Effect of an intraventricular injection of cyclic AMP on plasma prolactin and LH levels of ovariectomized, estrogen-treated rats.


No "ultra-short feedback mechanism" for ACTH.


Effect of neonatal hydrocortisone on corticosteroid circadian peroidicity, responsiveness to ACTH and stress in prepuberal and adult rats.


In vivo effect of estradiol benzoate on the accumulation of adenosine 3',5'-cyclic monophosphate in the rat hypothalamus.


The epidemiology, pathogenesis and control of endemic goitre and cretinism in New Guinea.


Goitre and cretinism in the high Himalayas.


In vivo blockade of the estradiol-binding-protein (EBP) by clomiphene citrate in human breast cancer.


In vivo blockade of the estradiol-binding-protein (EBP) by clomiphene citrate in human breast cancer. The effect of clomiphene citrate given in vivo upon the in vitro uptake of labeled estradiol (tritiated-E2) was investigated in a 60-year-old patient with breast cancer who had had a mastectomy 10 months earlier followed by radiotherapy.  Multiple subcutaneous metastatic nodules and enlargement of the liver were present but bone metastases could not be shown.  A biopsy from a subcutaneous nodule, taken prior to present treatment, showed 86 fmol estradiol binding sites per mg of cytoplasmic protein with a dissociation constant of the estradiol-estradiol binding protein interaction of 2.8 X 10 -10  M.  The patient was treated with 200 mg clomiphene citrate daily.  Subjective symptoms improved and a reduction of skin nodule size and of liver enlargement followed.  The serum enzymes alkaline phosphatase, nucleotidase, and phosphohexoseisomerase were diminished.  A 2nd biopsy taken at Day 26 of treatment with clomiphene citrate showed complete inhibition of labeled estradiol tritiated-E2 uptake by the cytosol protein.  This finding is thought to show the absence of free binding sites after clomiphene citrate therapy.  Microscopic studies of biopsy material were unchanged.  These results are thought to be the first to record human in vivo inhibition of trititated-E2 uptake for EBP by an antiestrogen compound, although similar in vitro observations have been made in human tumor specimens.  There is thought to be a potential value of antiestrogenic agents, alone or with inhibitors of prolactin secretion, to replace endocrine ablations and to predict the response to endocrine therapy.


Differences in the urea-extracted or fibrous proteins of mouse epidermis at various stages of malignant transformation.


Sedimentation of bacteria with polyethylene glycol.


Quantitative measurement in vivo of lipiodol in lungs especially in connection with lymphography.


99mTc-Sn-pyrophosphate complexes, an investigation of its possible structures.


Synthesis and properties of some cyclic AMP alkyl phosphotriesters. Cyclic AMP was converted to its phosphotriesters according to the classical approach of phosphate activation with a sulfonyl chloride, followed by esterification with an alcohol. The methyl, ethyl, propyl, butyl and cetyl triesters were prepared, and some of their physical-chemical properties determined. Alkaline hydrolysis of these alkyl phosphotriesters resulted predominantly in ring opening. On the other hand, nucleophilic attack by thiourea led to the formation of cAMP as the main product. The conclusion can be drawn from these results that cAMP phosphotriesters could serve as suitable storage forms of cAMP, and cyclic triesters may be the best vehicle of transporting nucleotides through biological membranes.


Histochemical study on nucleoside phosphatase activity in rabbit brain following circulatory hypoxia.


The nucleotide sequence of phenylalanine tRNA from Mycoplasma sp. (Kid). The nucleotide sequence of Mycoplasma sp. (Kid) phenylalanine tRNA was determined to be pG-G-U-C-G-U-G-U-A-G-C-U-C-A-G-U-C-G-G-D-A-G-A-G-C-A-G-C- A-G-A-C-U-G-A-A-m(1)G-C-Psi-C-U-G-C-G-U-m(7)G-U-C-G-G-C-G-G-U-Psi-C-A-A-U-U-C-C-G-U-C-C-A-C-G-A-C-C-A-C-C-A(OH). It is characterized by the absence of ribothymidine and the presence of only few modified nucleotides.


Recent trends in tuberculosis care.

Recent trends in tuberculosis care.


Nursing care of patients with asthma.

Nursing care of patients with asthma.


Urinary testosterone response to corticotrophin and dexamethasone in hirsute women.


Diurnal variation in the response to ACTH.


Measruement of immunological function in man: interaction between virus and human leukocytes.


Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary.


Nature of adipocyte response to insulin control of lipolysis.


Primary photochemical reactions in chloroplast photosynthesis.


In vivo investigations on microcirculatory disturbances induced by crenated erythrocytes following norepinephrine application.


Neonatal hepatitis typ B--a three-year follow-up.


Clinical aspects of cytomegalovirus infection in kidney-graft recipients.


Acute necrotizing herpes simplex virus encephalitis--diagnostic problems.


Use of BCG as an immunostimulant in the surgical treatment of carcinoma of the lung.


Pulmonary calcification following smallpox handler's lung.


Intrinsic activation of prothrombin potentiated by celite and reduced by kaolin.


An antiproteolytic and antifibrinolytic preparation obtained from the potato by means of chromatography on SE-sephadex C-50.


Hepatitis, encephalitis, and meningitis.


Effect of vinblastine on neurohypophysial and adenohypophysial microtubules.


Radiation effects on testes. IV. Studies on succinic dehydrogenase, cytochrome oxidase, adenosine triphosphate and physical behaviour of mitochondria following localized gamma irradiation.


Effects of anterior pituitary hormones on hepatic corticosterone metabolism in rats.


Receptor progesterone complex in the nuclear fraction of the rat uterus: demonstration by 3H-progesterone exchange.


Ten-year experience with maintenance hemodialysis for chronic uremia.


Aldosterone response to angiotensin II in patients with terminal renal failure and after bilateral nephrectomy.


Surface-immobilized prostaglandin as a platelet protective agent.


High efficiency oxford type oxygenator based on hemodialysis and transmembrane catalysis of hydrogen peroxide.


Crystalloid inclusions in hepatocyte mitochondria of dogs treated with levamisole.


Aortic body tumor in a duck.

Aortic body tumor in a duck.


Observations on the kidneys and urine of the wild Norway rat, Rattus norvegicus.


Ultrastructural observations of chronic progressive nephrosis in the Sprague-Dawley rat.


Pancreatitis associated with an adenovirus in a rhesus monkey.


Immunosuppressive effect of infectious bursal agent on vaccination against Newcastle disease.


Isolation of Mycoplasma agalactiae var bovis and infectious bovine rhinotracheitis virus from an outbreak of mastitis in France.


Isolation of M bovoculi from eye lesions of cattle in the Ivory Coast.


Virus infections of horses at Newmarket, 1972 and 1973.


Louping-ill virus in red grouse in Scotland.


Chemistry of the hypothalamic releasing factors. Studies on structure-function relationships in TRF and LRF.


Virus involvement in equine paresis.

Virus involvement in equine paresis.


Bacteriological control in the processing of poultry.


Synergistic effect of ferric oxide on dimethylnitrosamine carcinogenesis in the Syrian golden hamster.


Letter: Problem of the coughing horse.

Letter: Problem of the coughing horse.


Cluster orbital theory based on Mössbauer effect investigations of the (iron)4-sulfur clusters of Clostridium pasteurianum ferredoxin.


Charge-transfer interactions between nucleobases and metal ions: ESR and optical absorption studies.


The role of adenine and guanine nucleotides in the activity and response of adenylate cyclase systems to hormones: evidence for multi-site transition states.


The significance of insulin receptors in fat cells.


Insulin controlling calcium distribution in muscle and fat cells.


Receptor transformation in estrogen action.


Glucocorticoid binding proteins and their biological significance.


Androgen transport mechanisms in the testis and epididymis.


Principles of hormone action: the problem of molecular linguistics.


Alterations in hormone responsiveness of hepatic adenylate cyclase during ontogenesis and oncogenesis.


Metabolic regulation of the response of the glycogen phosphorylase system to hormones in rat heart and diaphragm.


Growth hormone and cyclic AMP in rat diaphragm muscle.


Molecular events in the action of insulin on cell metabolism. The significance of cyclic AMP dependent protein kinases.


The May-Hegglin anomaly. Further studies on leukocyte inclusions and platelet ultrastructure.


Autopsy study of primary liver carcinoma in Buenos Aires, Argentina.


Retrospective study on the evaluation of diagnostic procedure for hepatoma in patients with cirrhosis of the liver.


Ficoll density separation of enzymatically isolated rat liver cells.


Proceedings: The effect of ACTH and diazepam, administered to infant rats on the body-growth curve and some endocrine parameters measured in adult age.


Proceedings: Long term behavioural effects of diazepam and ACTH, administered early in life.


Blocking effects of a topical anesthetic composition containing Ketocaine on cutaneous C receptor responses in alert man.


Proceedings: Permanent effects of repeated administration of ACTH and diazepam in early postnatal period upon the dynamics of excitation and inhibition during habituation.


Effect of heat denaturation on glycerinated muscle fibers as studied by spin label Epr.


Contribution to the histoenzymology of subacute sclerosing panencephalitis.


Cellular monstrosity in embryonic neuronal neoplasm produced by human adenovirus in rats.


Surface structures of the human vestibular sensory regions.


Hormone binding and activation in the testis and epididymis.


Increased cardiovascular reactivity in renal infarction hypertension.


Effects of sodium fluoride treatment on adrenal function in the rat.


External factors affecting parasternal scintigraphy with technetium-99m sulfide colloid. An investigation in the rabbit.


Adrenergic innervation in the rabbit cochlea.


Extracardiac rhabdomyoma. Light and electron microscopic studies of two cases in the mandibular area, with a review of previous reports.


Pneumography in paraventricular and intraventricular tumours of the posterior fossa.


Abnormalities of myopathic subcellular fractions: composition and function.


Synaptic vesicles in the cochlea.

Synaptic vesicles in the cochlea.


Viral myocarditis in animals.

Viral myocarditis in animals.


The role of vitamin C in the treatment of acute infections of the upper respiratory pathways.


Inhibition of the immune response to pertussis vaccine during Plasmodium berghei yoelii infection in mice. Mice infected with Plasmodium berghei yoelii responded poorly to pertussis vaccine when administered at peak parasitemia. This was shown by serum agglutinin titers and lack of protection against intracerebral challenge with virulent Bordetella pertussis.


The diagnosis and treatment of the hyperlipoproteinemias: emphasis on Types IIa, IIb and IV.


Biochemistry of the peroxisome in the liver cell.


Genetic control of serum esterases in day-old pigs.


Comparative study of red-cell enzyme polymorphism in the pika and the rabbit.


Preparation and properties of mitochondrial cytochrome P-450 from bovine adrenal cortex.


The detection of different states of the P-450 cytochromes in adrenal mitochondria: changes induced by ACTH.


Effect of ACTH on adrenal mitochondrial cytochrome P-450 in the rat.


Control of substrate flux and adrenal cytochrome P-450.


Cholesterol metabolism in the adrenal cortex: studies on the mode of action of ACTH.


Testicular cytochrome P-450 and iron-sulfur protein as related to steroid metabolism.


The mitochondrial role in hepatic cell mixed-function oxidations.


Electron paramagnetic resonance spectroscopy as a tool to study the mechanism of electron transfer.


The determination of quartz in respirable dust samples by infrared spectrophotometry--I: The potassium bromide disc method.


The determination of quartz in respirable dust samples by infrared spectrophotometry--II: The direct analysis of quartz deposited on filters.


A micro/macrotechnique for the evaluation of ironfoundry dust samples.


Immunosuppressive therapy in neurological diseases.


Angiography of the female breast.

Angiography of the female breast.


Interaction of purulent material with antibiotics used to treat Pseudomonas infections. To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material. Carbenicillin activity was not significantly altered by incubation with pus. Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 mug/ml to 3 to 6 mug/ml. One milliliter of purulent sediment bound more than 700 mug of gentamicin and 1,500 mug of polymyxin B or colistin sulfate. This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution. Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.


Membrane concentration of infectious bovine rhinotracheitis virus from water. A membrane adsorption procedure was used to concentrate infectious bovine rhinotracheitis virus from 1-liter quantities of distilled water. Cellulose nitrate membrane filters (0.45-mum pore size) efficiently adsorbed this herpesvirus from water, and virus was recovered from the membrane by elution with 10 ml of fetal calf serum during sonic treatment. The average recovery rate was 70%.


Growth of foot-and-mouth disease virus in the different layers of bovine omasum in suspended cultures. When suspended cultures of bovine omasum were cultured without agitation, the epithelium soon degenerated and foot-and-mouth disease virus multiplied mainly in the corium cells. Five days of preincubation were needed to reach a population of corium cells that could yield virus at a titer of 10(6.70) to 10(6.95) mean tissue culture infective doses per ml. The virus was freely released from the cells into the medium only when the degenerated epithelium was removed from the subepithelial tissue prior to virus inoculation. In agitated cultures, the viability of the epithelium was retained, the virus multiplied in all the layers of the epithelium and was freely released into the medium, and a virus titer of 10(6.95) mean tissue culture infective doses per ml was obtained without preincubation. The omasal laminae could be separated along the line of apposition of the two mucous membranes of the organ. The virus yield from these thin separated membranes was 0.5 to 1.0 log higher than that obtained from nonseparated laminae.


Automated microtransfer technique for the assay of poliovirus- and mumps virus-neutralizing antibodies. Use of an automated apparatus to quantitate mumps virus- and poliovirus-neutralizing antibody is described. The automated titration equipment affords savings in effort, time, and reagents in conducting large-scale surveys for the determination of mumps- and poliovirus-neutralizing antibodies. This technique has been found to be reproducible and gives results comparable to other antibody assay methods.


Growth of Pseudomonas C on C1 compounds: continuoous culture. Pseudomonas C was grown in continuous culture on methanol, formaldehyde, or formate as sole carbon source. On methanol mu(max) = 0.49/h and yield constant (Y) = 0.54; on formaldehyde and on unsupplemented media, mu(max) was about 0.2/h and Y was 0.15, whereas addition of p-aminobenzoic acid, folic acid, serine, or glycine to the medium raised Y to about 0.26 to 0.29, and addition of p-aminobenzoic acid, folic acid, serine, nicotinamide adenine dinucleotide, and Tween 80 raised the yield to 0.35. On formate and on unsupplemented media, mu(max) = 0.2/h and Y = 0.02, whereas addition of 0.1 mM p-aminobenzoic acid increased mu(max) to about 0.47 and Y to about 0.23. At low cell concentrations or growth rates a beneficial effect of CO(2) was observed. Formaldehyde or formate, when added together with methanol, were utilized simultaneously with the methanol.


Proceedings: Dermal eccrine cylindroma, epithelioma adenoides cysticum of Brooke, and ecrine spiradenoma.


In vitro neuromuscular effects of delta9-trans-tetrahydrocannabinol (THC).


Interfering and interferon-inducing capacity of NDV. II. Relationship between pyrogenic, interfering, and interferon-inducing activities.


Interfering and interferon-inducing capacity of NDV. I. Quantitative analysis and physicochemical characteristics.


Properties of SV 40 rescued from actinomycin D-sensitive and actinomycin D-resistant transformed hamster cells. II. Transforming capacity, oncogenicity, TSTA induction.


Surface membrane antigens of PY-3T3 mouse fibroblasts.


Assay and antigenic interrelationships of the recently isolated bovine herpesviruses, DN599, FTC, and V11.


Polypeptides associated with the 250 S mengovirus-induced RNA polymerase structure.


Electron microscopy of murine cytomegalovirus: development of the virus in vivo and in vitro.


Studies on a paramyxovirus isolated from a finch.


Comparison of the structural polypeptides of four avian paramyxoviruses.


Inhibitors of foot-and-mouth disease virus. I. Effect of EDTA, temperature, and interferon on the viral growth cycle.


Studies with divinyl ether-maleic anhydride and foot-and-mouth disease vaccines in swine.


Carcinoma of Müllerian vestigial origin: report of a case.


Luteoma in pregnancy.

Luteoma in pregnancy.


Regulation of hepatic lipogenesis by plasma free fatty acids: simultaneous studies on lipoprotein secretion, cholesterol synthesis, ketogenesis and gluconeogenesis. 1. An inverse logarithmic relationship was found between lipogenesis and the concentration of serum free fatty acids perfusing the rat liver. 2. Increased concentrations of serum free fatty acids did not alter cholesterol synthesis, triglyceride secretion or increase gluconeogenesis. 3. No direct relationship was found between ketogenesis and either lipogenesis or gluconeogenesis.


The influence of osmolarity on the reduction of exogenous cytochrome c and permeability of the inner membrane of Jerusalem artichoke mitochondria. The stimulation of succinate-cytochrome c reductase in Jerusalem artichoke mitochondria by lowering osmolarity was found to be associated with conformational changes in the inner membrane rather than with rupture of the outer membrane. This conclusion is based on the following evidence. (1) When the activation of succinate dehydrogenase was measured by using either K(3)Fe(CN)(6) or exogenous cytochrome c as an electron acceptor, electron flow to cytochrome c was always 7% of that to K(3)Fe(CN)(6) throughout the activation process. (2) The rate of exogenous cytochrome c reduction by succinate and NADH was directly related to the maximum rate of electron flow as determined by oxygen utilization. These two observations are not consistent with the low rate of succinate-cytochrome c reductase being limited by a permeability barrier at the outer membrane. (3) In addition to stimulating the succinate-cytochrome c reductase, lowering the osmolarity caused simultaneous changes in the permeability of the inner membrane to ferricyanide and NADH. The data show that lowering the osmolarity results in progressive changes in the permeability of the inner membrane. The first change detected was an increased permeability to K(3)Fe(CN)(6), then a simultaneous increase in accessibility of the respiratory chain to exogenous cytochrome c and an increased permeability to NADH, followed finally by rupture as measured by the release of malate dehydrogenase.


A rapid, specific protocol for determination of available androgen receptor sites in unfractionated rat ventral prostate cytosol preparations.


Equilibrium relations between the oxidation-reduction reactions and the adenosine triphosphate synthesis in suspensions of isolated liver cells. 1. The redox state of cytochrome c, cytochrome a and the mitochondrial NAD couple, and the phosphorylation state of the adenine nucleotides, were measured in suspensions of isolated rat liver cells. 2. The DeltaG for the transfer of two electrons from the mitochondrial NAD to the cytochrome c couple is calculated to be 104kJ (24.8kcal). 3. The DeltaG associated with the synthesis of ATP at the measured phosphorylation state is calculated to be 95kJ (22.7kcal)/2mol of ATP. 4. The near equality of DeltaG of the electron-transport process and DeltaG required for ATP synthesis indicates near-equilibrium between the mitochondrial respiratory chain and the extramitochondrial phosphorylation state. 5. The existence of near-equilibrium in the coupled reactions implies that the respiratory activity depends on the ratio [ATP]/[ADP][P(i)] and not on the concentrations of the individual reactants. 6. If the overall system of oxidative phosphorylation is at near-equilibrium, all intermediary reactions must also be at equilibrium. Hence if the intramitochondrial and extramitochondrial phosphorylation states are indeed different, it follows that any differences in the activities of ATP, ADP and P(i) must be coupled to ion gradients and/or potentials across the inner mitochondrial membrane in such a way that translocation occurs without loss of free energy. 7. The metabolic state of the mitochondria in the cell can be defined by the turnover number of the cytochromes, the cytoplasmic phosphorylation state, and the oxidation-reduction potential of the NAD couple, rather than by the availability of ADP, substrate and O(2).


EPR studies on a Hipip type iron-sulfur center in the succinate dehydrogenase segment of the respiratory chain.


EPR studies on two ferredoxin-type iron-sulfur centers in reconstitutively active, inactive, and reactivated soluble succinate dehydrogenases.


The presence of phospholipids and diglyceride kinase activity in microtubules from different tissues.


Triplet states in photosynthesis.

Triplet states in photosynthesis.


Activation of adrenal sterol ester hydrolase by dibutyryl cAMP and protein kinase.


Regulation of human skin collagenase activity by hydrocortisone and dexamethasone in organ culture.


Editorial: The true task of the physiatrist.


The virological monitoring of water. II. Sea water.


Has alcohol psychotomimetic and convulsant properties?


Brain oedema: an experimental model.

Brain oedema: an experimental model.


Heterogeneity in Herpes simiae (B virus) and some antigenic relationships in the herpes group.


Mesangial localization of immune complexes in experimental canine adenovirus glomerulonephritis.


Pathogenesis of cupping of the optic disc.


Mitochondrial function under hypoxic conditions: the steady states of cytochrome alpha+alpha3 and their relation to mitochondrial energy states.


Biochemical and biophysical studies on cytochrome c oxidase. XIX. An EPR study of the photodissociation of carboxycytochrome c oxidase in the presence of azide.


Components of cytochrome c oxidase detectable by EPR spectroscopy.


Kinetics of appearance and disappearance of light-induced EPR signals of P700+ and iron-sulfur proteins(s) at low temperature.


Enzymatic radioiodination of porcine thyroid-stimulating hormone.


The corrected nucleotide sequence of valine tRNA from baker's yeast.


Preparation of (1-3H) polyprenyl pyrophosphates.


Amyloid polyneuropathy, type II (Indiana, or Rukavina type).


X-linked cataract: two pedigrees.

X-linked cataract: two pedigrees.


Ectopia lentis as part of the Marfan syndrome.


Genetic forms of pituitary dwarfism.

Genetic forms of pituitary dwarfism. Pituitary dwarfism represents a genetically heterogeneous group of disorders which may be classified on the basis of: associated developmental anomalies or degenerative disease; deficiency of, or peripheral insensitivity to HGH; the number of deficient hormones; the associated metabolic disturbances; and the mode of inheritance. Hereditary forms of pituitary dwarfism include: congenital absence of the pituitary, panhypopituitary dwarfism (autosomal and X-linked recessive forms), isolated HGH deficiency (Types I and II), Laron type of dwarfism, and peripheral unresponsiveness to HGH (the African Pygmies).


Recognition of ectopic hormone syndromes produced by tumors. Ectopic production of polypeptide hormones by tumors of nonendocrine tissues can serve as a clue to diagnosis of the tumor and as a focus for management of the patient with cancer. In the differential diagnosis of syndromes of endocrine hyperfunction, the ectopic hormone syndromes have achieved an increasingly prominent position. Available evidence on the properties of ectopic ACTH, MSH, parathyroid hormone, erythropoietin, gonadotropins, and thyrotropin is consistent with the unifying hypothesis of genetic derepression.


The dental defects of vitamin D-resistant rickets. Clinical, roentgenographic and morphologic features of teeth from patients with vitamin D-resistant rickets are described based on a study of 28 teeth from 5 patients. Clinically normal teeth become symptomatic and develop roentgenographic evidence of periapical infection. The exposed dentin is vulnerable to microbial invasion because of a defective globular-type calcification as seen in both ground and decalcified sections. The changes are distinctive and pathognomonic, but the effects of therapy (vitamin D) have not yet been ascertained.


Inherited defects in tooth structure.

Inherited defects in tooth structure.


Vitamin D-resistant rickets with dental abnormalities.


Micrognathia, hypodontia and syndactyly.


Basal cell nevus syndrome: normal responsiveness to parathyroid hormone. The basal cell nevus syndrome is an autosomal dominant trait which includes among its features jaw cysts, basal cell carcinomas, ectopic calcification and skeletal anomalies. It had been previously reported that such persons have had "resistance" to parathyroid hormone. In the current study, six persons with this syndrome from two families had a normal response to parathyroid hormone as measured by changes in serum calcium and phosphate and urinary excretion of calcium, phosphate and cyclic 3',5'-adenosine monophosphate. These results do not support the previous reports of "resistance" to parathyroid hormone in this syndrome.


Leopard syndrome in mother and daughter.


Focal dermal hypoplasia (Goltz syndrome): a follow-up.


Nevus sebaceus of Jadassohn with associated syringocystadenoma papilliferum.


Epidermolysis bullosa dystrophica.

Epidermolysis bullosa dystrophica.


Sturge-Weber syndrome with Klippel-Trénaunay-Weber syndrome.


Klippel-Trénaunay-Weber syndrome.

Klippel-Trénaunay-Weber syndrome.


Turban tumors (cylindromatosis).

Turban tumors (cylindromatosis).


Multiple trichoepithelioma and cylindroma.


Effect of tropolone on vascular sympathetic neuroeffector transmission.


Manganese ions and synaptic transmission in the superior cervical ganglion of the cat. 1 In the perfused superior cervical ganglion of the cat manganese ions (2.7 - 4.6 mM) caused a block of synaptic transmission and reduced the output of acetylcholine.2 Calcium ions (8.4-10.5 mM) relieved the synaptic block produced by manganese and partially restored the acetylcholine output.3 The presence of manganese also reduced the sensitivity of ganglion cells to injected acetylcholine.4 Both effects of manganese were completely reversible.


Dissociation of cardiac inotropic and adenylate cyclast activating adrenoceptors. 1 At higher temperatures, near the physiological range for mammals and nonhibernating frogs, the adrenoceptors for both inotropic responses to adrenaline and noradrenaline and for cyclic 3',5'-adenosine monophosphate (cyclic AMP) production in rat and frog isolated heart preparations, had typical beta characteristics. Phenoxybenzamine potentiated the inotropic response and the accumulation of cyclic AMP; conversely, propranolol inhibited the two responses.2 When the ambient temperature was reduced, the adrenoceptors mediating cyclic AMP production changed very little; they were blocked as effectively as at the higher temperature by propranolol and were not blocked by phenoxybenzamine. However, the adrenoceptors mediating the inotropic response were markedly changed by the decrease in temperature; phenoxybenzamine now inhibited this response and the inhibitory activity of propranolol was reduced about tenfold.3 These results indicate that the adrenoceptors that mediate cardiac inotropic responses at physiological temperatures are distinct from those that mediate the production of cyclic AMP, and that the activation of adenylate cyclase and the accumulation of cyclic AMP are probably not intermediate steps in cardiac inotropic responses to catecholamines.


The nature of the binding between LSD and a 5-HT receptor: a possible explanation for hallucinogenic activity. 1 (+)-Lysergic acid diethylamide (LSD) mimicked 5-hydroxytryptamine (5-HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora.2 Unlike 5-HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing.3 Both 5-HT and tryptamine prevented LSD from acting on the glands.4 LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine).5 The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system.


Pharmacological observations on the hypotensive action of extracts of teleost fish Urophyses (urotensin I) in the rat. 1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat.2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours).3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin.4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited.5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone.6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium).7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia.


The effects of bretylium and guanethidine on catecholaminergic transmission in an invertebrate. 1 Secretory potentials produced by stimulation of the salivary duct nerves were recorded intracellularly from cockroach isolated salivary glands. The secretory potential normally consisted of a 40-80 mV hyperpolarization of the gland cell.2 Bretylium (0.1-1 mM) reduced the amplitude of the secretory potential without affecting the response of the gland to dopamine (0.25-1 muM). In addition, bretylium caused an increase in the frequency of miniature secretory potentials and the appearance of nerve terminal action potentials.3 Guanethidine (1 mM) reduced the response to nerve stimulation without depressing the sensitivity of the salivary gland to dopamine (0.25-0.5 muM) and without causing an increase in the occurrence of miniature potentials. Higher concentrations (4-5 mM) completely eliminated secretory potentials but also reduced the sensitivity of the gland cell to dopamine.5 These results indicate a presynaptic depression of the secretory potential by both bretylium and guanethidine. It is suggested that, in this system, bretylium acts by depolarizing the nerve terminal while guanethidine does not.


The facilitatory actions of 5-hydroxytryptamine and bradykinin in the superior cervical ganglion of the rabbit. 1 The effects of 5-hydroxytryptamine (5-HT) on ganglionic transmission and on intrinsic modulation of transmission have been re-examined and compared with the effects of bradykinin by means of electrophysiological techniques.2 Early facilitation, which is maximal 40-75 ms after a conditioning stimulus, was considerably enhanced by 5-HT. This enhancement was concentration-dependent, the threshold concentration lying between 0.1 and 1 muM. With concentrations of 5-HT 10 muM or greater, there was some depression of the Sa response to the conditioning stimulus.3 5-HT reduced or abolished the inhibition of a test response induced by a conditioning response 100-300 ms earlier. Facilitation was observed at these intervals at concentrations of 5-HT of 25 muM or greater.4 Late facilitation, which is maximal 700-2000 ms after a conditioning stimulus, was increased by 5-HT, but the effect was not as great as on early facilitation and was not always seen with a concentration of 1 muM.5 Bradykinin reduced early facilitation but increased the amplitude of the transmitted action potential in response to a single stimulus. The threshold concentration producing these effects was between 1 and 2 muM.6 5-HT produced a rapid depolarization of the ganglion cell membrane which was followed by an after-hyperpolarization.7 Bradykinin either produced no measurable change in ganglion cell resting potential or only very small, transient depolarizations.8 The depression of transmission, enhancement of intrinsic facilitation and the depolarization of the ganglion cell membrane induced by 5-HT may indicate more than one mode of action of this amine at the ganglionic synapse.


Specific supersensitivity of smooth muscle to angiotensin II after nephrectomy. 1 The dose-response curves for angiotensin, 5-hydroxytryptamine and carbachol were obtained on rat uterus and colon excised 24 h after a bilateral nephrectomy or a sham operation.2 There was a shift to the left in the dose-response curves to angiotensin of organs from nephrectomized animals. Dose-response curves to 5-hydroxytryptamine and carbachol were not affected by nephrectomy.3 The interaction of the two competitive antagonists (1-Asn, 5-Ileu, 8-Ala)-angiotensin II and (1-Asn, 5-Ileu, 8-Ileu)-angiotensin II with angiotensin II receptors was tested in control and nephrectomized organs. There was a decrease of the K(I) values in colon muscle after nephrectomy.4 In conclusion, nephrectomy produces a specific supersensitivity to angiotensin that seems to be due to a change in the structure of angiotensin receptors, at least in colon smooth muscle. This increase in sensitivity may be the result of the elimination of a tropic factor that acts on angiotensin receptor sites.


Proceedings: Regulation of the cyclic AMP concentration in chick brain by beta-adrenoreceptors and histamine H2 receptors.


Modification of responses to sympathetic nerve stimulation by the renin-angiotensin system in rats. 1 Angiotensin I (AI) and AII elicited a dose-dependent potentiation of contractions by rat vas deferens produced by low frequency nerve stimulation without enhancing the contraction produced by exogenous noradrenaline. The AII-induced presynaptic potentiation was blocked by the specific antagonist cysteine(8)-AII.2 The vasoconstrictor response to periarterial stimulation of rat isolated perfused kidney was potentiated by AII and there was a lesser enhancement of the effect of exogenous noradrenaline.3 The response to stimulation of complete sympathetic outflow from the spinal cord to blood vessels in the pithed rat was enhanced by angiotensin or vasopressin in direct proportion to the increase in prestimulus muscular tone. The blood pressure in the pithed rats is primarily maintained by the renin-angiotensin system since the converting-enzyme inhibitor (SQ-20881) or bilateral nephrectomy caused further substantial lowering of systemic blood pressure after spinal cord destruction and after treatment with curare and atropine.


A modulating role of prostaglandins in contractions of the guinea-pig ileum. 1 The role of prostaglandins in contractions of the guinea-pig ileum evoked either directly by acetylcholine or indirectly by angiotensin and by coaxial stimulation has been investigated.2 Prostaglandin E(2) in low concentration (6 nM) slightly augmented both types of contraction. Indomethacin, an inhibitor of prostaglandin synthesis, markedly reduced the indirectly evoked contractions but did not affect contractions in response to acetylcholine. The addition of prostaglandin E(2) to the preparation treated previously with indomethacin restored the effect of indirect stimulation.3 The pretreatment of the preparation with guanethidine or alpha-methyl-p-tyrosine prevented the inhibitory effect of indomethacin on indirectly evoked contractions. Prostaglandin E(2) addition to such preparations considerably augmented both types of contraction.4 The stimulation of non-cholinergic, non-adrenergic inhibitory nerves in the taenia coli and ileum preparations evoked hyperpolarization and relaxation of the preparations followed by action potentials and contraction. These responses were not changed by indomethacin pretreatment and prostaglandin E(2), but rebound contraction was sometimes augmented by the prostaglandin.5 Two mechanisms for the effects of prostaglandin E(2) are suggested: a direct effect on smooth muscle, and an indirect action through the sympathetic nerves which by release of noradrenaline affect the acetylcholine release from parasympathetic nerve endings.


Proceedings: Cyclic nucleotides and ethanol withdrawal head-twitches in mice.


The vascular contribution to intraurethral pressure.


The effects of anticholinesterases on synaptic transmission through nicotinic and muscarinic receptors in rat sympathetic ganglia in vivo. 1 Stimulation of the entire spinal sympathetic outflow at supramaximal voltage and 25-100 Hz, in the chlorisondamine-treated, pithed, adrenalectomized rat produced a delayed pressor response (late pressor response; LPR).2 The LPR was abolished by phenoxybenzamine, bretylium or a small dose of atropine (25-50 mug/kg), suggesting the involvement of ganglionic muscarinic receptors.3 In the presence of atropine at a dose level (15 mug/kg) which did not influence the LPR, the anticholinesterases physostigmine, neostigmine and Ro 02-0683 but not BW 284C51 markedly enhanced and prolonged the LPR, whereas all of them reduced the pressor responses to AHR-602.4 After blockade of the ganglionic muscarinic receptors with a large dose of atropine (250 mug/kg) the four anticholinesterases did not influence responses to DMPP or noradrenaline and only slightly enhanced responses to preganglionic nerve stimulation at 6 Hz in the absence of chlorisondamine.5 It is concluded that inhibition of butyrylcholinesterase accounts for the enhancement and prolongation of the LPR by anticholinesterases.


Theophylline inhibition of nucleoside transport and its relation to cyclic AMP in skeletal muscle.


Changes in spleen weight, cyclic-AMP content, and serum-corticosterone levels of rats in response to CO2.


Lack of interaction between norepinephrine or histamine and theophylline on cardiac cyclic AMP.


Active bronchial anaphylaxis in the rat.


Effect of ablation of the subfornical organ on water intake elicited by systemically administered angiotensin-II.


Pharmacological studies on active bronchial anaphylaxis in the rat.


The adrenal cortex (excluding aldosteronism).


Mechanisms of lysosomal enzyme release from human leucocytes. III. Quantitative morphologic evidence for an effect of cyclic nucleotides and colchicine on degranulation.


Lactate dehydrogenase of Biomphalaria glabrata (Say, 1818) (Mollusca: Pulmonata) I. Physico-chemical characterization of lactate dehydrogenase of various tissues.


Comparative studies of serum lipoprotein and lipid profiles in subhuman primates.


Disorders of the autonomic nervous system.  Chapter 10.  Sweating.


An evaluation of clinical response to piperazine oestrone sulphate ('Harmogen') in menopause patients.


What form of steroid therapy in severe chronic asthma?


Current concepts in the medical management of metabolic bone disease.


The lung as a chemical filter.

The lung as a chemical filter.


Substituent effects on the pre-steady-state kinetics of oxidation of benzyl alcohols by liver alcohol dehydrogenase.


Escherichia coli ferredoxin, an iron-sulfur protein of the adrenodoxin type.


Structure and synthesis of a lipid-containing bacteriophage. Acyl-chain motion in the PM2 virus membrane.


Comparative morphological and histoautoradiographic study of multiple experimental intestinal tumours.


Hormone-dependent lipolysis in fat-cells from thyroidectomized rats.


Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone.


Oestradiol-17 beta binding proteins in the rat uterus: changes during postnatal development.


Glucagon-receptor interactions in fat cell membranes.


Proliferation of amphibian melanophores in vitro.


Function of the adrenal cortex in obese-hyperglycemic mice (gene symbol ob).


The preparation of, and studies on, free cell suspensions from mouse pancreatic islets.


Suprarenal cortical reserve capacity in kwashiorkor.


The fatty acid pattern of adipose tissue and liver triglycerides according to fat droplet size in liver parenchymal cells of diabetic subjects.


Suprarenal cortical reserve capacity in juvenile diabetes.


Vitamin D dependency or pseudo-vitamin D deficiency rickets.


Herpetic conjunctivitis as an unusual occupational hazard (endoscopists' eye).


Incorporation of 32P into the microsomal fraction of Tritrichomonas foetus.


Nuclear inclusions in the oviduct epithelium of the rat.


Polygraphic study on the nocturnal sleep of children with Down's syndrome and endogenous mental retardation.


Coexistent purulent leptomeningitis and herpes simplex encephalitis: case report with postmortem study.


Lithium ion and affective psychoses.

Lithium ion and affective psychoses.


Carcinogenic effects of low dietary levels of aflatoxin B1 in rats.


Accumulation of ingested sulphite- and sulphate-sulphur and utilization of sulphited proteins by rats.


Regulation of glycogenolysis through changes in intracellular calcium.


Simulation and enhancement of the adipose tissue insulin response by procaine hydrochloride: evidence for a role of calcium in insulin action.


Effect of prolactin and/or testosterone on cyclic AMP in the rat prostate gland.


A direct protein-binding assay for 25-hydroxycalciferol.


Antibody-mediated fusion of FL amnion cells infected with parainfluenza virus type 2.


Differential effects of dibutyryl cyclic AMP on the growth and morphology of an established human lymphocyte line.


Adenyl cyclase-stimulating catecholamines as modifiers of antibody formation.


Lymphocyte plasma membranes. III. Carbohydrate containing antigens of human lymphocytes bound by antilymphocyte sera.


Inhibition of cell-mediated cytotoxicity in the rat by anti-thymocyte serum.


Regulation of membrane changes, differentiation, and malignancy in carcinogenesis.


Influence of intraocularly-injected pineal indoles on PMS-induced ovulation in immature rats.


Plasma lipoproteins and apolipoproteins.


Endogenous agents in primary cell cultures with special reference to latent viruses.


Continuous dilution culture system for studies on gene-enzyme regulation in synchronous cultures of plant cells.


Collagen biology: structure, degradation, and disease.


Expression and detection of endogenous mouse C-type RNA viruses.


Enzyme histochemistry of the olfactory mucosa and vomeronasal organ in the mouse.


Studies on hormone-sensitive lipolytic activity.


Blind pinning of displaced supracondylar fractures of the humerus in children. Sixteen years' experience with long-term follow-up.


Cytolipin R and its possible precursor ceramide trisaccharide from metastatic rat mammary tumor.


A long-term follow-up of synovial sarcoma.


Adenosine 3',5'-cyclic monophosphate and adrenal tumor cell morphology.


Occurrence of Epstein-Barr virus in human leukocyte cultures.


Hormone secretion by cells dissociated from rat anterior pituitaries. A new procedure has been developed for dissociating anterior pituitary tissue and producing a viable suspension of single cells. The procedure involves incubation of small tissue blocks in 1 mg/ml trypsin (15 min), followed by incubation in 8 microg/ml neuraminidase and 1 mM EDTA (15 min), followed by mechanical dispersion. Cell yields are approximately 55%, based on recovered DNA. By electron microscopy five types of secretory cells (somatotrophs, mammotrophs, thyrotrophs, gonadotrophs, and corticotrophs) plus endothelial and follicular cells can be identified and are morphologically well preserved up to 20 h after dissociation. Throughout this period, the cells incorporate linearly [(3)H]leucine into protein for up to 4 h at a rate 90% greater than hemipituitaries, and they synthesize, transport intracellularly, and release the two major pituitary secretory products, growth hormone and prolactin. Immediately after dissociation the cells' ability to respond to secretogogues (high K(+) and dibutyryl cyclic AMP) is impaired, but after a 6-12-h culture period, the cells apparently recover and discharge 24% and 52%, respectively, of their content of prelabeled growth hormone over a 3-h period in response to these two secretogogues. This represents a stimulation of 109% and 470% over that released by cells incubated in control medium. The results demonstrate that function and morphologic integrity are preserved in this cell system. Therefore it is suitable for the study of various aspects of pituitary secretion and its control.


The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline. The effects of agents that elevate intracellular cyclic adenosine 3',5'-monophosphate (cAMP) have been studied with respect to phagocytosis by guinea pig polymorphonuclear leukocytes. The investigation depends upon the use of a precise method for following ingestion. Theophylline, dibutyryl cAMP, and prostaglandins inhibited the phagocytosis of starch particles. The inhibitions caused by prostaglandins E(1), E(2), and F(2alpha) (PGE(1), PGE(2), and PGF(2alpha)) were synergistic with that due to theophylline. Inhibition by PGA(1) and PGA(2) was not. At equal concentrations the order of increasing inhibition of phagocytosis (assayed at 10 min) by the prostaglandins was PGE(1) < PGF(2alpha) < PGE(2) < PGA(1) = PGA(2). Our results are consistent with the hypothesis that increased intracellular levels of cAMP impair the phagocyte's ability to ingest particles. The mechanism of the inhibition has not been defined. The increment in oxidation of [1-(14)C]glucose to (14)CO(2) that normally accompanies phagocytosis was found to be depressed in the presence of PGE(1) or theophylline, together or individually as expected from the inhibition of phagocytosis. Paradoxically, oxygen consumption although depressed by theophylline or PGE(1) plus theophylline, was stimulated by PGE(1) alone.


The cytochemical examination of poliovirus-induced cell damage.


Antagonism by dibutyryl adenosine cyclic 3',5'-monophosphate and testosterone of cell rounding reactions. In an attempt to understand further the mechanism of the morphological and functional "reverse transformation" of CHO-K1 cells induced by dibutyryl adenosine cyclic 3',5'-monophosphate (cAMP) and testosterone, the kinetics of variation in the susceptibility of cells to rounding after the addition or deletion of dibutyryl cAMP and testosterone have been investigated. Changes in susceptibility to cell rounding upon removal of divalent cations or pulse exposure to concanavalin A were complete within 0.5-1 h after addition or deletion of drug. In comparison, the gross conversion of CHO-K1 cells from epithelial- to fibroblast-like morphology after drug treatment or the converse change after drug removal required 8 or 4 h, respectively. The effects on cell rounding are not caused by an effect of dibutyryl cAMP upon cell growth rate. Inhibitor experiments indicate that the changes investigated do not require continued RNA or protein synthesis and are not prevented by agents which depolymerize microtubules.


Determination of the psychotropic drug thioridazine and its metabolites in blood by means of high pressure liquid chromatography in combination with fluorometric reaction detection.


Assessment of amoebiasis: serodiagnosis by immunofluorescence with lyophilized entamoebae.


Microbiological and technological aspects of crude collagenase production.


Morphological abnormalities in lymphocyte mitochondria associated with iron-deficiency anaemia. Morphological abnormalities in lymphocyte mitochondria of iron-deficient subjects are described. The abnormalities are of a degenerative type and are similar to those described in the mitochondria of other cells during iron deficiency.


Toxicological study of the long-term collagenase administration in rats and rabbits.


The effect of bacterial collagenase upon healthy and burned skin of pigs in vitro.


Experimental use of collagenase in the debridement of thermally damaged skin.


Clinical experience with enzymatic debridement of burned skin with the use of collagenase.


Collagenase in the treatment of ulcers in dermatology.


Experience with collagenase in skin complications during posttraumatic rehabilitation.


Systemic effects of single dermal administration of collagenase on one third of body surface in rats.


The incidence of trophoblastic disease in Siriraj Hospital.


Parturition in the cow: endocrine changes in animals with chronically implanted catheters in the foetal and maternal circulations.


Effects of premature weaning on adrenal function in intact and gonadectomized rats.


Effect of dibutyryl cyclic AMP on the release of melanocyte-stimulating hormone from rat neurointermediate lobes in vitro.


Parturition in the guinea-pig; plasma levels of steroid hormones, steroid-binding proteins, and oxytocin, and the effect of corticosteroids, prostaglandins and adrenocorticotrophin.


Effect of adrenocroticotrophin on (3H)uridine incorporation into glomerulosal cells of hypophysectomized rat adrenals.


The cellular basis of movement of the migrating grex of the slime mould Dictyostelium discoideum: chemotactic and reaggregation behaviour of grex cells.


Arginine analogues: effect on growth and on the first two enzymes of the arginine pathway in Pseudomonas aeruginosa.


Ontogenic development of a phosphodiesterase activator and the multiple forms of cyclic AMP phosphodiesterase of rat brain.


Properties and function of the calcium-dependent incorporation of choline, ethanolamine and serine into the phospholipids of isolated rat brain microsomes.


Functional organization of the cat's dorsal horn: spontaneous activity and central cell response to single impulses in single type I fibers.


The effects of solubilization procedures on the release and molecular state of acetylcholinesterase from electric organ tissue.


Proceedings: Angiotensin II levels in normal and hypertensive primigravid pregnancy.


Peripheral neuropathy in a coated fabrics plant.


Anterior pituitary function and its significance in the aetiology of endometrial carcinoma.


Clear cell sarcoma of tendon and aponeuroses with melanin production.


Water-soluble derivatives of 3-oxy-substituted 1,4-benzodiazepines.


Reactivities of enzymes toward hydroxyl radicals.


Effects of Ca (II) ion on the formation of free radicals in irradiated deoxyribonucleoprotein.


Effect of ACTH on reproductive organs of immature female northern grasshopper mice (Onychomys leucogaster).


Acute viral respiratory infections in a general practice during 1971.


Phosphorylation of proteins of ribosomes and nucleolar preribosomal particles from Novikoff hepatmoa ascites cells.


Refresher courses in pharmacology. 6. Mechanisms of drug action.


Three-dimensional structure of D-glyceraldehyde-3-phosphate dehydrogenase.


Nature of the ribosomal RNA transcribed from the X and Y chromosomes of Drosophila melanogaster.


Sequence and symmetry in ribosome binding sites of bacteriophage f1 RNA.


Effect of the viral proteins on the fluidity of the membrane lipids in Sindbis virus.


Superhelix density of replicating simian virus 40 DNA molecules.


Ultrastructure and calcium transport in microsomes from developing muscle.


Interferon production and resistance to viral infection induced by poly I-poly C in chick embryo cells. I. Effect of growth medium.


Ionic germination of spores of Clostridium perfringens type A.


A rapid and simple method for assaying interferon.


Antiviral activity of scillarenin, a plant bufadienolide.


Cutaneous clues to malignant disease.

Cutaneous clues to malignant disease.


Interfering and complicating adsorption effects in bioaffinity chromatography.


AMP and NAD as "General Ligands".

AMP and NAD as "General Ligands".


N6-immobilized 5 -AMP and NAD+: preparations and applications.


Rapid tissue fixation and extraction techniques.


Determination of cyclic GMP by formation of (beta-32P)GDP.


An automated chromatographic assay for adenylate cyclase and cyclic 3',5'-AMP phosphodiesterase.


Separation, purification and analysis of cyclic nucleotides by high pressure ion exchange chromatography.


Assay of cyclic nucleotide phosphodiesterases with radioactive substrates.


Cyclic 3',5'-nucleotide phosphodiesterase from bovine heart.


Assay of cyclic nucleotide phosphodiesterase by a continuous titrimetric technique.


Purification and characterization of cyclic nucleotide phosphodiesterase from skeletal muscle.


Purification and characterization of cyclic 3',5'-nucleotide phosphodiesterase from bovine brain.


Cyclic AMP phosphodiesterase of Escherichia coli.


Purification and properties of cyclic nucleotide phosphodiesterase from Dictyostelium discoideum (extracellular).


Preparation and characterization of multiple forms of cyclic nucleotide phosphodiesterase from liver.


Purification and characterization of a protein activator of cyclic nucleotide phosphodiesterase from bovine brain.


Separation of cyclic nucleotides by thin-layer chromatography on polyethyleneimine cellulose.


Techniques for the formation, partial purification, and assay of a cyclic AMP inhibitor.


Assay of cyclic AMP-dependent protein kinases.


Criteria for the classification of protein kinases.


Cyclic AMP-dependent protein kinase from bovine heart muscle.


Preparation of homogeneous cyclic AMP-dependent protein kinase(s) and its subunits from rabbit skeletal muscle.


Preparation and properties of cyclic AMP-dependent protein kinases from rabbit red blood cells.


Purification and characterization of cyclic GMP-dependent protein kinases.


Purification and characterization of an inhibitor protein of cyclic AMP-dependent protein kinases.


Techniques for the study of protein kinase activation in intact cells.


The purification and analysis of mechanism of action of a cyclic AMP-receptor protein from Escherichia coli.


The detection and characterization of cyclic AMP-receptor proteins in animal cells.


The preparation and use of cyclic AMP Sepharose.


Isolation of cyclic AMP by inorganic salt coprecipitation.


The preparation and use of diazomalonyl derivatives of cyclic AMP in isolating and identifying cyclic AMP receptor sites.


The preparation of acylated derivatives of cyclic nucleotides.


The synthesis of 1,N6-ethenoadenosine 3',5'-monophosphate; a fluorescent analog of cyclic AMP.


The synthesis of (32P) adenosine 3',5'-cyclic phosphate and other ribo- and deoxyribonucleoside 3',5'-cyclic phosphates.


Assay of cyclic nucleotides by receptor protein binding displacement.


Assay of cyclic AMP by the luciferin-luciferase system.


Assay of cyclic AMP by protein kinase activation.


Quantitation of cyclic GMP by enzymatic cycling.


The measurement of cyclic GMP with Escherichia coli elongation factor Tu.


Assay of cyclic GMP by activation of cyclic GMP-dependent protein kinase.


Assay of cyclic nucleotides by radioimmunoassay methods.


Reye's syndrome associated with adenovirus type 3 infection.


Glycoprotein hormones: gonadotrophins and thyrotrophins.


In vitro effect of metronidazole and tinidazole on anaerobic bacteria.


Propagation of equine infectious anemia virus in horse kidney cell cultures.


Establishment of tumor cell lines cultured from chickens with avian lymphoid leukosis.


Characterization of antigens and specific antibodies in the sera of chickens infected with Akiba caulleryi.


Unsuccessful attempts to propagate equine infectious anemia virus in lambs and small experimental animals.


Sensitive determination for adenylate cyclase activity by cyclic adenosine 3',5'-monophosphate protein binding assay.


Effect of detergents on 2',3'-cyclic nucleotide 3'-phosphohydrolase activity in myelin and erythrocyte ghosts.


Ultrastructural study of cytoplasmic inclusions in cases of viral hepatitis and hepatomas.


Histogenesis of angiomatous areas in meningiomas.  An electron microscope study.


Detection of fibrinolytic and elastase activity among clinical isolates of Serratia marcescens.


Gastrin response to calcium infusion: an aid to the improved diagnosis of Zollinger-Ellison syndrome in children.


Letter: Galactokinase deficiency in twins.


Task performance after awakenings from different stages of sleep.


Sequence analysis of nonradioactive RNA fragments by periodate-phosphatase digestion and chemical tritium labeling: characterization of large oligonucleotides and oligonucleotides containing modified nucleosides. A tritium derivative method for sequence analysis of polyribonucleotides is detailed, which is based on borotritide reduction of oligonucleotide dialdehydes generated by treatment of polyribonucleotides with alkaline phosphatase and excess periodate at pH 8 (borate buffer; no primary amine present in the reaction mixture). While neither phosphatase nor periodate possess any intrinsic exonuclease activity their combination mimics an RNA-specific exonuclease ("pseudo-exonuclease"). Procedures are described for separation and characterization of tritiumlabeled oligonucleotide derivatives. The sequence is deduced by identification of labeled 3'-termini following separation of the reduced nucleotide intermediates according to chain length. The sensitivity of the method is indicated by the fact that as little as 0.01 O.D.260 unit of a nonradioactive decanucleotide is sufficient for sequence determination.


Seven-membered cyclic phosphate: synthesis and properties of S-cycloadenosine 2',5'-cyclic phosphate and cordycepin 2',5'-cyclic phosphate. Studies of nucleosides and nucleotides. LXIV. 1). Purine cyclonucleosides 25. 8,3'-Anhydro-8-mercapto-9-beta-D-xylofuranosyladenine (8,3'-s-cycloadenosine) was phosphorylated with cyanoethyl phosphate and DCC to 5'-phosphate. After 6-amino group was benzoylated, the monophosphate was treated with DCC to give a cyclic phosphate (II). The structure of compound II was elucidated as 8,3'-s-cycloadenosine 2',5'-cyclic phosphate by UV, NMR and CD spectra, as well as enzymatic hydrolyses. When compound II was desulfurized with Raney nickel, cordycepin 2',5'-cyclic phosphate (III) was obtained. Although compound III could be obtained from cordycepin 5'-phosphate with DCC, the yield was extremely low.


Primary hepatoma presenting with central abdominal pain and diagnosed from a raised serum alpha-fetoprotein level.


Mood and sleep changes with monoamine-oxidase inhibitors.


Histochemistry of hypertrophic scars and keloids.


Glomus jugulare tumours.

Glomus jugulare tumours.


Glomus jugulare tumours: their clinical behaviour and management.


Treatment of glomus jugulare tumours by radiotherapy.


Cancer of the breast: forward look in the 1970s. Endocrine therapy-the future.


The treatment of breast cancer.

The treatment of breast cancer.


Problems of rickets in monkeys and apes.


Pathogenesis of amebic disease.

Pathogenesis of amebic disease.


Surgical amoebiasis.

Surgical amoebiasis.


Inhibition of bone collagen synthesis by prostaglandin E2 in organ culture.


Experimental studies of the epidemiology of bovine herpes mammillitis.


A laboratory technique for studying the mechanical transmission of bovine herpes mammillitis virus by the stable fly (Stomoxys calcitrans L.).


The histopathology of experimental pneumonia in pigs produced by Aujeszky's disease virus.


Ultrastructural changes in experimental enzootic pneumonia of pigs.


Ultrastructural changes in the lungs of pigs infected with Aujeszky's disease virus.


Observations on the alkaline phosphatase activity of leucocytes in adrenalectomised rats.


Enterovirus neutralizing activity in the milk of sows.


Ultrastructure of the kidney and urinary excretion of renal antigens in experimental canine adenovirus infection.


The immune response of cattle during pregnancy and early lactation.


The influence of thyroid gland on carbonic anhydrase activity of mouse submandibular gland.


Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death.


Cytophotometric analysis of DNA in enzymatically-dissociated submandibular gland cells of the mouse.


Production and characterization of hybrids of somatic cells of the mouse and Chinese hamsters.


Influence of infectious diseases on hereditary polymorphism with respect to the blood groups of the ABO system.


The effect of preliminary irradiation of barley grain with low doses of x-rays on the mutagenic activity of several monofunctional alkylating agents.


Virus infections in children in a respiratory intensive care unit during an influenza epidemic.


Metabolic effect of conjugated oestrogens (USP) on lipids and lipoproteins.


Two-dimensional diffusion in membranes.

Two-dimensional diffusion in membranes.


Cofactor requirements for the stimulation of ox growth hormone release in vitro.


Contacts and junctions between cells.

Contacts and junctions between cells.


Adenoid cystic carcinoma of the esophagus.


Renal tubular disorders in childhood.

Renal tubular disorders in childhood.


Heat sensitivity of tumor cells.

Heat sensitivity of tumor cells.


A clinico-pathological study on the prognosis of Wilms' tumor.


Ag(i): detection of an antithetical factor to Ag(h).


Extractability and intracellular localisation of urea cycle enzymes from rat liver.


The relationship between the plasma concentrations of renin and angiotensin with total exchangeable sodium in hypertension.


Serum human chorionic somatomammotropin as an aid in the diagnosis of gestational trophoblastic disease.


Influence of norepinephrine and dibutyryl cyclic AMP on ultrastructure of the pineal gland in organ culture.


The effect of simazin on the ultrastructure and activities of some hydrolases of the rat liver.


Influence of dibutyryl cyclic AMP on the ultrastructure of adenohypophysis in organ culture. Preliminary report.


Collagenolytic activity in rat ovary during ovulation.


Studies in normal male puberty.

Studies in normal male puberty.


Postsynaptic responses of hippocampal neurons to subcortical stimulation: differentiation of ascending pathways.


(32-P) Phosphoryl transfer by endogenous protein kinase at the glia and glioma cell surface in culture into extrinsic acceptor proteins.


The effect of angiotensin on isosmotic fluid absorption by the rabbit gall-bladder in vitro.


Comma-shaped bodies in histiocytes.

Comma-shaped bodies in histiocytes.


Some applications of the amplitude and frequency analysis of the EEG.


The effect of prolonged vibration on permeability of the vascular endothelium to proteins. Mechanism of extravascular displacement of proteins.


Cytophilic antibody as an auxiliary factor in cell-mediated immunity.


The polypeptides of human serum lipoproteins and their clinical significance.


Temperature-dependent properties of cells transformed by a thermosensitive mutant (ts-121) of polyoma virus.


Autoradiographic studies on the sites of protein and RNA syntheses in poxvirus-infected cells.


Microbial degradation of alkylbenzenesulphonates. Metabolism of homologues of short alkyl-chain length by an Alcaligenes sp. 1. An organism isolated from sewage and identified as an Alcaligenes sp. utilized benzenesulphonate, toluene-p-sulphonate or phenylethane-p-sulphonate as sole source of carbon and energy for growth. Higher alkylbenzenesulphonate homologues and the hydrocarbons, benzene, toluene, phenylethane and 1-phenyldodecane were not utilized. 2. 2-Phenylpropanesulphonate was metabolized to 4-isopropylcatechol. 3. 1-Phenylpropanesulphonate was metabolized to an ortho-diol, which was tentatively identified, in the absence of an authentic specimen, as 4-n-propylcatechol. 4. In the presence of 4-isopropylcatechol, which inhibited catechol 2,3-dioxygenase, 4-ethylcatechol accumulated in cultures growing on phenylethane-p-sulphonate. 5. Authentic samples of catechol, 3-methylcatechol, 4-methylcatechol, 4-ethylcatechol and 3-isopropylcatechol were oxidized by heat-treated extracts to the corresponding 2-hydroxyalkylmuconic semialdehydes. Ring cleavage occurred between C-2 and C-3. 6. The catechol derived from 1-phenylpropanesulphonate was oxygenated by catechol 2,3-dioxygenase to a compound with all the properties of a 2-hydroxyalkylmuconic semialdehyde, but it was not rigorously identified. 7. The catechol 2,3-dioxygenase induced by growth on benzenesulphonate, toluene-p-sulphonate or phenylethane-p-sulphonate showed a constant ratio of specific activities with catechol, 3-methylcatechol, 4-methylcatechol and 4-ethylcatechol that was independent of the growth substrate. At 60 degrees C, activity towards these substrates declined at an identical first-order rate. 8. Enzymes of the ;ortho' pathway of catechol metabolism were present in small amounts in cells grown on benzenesulphonate, toluene-p-sulphonate or phenylethane-p-sulphonate. 9. The catechol 1,2-dioxygenase oxidized the alkylcatechols, but the rates and the total extents of oxidation were less than for catechol itself. The oxidation products of these alkylcatechols were not further metabolized.


The effect of nickel on secretory systems. Studies on the release of amylase, insulin and growth hormone. The effects of Ni(2+) on the release of amylase from rat parotids, insulin from mouse pancreatic islets and growth hormone from bovine pituitary slices were investigated. In all these secretory systems, Ni(2+) was shown to inhibit release evoked by a variety of stimuli both physiological and pharmacological. Measurements of rates of substrate oxidation and tissue concentrations of ATP and 3':5'-cyclic AMP suggest that this inhibitory action of Ni(2+) does not arise through an effect on energy metabolism or cyclic AMP metabolism. It is concluded that although some effects of Ni(2+) may involve antagonism between Ni(2+) and Ca(2+) in stimulus-secretion coupling, others appear to be independent of Ca(2+). It is suggested that Ni(2+) may block exocytosis by interfering with either secretory-granule migration or membrane fusion and microvillus formation. The possible mode of action of Ni(2+) and its potential use as a tool in the study of exocytosis are discussed.


The inhibition of mitochondrial calcium transport by lanthanides and ruthenium red. An EGTA (ethanedioxybis(ethylamine)tetra-acetic acid)-quench technique was developed for measuring initial rates of (45)Ca(2+) transport by rat liver mitochondria. This method was used in conjunction with studies of Ca(2+)-stimulated respiration to examine the mechanisms of inhibition of Ca(2+) transport by the lanthanides and Ruthenium Red. Ruthenium Red inhibits Ca(2+) transport non-competitively with K(i) 3x10(-8)m; there are 0.08nmol of carrier-specific binding sites/mg of protein. The inhibition by La(3+) is competitive (K(i)=2x10(-8)m); the concentration of lanthanide-sensitive sites is less than 0.001nmol/mg of protein. A further difference between their modes of action is that lanthanide inhibition diminishes with time whereas that by Ruthenium Red does not. Binding studies showed that both classes of inhibitor bind to a relatively large number of external sites (probably identical with the ;low-affinity' Ca(2+)-binding sites). La(3+) competes with Ruthenium Red for most of these sites, but a small fraction of the bound Ruthenium Red (less than 2nmol/mg of protein) is not displaced by La(3+). The results are discussed briefly in relation to possible models for a Ca(2+) carrier.


The uptake and metabolism of (32-P)pyrophosphate by mouse calvaria in vitro. In order to study the uptake and metabolism of PP(i) by bone, (32)PP(i) was added to the medium surrounding explanted mouse calvaria maintained in organ culture. Most of the PP(i) was hydrolysed during incubation, but there was a measurable entry of intact PP(i) into bone. When (32)P(i) was added to the medium, synthesis of PP(i) and organic phosphates from P(i) was observed in bone. There was no detectable passage of PP(i) from bone into the medium. These results are discussed in terms of two models of pyrophosphate hydrolysis and exchange. Some quantitative estimates about the fate of PP(i) in bone were made.


Role of membrane-bound and free polyribosomes in the synthesis of cytochrome c in rat liver. The functional distinction of membrane-bound and free polyribosomes for the synthesis of exportable and non-exportable proteins respectively is not so strict as was initially thought, and it was therefore decided to investigate their relative contribution to the elaboration of an internal protein integrated into a cell structure. Cytochrome c was chosen as an example of a soluble mitochondrial protein, and the incorporation of [(14)C]leucine and delta-amino[(14)C]laevulinate into the molecule was studied by using different ribosomal preparations from regenerating rat liver. A new procedure was devised for the purification of cytochrome c, based on ion-exchange chromatography combined with sodium dodecyl sulphate-polyacrylamide-gel electrophoresis. In spite of cytochrome c being a non-exportable protein, the membrane-bound polyribosomes were at least as active as the free ribosomes in the synthesis in vitro of the apoprotein and the haem moiety. The detergent-treated ribosomes could also effect the synthesis of cytochrome c, although at a lower rate. Since in liver more than two-thirds of the ribosomes are bound to the endoplasmic-reticulum membranes, it is considered that in vivo they are responsible for the synthesis of most of the cytochrome c content of the cell. This suggests that in secretory tissues the endoplasmic reticulum plays a predominant role in mitochondrial biogenesis, although free ribosomes may participate in the partial turnover of some parts of the organelle. The hypothesis on the functional specialization of the different kinds of ribosomes was therefore modified to account for their parallel intervention in the synthesis of proteins associated with membranous structures.


Utilization of gluconate by Escherichia coli. Uptake of D-gluconate by a mutant impaired in gluconate kinase activity and by membrane vesicles derived therefrom. 1. From Escherichia coli strain K2.1.5(c).8.9, which is devoid of 6-phosphogluconate dehydrogenase (gnd) and 6-phosphogluconate dehydratase (edd) activities, a mutant R6 was isolated that was tolerant to gluconate though still edd(-), gnd(-). 2. Measurements of the fate of labelled gluconate, of the conversion of gluconate into 6-phosphogluconate, and of the induction of gluconate kinase by the two organisms show that, although both inducibly form a gluconate-transport system, strain R6 is impaired in its ability to convert the gluconate thus taken up into 6-phosphogluconate; it was therefore used for study of the kinetics and energetics of gluconate uptake. 3. Suspensions of strain R6 induced for gluconate uptake took up this substrate via a ;high affinity' transport process, with K(m) about 10mum and V(max.) about 25nmol/min per mg dry mass; a ;low affinity' system demonstrated to occur in certain E. coli mutants was not induced under the conditions used in this work. 4. The uptake of gluconate was inhibited by lack of oxygen and by inhibitors of electron transport; such inhibitors also promoted the efflux of gluconate taken up. 5. Membrane vesicles prepared from strain R6 also manifested these properties when incubated with suitable electron donors, at rates similar to those observed with whole cells. 6. The results indicate that the active transport of gluconate into the cells is the rate-limiting step in gluconate utilization by E. coli, and that the mechanism of this process can be validly studied with membrane vesicles.


Glutamate and aspartate transport in rat brain mitochondria. 1. Rat brain mitochondria did not swell in iso-osmotic solutions of ammonium or potassium (plus valinomycin) glutamate or aspartate, with or without addition of uncouplers. 2. Glutamate was able to reduce intramitochondrial NAD(P)(+); aspartate was able to cause partial re-oxidation. 3. These effects were inhibited by threo-hydroxy-aspartate in whole but not in lysed mitochondria. 4. The existence of a ;malate-aspartate shuttle' for the oxidation of extramitochondrial NADH was demonstrated. This shuttle requires the net exchange of glutamate for aspartate across the mitochondrial membrane. 5. Extramitochondrial glutamate did not inhibit intramitochondrial glutaminase under conditions in which the inhibition in lysed mitochondria was virtually complete. 6. The glutaminase activity of these mitochondria was not energy-dependent. 7. We conclude that these mitochondria do not possess a glutamate-hydroxyl antiporter similar to that of liver mitochondria nor a glutamate-glutamine antiporter similar to that of pig kidney mitochondria, but that they do possess a glutamate-aspartate antiporter.


Calcium and magnesium ions as effectors of adipose-tissue pyruvate dehydrogenase phosphate phosphatase. The metal-ion requirement of extracted and partially purified pyruvate dehydrogenase phosphate phosphatase from rat epididymal fat-pads was investigated with pig heart pyruvate dehydrogenase [(32)P]phosphate as substrate. The enzyme required Mg(2+) (K(m) 0.5mm) and was activated additionally by Ca(2+) (K(m) 1mum) or Sr(2+) and inhibited by Ni(2+). Isolated fat-cell mitochondria, like liver mitochondria, possess a respiration- or ATP-linked Ca(2+)-uptake system which is inhibited by Ruthenium Red, by uncouplers when linked to respiration, and by oligomycin when linked to ATP. Depletion of fat-cell mitochondria of 75% of their total magnesium content and of 94% of their total calcium content by incubation with the bivalent-metal ionophore A23187 leads to complete loss of pyruvate dehydrogenase phosphate phosphatase activity. Restoration of full activity required addition of both MgCl(2) and CaCl(2). SrCl(2) could replace CaCl(2) (but not MgCl(2)) and NiCl(2) was inhibitory. The metal-ion requirement of the phosphatase within mitochondria was thus equivalent to that of the extracted enzyme. Insulin activation of pyruvate dehydrogenase in rat epididymal fat-pads was not accompanied by any measurable increase in the activity of the phosphatase in extracts of the tissue when either endogenous substrate or (32)P-labelled pig heart substrate was used for assay. The activation of pyruvate dehydrogenase in fat-pads by insulin was inhibited by Ruthenium Red (which may inhibit cell and mitochondrial uptake of Ca(2+)) and by MnCl(2) and NiCl(2) (which may inhibit cell uptake of Ca(2+)). It is concluded that Mg(2+) and Ca(2+) are cofactors for pyruvate dehydrogenase phosphate phosphatase and that an increased mitochondrial uptake of Ca(2+) might contribute to the activation of pyruvate dehydrogenase by insulin.


Microbial metabolism of the pyridine ring. The metabolism of pyridine-3,4-diol (3,4-dihydroxypyridine) by Agrobacterium sp. 1. Pyridine-3,4-diol (3,4-dihydroxypyridine, 3-hydroxypyrid-4-one), an intermediate in 4-hydroxypyridine metabolism by an Agrobacterium sp (N.C.I.B. 10413), was converted by extracts into 1mol of pyruvate, 2mol of formate and 1mol of NH(3) at pH7.0. 2. Formate, but not the alternative likely product formamide, was further oxidized fivefold faster by 4-hydroxypyridine-grown washed cells than by similar organisms grown on succinate. 3. The oxidation of pyridine-3,4-diol by crude extracts at pH8.5 required 1mol of O(2)/mol of substrate, produced 1mol of acid and led to the formation of formate and a new compound with an extinction maximum of 285nm (Compound I). This step was believed to be mediated by a new labile dioxygenase (t((1/2))=4h at pH7.0, 4 degrees C) cleaving the pyridine ring between C-2 and C-3. 4. Many of the properties of this pyridine-3,4-diol dioxygenase paralleled those of the extradiol (;meta') oxygenases of aromatic-ring cleavage. The extreme lability of the enzyme has so far precluded extensive purification. 5. Compound I showed changes in the u.v.-absorption spectrum with pH but after acidification it was converted into a new product, 3-formylpyruvate, with an extinction maximum now at 279nm. 6. Both Compound I and 3-formylpyruvate were metabolized by extracts but at very different rates. The slower rate of metabolism of Compound I was nevertheless consistent with that of pyridine-3,4-diol metabolism. 7. On acidification Compound I released about 0.65mol of NH(3) and has been identified as 3-formiminopyruvate. 8. 3-Formylpyruvate was hydrolysed to formate and pyruvate (K(m) 2mum) by an acylpyruvate hydrolase active against several other dioxo homologues. The activity of this enzyme was much lower in extracts of succinate-grown cells.


Properties of a prolactin receptor from the rabbit mammary gland. Receptors for human, simian, ovine, bovine and murine prolactin, human growth hormone and human placental lactogen have been identified in plasma-membrane-containing subcellular particles isolated from rabbit mammary glands. The association and dissociation of (125)I-labelled prolactin are time- and temperature-dependent processes, both being maximal at 37 degrees C. (125)I-labelled prolactin prepared by the enzymic iodination procedure with lactoperoxidase binds better to receptors than does the preparation obtained by using chloramine-t as the oxidizing agent. The binding of (125)I-labelled prolactin to receptors is strongly influenced by pH and ionic composition but not by many low-molecular-weight compounds tested, e.g. steroids, nucleotides and several drugs. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipid moieties are essential for the binding of (125)I-labelled prolactin. The binding of (125)I-labelled prolactin to receptors is a saturable and reversible process. Scatchard and Lineweaver-Burk analyses suggest that (125)I-labelled prolactin has a high affinity for its receptor. Binding of (125)I-labelled prolactin to receptors does not result in the destruction of the hormone. Considerable prolactin-binding activity is also observed in subcellular fractions isolated from the adrenal gland, liver, ovary and kidney of the pregnant rabbit, a finding that is consistent with other reported actions of prolactin in these organs.


Comparative effect and fate of non-entrapped and liposome-entrapped neuraminidase injected into rats. Non-entrapped and liposome-entrapped Clostridium perfringens neuraminidase (0.5-0.6 unit) was injected into rats and its fate as well as its effect on plasma and erythrocyte N-acetylneuraminic acid was investigated. The following observations were made. (1) Although removal of both non-entrapped and liposome-entrapped neuraminidase from the circulation was completed within 5h after injection, their recovery in tissues was distinctly different; 7-10% of the injected non-entrapped enzyme was found in the liver and none in the liver lysosomal fraction or the spleen. In contrast, 20-26% of the liposome-entrapped enzyme was found in the liver of which 60-69% was in the lysosomal fraction. Spleen contained 3.6-5.0% of the enzyme. (2) The presence of the non-entrapped neuraminidase in blood led to the extensive desialylation of plasma and to a decrease in the concentration or total removal from the circulation of some of the plasma glycoproteins. (3) Injection of non-entrapped neuraminidase also led to the partial desialylation of erythrocytes the life span of which was diminished and their uptake by the liver and spleen augmented. (4) Entrapment of neuraminidase in liposomes before its injection prevented the enzyme from acting on its substrate in plasma or on the erythrocyte surface, and values obtained for plasma glycoproteins and erythrocyte survival were similar to those observed in control rats. (5) Entrapment in liposomes of therapeutic hydrolases intended for the degradation of substances stored within the tissue lysosomes of patients with storage diseases could prevent the potentially hazardous enzymic action of hydrolases in blood and at the same time direct the enzymes to the intracellular sites where they are needed.


Glycogen metabolism in the liver of the foetal rat. 1. The glycogen present in the liver of rat foetuses was labelled by injecting a trace amount of [6-(3)H]glucose into the mother at 19.5 days of gestation. The radioactivity incorporated in the glycogen 4h after the administration of the label was still present 38h later. A large proportion of this radioactivity was on the outer chains of the polysaccharide. These results indicate that there is normally almost no glycogen degradation in the foetal liver. In contrast, glycogen breakdown occurs very rapidly in the livers of foetuses whose mother is anaesthetized. 2. Glycogen synthetase is present in the liver at day 16 of gestation at a concentration as high as 30% of that in the adult, but essentially as an inactive (b) enzyme. The appearance of synthetase phosphatase between days 18 and 19 corresponds to that of synthetase a and to the beginning of glycogen synthesis. From day 19 to 21.5 the amount of synthetase a present in the foetal liver is just sufficient to account for the actual rate of glycogen deposition. 3. The content of total phosphorylase in the foetal liver increases continuously from day 16 to birth. However, a precise measurement of the a and b forms of the enzyme in the liver of non-anaesthetized foetuses is not possible. Taking the rate of glycogenolysis as an appropriate index of phosphorylase activity, we conclude that this enzyme is almost entirely in the inactive form in the foetal liver under normal conditions. 4. The accumulation of glycogen in the liver during late pregnancy may therefore be explained by a relatively slow rate of synthesis and a nearly total absence of degradation.


Isolation and characterization of a hydroxyproline-containing protein from soluble extracts of the leaves of sandal (Santalum album L.). 1. A hydroxyproline-containing protein was isolated from the soluble fraction of sandal leaves (Santalum album L.) and the purified protein was homogeneous by disc electrophoresis. 2. It is a glycoprotein containing 16% carbohydrate, the components of which were mainly arabinose, with only small amounts (about 5%) of galactose. The principal amino acids were glutamic acid, aspartic acid, glycine, alanine, arginine, lysine, proline and hydroxyproline, which together comprised 60% of the total. The number of acidic amino acids exceeds the number of basic amino acids. By Sephadex gel filtration, the approximate molecular weight was found to be about 63000. The ratio of residues of hydroxyproline to those of arabinose was 1:2. 3. The native protein is resistant to the action of several proteolytic enzymes. After partial hydrolysis with 0.1m-HCl, the protein became susceptible to attack by Pronase but remained resistant to collagenase.


Studies on the thiol group of lactose synthetase A protein from human milk and on the binding of uridine diphosphate galactose to the enzyme. The lactose synthetase activity of A protein from human milk was much decreased but not abolished by reaction with thiol-group reagents. Protection experiments indicated that a free thiol group on the enzyme is situated near the UDP-galactose binding site and inactivation of the enzyme with p-hydroxymercuribenzoate was probably due to prevention of UDP-galactose binding. Affinity chromatography showed that the mercuribenzoate substituent also decreased the affinity of A protein for N-acetylglucosamine but complex-formation between A protein-N-acetylglucosamine and alpha-lactalbumin was relatively unaffected. UDP-galactose appears to be bound to the enzyme mainly through its pyrophosphate group with Mn(2+) ion and through the cis hydroxyls of ribose, whereas its hexose moiety has little if any affinity for the enzyme. Lactose synthetase activity remaining after the reaction with thiol-group reagents indicates that a free thiol group is not an essential part of the A protein active site.


The kinetics of coupled enzyme reactions. Applications to the assay of glucokinase, with glucose 6-phosphate dehydrogenase as coupling enzyme. 1. A theory is developed to account for the kinetics of coupled-enzyme reactions without assuming that the second reaction follows first-order kinetics. 2. A simple procedure is described for applying the theory to the practical design of enzyme assays. 3. The validity of the theory is confirmed for the assay of glucokinase with glucose 6-phosphate dehydrogenase as coupling enzyme. 4. The possibility of extending the theory to three or more coupled reactions is discussed.


A collagen-like amino acid sequence in a polypeptide chain of human C1q (a subcomponent of the first component of complement). 1. A partial amino acid sequence of 95 residues of the 191 residues in the oxidized A chain of human subcomponent C1q was determined. The partial nature of the sequence is because one overlapping peptide is missing in the proposed sequence, also the proof of some of the overlapping peptides depends partly on their amino acid composition and not on their complete sequence. 2. This region of the A chain contained a repeating sequence of glycine-X-Y (where X is often proline and Y is often hydroxyproline) for 78 residues. 3. The five hydroxylysine residues and the five hydroxyproline residues present in the oxidized A chain were all in these 78 residues and only in the Y position of the repeating sequence. 4. Prolonged collagenase digestion of the oxidized A chain yielded a large, apparently C-terminal, peptide which contained most of the non-collagenous sequences present in the chain. 5. It is concluded that there is a collagen-like region in the A chain of subcomponent C1q which constitutes most of the N-terminal half of the chain and that similar collagen-like regions will be found in the B and C chains.


Catalytic properties of alkaline phosphatase from pig kidney. The enzymic properties of alkaline phosphatase (EC 3.1.3.1) from pig kidney brush-border membranes were studied. 1. It hydrolyses ortho- and pyro-phosphate esters, the rate limiting step (V(max.)) being independent of the substrate. It transphosphorylates to Tris at concentrations above 0.1m-Tris. 2. The pH optimum for hydrolysis was between 9.8 and 10. The pK of the enzyme-substrate complex is 8.7 for p-nitrophenyl phosphate and beta-glycerophosphate. Excess of substrate inhibits the enzymic activity with decreasing pH. The pK of the substrate-inhibited enzyme-substrate complex, 8.7, is very similar to that for the enzyme-substrate complex. The pK values of the free enzyme appear to be 8.7 and 7.9. 3. Inactivation studies suggest that there is an essential tyrosine residue at the active centre of the enzyme. 4. The energy of activation (E) and the heat of activation (DeltaH) at pH9.5 showed a transition at 24.8 degrees C that was unaffected by Mg(2+). 5. Kinetic and atomic-absorption analysis indicated the essential role of two Zn(2+) ions/tetrameric enzyme for an ordered association of the monomers. Zn(2+) in excess and other bivalent ions compete for a second site with Mg(2+). Mg(2+) enhances only the rate-limiting step of substrate hydrolysis. 6. Amino acid inhibition studies classified the pig kidney enzyme as an intermediate type of previously described alkaline phosphatases. It has more similarity with the enzyme from liver and bone than with that from placenta.


Kinetics of carbon monoxide binding and electron transfer by cytochrome c polymers. Studies on horse heart cytochrome c polymers were carried out by stopped-flow and photolysis techniques, to investigate the properties of the CO complex and the kinetics of electron transfer, mainly of the dimeric and tetrameric forms. CO binding, which does not occur with native monomers, proceeds at both pH7.0 and pH9.6, and appears to follow complex kinetics: an initial phase is observed, which is CO-concentration-dependent, followed by a very slow monomolecular phase (k~2x10(-3)s(-1) at pH7) before establishment of equilibrium. Photodissociation of the CO complex has a very low quantum yield, probably less than 0.1. Static titration data of the dimer gave an ;n' value of 0.4. These data strongly suggest heterogeneity of the population of binding sites, and have been interpreted in terms of the existence of different structures, probably owing to the non-unique type of binding of monomers during polymerization. Polymers of cytochrome c carboxymethylated on the methionine residue normally ligated to iron show simple CO recombination kinetics after photolytic removal (k(on)=1.5x10(6)m(-1).s(-1) at pH6). We therefore suggest that, for native cytochrome c, polymerization has an effect on the lability of the haem crevice, rendering the iron available for binding ligands, without, however, forming the structure of a truly open crevice. Electron transfer is, on the other hand, a simple process, and no gross differences are observed between monomer and polymers. A simple model, taking into account all these data, is suggested.


Specificity of glycerol kinase.

Specificity of glycerol kinase. The activity of a number of alcohols was examined as substrates or inhibitors of glycerol kinase (ATP-glycerol phosphotransferase; EC 2.7.1.30) from Candida mycoderma. On the basis of these and other results, a modified model is proposed to account for the substrate specificity of the enzyme.


Distribution of reducing equivalents on xanthine oxidase molecules and the rates of the intramolecular electron-transfer reactions. When xanthine oxidase turns over 1-methylxanthine aerobically at pH8.2, the time-sequence in development of its electron-paramagnetic-resonance signals is not primarily due to slow intramolecular reactions among its centres. It derives instead from gross differences in electron distribution within enzyme molecules reduced by the substrate in comparison with those that have subsequently been partly reoxidized by one-electron reaction with oxygen.


Specificity of anti-nucleoside antibodies. The method of conjugation of a nucleoside or related compound to a carrier protein may have a significant effect on the specificity of the antibodies elicited. It is demonstrated, by means of the membrane-filtration assay, that anti-isopentenyladenosine antibodies produced by the ;periodate procedure' are much more reactive with the periodate-oxidized form of the nucleoside than with the parent compound. In addition, the simplicity and specificity of the assay used suggests its use as a sensitive radioimmunoassay for this multifunctional nucleoside.


A new nicotinamide-adenine dinucleotide-dependent hydroaromatic dehydrogenase of Lactobacillus plantarum and its role in formation of (minus)t-3,t-4-dihydroxycyclohexane-c-1-carboxylate. 1. A new induced NAD-dependent hydroaromatic dehydrogenase was isolated from a cell-free extract of Lactobacillus plantarum 13a and purified 175-fold. 2. The enzyme catalyses the oxidation of (-)-quinate, (-)-shikimate, (-)-dihydroshikimate and (-)t-3,t-4-dihydroxycyclohexane-c-1-carboxylate with NAD(+), and the reverse action with NADH. 3. The K(m) values at the optimal pH10.0 for these substrates are 0.85, 0.75, 0.52 and 0.74mm respectively, and the corresponding values for NAD(+) are 0.45, 0.26, 0.34 and 0.36mm respectively. 4. The stereochemical requirements of the enzyme and the role it may play in the reduction of (-)-quinate to (-)t-3,t-4-dihydroxycyclohexane-c-1-carboxylate are discussed and a pathway is suggested.


The isolation and amino acid sequence of an adrenocorticotrophin from the pars distalis and a corticotrophin-like intermediate-lobe peptide from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias. An adrenocorticotrophic hormone (ACTH) was isolated from extracts of the pars distalis of the pituitary of the dogfish Squalus acanthias by gel filtration and ion-exchange chromatography. It had 15% of the potency of human ACTH in promoting cortico-steroidogenesis in isolated rat adrenal cells. Sequence analysis revealed it to be a nonatria-contapeptide with the following primary structure: Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Met-Gly-Arg-Lys-Arg-Arg-Pro-Ile-Lys-Val-Tyr-Pro-Asn-Ser-Phe-Glu-Asp-Glu-Ser-Val-Glu-Asn-Met-Gly-Pro-Glu-Leu. The N-terminal tridecapeptide sequence was identical with the proposed structure of dogfish alpha-melanocyte-stimulating hormone (alpha-MSH). On comparison with human ACTH eleven amino acid differences were seen, nine of which are in the 20-39 region of the molecule which is not essential for the steroidogenic activity of ACTH. A peptide identical with the 18-39 portion of this new ACTH was similarly isolated from the neurointermediate lobe of the pituitary where considerable amounts of dogfish alpha-MSH were found. This supported our view that ACTH as well as having a distinct biological role of its own is also the precursor of alpha-MSH.


Structural studies of alpha-melanocyte-stimulating hormone and a novel beta-melanocyte-stimulating hormone from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias. A melanocyte-stimulating hormone (MSH) has been isolated from extracts of the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias by gel-filtration and ion-exchange chromatography. It had approximately 1% of the potency of mammalian alpha-MSH on bioassays in vitro on frog skin and dogfish skin. Sequence analysis revealed it to be a hexadecapeptide with the following primary structure: Asp-Gly-Asp-Asp-Tyr-Lys-Phe-Gly-His-Phe-Arg-Trp-Ser-Val-Pro-Leu. It appears to be related to the beta-MSH species of mammalian species but has only the sequence -His-Phe-Arg-Trp- in common with the heptapeptide core -Met-Glu-His-Phe-Arg-Trp-Gly- which is characteristic not only of the MSH peptides but also of the adrenocorticotrophins and lipotrophins studied so far. An alpha-MSH was also isolated, 50% of which was amidated at the C-terminus group. Sequence data from this study taken in conjunction with those from a previous study (Lowry & Chadwick, 1970b) revealed it to be a tridecapeptide which is identical with the N-terminal sequence of dogfish adrenocorticotrophin.


The reduction of carboxymethyl-cytochrome c by chromous ions. The reduction of ferricytochrome c and ferricytochrome c carboxymethylated at the haem-linked methionine (residue 80) by Cr(2+) ions was studied by stopped-flow techniques. At pH6.2 the kinetics of reduction of ferricytochrome c are simple and correspond to a second-order rate constant of 1.21x10(3)m(-1).s(-1). Under identical conditions the kinetics of reduction of the carboxymethyl derivative, carboxymethyl-cytochrome c, are complex; two Cr(2+)-concentration-dependent processes (1.5x10(4)m(-1).s(-1) and 1.3x10(3)m(-1).s(-1)) lead to the formation of an intermediate which decays in monomolecular fashion (0.15s(-1)) to form the normal fully reduced material. The kinetic difference spectrum for the overall process corresponds to that found statically, whereas the kinetic difference spectrum of the intermediate minus the oxidized form resembles that of the low-spin ferrous form of carboxymethyl-cytochrome c minus oxidized carboxymethyl-cytochrome c. A model is proposed in which the reduction of low-spin ferric carboxymethyl-cytochrome c to high-spin ferrous carboxymethyl-cytochrome c involves a low-spin ferrous intermediate. The monomolecular step involving the decay of this low-spin ferrous intermediate is associated with an activation energy of approx. 126kJ.mol(-1) and is thought to involve both a change of spin state and a protein-conformational event. Although carboxymethyl-cytochrome c represents a mixture of species separable on a charge basis, the above observations were independent of which species was chosen for study.


Structures for polyinosinic acid and polyguanylic acid. X-ray-diffraction analysis of oriented, partially crystalline fibres of polyinosinic acid has resulted in a new molecular model. This model consists of four identical polynucleotide chains related to one another by a fourfold rotation axis. The coaxial helices are righthanded (screw symmetry 23(2)) and have an axial translation per residue h=0.341nm and a rotation per residue t=31.3 degrees . Incorporated in the model are standard bond lengths, bond angles and C-2-endo furanose rings. The nucleotide conformation angles, determined by linked-atom least-squares methods, are orthodox and the fit with the X-ray intensities is good. Each hypoxanthine base is linked to two others by hydrogen bonds involving O-6 and N-1. Further stability may arise from intrachain hydrogen bonds between each ribose hydroxyl group and the phosphate oxygen O-3. If guanine were to be substituted for hypoxanthine in an isogeometrical molecular structure, additional hydrogen bonds could be made between every N-2 and N-7.