Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain. 1. Cortical slices from rat brain were incubated in media containing the irreversible cholinesterase inhibitor soman and a high KCl concentration, and the release and synthesis of acetylcholine (ACh) were determined.2. Atropine enhanced the release and synthesis of ACh.3. Tetrodotoxin, a substance which blocks nervous conduction, did not influence the release and synthesis of ACh, in the absence or in the presence of atropine. Therefore the nerve endings are probably the site at which atropine acts when stimulating the release and synthesis of ACh.4. Pretreatment of the slices with botulinum type A toxin partially blocked the release and synthesis of ACh and reduced the extra amounts of ACh released and synthesized under the influence of atropine.5. Lowering the calcium or raising the magnesium concentration in the incubation medium reduced the release and synthesis of ACh and their enhancement by atropine.6. Physostigmine decreased the total extractable ACh content of the slices during incubation in a 25 mM KCl containing medium. This decrease was nearly prevented when the release and synthesis of ACh were inhibited by omission of the calcium ions from the medium, but was enhanced by atropine.7. The observations made with pretreatment by botulinum type A toxin, with changes in the calcium and magnesium concentration as well as with physostigmine, all support the theory that it is primarily the release of ACh which is enhanced by atropine and that its stimulating action on the synthesis results from the increased release.


Effects of chronic metaraminol treatment on the sympathetic activity of intact and adrenal demedullated rats kept in warm or cold environments. 1. Rats were placed at 27 degrees C or 4 degrees C and given metaraminol ((10 mg/kg)/day) in their drinking water for 8 weeks. One experiment was run using adrenal demedullated rats. These animals were treated with metaraminol, as mentioned above, and kept at 4 degrees C for 4 weeks.2. Body temperature and metabolic rate were determined at selected intervals. Urine was collected on day 7 of each week and analysed for adrenaline, noradrenaline, metanephrine, normetanephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG). At the end of each study the rats were killed and the tissues removed and analysed for metaraminol, adrenaline and noradrenaline.3. All animals survived the metaraminol treatment and no change in metabolic rate or body temperature was seen. Metaraminol depressed the growth rate of the rats.4. Metaraminol caused a fall in tissue noradrenaline concentrations, with only negligible quantities being found in brain, heart, lung, liver, kidney and spleen. Only the adrenals contained significant quantities of catecholamines. All tissues contained large amounts of metaraminol.5. Despite the almost complete depletion of noradrenaline from sympathetic nerves, metaraminol did not depress the excretion of noradrenaline, normetanephrine and MHPG, in fact excretion of the latter two substances was higher in the treated animals. The failure of the drug to impair the normal cold-induced increase in noradrenaline secretion explains the survival of the rats at 4 degrees C.6. Adrenal demedullation did not prevent the metaraminol-treated rats from excreting large quantities of noradrenaline, normetanephrine and MHPG in the cold. It is apparent, therefore, that in the intact rats the noradrenaline emanated from the practically depleted nerves. The increase in MHPG excretion, seen during metaraminol treatment, suggests an increased rate of noradrenaline turnover.7. In conclusion, although metaraminol uptake is accompanied by a fall in tissue noradrenaline concentrations, the presence of metaraminol does not depress noradrenaline release. These results do not support the concept that metaraminol can replace noradrenaline and function as a false transmitter.


Distribution and metabolism of L-3-O-methyldopa in rats. 1. After intraperitoneal administration of L-2-(14)C-3-O-methyldopa ((14)C-O-methyldopa) to rats, the amino-acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. (14)C-O-methyldopa showed a biological half-life of about 12-13 h in blood, brain and heart.2. The concentration curve of (14)C-O-methyldopa in brain (after increasing doses of the amino-acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h.3. The concentrations of (14)C-O-methyldopa metabolites (mainly homovanillic acid and 4-hydroxy-3-methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue.4. Twenty-four hours after administration of (14)C-O-methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main (14)C-homovanillic acid and (14)C-4-hydroxy-3-methoxyphenyllactic acid) and of 5% of unchanged (14)C-O-methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end-products.5. It is concluded that (14)C-O-methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino-acid undergoes a slow metabolism. The different shape of the concentration curves for (14)C-O-methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino-acid.


The effects of calcium and magnesium on the response of intestine smooth muscle to drugs. 1. The sensitivity of the longitudinal muscle of the guinea-pig ileum to muscarinic drugs producing contraction depends on optimum concentrations of calcium and magnesium. It can also be reduced by changes in sodium concentration and osmolarity.2. The rubidium efflux response to these same drugs is insensitive to any of these changes in the external medium.3. Raised calcium or magnesium concentration has the effect of largely annulling the differences in structure-activity relationships of the two responses as they exist in optimal media.4. The effects are explained in terms of a labile coupling process between a single receptor and the contractile process compared with a stable coupling process of the efflux process.


Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs. 1. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5-hydroxytryptamine (5-HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml.2. The removal of 5-HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10(-6)-10(-5)M).3. The monoamine oxidase inhibitors, mebanazine and iproniazid (10(-6)-10(-5)M), inhibited the initial removal slightly, but their main effect was to preserve the 5-HT taken up and this 5-HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 x 10(-7)-10(-6)M) showed a combination of amitriptyline-like and mebanazine-like effects on the 5-HT removal in rat lung.4. Experiments with (3)H-5-HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5-HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5-hydroxyindoleacetic acid.5. The following amines were without effect on the removal of 5-HT by rat lungs: noradrenaline (6 x 10(-7)M), normetanephrine (5 x 10(-6)M), metaraminol (10(-6)M), reserpine (10(-6)-10(-5)M) and phenoxybenzamine (10(-5)M).6. We conclude that the removal of 5-HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake(2). The cells involved in this process might be either capillary endothelial cells or septal cells.


Influence of pH on the inhibitory action of local anaesthetics on smooth muscle contraction. 1. The guinea-pig isolated ileum kept in a calcium-free depolarizing solution contracts when calcium is added; the responses are proportional to the concentration of calcium and are reversed by washing.2. The contractions elicited by calcium are inhibited by three different classes of compounds: local anaesthetics, pentobarbitone and ethanol. The inhibitory action of the local anaesthetics increases with an increase in pH, the inhibitory action of pentobarbitone increases with a decrease in pH and the inhibitory action of ethanol is not affected by variations in Tyrode pH.3. It is suggested that the antagonists are active when unionized and that the inhibition is obtained when unionized compounds have dissolved in the lipid material of the cell membrane. The possible site of action of the antagonists is discussed.


Diffusion of drugs through stationary water layers as the rate limiting process in their action at membrane receptors. 1. Preparations bathed in a well stirred solution have been considered as heterogeneous systems in which the solid phase is enveloped by a thin layer of stationary liquid. Any substance applied into the bulk solution must pass through this layer by diffusion before reaching the receptors.2. The rate of diffusion through the stationary layer can govern the time course of the cellular responses to applied drugs provided that (i) all receptors involved in the response are situated at an equal distance from the solution and (ii) interaction with the receptor and consequent cellular events are very rapid.3. These conditions have been verified for two responses: the contraction of guinea-pig ileum by acetylcholine (ACh), carbamylcholine (CCh), histamine and KCl, and the depolarization of the rat isolated sympathetic ganglion by ACh in the presence of eserine. A method of analysis has been applied which allows a complete dose-response curve to be obtained from only two responses.4. Diffusion half-times measured for pieces of ileum were 4.13 +/- 0.13 s (S.E. of mean) for Ach, 3.60 +/- 0.05 s for CCh and 1.01 + 0.05 s for KCl. The equivalent thickness of the stationary layer calculated from these values was respectively 93 mum, 87 mum and 70 mum. The average diffusion half-time for ACh in sympathetic ganglia was 14.19 +/- 1.05 s. This gives an equivalent thickness of 173 mum.5. Diffusion half-times were increased by increasing the viscosity of the bathing solution without changing the concentration response relationship.6. The time course of contractions of guinea-pig ileum are no longer diffusion limited in the presence of a competitive antagonist or when the temperature is lowered from 35 degrees to 25 degrees C.


Uptake of dopamine by platelets in vivo. Circulating platelets of cats infused with (14)C-dopamine take up the amine against a concentration gradient, with maximal concentration occurring 10 min after infusion. 58%, of the platelet-bound radioactive dopamine was localized in a subcellular fraction rich in 5-hydroxytryptamine (5-HT) storage organelles. The results support earlier work with human platelets showing in vitro dopamine uptake by normal platelets, and in vivo accumulation in parkinsonian patients treated with L-dopa.


Inotropic effects of thyroxine and related compounds on guinea-pig left atria in vitro. Triiodothyronine, diiodothyronine and diiodotyrosine have positive inotropic activity on normal guinea-pig left atria in vitro. The increases produced by triiodothyronine and diiodothyronine are small but their detection shows that the inotropic responses to these agents can be studied in vitro. Thyroxine, thyronine and monoiodotyrosine are inactive. Reserpine pre-treatment reduces the inotropic effect of diiodotyrosine but does not reduce those of triiodothyronine and diiodothyronine.


Positive correlation between initial pupil diameter and amplitude of miotic response to pilocarpine in rabbits and to carbachol in man. A linear correlation between amplitude of miotic response and initial pupil diameter has been demonstrated in rabbits using various concentrations of pilocarpine HC1. The same correlation was found when published results in humans using carbachol were examined and it is likely that the correlation also applies to pilocarpine in humans. No such correlation was observed with physostigmine.


Inhibition of catecholamine Uptake-2 by steroids in the isolated rat heart. Various steroids (17-beta-oestradiol, corticosterone, deoxycorticosterone, progesterone, testosterone and androsterone) produced a dose-dependent inhibition of the uptake of (3)H-noradrenaline by the Uptake(2) mechanism in the isolated perfused heart. It is suggested that these results may explain the potentiating effects of such steroids on the responses of vascular smooth muscle to catecholamines.


pP2 of eserine and neostigmine on acetylcholine responses of isolated ileum. pP(2) values of 7.9 and 8.0 for eserine and neostigmine show that these compounds are respectively about 200 and 300 times more potent in potentiating acetylcholine (ACh) responses on isolated cavy ileum than was previously found on frog rectus muscle. The increased tone and spontaneity usually produced by eserine and neostigmine were not prevented by morphine (10 to 100 mug/ml), which itself potentiated both ACh and histamine responses.


Metabolic inhibition in primary cell cultures by lipid-soluble molecules.


Destruction of chlorpromazine during absorption by rat intestine in vitro.


The kinin-forming system in rabbit hind limb lymph after thermal injury.


The effects of saponins on the transporting epithelium of isolated frog skin.


Platelet aggregation by very low intensity acoustical energy and its inhibition by drugs.


Formation and release of prostaglandins by platelets in response to thrombin.


Release of vaso-active substances from lungs by injection of particles.


The relationsjhip between ascorbic acid concentrations and cortisol production during the development of scurvey in the guinea-pig.


Isolation of dense-cored granules from the neurosecretory system of the vena cava of the small octopod, Eledone cirrosa.


Relative susceptibility of peripheral sympathetic nerves to adrenergic neurone blockade by bethanidine.


Extrinsic and intrinsic acetylcholine and barbiturate effects on frog skeletal muscle.


The effects of hexamethonium, morphine and adrenaline on the output of acetylcholine from the myenteric plexus-longitudinal muscle preparation of the ileum.


Presynaptic inhibition of acetylcholine release by endogenous and exogenous noradrenaline at high rate of stimulation.


The detection and assay of noradrenaline released from isolated tissues during intramural nerve stimulation.


Motor transmission in the vas deferens: the inhibitory action of noradrenaline.


Adrenaline uptake mechanisms in the rat uterus.


Changes in the responsiveness of the colon and vas deferens to nerve stimulation and injected transmitters in the pithed rat following chronic morphine treatment.


Potentials in isolated rat superior cervical ganglia produced by nicotine.


The effect of drug pretreatment on synaptic activity in Helix brain.


Actions of phenelzine on the interactions of the metabolism of tryptophan and dopamine in brain.


Acute hypothermic response of the rat to intraventricular injection of 6-hydroxydopamine.


The relationship between leucocyte ascorbic acid and plasma iron.


Cardiovascular effects of pancuronium in anaesthetized man.


The use of post-operative vomiting as a means of evaluating anti-emetics.


The effect of ingested alcohol on hand blood flow in resting man.


Vascular actions of clonidine in man.

Vascular actions of clonidine in man.


A new method for studying the pharmacology of the superficial veins in conscious man.


A method for studying spinal pharmacology in man.


The influence of dose on the distribution and elimination of amylobarbitone in healthy subjects.


The release of rabbit aorta contracting substance (RCS) from chopped lung and its antagonism by anti-inflammatory drugs.


Simplified thin-layer chromatography of prostaglanding in biological extracts.


The effect of isoprenaline on the responses of the guinea-pig isolated heart to vagal stimulation and to acetylcholine.


The Vidian nerve and the sphenopalatine ganglion in relation to lacrimation in the cat.


The release of biologically active substances from isolated lungs by 5-hydroxytryptamine and tryptamine.


Acetylcholine receptors of invertebrate neurones.


Electron microscopical examination of the junction between the myenteric plexus and the longitudinal muscle of the guinea-pig ileum.


The induction of physical dependence to morphine in the rat using a subcutaneously implanted reservoir.


Measurement and printout of average heart rate using digital techniques.


Tolerance to neostigmine.

Tolerance to neostigmine.


Simultaneous determination of choline acetylase and cholinesterase activity.


Determination of the iontophoretic release of adenosine diphosphate from micropipettes.


Interaction between anticonvulsant drugs and vitamin D.


A method for the determination of residual quantities of halothane in blood.


Pharmacologically active substances in malignant ascites fluid.


The measurement of renal blood flow during anaesthesia by means of a single-shot urineless technique with 131-I-hippuran.


A three-channel telephone data link for the transmission of physiological variables.


An improved method of measuring drug-induced peripheral vascular responses in conscious man.


Comparison of atropine and (--)-hyoscyamine on heart rate in man.


A class experiment to investigate the side-effects of anti-emetics.


The mathematical relationship of drinking water lithium and rainfall to mental hospital admission.


Infectious hepatitis: protection by immunoglobulin.


Treatment of postural hypotension.

Treatment of postural hypotension.


Study of the role of non-agglutinating vibrios in the aetiogenesis of Asiatic cholera.


Antibiotic sensitivity pattern of vibrio strains isolated from different parts of India during 1968.


V. Cholerae (biotype El Tor) infection in Patna.


Vibrio parahaemolyticus in Calcutta.

Vibrio parahaemolyticus in Calcutta.


Perspectives in cholera research.

Perspectives in cholera research.


Relationship between volume flow and velocity in the cerebral circulation. The relationship between the velocity of the cerebral circulation and the cerebral blood flow was explored at varying levels of PaCO(2), systemic arterial pressure, intracranial pressure, and perfusion pressure, using radioisotope techniques in baboons. Only at low flow rates did velocity increase with flow, and then non-linearly; at high rates velocity increased progressively less. Changes in flow are reflected by changes in velocity in such restricted circumstances that mean circulation time is a very unreliable indication of cerebral blood flow.


Effects of hyperbaric oxygen on intracranial pressure and cerebral blood flow in experimental cerebral oedema. Increased intracranial pressure was induced in anaesthetized dogs by application of liquid nitrogen to the dura mater. Intracranial pressure and cerebral blood flow were measured, together with arterial blood pressure and arterial and cerebral venous blood gases.Carbon dioxide was administered intermittently to test the responsiveness of the cerebral circulation, and hyperbaric oxygen was delivered at intervals in a walk-in hyperbaric chamber, pressurized to two atmospheres absolute.Hyperbaric oxygen caused a 30% reduction of intracranial pressure and a 19% reduction of cerebral blood flow in the absence of changes in arterial PCO(2) or blood pressure, but only as long as administration of carbon dioxide caused an increase in both intracranial pressure and cerebral blood flow. When carbon dioxide failed to influence intracranial pressure or cerebral blood flow then hyperbaric oxygen had no effect. This unresponsive state was reached at high levels of intracranial pressure.


Regional cerebrovascular responses to acute ischaemia in normocapnia and hypercapnia. An experimental study in baboons. Arterial and venous pressures have been measured in the cortical circulation of baboons. Arterial perfusion pressure was found to be relatively lower in hypercapnia than in normocapnia, while venous pressure was higher in hypercapnia than normocapnia. In hypercapnia, during middle cerebral occlusion, the arteriovenous pressure differences virtually disappeared and evidence of collateral inflow to the ischaemic zone was absent. Reactive hyperaemia after middle cerebral occlusion was reduced or abolished in hypercapnia. The significance of these findings in relation to treatment of ischaemic vascular disease with CO(2) is discussed.


In vitro staining of intramuscular nerve endings. A method is described for vital staining of the human intramuscular nerve endings after the muscle biopsy has been removed from the patient. The muscle is transferred from the site of operation to the laboratory in oxygenated physiological saline. Methylene blue solution (0·015%) is injected into the muscle strip, and development of the stain can be observed under the microscope after exposure of the muscle to air. Permanent squash preparations can be made of the stained muscle and these are identical in appearance to muscles stained by injection of methylene blue in vivo.


Effect of speed of muscle contraction on physiological tremor in normal subjects and in patients with thyrotoxicosis and myxoedema. The speed of the ankle jerk and physiological finger tremor in patients with thyrotoxicosis and myxoedema have been compared with those in age-matched control subjects. Tremor amplitude depends on the speed of muscle contraction; the faster muscle contracts the greater is the amplitude of tremor, and vice versa. The frequency of the dominant tremor peak is not affected by the speed of contraction but its size increases as muscle contracts faster. Muscle dynamics is clearly one of many factors influencing physiological tremor but is not responsible for the dominant frequency of tremor at round 9 c/sec.


Acid maltase levels in muscle in heterozygous acid maltase deficiency and in non-weak and neuromuscular disease controls. Acid maltase (AM) deficiency carriers can be detected by muscle enzyme assay. The assay indicates that, just as in infantile and childhood cases, adult cases of the disease are transmitted by autosomal recessive inheritance. With the maltose hydrolysis assay, in some neuromuscular diseases, muscle AM activity can be as low as in heterozygous AM deficiency. A relatively low muscle AM activity in myxoedema myopathy is confirmed. In human muscle, the K(m) of the enzyme for maltose hydrolysis is 7·2 to 9 × 10(-3)M. A modification of the enzyme assay based on this fact is recommended.


The effect of acrylamide on the peripheral nervous system of the baboon. In the baboon, acrylamide produces a clinical illness characterized by weakness and ataxia of the limbs, weakness of bulbar muscles, and finally tetraplegia. Histological examination shows extensive involvement of peripheral nerves, the main histological change being a Wallerian type of degeneration affecting the distal ends of the largest diameter nerve fibres. The phenomenon of `dying back' has been demonstrated in single teased fibres. Changes also occur in the paranodal myelin; these are not necessarily associated with degeneration of the axon, since intercalated segments and extension of myelin from neighbouring internodes are present in recovering animals. Demyelination of whole internodes is rare. Paranodal changes may be found a few millimetres proximal to complete degeneration, but may also occur on fibres which are otherwise normal in the length examined. The mechanism of the paranodal changes is uncertain, but they may indicate a secondary response of the Schwann cell to a primary change in the axon.


Motor neurone disease and exposure to lead. Disease of the lower motor neurone is a recognized hazard of lead toxicity, but the importance of contact with lead in the causation of motor neurone disease has not previously been ascertained. In 74 cases of motor neurone disease, 15% had a history of extensive exposure to lead, compared with 5·4% of a control group. The five year survival rate of these patients was 54%, compared with 16% in the remainder. The more benign course of the disease in some of these cases may be due to treatment with chelating agents. A history of either disease of the axial skeleton or previous fracture was obtained in 25% of patients compared with 9·4% of controls. There may be a relationship between skeletal demineralization and the development of motor neurone disease. The lead content of iliac crest bone biopsy specimens in 25 patients with motor neurone disease was no greater than that of a control group, but this does not exclude the possibility that lead liberated from bone might affect the motor neurone.


Considerations concerning the neuro-endocrine characterization of sportsmen.


The olympic ideology.

The olympic ideology.


Effect of ultraviolet irradiation on the survival of simian virus 40 functions in human and mouse cells. The relative sensitivities to ultraviolet light of various simian virus 40 (SV40) functions were studied in human and mouse cells. Transformation appeared to be less ultraviolet (UV)-sensitive than either T or V antigen when all functions were compared in the same cell. However, the time course of both T- and V-antigen appearance was delayed with UV-irradiated virus, so that the survival curves of these functions changed with time. Mouse and human cells which were transformed by UV-SV40 all contained SV40 T antigen. Infectious virus could be recovered from many more transformants than would be expected from the infectivity in African green monkey kidney cells of the irradiated virus. The results suggest that human and mouse cells are capable of reactivating UV-damaged SV40.


Control of the replication complex of bacteriophage P22. A replication complex for the vegetative synthesis of the deoxyribonucleic acid (DNA) of the temperate phage P22 previously has been described. This complex is an association of parental phage DNA, most of the newly synthesized phage DNA made during pulses with (3)H-thymidine, and other cell constituents, and has a sedimentation rate in neutral sucrose gradients of at least 1,000S. The complex is one of the intermediates, intermediate I, in the synthesis and maturation of phage P22 DNA after infection or induction. Evidence supporting the replicative nature of intermediate I is presented. Phage replication is repressed in lysogenic bacteria. On superinfection of P22 lysogens with nonvirulent phage, little association of the input phage DNA with a rapidly sedimenting fraction is demonstrable. However, after induction with ultraviolet light, the superinfecting parental phage DNA quickly acquires the rapid sedimentation rate characteristic of intermediate I; phage DNA synthesis follows; and progeny phages are produced. Infection with a virulent mutant of P22 produces progeny phages in lysogens. Its DNA associates with intermediate I. In mixed infection with the virulent phage, replication of nonvirulent phage P22 is still repressed, even though the virulent replicates normally. The nonvirulent input DNA does not associate with intermediate I. The repressor of the lysogenic cell prevents replication by interfering with the physical association of template material with intermediate I. A phage function is required for association of phage template with the replication machinery.


Soluble components of adenovirus type 8. Soluble components of type 8 adenovirus have been studied. Four different components were isolated by anion-exchange chromatography and purified by further chromatographic procedures, by zonal centrifugation, and by erythrocyte absorption and elution. The four components exhibited the following characteristics. (i) Fiber antigen was trypsin-resistant and functioned as incomplete hemagglutinin (agglutinated rat and human erythrocytes only in the presence of certain types of adenovirus antisera). (ii) The penton was trypsin-sensitive, exerted a cytotoxic effect, and also showed incomplete hemagglutination, being active in the presence of a majority of heterotypic adenovirus antisera studied. (iii) The group-specific hexon antigen reacted in complement fixation reaction and gel precipitation with sera prepared against other types of adenoviruses, besides showing characteristics indicating the presence of a type-specific antigen component. (iv) The soluble complete hemagglutinin was trypsin-sensitive, displayed cytotoxic effect, adsorbed easily to human and rat erythrocytes, and could be eluted from them by means of receptor-destroying enzyme. The three hemagglutinins of adenovirus type 8 proved to be highly unstable, and their demonstration was only successful by using a large quantity of freshly prepared concentrated virus material. Considering these conditions, a method was developed for their concentration and purification.


Action of interferon: kinetics and differential effects on viral functions. A highly purified rabbit interferon was tested for its capacity to inhibit various manifestations of infection of primary rabbit kidney (RK) cells with vesicular stomatitis (VS) virus. A kinetic analysis of the actinomycin-sensitive phase of interferon-induced cellular resistance revealed that RK cells could transcribe virtually all of the hypothetical antiviral messenger ribonucleic acid (mRNA) within 3 hr. Similar exposure to interferon reduced virus yield by 95 to 99% and markedly inhibited cytopathic effect on RK cells infected at a multiplicity of 10 or less. Interferon was less effective in blocking cytopathic effects when RK cells were infected at a multiplicity of 100. However, RK cells pretreated with the same amount of interferon and infected at a multiplicity of 100 failed to incorporate (3)H-amino acids into structural or nonstructural proteins of VS virus identified by polyacrylamide gel electrophoresis. Despite this inhibition of viral protein synthesis, interferon did not prevent the switch off by VS virus of cellular protein synthesis. The rapidity with which a high multiplicity of VS virus switched off cellular protein synthesis, even in cells rendered resistant to viral infection by interferon, is further evidence that this reaction is caused by an infecting virion component rather than by a newly synthesized viral product.


Effect of elevated temperature on deoxyribonucleic acid synthesis in bacteriophage phi-29-infected Bacillus amyloliquefaciens. Deoxyribonucleic acid (DNA) synthesis in bacteriophage phi29-infected Bacillus amyloliquefaciens was studied at 37 and 45 C. Infectious intracellular particles appear at the same time at both temperatures, but the average burst size is reduced 45 to 50% at 45 C. There is a transient inhibition of cellular mass increase at 45 C which is not observed at the lower temperature. In addition, the rate of host DNA synthesis is reduced and the onset of viral-specific DNA replication is delayed for 6 to 9 min at 45 C. These findings allowed us to screen phage phi29 mutants which are sensitive to growth at 45 C for their ability to synthesize phi29 DNA in the absence of host DNA replication. We obtained mutants which make no viral DNA, reduced levels of DNA, or normal quantities of DNA under nonpermissive conditions. Pulse-labeled viral DNA which sediments more rapidly than mature phi29 DNA molecules was observed after gentle cell lysis and zone sedimentation. This DNA is not a precursor of normally sedimenting phi29 DNA and apparently consists of mature phi29 DNA molecules aggregated with large pieces of bacterial DNA.


Association of viral ribonucleic acid with cellular membranes in chick embryo cells infected with Sindbis virus. Membranes from cells infected with Sindbis virus had associated with them viral ribonucleic acid (RNA) polymerase and about 60 to 70% of the viral RNA labeled when short pulses were used. This RNA contained most of the replicative intermediate and replicative form of viral RNA found in the infected cells. The use of "Mg(2+) sarkosyl crystals" permitted the isolation of membrane-bound nucleic acids and allowed the demonstration that Sindbis virus RNA was synthesized on a membrane-viral RNA complex. Viral RNA from the infecting virions first became associated with the membranes during the latent period and, subsequently, slowly detached. The attachment of the viral RNA to the membranes did not require active viral RNA polymerase, since RNA from ts6, an RNA(-) temperature-sensitive mutant of Sindbis virus, associated with cellular membranes at a nonpermissive temperature. However, the subsequent detachment of the RNA from the membranes was restricted in the absence of viral RNA synthesis. The results indicate that association of viral RNA with cellular membranes may represent an early step occurring during the replication of Sindbis virus RNA.


Isolation and characterization of two basic internal proteins from the T-even bacteriophages. Two species of basic internal proteins were found in osmotic shock supernatant solutions of bacteriophages T4B, T4D, T2H, T2L, and T6. The major species of protein isolated had a molecular weight of approximately 21,000 daltons, whereas the minor protein molecular weight was near 9,500 daltons. The two protein species exhibited unique isoelectric points and amino acid compositions. The 21,000-dalton protein of T2L showed major electrophoretic and compositional differences from the other 21,000-dalton proteins isolated. Similarities between the 21,000-dalton proteins and phage lysozyme are discussed.


Intracellular development of bacteriophage phi-R. II. Fractionation of replicative form deoxyribonucleic acid associated with rapidly sedimenting host cell components. When Escherichia coli is infected with bacteriophage phiR, parental deoxyribonucleic acid (the single- or double-stranded DNA containing the isotopic label of the infecting phage) becomes firmly attached to a cellular structure and can be isolated as a rapidly sedimenting component as described earlier for phiX174. If this component is centrifuged to equilibrium, two peaks of infective DNA are observed at densities of 1.30 and 1.15 g/ml. At low multiplicities of infection, (32)P-labeled parental DNA is found associated with only the cellular components in the dense band; as the multiplicities of infection are increased, the dense band becomes saturated and parental DNA molecules are then found at the light density as well. Actively replicating host DNA is found only in the dense band, whereas progeny DNA, which does not replicate semiconservatively, can become associated with cellular components in the light band. This fractionation of cellular components on the basis of their buoyant density separates primary sites of DNA replication associated with the dense band from nonfunctional binding sites in the light band.


Sedimentation properties of simian virus 40-specific ribonucleic acid present in green monkey cells during productive infection and in mouse cells undergoing abortive infection. The size distribution of polyribosome-associated simian virus 40 (SV40) ribonucleic acid (RNA) was examined at various times after productive infection. Eight hours after infection, virus-specific RNA was detected in the 14 to 17S region of a sucrose gradient by deoxyribonucleic acid (DNA)-RNA hybridization; RNA present in fractions sedimenting more rapidly did not react with SV40 DNA. At successively later times, SV40 RNA was detected in more rapidly sedimenting regions. By 24 hr, a portion of the SV40 RNA was detected in the 28S region, sedimenting slightly more rapidly than a MS2 RNA marker. Nuclear SV40 RNA, prepared from cells 48 hr after infection, was distributed in more rapidly sedimenting regions of the gradient, peaking at about 32 to 34S. Some nuclear virus-specific RNA could be detected in the 45 to 50S region. During the abortive infection of mouse cells, the sedimentation profile of SV40 RNA was very similar to that observed during the early phases of the lytic cycle.


Susceptibility of human cell strains to transformation by simian virus 40 and simian virus 40 deoxyribonucleic acid. Marked differences were found in the susceptibility of human fibroblasts to transformation by simian virus 40 (SV40). Highly susceptible cell strains were derived from patients with diseases associated with chromosomal abnormalities and a high incidence of tumors. In the present study, SV40 transformation-susceptible cell strains were not found to have a generalized increase in viral sensitivity. The differences in transformation frequency among cell strains with whole virus are eliminated by the use of isolated SV40 deoxyribonucleic acid, suggesting that the relative resistance of most cell strains to transformation by whole virus is due to a block at an early step in infection.


Interferon production and inhibition of host synthesis in cells infected with vesicular stomatitis virus. Infection of L cells with wild-type (L(1)) vesicular stomatitis virus at high or low multiplicities does not result in the production of interferon; however, infection of L cells with low multiplicities of a small-plaque mutant (S(2)) results in the synthesis of large amounts of interferon. In chick embryo (CE) cells, both viruses induce synthesis of interferon; there is no significant multiplicity effect in CE cells. The rate and efficiency of shutoff of macromolecular synthesis in the different host cells is a critical factor in determining the ability of the viruses to induce interferon synthesis. If host ribonucleic acid or protein synthesis is shut off by the virus before the required new ribonucleic acid is transcribed or translated, interferon production does not occur. The relative yield of the two viruses in CE and L cells is not related to the effects of interferon produced during the course of infection.


Inhibition of Poxvirus replication by streptovaricin. A component of streptovaricin complex inhibits the replication of poxvirus. To be effective, the inhibitor must be introduced early in the replication cycle; it appears to inhibit early messenger ribonucleic acid synthesis by viral cores, thus interfering with all subsequent events. Neither of the two major components of the complex, streptovaricin A or C, was the active component.


Isolation of hemagglutinin and neuraminidase subunits of hemagglutinating virus of Japan. When purified hemagglutinating virus of Japan (HVJ) was treated with trypsin, two major surface antigens were released from the virus. The "hemagglutinin" subunits obtained by this method were reactive with homologous hemagglutination-inhibition antibody and could be detected by an antibody-blocking test. They adsorbed to but did not agglutinate red cells and thus appeared to be "monovalent." The neuraminidase subunits were obtained in fully active form and did not adsorb to red cells. This finding suggests that these two activities of HVJ are associated with different subunits of the virus particle. The hemagglutinin and neuraminidase subunits could be partially separated by zonal rate centrifugation or gel filtration on Sephadex G-200. The molecular weights estimated for these subunits were approximately 124,000 and 114,000, respectively. After treatment with trypsin, virus-associated hemagglutinin and neuraminidase activities were both reduced significantly. The electron micrographs of such trypsinized virus particles showed complete or partial loss of surface projections. These results suggested that the subunits obtained by this method seemed to be those projections liberated from the virus by the action of trypsin.


Dengue virions and antigens in brain and serum of infected mice. The temporal relationships of the production of infectious dengue-2 virus and its antigens were investigated in intracerebrally infected suckling mice. Infectious virus, a slowly sedimenting noninfectious hemagglutinin (SHA), and a noninfectious soluble complement-fixing antigen (SCF) were found in the brain. Serum contained high concentrations of SCF antigen relative to infectivity when compared to SCF to infectivity ratios in the brain. Degradation of virions by Tween-80 and ether produced two antigens with sedimentation characteristics similar to the noninfectious antigens occurring naturally in infected tissues. However, the virionderived SHA differed from native SHA when examined by electron microscopy and by equilibrium centrifugation in cesium chloride. Virion-derived SCF (as well as the virions and both SHA antigens) was denatured by sodium lauryl sulfate (SLS) and 2-mercaptoethanol (2-ME), whereas native SCF retained its complement-fixing activity. SLS and 2-ME treatment of dengue-1 and dengue-2 sucrose-acetone antigens increased their serotypic specificity. The hemagglutinin present in sucrose-acetone antigens was predominantly native SHA.


Arenoviruses in Vero cells: ultrastructural studies. Thin-section electron microscopy was carried out on Vero green monkey kidney cell cultures infected with some viruses of the newly constituted arenovirus group. Junin, Machupo, Amapari, Pichinde, Parana, Tamiami, and Latino viruses were morphologically identical and indistinguishable from lymphocytic choriomeningitis virus, the prototype virus of the group. Virus particles were round, oval, or pleomorphic, 60 to 280 nm in diameter, and matured via budding from plasma membranes. Most characteristically, particles contained various amounts of homogeneous, 20- to 25-nm, dense granules; these granules in large masses also formed distinctive intracytoplasmic inclusions. In negative-contrast preparations from infected Vero cell culture supernatant fluids, several of the viruses appeared as pleomorphic membrane-bound forms with rather pronounced surface projections. Most particles were between 90 and 220 nm in diameter, although some reached 350 nm in their longest dimension. Internal structure was not resolved by negative-contrast electron microscopy. All observations supported the current delineation of a distinct arenovirus group.


Interruption by Rifampin of an early stage in vaccinia virus morphogenesis: accumulation of membranes which are precursors of virus envelopes. Assembly of vaccinia virus envelopes and immature vaccinia particles was interrupted in HeLa cells treated with rifampin (rifampicin). The primary action of rifampin on vaccinia morphogenesis appeared to occur during the stage of envelope formation. When envelopes and immature particles were already present, maturation could continue, even in the presence of rifampin. It was demonstrated that the trilaminar membranes of irregular contour which accumulate in the presence of rifampin are precursors of virus envelopes. When rifampin was removed under controlled conditions, synchronous transitions were observed as the precursor membranes rapidly converted into uniformly curved envelope units with a 10- to 12-nm coat on the convex surface. These experiments provided an opportunity to examine the sequence of some early events in vaccinia morphogenesis. Initially, nascent envelopes remained in clusters around dense viroplasm. Large numbers of single immature particles appeared within 10 min. Nucleation of immature particles was the first evidence of core differentiation and began within 5 to 10 min. Development of lateral bodies and modeling of the biconcave cores was observed within 30 min, and structurally mature virions were present by 2 hr after the removal of rifampin. High resolution autoradiography showed that viral deoxyribonucleic acid, which labeled with (3)H-thymidine during rifampin treatment, was incorporated by the mature vaccinia which formed after rifampin was removed. Concentration of the viral deoxyribonucleic acid in core material evidently occurred after envelope assembly, probably coincident with nucleoid formation. Cytoplasmic crystalloid bodies accumulated during rifampin treatment; they appeared morphologically identical to vaccinia nucleoids and were heavily labeled by (3)H-thymidine.


Characterization of T-even bacteriophage substructures. I. Tail fibers and tail tubes. T-even bacteriophages were grown and purified in bulk quantities. The protein coats were disrupted into their component substructures by treatment with 67% dimethyl sulfoxide (DMSO). Tail fibers and tubes were purified on glycerol-CsCl-D(2)O gradients and examined with respect to sedimentation properties, subunit molecular weights, amino acid composition, isoelectric points, and morphology. It was found that intact tail fibers had a sedimentation coefficient of 12 to 13S and that dissociated fibers consisted of three classes of proteins having molecular weights of 150 K +/- 10, 42 K +/- 4, and 28 K +/- 3 daltons. A model was constructed in which the 150-K subunit folded back on itself twice to give a three-stranded rope. Each 150-K subunit then represented a half-fiber and it was proposed that the role of the 42- and 28-K subunits was to hold each half-fiber together as well as serve as a possible link with other substructures. Isoelectric point studies also indicated that there were three different proteins with pI values of 3.5, 5.7, and 8.0. Amino acid analyses indicated that fibers had a composition distinct from other phage substructures. In addition, a striking difference was noted in the content of tryptophan among the phages examined. T4B had three to five times more tryptophan than did T2L, T2H, T4D, and T6. Intact tail tubes had an S(20,w) of 31 to 38S and dissociated tubes consisted of three proteins of molecular weights 57 K +/- 5, 38 K +/- 4, and 25 K +/- 3 daltons. Based on degradation studies with DMSO, it was proposed that these three proteins were arranged in a helical array yielding the tube structure. Isoelectric point studies indicated that there were three major proteins in the tube whose pI values were 5.1, 5.7, and 8.5. No significant differences were observed in the amino acid content of tubes obtained from all the T-even bacteriophages.


Characterization of T-even bacteriophage substructures. II. Tail plates. Tail plates obtained from T4D amber mutants were examined with respect to sedimentation behavior, subunit molecular weights, amino acid composition, isoelectric points, and morphology. Intact plates had an S(20,w) of 77S from pH 5 to 9. The only conformational change noted was that below pH 5 tail plates readily dimerized yielding vis-à-vis dimers with an S(20,w) of 124S. Dissociated plates consisted of three major proteins with molecular weights of 53 K +/- 5, 31 K +/- 3, and 17 K +/- 2 daltons. The amino acid analyses indicated that plates had a composition distinct from fibers and tubes and were relatively rich in tryptophan. Degradation studies with dimethyl sulfoxide (DMSO) indicated that tail plates had a unique biological structure. After treatment with DMSO, and to some extent without DMSO, or from lysates of defective mutants, tetrad structures were observed in the electron microscope. These structures had an amino acid content and relative amounts of types of subunits similar but not identical to intact plates. It was proposed that plates were composed of nine such tetrads giving rise to a structure with six- and threefold symmetry.


Quantitative determination of neuraminidase-active foci in cell monolayer cultures infected with influenza or newcastle disease virus. A synthetic neuraminidase substrate [2-(3'-methoxyphenyl)-N-acetyl-alpha-neuraminic acid] was used to detect myxo- and paramyxovirus replication in tissue culture. This method allowed estimation of viral growth even in the absence of cytopathogenic effects.


Incorporation of deoxyribonucleic acid precursors by T4 deoxyribonucleic acid-protein complexes retained on glass fiber filters. Bacteriophage T4 deoxyribonucleic acid (DNA)-protein complexes were retained preferentially on glass fiber filters. DNA polymerase activity in the complex was detected through the incorporation of (3)H-labeled DNA precursors. The primer-product DNA hybridized with both phage and Escherichia coli DNA. Density labeling experiments showed that about 30% of incorporated (3)H-deoxyadenosine triphosphate was found in DNA which hybridized with phage DNA; this DNA was found to be covalently attached to the primer DNA.


Ribonucleoside triphosphate-dependent pyrophosphate exchange of Reovirus cores. Reovirus cores catalyze a ribonucleoside triphosphate (rNTP)-dependent pyrophosphate exchange reaction in the presence of all four rNTP species. When rNTP species are tested individually, only guanosine-5'-triphosphate supports pyrophosphate exchange.


The effect of carnitine on the oxidation of palmitate in alcohol-fed rat liver mitochondria.


Molecular weight of Adenovirus type 2 hexon polypeptide. The fully dissociated hexon polypeptide of adenovirus type 2 has a molecular weight of 129,000 (+/-10,000) daltons as determined by high-speed sedimentation equilibrium in 6 m guanidine.


Effect of vitamin B12 on the formation of collagen and nucleic acids in the albino rat skins and granulomas.


3H-vitamin A and rat skin. Autoradiographic observations.


Biosynthesis of thiamine in plants. I. Enzymic formation of thiamine from pyrimidine and thiazole moieties.


Effect of ascorbic acid on hydroxylase activity. I. Stimulation of tyrosine hydroxylase and tryptophan-5-hydroxylase activities by ascorbic acid.


Studies on the induction of tyrosine transaminase by large dose administration of vitamin B6.


Studies on the nutritional value of tempeh. 3. Changes in biotin and folic acid contents during tempeh fermentation.


Biogenesis of riboflavin in green leaves. VII. Isolation and characterization of spinach riboflavin synthetase.


Studies on fatty acid esters of flavins. VII. Reaction of riboflavin tetrabutyrate with linoleic acid under ultra violet light irradiation.


Effect of dimethyl sulphoxide on charge transfer complexes of D-amino acid oxidase under low temperatures.


Histochemistry of the pigments found in the liver, spleen and kidney of the fresh-water fish.


Studies on the phosphate requirement for xanthine dehydrogenase activity. IV. Effect of sodium deoxycholate upon the enzyme.


Nucleic acids synthesis during the 3rd molt period of Rhynchosciara americana.


A method for simultaneous brain stimulation and electrocardiographic recording in unanesthetized free-moving cats.


Correlation between behavioural and electrophysiological effects of pyrithoxine in unrestrained cats and rabbits.


Blood iron metabolism in fowl and rabbit.


The present development of psychiatry and its consequences for the training of future psychiatrists.


Surgical treatment of trigeminal neuralgia following the method of Dandy. Some historical remarks and technical suggestions.


Enzymic obtaining of U-14C 4-aminobutyric acid from U-14C glutamic acid.


Simple elution procedure for estimation of the serum protein bands separated by disc electrophoresis in polyacrylamide gel.


Repair of a large eyelid defect. Case report.


Enzyme histochemical studies on rat skin autografts.


Sympathetic denervation and reinnervation of cutaneous blood vessels following surgery. An experimental study on rats by means of a histochemical fluorescence method.


Skin allografts in rats with extensive skin loss.


Urinary estrogen assay by isotope dilution method in normal pregnancy.


Automatic control of temperature in the incubator.


Apparent sound displacement during vestibular stimulation.


Effects of cyclophosphamide on the patho-physiological course of steroid nephropathy in rabbits.


A test of a perspective theory of geometrical illusions.


Effects of early experience on fear behaviour of Coturnix coturnix.


Mouthbreeding in fishes.

Mouthbreeding in fishes.


One versus two discrimination by whitenecked ravens (Corvus cryptoleucus) with non-number dimensions varied.


Hypothermia and behavioural thermoregulation by the hamster (Mesocricetus auratus).


The influences of the sex of littermates on body weight and behaviour in rat pups.


Locomotor activity rhythms in homing pigeons (Columba livia).


Monocular discrimination of mirror-image obliques by pigeons: evidence for lateralized stimulus control.


The role of stimulus female novelty in the rearousal of copulation in male laboratory rats (Rattus norvegicus).


Rhinovirus strain as a possible cause of equine respiratory infection.


Nodular dermal allergide of Gougerot. Report of a case.


The role of adenine and adenosine as precursors for adenine nucleotide synthesis by fresh and preserved human erythrocytes.


An internal standard for the determination of buoyant density of RNA in CsCl density gradient.


Bological activity of phi X174 replicative form DNA fragments.


Chemical protection against breaks induced in DNA of human and bacterial cells by x-irradiation.


Degradation of DNA in a temperature-sensitive mutant of Escherichia coli defective in DNA synthesis, harboring the colicinogenic factor E1.


Significance of electrical reactions in facial palsy of newborn. A case report.


Purification and properties of Escherichia coli CTP (ATP)-tRNA nucleotidyltransferase.


Inhibition of transfer RNA methylases by bull semen. I. Localization, identification and properties of the inhibitor.


Differential labelling of the carboxymethyl and methyl substituents of 5-carboxymethyluridine methyl ester, a trace nucleoside constituent of yeast transfer RNA.


Differential labelling of the thio, carboxymethyl and methyl substituents of 2-thio-5-carboxymethyluridine methyl ester, a trace nucleoside constituent of yeast transfer RNA.


Estrogen-induced variation of lysine transfer ribonucleic acid isoacceptors in chicken liver.


Brain function, carbon dioxide, anticonvulsants, and tranquilizers. Spinal fluid PH in brain diseases.


Temperature- and phenol-induced alterations in sedimentation rates of 29-S and 18-S ribosomal RNA's from Novikoff hepatoma cells.


On the mechanism of the biosynthesis of ribosomal RNA in yeast.


Formaldehyde and ribosomal conformation.


Effect of edeine on aminoacyl-tRNA binding to ribosomes and its relationship to ribosomal binding sites.


Formation of a complex between GTP, G factor, and ribosomes as an intermediate of ribosome-dependent GTPase reaction.


Interaction of informational macromolecules with ribosomes. 3. Binding of nuclear RNA by normal liver and hepatoma ribosomes.


Studies on the metabolism of RNA of free and membrane-bound polysomes from rat liver.


In vitro RNA synthesis and nuclear proteins of isolated sea urchin embryo nucleo.


RNA and protein synthesis in protoplasts isolated from tobacco leaves.


Induction of enzymes in dormant spores of Aspergillus oryzae. II. Effects of some aliphatic and aromatic alcohols.


The interaction of natural and synthetic polyanions with mammalian nucleo. I. DNA synthesis.


The interaction of natural and synthetic polyanions with mammalian nucleo. II. Nuclear swelling.


Protein synthesis of polytene nuclei in vitro.


Aflatoxin inhibition of template activity of rat liver chromatin.


An analysis of a possible base sequence complementarity of mitochondrial and nuclear DNA in yeast.


A possible role of the AUG codon in the initiation of polypeptide synthesis in a eukaryotic orgamism.


RNA and protein synthesis during germination of spherules of Physarum polycephalum.


Studies on methionyl-tRNA synthetase from Bacillus brevis by isoelectric focusing.


Benzoylated DEAE-sephadex. Its preparation and application.


Different sensitivity to ribonuclease of complexed and free ribosome.


Inability of rifampicin to inhibit circadian rhythmicity in Acetabularia despite inhibition of RNA synthesis.


On the extraction and characterization of ribosomal RNA from Acetabularia.


In vivo stimulation of 14C-amino acid incorporation into nonhistone proteins in rat liver chromatin induced by insulin and cortisol.


A DNA polymerase-DNA complex isolated from Escherichia coli.


Limits on DNA coding.

Limits on DNA coding.


The flexibility of a complex of DNA with methylated proflavine.


On the existence of intrastrand crosslinks in DNA alkylated with sulfur mustard.


Sedimentation properties of phage DNA molecules containing light-induced psoralen cross-links.


Sedimentation analysis of the rapidly labeled mitochondrial RNA of cultured hamster cells.


Success and failure among social scientists and health scientists at a technological university.


Stimulation of chromatin-bound RNA polymerase activity by a soluble factor.


Brightness contrast and the perceptual scale.


The relationships between personality, study methods and academic performance.


Values in deviancy theory and society.

Values in deviancy theory and society.


Genetic-evolutionary studies on cultivated Cannas. 3. Variation in meiotic system.


Bureaucratic flexibility: some comments on Robert Merton's 'Bureaucratic Structure and Personality'.


Neurosecretion and feed back mechanism in Clarias batrachus Linn. Ovariectomy and administration of exogenous sex hormones.


Growth and differentiation of the follicle epithelium in relation to vitellogenesis in Panorpa communis L. (Mecoptera, Insecta).


The control of tuberculosis in Matabeleland.


Endotoxic shock in Gram negative septiaemia.


The internal reproductive organs of Cydnus indicus Westw. A histological study (Cydnidae, Heteroptera, Insecta).


Recent developments in the chemistry of phospholipids.


Prolonged in vitro retention of oestradiol by cycloheximide in rat uterus.


Blood flow, blood pressure and heart rate changes accompanying hind leg flexion in conditional and unconditional reflexes.


Studies on the metabolism of steroids in the foetus. Biosynthesis of 16alpha-hydroxytestosterone in the human foetal liver.


Karyometrical studies on the effect of castration, stilboestrol and both castration and stilboestrol on adrenal cortex of adult male rats.


The smoke reflex in rabbits. An example of autonomic control of cardiorespiratory function.


Seasonal variations in the cyanophils and the gonadotropic potency of the pituitary in relation to gonadal activity in the catfish, Mystus vittatus (Bloch).


The influence of sex hormones during the hypothalamic differentiation and maturation phases on gonadal function and sexual behaviour during the hypothalamic functional phase.


Clinical electromyography and some questions relating to the neurophysiology of movements.


Pavlov and contemporary physiological psychology.


A comparative analysis of H- and M-responses and of general muscular electrogenesis in spasticity.


A comparative electromyographic study before and after operations for protruded lumbar disc.


A simple thin-layer chromatography procedure of isolation and estimation of corticosterone from the adrenal vein blood of rats.


A rapid centrifugation method for the counting of platelets with the Coulter counter.


A new technique for the extraction of the activity of single motor units from the electromyography of maximal contraction.


Congenital malformations of the tricuspid valve: a wide spectrum.


Bacterium anitratum meningitis. A case report.


Emotional concomitants of visual mastery in infants: the effects of stimulus movement on smiling and vocalizing.


The harmonies of movement recorded electromyographically.


Frustration tolerance and college grade point average.


Effects of brief sensory deprivation and somatic concentration on two measures of field dependence.


Effects of knowledge of the ITI on time estimates: method of production.


Language predictability and psychiatric interviews.


Tactual and visual concept identification.


Peripheral recognition thresholds for digits.


Fluctuations of perceptual organization and orientation: stochastic (random) or steady state (satiation)?


Note on amphetamine and food-motivated discrimination.


Field dependence and inner-other directedness.


Psychological test results of subjects with known cerebral lesions and Parkinson's disease as compared to controls.


Effects of knowledge of results and spacing of practice trials in training of control of binocular rivalry.


Relationship of kinesthetic figural aftereffect to masculinity-femininity and expectation for internal versus external control of reinforcement.


Effects of eye position on person perception.


Effect of frustration on stereotyped body rocking: follow-up.


Autokinetic word writing.

Autokinetic word writing.


Retinal size in the visual cliff situation.


Context effects in person perception as a function of dogmatism.


Visual-tactual dominance relationship as a function of accuracy of tactual judgment.


Note on perceived personality of a nude.


Perception on self as related to perception of the "ideal personality".


Minimum visual feedback processing time for amendment of an incorrect movement.


Further prototypes of ego formation: a working paper from a research project on early development.


Psychoanalytic theory and the psychoanalytic process.


Histological and histochemical studies of a new species of Thapariella (Trematoda: digenea).


On two species of intestinal flagellates of the gerbil, Gerbillus indicus.


Lecithobotrys vitellosus n. sp. (Haploporidae: Trematoda) from India.


Two new species of Tylencholaimellus N.A. Cobb in M.V. Cobb, 1915 (Dorylaimoidea: Leptonchidae) from Marathwada, India.


Some known and new genera and species of the family Thelastomatidae Travassos, 1929.


Differentiation of some taxonomic groups of Arthropoda by disk-electrophoretic analysis of protein extracts.


Taxonomic identity of Spinitectus major Khera 1954, and Spinitectus fossili Chandan Lal, 1966 (Nematoda: Rhabdochonidae: Spinitectinae).


The contractile ring. I. Fine structure of dividing mammalian (HeLa) cells and the effects of cytochalasin B.


Spermatogenesis in animals as revealed by electron microscopy. XIX. Peculiar granular body clusters in early spermatid nuclei of Grasshopper.


Longitudinal fibre division in skeletal muscle: a light- and electronmicroscopic study.


Ultrastructural changes in the nerves innervating the cerebral artery after sympathectomy.


Thermoregulatory effects of hypoxia in new-born rats and their correlation to body temperature and heat production prior to and after exposure to hypoxia.


Seasonal variations of the corticosteroid fractions in guinea pig tissue and organs.


Frequency-specific response of the pituitary-adrenocortical system on pontine stimulation.


Olfaction guided approaching behaviour of infantile rats to the mother in maze box.


Capillary resistance in the skin of rats fed flavone-free and atherogenic diets, and their response to hesperidin-methylchalcone.


Disturbances of porphyrin metabolism in schizophrenia.


Comparison of the cardiodepressant and antiarrhythmic effects of 2-piperidinyl-1-alpha-naphthyl-1-propanol HC1 (S-1043) and propranolol.


Effect of human serum albumin on renal blood flow autoregulation in the anaesthetized dog.


Effect of tourniquet on total lactate dehydrogenase (LDH) activity and isozyme pattern of rat serum.


Hepatic transport of iodipamide in various animal species.


Biliary secretion of rose bengal in the dog.


Cardiac output estimation by a thermodilution method involving intravascular heating and thermistor recording.


Increased sympathetic innervation of the rabbit heart. Explanation of the lability of the ECG in the rabbit.


Some effects of hypertonic NaCl solution on the mechanical and electrical responses of slow and fast muscles of the cat.


Effect of hypothalamic stimulation on adrenal blood flow and glycocorticoid release prior to and after acute hypophysectomy.


Serotonin and histamine contents as vital reactions. II. Autopsy studies.


Thermoregulatory effects of hypercapnia in the new-born rat. Comparison with the effect of hypoxia.


Advances in food technology and its social implications.


How do cells know where they are?

How do cells know where they are?


Effects of particles on lysosomes.

Effects of particles on lysosomes.


The chain of discovery.

The chain of discovery.


Fright, flight or fight.

Fright, flight or fight.


The role of lysosomes in arthritis.

The role of lysosomes in arthritis.


The coulometric titration of sodium seconal and sodium sandoptal and its application to the analysis of standard blood serum samples.


A rapid method for the detection and determination of captan.


Viral and morphologic studies on hepatomas in mice of strain C3H-Avy, with observations of a cultured hepatoma.


Ascitic transformation of a rat tumour derived from a human melanocarcinoma.


A comparison of the changes produced in reticuloendothelial organs of mice during host-versus-graft and graft-versus-host reactions.


The mechanism of action of heterologous antilymphocytic serum: the biological activity of rabbit macrophage-cytophilic antilymphocytic antibody in mice.


Immunity in the invertebrates. The fate and distribution of bacteria in normal and immunised crayfish (Parachaeraps bicarinatus).


Immunity in the invertebrates. Correlation of the phagocytic activity of haemocytes with resistance to infection in the crayfish (Parachaeraps bicarinatus).


Separation and characterization of cells produced by the antigenically stimulated lymph node.


Thiol distribution and mercaptalbumin reactivity in the blood plasma of different vertebrates.


Anomalous behaviour of blood volume following acute severe haemorrhage.


The assessment of a selected set of bacteriophages in the typing of Staphlococcus aureus of bovine origin in Australia.


The in vivo carbon dioxide titration curve in man during rebreathing.


Stimulus--cardiorespiratory effector response profile during arterial hypoxia in the unanaesthetized rabbit.


Immunoglobulin levels for maternal and foetal serum, amniotic fluid and foetal gastric juice in normal pregnancy.


Editorial.

Editorial.


Report of the twentieth Baker travelling fellow.


Undergraduate radiological anatomy.

Undergraduate radiological anatomy.


Cardiac catheterization. II. Detection and assessment of common cardio-vascular abnormalities.


Cardiac catheterization. 3. Angiocardiography.


Intravenous urography and pre-eclamptic toxaemia.


Urography with the iothalamate dimer and trimer.


Tendon sheaths and bursae involved by rheumatoid disease at the foot and ankle.


Cloverleaf skull and thanatophoric dwarfism.


A review of the physical data used in radium and radon dosimetry.


Thanatophoric dwarfism. A case report.

Thanatophoric dwarfism. A case report.


First World Congress of Nuclear Medicine and Biology. Université de Montréal, Montreal, Canada 30th August-4th September, 1971.


Analysing for alcohol.

Analysing for alcohol.


A reply to Douglas Wilkie.

A reply to Douglas Wilkie.


A reply to Linus Pauling and A. F. Huxley.


Calcium-45 uptake as a measurement of freeze-thaw injury to hicken spermatozoa in the presence or absence of cryopreservatives.


Enzyme changes during deacclimation of willow stem.


Ultrastructural damage in "protectively" treated, frozen-thawed, tomato fruit parenchyma.


Survival of dog kidneys subjected to high pressures: necrosis of kidneys after freezing.


Freeze-thaw behavior of a moderately halophilic bacterium as a function of salt concentration.


Low temperature preservation of monkey marrow in dimethyl sulfoxide.


Radiation risks from radiodiagnostic procedures.


Functional recovery of smooth muscle after exposure to dimethyl sulfoxide and low temperatures.


A note on the preservation of soil amebas by drying in vacuo.


Oraldene--an antiseptic mouthwash.

Oraldene--an antiseptic mouthwash.


Some of the problems associated with the freezing and thawing of kidneys.


Preliminary results with a new renal preservation unit.


Glycerol metabolism in untreated, cold-shocked, and frozen human spermatozoa.


Distribution of glutamic oxalacetic transaminase and lactic dehydrogenase activities in boar semen after cold shock and freezing.


The operation of the kidney bank of Buffalo.


Auxiliary monitoring system for a liquid nitrogen freezing chamber.


The kinetics of the inactivation of thylakoid membranes by freezing and high concentrations of electrolytes.


Oxygen utilization by rat skin exposed to several cryoprotective solutions during liquid nitrogen storage.


Some problems associated with the freezing of hearts.


An in vivo evaluation of various perfusates employed in renal preservation.


Analytical prediction of the temperature field emanating from a cryogenic surgical cannula.


IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Nomenclature for vitamins B6 and related compounds tentative rules.


Isolation and characterization of bovine thyrocalcitonin.


Nuclear magnetic relaxation dispersion in protein solutions. 3. Copper transferrin and bicarbonate-free copper transferrin.


Characterization of an ammonium transport system in filamentous fungi with methylammonium-14C as the substrate.


Protein biosynthesis in Escherichia coli. Purification and characteristics of a mutant G factor.


Further studies of a thymus nucleohistone-associated protease.


Mode of inhibition of beta-hydroxydecanoyl thioester dehydrase by 3-decynoyl-N-acetylcysteamine.


Biogenesis of chloroplast membranes. VI. Cooperation between cytoplasmic and chloroplast ribosomes in the synthesis of photosynthetic lamellar proteins during the greening process in a mutant of Chlamydomonas reinhardi y-1.


Crystallization of lysyl transfer ribonucleic acid synthetase from yeast.


Studies on poly(adenosine diphosphate ribose). IX. Direction of hydrolysis of poly(adenosine diphosphate ribose) by rat liver phosphodiesterase.


Studies on adrenal histones. Characterization, biosynthesis, enzymatic phosphorylation, and acetylation of histones from a human adrenal carcinoma.


Sites of synthesis of chloroplast membrane polypeptides in Chlamydomonas reinhardi y-1.


Constitutive inorganic pyrophosphatase of Escherichia coli. 3. Molecular weight and physical properties of the enzyme and its subunits.


Constitutive inorganic pyrophosphatase of Escherichia coli. IV. Chemical studies of protein structure.


Constitutive inorganic pyrophosphatase of Escherichia coli. V. Reconstitution of native enzyme particles from subunit polypeptide chains.


Constitutive inorganic pyrophosphatase of Escherichia coli. VI. Inactivation by chemical modification of lysine residues.


Biosynthesis of the pyrrolopyrimidine nucleoside antibiotic, toyocamycin. VII. Origin of the pyrrole carbons and the cyano carbon.


Functional aspects of the subunit association-dissociation equilibria of hemoglobin.


Ketone body metabolism in the ketosis of starvation and alloxan diabetes.


The function of pseudouridylic acid in transfer ribonucleic acid. IV. Cyanoethylation of fragments of Escherichia coli formylmethionine transfer ribonucleic acid and reconstitution of acceptor activity.


The purification and physical properties of glutamate dehydrogenase from rat liver.


The metabolism of O-phosphorylethanolamine in animal tissues. I. O-phosphorylethanolamine phospho-lyase: partial purification and characterization.


Aromatic alpha-keto acid reductase from rat kidney.


The alkaline reaction of nicotinamide adenine dinucleotide, a new transient intermediate.


Mammalian alpha-keto acid dehydrogenase complexes. VI. Nature of the multiple forms of pig heart lipoamide dehydrogenase.


Biosynthesis of urea. 8. Dissociation-association kinetics and equilibria of argininosuccinase.


Nature of the ribonucleic acid formed prior to deoxyribonucleic acid synthesis in kidney cortex cells cultured directly from the rabbit.


Biosynthesis of a fucose-containing glycopeptide from rat small intestine in normal and vitamin A-deficient conditions.


Relationship of the MS nucleotides to the regulation of ribonucleic acid synthesis in Escherichia coli.


CO2 fixation and the involvement of allophanate in the biotin-enzyme-catalyzed cleavage of urea.


Dissociation of Semliki Forest virus into biologically active components.


Studies on rubella virus strain variation by kinetic haemagglutination-inhibition tests.


Failure to demonstrate the interaction of subunits of thymidine kinase in cells simultaneously infected with herpes virus and a kinaseless mutant.


Adeno-associated satellite virus growth supported by a temperature-sensitive mutant of human adenovirus.


Properties of Proteus mirabilis phage 13vir.


Clues to the possible mode of action of cigarette smoke in the pathogenesis of lung cancer.


Distribution of rhesus blood groups amongst Maharashtrians and its association with ABO blood groups.


Immunization against tetanus in cases of otitis media and dental sepsis.


Rural medical practitioners in Andhra Pradesh and West Godavary District.


Rod-cone independence for sensitizing interaction in the human retina. 1. Illumination of a retinal area adjoining a tested area can cause either desensitization or sensitization through lateral interaction, depending on whether the distance separating the illuminated and tested areas is small or large. This interaction occurs both in the rod and the cone mechanisms of the retina when each is tested separately by selection of appropriate adapting and testing stimuli.2. In the mixed rod/cone region of the near periphery of the human retina the spatial parameters of interaction within the rod and cone systems were different when mapped out by using only one kind of adapting stimulus and sampling the excitatory state of the rod and cone systems by different probing stimuli.3. Sensitizing interaction signals generated by the rod system are incapable of causing sensitization of the cone system.


Specificity of cone mechanisms in lateral interaction. 1. The increment threshold for a brief, small probing light flash was used as an indicator of the state of adaptation of the human fovea. It shows that illumination of a zone up to 7 min of arc in diameter desensitizes the retina and that the additional illumination of a surrounding zone acts to counteract the desensitization.2. The red and green colour mechanisms were isolated by selecting light of appropriate wave-lengths for the adaptation and the increment stimuli and it was demonstrated that the desensitizing and sensitizing adaptation zones exist within each mechanism.3. Using the constancy of the increment threshold for a brief, small probing flash as a null-indicator for equivalence of annuli of various wave-lengths to produce a given amount of sensitization, the action spectrum for the laterally interacting region was obtained for both the red and the green mechanisms.4. For the red mechanism, the surrounding sensitizing zone has the action spectrum also of the red mechanism. For the green mechanism the surrounding sensitizing zone has a green action spectrum.


Distance effects in human scotopic retinal interaction. 1. Using the threshold for a small, brief test flash as a measure, the effect of light stimulation of small adjacent retinal regions of the human retina was investigated during adaptation to a medium scotopic illuminance.2. Within about (1/2) degrees of the tested area, light causes a desensitization gradually decreasing with distance. Beyond that there is a sensitizing zone which in turn gives way to an outer desensitizing zone. The sign of these effects is reversed if the peripheral stimulus is a patch of darkness.3. Evidence for non-linearity of summation of individual patches was found. Occlusion of each other's sensitizing influence is observed if two regions are closely adjacent to each other.


Synthesis, storage and release of [14C]acetylcholine in isolated rat diaphragm muscles. 1. Segments of rat diaphragms were kept in choline-free media for 4 hr and were then exposed to a physiological concentration of [(14)C]-choline (30 muM) at 37 degrees C. The synthesis, storage and subsequent release of [(14)C]acetylcholine by the muscles was assessed by isotopic- and bio-assays after isolation of the transmitter by paper electrophoresis.2. Replacement of endogenous acetylcholine (0.92 mu-mole/kg) with labelled acetylcholine proceeded slowly at rest, but rapidly during nerve stimulation. [(14)C]Acetylcholine accumulated most rapidly when hydrolysis of the released transmitter, and thus the re-use of endogenous choline, was prevented by an esterase inhibitor. Fully replaced stores were maintained during nerve stimulation by synthesis rates sufficient to replenish at least 35% of the store size in 5 min.3 In the presence of hemicholinium-3, which inhibits choline uptake, acetylcholine stores declined rapidly during stimulation, and residual synthesis was slight, indicating little intraneural choline. Net choline uptake into nerve terminals was estimated from the highest observed synthesis rate and from previous measurements of the number and size of terminals, as 3-6 p-mole/cm(2) sec.4. Transmitter synthesis was localized in the region of end-plates, and was reduced to a few per cent of normal 6 weeks after phrenic nerve section. Release experiments suggested that at least half of the acetylcholine in phrenic nerves is in their terminals; from this content and the morphology of the terminals, the average concentration of transmitter in the whole endings would appear to be about 50 m-mole/l. Homogenization of the muscles freed choline acetyltransferase into solution, but left some [(14)C]acetylcholine associated with small particles, presumably synaptic vesicles.5. Resting transmitter release was about 0.013% of stores/sec. With 360 nerve impulses at 1-20/sec, release increased up to 0.43% of stores/sec, and amounted to 3.5-7 x 10(-18) moles per end-plate per impulse. The release rate was unaffected by the doubling of store size which occurred with eserine, but the extra transmitter did help to maintain releasable stores during prolonged stimulation. Experiments with fractional store labelling indicated that newly synthesized acetylcholine was preferentially released.6. Preformed [(3)H]acetylcholine was not taken up and retained by muscle or nerve cells in the absence of an esterase inhibitor. With eserine present, labelled acetylcholine was taken up uniformly by muscle segments; when eserine was then removed, radioactive acetylcholine remained only near neuromuscular junctions.


The dorsal nucleus of the vagus as a centre controlling gastric motility in sheep. 1. A preparation is described for investigating the central nervous control of gastric motility in decerebrate decerebellate sheep.2. The dorsal vagal nucleus has been electrically stimulated in thirty decerebrate sheep, and the effect on the mechanical responses of the different parts of the reticulo-rumen have been determined.3. In the absence of recurrent rhythmic gastric contractions, punctate electrical stimulation of the dorsal vagal nucleus did not elicit gastric contraction until the intensity of stimulation was sufficiently high to excite efferent vagal fibres.4. Direct stimulation of the vagus nerve, or of motor fibres running from the nucleus to this nerve, always caused contraction of the reticulum, and dorsal and ventral ruminal sacs.5. Electrical stimulation of certain points within the medulla oblongata, during rhythmic gastric motility, inhibited motility for one or more contraction cycles. These inhibitory points lay on a line commencing at the mid-point of the dorsal vagal nucleus, and extending forward and ventral to this.6. Excitatory responses were less frequent, and were seen along a line running parallel to, but about 1 mm below, the anterior half of the line of maximum inhibition. They usually followed a period of inhibition, were generally shorter in duration, and consisted of a series of small reticular contractions at a rate of about 1/10 sec.7. The presence of a powerful inhibitory influence on the dorsal vagal nucleus, mediated from an area lying anterior to the nucleus, is argued and its probable action at the level of the gastric motor nucleus is discussed.


The size of rod signals.

The size of rod signals. 1. This investigation is based upon Alpern's (1965) contrast flash observations. The threshold for the test flash lambda (Fig. 2a) is raised if a second flash varphi falls on the annular surround. Moreover, if lambda excites rods at threshold, it is only the rods in the surround that contribute to the threshold rise.2. The possibility that the rise in lambda threshold might be due to light physically scattered from surround to centre we exclude by several different experiments. We conclude (Fig. 1b) that the varphi flash sets up a nerve signal N which is conducted to some place C where it inhibits the signal from the centre.3. If the luminous surround, instead of being a full circle (Fig. 2a) consists only of the sectors shown black in Fig. 2b, that occupy 1/m of the surround area, it is found (in the physiological range) that the light/area on those sectors must be m times as great to produce the same threshold rise at centre, i.e. the total surround illumination must remain the same.4. This result would obviously follow if N, the inhibitory nerve signal, were proportional to the total surround illumination. We have established the converse; the signal must be proportional to the quantum catch.5. Light can be increased indefinitely, nerve signals cannot. When varphi increases sufficiently, N saturates in the same way that S-potentials and receptor potentials saturate, namely according to N = varphi/(varphi + sigma) where sigma, the semi-saturation constant is about 200 td sec, or 800 quanta absorbed per rod per flash.6. Thus the nerve signal N is proportional to the quantum catch over 4 log units in the physiological range, namely from 1 quantum per 100 rods to 100 quanta per rod per flash. Above this for another 2 log units N continues to increase, but now more slowly, after the manner of S-potentials and receptor potentials.


A reconsideration of the Poisson hypothesis for transmitter release at the crayfish neuromuscular junction. 1. Transmitter release from excitor nerve terminals in the crayfish opener muscle was studied with both intra- and extracellular electrodes.2. The amplitude distribution of quanta recorded extracellularly from a single release site did not fit the compound Poisson hypothesis in two thirds of the data sets.3. Some data appeared to be non-Poisson because specific quantal multiples were released; the non-Poisson nature of release for other sets could be due to variable invasion of the axonal spike into the terminal region.4. In some muscle fibres, the number of quanta released at one ending to any given impulse in a stimulus train was correlated with the number of quanta released at other endings on the same fibre. This suggests that such endings may be supplied by nerve twigs arising from a common branch point with a very low safety factor for transmission.5. No consistent relationship was found between the amplitudes of the intra- and extracellular spontaneous potentials recorded from the same muscle fibre.


The attenuation of rod signals by backgrounds. 1. The paper which precedes this investigated the nerve interaction between two flashes, lambda at centre (Fig. 1a) and varphi on the surround region (but not on the centre). The size of the inhibitory nerve signal V generated by varphi is given by V = varphi(varphi + sigma), where sigma is the semi-saturation constant.2. A former paper (Alpern & Rushton, 1967) had shown that when the flash varphi falls upon a steady background theta, V suffers attenuation in the G-box (Fig. 1b) down to the fraction theta(D)/(theta(D) + theta) where theta(D) is the eigengrau or receptor noise. Thus, in general, the nerve signal N is given by [Formula: see text].3. This formula had only been established for a moderate range of values. In this paper we use extreme values to explore the limits of its validity. We find the equation to be true over the entire intensity range where N is measurable.4. Six different types of experiment have been performed to test various features of the equation. For instance, if log N is plotted against log varphi for various fixed values of theta, the curve is always the same with simply a vertical shift. And the shift is equal to log(1 + theta/theta(D)) for all values both of theta and of varphi.5. The most interesting curve is the plot of log varphi against log theta for fixed N. This is similar to the Weber-Fechner increment threshold but the criterion is not that varphi be strong enough to be detected, but strong enough to generate an N signal just sufficient to inhibit some fixed lambda flash. These curves (below the onset of saturation) are all the same except for vertical separation, and prove that the condition for flash detection is that a fixed signal, N(0), is generated of size 10(-5) of the maximum signal obtainable (i.e. with varphi large and theta zero).6. With strong backgrounds the curves of (5) above exhibit a marked saturation of the Aguilar & Stiles' type (1954). The family of curves each with a fixed N value shows a remarkable symmetry (Fig. 8) which in fact follows from the equation in (2) above. It has nothing to do with bleached pigment, but follows from the equation in (1) above. V there cannot exceed unity, thus when scaled by the G-box below the criterion level, further increase in varphi will not bring improvement.


The development of the metabolic response to thyroxine in the new-born pig. 1. Rectal temperature and the rate of oxygen consumption in the new-born pig were measured following the subcutaneous injection of L-thyroxine.2. Thyroxine stimulated oxygen consumption during the post-natal period; both immediate and latent increases were observed.3. The immediate effect occurred after thyroxine, 80 mug/kg, in suckled pigs aged 1-11 days; it was most marked at about 1-4 days of age with a peak increase (20%) in oxygen consumption and a rise in rectal temperature at about 4 hr following the injection.4. The peak increase (30%) in oxygen consumption associated with the latent effect of three successive daily injections of thyroxine, 300 mug/kg, occurred at 5-7 days of age, whether the pigs were first injected at 1 or at 4 days of age.5. It is concluded that there is a high sensitivity to thyroxine in the pig during the first week after birth, when the hormone is not bound to plasma proteins to the same degree as in the older animal.


Cerebral and cardiac enzymic activity and tolerance to asphyxia during maturation in the rabbit. The tolerance of neonatal rabbits to asphyxiation in 95% N(2) + 5% CO(2) was studied under conditions of controlled body temperature, and the enzymic activities of succinoxidase and lactic dehydrogenase were quantitatively determined in the heart and brain of untreated litter-mates.1. In new-born rabbits tolerance to asphyxia increases progressively as body temperatures are reduced until at 15 degrees C it is four times that at 39 degrees C. At colonic temperatures below 15 degrees C, tolerance to asphyxia decreases rapidly.2. All new-born rabbits having colonic temperatures of 15 degrees C recover spontaneously from asphyxia two to four times as long as that which is lethal for their warm litter-mates. Recoveries from asphyxia five and six times as long occur in 80%.3. At 39 degrees C colonic temperature, the tolerance of new-born rabbits to asphyxia decreases over ninefold from birth to young adulthood.4. In all tissues studied succinoxidase activity increases during the post-natal period. In the heart and frontal lobe, lactic dehydrogenase activity tends to parallel that of succinoxidase and is lower in the new-born than one might expect in view of the tolerance to asphyxia at this time.5. In the medulla oblongata an increase in succinoxidase activity occurs without a parallel increase in lactic dehydrogenase activity. This may reflect an increased dependence on aerobic pathways during post-natal development, with no parallel increase in the capacity for anaerobic glycolysis. Such changes may explain in part why the sensitivity of the medullary respiratory centre complex to oxygen lack is so much greater in the adult than in the new-born.


Effect of calcium on excitatory neuromuscular transmission in the crayfish. 1. The effects of varying the external Ca concentration from 1.8 to 30 mM/l. ((1/8)-2 times normal) have been studied at the in vitro crayfish excitatory neuromuscular junction. Electrophysiological techniques were used to record transmembrane junctional potentials from muscle fibres and extracellular junctional currents from the vicinity of nerve terminals.2. The excitatory junctional potential amplitude was proportional to [Ca](0) (n), where n varied between 0.68 and 0.94 (mean 0.82) when [Ca](0) was varied from 1.8 to 15 mM/l.3. The increase in junctional potential amplitude on raising [Ca](0) resulted primarily from an increase in the average number of quanta of excitatory transmitter released from the presynaptic nerve terminal by the nerve impulse.4. The size of the quanta, synaptic delay, presynaptic potential and electrical properties of the muscle membrane were little affected by changes in calcium concentration in the range studied.


Quantitative aspects of gain and latency in the cat retina. 1. The gain of the central response mechanism and the latency of the pure central response of on-centre ganglion cells were studied by recording from single optic tract fibres the responses evoked by slow square-wave stimuli applied against some steady background.2. The concept of effective flux was introduced and defined: if any portion of a stimulus extends beyond Ricco's area of complete summation, then that stimulus has an actual flux, equal to the product of its area and luminance, but it also has an effective flux which is that fraction of its actual flux which equals the actual flux of another stimulus which, when it falls entirely within Ricco's area, evokes an isobolic pure central response or has the same adaptive effect upon the central response mechanism as the first stimulus.3. The most significant finding was that when the cell responded with a pure central response to the incremental flux (the square wave) applied against a steady effective background flux, then the gain and the latency were functions exclusively of the sum of the two fluxes (the total flux), not of the incremental or background flux as such. This shows that the level of field adaptation of the central mechanism is reset within the latent period of the response to an incremental flux.4. Increment sensitivity curves based on isobolic suprathreshold responses all had the same slope of 0.9, when the log of the incremental flux was plotted against the log of the total flux. A plot of log latency against log total effective flux had a slope of -0.1.5. The stimulus-response relation derived from (3) and (4) was [Formula: see text] and [Formula: see text], where R is the response amplitude, F(et) the total flux, DeltaF(e) the incremental flux and K(1) and K(2) are constants.


Responses to directional stimuli in retinal preganglionic units. 1. Extracellular recordings were made from directionally selective ganglion cell units in the isolated frog retina and decapitated Necturus preparation.2. Intracellular recordings were made from individual photoreceptor cells in the frog and Necturus retinae while stimuli which had evoked directionally selective responses at the ganglion cell level were presented. No evidence for inhibition of photoreceptors for any direction of movement of the light stimulus was found. This appeared to rule out a mechanism for directional selectivity involving inhibition of photoreceptor potentials.3. Intracellular recordings were made from the nuclear layer between photoreceptors and ganglion cells in Necturus. The responses were of two types: either transitory or sustained.4. The sustained type responses could be divided into two classes depending on their receptive field organization. One type of sustained potential had a large receptive field without any evidence for a centre-surround antagonism and corresponded to the luminosity type S-potential recorded in fish. The other type had a smaller receptive field and showed a difference in sign of response between centre and surround if the centre was flooded with a steady light. This is very similar to what has been described for a type of on-centre, off-surround ganglion cell.5. The transitory type of responses showed some centre-surround antagonistic organization. Some of these transitory units also appeared to show some discrimination in response as a function of the distribution of light on the retina.6. No specific directional selectivity was found from units at the inner nuclear layer. This further excluded any mechanism of directional sensitivity which involves selectivity at the photoreceptor level.7. It was concluded that although inner nuclear layer units may play a role in the mechanism of directional selectivity, no specific directionality was found at the first synaptic level of the retina.


Establishment of a strain of actively proliferating mouse peritoneal macrophages.


Responses of fastigial nucleus neurones to stimulation of a peripheral nerve.


Correlation of latencies of e.r.g. components and ganglion cell spike discharges in the frog's eye.


Narrow 'tuning' of cochlear nerve fibre responses in the guinea-pig.


The effects of salicylate upon temperature regulation in the rabbit.


Measurement of human respiratory tract impedance at moderate forcing frequencies.


Acetoacetate tolerance before, during and after exercise.


Oronasal distribution of inspiratory flow during various activities.


Investigation of lung perfusion by simultaneous use of scintigraphy and aminophylline.


The effects of hypophysial portal plasma on the content of immunoreactive growth hormone in the anterior pituitary. 1. Blood plasma obtained from the hypophysial portal vessels of rats has been tested in assay animals for effects on the content of growth hormone in the anterior pituitary.2. Growth hormone was estimated by radioimmuno-assay at 15 min, 30 min, 1 hr and 2 hr after intracarotid or intravenous infusion of portal plasma. There was a significant increase in growth hormone content at 15 min after infusion, but not at 30 min, 1 hr and 2 hr.3. Insulin, cold stress, haemorrhage and treatment with growth hormone had no effect on growth hormone content of the pituitary under the conditions of application of these stimuli.4. Growth hormone was measured in plasma obtained from the pituitary of control and insulin-treated animals. In control animals the amount of growth hormone in this plasma was higher than in base line samples and in the insulin-treated animals it was lower than in base line samples. A calculation based on the growth hormone content of blood obtained directly from the pituitary indicates a daily rate of synthesis and release of about 10 mug.5. The hypothesis that portal plasma stimulated the synthesis of immuno-assayable growth hormone by the anterior pituitary is considered.6. Discrepancies between our results using immuno-assay and those of others using bio-assay are discussed.


Sensitivity of pulmonary vessels to hypoxia and hypercapnia.


The series elastic component of frog gastrocnemius. 1. The force-extension curve of the series elastic elements of the frog gastrocnemius has been determined up to the force attained during stretching by means of the isotonic quick-release method, modified in order to allow the release of the muscle immediately after stretching.2. The series compliance decreases progressively up to a stress value of about 2 kg/cm(2) and then it remains constant up to the maximal values of stress attained (about 10 kg/cm(2)).3. The lengthening of the series elastic elements when the stress rises to its full isometric value (P(0)l(0)/M = 5.2 kg/cm(2)) is about 3% of the muscle resting length, l(0). The Young's modulus in the linear part of the diagram is 294 kg/cm(2).4. The elastic energy stored up to P(0) is on average 55 g cm/g; an additional amount of 63 g cm/g is stored during stretching the contracted muscle.


Fat metabolism in brown adipose tissue in vivo. 1. Noradrenaline infusions (I.V. for 30 min) in new-born and 1-week-old unanaesthetized rabbits caused a rapid and sustained rise in oxygen consumption and an increase in blood glucose, free fatty acid and glycerol concentrations. Similar changes occurred in anaesthetized 1-week-old rabbits.2. A simple direct method was used to measure the net exchange of metabolites across brown adipose tissue in anaesthetized young rabbits. It was found that the brown adipose tissue of rabbits reared from birth in a thermoneutral environment and studied when their next feed was due took glucose from and released fatty acids and glycerol into the circulation.3. Similar rabbits kept unfed for a further 48 hr in a warm environment released fatty acids and glycerol from their brown adipose tissue at a far greater rate, but the rate of glucose uptake was reduced.4. On the other hand the brown adipose tissue of rabbits kept unfed in a cold environment (20 degrees C) took up circulating free fatty acids as well as glucose and did not release glycerol. The brown adipose tissue of these rabbits was depleted of fat.5. The rate of blood flow through brown adipose tissue and the exchange of all three metabolites increased fourfold during noradrenaline infusion in the three groups of rabbits.6. It is concluded (i) that brown adipose tissue releases significant amounts of fatty acids and glycerol into the circulation and that this contribution is greatly increased with noradrenaline infusion and presumably cold exposure, and (ii) that brown adipose tissue depleted of fat produces heat by drawing free fatty acids as well as glucose from the circulation.


The effect of suxamethonium on the spindles of frog sartorius and ilio-fibularis muscles.