was little changed by this treatment. 2. Conditions of high-speed centrifugation were found which appear to permit the separation of the polymeric and protomeric forms of the enzyme in fat-pad extracts. After the exposure of the fat-pads to insulin (in the presence of glucose), the proportion of the enzyme in the polymeric form was increased, whereas exposure to adrenaline (in the presence of glucose and insulin) led to a decrease in enzyme activity. 3. These changes are consistent with a role of citrate (as activator) or fatty acyl-CoA thioesters (as inhibitors) in the regulation of the enzyme by insulin and adrenaline; no evidence that the effects of these hormones involve phosphorylation or dephosphorylation of the enzyme could be found. 4. Changes in the whole tissue concentration of citrate and fatty acyl-CoA thioesters were compared with changes in the initial activity of acetyl-CoA carboxylase under a variety of conditions of incubation. No correlation between the citrate concentration and the initial enzyme activity was evident under any condition studied. Except in fat-pads which were exposed to insulin there was little inverse correlation between the concentration in the tissue of fatty acyl-CoA thioesters and the initial activity of acetyl-CoA carboxylase. 5. It is suggested that changes in the concentration of free fatty acyl-CoA thioesters (which may not be reflected in whole tissue concentrations of these metabolites) may be important in the regulation of the activity of acetyl-CoA carboxylase. The possibility is discussed that the concentration of free fatty acyl-CoA thioesters may be controlled by binding to a specific protein with properties similar to albumin.


Regulation of guanylate cyclase in guinea-pig islets of Langerhans. 1. Guanylate cyclase activity was determined in homogenates of guinea-pig islets of Langerhans by measurement of the conversion of [alpha-(32)P]GTP into cyclic [(32)P]GMP, the reaction products being separated on columns of neutral alumina. 2. The pH optimum of the enzyme was 7.3; it showed a requirement for bivalent cations, the effectiveness of the cations tested being Mn(2+)>>Ca(2+)>Mg(2+). 3. About 70% of enzyme activity was sedimented by centrifugation at 105000g for 60min; activity was increased 2.3-fold by treatment of homogenates with 0.1% Triton X-100. 4. Guanylate cyclase activity of homogenates was increased by acetylcholine, secretin or pancreozymin, but was inhibited by adrenaline, noradrenaline or ATP. Insulin, glucagon, prostaglandins E(1) or E(2), glucose, F(-), diazoxide or glibenclamide were ineffective. 5. Determination of cyclic GMP amounts in islets by radioimmunoassay showed a basal concentration of 2.0pmol/mg of protein, which was increased by incubation of the islets in the presence of acetylcholine or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, but was unaffected by glucose. 6. Dibutyryl cyclic GMP had significant stimulatory effects on rates of insulin biosynthesis in isolated rat islets of Langerhans. 7. These results suggest a possible role for cyclic GMP in the regulation of insulin biosynthesis and secretion.


Comparative studies of NADP-malic enzyme from C-4 and C-3 plants.


Purification and characterization of guanylate cyclase from Caulobacter crescentus.


Ethanol and drug metabolism in mouse liver microsomes subsequent to lipid peroxidation-induced destruction of cytochrome P-450.


Effect of glycyrrhetinic acid on the cyclic nucleotide system of the rat stomach.


Mitochondrial ATP-Pi exchange complex.

Mitochondrial ATP-Pi exchange complex.


Stimulation of drug metabolism by ascorbic acid in weanling guinea-pigs.


Inhibition of hepatic mixed function oxidase activity by propyl gallate.


Mediation of reduced nicotinamide adenine dinucleotide phosphate dependent reduction of cytochrome c by morphine.


Myocardial adenine nucleotides, hexose phosphates and inorganic phosphate, and the regulation of phosphofructokinase activity during fluoroacetate poisoning in the rat.


Effect of trimetoquinol on the cyclic AMP level in the tracheal muscle of guinea-pig.


Reduced glucagon induction of tyrosine aminotransferase in perfused livers after ethanol treatment.


A direct test for mono-oxygenase activity of intact small intestine using surface reflectance fluorimetry.


Nitroreduction of 5-nitrofuran derivatives by rat liver xanthine oxidase and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase.


Ontogenesis of choline acetyltransferase, tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase in the superior cervical ganglion of swine.


The effects of amiodarone (L 3428), an alpha and beta receptor antagonist, on overflow of transmitter and uptake of noradrenaline in the cat spleen.


Azotomycin--toxicologic, biochemical and pharmacologic studies in mice.


Caries experience in english children and young adults during the years 1947-1972.


Controlled clinical trials and caries prevention.


Rampant dental caries in 5-year-old children from a fluoride and from a non-fluoride community.


Dental caries: the distinction between delay and prevention.


Effect of a new beta-adrenergic blocking agent, ICI 66o82, on exercise haemodynamics and airway resistance in angina pectoris.


Immunology of malignancy. Papers presented at the Symposium held at the Charles Salt Research Centre, the Robert Jones and Agnes Hung Orthopaedic Hospital, Oswestry, Shropshire, England 26-28 March 1973.


Management of bronchospasm.

Management of bronchospasm.


Leucocyte separation and transfusion.

Leucocyte separation and transfusion.


The cellular origin of bioluminescence in the colonial hydroid Obelia.


Abolition of the allogeneic inhibition of hematopoietic stem cells by means of syngeneic lymphocytes.


Psychometric patterns as predictors of outcome following hip surgery.


Proceedings: NMR studies of the binding of substrate analogues to L. casei dihydrofolate reductase.


Proceedings: Histamine receptors in the cardiovascular system of the cat.