The small-scale isolation and characterization of adrenocorticotrophin. Several methods for isolating adrenocorticotrophin from small quantities of porcine and bovine pituitary tissue are compared. Initial extraction of the hormone by an acid-acetone technique was simpler and more efficient than one employing acetic acid extraction and ether precipitation. Subsequent purification procedures utilizing adsorption of the peptide on to oxycellulose realized the highest yields. CM-cellulose-column chromatography followed by Sephadex-gel filtration were suitable final steps for obtaining highly purified adrenocorticotrophin. The purity of the hormone was demonstrated by determining its amino acid composition, C-terminal analysis, polyacrylamide-gel electrophoresis, chymotrypsin digestion and paper electrophoresis and by radioimmunoassay and bioassay. Adrenocorticotrophin was found to be rapidly destroyed in intact and especially in homogenized glands kept at room temperature. At 4 degrees the rate of destruction was less rapid and at -20 degrees losses were minimal.


The inhibition of pyruvate and Ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria. 1. The effects of succinate oxidation on pyruvate and also isocitrate oxidation by rat liver mitochondria were studied. 2. Succinate oxidation was without effect on pyruvate and isocitrate oxidation when respiration was maximally activated with ADP. 3. When respiration was partially inhibited by atractylate, succinate oxidation severely inhibited the oxidation of pyruvate and isocitrate. 4. This inhibitory effect of succinate was associated with a two- to three-fold increase in the reduction of mitochondrial NAD(+) but no change in the reduction of cytochrome b. 5. It is concluded that, in the partially energy-controlled state, respiration is more severely inhibited at the first phosphorylating site than at the other two. 6. The effects of succinate oxidation are compared with those of palmitoylcarnitine oxidation. It is concluded that a rapid flow of electrons directly into the respiratory chain at the level of cytochrome b is in itself inadequate to inhibit the oxidation of intramitochondrial NADH. 7. The effects of succinate oxidation on pyruvate oxidation were similar in rat heart and liver mitochondria.


Changes in the concentrations of hepatic metabolites on administration of dihydroxyacetone or glycerol to starved rats and their relationship to the control of ketogenesis. 1. Glycerol and dihydroxyacetone, both antiketogenic and readily metabolized, but differing in their effects on the redox state of the hepatic NAD couples, were given to starved rats and the contents of metabolites were measured in freezeclamped liver and in the blood. The object was to study the effects of changes in the redox state and of the availability of oxidizable substrates on the rate of ketone-body formation. 2. Intramuscular administration of dihydroxyacetone, glycerol or glucose to starved rats decreased the concentrations of acetoacetate and 3-hydroxybutyrate in the blood by 70-80% within 60min., whereas there was no major change in the free fatty acid concentration. 3. Dihydroxyacetone, but not glucose or glycerol, caused an immediate and sustained twofold increase in the blood lactate concentration. 4. Dihydroxyacetone and glycerol caused a rapid fall in the hepatic concentrations of ketone bodies, dihydroxyacetone being more effective. 5. This decrease was not accompanied by significant changes in the concentrations of acetyl-CoA, long-chain acyl-CoA or free CoA. 6. The hepatic glycerophosphate concentration rose about 40-fold on administration of glycerol, whereas with dihydroxyacetone the increase was only about 50%. The large increase in glycerophosphate concentration after administration of glycerol was completely prevented by pretreatment of the rats with tri-iodothyronine. Triiodothyronine-treated rats showed the same decrease in ketone-body concentrations after administration of glycerol as the untreated rats. 7. Glycerol and dihydroxyacetone caused an increase in the hepatic lactate concentration; the pyruvate concentration rose only after injection of dihydroxyacetone. 8. Both compounds increased liver glycogen. 9. Calculation of the [free NAD(+)]/[free NADH] ratios indicated that dihydroxyacetone increased the ratio in cytoplasm and mitochondria, whereas glycerol caused a prompt fall in both compartments, followed at 10min. by a slight rise in the mitochondrial compartment. 10. Dihydroxyacetone did not alter the hepatic content of ATP. 11. The findings suggest that the main reason for the antiketogenic effect of glycerol and dihydroxyacetone was a consequence of their ready metabolism and the provision of an increased supply of C(3) intermediates for conversion into oxaloacetate. Under the test conditions, neither the hepatic content of alpha-glycerophosphate nor the redox state of the NAD couples appeared to play a major role in the regulation of ketogenesis.


Chemical modification of glutamate dehydrogenase by 2,4,6-trinitrobenzenesulphonic acid. 1. Modification with 2,4,6-trinitrobenzenesulphonic acid was studied for its effect on the structure, activity and response to regulatory effectors of ox liver glutamate dehydrogenase. 2. The modification affected amino groups only, and the relative reactivities of the amino groups of the enzyme are described. 3. A biphasic inactivation of the enzyme was observed and analysis of the course of inactivation and of modification showed that the rapid reaction of one amino group/subunit leads to loss of 80% of the enzymic activity. 4. NADH retarded the inactivation by 2,4,6-trinitrobenzenesulphonic acid, the protection increasing with NADH concentration. This, together with the previous observation, suggests that the rapidly reacting group is essential for the activity of the enzyme. 5. The effects of modification on the optical-rotatory-dispersion and sedimentation behaviour of the enzyme were studied. 6. The enzyme's response to the allosteric effector GTP was rapidly lost on modification, whereas its response to ADP was unaffected. Comparison of the inactivation and desensitization suggests that the reactive amino group is essential for both activity and GTP response, and that only a completely unmodified enzyme oligomer responds fully to GTP. 7. The merits of chemical-modification studies of large enzymes are discussed critically in connexion with the interpretation of these results.


Stereochemistry of phytoene biosynthesis by isolated chloroplasts. The incorporation of [2-(14)C,(5R)-5-(3)H(1)]MVA* and [2-(14)C,5-(3)H(2)]MVA into geranylgeraniol and phytoene by a preparation of ;non-aqueous' bean leaf chloroplasts has been studied. In the formation of phytoene from two molecules of geranylgeranyl pyrophosphate, the loss of hydrogen is stereospecific, the hydrogen atom lost from C-1 of each molecule of geranylgeranyl pyrophosphate being that which was originally the pro-S hydrogen atom from C-5 of mevalonate. All the pro-R hydrogen atoms from C-5 of mevalonate are retained. These results with a cell-free system confirm and extend the observations made in previous work with tomato slices.


Brain hexokinase. The preparation of inner and outer mitochondrial membranes.


Myosin modification as studied by spin labeling.


The synthesis of guanosine 5'-diphosphate D-rhamnose.


Characterization of rat heart myosin. II. Enzymatic properties.


Kinetic studies of the mechanism and allosteric activation of the reaction catalyzed by nucleoside diphosphatase.


Purification and properties of two vitamin B12 binders from chicken serum.


Estimation of 5'-nucleotidase activity in nervous tissue.


Some clinical aspects of peripheral nerve lesions.


Mössbauer studies of bonding in iron porphyrin-ligand systems.


Relationships between the concentration of liver metabolites and ketogenesis in chickens fed "carbohydrate-free" diets.


Respiration of isolated liver mitochondria from chickens fed "carbohydrate-free" diets.


Effects of electroanesthesia on synaptic ultrastructure.


Rapid eye movements and rapid eye movement periods.


Calcium-binding protein and calcium absorption after vitamin D administration.


A study on some spectral properties of P-450 in a submicrosomal particle.


Studies on oxidative phosphorylation. XIX. Functional site of factor B in energy transfer reactions.


Neuropathy induced by hemorrhage.

Neuropathy induced by hemorrhage.


Purification of mouse brain phosphoserine phosphohydrolase and phosphotransferase.


Posterior interosseous nervepalsy in the absence of trauma.


The effects of pH and citrate on the activity of nicotinamideA-denine dinucleotide-specific isocitrate dehydrogenase from pea mitochondria. 1. The effect of pH on the co-operative activation of the NAD-specific isocitrate dehydrogenase from pea mitochondria by isocitrate is shown. 2. The interlinked effects of pH on the affinity of the NAD-specific isocitrate dehydrogenase for isocitrate and the dependence of the pH optimum on the substrate concentration are presented. 3. A consideration of the conditions of pH and substrate concentration under which citrate activates the NAD-specific isocitrate dehydrogenase demonstrates similarities between the binding of isocitrate and citrate. 4. A comparison of the effects of citrate and pH on the gross structure of the enzyme is investigated by density-gradient centrifugation. 5. The kinetic interpretations of these results are briefly considered. 6. The metabolic significance of these studies is discussed.


The effects of calcium and magnesium ions on the adenosine triphosphatase and inosine triphosphatase activities of myosin A. 1. The effects of Ca(2+) and Mg(2+) on the enzymic activity of myosin were studied with myosin preparations treated by the ion-exchange resin Chelex-100. A reaction mixture containing 0.05m-potassium chloride was chosen in which the effects of univalent ions such as K(+), Na(+) and Cl(-) do not change significantly with small variations in their concentrations. 2. The relationship between the rate of hydrolysis of ATP or ITP and the concentration of Ca(2+) suggests that a relatively weak binding of Ca(2+) either to myosin or to the substrate nucleotide is responsible for the activation of the enzymic activity. According to the experiments with an ultrafiltration technique, the binding of Ca(2+) to myosin proceeds in at least two steps, the first occurring at one site on every 500000 atomic mass units of myosin with an apparent association constant, K(app.), 1.3x10(6)m(-1), and the second seeming to be so weak that its binding parameters cannot be determined by the method used. The first type of Ca(2+) binding is not observable with N-ethylmaleimide-modified myosin, yet this modified myosin shows activation by Ca(2+) of its adenosine triphosphatase and inosine triphosphatase. 3. The inhibition by Mg(2+) can be related to a binding reaction of Mg(2+) with myosin having K(app.) approximately 10(6)m(-1). Mg(2+) replaces the Ca(2+) bound tightly to myosin. The K(app.) for Mg(2+)-myosin binding calculated by assuming a competition between Ca(2+) and Mg(2+) for the same site is 2.1x10(5)-3.0x10(5)m(-1). When myosin is modified with a thiol reagent (p-mercuribenzoate) at a certain ratio to myosin, the inhibition by Mg(2+) becomes unobservable. 4. The behaviour of the hydrolytic activity of myosin on ATP or ITP in the presence of both Ca(2+) and Mg(2+) is consistent with the explanation that the inhibition by Mg(2+) is due to the tight binding of Mg(2+) to myosin, whereas the activation by Ca(2+) is caused either by a weak binding of Ca(2+) to myosin or by CaATP(2-) or by both.


Artificial substrates for prenyltransferase. Four out of 16 new allylic pyrophosphates synthesized were found to be artificial substrates for liver prenyltransferase (EC 2.5.1.1). These were the trans-and the cis-3-ethyl-3-methylallyl, the 3,3-diethylallyl and the (mixture of cis and trans) 3-methyl-3-n-propylallyl pyrophosphates. The products synthesized from these substrates and isopentenyl pyrophosphate were the appropriate homo- and bishomo-farnesyl pyrophosphates. Substitution of 3,3-dimethylallyl pyrophosphate at C-2 with a methyl group destroyed its reactivity with the enzyme. Neither the unsubstituted allyl pyrophosphate nor the cis- or trans-3-methylallyl pyrophosphate could be condensed with isopentenyl pyrophosphate. Thus the simplest allylic substrate for prenyltransferase is 3,3-dimethylallyl pyrophosphate.


Dietary regulation of glycolytic enzymes. IV.


Organ culture of fetal rat pancreas. I. Insulin release induced by caffeine and by sugars and some derivatives.


Biosynthesis of cyanide from [2-14C-15N]glycine in Chromobacterium violaceum.


Determination of enzymatically produced adenosine 3',5'-monophosphate.


Studies on the action of insulin in isolated adipose tissue cells. II. 3',5'-Nucleotide phosphodiesterase and antilipolysis.


Carnitine and derivatives in embryonic chick tissue.


Synthesis and regulatory properties of an adenosine 5'-phosphate analogue, N6-methoxyadenosine 5'-phosphate.


Effects of prednisoloe on esterases in heteroploid cells on human origin.


Clearance studies of angiotensin II and [35S] phenylthiocarbamyl-angiotensin II in the sheep and dog.


Studies on the secretion of pancreatic glucagon.


Effects of tetanization on transmitter dynamics.


Urethral resistance: its components and implications. I. Smooth muscle component.


Ovine urolithiasis: some mineralogic and physiologic observations.


The effect of silicosis on the antibacterial defense mechanisms of the murine lung.


Pericarditis and myocarditis in germfr and colostrum-deprived pigs experimentally infected with a porcine polioencephalomyelitis virus.


Cerebral physiology in dogs after brain-tumor induction with Schmidt-Ruppin Rous sarcoma virus: experiences with radioiodinated normal and antiviral immunoglobulin G.


Electron microscopic observations on the association of viruses with membrane systems in hamster tumor cells propagated in tissue culture.


Malignant lymphomas of extrathymic origin induced in rats by murine erythroblastosis virus.


Central benign and malignant neural neoplasms of the jaws: a review.


Pseudohypophosphatasia.

Pseudohypophosphatasia.


Foot and mouth disease in Great Britain.


The composition of nervous membranes.

The composition of nervous membranes.


Ion movements in isolated preparations from the mammalian brain.


Radicals induced in thymine and some of its derivatives by ionizing radiation and thermal hydrogen atoms.


The bacterial content of the small intestine of young calves.


Synaptic current at the squid giant synapse. Transmission in the giant synapse of squid was studied by measuring synaptic currents in the voltage-clamped postsynaptic giant axon. These currents varied linearly with the axon's membrane potential, and showed an intercept on the voltage axis at, or near, the sodium equilibrium potential. The intercept shifted in seawater containing less sodium by even more than the shift in the sodium equilibrium potential. It is concluded that the transmitter at this synapse causes a significant change in the sodium conductance only.


Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals. Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine.


Oculomotor neurons in fish: electrotonic coupling and multiple sites of impulse initiation. Oculomotor neurons are electrotonically coupled in three teleosts. Electron microscopy revealed axosomatic synapses with close appositions of pre- and postynaptic membranes. Similar junctions are associated with electrotonic coupling in many other cases. Stimulation of the ipsilateral eighth nerve usually initiated impulses at sites distant from the cell bodies; stimulation of the ipsilateral ophthalmic nerve initiated impulses close to the cell bodies. Electrotonic coupling may synchronize impulses arising near the, cell bodies to generate synchronous muscle contractions. Impulses arising distant from the cell bodies may lead to contractions of graded strength.


Axonal transport of proteins in experimental neuropathies. Axoplasmic flow of proteins is interrlupted in cats with neuropatlhy induced by acrylamide, but it is niot initerrupted in nzormlal cats and in those with neuropathy induced by tri-orthocresyl phiospliate. The proteins move from lumbosacral motor neurons along the ventral roots and from ganglion cells toward the spinal cord along the dorsal roots at about 1(1/2) millimeters per day.


Rapid eye movement sleep: asleep-dependent process.


Effect of acclimation temperature on mitochondrial enzymes in fish. BNWL-714.


Assay of arbovirus neutralizing antibody by micro methods.


A specific enzymic assay of D-glyceraldehyde and dihydroxyacetone.


A rapid assay for 14C-labeled hydroxylysine in collagen and related materials.


Interference by oxidized lipids in the determination of protein by the Lowry procedure.


A method for the determination of the molecular distribution of free and esterified cholesterol in serum by thin-layer chromatography.


Quantitative determination of phospholipid classes in human serum by combined thin-layer chromatography and phosphorus analysis.


A method for determination of 3',5'-cyclic adenosine monophosphate based on adenosine triphosphate formation.


Phosphodiesterase of some snake and arthropod venoms.


Effect of pH, temperature, antivenin and functional group inhibitors on the toxicity and enzymatic activities of Crotalus atrox venom.


Establishment of new ascites hepatomas.

Establishment of new ascites hepatomas.


The simultaneous fluorimetric determination of corticosterone and cortisol in human plasma.


Immunological studies on the membrane systems of cancer cells. II. Immunochemical specificity of the mitochondria from chemical carcinogen induced carcinoma cells.


Right hepatic lobectomy in children.

Right hepatic lobectomy in children.


Control of respiration and metabolism in growing Klebsiella aerogenes. The role of adenine nucleotides. 1. A rapid-sampling technique was used to obtain perchloric acid extracts of cells growing in a chemostat culture, so that meaningful values for ATP content could be obtained in spite of the fact that the turnover time for the total ATP content was about 1sec. 2. For steady-state growth, it was found that, in a glucose-limited chemostat culture, the ATP/ADP concentration ratio was approximately constant with changes in dissolved-oxygen tensions above the critical value, but fell when the culture was grown under oxygen-limited conditions and was at a minimum in anaerobically grown cultures. The steady-state ATP content was lower in cells growing under nitrogen-limited conditions with glucose in excess than in glucose-limited cells. The steady-state ATP content was independent of growth rate at growth rates over 0.1hr.(-1). 3. When the respiration rate of the cells was stimulated by lowering the oxygen tension the ATP content did not increase, indicating either an increased turnover rate of ATP or a fall in the P/O ratio. The sudden addition of extra glucose or succinate to a glucose-limited culture increased the respiration rate of the cells, but the ATP content quickly returned to the steady-state value after initial perturbations. This control over ATP content is explained in terms of regulation by adenine nucleotides of the catabolism and anabolism of glucose. An exception to this control over ATP content was found when the respiration rate was stimulated by addition of an antifoam.


Changes in the patterns of synthesis of ribonucleic acid species in immature rat uterus in response to oestrdiol-17 beta. 1. After treatment of immature rats with diethylstilboestrol, the wet weight and RNA content of uterine tissue increased rapidly, reaching a peak at 40hr. After an initial lag of a few hours, the acid-soluble ribose and protein contents also rose to maxima at 40hr. No increase in DNA content occurred until at least 24hr. after treatment. 2. The RNA from immature rat uterus isolated at various times up to 6hr. after administration of oestradiol-17beta was labelled by injecting [(3)H]uridine and [(3)H]guanosine intraperitoneally 30min. before the animals were killed. It was fractionated on columns of kieselguhr coated with methylated serum albumin and the radioactivity in fractions corresponding to transfer RNA, 7s RNA, ribosomal RNA, Q(1)-RNA, Q(2)-RNA and DNA-like RNA was determined. 3. The radioactivity of the whole RNA increased steadily for 6hr. after hormone treatment. The earliest changes occurred in the Q(1)-RNA (ribosomal RNA precursor), whereas at longer time-intervals the radioactivity of the ribosomal RNA, 7s RNA and transfer RNA increased by four- to five-fold. The radioactivity of the DNA-like RNA increased by about 50%, but only at the longer time-intervals. 4. It is concluded that one of the earliest changes in response to oestradiol treatment is a major increase in synthesis of ribosomal RNA followed later by a similar increase in synthesis of transfer RNA and by a much smaller increase in synthesis of DNA-like RNA. The change in synthesis of ribosomal RNA in immature rat uterus may represent one of the most important responses to oestradiol treatment.


The influence of metal ions on the orthophosphatase and inorganic pyrophosphatase activities of human alkaline phosphatase. 1. The differential effects of adding Zn(2+) and Mg(2+) on the orthophosphatase and inorganic pyrophosphatase activities of human intestinal alkaline phosphatase were studied. 2. In the presence of excess of Zn(2+), inorganic pyrophosphatase activity is inhibited. At higher concentrations of pyrophosphate, hydrolysis of this substrate takes place, but is inhibited competitively by the Zn(2+)-pyrophosphate complex. This complex also acts as a competitive inhibitor of orthophosphate hydrolysis. 3. Excess of Mg(2+) also inhibits pyrophosphatase action by removal of substrate; at low concentrations, this ion activates pyrophosphatase, as is the case with orthophosphatase. 4. It is concluded that, when interactions between metal ions and pyrophosphate are taken into account, the effects of these ions are consistent with the view that alkaline phosphatases possess both orthophosphatase and inorganic pyrophosphatase activities.


Analogues of ribose 5-phosphate and 5-phosphoribosyl pyrophosphate. The preparation and properties of ribose 5-phosphorothioate and 5-phosphoribosyl 1-methylenediphosphonate. 1. 5-Phosphoribosyl 1-methylenediphosphonate was isolated after reaction of ribose 5-phosphate and O-adenylyl methylenediphosphonate with 5-phosphoribosyl pyrophosphate synthetase from Ehrlich ascites-tumour cells. 2. The analogue reacted with adenine phosphoribosyltransferase, hypoxanthine phosphoribosyltransferase and nicotinamide phosphoribosyltransferase [K(m) (analogue)/K(m) (5-phosphoribosyl pyrophosphate) 0.17, 0.19 and 6.3 respectively; V(max.) (analogue)/V(max.) (5-phosphoribosyl pyrophosphate) 0.011, 0.26 and 1.1 respectively]. 3. The analogue was not a substrate for 5-phosphoribosyl pyrophosphate amidotransferase or orotate phosphoribosyltransferase. 4. Ribose 5-phosphorothioate was synthesized by allowing ribose to react with thiophosphoryl chloride in triethyl phosphate. The analogue was a substrate for 5-phosphoribosyl pyrophosphate synthetase from Ehrlich ascites-tumour cells. When this reaction was coupled to either adenine phosphoribosyltransferase or hypoxanthine phosphoribosyltransferase, adenosine 5'-phosphorothioate or inosine 5'-phosphorothioate was formed respectively.


The subcellular distribution of 32P-labelled phospholipids, 32P-labelled ribonucleic acid and 125I-labelled odoprotein in pig thyroid slices. Effect in vitro of thyrotrophic hormone and dibutyryl-3',5'-(cyclic)-adeosine onophosphate. 1. The incorporation in vitro of [(32)P]phosphate into phospholipids and RNA and of [(125)I]iodide into protein-bound iodine by pig thyroid slices incubated for up to 6hr. was studied. The subcellular distribution of the labelled products formed after incubation with radioactive precursor in the nuclear, mitochondrial, smooth-microsomal, rough-microsomal and cell-sap fractions was also studied. 2. Pig thyroid slices actively took up [(32)P]phosphate from the medium during 6hr. of incubation; the rate of incorporation of (32)P into phospholipids was two to five times that into RNA. 3. The uptake of [(125)I]iodide by the slices from the medium was rapid for 4hr. of incubation, 6-10% of the label being incorporated into iodoprotein. 4. Much of the (32)P-labelled phospholipid accumulated in mitochondria and microsomes, whereas the nuclear fraction contained most of the (32)P-labelled RNA. After 2hr. of incubation most of the (32)P-labelled cytoplasmic RNA accumulated in the rough-microsomal fraction. The major site of localization of proteinbound (125)I was the smooth-microsomal fraction, and gradually increasing amounts appeared in the soluble cytoplasm fraction, suggesting a vectorial discharge of [(125)I]iodoprotein (presumably thyroglobulin) from smooth vesicles into the colloid. 5. The addition of 0.1-0.4 unit of thyrotrophic hormone/ml. of incubation medium markedly enhanced the accumulation of (32)P-labelled phospholipids in the microsomal fractions and to a much smaller extent that of (32)P-labelled RNA without any increase in the total uptake of the label. Almost simultaneously the hormone increased the uptake of [(125)I]iodide by the slices and enhanced the accumulation of protein-bound (125)I in the smooth-microsomal fraction. 6. As a function of time of incubation, thyrotrophic hormone had a biphasic effect on [(125)I]iodide uptake and protein-bound (125)I formation, the stimulatory effect being reversed after 4hr. of incubation. 7. 6-N-2'-O-Dibutyryl-3',5'-(cyclic)-AMP, but not 3',5'-(cyclic)-AMP or 5'-AMP, mimicked the action of thyrotrophic hormone on iodine uptake as well as on iodination of protein. On the other hand, the mimicry by 6-N-2'-O-dibutyryl-3',5'-(cyclic)-AMP of the stimulatory effect of thyrotrophic hormone on the formation of labelled thyroid phospholipids and RNA was only an apparent one resulting from an enhanced uptake of [(32)P]phosphate. 8. It is concluded that thyrotrophic hormone causes a co-ordinated increase in the formation or accumulation of phospholipids, RNA and iodoprotein associated with the endoplasmic reticulum, and that 6-N-2'-O-dibutyryl-3',5'-(cyclic)-AMP mimics the more rapid effects of thyrotrophic hormone on transport and metabolic functions of thyroid cells, but does not influence their slower biosynthetic responses to the hormone.


The distribution of phospholipase D in developing and mature plants. 1. The distribution of phospholipase D (phosphatidylcholine phosphatido-hydrolase, EC 3.1.4.4) was examined in the tissues of a number of plants and seeds. 2. The highest activities were found in various swollen storage tissues of certain plants: cabbage, central stalk; cauliflower, flower; celery, swollen leaf stalk; Kohl rabi, swollen stem; carrot, root; pea and marrow, seed. 3. Appreciable activity was retained in pea seeds for at least 1 year after drying. After germination and growth in the dark the total activity present in the cotyledons and also in the whole seedling decreased. 4. In the growing pea seedling (7 days old), about 3% of the total activity was in the plumule, 9% in the root and the remainder in the cotyledons. However, the activity in the root on a dry-weight basis was higher than that in the cotyledons. In both the root and the plumule the activity on a wet- or a dry-weight basis was highest in the growing tip. 5. The activity per dry weight in the roots and aerial parts of pea plants declined to low values as growth continued, but roots struck from cuttings of mature plants showed the same high activity as found in roots from young seedlings with cotyledons attached. 6. The total phospholipids present in the cotyledons of pea seeds were depleted on germination and growth. Of the individual phospholipids, phosphatidylcholine and phosphatidylethanolamine showed the same loss in 11 days as the whole phospholipid fraction, whereas phosphatidylinositol was decreased to a greater extent and cardiolipin and phosphatidylserine were not decreased. There was no increase of phosphatidic acid, as might have been expected if the phospholipids had disappeared through phospholipase D hydrolysis. 7. It is concluded that phospholipase D in plant storage tissues and seeds may be related to the rapid growth involved in their formation rather than being necessary for the utilization of their food reserve substances.


Immunofluorescence studies in human leukemia.


Further observations on prognostic factors in cancer of the female breast.


Atypical epithelial hyperplasia associated with breast cancer and fibrocystic disease.


Mucous gland tumors of paranasal sinuses.


Adenoid cystic carcinoma of the breast. An analysis of 21 cases.


Treatment of pulmonary metastatic disease with radiation therapy and adjuvant actinomycin D. Preliminary observations.


Development of myeloblastoma with massive breast and ovarian involvement during remission in acute leukemia.


Conversion of D-mannuronolactone into D-mannaric acid in mammalian systems.


Dynamics of immunomorphological changes in the organs of chickens after immunization with BPL vaccine and after challenge with fowl plague virus.


The prevention of enterotoxaemia (pulpy kidney disease) by vaccination.


Further developments of International Biological Standards for anaerobic immunological substances.


Serotonin-induced swelling of rat liver mitochondria.


Granular localization of corticotropin-releasing activity in horse hypophysial stalk homogenate.


Electrom microscopic study of the anencephalic adenohypophysis with reference to the adrenocorticotrophs and their correlation with the functional differentiation of the hypothalamus during the foetal life.


Pyrophosphate enhancement of hypocalcemic effect of thyrocalcitonin in rat.


ACTH secretion from the pituitary transplanted in apposition with the adrenal cortex under the renal capsule.


Pituitary regulation of preovulatory estrogen secretion in the rat. The factors stimulating estrogen secretion in the preovulatory phase and an attempt to explain the mechanism of termination of estrogen secretion are discussed.  Female Wistar rats, hypophysectomized at 1 p.m. in proestrus, were injected with rat pituitary extracts.  Ovarian venous blood was collected and the estrogen activity of the plasma was measured.  The estrogen secretion was minimized within 3 hours after hypophysectomy.  The rat pituitary extract caused an 11-fold increase of estrogen concentration in the ovarian venous blood within 1 hour.  Either LH or FSH alone was able to restore the estrogen secretion: LH took 1 hour to reach maximal response, FSH 2 hours.  In the 1-hour test, the minimal effective dose for LH appeared to be less than .25 mcg per rat, for FSH, 2.5 mcg per rat.  The total ability of the two preparations to produce estrogen appeared to be the same.  10 I.U. of prolactin slightly stimulated estrogen secretion, but 20 mU of ACTH was quite negative.  These results demonstrate the pituitary gonadotropin dependency of estrogen secretion from the ovary having ripened follicles.  It also showed that the ovary, after completion of ovulatory surge of LH, abolished its reactivity to the pituitary extract containing sufficient amount of substances in promoting estrogen secretion.  Either LH or FSH was able to terminate estrogen secretion even at minute doses as small as 10 mcg.  This shows that both FSH and LH provide a dual effect on ovarian estrogen secretion at the preovulatory stage, promotion and suppression.  Promotion is an acute and direct action of hormones on steroidogenesis and suppression probably a delayed and indirect action of ovulation-inducing hormone, the release of which initiates the differentiation of estrogen-forming cells towards  ovulation unfavorable to estrogen synthesis.


Haemorrhage and the sensitivity of canine mesenteric vascular bed to angiotensin and norepinephrine.


Effects of chloroquine pretreatment on lethal dose of morphine and on morphine metabolism in rats.


Effect of cold exposure on amino acid transport and incorporation into rat anterior pituitary in vitro.


Cytochemical demonstration of nucleoside phosphatase activity in myelinated nerve fibers of the rat.


Continuous splitting off of phosphate from phosvitins by phosphoprotein phosphatase.


Inhibitory effect of substrate analogs on isopentenyl pyrophosphate isomerase and prenyltransferase.


Isolation and characterization of enzymes with nicking action from phage T4-infected Escherichia coli.


Localization of cytochrome c peroxidase in anaerobically grown yeast cells.


Studies on oxygenases. I. Comparative studies on 3,4-dihydroxyphenylacetate-2,3-oxygenase and pyrocatechase by electron spin resonance spectroscopy.


Isolation and comparison of phosphorylase b isozymes in pig heart.


Characteristics of antibody to a limited antigenic stimulus.


The growth requirements of Haemophillus aphrophillus.


Transport of calcium into adipose tissue in response to adrenocorticotropic hormone.


A comparative study of standard methods and organ culture for the isolation of respiratory viruses.


The effect of cyclophosphamide on Sendai virus infection of mice.


The effect on drinking in the rat of intravenous infusion of angiotensin, given alone or in combination with other stimuli of thirst. 1. Intravenous infusion of angiotensin causes rats which are in water balance to drink water.2. The mean amount of angiotensin needed to initiate drinking was 29.1 +/- 4.6 mug/kg (S.E. of mean) in twenty normal rats, and 15.7 +/- 2.1 mug/kg in thirty-four nephrectomized rats.3. The nephrectomized rat is therefore more sensitive to this action of angiotensin than the rat with intact kidneys.4. The rates of infusion (0.05-3.0 mug/kg(-1) min(-1)) which cause drinking are comparable to those used to produce other effects in rats.5. Angiotensin restores the drinking response of the nephrectomized rat subjected to caval ligation to a value similar to that obtained in the uninfused normal rat subjected to caval ligation.6. The effects of angiotensin and hypertonic saline on drinking are additive when both substances are administered to nephrectomized rats.7. These experiments provide further support for the view that the renin-angiotensin system is concerned in extracellular thirst.


A possible role of acetylcholine in the central control of body temperature in sheep.


The rate of penetration of K+ into the intertransverse caudal muscles of the rat.


Interferon-like inhibitor detected in culture fluids of normal HeLa cells.


The tensile strength of wounds and factors that influence it.


Studies on phenolic steroids in human subjects. XII. In vitro metabolism of estradiol-6,7-3H-3-glucosiduronate-14C and of estrone-6,7-3H-glucosiduronate by human placental estradiol-17beta-dehydrogenase.


Studies on fibrinolytic enzymes in the field of obstetrics and gynecology, especially tissue activator. 4. Antifibrinolytic action of sex hormones, especially a conjugated estrogen (Premarin) and its application.


Adenoviruses of animals other than man.

Adenoviruses of animals other than man.


The etiology and control of urolithiasis.


Kinetic studies on the interaction of TMPD with cytochrome c and cytochrome c oxidase.


Glycerylphosphorylcholine diesterase: effects of metal-binding agents.


Polypoid adenocarcinoma of the cervical esophagus.


Characteristics of cells dissociated from mouse mammary glands. I. Method of separation and morphology of parenchymal cells from lactating glands.


Temperature and the regulation of enzyme activity in poikilotherms. Properties of lungfish fructose diphosphatase. 1. The properties of fructose diphosphatase from liver of South American lungfish (Lepidosiren paradoxa) were examined. 2. Saturation curves for substrate (fructose diphosphate) and both cofactors (Mn(2+) and Mg(2+)) are sigmoidal and Hill plots of these results suggest about 2 interacting substrate and cofactor sites/molecule of enzyme. 3. Mn(2+) is an efficient positive modulator of the enzyme and K(a) for Mn(2+) is about 20-30-fold lower than the K(a) for Mg(2+). 4. Lungfish fructose diphosphatase is inhibited by low concentrations of AMP, and the affinity of the enzyme for AMP is insensitive to temperature. 5. The affinities of fructose diphosphatase for fructose diphosphate and Mn(2+) appear to be dependent on temperature, whereas affinity for Mg(2+) is temperature-independent. 6. The pH optimum of the enzyme depends on the presence of the particular cofactor. As pH increases, the K(a) values of both cations are lowered, maximum velocities are increased and the saturation curves for cofactor become hyperbolic. 7. The possible roles of these ions, pH and substrate in the modulation of fructose diphosphatase and gluconeogenic activity in the lungfish are discussed in relation to aestivation and temperature adaptation.


Non-degraded incorporation of highly polymerized DNA and isolated metaphase chromosomes into cultured mammalian cells and replication of the incorporated heterologous chromosomes in the cultured cells.


Ischio-rectal fossa tumour.

Ischio-rectal fossa tumour.


Histochemical investigation of the mucosa of the exteriorized small intestine of the rat exposed to x-radiation.


Cancer of the breast in women. A retrospective clinical study of 2416 cases.


Intracellular distribution of respiratory enzymes in hamster and rat brown fat. ANL-7535.


Angiography in primary hepatic tumours in children.


Angiography in Wilms' tumour.

Angiography in Wilms' tumour.


Renal pelvis appearances in nephro- and neuroblastomas. Diagnostic value of true lateral projections.


Down's syndrome: a study of sleep patterns related to level of mental retardation.


Mandibular erosion in tumours of the major salivary glands.


"Panta'rhei"--and so flow our nerves.

"Panta'rhei"--and so flow our nerves.


Flurandrenolone (Cordran) tape and carbohydrate metabolizing enzymes. Use in the epidermis of people with psoriasis.


Histogenesis of skin appendage tumors.

Histogenesis of skin appendage tumors.


Heterogeneity of paramagnetic species in two iron-sulfur proteins: Clostridium pasteurianum ferredoxin and milk xanthine oxidase.


Eczema herpeticum.

Eczema herpeticum.


The nature of the intramolecular cross-link in collagen.


Hormone stimulation of ketogenesis in rat liver homogenates.


Studies on non-heme iron proteins and the piericidin A binding site of submitochondrial particles from Candida utilis cells grown in media of varying iron concentrations.


Polymerization of 5'-desoxyribonucleotides with beta-imidazolyl-4(5)-propanoic acid.


Differences in RNA from rat liver and hepatoma revealed by DNA-RNA hybridization.


Substrate induced spin state changes in cytochrome P-450.


Sphingolipids of animal nervous tissue. I. A comparative study of polar lipids sphingosine bases.


Inhibition of sterol synthesis in vitro by metabolites of phenylalanine.


Enzymatic hydrolysis of glycerophosphoryl esters. II. Cleavage of d-glycerol-1-phosphoryl-L-glycerol.


Studies of the heme components of cytochrome c oxidase by EPR spectroscopy.


One-electron transfer reactions in biochemical systems. IV. A mixed mechanism in the reaction of milk xanthine oxidase with electron acceptors.


Amniotic fluid in a case of multiple congenital anomalies.


Tumor induction in C57BL-6 mice by a single administration of cycasin.


Influence of toyocamycin on RNA synthesis in chick embryo cells noninfected and infected with strain MC29 avian leukosis virus.


Studies on chemical carcinogens. IX. Homolytic degradation of O,O'-Diacetyl-4-hydroxyaminoquinoline 1-oxide (1-acetoxy-4-acetyloxyimino-4-dihydroquino- line).


A comparative study of gamma-aminobutyric acid uptake in crustacean nerve-muscle preparations.


Lysosomal enzymes in aquatic species. I. Distribution and particle properties of muscle lysosomes of the goldfish.


Studies of long term administration of aflatoxin to rats as a natural food contaminant.


Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems. The mechanism responsible for the hyperdynamic circulatory state in hyperthyroidism has not been defined. Although certain cardiac manifestations resemble those caused by excessive adrenergic stimulation, recent evidence suggests that thyroid hormone exerts an effect on the heart that is independent of the adrenergic system. Since the inotropic and chronotropic effects of norepinephrine appear to be mediated by activation of adenyl cyclase, the possibility that thyroxine and triiodothyronine are also capable of activating adenyl cyclase was examined in the particulate fraction of cat heart homogenates.L-thyroxine and L-triiodothyronine increased the conversion of adenosine triphosphate-(32)P (ATP-(32)P) to cyclic 3',5'-adenosine monophosphate-(32)P (3',5'-AMP-(32)P) by 60 and 45% respectively (P < 0.01). A variety of compounds structurally related to the thyroid hormones, but devoid of thyromimetic activity did not activate adenyl cyclase: these included 3,5-diiodo-L-thyronine, L-thyronine, 3,5-diiodotyrosine, monoiodotyrosine, and tyrosine. D-thyroxine activated adenyl cyclase and half maximal activity was identical to that of the L-isomer. Although the beta adrenergic blocking agent propranolol abolished norepinephrine-induced activation of adenyl cyclase, it failed to alter activation caused by thyroxine. When maximal concentrations of L-thyroxine (5 x 10(-6) moles/liter) and norepinephrine (5 x 10(-5) moles/liter) were incubated together, an additive effect on cyclic 3',5'-AMP production resulted. THIS INVESTIGATION DEMONSTRATES: (a) thyroid hormone is capable of activating myocardial adenyl cyclase in vitro and (b) this effect is not mediated by the beta adrenergic receptor. Moreover, the additive effects of norepinephrine and thyroxine suggest that at least two separate adenyl cyclase systems are present in the heart, one responsive to norepinephrine, the other to thyroid hormone. These findings are compatible with the hypothesis that the cardiac manifestations of the hyperthyroid state may, in part, be caused by the direct activation of myocardial adenyl cyclase by thyroid hormone.


Hormonal regulation of lipolysis and phosphorylase activity in human fat cells. Prostaglandin E(1) (PGE(1)) at a concentration of 1 ng/ml antagonized theophylline, and norepinephrine induced release of glycerol and free fatty acids (FFA) in human fat cell preparations. Insulin at higher doses also inhibited theophylline-stimulated lipolysis. The N(6)-2-0'dibutyryl derivative of cyclic adenosine monophosphate (DCAMP) stimulated lipolysis. Prostaglandin E(1) did not significantly inhibit the lipid mobilizing effects of DCAMP. Changes in glycogen phosphorylase activity after treatment with theophylline, norepinephrine, DCAMP, and PGE(1) paralleled those of lipolysis. These results suggest that in man as in experimental animals lipolysis and phosphorylase activity are regulated through processes involving cyclic AMP and that PGE(1) appears to exert its antilipolytic effect in human fat cells, as in rat fat cells, by interfering at the level of adenyl cyclase with the accumulation of cyclic AMP.


Assessment of hypothalamic-pituitary-adrenal function in the geriatric age group.


Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone. Urinary excretion of cyclic adenosine 3',5'-monophosphate (3',5'-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3',5'-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3',5'-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney.


The gibbon (Hylobates lar); a new primate host for Herpesvirus hominia. I. A natural epizootic in a laboratory colony.


Australia antigen and viral hepatitis.

Australia antigen and viral hepatitis.


Herpes simplex infection of the female genital tract. II. Association of cytopathic effect in cell culture with site of infection.


Monkey pox. IV. Modification of disease pattern by antilymphocytic sera.


Alkaline phosphodiesterase activity of goat brain cortex ribosomes.


The biosynthesis of triiphosphoinositide by purified myelin of peripheral nerve.


Cytochrome oxidase activity in platelet-free preparations of Plasmodium knowlesi.


Succinic dehydrogenase and cytochrome oxidase in the liver of mice infected with Trypanosoma cruzi.


Protective effect of interferon and polyacrylic acid in newborn mice infected with a lethal dose of vesicular stomatitis virus.


Pulmonary activation of synthetic angiotensin I.


Retained products of conception. Histologic viability of placental polyps.


Effects of neurohypophyseal hormones, theophylline and nucleotides on the smooth muscle of the toad bladder.


Radiation therapy of brain-stem tumors.

Radiation therapy of brain-stem tumors.


Megavoltage radiation therapy and lymphangiography in ovarian cancer.


Malignant tumors of the ovary managed with postoperative megavoltage irradiation.


Herpetic sciatica.

Herpetic sciatica.


Postirradiation malignant neoplasms of the uterine fundus.


The relationship between the transport of glucose and cations across cell membranes in isolated tissues. V. Stimulating effect of ouabain, K+-free medium and insulin on efflux of 3-O-methylglucose from epidimal adipose tissue.


Adenine nucleotide metabolism of blood platelets. V. Subcellular localization of some related enzymes.


The effect of acute exercise on amino acid incorporation into mitochondria of rabbit tissues.


RNA synthesis in Taper hepatoma and mouse-liver cells.


Erythrocytic enzyme defects in infancy. Biochemistry of erythrocytes of the newborn.


Altered transfer RNA methylase patterns induced by an avian oncogenic virus.


Polysyndactyly, a new mutant gene in the mouse.


The nature of inhibitors of DNA synthesis in rat-liver hepatoma cells.


Humoral immunity factors to parainfluenza viruses type 1, 2 and 3 in infants under the age of one year.


Course of air-borne infection caused by B virus (Herpesvirus simiae). 3. Immunofluorescence findings in some organs of rabbits infected with large doses of B-virus aerosol.


Effect of 1 percent phenol on several bacterial and viral species.


Dynamics of incidence of antibiotic-(chemotherapeutic-) resistant E. coli in pigs and types of polyresistance of the isolated strains depending on addition of aureovit12 C20 to food.


Methaqualone (Quaalude-300) and REM sleep.


Time cycle for intracellular synthesis of mirine leukaemia virus.


Morphology of ascites sarcoma RAB I of the mouse.


Cytomegalovirus infection in infancy: report of 9 cases and brief review of the literature.


Cancer of the lung in Natal Bantu--a new cancer problem. A review of 472 cases, 1964-1966.


Inactivation of the bovine mammillitis herpesvirus by disinfectants.


Association of herpes-like virus infection with infectious mononucleosis.


Factors affecting urate excretion following diuretic administration in man.


Cushing's syndrome with a paradoxical response to dexamethasone.


Bilateral multiple otosclerotic foci and endolymphatic hydrops, histopathological case report.


Persistent antidiuresis with hypoaldosteronism and sodium wasting in hypopituitarism.


Antiviral activity of 9-beta-D-arabinofuranosyladenine. 3. Reduction in evidence of encephalitis in treated herpes Simplex-infected hamsters.


Antiviral activity of 0-beta-D-arabinofuranosyladenine. IV. Activity against intracerebral herpes simplex virus infections in mice.


Antiviral activity of 9-beta-D-arabinofuranosyladenine. V. Activity against intracerebral Vaccinia virus infections in mice.


Atraumatic nasal biopsy for studies of respiratory virus infection in volunteers.


Inhibitory effect of statolon on murine leukemia and sarcoma viruses in cell culture.


Incidence of cytomegalovirus infection in uremic patients.


Effect of the nutritional environment on the development of resistance to polymyxin B in Pseudomonas aeruginosa and its prevention by atabrine.


25-hydroxycholecalciferol. The probable metabolically active form of vitamin D3: its identification and subcellular site of action.


The nature of vitamin D resistance of patients with chronic renal disease.


Clinical experience with human growth hormone immunoassay by a two-antibody method.


Acanthosis nigricans and obesity, an endocrine abnormality?


Intermolecular disulfide oss-linkages in the collagen from the muscle layer of Ascaris lumbricoides.


Collagen-protein-polysaccharide interactions in human intervertebral disc.


On the binding of adrenocorticotropin to proteins during isolation.


Aglossia congenita with bony fusion of the jaws.


Adrenal function during topical oral corticosteroid treatment. Plasma cortisol (hydrocortisone) levels were measured in 42 subjects before and during administration of topical oral corticosteroids. Topical administration of 0.3-0.4 mg. of betamethasone disodium phosphate daily caused partial suppression of adrenal function in 8 out of 10 subjects tested. The adrenal function remained normal in 14 patients treated with 10 mg. of hydrocortisone hemisuccinate daily for periods of up to three years. Betamethasone 17-valerate also failed to cause adrenal suppression in doses of 0.4 mg. per day in 17 patients. The adrenal glands failed to respond normally to stimulation with Synacthen (tetracosactrin) in selected subjects with depressed plasma cortisol levels. Therapeutic doses of topical oral hydrocortisone hemisuccinate and betamethasone 17-valerate may be used in adults with oral lesions without fear of affecting adrenal function. Betamethasone disodium phosphate, however, should be avoided, as it may cause adrenal suppression.


Metabolic differentiation of distinct muscle types at the level of enzymatic organization.


The subcellular distribution of lysophospholipase in bovine adrenal medulla.


A quantitative study of the biosynthesis of cytochrome c.


Spectroscopic differentiation of the electron-accepting sites in fungal laccase. Association of a near ultraviolet band with a two electron-accepting unit.


Regulation of the level of key enzymes of glycolysis and gluconeogenesis in liver.


The proption of the incorporation of leucine into albumin to that into totaprotein in rat liver and hepatoma Morris 5123 TC.


Thrombosthenin M. Purification and interaction with thrombin.


An optical rotatory dispersion vestigation of fungal laccase.


Koch's phenomenon involving the flexor tendon sheath. Adjuvant-induced tenosynovitis in man.


Identification of vitamin D3 in human skin.


Ionic permeability of the inhibitory postsynaptic membrane of lobster muscle fibers. Reversal potentials (E(IPSP)) of the inhibitory postsynaptic potential and the membrane resting potentials (E(M)) of lobster muscle fibers were determined with intracellular recording under a variety of ionic conditions. E(IPSP) is solely dependent on the electromotive force of anionic batteries; i.e., on the electrochemical gradient for a "mobile" fraction of intracellular Cl (Cl(i)) which is considerably smaller than the total intracellular Cl. The active inhibitory membrane is more permeable to certain "foreign" anions in the order NO(3) > SCN > Br > Cl. The membrane is impermeable to BrO(s), isethionate, and methylsulfate, but is slightly permeable to acetate and propionate. The level of Cl(i) appears to be determined in part by some active (pump?) process and most of the anions studied appear to interfere with the steady-state level of Cl(i).


Influence of diethylaminoethyl-dextran on uptake and degradation of polyoma virus deoxyribonucleic acid by mouse embryo cells. The uptake of (32)P-labeled polyoma virus deoxyribonucleic acid (DNA) (I and II + III) by mouse embryo cells was increased from two- to fivefold in the presence of 500 mug of diethylaminoethyl-dextran (DEAE-D) per ml. This concentration of DEAE-D gives maximal enhancement of infectivity; however, the increase is many thousand-fold. As the DEAE-D concentration was increased from 0 mug/ml, uptake and infectivity increased to flat maxima and then decreased in a similar manner, except that at low DEAE-D concentrations uptake was relatively much greater than infectivity. Several other polycations also increased DNA uptake but did not enhance infectivity, and uptake of viral DNA was unaffected by the presence of mouse DNA, although infectivity was reduced. Thus, increased uptake is not the sole basis for the enhancement of infectivity produced by DEAE-D. The possibilities that DNA complexed with DEAE-D penetrates more rapidly or is stabilized against degradation do not completely account for enhancement since complexes formed in mixtures of DNA and DEAE-D, which sedimented heterogeneously from 40 to 60S, were infectious only for monolayers treated with DEAE-D. A more likely factor in enhancement is inhibition of the cellular nuclease activity detected, since virus DNA exposed to cells was much more degraded in the absence than in the presence of DEAE-D. The nuclease activity produced single-strand breaks in double-stranded DNA. Treatment of monolayers with deoxyribonuclease after adsorption of DNA in the presence of DEAE-D reduced cell-associated radioactivity by about 70%, although the number of plaques formed was not affected. In the absence of DEAE-D, 90 to 100% was removed by deoxyribonuclease. Thus, in both cases most of the DNA was adsorbed extracellularly. The greater deoxyribonuclease-resistant fraction in the presence of DEAE-D would be consistent with another possibility: that enhancement results from an increase in DNA penetration rate due to some action of DEAE-D on the cell.


Site of host restriction of simian virus 40 mutants in an established African green monkey kidney cell line. A previously described large-plaque morphology mutant of SV40 (SV-L) in primary African green monkey kidney (AGMK) cells has been shown to be restricted in the established AGMK line CV-1. The site of restriction is an early step in infection, involving the virus particle. A block in penetration or uncoating has been tentatively proposed. Restriction is observed in a number of other established lines, including monkey, human, and mouse. Independent large-plaque mutants were isolated in AGMK and their properties were compared with SV-L (temperature restriction, host restriction, and virion antigen). They can be separated into two classes. Both are restricted on CV-1, though to a lesser degree than SV-L. Further-more, both are coat mutants as determined by immunological analysis of their virions, suggesting a relationship between coat mutants associated with large-plaque morphology in AGMK and host restriction in established cell lines. Temperature restriction is seen with one but not the other of the mutants.


Analysis of the ribonucleic acid of murine leukemia virus. Cells producing the Rauscher strain of murine leukemia virus (MLV) were exposed to (3)H-uridine, and labeled virus was collected at hourly intervals. Ribonucleic acid (RNA) extracted from virions (vRNA) had a characteristic single peak when analyzed by electrophoresis in polyacrylamide-agarose composite gels. Exposure of vRNA to dimethyl sulfoxide, urea, formaldehyde, or heat altered the mobility to a faster moving form (vRNA'). This vRNA' sedimented more slowly than native vRNA in sucrose gradients. Incubation of labeled virions at 37 C resulted in fragmentation of viral RNA which was detectable only after denaturation. Also, large differences in the temperature required for the change from vRNA to vRNA' were seen with alterations in NaCl concentration. These experiments demonstrate that the vRNA of MLV is held in a specific conformation by hydrogen bonds distributed over a large part of the molecule. The possibility that an undefined factor is associated with viral RNA is discussed.


Electron microscopic observations on the ribonucleic acid of murine leukemia virus. The ribonucleic acid (RNA) of murine leukemia virus (MLV) Rauscher strain was observed by the aid of electron microscopy with the use of the protein monolayer technique. RNA was observed directly after release from virus particles or after isolation by sedimentation in sucrose density gradients. Molecules were found in an extended linear form. Many of the RNA filaments released by detergent treatment contained curled regions, suggesting the linear filaments were originally coiled within the virus particle. The relationship of the curled areas to the containment of the RNA within the virus particle is discussed, and a mechanism for the inclusion of RNA in the budding virion is proposed. Treatment of the extended MLV-RNA with dimethyl sulfoxide resulted in the collapse of the molecule forming a tangled complex. Treatment with urea or heating at 50 C in 3 mm NaCl also produced this effect. Also under the conditions in which MLV-RNA was linear, RNA from Rous sarcoma virus also was linear, but Newcastle disease virus RNA and ribosomal RNA of rat liver had collapsed structures. The results indicated that the RNA of MLV, and perhaps other RNA-containing tumor viruses, has a specific unique conformation dependent upon hydrogen bonds.


Biological effects of substituting cytosine for 5-hydroxymethylcytosine in the deoxyribonucleic acid of bacteriophage T4. Previous work from this laboratory has shown that the cytosine-containing T4 deoxyribonucleic acid (DNA) made by deoxycytidine triphosphatase (dCTPase) amber mutants is extensively degraded, and that nucleases controlled by genes 46 and 47 participate in this process. In this paper, we examine other consequences of a defective dCTPase. Included are studies of DNA synthesis and phage production, and of the control of both early and late protein synthesis after infection of Escherichia coli B with various T4 mutants defective in genes 56 (dCTPase), 42 (dCMP hydroxymethylase), 1 (deoxynucleotide kinase), 43 (DNA polymerase), 30 (polynucleotide ligase), 46 and 47 (DNA breakdown) or e(lysozyme). By varying the temperature of infection with a temperature-sensitive dCTPase mutant, we have been able to control intracellular dCTPase activity, and thus vary the cytosine content of the phage DNA. We have produced and characterized viable T4 phage in which cytosine replaces 20% of the 5-hydroxymethylcytosine (HMC) in the DNA. We present evidence which suggests that intact, cytosine-containing T4 DNA is much less efficient than is normal T4 DNA in directing the synthesis of tail-fiber antigen. Lysozyme production is much less affected by progressively decreasing dCTPase activity; however, complete substitution of cytosine is correlated with a depression of lysozyme synthesis greater than expected from the defective synthesis of DNA. Low but significant lysozyme synthesis is observed late after infection of E. coli B with T4 amber mutants defective in a number of genes controlling DNA synthesis. The "20% cytosine" T4 phage, once produced, can initiate an apparently normal infection at permissive temperatures; the synthesis of early enzymes, DNA, and phage does not appear to be impaired. Two roles for HMC in T4 DNA have been indicated previously: (i) involvement in host-controlled restriction of the phage, in which glucosylation of the hydroxymethyl group plays a crucial role (16, 29, 53, 58), and (ii) protection of vegetative DNA against phage-controlled nucleases, a protection not dependent on glucosylation (41, 66, 67). A third role is suggested by our present results: transcription of at least some late genes can occur only from HMC-containing DNA and not from cytosine-containing DNA.


Replication of canine herpesvirus. II. Virus development and release in infected dog kidney cells. The studies reported in this paper demonstrate that, although canine herpesvirus differs from other herpesviruses in that it is characterized by a restricted host range, the pattern of virus development in the permissive host closely resembles that previously described for herpes simplex virus. These experiments also reveal the formation in the infected dog kidney cells of a system of tubules and channels in which virions accumulate. It is suggested that these membrane-bound structures serve to protect enveloped virus from being uncoated in the cytoplasm and function in virus release from the infected cells.


Molecular weight of poliovirus ribonucleic acid. Purified poliovirus single- and double-stranded ribonucleic acids (RNA) were examined by electron microscopy. The length of both molecules was found to be 2.37 mum. The uncorrected sedimentation coefficient for single-stranded RNA is 33S, as compared to 27S for the RNA of tobacco mosaic virus. It is calculated from these results that the molecular weight of the sodium form of poliovirus is 2.6 x 10(6) daltons.


Mengovirus-induced cytopathic effect in L-cells: protective effect of interferon. The effect of interferon on mengovirus-induced cytopathic effect (CPE) in L cells, the cut-off of host-cell protein synthesis, and production of mature virus were found to be dependent on the concentration of interferon. CPE and inhibition of host protein synthesis were not affected until the concentration of interferon was increased 100-fold over that required to reduce viral yields by 90%.


Genetic analysis with human--mouse somatic cell hybrids.


Abortive transformation by the Tsa mutant of polyoma virus.


Entry and release of poliovirus as observed by electron microscopy of cultured cells. Cells of differing culture types were inoculated with poliovirus at 37 C, sampled at intervals during the replicative cycle, and examined in thin sections by electron microscopy. The earliest samples, taken at 2 and 5 min postinoculation, showed virus particles adjacent to the exterior of the plasma membrane and others that had apparently penetrated it directly; later samples showed fewer such particles or none. Particles lying in the peripheral cytoplasm frequently appeared swollen and distorted in shape. No sign of virus entry by a pinocytotic process was found at any time. At 3 hr, and subsequently during the replication cycle, particles of progeny virus appeared in the cytoplasm. They were found free in the cytoplasmic matrix, aligned along the elements of filamentous complexes, and enclosed within vesicles. Some of the vesicles were found to be open to the extracellular space, indicating a likely mechanism of virus release.


Cerebral blood flow during sleep in patients with raised intracranial pressure.


Cytochrome a3: destruction by light.

Cytochrome a3: destruction by light. Spectroscopic measurements on cultures of Prototheca zopfii irradiated with blue light revealed that inhibition of respiration was accompanied by destruction of cytochrome a(3). One of the three b-type cytochromes and one of the two c-type cytochromes of this organism were also affected. Cytochrome oxidase of yeast (not resolved into the a and a(3) components) and cytochrome a(3) of beef-heart mitochondria were also destroyed by blue light.


Role of peripheral chemoreceptors on adrenocortical secretory rates during hypoxia.


A nationwide serum survey of Colombian military recruits, 1966. I. Description of sample and antibody patterns with arboviruses, polioviruses, respiratory viruses tetanus, and treponematosis.


An outbreak of respiratory infection in children associated with rhinovirus types 16 and 29.


Evidence for protective effect of an inactivated rhinovirus vaccine administered by the nasal route.


Serologic evidence of arbovirus infections in wild ruminants.


Total hepatic angiography and vascular dynamics in liver disease.


Acute neuromuscular transmission failure in vas deferens after reserpine.


Treatment of neoplasms of the liver.

Treatment of neoplasms of the liver.


A role for glucagon in cardiac therapy.

A role for glucagon in cardiac therapy.


Is noradrenaline an inhibitory transmitter to motoneurones?


Renal autoregulation during infusion of noradrenaline, angiotensin and acetylcholine.


Stabilized neutral orthotolidine, SNORT, colorimetric method for chlorine.


Partial purification and some properties of the factor in normal and leukaemic human urine stimulating mouse bone marrow colony growth in vitro.


Variations in the ability of yeasts cultured in oxygen-controlled environments to oxidize NADH.


Control of spontaneous ventricular fibrillation during induced hypothermia in cats by acute cardiac sympathectomy.


Inhibition of mammalian uridinediphosphoglucose 4-epimerase by the dithiothreitol-stimulated formation of NADH.


Properties of the xanthine oxidase from human liver.


Similar modifying effects of oligomycin and ATP on the K+-dependent p-nitrophenylphosphatase activity of the (Na+ + K+)-activated ATPase.


Reaction of the sulphydryl groups of lobster-muscle glyceraldehyde-3-phosphate dehydrogenase with organic mercurials.


Kinetic studies of succinate dehydrogenase by electron paramagnetic resonance spectroscopy.


Mechanism of the salicylate hydroxylase reaction. 3. Characterization and reactivity of chemically or photochemically reduced enzyme-flavin.


On the possible role of crystals in the origins of life. I. The adsorption of nucleosides, nucleotides and pyrophosphate by apatite crystals.


Hepatic amoebiasis; amoebic hepatitis and amoebic abscess with particular reference to connective tissues reaction and distribution of amoebae.


Action of the Trenimon "Bayer" cytostatic on the morphological picture and some histochemical reactions of the intestinal mucosa of the rat.


Amoebiasis in an experimental model--some observations.


Free radicals in pyrimidines: E.S.R. of gamma-irradiated single crystals of alloxantin.


Isolation and identification of clostridia from North Sea sediments.


Neomycin-containing media in the isolation of Clostridium botulinum and food poisoning strains of Clostridium welchii.


Persistent rubella virus infection in hamster lung cells.


Wilms' tumor and congenital aniridia.

Wilms' tumor and congenital aniridia.


Relationship between potentiation of H-1 growth by human adenovirus 12 and inhibition of the 'helper' adenovirus by H-1.


Inherent photosensitivity of herpes virus and other enveloped viruses.


Surface structure of vesicular stomatitis virus.


Control of airborne dust produced by pneumatic jackpicks. II.


Surveillance of paralytic poliomyelitis in the United States. 1966 and 1967 cases, and 1965-1967 cases associated with oral poliovirus vaccine.


Studies on the lipids of sheep red blood cells. 3. The fayy acid composition of phospholipids in HK and LK cells.


Hyponatremia in pituitary insufficiency.


Inhibition of trans-synaptically increased tyrosine hydroxylase activity by cycloheximide and actinomycin D.


Occurrence and levels of 5-hydroxytryptamine in Schistosoma mansoni.


Factors affecting the release of melanocyte-stimulating hormone in mammals.


Loss of sleep.

Loss of sleep.


Immune responses to virus-induced tumours.


Histochemical studies on thiaminepyrophosphatase localization in the adult, embryonic and neoplastic liver cells using light and electron microscopy.


Electron microscopic studies on the localization of guanosine-5'-triphosphatase A activity in cell nuclei.


Histochemical studies on the distribution of phosphatases in Trichomonas vaginalis.


Antagonism between prostaglandin E2 and phenoxybenzamine on noradrenaline release from the cat spleen.


Glucose 6-phosphatase: a multifunctional enzyme.


Facial nerve tumors.

Facial nerve tumors.


The effect of various 3'5' cyclic nucleotides on gluconeogenesis and glycogenolysis in the perfused rat liver.


After-care for alcoholics--a follow-up study.


Inhibition of spontaneous breast tumors in a high MTV strain.


32P-Distribution in oligonucleotides of rapidly sedimenting nucleolar RNA's of hepatomas and normal rat liver.


Study of antiviral activity of tender leaves of Margosa tree (Melia azadericta) on vaccinia and variola virus: a preliminary report.


Problems in haemagglutination test with faecal viruses.


Search for herpes simplex, mumps and lymphocytic choriomeningitis associated with central nervous system disease at Vellore, Southern India.


Traveling-wave velocity in the human cochlea.


Time-domain measurements of cochlear nonlinearities using combination click stimuli.


Lipids of Acanthamoeba castellanii. Composition and effects of phagocytosis on incorporation of radioactive precursors. The lipids of Acanthamoeba castellanii (Neff) consist of 52% neutral lipids and 48% polar lipids. Triglycerides account for 75% and free sterols for 17% of the neutral lipids. The major phospholipids are phosphatidylcholine (45%), phosphatidylethanolamine (33%), phosphatidylserine (10%), a phosphoinositide (6%), and diphosphatidylglycerol (4%). The phosphoinositide is unique in that it contains fatty acids, aldehyde, inositol, and phosphate in the ratio of 1.4:0.5:1.1, but it contains no glycerol. Sphingomyelin, cerebrosides, psychosine, and glycoglycerides were not detected, but small amounts of unidentified long chain bases and sugars are present. The rates of uptake of palmitate-1-(14)C and of its incorporation into glycerides and phospholipids were not affected by the phagocytosis of polystyrene latex beads. Although phagocytosis usually decreased the uptake by amebas of phosphate-(32)P, serine-U-(14)C, and inositol-2-(3)H, their subsequent incroporation into phospholipids was not demonstrably stimulated or inhibited by phagocytosis. Phagocytosis did seem to increase the incorporation into ameba phospholipids of phosphatidylcholine-1 ,2-(14)C but not that of phosphatidylethanolamine-1 ,2-(14)C. These experiments, in which the incorporation of radioactive precursors into total cell lipids was measured, do not, of course, eliminate the possibility that localized effects may occur.


The association of cholesterol, 5'-nucleotidase, and alkaline phosphodiesterase I with a distinct group of microsomal particles.


Collagenases in human synovial fluid.

Collagenases in human synovial fluid. An enzyme which degrades native collagen at neutral pH has been isolated from cultures of rheumatoid synovium in vitro, but little or no collagenolytic activity has been found in homogenates of fresh rheumatoid synovium. Similar to most other mammalian collagenases this synovial enzyme is readily inhibited by serum proteins. Proteins of synovial fluid are derived largely from serum and synovial fluid from noninflamed joints was found to inhibit synovial collagenase; the inhibitor was destroyed by trypsin, but not by hyaluronidase. Inhibitory activity was reduced in approximately one-half of the fluids from patients with rheumatoid arthritis. In a total of nine synovial fluids, collagenolytic activity was detectable. This activity was not present in constant amounts in synovial fluids aspirated at different times from the same patient and tended to vary inversely with the titer of inhibitory proteins. The collagenolytic activity in the synovial fluids from different patients was variably inhibited by serum proteins. Two distinct collagenases were detected in some rheumatoid synovial fluids and separated by gel filtration. One, labeled "B" enzyme, with an estimated molecular weight 20,000-25,000 resembled the collagenase obtained from synovial cultures. The other, labeled "A" enzyme degraded collagen fibrils as well as collagen in solution. Disc electrophoresis on acrylamide gels and electron microscopy of segment long spacing (SLS) aggregates of reaction products of the enzymes at 27 degrees C demonstrated that both "A" and "B" enzymes cleaved collagen molecules at a point three-quarters from the amino terminal end of the molecule. Thus collagen degradation in rheumatoid arthritis could result from the operation of these two collagenases.


Phagocytosis of latex beads by Acahamoeba castellanii (Neff). 3. Isolation of the phagocytic vesicles and their membranes. A method is described for the rapid and efficient isolation of phagocytic vesicles from large scale cultures of Acanthamoeba castellanii (Neff) that have been incubated with polystyrene latex beads. Cells were allowed to phagocytose latex beads for 30 min and then were homogenized, and the phagocytic vesicles were isolated by one centrifugation through several layers of sucrose. Identity and purity of the phagocytic vesicles were determined by electron microscopy, chemical analyses, and assays of acid phosphatase, alpha- and beta-glucosidase, and reduced nicotinamide adenine dinucleotide dehydrogenase. When phagocytosis was allowed to occur for longer periods the phagocytic vesicles appeared to fuse with each other and perhaps with digestive vacuoles. The resultant vesicles which contained many beads were heavier than those which consisted of only one bead or a few beads with a closely applied membrane. Ultrasonication ruptured the isolated vesicles, and the membranes could then be isolated in 30-50% yield based on phospholipid analysis. These membranes were essentially free of acid hydrolases and, presumably, other soluble proteins, as was also indicated by their low ratio of protein to phospholipid. The membranes have been prepared both as closed vesicles and as open sheets.


Lipid metabolism in human platelets. II. De novo phospholipid synthesis and the effect of thrombin on the pattern of synthesis. Washed human platelets were incubated with radioactive glycerol; the platelets were able to synthesize de novo the major phosphoglycerides including phosphatidic acid, phosphatidylinositol, phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine. The specific activities of the phosphoglycerides obtained after glycerol incorporation indicate that phosphatidic acid, phosphatidylinositol, and phosphatidyl choline are metabolically active relative to phosphatidyl ethanolamine and that formation of phosphatidyl serine occurs to a much more limited extent. When platelets were incubated with bovine thrombin, 1 U/ml, the pattern of glycerol incorporation into phospholipid was changed. There was a 3-fold decrease in the total incorporation into lipid in 30 min with a relative 5-fold decreased incorporation into phosphatidyl choline and phosphatidyl ethanolamine and a 5-fold increased incorporation into phosphatidyl serine. The increased incorporation into phosphatidyl serine. The increased incorporation into phosphatidyl serine was maximal within the first 2 min but was transient, since within 20 minutes, the rate returned to that seen in platelets incubated with glycerol alone. Purified human thrombin also produced this same effect on phospholipid synthesis in platelets. Trypsin produced effects on phosphoglyceride formation similar to those seen with thrombin, and the trypsin-induced effect was inhibited by prior incubation of trypsin with soybean trypsin inhibitor, suggesting that proteolysis may be required for the observed effects on phospholipid synthesis.


The effect of valinomycin on the toad bladder: antagonism to vasopressin and aldosterone.


The distribution and concentration of 75Se-selenomethionine in man.


Vitamin D3 metabolism in renal osteodystrophy.


Release to the cerebral ventricles of substances with possible transmitter function in the caudate nucleus. 1. One caudate nucleus of the anaesthetized cat was superfused by perfusing the anterior horn of one lateral cerebral ventricle. The perfusates were examined for their content in acetylcholine (ACh), dopamine, homovanillic acid (HVA) and 5-hydroxytryptamine (5-HT), at rest and after a variety of stimuli.2. When prostigmine was added to the perfusion fluid, ACh appeared in the effluent; its concentration tended to rise in the course of an experiment. Various afferent stimuli, all of which caused evoked responses recorded from the contra-lateral caudate nucleus, increased the ACh content of the effluent. Effective stimuli were noise and electrical stimulation of afferent nerves or of certain regions of the brain including the ipsi-lateral substantia nigra.3. The dopamine content of the effluent was extremely low (of the order of 50 pg/min) at rest, but, on occasion, rose sharply when the substantia nigra was stimulated electrically with trains of pulses repeated once every 3 sec. The results were inconsistent.4. Since dopamine in tissue is rapidly transformed enzymically into HVA, the appearance of this acid in the perfusate was examined.5. At rest, HVA was found to appear in the effluent at a rate of 2-8 ng/min. Its concentration was rapidly depressed by increasing the depth of anaesthesia.6. Stimulation of the substantia nigra for periods of 3 or 4 min caused an increment in the HVA content of the effluent lasting 1 hr or more. It was frequently seen when two points of the substantia nigra were stimulated simultaneously, less regularly with only one stimulating electrode, and rarely if this was placed in the most caudal part of the substantia nigra.7. These results strongly support the view that there is a dopaminergic nigro-striatal pathway. The following assumption would explain the erratic appearance of dopamine and the long duration of increments in HVA: many of the axons originating in the substantia nigra end either in the putamen or in parts of the caudate nucleus which are far away from the ventricular surface; any dopamine released from these axons will not reach the ventricular surface at all, and HVA will, at best, reach it very slowly.8. Small amounts of 5-HT appeared in the ventricular perfusate, and the quantity rose after the administration of monoamine oxidase inhibitors. It was not increased by the type of stimuli used in this work to elicit the release of ACh or HVA.


Femoral neuropathy secondary to retroperitoneal hemorrhage.


Web-foot or syndactylism in the fowl.

Web-foot or syndactylism in the fowl.


Current concepts. Vitamin D.

Current concepts. Vitamin D.


Hepatic source of plasma amino acids.

Hepatic source of plasma amino acids.


Perceptual aspects of psychopathology.

Perceptual aspects of psychopathology.


Electron paramagnetic resonance study of x-ray and gamma-ray irradiated peptides in the solid state.


Schizophrenia: evidence of a pathologic immune mechanism.


The value of selective angiography in the diagnosis of tumors in pancreas and liver.


Effect of liver cell fragments on Entamoeba histolytica in monobacterial cultures.


Differentiation of intrahepatic and extraheptic masses by arteriography.


A surface-active lysosome in Entamoeba histolytica.


Mucinous urachal adenocarcinoma. A case report and a review of the literature.


Studies on syndrome of diabetes insipidus associated with oligosyndactyly in mice.


Studies on the urinary excretion, biological effects and origin of oestrogens in post-menopausal women.


A subcellular agent inducing plasma cell leukemias in mice. The relation of this agent to amyloidosis and chronic murine pneumonia.


Regulation of riboflavin-metabolizing enzymes in riboflavin deficiency.


Angiotensin-protective cofactor.

Angiotensin-protective cofactor.


In vivo perfusion of proximal tubules of the rat: glomerulotubular balance.


Effects of fasting and diabetes on fatty acid synthesis by heart mitochondria.


Critical evaluation of specificity in electron microscopical radioautography in animal tissues.


Effects of streptozotocin in a patient with islet cell carcinoma.


Enzymic activities during the transformation of crypt to columnar intestinal cells.


Response of somatic cell hybrids to exposure to adenovirus type 2 and 12.


Studies on induced cellular autophagy. II. Characterization of the membranes bordering autophagosomes in parenchymal liver cells.


The isolation and structure identification of uridine 5-(2-acetamido-2-deoxy-alpha-D-glucopyranosyluronic acid pyrophosphate) from Micrococcus lysodeikticus cells.


The composition and structure of the carbohydrate of pineapple stem bromelain.


Characterization of a phosphatase specific for phosphorylated histones and protamine.


Assembly of the mitochondrial membrane system. I. Characterization of some enzymes of the inner membrane of yeast mitochondria.


The behavior of horse liver alcohol dehydrogenase in guanidine hydrochloride solutions.


Observations on synovial sarcoma in Indians.


Inhibition of glucagon effects in perfused rat liver by (+)decanoylcarnitine.


Mouse cytomegalovirus: placental infection.


Murine leukemialike virus and the immunopathologic disorders of New Zealand black mice.


Effects of procaine, pentobarbital and halothane on synaptic transmission in the central nervous system.


A comparison of the sensitivity to chemical stimuli of adrenergic and cholinergic neurons in the cat stellate ganglion.


Trans-synaptic induction of adrenal tyrosine hydroxylase.


Dissociation of the increased formation of cardiac adenosine 3',5'-monophosphate from the positive inotropic effect of norepinephrine.


The cardiovascular effects of cranial artery infusions of acetylcholine in the dog and their relevance to the angiotensin response.


Dose-dependent, biphasic effects of angiotensin on fluid transfer by rat colon.


Identification of adenosine triphosphate in human plasma and the concentration in the venous effluent of forearm muscles before, during and after sustained contractions. 1. When diluted human plasma is perfused through a frog heart, a marked augmentation of the heartbeat is produced which is very similar in action to that of low concentrations of adenosine triphosphate (ATP) on the heart.2. It was established that the substance in the plasma responsible for the heart stimulation was ATP. The following tests were used: (a) the diluted plasma emitted light from firefly lantern extract characteristic of the light signal produced by a solution of ATP; (b) the stimulatory effect on the frog heart and luminescent effect upon the firefly extract were abolished by incubation of the plasma solution with the enzyme apyrase, which converts ATP to adenosine monophosphate (AMP); AMP does not stimulate the heart or cause light to be emitted from firefly extract; (c) the stimulatory substance in the plasma was eluted through a column of Sephadex G-25 in the same pattern as ATP; and (d) simultaneous assay of plasma solutions on frog heart and firefly extract produced the same quantitative result as that produced by a solution of ATP.3. The amount of ATP in plasma from the venous blood of resting subjects ranged from 0.19 to 0.95 mug/ml. (mean 0.63 mug/ml., S.D. +/- 0.25); up to half of the ATP detected could be attributed to blood platelet damage. Simultaneous arterial and venous samples of blood from four subjects at rest had mean concentrations of 0.19 mug/ml. (0.07-0.26 mug/ml.) and 0.70 mug/ml. (0.57-0.84 mug/ml.) respectively.4. The concentration of ATP in the venous effluent from exercising forearm muscles was measured. The venous concentration consistently increased over the resting values in response to exercise while in one subject little change occurred in the arterial blood concentration during the exercise. It was concluded that the ATP was added to the blood in its passage through the muscle bed.5. The origin of the ATP, including erythrocytes, blood platelets and active skeletal muscle, is discussed.


An automatic 2+2 dose assay using the rat blood pressure.


Vascular resistance in the perfused isolated rat tail.


Further evidence that acetylcholine is not a transmitter at chemoreceptors.


The influence of transplantable Crocker sarcoma on growth of transplantable chrysoidin hepatoma in mice.


High frequency electro-shock seizures and their antagonism in developing mice. 3. Effects of cortisol, corticosterone, deoxycorticosterone, dexamethasone and a synthetic corticotropine.


Adenyl cyclase and phosphodiesterase activities in brain areas of man, monkey and rat.


Hyperreactio luteinalis: postpartum persistence.


Viral isolations from bovine eye tumors.


Malignant mixed tumors of salivary gland origin.


Comparative study of the effect of three antibiotics on renal function. 1. Therapeutic doses of colistin sulphomethate sodium B.P. (Colomycin), pento-N sulphomethylpolymyxin B sodium (Thiosporin) and ampicillin B.P. (Penbritin) as well as normal saline have been given to volunteers with normal kidney function.2. A blind crossover technique was used and the effects of the compounds on blood levels and clearances of urea and creatinine studied.3. All four treatments resulted in some changes in the parameters measured but were reversible. The most marked changes were found with pento-N sulphomethylpolymyxin B sodium and were also associated with severe side-effects.4. In contrast to penicillins it is established that the process of tubular secretion sensitive to probenecid block plays no part in the renal excretion of polymyxins.


Detection of a small virus in a cultivated human Wilms' tumor.


Defective photochemical repair in epithelium predisposed to field cancerization.


Effect of hypocalcemia and vitamin D-induced hypercalcemia on the incidence of metastases in rats.


Aldolase isozymes in human tissue and serum. With special reference to cancer diagnosis.


Synthesis of corticotrophin-like polypeptides and protein by bovine hypothalamus, median eminence and pituitary tissue slices.


Assessment of a test of adrenocortical function using beta1-25 corticotrophin.


Autoradiographic studies of uridine-5-H3 uptake in Entamoeba histolytica in the CLG medium.


Lysosomal hydrolases in Acanthamoeba sp.


Longitudinal banded pigmentation of nails following adrenalectomy for cushing's syndrome.


Childhood cancer and congenital defects. A study of U.S. death certificates during the period 1960-1966.


The replete pediatrician and the etiology of lower respiratory tract infections. Presidential address to the Society for Pediatric Research.


Biochemical patterns in brain tumours. II. Enzymes of the tricarboxylic acid cycle.


Formation of extracellular adenosine triphosphate by human erythrocytes.


Effects of radiation damage to bone marrow on susceptibility of chicks to erythroleukemia virus.


Replication of oncogenic viruses in virus-induced tumor cells-their persistence and interaction with other viruses.


Methylation of herpes-simplex-virus deoxyribonucleic acid.


The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase. 1. Organophosphorus compounds that produce a delayed neurotoxic effect in hens phosphorylate a specific site in the brain soon after administration. 2. Phosphorylation of the specific site by di-isopropyl [(32)P]phosphorofluoridate in vitro is blocked by the prior addition of phenyl phenylacetate. 3. A small proportion of the total activity of hen brain hydrolysing phenyl phenylacetate in vitro was shown to be due to an enzyme different from two others previously described. 4. This enzyme is only slightly inhibited in vitro by concentrations of tetraethyl pyrophosphate and paraoxon (diethyl 4-nitrophenyl phosphate) up to 64mum and is completely inhibited by 6mum-di-isopropyl phosphorofluoridate and 128mum-mipafox. 5. It is also inhibited in vivo by effective doses of neurotoxic organophosphorus compounds but not by high doses of non-neurotoxic analogues. 6. It is deduced that the active site of this enzyme is the phosphorylation site associated with the genesis of delayed neurotoxicity.


"Rapidly appearing" molybdenum electron-paramagnetic-resonance signals from reduced xanthine oxidase. Further electron-paramagnetic-resonance studies relating to the role of molybdenum in the enzymic mechanisms of xanthine oxidase were carried out. The classification of the various molybdenum signals obtained on reducing the enzyme is briefly discussed. The group of ;Rapidly appearing' signals, which are obtained with all substrates within the turnover time and which show interaction with exchangeable protons, were studied in detail. Signals with salicylaldehyde, purine and xanthine in H(2)O and in 95% D(2)O were examined at 9 and 35GHz and interpreted with the help of computer simulation. Molybdenum atoms in a number of different chemical environments are involved, each substrate giving rise to two superimposed spectra with slightly different parameters; g values and proton splittings were determined. The spectrum with salicylaldehyde is believed to represent the reduced enzyme alone not in the form of a complex with substrate and its two constituents are believed to represent the two molybdenum atoms bonded slightly differently within the enzyme molecule. With purine and xanthine the spectra are thought to represent complexes of reduced enzyme with substrate molecules. With xanthine one signal-giving species shows coupling to two equivalent protons, whereas in all the other species observed two non-equivalent protons are involved. The origin of the protons is discussed in the light of the direct hydrogen-transfer mechanism implicated earlier for the enzyme. It is concluded that the proton derived from the substrate is located at least 3å from the molybdenum atom with which it interacts.


Complex-formation between reduced xanthine oxidase and purine substrates demonstrated by electron paramagnetic resonance. The origin of the Rapid molybdenum electron-paramagnetic-resonance signals, which are obtained on reducing xanthine oxidase with purine or with xanthine, and whose parameters were measured by Bray & Vänngård (1969), was studied. It is concluded that these signals represent complexes of reduced enzyme with substrate molecules. Xanthine forms one complex at high concentrations and a different one at low concentrations. Purine forms a complex indistinguishable from the low-concentration xanthine complex. There are indications that some other substrates also form complexes, but uric acid, a reaction product, does not appear to do so. The possible significance of the complexes in the catalytic cycle of the enzyme is discussed and it is suggested that they represent substrate molecules bound at the reduced active site, waiting their turn to react there, when the enzyme has been reoxidized. Support for this role for the complexes was deduced from experiments in which frozen samples of enzyme-xanthine mixtures, prepared by the rapid-freezing method, were warmed until the signals began to change. Under these conditions an increase in amplitude of the Very Rapid signal took place. Data bearing on the origin of the Slow molybdenum signal are also discussed. This signal disappears only slowly in the presence of oxygen, and its appearance rate is unaffected by change in the concentration of dithionite. It is concluded that, like other signals from the enzyme, it is due to Mo(v) but that a slow change of ligand takes place before it is seen. The Slow species, like the Rapid, seems capable of forming complexes with purines.


The distribution of vitamin D3 metabolites in human serum and tissues.


The metabolism of 4-hydroxypyridine by Agrobacterium sp.: a new ring cleavage of the pyridine nucleus.


Studies in vitro on the effects of 1H,2H,4H(5H)-octafluorocyclohexane and 1H,4H(2H)-nonafluorocyclohexane on enzymes and organelles. A comparison has been made of the effect of 1H,2H,4H(5H)-octafluorocyclohexane, which is highly toxic (LD(50) 17mg./kg. in rats), and of 1H,4H(2H)-nonafluorocyclohexane, which is relatively non-toxic (LD(50)>440mg./kg. in rats), on the respiration of rat liver homogenates and mitochondria in vitro. 1H,2H,4H(5H)-Octafluorocyclohexane strongly inhibited the respiration of both homogenates and mitochondria, but neither compound had any significant effect on glycolysis or on glutamate dehydrogenase or NADH-cytochrome c reductase activity. 1H,2H,4H(5H)-Octafluorocyclohexane, however, caused a very marked inhibition of cytochrome oxidase activity, causing an almost complete lesion in this region of the respiratory chain. 1H,4H(2H)-Nonafluorocyclohexane was without effect in this respect. A marked decrease in turbidity of mitochondrial suspensions at 520nm. was caused by addition of both compounds, the effect being greater with 1H,2H,4H(5H)-octafluorocyclohexane. ATP, Mg(2+) and bovine serum albumin did not reverse these changes. Mitochondrial adenosine triphosphatase activity was increased twofold by the toxic compound, but only slightly by the non-toxic compound. Electron-microscopic examination of mitochondria treated with 1H,2H,4H(5H)-octafluorocyclohexane revealed gross morphological damage, whereas the effect of 1H,4H(2H)-nonafluorocyclohexane appeared to be merely to cause swelling. The results obtained account, to some extent at any rate, for the toxic effects of 1H,2H,4H(5H)-octafluorocyclohexane.


Multiple light-induced reactions of cytochromes b and c in Rhodopseudomonas spheroides. Illumination of chromatophore preparations from Rhodopseudomonas spheroides causes the oxidation of a cytochrome c and a slight oxidation of a cytochrome b with a maximum at 560nm. When illuminated in the presence of antimycin A the oxidation of cytochrome c was more pronounced and cytochrome b(560) was reduced; the dark oxidation of cytochrome b(560) was biphasic in the presence of succinate, but not in the presence of NADH, a less effective reductant. Split-beam spectroscopy showed that, in addition to the reduction of cytochrome b(560), another pigment with maxima at 565 and 537nm. was reduced and was more rapidly oxidized in the dark than cytochrome b(560). This pigment, tentatively identified as cytochrome b(565), was also detected in spectra at 77 degrees k, after brief illumination at room temperature; the maxima at 77 degrees k were at 562 and 536nm. In the absence of antimycin A, light caused a transient reduction of cytochrome b(565) and an oxidation of cytochrome b(560). Dark oxidation of b(565) was rapid, even in the presence of antimycin A and succinate. Difference spectra, at 77 degrees k, of ascorbate-reduced minus succinate-reduced chromatophores or of anaerobic succinate-reduced minus aerobic succinate-reduced chromatophores suggested that two cytochromes c were present, with maxima at 547 and 549nm. When chromatophores frozen at 77 degrees k were illuminated both these cytochromes c were oxidized, indicating a close association with the photochemical reaction centre. A scheme involving two reaction centres is proposed to explain these results.


The importance of alpha-glycerophosphate oxidase in oxidation of extramitochondrial reduced nicotinamide-adenine dinucleotide in vertebrate and insect muscle.


The effects of calcium ions on the activites of hexokinase, phosphofructokinase and fructose 1,6-diphosphatase from vertebrate and insect muscles.


Meningeal tumors induced in calves with the bovine cutaneous papilloma virus.


Primary tumors in the CNS of carnivores.


Organ-culture propagation of infectious canine hepatitis virus.


Armour-Baldwin tools up for stockpiling of clostridium perfringens antitoxin to meet emergency needs.


Specificity and evolutionary divergence of the antigenic structure of the polypeptide chain elongation factors. Antisera have been prepared against two electrophoretically homogeneous "polypeptide chain elongation factors," T and G, from Escherichia coli. Inactivation and precipitation tests showed that these two fractions were antigenically distinct with no cross-reaction. The immune inactivation curve of G factor from E. coli was distinguishable from that of G factor from Pseudomonas fluorescens. Mammalian factors were not inhibited by antibody directed against the E. coli T and G factors. By Ouchterlony diffusion tests, the antisera also detected significant antigenic variability among different bacterial species. It is concluded that the factors have undergone considerable evolutionary divergence in their antigenic structure.


Immunochemistry of a formamide-extracted antigen from Clostridium perfringens cell walls. The type-specific antigen of a strain of Clostridium perfringens involved in food poisoning was isolated from the cell wall by the use of hot formamide. The antigen appears to consist of polysaccharide or mucopeptide. The formamide extract was shown to be heterogeneous by gel filtration on Sephadex G-200. The serologically active fraction contained about 25% of the amount of protein present in the original formamide extract. Hexosamine, acetyl groups, and carbohydrate also were detected. The formamide extract showed a high degree of serological activity. The serological activity was increased twofold on Sephadex gel filtration.