Proceedings: Some observations on electrically-inexcitable cells (neuroglia?) in rat sympathetic ganglia.


Proceedings: Evaluation of iontophoretic N-methylbicuculline and other inhibitory amino-acid antagonists in rat brain stem.


Proceedings: Pharmacological studies on single neurones in the substantia nigra of the rat.


Proceedings: Assessment of the agonist and antagonist activities of narcotic analgesic drugs by means of the mouse vas deferens.


Proceedings: Modification of the antinociceptive activity of narcotic agonists and antagonists by intraventricular injection of biogenic amines in mice.


The effects of a new beta-adrenoceptor blocking compound, tolamolol, on haemo-dynamics and myocardial function in man. 1 The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.2 The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 +/- 7 to 62 +/- 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 +/- 0.9 to 3.5 +/- 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.3 There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dt(max)) and the derived index of the left ventricular contractile state (V(max)).4 These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.


Effects of Gymnodinium breve toxin on the smooth muscle preparation of guinea-pig ileum. 1 The effects of Gymnodinium breve neurotoxin (GT) on smooth muscles were studied using the guinea-pig isolated ileum.2 The toxin caused strong spasmogenic effects at 1-4 mug/ml, characterized by prolonged tonic contraction with superimposed pronounced pendular movements. Tachyphylaxis was observed upon administration of successive doses.3 Atropine blocked the contractile response elicited by GT, whereas mepyramine and hexamethonium failed to do so. These findings tentatively suggested a cholinergic involvement at a post-ganglionic site of action.4 In the presence of tetrodotoxin the effects of GT were abolished, excluding direct action of the toxin on the smooth muscle.5 It is concluded that GT exerts its spasmogenic effects through stimulation of the post-ganglionic cholinergic nerve fibres.


Role of endogenous catecholamines in the anti-inflammatory activity of alpha-adrenoceptor blocking agents. 1 Drugs which release or modify the response to catecholamines were examined for their effect on the permeability of the mouse peritoneal vascular bed to circulating plasma albumin, labelled with Evans blue.2 Phenoxybenzamine, phentolamine, piperoxane, yohimbine or cocaine reduced the extravasation of Evans blue into the peritoneum, an effect which was antagonized by beta-adrenoceptor blocking drugs. The inhibitory effect of desipramine on the extravasation of Evans blue was less completely antagonized by beta-adrenoceptor blockade.3 Inhibition of catecholamine biosynthesis, ganglion blockade or adrenergic neurone blockade antagonized the reduction in dye extravasation by alpha-adrenoceptor blocking agents and cocaine, but had no significant effect on the response to desipramine. The inhibitory effects of alpha-adrenoceptor blocking agents on dye extravasation were not prevented by bilateral adrenalectomy.4 Mice subjected to the procedure for estimation of vascular permeability excreted increased amounts of adrenaline and noradrenaline. Pretreatment with phenoxybenzamine, piperoxane or cocaine further increased catecholamine excretion, but desipramine caused only a small increase in catecholamine excretion which did not correlate with its effect on dye extravasation.5 It is suggested that phenoxybenzamine, phentolamine, piperoxane and cocaine reduce vascular permeability in the mouse peritoneum by releasing and/or potentiating the effects of endogenous catecholamines on beta-adrenoceptors. Endogenous catecholamines do not appear to be involved in the anti-inflammatory activity of desipramine.


The haemodynamic effects of prolonged oral administration of oxyfedrine, a partial agonist at beta-adrenoceptors: comparison with propranolol. 1 Haemodynamic changes have been studied in cats after the chronic oral administration of oxyfedrine (14 mg/kg for 3-4 weeks) or of placebo (lactose). The initial part of the study was carried out under double-blind conditions. The arterial blood pressure was between 19 mmHg (diastolic) and 27 mmHg (systolic) higher in the oxyfedrine treated animals, but there were no differences between the two groups with regard to cardiac output, left ventricular dP/dt max, heart rate or systolic ejection time.2 In cats similarly treated with propranolol (4 mg/kg) there was a slight (12%), but significant, reduction in cardiac output.3 Isoprenaline dose-response curves were shifted to the right in the cats administered oxyfedrine as well as in those administered propranolol. The degree of shift was five-fold (positive chronotropic response) and 20-fold (decrease in diastolic blood pressure) in the oxyfedrine group and 10- and 80-fold, respectively, in the propranolol group.4 In contrast to the partial blockade of the effects of isoprenaline, the haemodynamic response to oxyfedrine was largely unaltered, both in the cats pretreated with propranolol and in those pretreated with oxyfedrine. The pressor response to noradrenaline was potentiated in the cats pretreated with oxyfedrine.5 These results provide an explanation for the anti-anginal action of oxyfedrine. Some degree of beta-adrenoceptor blockade is achieved without a reduction in cardiac output or left ventricular dP/dt max. The relevance of these findings to the haemodynamic situation in angina is discussed.


Editorial: Bone marrow transplants in leukemia.


A memorable decade in the history of neurology 1874-84. I.


Letter: Lorazepam poisoning.

Letter: Lorazepam poisoning.


Letter: Prevention of exercise-induced asthma by indoramin.


Neurotransmitter synthesis in cephalopod retina.


Tyrosine hydroxylase inhibition by cycloheximide and anisomycin is not responsible for their amnesic effect.


Biosynthesis of branched long-chain fatty acids by species of Bacillus: relative activity of three alpha-keto acid substrates and factors affecting chain length.


Trimethylamine oxide reduction by Salmonella.


Polyarteritis nodosa complicated by a multiple sclerosis like syndrome. A case is presented of a 16-year-old boy with angiographically proven polyarteritis nodosa who developed a multiple sclerosis like syndrome affecting the brain stem and cerebrum. His serum demyelinated nerve in tissue culture. The case is reviewed in detail and the mechanism of myelotoxicity is discussed.


Monthly intermittent chemotherapy of chronic schizophrenic outpatients with pipothiazine palmitate.


The clinical pharmacology of commonly used antihypertensive drugs.


Current concepts in the drug management of angina pectoris.


Choice of antihypertensive drugs for the treatment of hypertension, including hypertensive emergencies.


Assessment of causal prophylactic activity in Plasmodium berghei yoelii and its value for the development of new antimalarial drugs. The causal prophylactic activity of several reference and experimental antimalarial compounds was assessed in sporozoite-induced infections of NMRI mice with Plasmodium berghei yoelii (strain 17X). The animals were inoculated with 10 000 sporozoites per mouse and treated once 2-4 hours later. The test system has proved to be very suitable in experiments involving more than 3 000 mice. The infection rate in 448 untreated controls was 97.3%. Lowering the sporozoite content of the inoculum to 1 000 or 100 sporozoites markedly reduced the rate (65.1% and 32.7%). In experiments with primaquine the causal prophylactic activity was also influenced by the time of drug administration before or after sporozoite inoculation. No causal prophylactic effect was demonstrable with quinine, chloroquine, amodiaquine, amopyroquine, RC-12, or B 505. Primaquine was active, but pamaquine and pentaquine were only sporadically active. The pre-erythrocytic stages of P. b. yoelii were only slightly sensitive to dapsone, sulfadiazine, and sulformethoxine; they were 10-100 times more susceptible to proguanil, cycloguanil, and pyrimethamine. The experimental 6-aminoquinolines NI 147/36, NI 187/82, and BA 138/111 and the 7-chlorolincomycin derivative U 24729 were also studied. Experiments in which curative activity against blood-induced infections of P. b. yoelii was evaluated showed that the causal prophylactics act more specifically against the pre-erythrocytic than against the erythrocytic forms. This specificity was most pronounced among the DHFR-inhibitors, whose outstanding activity may be explained by the fact that the rate of multiplication of the pre-erythrocytic forms of P. b. yoelii is greater than that of other plasmodia used hitherto; it is also greater than the rate shown by the malaria parasites of man and that of the erythrocytic forms of P. b. yoelii itself. We believe that this feature will render P. b. yoelii very useful for determination of the causal prophylactic activity of new compounds, but it may also overrate the potency of drugs that interfere with nucleic acid biosynthesis.


A cytofluorometric study of the myenteric plexus in the guinea pig.


Population dynamics and age grading of mosquitos. The dynamics of a vector population follows a characteristic pattern determined by the normal or modified environmental conditions of the biotope and by vector behaviour. The wide use of the precise method of age grading developed by Detinova and Polovodova has led to the conclusion that the dynamics of the various age groups may indicate behavioural, environmental, and epidemiological trends and changes and their significance. Age grading is useful for the qualitative assessment of vector density in general and of man-mosquito contact from the operational and epidemiological points of view, but only when sampling in time and space and the processing of the material collected have been correctly performed.


Allied health personnel in anesthesia.

Allied health personnel in anesthesia.


Structure, function, and possible origin of a bifunctional allosteric enzyme, Escherichia coli aspartokinase I-homoserine dehydrogenase I.


Psychiatric aspects of learning disabilities.


Control of fatty-acid biosynthesis by long-chain acyl CoAs and by lipid membranes.


The synthesis of adenine-substituted derivatives of NADP and their potential as active coenzymes and affinity adsorbents.


Effect of temperature on the transmitter release from the "purinergic" nerves in the guinea-pig taenia coli.


Prediction of the non-specific cardiodepressant effects of beta-adrenoceptor blocking agents in vitro and in vivo by means of the Hansch analysis.


Coenzyme dependency of alcohol dehydrogenase in the retina of the rat. III. Effect of light-and dark adaptation on the redox state of the pyridine nucleotides.


Coenzyme dependency of alcohol dehydrogenase in the retina of the rat. IV. Retinol dehydrogenase (RDH) activity in the developing normal and retinitis rat retina, and the effect on enzyme activity of increasing concentrations of NAD or NADP.


Effects of glutamate and GABA on specific response properties of neurones in the visual cortex.


The differential sensitivity of spinal interneurones and Renshaw cells to Kainate and N-methyl-D-aspartate.


The umbrellar growth process in the leptomedusae Phialidium hemisphaericum (syn. Campanularia johnstoni).


Effect of burimamide and metiamide on pentagastrin-stimulated gastric acid secretion and gastric mucosal blood flow in cats.


A soluble transhydrogenase enzyme from Rhodospirillum rubrum chromatophores.


Kinetic isotope effects in the NAD- and NADP-specific isocitrate dehydrogenases of pig heart.


Protochlorophyll and protochlorophyllide as precursors for chlorophyll synthesis in vitro.


The effects of artificial cryptorchidism on the composition of epididymal plasma in the rabbit.


Regional graft-versus-host and host-versus-graft reactions: histology of the popliteal lymph nodes.


Protein turnover in rat testis.

Protein turnover in rat testis.


Sulthiame and behaviour.

Sulthiame and behaviour.


The employee health service and infection control.


Settle plate assessment of airborne infections.


The impact of institutionalization.

The impact of institutionalization.


Sanitation codes help curb food poisoning.


A Canadian patient's bill of rights.

A Canadian patient's bill of rights.


Enzymes of carbohydrate and fat metabolism in anti-insulin serum diabetes; inactivation by free fatty acids and the protective effect of cellular protein.


Analysis of lymphoid cell types developing in mouse foetal liver.


Studies of metabolism in embryonic development. V. Biosynthesis of corticosteroids by trout embryos.


Oxidative enzymes in the development of Fasciola hepatica L. I. Tetrazolium reductases and oxidases in miracidium.


The determination of methyprylon and its metabolites in biological fluids by gas chromatography.


Penicillium viridicatum mycotoxicosis in the rat. IV. Attempts to modify the tissue responses.


The clinical spectrum of prune belly syndrome.


Prune belly syndrome with gastrointestinal tract anomalies.


Halogenated hydrocarbon solvents: long term effects and biological sampling in human beings. International conference, Hamburg, October 24-26,1973. Conclusions and recommendations.


The control of dental disease by prevention.


Current experiments in the delivery of dental services.


Behavioral approaches for problems with alcohol.


Psychological and social variables and personality patterns of drug abusers.


Amphetamines in the District of Columbia. III. Stimulant abuse in narcotics addicts in treatment, with an emphasis on phenmetrazine.


Naloxone and the narcotic abuser: a controlled study of partial blockade.


Vesical distension and ureteral activity in the canine.


Proceedings: Chronic granulomatous disease.


The role of circulating hepatitis B antigen/antibody immune complexes in the pathogenesis of vascular and hepatic manifestations in polyarteritis nodosa. To investigate further the role of hepatitis B antigen (HBs Ag) and specific immune complexes in polyarteritis, sera from 55 histologically confirmed cases were tested for the presence of hepatitis B antigen-associated particles and hepatitis B-antibody (anti HBs) by solid phase radio-immunoassay, electron microscopy, and passive haemagglutination. Results of these findings have been correlated with the clinical course of the disease.HBs Ag was detected in 30 patients (54.5%) and anti HBs in 13/45 (28%). Subtyping in 20 patients revealed that 11 were Y and 9 D. Thirty-seven cases (69%) demonstrated either HBs Ag or anti HBs and 5/45 (11%) had both. Electron microscopic examination showed 20 nm spherical and tubular particles in sera of 20/27 patients with 42 nm particles in 11 cases and clumped particles in 12 (60%). No correlation was found between detection of immune complexes and liver disease whereas the presence of coexisting hepatitis B antigen and antibody or aggregated particles was restricted to cases of active vasculitis. Seroconversion or the presence of hepatitis B antibody alone was associated with improved prognosis. Circulating hepatitis B antigen antibody complexes may be responsible for vasculitis or polyarteritis but do not appear to be pathogenic for the liver.


A mosquito egg counter by simple modification of a colorimeter.


The personal and marital adjustment of parents as related to observed child deviance and parenting behaviors.


Psychopharmacology in the aged. Research considerations in geriatric psychopharmacology.


Psychopharmacology in the aged. Use of psychotropic drugs in geriatric patients.


Current leprosy research: a report on the 10th Internation Leprosy Congress.


Psychopharmacology in the aged. Discussion.


Proceedings: Effect of age on steroidogenesis in experimental bilateral cryptorchid rats.


Proceedings: Human erythrocyte glucose 6-phosphate dehydrogenase. Content of tightly bound NADP.


Proceedings: A proposed model of the neurotransmitters involved in the control of corticotrophin releasing hormone.


Proceedings: Clinical and hormonal effect of human chorionic gonadotrophin in prepubertal crytorchid boys.


Proceedings: The mechanism of hypertriglyceridaemia in oestrogen-treated rats.


Identification and tooth morphology.

Identification and tooth morphology.


Changes in intracellular free calcium concentration during illumination of invertebrate photoreceptors. Detection with aequorin. Aequorin, which luminesces in the presence of calcium, was injected into photoreceptor cells of Limulus ventral eye. A bright light stimulus elicited a large increase in aequorin luminescence, the aequorin response, indicating a rise of intracellular calcium ion concentration, Ca(i). The aequorin response reached a maximum after the peak of the electrical response of the photoreceptor, decayed during a prolonged stimulus, and returned to an undetectable level in the dark. Reduction of Ca(o) reduced the amplitude of the aequorin response by a factor no greater than 3. Raising Ca(o) increased the amplitude of the aequorin response. The aequorin response became smaller when membrane voltage was clamped to successively more positive values. These results indicate that the stimulus-induced rise of Ca(i) may be due in part to a light-induced influx of Ca and in part to release of Ca from an intracellular store. Our findings are consistent with the hypothesis that a rise in Ca(i) is a step in the sequence of events underlying light-adaptation in Limulus ventral photoreceptors. Aequorin was also injected into photoreceptors of Balanus. The aequorin responses were similar to those recorded from Limulus cells in all but two ways: (a) A large sustained aequorin luminescence was measured during a prolonged stimulus, and (b) removal of extracellular calcium reduced the aequorin response to an undetectable level.


Diagnostic accuracy of clinical data, quantitative electromyography and histochemistry in neuromuscular disease. A study of 105 cases.


Muscle transplantation and regeneration in the dystrophic hamster. Part 2. Histochemical studies.


The group supervisory conference.

The group supervisory conference.


Computer-assisted learning in graduate psychiatric nursing.


The disadvantaged student in nursing education.


CAMP: computer and me: psychotherapeutically.


Collegiate nursing education: an ambivalent professionalism.


Experiential learning in groups.

Experiential learning in groups.


A brief bibliography on fatigue and fitness.


Countercurrent immunoelectrophoresis in the evaluation of childhood infections. Samples of CSF, serum, and urine from 162 children with a clinical diagnosis of possible bacterial infection were examined by CIE within 1 hr of admission to the hospital. Results obtained were compared to information derived from gram stain and bacterial cultures of these specimens. Thirty-eight of 59 patients with culturally proved bacterial infections had positive CIE determinations at the time of admission. Highest correlation between culture and CIE results was in patients with meningitis due to Hemophilus influenzae type b while poorest correlation was obtained in children with pneumococcal septicemia. PRP within serum or CSF was quantitated on 21 occasions in patients with H. influenzae meningitis. Patients who experienced sequelae of their meningitis had significantly (p less than 0.005-0.025) higher levels of PRP within CSF and serum than those whose recovery was uneventful.


Mycobacterium fortuitum osteomyelitis of the calcaneus secondary to a puncture wound.


Hepatic microsomal drug oxidation and electron transport in newborn infants. Many drugs require oxidative metabolism for termination of action and/or for elimination from the body. Many oxidative reactions are catalyzed by hepatic microsomal enzymes. The activities of various drug-metabolizing enzymes, namely, NADPH cytochrome c reductase, NADPH oxidase, aminopyrine-N-demethylase, and analine P-hydroxylase, and the content of cytochrome P-450, were measured in hepatic microsomes obtained from seven newborn infants and four adult patients. The results in the newborn infant show increasing activities of these enzymes (except aminopyrine-N-demethylase) related to advancing age. Good correlation between three components of the hepatic microsomal mixed function oxidase system and aniline p-hydroxylase was established, whereas only NADPH oxidation correlated with aminopyrine N-demethylation. The rate of substrate or drug oxidation and the activities of the components of the microsomal electron transport pathway were lower than comparable values in the adult. The data demonstrate a possible biochemical basis for the transient deficiency in drug metabolism seen in newborn infants.


Item content of the Group Personality Projective Test.


"Short-form" content scales for the MMPI.


Proceedings: Aequorin-light and tension responses from bundles of myofibrils following a sudden change in free calcium.


Manifest hostility as modified by the K and SO-R scales of the MMPI.


The effects of population density on the overt behavior of mental patients.


Correlation of placebo responses and personality characteristics in myofascial pain-dysfunction (MPD) patients.


Investigation of the cellular immunocompetence in chronic lymphatic leukemia and malignant lymphoma patients as assessed by the local graft versus host reaction in rats.


Psychological potentials of chronic pain.


Purification of a plasma membrane-bound adenosine triphosphatase from plant roots.


Cultured cell systems and methods for neurobiology.


Solubilization and polyacrylamide gel electrophoresis of membrane enzymes with detergents.


Rosette forming cells in neonatal animals.


Biogenesis and modulation of membrane properties in greening Chlamydomonas reinhardi, y-1 cells.


Drugs for cardiac complaints--part 2.

Drugs for cardiac complaints--part 2.


Age-dependent induction of isoenzymes of tyrosine aminotransferase of the liver of the rat.


Amino acid neurotransmitters and the brain. Beattie Smith lecture, March 28, 1974.


Letter: Tetracycline-resistant pneumococci.


Association of Operating Room Nurses Congress 1974.


Acid base balance in relation to gastric acid secretion stimulated by histamine and pentagastrin in cats.


Macrophages activation during graft-versus-host reaction.


An analysis of the alpha- and beta-effects of isoprenaline on the isolated nictitating membraen.


The effect of histamine-H2-receptor-antagonists on gastric acid secretion, gastric mucosal blood flow and acid base balance in cats.


The action of bicuculline upon acetylcholine-induced excitations of central neurones.


To practice or not to practice: developing state law and policy on physician assistants.


Psychological management of Crohn's disease.


The lymphocyte surface. III. Function of Fc receptor, C'3 receptor and surface Ig bearing lymphocytes: identification of a radioresistant B cell.


Leishmania in phlebotomid sandflies. I. Modifications of the flagellum associated with attachment to the mid-gut and oesophageal valve of the sandfly.


Catalysis, binding and enzyme-substrate complementarity.


The synaptic organization of optic afferents in the amphibian tectum.


Pigment epithelial cell ensheathment of cone outer segments in the retina of the domestic cat.


Functional synaptic relations during the development of the retino-tectal projection in amphibians.


Evolution and adaptive radiation in the macrothricidae (Crustacea: Cladocera): a study in comparative functional morphology and ecology.


Determination of drug-induced changes in sleep quality based on digital computer "sleep prints".


Note on treatment of heterosexual anxiety using short-term massed desensitization.


Control of pain by drugs.

Control of pain by drugs.


Comparative parental MMPI protocols of children evaluated at a child development clinic.


Facilitation of group desensitization of test anxiety.


Contrasting assumptions and directions in MMPI research on alcoholism.


Physical fitness and personality in alcoholism. Canonical analysis of measures before and after treatment.


The hormones of the hypothalamus.

The hormones of the hypothalamus.


An assessment of oral disease among primary school children in Lebanon. 1. Assessment of dental caries.


Pavlovian conditioned inhibitory processes in behavior therapy.


Intracranial injection of neurotransmitters and hormones and feeding in sheep.


Scientific aspects of behavior therapy.

Scientific aspects of behavior therapy.


Perspective on flooding.

Perspective on flooding.


Behavioral methods in group and family therapy.


Biofeedback and visceral learning: clinical applications.


Phobias: broad-spectrum behavioral views.


The effects of certain pharmacological compounds and ions on fish hearts.


Research and training needs in behavior therapy.


Toward hypotheses for a biochemical component in the vulnerability to schizophrenia.


Anaphylactic shock clinical forms, pathogenesis and treatment.


Recent advances in cardiovascular pharmacology.


Chemical sensitivity at different temperatures of the Br-type, bimodal pace-maker neurone in the CNS of the snail Helix pomatia l.


Organization of visual cortex primary response.


Suppresion by bivalent cations of the recycling system composed of glucose-6-phosphate dehydrogenase and glutathione reductase.


Child health in the People's Republic of China.


Differentiation of H1- and H2-receptors mediating positive chrono- and inotropic responses to histamine on atrial preparations of the guinea-pig.


Cardiovascular effects of burimamide and metiamide.


The pharmacology of azatadine, a potential antiallergy drug.


Metabolism of the bloodmeal in tsetse flies (a review).


The African attitude toward sickness. Its relation to sculpture.


Autoimmunity in trypanosome infections. III. The antiglobulin (Coombs) test.


Autoimmunity in trypanosome infections. IV. Natural infections in hartebeest, hyaena and lion in the Serengeti National Park, Tanzania.


Lack of incorporation of tritiated thymidine in Trypanosoma vivax in vitro.


Hydatid disease in India.

Hydatid disease in India.


Metabolism of drugs by microorganisms in the intestine.


The pattern of flight muscle damage in relation to the distribution of developing filarial larvae in Aedes aegypti and Mansonia uniformis.


Arbovirus infections in Sarawak, October 1968--February 1970: Japanese encephalitis virus isolations from mosquitoes.


Autonomic drug-receptor interaction in the presence and absence of extracellular calcium in mammalian myocardium.


Modifications of the pressor response to hog renin by adrenalectomy, demedullation, adrenoceptor blocking drugs and catecholamine depletors in anaesthetized rats.


Gamma-glutamyl transpeptidase activity (GGTP) in ontogenetic development of the guinea pig.


Purification and some properties of gamma-glutamyl transpeptidase from cow's milk.


Principles of immunity. II. Cellular immunology and immunogenetics.


Localization of gamma-glutamyl transpeptidase (GGTP) in the rat small intestine. Adaptive response of the enzyme after massive small bowel resection.


Vanadium in whole human enamel and its relationship to dental caries.


Sucrose taste thresholds in caries-free naval recruits.


A 15-yr retrospective survey of the distributions of clinical caries attacks in human permanent maxillary incisors.


The responses of the human temporal and rabbit ear artery to 5-hydroxytryptamine and some of its antagonists.


I. Synchrony and desynchrony in fear and avoidance.


The epidemiology of self-poisoning in Hobart, 1968-1972.


II. Desynchrony in measures of fear.

II. Desynchrony in measures of fear.


Effect of nitrate on the synthesis and decay of nitrate reductase of Neurospora. 1. A method was developed to examine the turnover of nitrate reductase by the use of tungstate. 2. Evidence is presented which suggests that the disappearance of nitrate reductase activity from Neurospora mycelia exposed to non-inducing conditions is due to the disappearance of the enzyme protein(s) from the mycelia, and not merely due to the disappearance of its (their) catalytic power. 3. The presence of NO(3) (-) in the culture medium slows down the rate of degradation of nitrate reductase in Neurospora in vivo.


The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets. 1. Rates of insulin secretion, glucose utilization, lactate output, incorporation of glucose into glycogen, contents of glucose 6-phosphate, fructose 1,6-diphosphate and ATP, and maximally extractable enzyme activities of hexokinase, high-K(m) glucose-phosphorylating activity (;glucokinase'), glucose 6-phosphatase and unspecific acid phosphatase were measured in isolated pancreatic islets from fed and 48-h-starved mice. 2. In the fed state insulin secretion from isolated islets was increased five- to six-fold when the extracellular glucose concentration was raised from 2.5mm to 16.7mm; 5mm-caffeine potentiated this effect. The secretory response to glucose of islets from mice starved for 48h was diminished at all glucose concentrations from 2.5mm up to approx. 40mm. Very high glucose concentrations (60mm and above) restored the secretory response to that found in the fed state, suggesting that the K(m) value for the overall secretory process had been increased (approx. fourfold) by starvation. Addition of 5mm-caffeine to islets from starved mice also restored the insulin secretory response to 2.5-16.7mm-glucose to normal values. 3. Extractable hexokinase, ;glucokinase', glucose 6-phosphatase and unspecific phosphatase activities were not changed by starvation. 4. Glucose utilization and glycolysis (measured as the rate of formation of (3)H(2)O from [5-(3)H]glucose over a 2h period) was decreased in islets from starved mice at all glucose concentrations up to approx. 55mm. At still higher glucose concentrations up to approx. 100mm, there was no difference between the fed and starved state, suggesting that the K(m) value for the rate-limiting glucose phosphorylation had been increased (approx. twofold) by starvation. Preparation of islets omitting substrates (glucose, pyruvate, fumarate and glutamate) from the medium during collagenase treatment lowered the glucose utilization measured subsequently at 16.7mm-glucose by 38 and 30% in islets from fed and starved mice respectively. Also the 2h lactate output by the islets at 16.7mm extracellular glucose was diminished by starvation. Incorporation of glucose into glycogen was extremely low, but the rate of incorporation was more than doubled by starvation. 5. After incubation for 30min at 16.7mm-glucose the content of glucose 6-phosphate was unchanged by starvation, that of ATP was increased and the concentration of (fructose 1,6-diphosphate plus triose phosphates) was decreased. 6. Possible mechanisms behind the correlated impairment in insulin secretion and islet glucose metabolism during starvation are discussed.


The synthesis of naturally occurrring phosphonolipids.


Changes in phylloquinone epoxidase activity related to prothrombin synthesis and microsomal clotting activity in the rat. The oxidation of phylloquinone to the 2,3-epoxide (by phylloquinone epoxidase) was studied in liver from control and warfarin-resistant rats. The reaction requires microsomal fraction, soluble protein, a heat-stable soluble factor and O(2). It is not inhibited by CO or CN(-). Epoxidase activity was stimulated if plasma prothrombin was lowered either by anticoagulants or the absence of vitamin K. The activity of the enzyme rapidly returned to normal values after the administration of vitamin K to hypoprothrombinaemic rats. These differences in the activity of the enzyme occur in the microsomal fraction and not the cytosol. A thrombin-generating polypeptide that accumulates in microsomal fraction of hypothrombinaemic rats correlated directly with epoxidase activity. These data support the view that enzymic interconversion of phylloquinone and its 2,3-epoxide participates in the biological activity of vitamin K.


Diurnal rhythms of hepatic carbohydrate metabolism during development of the rat. The ;8+16' feeding schedule (8h feeding and 16h without food in each 24h cycle) was applied to nursing mother rats to study enzyme development in neonatal rats in the absence of solid food. A ;16+8' suckling schedule (16h with the mother and 8h while the mother is fed in a separate cage) was used to show that the increases in pyruvate kinase, glucokinase and aldolase B activities that occur in the late suckling period of liver development do not require the intake of solid food at this time. Their activities may, however, be modulated by the composition of the diet at the time of weaning. Adaptation to the composition of the diet can occur within one feeding period, and to the periodicity of food provision in one or two feeding periods. In the early neonatal period, diurnal rhythms of tyrosine aminotransferase, liver glycogen and glucokinase are either greatly suppressed or absent, but develop rapidly after weaning. Food-dependent rhythms of glycogen and tyrosine aminotransferase were included in the late suckling period (day 14).


Regulatory mechanisms for liver acetyl coenzyme A carboxylase.


Metabolic regulation in the release and action of excitatory and inhibitory amino acids in the central nervous system.


Neuronally mediated enzyme induction in adrenergic neurons and adrenal chromaffin cells.


Regulatory significance of the release and action of adenine derivatives in cerebral systems.


Beta-adrenoreceptor blocking properties of new thienylethanolamine derivatives.


Cardiovascular and antiarrhythmic effects of 1-(4,5-dichloro-2-thienyl)-2-t-butylaminoethanol (QM-5119), a new beta-adrenergic blocking agent.


Effect of camazepam (SB-5833), a new antianxious drug, on cardiac contractility and coronary hemodynamics.


Prolongation of anoxia-induced hyperemia in healthy middle-aged men treated with cinnarizine and flunarizine.


The prevalence of dental caries in 3-year-old children. Some social differences and a method of assessing pre-school needs at a local level.


Adult dental health in Scotland 1972.

Adult dental health in Scotland 1972.


Personality characteristics of adolescent amphetamine users as measured by the MMPI.


Personality and demographic characteristics of two sub-types of drug abusers.


Combination of carcinoembryonic antigen and gamma glutamyl transpeptidase in the study of the evolution of colorectal cancer. Plasma CEA values and serum γ glutamyl transpeptidase activities have been compared in control subjects and 109 patients with colorectal carcinoma and 35 with non-malignant hepatic disease. CEA values alone differentiate hepatic metastases from non-malignant hepatic disease with a high degree of certainty. While CEA may be elevated with metastases, irrespective of site, γGT is elevated mainly in association with hepatic metastases. The combination of CEA and γGT is helpful in identifying hepatic metastases and in their differentiation from local recurrences or metastases to other sites.


Pharmacology of the aorta. A brief review.


A study of the factors affecting the sleeping time following intracerebroventricular administration of pentobarbitone sodium: effect of prior administration of centrally active drugs. 1 Injection of pentobarbitone sodium into a lateral cerebral ventricle of rats produced a loss of righting reflex. The duration of anaesthesia was dose-dependent.2 The optimum dose of pentobarbitone to allow study of the factors affecting the sleeping time was considered to be 650 mug injected in 25 mul water.3 In a study of the effect of age and sex on the sleeping time, the youngest rats used (88 g body weight) were found to be the most sensitive to barbiturate. Female rats were more sensitive than male animals.4 The duration of anaesthesia was not affected by induction or inhibition of hepatic drug-metabolizing enzyme activity.5 Prior administration (acute) of central nervous system depressant drugs shortened the latent period and prolonged the duration of sleep. Prior administration of stimulant drugs antagonized the effect of pentobarbitone.6 Animals withdrawn following chronic administration of a number of drugs, barbitone, barbitone/bemegride mixture, Mandrax (methaqualone: diphenhydramine; 10: 1), chlordiazepoxide, nitrazepam, chlorpromazine or ethanol, exhibited a significant tolerance to intracerebroventricularly administered pentobarbitone.7 Withdrawal of amphetamine, morphine, methyprylon or diazepam did not result in tolerance to intracerebroventricularly administered pentobarbitone.8 Chronic administration of all drugs except amphetamine and morphine induced a tolerance to intraperitoneally administered hexobarbitone (100 mg/kg).9 The usefulness of sleeping time determination following intracerebroventricular administration of pentobarbitone as an assessment of central nervous system excitability is discussed. It is concluded that this method gives a valid indication of the sensitivity of the central nervous system to barbiturate and of the level of excitability in general. The method is particularly applicable in situations where the activity of hepatic drug-metabolizing enzyme activity may be altered.


Analysis of the effects on body temperature of intracerebroventricular injection in anaesthetized dogs of gamma-aminobutyric acid. 1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum.2 gamma-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia.3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative.4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances.5 Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent.6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs.7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA.8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline.


Quinones as anticancer agents: potential bioreductive alkylating agents.


Inhibition by non-steroid anti-inflammatory agents of rabbit aorta contracting activity generated in blood by slow reacting substance C. 1 A crude and a partially purified preparation of slow reacting substance C (SRS-C) as well as arachidonic acid decreased resistance to perfusion of the dog hind paw. This effect was suppressed by treatment with non-steroid anti-inflammatory drugs.2 Injections of SRS-C or of arachidonic acid induced marked and reproducible contractions of strips of rabbit aorta and a rat stomach which were bathed in blood from an anaesthetized dog. The effect on the rabbit aorta is attributed to formation of a rabbit aorta contracting substance (RCS). The contractions were suppressed when the dog was treated with a non-steroid anti-inflammatory drug.3 Incubation of blood or of platelet-rich plasma with SRS-C or arachidonic acid resulted in the formation of similar materials. This formation was suppressed by anti-inflammatory drugs.4 SRS-C, linoleic, linolenic, and arachidonic acids are suitable substrates for soybean lipoxidase for the generation of RCS.5 It is suggested that RCS and prostaglandin are formed within platelets, when SRS-C or arachidonic acid are injected into animals or added in vitro. Non-steroid anti-inflammatory drugs suppress these effects, possibly by inhibiting prostaglandin synthetase.


Effect of autonomic blockade on the transient changes in cardiac frequency on relief of hypoxia in man.


Methods of measuring the reliability of caries prevalence and incremental data.


Prevalence and interrelationships of root surface caries on Lufa, Papua New Guinea.


Social inequality and caries studies in 1,719 Danish military recruits.


The treatment of arterial hypertension with a new alpha-blocker, indoramin.


Evaluation of benapryzine in psychotic patients treated with phenothiazines.


Assessment of lorazepam in severe neurotic states.


Quantitative microscope-photometric determination of enzyme activities in cryostat sections.


Studies on the metabolism of embryonic bone and its modification by parathyroid extract.


Quantitative histochemistry of glucose metabolism in the islets of Langerhans.


Some recent refinements of quantitative histochemical analysis.


Malignant hypertension.

Malignant hypertension.


Biperiden (Akineton): effective prophylactic and therapeutic anti-parkinsonian agent.


Tissue distribution and binding of radioactivity from 14C-thiourea in the rat.


The metabolism of safrole and 2',3'-epoxysafrole in the rat and guinea pig.


In vitro acetylation of drugs by human blood cells.


Studies on seed-oil triglycerides. Factors controlling the biosynthesis of fatty acids and acyl lipids in subcellular organelles of maturing Crambe abyssinica seeds.


The reversible reduction of testosterone to androst-4-ene-3alpha, 17beta-diol by a soluble enzyme of rat liver.


The flux of intermediates and products in aromatizaton of C19 steroids by human placental microsomes.


In vitro metabolism of 14C-pesticidal carbamates by fetal and maternal brain, liver, and placenta of the rat.


Synergism between lymph node and bone marrow cells for production of granulocytes. I. Requirement for immunocompetent cells.


Quantitation of plasma levels of propoxyphene and norpropoxyphene by combined use of stable isotope labeling and selected ion monitoring.


Transfer of deuterium from (1-2H2) ethanol to Krebs cycle and related acids of rat liver in vivo.


Synergism between lymph node and bone marrow cells for production of granulocytes. II. Enhanced colony-stimulating activity of sera of mice with graft-versus-host reaction.


Comparative stimulatory effects of four phenothiazines on hepatic microsomal enzymes.


Effect of metiamide on histamine metabolism in man.


Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene.


Partial resolution of the mixed-function oxidase system of bovine adrenocortical microsomes into two fractions in the absence of detergents.


Effects of sympathetic denervation of the rabbit oviduct on normal ovum transport and on transport modified by estrogen and progesterone.


Effects of sulphasalazine (Salazopyrin) on faecal flora in patients with inflammatory bowel disease. The faecal flora of 21 patients with proctocolitis and five patients with Crohn's disease of the large bowel was examined both while sulphasalazine was being administered and during control periods. Patients with proctocolitis and Crohn's disease who were not receiving sulphasalazine had a similar flora which did not differ in any way from the normal. The effect of sulphasalazine was to decrease the numbers of opalescent-negative clostridia, enterobacteria, and total non-sporing anaerobes. It is suggested that this antibacterial effect of sulphasalazine, which has not been previously demonstrated, may be related to the beneficial effects of this drug in proctocolitis and should be investigated further.


Virological investigations of mosquitoes in some biotopes of southern Moravia in summer season 1972.


Oxidation of exogenous NADH by corn mitochondria.


Cyclophosphamide induced abnormalities of internal organs in rat foetuses.


Effect of environmental factors on thyroid gland in vitro.


A case of hereditary methemoglobinemia with NADH-methemoglobin reductase (diaphorase) deficiency.


Social and psychological factors associated with length of stay in a drug treatment facility.


Opiates, amphetamines, alcohol: a comparative study of American soldiers.


Proceedings: Sites of gamma aminobutyrate transaminase (GABA-T) activity in the rat cerebellar cortex.


A profile of non-specific arteritis as observed in Eastern India.


The Goldberg rules in the detection of MMPI codebook modal diagnoses.


The localization of enzymes in fixed sections of soybean root nodules by electron microscopy.


Some correlates of Category Test scores for nonorganic psychiatric patients.


How to make your next conference count.

How to make your next conference count.


The MMPI response consistencies of normal, neurotic and psychotic women.


Depression as a function of levels of desired and obtained pleasure.


Test-retest stability of long and short MMPI scales over two years.


Alcoholic personality types: identification and correlates.


Discriminating criminal types and recidivism by means of the MMPI.


Minnesota Multiphasic Personality Inventory correlates of dysphasic language disturbances.


The morphogenetic properties of the node in Clytia johnstoni.


The effect of inhibitors on the electron-transport chain of Bacillus brevis. Evidence for branching of the NADH oxidase respiratory chain.


Cytochromes in Streptococcus faecalis var. zymogenes grown in a haematin-containing medium.


Effects of D-glutamate on mycelial growth and glutamate dehydrogenase enzymes of Coprinus lagopus.


Riboflavin deficiency and respiratory flavoproteins of Bacillus subtilis.


Physiological and pharmacological properties of Purkinje cells in rat cerebellum degranulated by postnatal x-irradiation.


A useful transformation for comparing dose-response curves.


Competitive inhibition of Asp1-beta-amide-Val5-angiotensin II by Sar1-Ile5-Ile8-angiotensin II in cat isolated cardiac muscle and coronary vessels.


The role of cerebral blood flow for the recovery of the brain after prolonged ischemia.


Effect of neuroleptics on the disappearance rate of (14C) labelled catecholamines formed from (14C)tyrosine in mouse brain.


Hypothermic and toxic actions of 2-butyne-1, 4-diol and other related diols in the rat.


Inhibitory effect of L-glutamine on the aspirin-induced gastric lesions in the rat.


Inhibition of alpha-chymotrypsin by dibenamine.


Phase studies of mixed phosphated surfactants, n-hexane and water.


Computer analysis of multicomponent ultraviolet spectra.


A note on the interaction between two phosphated surfactants.


A field test for hallucinogens: further improvements.


The binding of chlorpromazine to human serum albumin.


Improved method for isolation of hypoglycins A and B from fruit of Blighia sapida.


Regulation of (3H)5-hydroxytryptamine release from rat brain slices.


Influence of alpha- and beta-adrenoceptors on the release of noradrenaline from field stimulated atria and cerebral cortex slices.


Increase in adrenal dopamine following 6-hydroxydopamine.


The involvement of noradrenergic systems in the locomotor activity stimulation in mice produced by beta-phenethylamine.


Enhancement of noradrenaline turnover in rat brain by L-dopa.


The effects of indomethacin on the development of tolerance to amphetamine-induced hyperthermia. Are prostaglandins involved?


Inactivation of prostaglandin E2 by rabbit lung homogenates.


Effects of a human plasma fraction on skin reactions in the rat and rabbit.


Do adrenergic fibres have muscarinic inhibitory receptors?-- a reply.


The choice of paper and thin-layer chromatographic systems for the analysis of basic drugs.


Measurement of the 'spontaneity' of self-emulsifiable oils.


Multicomponent analysis of ultraviolet spectra: application to pharmaceutical dosage forms.


The depressant action of morphine on transmission at a skeletal neuromuscular junction is non-specific.


Conditions affecting the interaction of cholinergic agents on the longitudinal muscle of the guinea-pig ileum--unexpected effects with hexamethonium.


Glucose intolerance in thiamine-deficient rats.


A pharmacokinetic investigation of the distribution and elimination of diethylpropion and its metabolites in man.


Anthracene derivatives in tissue culture of Cassia senna L.


Reversal of yeast-induced motor impairment in rats as a test for narcotic and non-narcotic analgesics.


Reversal by prostaglandin E2 of the inhibitory effect of indomethacin on contractions of guinea-pig ileum induced by angiotensin.


Effect of isoprenaline on the phosphodiesterase activity of the rat heart.


The conformation of dopamine at its uptake site; further studies with rigid analogues.


Effects of oxotremorine and physostigmine on the turnover of dopamine in the corpus striatum and the limbic system.


An isolated perfused coronary artery preparation from the kitten.


Further evidence for the stimulation of rat brain dopamine receptors by a cyclic analogue of dopamine.


Antagonistic effects of neuroleptics and apomorphine on synaptosomal tyrosine hydroxylase in vitro.


Regional differences in homovanillic acid concentrations after acute and chronic administration of antipsychotic drugs.


Distribution of amphetamine and its hydroxylated metabolites in various areas of the rat brain.


Red back spider venom and inhibitory transmission.


The effects of a human plasma fraction on adjuvant arthritis and granuloma pellet reactions in the rat.


Pharmacokinetic studies on the selective beta1-receptor antagonist metoprolol in man.


Electron-capture GLC determination of blood levels of 7-chloro-1,3-dihydro-5-(2'-chlorophenyl)-2H-1,4-benzodiazepin-2-one in humans and its urinary excretion as lorazepam determined by differential pulse polarography.


The effects of isoxsuprine hydrochloride on the cyclic nucleotide system in the rat uterus.


Tryptaminergic and dopaminergic responses of Schistosoma mansoni.


The internal anal sphincter in the cat: a study of nervous mechanisms affecting tone and reflex activity. 1. Smooth muscle activities in rectum and internal anal sphincter have been recorded using intraluminal balloons.2. Reflex activation of the sphincter, caused by distension of the rectum, has been assessed before and after various combinations of blocking drugs.3. Responses to stimulation of hypogastric or sacral nerves, or to the administration of drugs with autonomic actions have been tested before and after various combinations of blocking drugs.4. Results indicate that the tone of the internal anal sphincter is influenced by a number of neural mechanisms. These include motor pathways involving both alpha-adrenergic and cholinergic mechanisms and inhibitory pathways involving both beta-adrenergic and non-adrenergic non-cholinergic mechanisms.5. Cholinergic contractions of the sphincter were converted to relaxations after alpha-adrenergic blockade. This indicates that the contractions are an indirect effect operating through an adrenergic reflex. Cholinergic relaxations may also be indirect and operate through reflex inhibition secondary to rectal contractions.6. Sphincteric motor activity is controlled largely through alpha-adrenergic mechanisms by adrenergic nerves acting directly on the muscle. beta-Adrenergic inhibitory mechanisms are thought to operate indirectly via ganglia.7. The over-all control of the sphincter is by complex reflex mechanisms involving numerous pathways and the activity of the sphincter at any one time is determined by the net balance between motor and inhibitory influences.8. Sacral nerve stimulation indicated that it contains cholinergic nerves to the rectum, non-adrenergic non-cholinergic inhibitory axons to the sphincter and variable numbers of adrenergic axons to the sphincter.9. Responses of the sphincter to drugs and nerve stimulation were often variable, as has been described many times in the literature. It is considered that this is due to complex combinations of indirect reflex effects, secondary to activation of structures outside the sphincter, operating with or against direct effects on the sphincter itself.


On the transmitter function of 5-hydroxytryptamine at excitatory and inhibitory monosynaptic junctions. 1. Two symmetrical giant neurones located in the cerebral ganglion of Aplysia californica contain 4-6 p-mole 5-hydroxytryptamine (5-HT) and are able to synthesize it (Weinreich, McCaman, McCaman & Vaughn, 1973; Eisenstadt, Goldman, Kandel, Koike, Koester & Schwartz, 1973). Stimulation of each of these neurones evokes excitatory and inhibitory potentials in various cells of the ipsilateral buccal ganglion. In nine buccal neurones it evokes excitatory potentials, in other three, ;classical' inhibitory potentials and in one neurone an ;atypical' inhibitory potential.2. The connexion between the giant cerebral neurone and the cells receiving either an excitatory or a ;classical' inhibitory input from it are monosynaptic. TEA injection into the cerebral giant neurone, which prolongs the presynaptic spike, causes a gradual increase of both the excitatory and the inhibitory potentials. On the other hand, high Ca(2+) media, which block polysynaptic pathways, do not suppress these synaptic potentials.3. The iontophoretic application of 5-HT to the buccal neurones receiving excitatory input from the giant cerebral neurones evokes depolarizations showing the pharmacological properties of both A- and A'-responses to 5-HT (see preceding paper). Antagonists which block only the A-receptors (curare, 7-methyltryptamine, LSD 25) block partially the synaptic depolarizing potentials. Bufotenine, which blocks both the A- and A'-receptors, completely blocks the excitatory potentials. Thus, the post-synaptic membrane of these buccal neurones appears to be endowed with both A- and A'-receptors to 5-HT.4. The ;classical' inhibitory potentials elicited in three buccal neurones are hyperpolarizations which reverse at - 80 mV and are due to an increase in K(+)-conductance. The iontophoretic application of 5-HT to these post-synaptic neurones evokes hyperpolarizing B-responses which are also generated by an increase in K(+)-conductance. Antagonists which block the B-responses (bufotenine, methoxygramine) also block the inhibitory potentials.5. The ;atypical' inhibitory potential evoked in one buccal neurone consists in an hyperpolarization which increases in amplitude with cell hyperpolarization. Iontophoretic application of 5-HT to this buccal cell evokes an hyperpolarizing beta-response which also increases in amplitude with cell polarization and results from a decrease in both Na(+)- and K(+)- conductances. The monosynaptic character of the ;atypical' inhibitory potential is not yet fully proven.6. It can be concluded that the excitatory and inhibitory synaptic effects evoked in the buccal neurones by the stimulation of the 5-HT-containing-giant cerebral neurones are very likely mediated by 5-HT.


The practical and potential contributions of immunology to the problems of developing countries.


Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine. 1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5-hydroxytryptamine (5-HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed.2. Four of the responses to 5-HT (named A, A', B and C) are consequent upon an increase in membrane conductance whereas the other two (named alpha and beta) are caused by a decrease in membrane conductance.3. The A-response to 5-HT consists of a ;fast' depolarization due to an increase mainly in Na(+)-conductance; the A'-response is a ;slow' depolarization also associated with a Na(+)-conductance increase. Receptors mediating the A- and A'-depolarizations have different pharmacological properties and may exist side by side on the same neurone.4. Both the B- and C-responses are inhibitory. The B-response is a ;slow' hyperpolarization due to an increase in K(+)-conductance, the C-response is a fast hyperpolarization associated with an increase in Cl(-)-conductance.5. The alpha-response to 5-HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at -75 mV; it is caused by a decrease in K(+)-conductance. The beta-response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at -20/-30 mV. It results from a decrease in conductance to both Na(+) and K(+) ions.6. The receptors involved in the 5-HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7-methyltryptamine blocks only the A-receptors, 5-methoxygramine only the B-receptors and neostigmine only the C-receptors. Curare blocks the A- and C-receptors and bufotenine, the A-, A'- and B-receptors. No specific antagonists have yet been found for the 5-HT responses caused by a conductance decrease.7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper.


Early and delayed phases of hind paw edema in rats.


Coenzyme A and affinity chromatography.

Coenzyme A and affinity chromatography.


Use of pyridoxamine phosphate in affinity chromatography.


Immobilized nucleotides for affinity chromatography.


Purification of an enzyme containing a NADP-protected cysteine on organomercuri-agarose 17beta-estradiol dehydrogenase.


The effect of diazepam on spinal cord activities: possible sites and mechanisms of action.


Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Alpha-sympathomimetic inhibition of Neurogenic vasoconstriction.


Effects of gamma-aminobutyric acid (GABA) and GABA antagonist drugs on ACTH release.


Micro-organisms from necrotic pulp of traumatized teeth.


Pharmacology of zolimidine (2-(p-methylsulfonylphenyl)-imidazo (1,2-a) pyridine) a new non-anticholinergic gastroprotective agent. I) Protective activity against experimental neurogenic gastric ulcers and other pharmacologic properties.


Pharmacology of zolimidine (2-(p-methylsulfonylphenyl)-imidazo (1,2-a) pyridine) a new non-anticholinergic gastroprotective agent. II) Protective activity against drug-induced experimental ulcers.


Financial management for school of nursing. Papers presented at the 1973-74 regional workshops sponsored by the Council of Diploma Programs held in Cincinnati, Chicago and New York.


Pharmacology of zolimidine (2-(p-methylsulfonylphenyl)-imidazo (1,2-a) pyridine) a new non-anticholinergic gastroprotective agent. III). Gastric antisecretory activity, antagonism against acid hypersecretion induced by pentagastrin and histamine, and other effects.


Pharmacology of zolimidine (2-(p-methylsulfonylphenyl)-imidazo (1,2-a) pyridine) a new non-anticholinergic gastroprotective agent. IV) Enhancement of gastric mucus production in different experimental models.


Dental caries in five year old schoolchildren.


Antipsychotic drugs stimulate prolactin release.


GABA blockade, dopamine and schizophrenia: experimental studies in the cat.


A survey of congenital defects of sheep.


Decayed, missing, and filled teeth among youths 12-17 years.


A model of the vertebrate nervous system based largely on disinhibition: a key role of the GABA system.


The role of astroglia as modulators of neuronal function in cerebral cortex: comparative data, and observations in vivo and in vitro in fluid, electrolyte and amino acid interrelationships.


The medical assistant: an intermediate level of health care personnel.


The medical assistant: an intermediate level of health care personnel. Adress.


The medical assistant. Career status.

The medical assistant. Career status.


The medical assistant. Acceptance, public and professional.


The medical assistant. Assurance of quality, competence, and accountability. Accreditation.


The medical assistant. Assurance of qulaity, competence, and accountability. Legal aspects.


The medical assistant: an intermediate level of health care personnel. The principle obstacles and problems.


The medical assistant: an intermediate level of health care personnel. Opening address.


The medical assistant: an intermediate level of health care personnel. The future prospect.


The medical assistant: an intermediate level of health care personnel. Purposes of the conference.


Health services in the USA: trends in the education and training of health personnel.


The medical assistant: an intermediate level of health care personnel. Defintion of terms.


The medical assistant: an intermediate level of health care personnel. Discussion.


Principal training programmes in the USA. Physician's assistant--physician's associate.


Principal training programmes in the USA. MEDEX.


The community health medic in Indian America.


Medical assistants in the USA as viewed by the professions. The physician's view.


Medical assistants in the USA as viewed by the professions. The nurse's view.


Roles for the medical assistant.

Roles for the medical assistant.


Leucocidic substances for Aeromonas hydrophila.


Serological studies of Leptospiras by immunodiffusion.


Pathogenicity of Leptospires of various serological types for some species of wild rodents.


Effect of amino acids on the growth and phospholipid composition of some pathogenic fungi.


Classification of Micrococcaceae isolated from clinical sources.


Purification and some properties of a heat-labile enterotoxin from escherichia coli.


On the significance of L antigens for the serology, immunology and pathogenicity of Escherichia species.


Morphological, cultural and biochemical characteristics of so called NAG vibrios isolated from human faeces and vomitus. Preliminary report.


R-factor-induced resistance levels.

R-factor-induced resistance levels.


Thermoresistant antigen in leptospires. Possibility of a macroscopic diagnosis of leptospirosis with a single antigen.


Prevalence of avian mycoplasma species in India. I. Biological properties of avian mycoplasma species.


Occurrence of a seven-drug-resistance plasmid in two strains of Salmonella typhi murium from diarrheatic patients.


The property changes of two Tahyna virus strains by influence of serial passages in various environments.


Plaque S- variant of Semliki Forest virus in poikilothermic cell culture at 20 degrees C.


Purification of CV virus by CsCl density gradient centrifugation and extraction of viral DNA by MAK column chromatography.


Studies on phage tail bacteriocins of Proteus rettgeri.


Continued epidemiological surveillance of Serratia marcescens infections by bacteriocin typing, with particular reference to strains isolated at Erlangen.


Studies on group A (phage tail) bacteriocins of Serratia marcescens. II. Further characterization of subgroup I and II bacteriocins.


Transferable tetracycline resistance in Salmonella cholerae-suis var. Kunzendorf.


A study of staphylococci isolated from the upper respiratory tract of different animal species. VI. Physiological properties of Staphylococcus aureus strains from horses.


R factors and colicins in Escherichia coli strains causing infections of the urinary apparatus.


Studies on group A (phage tail) bacteriocins of Serratia marcescens. III. Inhibition of beta-galactosidase activity (ONPG-hydrolysis) in sensitive indicator cells.


Studies on group A (phage tail) bacteriocins of Serratia marcescens. IV. Preliminary characterization of receptors of subgroup II bacteriocins.


Global ecological surveillance.

Global ecological surveillance.


Obstructive arteritis of Takayasu's type complicated by acute myocardial infarction.


Comparison of the effect of gamma-aminobutyric acid and of sodium salt of gamma-hydroxybutyric acid during the ontogeny of rats.


Proceedings: Modification of epileptogenic focus by simultaneous application of drugs.


Comparison of the antihistaminic effects in skin of a tertiary (promethazine) and a quarternary phenothiazine (N-hydroxyethylpromethazine).


Desensitizing treatment in allergy to synthetic corticotrophin: study of three cases.


Which must be the concept of adrenergic blockade and potentiation nowadays?


Psychopharmacology for non-psychiatrists: a review.


Beta-Blockers in the management of myocardial ischemia.


Legal and related barriers to increased utilization of new health practitioners.


The determination of some 1,4-benzodiazepines and their metabolites in body fluids. A review.


The role of cytochrome P-450 and P-448 in drug and steroid hydroxylations.


Studies on the partially purified heme protein P-450 from the adrenal cortex.


Kinetic studies on the mechanism of conversion of cholesterol to pregnenolone.


Drugs, alcohol and sex hormones: a molecular perspective of the receptivity of cytochrome P-450.


Activator and inhibitor factors in cholesterol side-chain cleavage.


The in vivo effect of ACTH on utilization of reducing energy for pregnenolone synthesis by adrenal mitochondria.


Lifetime of adrenal cytochrome P-450 as influenced by ACTH.


Studies on the aromatization of C-19 androgens.


Comparative studies on mitochondrial and partially purified bovine corpus luteum cytochrome P-450.


Biochemical studies on cytochrome P-450 solubilized from liver microsomes: partial purification and mechanism of catalysis.


Eelctron transport system for adrenocortical mitochondrial steroid hydroxylation reactions: the mechanism of the hydroxylation reactions and properties of the flavoprotein-iron-sulfur protein complex.


Hydralazine and beta-adrenergic blockade in the treatment of hypertension.


Cutaneous periarteritis nodosa.

Cutaneous periarteritis nodosa.


Influence of serotonin on water intake and the renin-angiotensin system in the rat.


The energy-yielding reactions of Peptococcus prévotii, their behaviour on starvation and the role and regulation of threonine dehydratase.


Pharmacological studies on some anaphylactic reactions in mice.


A dental survey of an antenatal population.


Diagnosis, treatment planning and referral by school dental therapists.


Community dental health survey. Sydney Metropolitan Area-1972.


General medical care in China.

General medical care in China.


7 Alpha-hydroxylation of cholesterol by reconstituted systems from rat liver microsomes.


Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain. 1. The effects of 2-oxo-4-methylpentanoate, 2-oxo-3-methylbutanoate and 2-oxo-3-methylpentanoate on the activity of pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase, (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old rats were investigated. 2. The pyruvate dehydrogenase enzyme activity was competitively inhibited by 2-oxo-3-methylbutanoate with respect to pyruvate with a K(i) of 2.04mm but was unaffected by 2-oxo-4-methylpentanoate or 2-oxo-3-methylpentanoate. 3. The citrate synthase activity was inhibited competitively (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~7.2mm) and 2-oxo-3-methylbutanoate (K(i)~14.9mm) but not by 2-oxo-3-methylpentanoate. 4. The acetyl-CoA carboxylase activity was not inhibited significantly by any of the 2-oxo acids investigated. 5. The fatty acid synthetase activity was competitively inhibited (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~930mum) and 2-oxo-3-methylpentanoate (K(i)~3.45mm) but not by 2-oxo-3-methylbutanoate. 6. Preliminary experiments indicate that 2-oxo-4-methylpentanoate and 2-oxo-3-phenylpropionate (phenylpyruvate) significantly inhibit the ability of intact brain mitochondria from 14-day-old rats to oxidize pyruvate. 7. The results are discussed with reference to phenylketonuria and maple-syrup-urine disease. A biochemical mechanism is proposed to explain the characteristics of these diseases.


Steriod metabolism by human normal thyroid, nodular goitre and thyroid cancer.


Effect of tolamolol versus propranolol on cardiovascular haemodynamics in patients with angina.


The effect of cultural conditions on the susceptibility of staphylococci to killing by the cationic proteins from rabbit polymorphonuclear leucocytes.


Factors affecting muscle activation in the hydroid Tubularia.


The reduction of 3-phosphoglycerate by reconstituted chloroplasts and by chloroplast extracts.


The shikimate pathway : II. Stereospecificity of hydrogen transfer catalyzed by NADPH-dehydroshikimate reductase of E. coli.


A familial syndrome of short stature associated with facial dysplasia and genital anomalies. The following report presents the clinical findings and natural history of a growth disorder affecting seven male patients from the same family. In addition to short stature they all had a similar pattern of anomalies and the condition appears to constitute a previously undescribed, probably X-linked recessive, nosologic entity.


Multiple endocrine adenomatosis presenting as Zollinger-Ellison syndrome, nonbeta islet cell adenoma, parathyroid adenoma, renal calculi, bronchial carcinoid, insulinoma, hepatic hamartoma, etc.


Relationship of hyperparathyroidism to multiple endocrine adenomatosis. An experience with 8 families with 56 members affected with hyperparathyroidism has emphasized that heredity is an important etiologic factor in this disease. The finding of other endocrine involvement in several members of these families has suggested that hereditary hyperparathyroidism is only a part of the autosomal dominantly inherited multiple endocrine adenomatosis syndrome. This association with hyperparathyroidism, a disease being found with increasing frequency as an inherited condition, provides evidence that multiple endocrine adenomatosis is more common than previously suspected.


Genetic disorders involving parathyroid hormone and calcitonin. There are several genetic disorders that cause abnormalities in the hormonal regulation of calcium metabolism. These include familial hyperparathyroidism, multiple endocrine adenomatosis, pseudohypoparathyroidism and kindreds with multiple cases of medullary carcinoma of the throid. The clinical characteristics of these several syndromes are outlined. Several tests of endocrine function, either determination of hormone secretory rates or biochemical manifestations of the action of hormones, are helpful in delineating genetic modes of transmissions of these disorders. radioimmunoassays are becoming important adjuncts in the diagnosis of hyperparathyroidism and medullary carcinoma of the thyroid. Determination of 3',5'-adenosine monophosphate in urine in response to parathyroid hormone allows accurate diagnosis of pseudohypoparathyroidism.


Familial tumor endocrinopathies.

Familial tumor endocrinopathies. The spectrum of familial tumor endocrinopathies is broad; what has been described here probably represents only a small part of the entire subject. No consideration has been given to treatment, as this is covered in standard tests. It is important to recognize that, potentially, any endocrine tumor may be familial, and both a detailed family study and longitudinal follow-up are necessary if the mode of inheritance and the degree of clinical variability are to be established with certainty.


An unidentified syndrome with abnormality of skin and hair.


Dermatologic disorders in institutionalized mental defectives. Skin diseases among the retarded fall into four categories--common dermatoses, behavioral disorders, iatrogenic manifestations produced by drug therapy and a group of congenital, hereditary and unexplained cases. The last three classifications are briefly reviewed in the following article.


Blockade of peripheral vascular responses to isoprenaline by three beta-adrenoceptor antagonists in the anaesthetized dog. 1 A dog's hind limb was vascularly isolated by strong nylon snares and its sympathetic nerve supply interrupted. Blood was perfused at constant flow into the femoral artery and drained from the femoral vein. In some dogs the cardiac nerves were cut.2 Isoprenaline infused intravenously caused an increase in heart rate and a decrease in arterial resistance.3 Practolol (2 mg/kg) effectively blocked heart rate responses to isoprenaline infused at up to 10 mug/min but was relatively ineffective in blocking arterial responses. ICI 66082 (2 mg/kg) reduced vasomotor responses and propranolol (0.5 mg/kg) abolished vasomotor responses.4 Small cumulative doses of beta-adrenoceptor antagonists were given to some dogs. Practolol blocked heart rate responses in lower doses than were required to block vasomotor responses. Propranolol preferentially blocked vasomotor responses and ICI 66082 was intermediate between the other two in its effects.


The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart. 1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 mug/ml.3 ICI 66082 (0.5-1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean +/- 139 mm Hg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).4 ICI 66082 (1.0-1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40-50 mg/kg.5 It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.


Effects of tiprenolol, practolol and propranolol on experimental ventricular tachyarrhythmias. 1 Low doses of tiprenolol (0.01-0.02 mg/kg) and propranolol (0.05 mg/kg) abolished the ventricular arrhythmias produced by the intravenous injection of adrenaline in anaesthetized dogs respired with halothane.2 Larger doses of tiprenolol (2.0-4.0 mg/kg) restored sinus rhythm in four of five dogs with ventricular tachycardia produced by toxic doses of ouabain. Propranolol (2.0-4.0 mg/kg) had the same effect in each of four dogs.3 Both tiprenolol (4.0-8.0 mg/kg) and propranolol (4.0 mg/kg) increased the frequency of sinus beats and reduced the ventricular rate in dogs with ventricular tachycardia 20-44 h after ligation of a coronary artery.4 Practolol (0.5-16.0 mg/kg) did not reduce the ventricular rate or increase the frequency of sinus beats in dogs with ventricular tachycardia after ligation of a coronary artery.5 In dogs with ouabain-induced ventricular tachycardia mean arterial pressure was reduced after the administration of tiprenolol (0.5-8.0 mg/kg) or propranolol (4.0-8.0 mg/kg). Depression of sinus and atrioventricular nodal function, and of intraventricular conduction developed in some of the dogs given tiprenolol (4-8 mg/kg) or propranolol (8.0 mg/kg).6 The administration of tiprenolol (1.0-8.0 mg/kg) or propranolol (4.0-8.0 mg/kg) depressed the arterial pressure and caused the deaths of some dogs in which a coronary artery had been ligated. Such deaths did not occur in the group which had been given toxic doses of ouabain.


Investigations on the mode of action of ergotamine in the isolated femoral vein of the dog. 1 Experiments on spiral strips cut from the femoral vein of dogs suspended in Krebs-Henseleit solution were carried out.2 Ergotamine caused stimulation in concentrations about 350 times lower than noradrenaline (ED(50) of ergotamine = 2.2 x 10(-9) M; ED(50) of noradrenaline = 7.6 x 10(-7) M), but the maximal responses to ergotamine were only about one third those to noradrenaline.3 The pA(2) value of ergotamine against noradrenaline was 8.8.4 The effects of ergotamine can be blocked by prior administration of phentolamine. The pA(2) value for phentolamine against ergotamine was 6.8 and the pA(2) value for phentolamine against noradrenaline was 7.5.5 It is concluded that the stimulant action of ergotamine on smooth vascular muscle probably is mediated mainly via alpha-adrenoceptors.


Influence of SKF-525A congeners, strophanthidin and tissue-culture media on desensitization in frog skeletal muscle. 1 Microelectrodes have been used to follow changes in membrane potential at end-plate regions of frog skeletal muscle fibres exposed to carbachol; the depolarizing drug was applied to narrow strips of muscle in a rapidly flowing solution containing relatively impermeant anions rather than chloride.2 During prolonged applications of carbachol (10 to 20 muM), the depolarization caused by the drug showed a gradual decline which was attributed to desensitization.3 Desensitization was little if at all affected by supplementing the external solution with factors present in tissue-culture media, or by treating the muscle with strophanthidin (25 muM).4 The rate of repolarization in the presence of carbachol (10 to 20 muM) was greatly increased by the SKF-525A congeners pipenzolate bromide (10 muM) and adiphenine hydrochloride (1 muM). The desensitization-enhancing action of these compounds is discussed.


The action of indoramin and other compounds on the uptake of neurotransmitters into rat cortical slices. Indoramin has been tested for its ability to inhibit the uptake of tritiated (-)-noradrenaline and 5-hydroxytryptamine into rat brain cortical slices. Other alpha-blocking agents and tricycic antidepressants were included for comparison. Activity against noradrenaline uptake is probably not important in the therapeutic action of indoramin. However, inhibition of 5-hydroxytryptamine uptake may be responsible for the sedation in high dosage noted by some investigators,


Effect of preganglionic nerve stimulation on sensitivity of the superior cervical ganglion to nicotinic blocking agents. 1 Periodic stimulation (every 10 min) of the cervical sympathetic nerve increased the ganglionic block by low concentrations of chlorisondamine (CHL) in the superior cervical ganglion of the cat when compared to the contralateral unstimulated side.2 Periodic stimulation of the postganglionic nerve was ineffective in increasing the block.3 Ganglionic block by low concentrations of mecamylamine had the same stimulus dependency, but ganglionic block by any dose of hexamethonium was not influenced by nerve stimulation.4 Physostigmine infused together with CHL increased the rate of onset of block produced by CHL. Atropine had no apparent effect on the development of ganglionic block by CHL.5 Repeated intra-arterial injections of 1,1-dimethyl-4-phenylpiperazinium into the circulation of the superior cervical ganglion increased the magnitude of block produced by CHL. Similar injections of methacholine had no effect on ganglionic block produced by CHL.6 The results are interpreted to indicate that activation of ganglionic nicotinic receptors increased the affinity of receptors for CHL and mecamylamine.


The long-term regulation of tyrosine hydroxylase activity in cultured sympathetic ganglia: role of ganglionic noradrenaline content. 1 An organ culture system is described for the in vitro maintenance of superior cervical sympathetic ganglia taken from mice of any age. The relation of tyrosine hydroxylase (T-OH) activity to ganglionic noradrenaline (NA) content has been investigated under various culture conditions.2 Depolarizing stimuli such as raised extracellular potassium and ouabain evoked increases of approximately 70% in the T-OH activity of cultured ganglia over a 48 h period. Exposure to a high concentration of potassium (high K(+)) for 30 min at the start of a 48 h culture was sufficient to elicit significant increases in T-OH activity.3 Depolarization-induced rises in T-OH activity were observed after culture in the presence or absence of nerve growth factor.4 The NA content of ganglia, cultured for 48 h in the presence of high K(+), ouabain, reserpine, clorgyline and alpha-methyl-p-tyrosine, showed no constant relation to their T-OH activity.5 Dibutyryl cyclic adenosine 3'-5'-monophosphate (dibutyryl cyclic AMP) mimicked high K(+) in its effect on ganglionic T-OH activity and NA content. Theophylline enhanced the potassium effects.6 Rises in the T-OH activity of ganglia cultured in the presence of high K(+) and dibutyryl cyclic AMP were abolished if the protein synthesis inhibitors cycloheximide or actinomycin D were present in the culture medium.7 It is concluded that the link between prolonged depolarization and rises in T-OH activity does not seem to depend upon changes in ganglionic NA content. In the intact animals, trans-synaptic modulation may take the form of a depolarization-induced rise in the cyclic AMP content of sympathetic ganglionic neurones leading to nuclear mediated synthesis of T-OH.


The specificity of some agonists and antagonists for nicotine-sensitive receptors in ganglia. 1 The guinea-pig isolated ileum has been used to estimate the ability of substituted phenylalkylonium salts (related to nicotine) to stimulate or block receptors in ganglia. The effects of hexamethonium were used to indicate which were the most specific ganglion stimulants; these were tested on the blood-pressure of pithed rats and for neuromuscular blocking activity on the rat diaphragm preparation.2m-Hydroxyphenylpropyltrimethylammonium and 3,4-dihydroxyphenethyltrimethylammonium (coryneine, ;quaternary dopamine') were the most active and specific ganglion stimulants but their usefulness in vivo may be limited by their neuromuscular blocking activity. The analogous tertiary compounds are being investigated.3 The affinities of substances which were blocking agents at ganglionic receptors were measured on the isolated ileum with m-hydroxyphenylpropyltrimethylammonium as agonist. The affinities of selected compounds for postganglionic receptors were measured in experiments on the ileum in the presence of hexamethonium and with carbachol as agonist. Some of the compounds were tested for neuromuscular blocking activity on the rat diaphragm.4 Phenylbutyldiethylamine had ganglion-blocking activity greater than pempidine and little postganglionic blocking or neuromuscular blocking activity. Its triethylammonium analogue had higher ganglion-blocking activity but had appreciable neuromuscular blocking activity.5 The aromatic ring system is not essential either for activity or affinity and the effects of substituents are not related to their effects on electron distribution. Stimulant activity is enhanced only by hydroxyl or amino groups in suitable positions; it is not improved by the presence of rigid features (double or triple bonds or a cyclopropane ring) in the side chain. Affinity is slightly increased by chloro or bromo groups in suitable positions but the unsubstituted compounds are among those with the highest affinity. Substituents have similar effects on affinity for postganglionic receptors, though for these receptors the compounds mostly have only about one-tenth of their affinity for ganglionic receptors.


Antagonism of inhibitory amino acid action by tubocurarine. A comparison has been made of the antagonism by microelectrophoretically administered (+)-tubocurarine, bicuculline methochloride and strychnine of the inhibition of spinal interneurones and Renshaw cells in the cat by glycine and gamma-aminobutyric acid. The results indicate that (+)-tubocurarine would be of little use in assessing which of these amino acids was the transmitter at central inhibitory synapses.


Actions of putative transmitters in the chicken vagus nerve/oesophagus and Remak nerve/rectum preparations. 1 Histamine (0.02-0.1 mug/ml) contracted the chicken rectum preparation. This effect was antagonized by mepyramine (0.01 mug/ml) but not by hyoscine (0.02 mug/ml).2 5-Hydroxytryptamine (0.05-0.25 mug/ml) relaxed the rectum preparation and at higher concentration produced a biphasic response. These responses were not antagonized by methysergide (0.01 mug/ml), and the relaxation was not antagonized by tetrodotoxin (0.1 mug/ml) or a combination of propranolol (0.05 mug/ml) and phentolamine (0.1 mug/ml).3 Neither mepyramine (0.1 mug/ml) nor methysergide (0.01 mug/ml) antagonized the contractions produced by nerve stimulation in vagus nerve/oesophagus and Remak nerve/rectum preparations.4 5-Hydroxytryptamine (2 mug/ml) in the presence of methysergide (0.01 mug/ml), inhibited the contractions produced by nerve stimulation in Remak nerve/rectum and vagus nerve/oesophagus preparations.5 Adenosine, adenosine 5'-phosphate (AMP), adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP), in order of decreasing potency, produced slow contractions in most oesophagus preparations. The action of ATP in this preparation was antagonized by tetrodotoxin (0.1 mug/ml), hyoscine (0.1 mug/ml) and strychnine (5 mug/ml).6 Desensitization of the vagus nerve/oesophagus preparation to ATP did not produce any antagonism of the contractions to nerve stimulation.7 Adenosine and AMP produced relaxations and ADP and ATP contractions in the rectum preparation. ATP was about 100 times as potent as ADP in producing fast contractions which were not antagonized by tetrodotoxin, hyoscine or strychnine.8 Desensitization of the Remak nerve/rectum preparation to ATP resulted in the contractions to nerve stimulation and acetylcholine being inhibited to the same extent.9 Prostaglandin E(2) produced slow contractions in the oesophagus and rectum preparations which were not antagonized by tetrodotoxin (0.1 mug/ml). Polyphloretin phosphate (10 mug/ml) antagonized spontaneous movements and responses to prostaglandin E(2) in the rectum but not the oesophagus.10 Neither polyphloretin phosphate (60 mug/ml) nor indomethacin (20-100 mug/ml) antagonized the contractions produced by nerve stimulation in vagus nerve/oesophagus (with hyoscine in the bathing solution) and Remak nerve/rectum preparations.11 These experiments seem to exclude histamine, 5-hydroxytryptamine, adenosine and its nucleotides and prostaglandin E(2) as possible motor transmitters in synapses and neuromuscular junctions in the chicken vagus nerve/oesophagus and Remak nerve/rectum preparations.


Proceedings: Convulsant substances as antagonists of GABA and presynaptic inhibition in the cuneate nucleus.


Proceedings: The action of cinnarizine and of phentolamine on the noradrenaline-dependent calcium influx in vascular smooth muscle.


Proceedings: Vascular histamine receptors in the cat.


Proceedings: Pharmacological studies with LL 21-945, a new beta-adrenoceptor blocking agent with a long duration of action.


Proceedings: The hypoglycaemic action of ICI 66082 (4-(2-hydroxy-3-isopropyl-aminopropoxy) phenyl acetamide) in the rat.


Bicuculline and the frog spinal cord.

Bicuculline and the frog spinal cord. 1 The effects of bicuculline on dorsal and ventral root activity and upon the depressant effect of gamma-aminobutyric acid (GABA) and glycine on ventral root responses have been studied on the isolated spinal cord of the frog.2 In the absence of stimulation, the alkaloid induced a variety of activity of which the most notable was phasic simultaneous slow wave depolarization in the dorsal and ventral roots which could be reduced or suppressed by magnesium.3 With low concentrations of bicuculline, the adjacent dorsal root response evoked by a single stimulus was depressed maximally before an increase in the ventral root response could be discerned.4 The bicuculline-induced dorsal root activity (in the absence of stimulation) was still apparent at times when the evoked dorsal root response was reduced.5 Bicuculline did not differentiate between the depressant effects of GABA and glycine on the evoked ventral root responses.6 The excitant effects of bicuculline reported here did not appear to be attributable to specific antagonism of the postsynaptic depressant action of GABA.


Implication of gastric mucosal histamine in inhibition by isoprenaline of pentagastrin-induced gastric secretion. 1 The effect of isoprenaline on pentagastrin-induced gastric secretion was studied in conscious rats with Heidenhain pouches. The influence of isoprenaline on pentagastrin-induced release and formation of gastric mucosal histamine was also examined.2 Isoprenaline strongly inhibited pentagastrin-induced acid secretion, an inhibition which could not be overcome by increasing the dose of pentagastrin.3 Propranolol blocked the inhibitory effect of isoprenaline on pentagastrin-induced acid secretion.4 Isoprenaline enhanced pepsin secretion induced by pentagastrin, an effect which was blocked by propranolol.5 Isoprenaline reduced the increase in formation and release of gastric mucosal histamine following pentagastrin infusion, an inhibitory influence which was almost completely blocked by propranolol.6 The inhibition by isoprenaline of pentagastrin-induced acid secretion is tentatively related to alterations in gastric mucosal histamine occurring simultaneously.


A non-adrenergic inhibitory nervous pathway in guinea-pig trachea. 1 Electrical stimulation of the guinea-pig isolated tracheal tube causes a biphasic response, initially excitatory and then inhibitory. The excitatory response was abolished by atropine leaving the inhibitory response unaffected.2 The inhibitory response was greatly reduced but not abolished by propranolol or guanethidine. A residual inhibitory response was still present in tracheas in which sympathetic nerve function had been abolished by pretreatment with syrosingopine or 6-hydroxydopamine. These results show that the inhibitory response is predominantly adrenergic but that a small non-adrenergic component is also present.3 The non-adrenergic inhibitory response was abolished by lignocaine and tetrodotoxin suggesting that it is nervous in origin.4 Optimal stimulation parameters for the predominantly adrenergic inhibitory response were a pulse width of 0.7-2 ms, a stimulation period of 7 s and a frequency of 20 Hz. For the non-adrenergic inhibitory response, optimal stimulation parameters were a pulse width of 2 ms, a stimulation period of 12 s and a frequency of 20 Hz.5 Evidence obtained with pharmacological antagonists, enzyme inhibitors and activators suggested that the transmitter mediating the non-adrenergic inhibitory nervous response is unlikely to be: acetylcholine, histamine, 5-hydroxytryptamine, cyclic 3',5'-adenosine monophosphate or a prostaglandin.6 The adenosine uptake blocking drugs dipyridamole, hexobendine and Dilazep potentiated the non-adrenergic inhibitory nervous response and unmasked inhibitory responses to adenosine and adenosine 5'-triphosphate.7 It is concluded that electrical stimulation of the guinea-pig trachea, in addition to activating cholinergic and adrenergic nervous pathways, may activate a separate and distinct inhibitory nervous pathway. This pathway has some features in common with the non-adrenergic non-cholinergic inhibitory pathways in gastro-intestinal muscle.


The rabbit rectococcygeus: a ganglion-free parasympathetically innervated preparation. 1 Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1-50 pulses (0.2-0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin-resistant myogenic contractions.2 Twitches elicited by 0.2-0.4 ms pulses were due to post-ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion-paralyzing concentrations of nicotine.3 The acetyl- and butyryl-cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5-bis-(4-allyl-dimethylammonium-phenyl)-pentan-3-one dibromide) and iso-OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single-pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.4 The preparations could not be made to contract by nicotine (2.1-21 muM) even after cholinesterase inhibition, suggesting an absence of ganglion-cells; with nicotine (105-210 muM) small, atropine-susceptible responses were elicited, which were non-ganglionic because they were not reduced by tetrodotoxin.5 Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.6 The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.7 Inhibitory adrenoceptors and scanty motor alpha-adrenoceptors were detected in the smooth muscle.8 Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.9 Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1-2 cm of the motor nerve pathway to this muscle.10 Some contrasting properties of the adjacent caudo-anal muscle, including the poor motor responses to transmural stimulation, are described.


Prostaglandin inactivation in guinea-pig lung and its inhibition. 1 Several compounds were tested for their ability to inhibit prostaglandin metabolism in guinea-pig lungs.2 In isolated perfused lungs polyphoretin phosphate (PPP) inhibited prostaglandin metabolism being active at concentrations greater than 100 ng/ml and having an ID(50) of 2.15 mug/ml against prostaglandin E(2) metabolism and 1.55 mug/ml against prostaglandin F(2alpha) metabolism.3 At these doses no antagonism of the actions of prostaglandins was seen.4 Diphloretin phosphate (DPP) was more active on a weight for weight basis and inhibition of inactivation of prostaglandins was seen at concentrations greater than 10 ng/ml, the ID(50) being 0.54 mug/ml against both prostaglandins E(2) and F(2alpha).5 At concentrations greater than 5 mug/ml DPP antagonized the actions of prostaglandin F(2alpha).6 The sulphydryl-binders N-ethyl maleimide (NEM) and sodium p-chloromercuriphenyl sulphonate (PCMS) also inhibited prostaglandin inactivation by guinea-pig isolated lungs.7 All four compounds inhibited prostaglandin metabolism by a crude enzyme preparation from guinea-pig lungs.


Effect of sympathomimetic amines on the histamine forming capacity of human leucocytes. 1 The effects of alpha- and beta-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 beta-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10(-6)-10(-3)M) significantly inhibited the HFC of human leucocytes in the presence and absence of antigen. At concentrations lower than 10(-6)M, this effect was not observed. In general the degree of inhibition of HFC by beta-adrenoceptor stimulants followed their potency as beta-adrenoceptor stimulants.4 alpha-Adrenoceptor stimulants significantly stimulated leucocyte HFC; noradrenaline within a limited concentration of 10(-6)M, while stimulation was seen consistently with phenylephrine at concentrations of 10(-7)-10(-4)M. Adrenaline, which stimulates both alpha- and beta-adrenoceptors, produced small inhibition, no effect, or a degree of stimulation.5 Phentolamine, an alpha-adrenoceptor blocking agent, produced an effect opposite to that of the alpha-adrenoceptor stimulants, i.e. a significant inhibition of the HFC of human isolated leucocytes.


The effects of three beta-adrenoceptor blocking drugs on isolated preparations of skeletal and cardiac muscle. 1 The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described.2 Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 mug/ml), by oxprenolol (100 mug/ml) and by practolol (500 mug/ml).3 Depression of the twitch responses of the papillary muscles was produced by propranolol (20 mug/ml) by oxprenolol (100 mug/ml) and by practolol (200 mug/ml).4 No increase of twitch tension was produced by oxprenolol or practolol on either tissue.5 It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of beta-adrenoceptors and which occurs at doses which are well in excess of those doses required to produce beta-blockade.