Synaptic inhibition in pyramidal tract neurons: membrane potential and conductance changes evoked by pyramidal tract and cortical surface stimulation.


Motor organization and generation of rhythmic feeding output in buccal ganglion of Pleurobranchaea.


Effects of projected cortical epileptiform discharges on neuronal activities in cat VPL. I. Interictal discharge.


Effect of amino acid supplement on liver lipid content and lipid metabolism of rats fed a nonprotein diet.


Active transport of thiamine from rat small intestine.


Purification and properties of quinolinate phosphoribosyltransferase from the "Shiitake" mushroom (Lentinus edodes).


Characteristics of quinolinate phosphoribosyltransferase from the "Shiitake" mushroom (Lentinus edodes).


Preventive effect of riboflavin 2',3',4',5'-tetrabutyrate on inactivation of rat liver microsomal enzymes induced by carbon tetrachloride.


The mechanism of action of oestrogen in the human female.


Cystic adenoma of a minor salivary gland: a histochemical study.


Enzyme patterns in non-neoplastic and spontaneously transformed tissue culture cells: a histochemical and biochemical study.


Extensive calcification in the stroma of a primary hepatic carcinoma.


Microsporidan infection of Simulium damnosum in West Africa.


Swellings of the salivary glands. Part II, neoplasms.


Letter: Bioavailability of digoxin in presence of antacids.


Synthetic procedures for deuterium-labeled acetylcholine perchlorates.


Letter: Nonaqueous titration of procainamide hydrochloride.


Renin and angiotensin-like levels in foetal, new-born and adult sheep. 1. Plasma renin (measured as rate of formation of angiotensin I ng/ml.hr(-1) in the presence of added substrate at pH 7.5 and 37 degrees C) was much lower in recently nephrectomized foetal, new-born and older lambs than in intact siblings or other similar lambs.2. Angiotensin II-like concentrations were measured using a superfusion technique in an extracorporeal circuit. Resting concentrations in acute experiments under anaesthesia were deduced by comparison of carotid blood of intact lambs with that from recently nephrectomized lambs.3. Angiotensin II-like activity (mean +/- S.E. of mean, 315 +/- 117 pg/ml.) was readily detectable in foetal blood at 123-138 days gestation. The highest concentrations (mean +/- S.E. of mean 839 +/- 96 pg/ml.) were found in lambs less than 8 hr old, delivered vaginally. The lowest concentrations of angiotensin II-like activity occurred in lambs delivered by Caesarean section (mean +/- S.E. of mean < 123 +/- 12 pg/ml.). Concentrations declined with post-natal age.4. Hypovolaemia as a result of haemorrhage evoked an increase in angiotensin II-like concentrations in foetus, new-born lambs and adult sheep. The greatest increase of angiotensin-like concentrations was seen in new-born lambs. This rise was associated with increase of plasma renin.5. The rise of arterial pressure during bilateral carotid occlusion in new-born lambs was accompanied by an increase of angiotensin II-like concentration.6. It is concluded that the renin-angiotensin system is functional and can be stimulated during intra-uterine life. The increase of angiotensin II-like concentration following parturition is probably transient and associated with the trauma of delivery. This contrasts with observations made in the rabbit which suggest that full functional maturity of the renin angiotensin system is delayed until the second week of life.


Synapse formation during embryogenesis on ganglion cells lacking a periphery. 1. The development of transmission was studied in chick ciliary ganglia that had been deprived of their periphery during early embryonic development.2. Peripherally deprived neurones in the ganglion differentiate in normal numbers and send functional axons into the post-ganglionic nerve.3. Ganglion cells lacking a periphery follow the normal developmental sequence sending out transient dendrites at the time ganglion cell synapses are formed, and later retracting them when calyces appear.4. Synapses, which appear functionally and ultrastructurally normal, form on all ganglion cells at the normal time and transmission is normal until Stage 34. Therefore information from the periphery is not required for ganglion cell synapse formation per se.5. From Stages 35 to 38 most cells die, so that only 8% of the original number of cells remain in the operated ganglion. Transmission fails in many cells during this same time, but precedes cell loss by only a short time, so that deafferentation probably does not contribute substantially to cell death.6. Both ciliary and choroid cells achieve full cytologic differentiation and are distinct from each other, indicating that the periphery is not required for the elaboration of the distinctive characteristics of these cells. Presynaptic fibres also differentiate into typical bouton as well as calyciform endings. Therefore, the type of preganglionic ending does not depend on ganglion cells establishing proper peripheral contacts.7. It has not been possible to ascertain whether ganglion cell specificity is affected by the periphery.8. Peripheral removal affects ganglion cell migration, so that two ganglia are formed. Approximately half of the cells migrate into the remnant optic cup forming a second misplaced ganglion. Ciliary and choroid cells occur in both ganglia and these cells go through the typical sequence of events described above.


Synaptic transmission and cell death during normal ganglionic development. 1. During normal embryonic development of the chick ciliary ganglion, cell death over a 4-day period (Stages 35-39) reduces the number of ganglion cells by half, from 6500 to 3200. Both ciliary and choroid populations are affected by approximately the same amount.2. Previous to cell death, preganglionic fibres form functional synapses on all ganglion cells, indicating that synapses form on cells which are destined to die.3. Shortly before the period of cell death, there is a failure of transmission in approximately half the cells. Some evidence suggests that transmission failure in at least some of the cells is of preganglionic origin.4. Cell death is nearly synchronous with the establishment of peripheral connexions by ganglion cells, at least with respect to the ciliary population which forms functional synapses with iris muscle. This implies that those cells which die do so because they have failed to form adequate peripheral connexions.5. It is suggested that many of the cells in which transmission has failed die, bringing transmission through the ganglion back to 100%. However, transmission failure appears to be a transitory phenomenon in other cells which survive and probably results from death of their preganglionic elements. Restoration of transmission would then be brought about by the formation of new or more effective synapses by surviving preganglionic fibres.


Quantitative and graphic analysis of prosthetic treatment for "nasalance" in speech.


The effects of caffeine on sodium transport, membrane potential, mechanical tension and ultrastructure in barnacle muscle fibres. 1. The effects of graded concentrations of caffeine on the Na efflux were investigated. External application of 10 mM caffeine usually caused a biphasic response, viz. a fall, followed by a rise in the Na efflux. 1 and 5 mM caffeine usually caused stimulation. Only the stimulatory phase of this response depended on the presence of external Ca(2+).2. Internal application of 100 mM caffeine caused a small rise in the Na efflux, the magnitude of which was independent of external Ca(2+) and comparable to that obtained with external application of 1 mM caffeine. This action, however, could be greatly augmented by pre-treating the fibre with 5 x 10(-5)M ouabain.3. The rise in Na efflux caused by external application of 10 mM caffeine could be greatly augmented by pre-treating the fibre with 5 x 10(-5)M ouabain. The observed stimulatory response was biphasic, more so in the absence of external Ca(2+). Restoration of external Ca(2+) following the onset of the second stimulatory phase resulted in further rise of the Na efflux. Measurements of the Na efflux during treatment with graded concentrations of ouabain and 10 mM caffeine showed that the rate coefficient for Na efflux varied with the ouabain concentration in the range 10(-8)-10(-4)M. Measurements of the ouabain-insensitive Na efflux before and during treatment with 10 mM caffeine in bathing media containing varying concentrations of Ca, disclosed the existence of two Ca(2+)-thresholds, one in the 0-2.5 mM range and the other in the 12.5-15 mM range.4. Comparisons were made between the effects on the Na efflux of 10 mM caffeine followed by external acidification, and external acidification, followed by 10 mM caffeine. The magnitude of the response of the ouabain-insensitive Na efflux to external acidification before treatment with 10 mM caffeine was greater than that found when external acidification followed external application of the alkaloid. It also was considerably greater than that of the response to external application of 10 mM caffeine before external acidification.5. External application of 10 mM procaine prevented 10 mM caffeine from stimulating the Na efflux, and from inducing contractures. Internal application of 100 mM-EGTA reduced the response of the Na efflux to 10 mM caffeine, and also prevented the fibre from contracting. External application of 10(-4)M diphenylhydantoin reduced the response of the Na efflux to 10 mM caffeine but failed to prevent the development of contractures.6. Internal application of 0.05 M-cGMP, cAMP or its dibutyryl derivative caused a large rise in the Na efflux. The magnitude of the effects observed in ouabain-poisoned fibres was often greater than that in unpoisoned fibres. Internal application of 2.5 units/ml. phosphodiesterase beforehand failed to reduce the magnitude of the stimulatory response to injected cyclic nucleotides. Injected phosphodiesterase also failed to reduce the response of the Na efflux to 10 mM caffeine.7. External application of 10 mM caffeine to unpoisoned and ouabain-poisoned fibres caused a fall of approximately 10 mV in the membrane potential. In unpoisoned fibres this effect was transitory. The response of the membrane potential to internal application of graded concentrations of CaCl(2) was biphasic. When low concentrations of CaCl(2) were used the membrane potential underwent a small rise but when high concentrations were used the opposite was found. These results could not be repeated with graded concentrations of MgCl(2).8. The effects of graded concentrations of caffeine on tension development were also studied. Strong contractures were observed with caffeine concentrations as low as 4 mM, while peak tetanus tension was usually exceeded with 7-8 mM concentrations. The tension-external Ca(2+) curve was sigmoidal in shape.9. Electron microscopic studies showed that 10 mM caffeine in ASW caused little or no distension and disorganization of cisternal fine structure. Such structural changes, however, were far more pronounced in fibres suspended in Ca(2+)-free ASW and then treated with 10 mM caffeine in Ca(2+)-free ASW. Fibres soaked in Ca(2+)-free ASW had ruptured mitochondria and mitoplasts, whereas those additionally treated with 10 mM caffeine had relatively intact mitochondria.10. The main conclusions drawn from this work are: (i) that caffeine stimulates the ouabain-insensitive Na efflux (and inhibits the transport enzyme) by raising the internal free Ca(2+) concentration; (ii) that in the presence of inhibition of the transport enzyme, the magnitude of the stimulatory response to 10 mM caffeine depends not only on the external Ca(2+) concentration but mainly on the residual level of activity of the transport enzyme; (iii) that the Ca(2+)-sensitive and CO(2)-sensitive components of the ouabain-insensitive Na efflux, though not the same, may overlap at the level of the plasma membrane or share a common metabolic step away from the membrane; (iv) that cyclic nucleotides participate in the control of the magnitude of the ouabain-insensitive Na efflux, and that the phosphodiesterase system under the present experimental conditions does not seem to be involved in the mechanism underlying the stimulatory action of caffeine; (v) that the membrane potential changes caused by caffeine fail to explain the stimulatory response of the Na efflux, as well as contracture of these fibres; (vi) that the contractile machinery in these fibres is considerably more sensitive to caffeine than that in vertebrate muscle and the muscles of other arthropods, and (vii) that the Ca(2+) released by the sarcoplasmic reticulum which leads to a biphasic response of the Na efflux is the result of cisternal disorganization caused by caffeine.


On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock. 1. Long-lasting haemorrhagic hypotension (4.5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP(9a)), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP(9a) was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock.4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period.5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period.7. BPP(9a) had no measurable effect on the course of endotoxic shock.8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed.


Wilms' tumor and neuroblastoma. Survey of a ten year experience.


Relationship between Epstein-Barr virus-determined complement-fixing antigen and nuclear antigen detected by anticomplement fluorescence.


Interferon inhibition of autogenously induced virions (C particles) in synchronized L-929 cell cultures.


A preliminary investigation into the role of immunity in modifying the blood- borne spread of chemically induced rat sarcomas.


A complement-fixation test for the bovine leukemia (C-type) virus.


Naturally occurring sarcoma virus of the BALB/cCr mouse.


Inhibition of murine sarcoma development by deoxycorticosterone acetate.


Detection of mouse mammary tumor virus in cat kidney cells infected with purified B particles from RIII milk.


Atypical C particles in adenocarcinomas induced by implantation of FUKU cells.


Type-C virus particles in a feline angioma: a case report.


Renal malignant histiocytoma.

Renal malignant histiocytoma.


Belated recognition of adrenocorticotropic hormone-producing tumors in post-adrenalectomized Cushing's syndrome.


Serological indication of canine distemper and of infectious canine hepatitis in wolves (Canis lupus L.) in northern Canada.


Relationship of pulmonary particulates in English sparrows to gross air pollution.


Vulvovaginitis in wildebeest caused by the virus of infectious bovine rhinotracheitis.


Survey of diseases in free-living California sea lions.


Effect of several proteinase inhibitors on renin reaction.


Clinical applications of synthetic angiotensin II analogue.


Pressor responsiveness, hemodynamics and plasma renin activity in essential hypertension.


Effects of angiotensin on catecholamine metabolism in rat.


Analysis of relationship between renin-angiotensin system and blood pressure in experimental hypertension induced by kidney extract.


The kidney factors in the production of acute hypertensive vascular lesions.


Successful medical adrenalectomy with amino-glutethimide. Role of altered drug metabolism.


Management of hyperlipidemias.

Management of hyperlipidemias.


Effect of Ca on renin release in vitro and in vivo.


Renin content in subcellular fractions of kidney extract of renovascular hypertensive rats.


Detection of alpha-fetoprotein in mice infected with mouse hepatitis virus.


Presence of glucosyl ceramide and lactosyl ceramide in human intracranial tumours.


Properties of hemolytic streptococci grown in glucose-containing medium.


Separation of the contributions of voluntary and vibratory activation of motor units in man by cross-correlograms.


The ubiquitous effects of histamine phosphate on the atria of the albino mouse.


Starch estimation in leaf tissue--a comparison of results using six methods.


Hexachlorophene-induced changes in central and peripheral myelinated axons of developing and adult rats.


The metabolic consequences of trauma.

The metabolic consequences of trauma.


The valve action of intensity receptor.

The valve action of intensity receptor.


Regulation of size and birefringence of the in vivo mitotic apparatus.


The proximate chemical composition and the amino acid content of some Nigerian oil seeds.


Localized oscillations in neural networks. I. General considerations with nonlinear differential equations.


Endoscopy of the thoracic duct (lymphoscopy) via the external jugular vein in dogs.


A new technique for cannulating lymphatic vessels: experience in 150 extremities.


Lymphography without the aid of vital dyes.


Agencies' perceptions of factors affecting home care referral.


Hormones and sudden deafness.

Hormones and sudden deafness.


Glomus tumors: diagnosis and treatment.

Glomus tumors: diagnosis and treatment.


Electrical promontory testing in differential diagnosis of sensori-neural hearing impairment.


Juvenile angiofibroma: a more rational therapeutic approach based upon clinical and experimental evidence.


The prostaglandins: their significance in clinical practice.


Radioimmunoassay of polypeptide hormones and enzymes.


Newer developments in the determination of cyclic AMP and other cyclic nucleotides, adenylate cyclase, and phosphodiesterase.


The use of subzero temperatures in biochemistry: slow reactions.


In vitro study of the influence of some factors important for any physicochemical characterization of loose connective tissue in the microcirculation.


Peripheral neuropathy.

Peripheral neuropathy.


Electron microscopic studies on various types of inclusions found in autopsy cases. PART 111. Observation on fine structure of cytomegalovirus in paraffin embedded tissue.


Models of the quaternary structure of collagenase.


Physiology and genetics of carbamoylphosphate synthesis in Escherichia coli K12.


Kinetic scheme and kinetic parameters of the exchange of ATP-32P-pyrophosphates, catalyzed by tryptophanyl-tRNA synthetase from beef pancreas.


Chloroquine inhibition of repair of DNA damage induced in mammalian cells by methyl methanesulfonate.


Amino acid esters of 2'-O-methyladenosing -peptide acceptors in the ribosome. The role of 2'-hydroxyl.


Comparative studies of host-cell reactivation, colony forming ability and excision repair after UV irradiation of xeroderma pigmentosum, normal human and some other mammalian cells.


Detection of somatic recombination and mutation in Drosophila. A method for testing genetic activity of chemical compounds.


Effect of heterologous transplantation of H 4-II-E rat hepatoma cells into the cheek pouch of irradiated hamster.


Utilization of methadone hydrochloride for opiate addiction.


An SV40-induced initiation factor for protein synthesis concerned with the regulation of permissiveness.


Separation of parathyroid hormone and calcitonin-sensitive cells from non-responsive bone cells.


Excitatory action of hypothalamic substance P on spinal motoneurones of newborn rats.


Pseudotype formation between enveloped RNA and DNA viruses.


Effect of dexamethasone on herpes simplex virus type 2 infection in vitro.


Increased susceptibility to virus oncogenesis of congenitally thymus-deprived nude mice.


Inhibition of rat lymph node cell cytotoxicity by hepatoma-associated embryonic antigen.


[Site of transplantation and morphology of chemically induced gliomas in the rat].


Changes induced in rabbit plasma lipoproteins by polyunsaturated fat.


Establishment of continuous cell lines from leukocytes culture of a hamadryas baboon with leukosis-reticulosis.


Peripheral neuropathy in chronic renal failure.


Purified ovine growth hormone releasing factor: effects on growth hormone secretion and pituitary cyclic nucleotide accumulation.


Pituitary nuclear retention of dexamethasone and ACTH biosynthesis.


Action of hemicholinium-3 on cholinergic nerve terminals after alteration of neuronal impulse flow.


Spontaneous skin potential responses during sleep: comparative studies in newborns and babies between 2 and 5 months of age.


Concurrent pulmonary tuberculosis and bronchogenic carcinoma. Experience in large municipal hospital.


Letter: Hydrocyanic acid poisoning of cattle associated with sudax grass.


Biologic behavior of primary ovarian malignancy.


Metabolic properties of mouse transplantable adenocarcinoma. III. Oxidative phosphorylation by tumor and normal submaxillary gland mitochondria.


In vitro assay for human breast cancer hormone responsiveness. A study of 25 cases with clinical correlation. The in vitro effects of cortisol, estradiol, progesterone, and testosterone on the uptake of tritiated thymidine into the tumor cells of 25 women with primary or metastatic breast cancer were studied and compared with the objective clinical  response to ablative endocrine surgery.  A correlation between the clinical results with endocrine therapy and the in vitro assay results obtained in 23 of the 25 patients.  8 patients who did not respond to clinical endocrine therapy did not respond in vitro.  A significant clinical response (p less than .05) to ablative endocrine surgery, lasting for at least 6 months, was observed in 9 of 15 patients whose tumors responded in vitro.  Precise determination of the predictive capacity of the assay will require a blind prospective evaluation.


Verruciform xanthoma. A clinical, light microscopic, and electron microscopic study of two cases.


Metastasis to the gingiva. Report of a case of metastasis from the breast and review of the literature.


A comparison of the bone seeking properties of short-chained 99mTc-Sn-polyphosphates.


Renaturation of inactivated interferons by "defensive reversible denaturation".


Impact of adenoviruses in human disease.


Respiratory syncytial virus in infants and children.


Parainfluenza virus infections.

Parainfluenza virus infections.


Sexually transmitted diseases.

Sexually transmitted diseases.


Acute viral gastroenteritis.

Acute viral gastroenteritis.


Enzymatic mechanisms in the chemotaxis of neutrophils.


Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia. A new mechanism is described for the cellular esterification of cholesterol derived from extra-cellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30- to 40-fold increase in the rate of incorporation of either [(14)C]acetate or [(14)C]oleate into the fatty acid fraction of cholesteryl [(14)C]esters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterfication process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.


Proton magnetic resonance spectra of Rhodospirillum rubrum cytochrome c2. Nuclear magnetic resonance spectra of ferro- and ferricytochrome C(2) from the facultative photoheterotroph, Rhodospirillum rubrum, obtained with a 220-MHz spectrometer, are presented. Assignments to protons of various important structural groups in contact with or near the prosthetic heme group are given. These include (a) in the ferro-form, methyl, cbeta and cgamma protons of the extraplanar ligand residue, methionine 91, and methyl protons of the residue leucine 32; and (b) corresponding protons in the ferri-form with the addition of methyl protons from the condensation of a heme vinyl group with cysteine 17, a single proton from the condensation involving cysteine 14, and protons from the ring methyls. These resonances are compared with those corresponding to the same groups in horse heart cytochrome c.


Differential lectin agglutination of fetal, dividing-postnatal, and malignant hepatocytes. Numerous studies have reported the capacity of the lectin, concanavalin A, to agglutinate selected cell-types. The finding that cells transformed in culture, embryonic cells, and malignant cells are all agglutinated by this substance, may contribute to our understanding of the oncogenic process. The present study compared the response to concanavalin A of rat hepatocytes derived from livers of differing developmental and mitotic-status as well as those derived from malignant liver tumors (hepatomas). Fetal hepatocytes and hepatoma cells were highly susceptible to agglutination while hepatocytes from post-natal livers, whether dividing or quiescent, were not. Treatment with protease(s) did not make the interphase hepatocyte agglutinable. These data emphasize the importance of examining a wide variety of cells in attempting to understand the interaction of lectins on cell surfaces, and further, demonstrate the value of obtaining cells directly from tissue(s) during differing physiologic and pathologic states.


Evolution of type C viral genes: I. Nucleic acid from baboon type C virus as a measure of divergence among primate species. Hybridization studies with a [(3)H]DNA probe from an endogenous baboon type C virus were used to detect nucleic acid sequences of type C virus in primate cellular DNA. Sequences related to those of the baboon type C virus are found in all other Old World monkey species, higher apes, and man.


Characterization of binding components for progesterone and 5alpha-pregnane-3,20-dione in the hamster uterus. In the hamster uterus, a specific progesterone (pregn-4-ene-3,20-dione) receptor has been identified in the cytosol fraction. In the present study, we examined hamster uterine cytosol for the possible existence of specific macromolecules that bind the progesterone metabolite, 5alpha-pregnane-3,20-dione. When cytosol was analyzed by density-gradient centrifugation with sucrose-glycerol gradients and by Scatchard plot analysis of [(3)H]5alpha-pregnane-3,20-dione binding data, there was no evidence of specific binding components for this metabolite. In vivo treatment of proestrous hamsters with unlabeled progesterone, 5alpha-pregnane-3,20-dione, or cortisol for 1 hr revealed that only progesterone caused the depletion of progesterone-receptor sites from the uterine cytosol fraction. Incubation of uterine strips which had been preloaded with two different concentrations of [(3)H]-progesterone demonstrated that progesterone was metabolized to 5alpha-pregnane-3,20-dione and to a greater extent to 3alpha-hydroxy-5alpha-pregnan-20-one. The accumulation of 5alpha-pregnane-3,20-dione during progesterone metabolism appeared to be related to the availability of nonspecifically bound hormone. These studies (i) strongly suggest there is no specific receptor system for 5alpha-pregnane-3,20-dione in the uterine cytosol fraction, (ii) confirm the existence of a specific progesterone receptor in uterine cytosol, and (iii) provide evidence that progesterone itself mediates the uterine progestational response via interaction with a specific receptor system.


Regulation of herpesvirus macromolecular synthesis: nuclear retention of nontranslated viral RNA sequences. We report two instances of selective accumulation of herpes simplex 1 RNA transcripts in different compartments of infected HEp-2 cells. In the first, transcripts derived from about 50% of the viral DNA accumulated in the nuclei of cells 8 hr after infection. However, only 40-42% of the DNA was represented in transcripts accumulating in both cytoplasm and polyribosomes. A more striking disparity in the distribution of transcripts between nuclei and cytoplasm occurred when viral infection was initiated and maintained for several hours in the absence of protein synthesis. RNA complementary to about 50% of the viral DNA accumulated in the nuclei, while transcripts derived from only about 10% of the DNA were detectable in the cytoplasm. The transcripts that were selectively transported in the presence of cycloheximide seem to be functional messenger RNA molecules, since they were found on polysomes immediately after cycloheximide reversal. In contrast, RNA retained in the nuclei during the period of cycloheximide treatment was not mobilized when protein synthesis subsequently resumed. The two instances of selective RNA transport observed during herpesvirus infection suggest that only viral transcripts competent to function in translation are exported from the nucleus.


Polyriboadenylate sequences at the 3'-termini of ribonucleic acid obtained from mammalian leukemia and sarcoma viruses. The location of poly(A) sequences in the RNA of mammalian RNA-tumor viruses was determined by enzymatic analyses. The 56-64S viral genomic RNAs, the 20-40S viral subunit RNAs, and the 4-5S poly(A) sequences excised from these viral RNAs were subjected to either hydrolysis with a 3'-OH specific exoribonuclease from Ehrlich ascites tumor cells or phosphorolysis from the 3'-termini with polynucleotide phosphorylase from Micrococcus luteus. Purified adenosine-labeled poly(A) fragments, excised from genomic viral RNAs by RNase A and T(1) digestion, were hydrolyzed with the 3'-OH specific exoribonuclease for various periods of time. Poly(U) filter binding studies of the residual poly(A) indicated that 97% of the poly(A) fragments were hydrolyzed. Adenosine-labeled genomic and subunit viral RNAs and excised poly(A) fragments were phosphorolyzed from their 3'-termini for various periods of time with polynucleotide phosphorylase. The degree of phosphorolysis was monitored by poly(U) filter binding studies, and CCl(3)COOH insolubility and solubility determinations. There was an initial preferential rate of phosphorolysis of the poly(A) sequences of genomic and subunit viral RNAs as compared to the total adenosine-labeled viral RNAs. The data from these two different enzymatic mechanisms of action indicated conclusively that the poly(A) sequences were located at the 3'-termini of genomic and subunit viral RNAs.


Characterization of the end groups of RNA of Rous sarcoma virus. The 3' terminus of the 30-35S RNA of Rous sarcoma virus is adenosine. Its amount indicates an average molecular weight for that RNA of about 3 x 10(6). The 5' terminus of 30-35S RNA of Rous sarcoma virus was not di- or triphosphorylated, whether isolated by the standard procedure or from virus collected within 3 min of its release from the cells.


Nuclear coupling of 33S and the nature of free radicals in irradiated crystals of cystine dihydrochloride: Part II, charged radicals. The (33)S hyperfine structure has been observed in negatively charged cystine molecule-radicals RCH(2)(SS)(-)CH(2)R. The coupling, found to be axially symmetric about the SS bond, proved the orbital of the unpaired electron to be an antibonding SS sigma(*) orbital with the spin density shared equally between 3p(sigma(*)) orbitals of the two sulfurs. The (33)S hyperfine structure could not be detected for a second radical produced by irradiation of the cystine hydrochloride crystal at 77 degrees K, but interpretation of the proton hyperfine structure and g tensor observed by others led to the conclusion that this radical is the positively charged cystine molecule RCH(2)S(+)SCH(2)R with the spin density concentrated in a 3p orbital of one S and perpendicular to the SS bond.


Physical and physiological evidence for two phase transitions in cytoplasmic membranes of animal cells. Electron spin resonance analysis of suspensions of animal cell plasma membranes consistently reveals four characteristic temperatures for lateral phase separations in the membrane lipids. Similar analysis of an aqueous dispersion of lipids extracted from these membranes reveals only two characteristic temperatures, indicating that some aspect of lipid organization in membranes is destroyed by the extraction procedure. The characteristic temperatures for surface membranes from two different species of homeothermic animals were nearly identical and were approximately 37 degrees , 31 degrees , 21 degrees , and 15 degrees . A treatment of the physical data revealed that these temperatures could identify independent phase transitions for two hydrocarbon compartments of approximately equal size with lower and upper characteristic temperatures of 21 degrees and 37 degrees , and of 15 degrees and 31 degrees . The analysis of the effects of temperature on a number of physiological parameters indicates that 21 degrees and 37 degrees are likely to define the boundaries for lateral phase separations in the inner monolayer and 15 degrees and 31 degrees the boundaries for lateral phase separations in the outer monolayer.


Gap junction formation between reaggregated Novikoff hepatoma cells. We have combined freeze-fracture and electrophysiological methods in a study of gap junction formation between reaggregated Novikoff hepatoma cells. Cell clumps are dissociated with EDTA, and the resulting single cells are allowed to reaggregate (5-180 min) in loose pellets in the presence of calcium at 37 degrees . The earliest electron microscopic evidence for the genesis of new junctions is the appearance of flattened regions of the plasma membrane with a relative paucity of small intramembranous particles. These regions contain instead loosely organized groupings of 9- to 11-nm intramembranous particles, which are seen on the A face of the fractured plasma membrane, while corresponding pits occur on the membrane B face. We have termed the specialized membrane regions "formation plaques." They are seen as early as 5 min after reaggregation and are quite numerous by 30 min. Larger plaques are observed at later times. Plaques seen at 30 min are consistently matched with other plaques on apposed cells, although the extracellular space separating these structures still exceeds 10 nm. By 60 min, some matched plaques display a reduced extracellular space, resembling that of normal gap junctions. Between 30 and 60 min, aggregates of closely packed particles on A faces and hexagonally arranged pits on B faces frequently appear in the formation plaques. The aggregates, which are indistinguishable from small gap junctions, appear to enlarge over the subsequent 2-hr period as the number of unaggregated 9- to 11-nm particles declines. Microelectrode studies demonstrate progressive increases in the percent of interfaces containing lowresistance junctions and in the degree of elctrical coupling in preparations incubated up to 2 hr. Coupling is first detected at about the same time as particle aggregates (or formation plaques with reduced extracellular spaces), and increases as aggregate sizes increase.


Structure and molecular weight of the 60-70S RNA and the 30-40S RNA of the Rous sarcoma virus. The structure and molecular weight of the 60-70S RNA complex and the 30-40S RNA species of Rous sarcoma virus were analyzed in an electron microscope after treatment of the RNAs with the bacteriophage T4 gene-32 protein to stretch out the RNA strands. Although all RNA preparations treated with gene-32 protein showed considerable heterogeneity in length, a significant fraction of the RNA retained its original sedimentation coefficient after treatment to allow the following conclusions to be made: The 30-40S RNA was confirmed to be a linear polynucleotide with a molecular weight of about 3 x 10(6). The 60-70S RNA exhibited a network structure with a molecular weight predominantly of about 6 x 10(6). Therefore, the subunit hypothesis for the 60-70S RNA is confirmed. A model for the structure and molecular weight of the 60-70S RNA postulates that the complex consists of two 30-40S RNA subunits held together at many points. This model elucidates the biological observation that the infectivity of RNA tumor viruses is proportional to the amount of 30-40S RNA in a virus preparation and not to the amount of 60-70S RNA.


Intramolecular hydrogen bonding in flavin adenine dinucleotide. Data obtained by means of proton magnetic resonance spectroscopy indicate that specific association of FMN occurs with AMP in aqueous solution, because much weaker interaction is observed with FMN of either GMP or CMP. A comparison of FAD with a 1:1 mixture of FMN and AMP suggests that the flavin is involved in an intramolecular hydrogen bonding with the adenine moiety of FAD. The temperature dependence of chemical shifts would seem to indicate that the pyrophosphate linkage acts to reinforce stacking interactions as well as hydrogen bonding in the coenzyme. The linkage also limits the number of cyclic hydrogen bonding configurations, and a model is proposed to describe a fraction of unstacked FAD in aqueous solution.A parallel study was made of NAD(+) and its analogues; in contrast to FAD, no clear evidence of cyclic hydrogen bonding was obtained with the pyridine coenzymes.


Purification and properties of rat liver microsomal stearyl coenzyme A desaturase. The terminal enzyme of the NADH-dependent stearyl coenzyme A desaturase system has been isolated from rat liver microsomes. This desaturase is a single polypeptide of 53,000 daltons containing 62% nonpolar amino-acid residues and one atom of non-heme iron. The purified protein forms high molecular weight aggregates that can be dispersed by detergent procedures. Desaturase activity requires NADH, stearyl coenzyme A, oxygen, lipid, and the three enzymes, cytochorme b(5) reductase (EC 1.6.2.2), cytochrome b(5), and desaturase. Cytochrome b(5) is the direct electron donor to the desaturase, which appears to utilize the iron in the oxidation-reduction sequence during desaturation of stearyl coenzyme A.


Behavior of three types of ribovirus-like particles in segregating hamster times mouse somatic hybrids. An electron microscopic study of somatic hybrids resulting from a cross between hamster melanoma cells harboring R-type particles and mouse fibroblasts harboring intracisternal A-type and (mostly) immature C-type particles was performed. The major findings are: (a) hybrid cells that retain a large fraction of both hamster and mouse chromosomes produce all three types of particles; (b) the loss of mouse chromosomes is followed by that of intracisternal A- and C-type particles; (c) the continued production of A- and C-type particles is dependent on the retention of different mouse chromosomes; (d) the mixed intracellular population of R- and A-particles comprises a small number of complex structures in which the two types of virions are enclosed within a common envelope.


Adenylate cyclase from Brevibacterium liquefaciens. III. In situ regulation of adenylate cyclase by pyruvate. In the presence of DL-alanine intracellular cyclic AMP in nonproliferating cells of Brevibacterium liquefaciens increased rapidly to the maximum level of approximately 180 muM, and extracellular cyclic AMP increased to 100 muM within 4 hr at 25 degrees . Adenylate cyclase (EC 4.6.1.1) induction was not observed during this incubation. The concentration of pyruvate in the total culture increased concomitantly with that of cyclic AMP and reached approximately 20 mM after 4 hr of incubation. Since the activity of cyclic nucleotide phosphodiesterase is extremely low in this bacterium, the accumulation of cyclic AMP with DL-alanine appeared to be due to the activation of adenylate cyclase by pyruvate. D-alanine was more effective than L-alanine in producing pyruvate, and a high activity of D-alanine oxidation was detected in the cell lysate of B. liquefaciens.Thus, adenylate cyclase in this bacterium appeared to be regulated in vivo by pyruvate which was formed, in this case, predominantly from D-alanine through the action of D-aminoacid oxidase (EC 1.4.3.3). Pyruvate, added extracellularly, also caused a rapid accumulation of intracellular cyclic AMP. Glucose did not change the level of cyclic AMP significantly. It also did not affect the intracellular accumulation of cyclic AMP with DL-alanine.


Participation of N1-oxide derivatives of adenine nucleotides in the phosphotransferase activity of liver mitochondria. The modified adenine nucleotides ATP-NO, ADP-NO, and AMP-NO were tested as potential substrates and/or inhibitors of mitochondrial phosphotransferases. ADP-NO is not recognized by the translocase system located in the inner mitochondrial membrane; however, it is rapidly phosphorylated to ATP-NO in the outer compartment of mitochondria, by way of the nucleosidediphosphate kinase (EC 2.7.4.6) reaction, provided there is sufficient ATP in the mitochondria. AMP-NO is not phosphorylated by liver mitochondria to the corresponding nucleoside diphosphate; it cannot serve as substrate for adenylate kinase (EC 2.7.4.3). ATP-NO and ADP-NO, however, are substrates of this enzyme. The apparent equilibrium constant for the reaction, ADP-NO + ADP right harpoon over left harpoon ATP-NO + AMP, of 0.908 at pH 7.4 and 5 mM Mg(2+) is significantly higher than that of the reaction with natural nucleotides. Although adenosine N(1)-oxide is easily phosphorylated to AMP-NO by adenosine kinase [Schnebli et al. (1967) J. Biol. Chem. 242, 1997-2004], the formation of corresponding nucleoside triphosphate in vivo seems also to be limited by adenylate kinase; adenosine N(1)-oxide cannot replace adenosine in restoring the normal ATP level in ethionine-treated rats.


Effect of a fibroblast growth factor, insulin, dexamethasone, and serum on the morphology of BALB/c 3T3 cells. The effects of serum, fibroblast growth factor, dexamethasone, and insulin on the morphology of two lines of BALB/c 3T3 cells are described and illustrated. Fibroblast growth factor, a polypeptide purified from bovine brain and pituitary glands, stimulates DNA synthesis and cell division in both sparse and confluent cultures of quiescent 3T3 cells. When cells are grown in the presence of the factor, they go through one or two cycles of division and their morphology differs from that of cells either growing in 10% serum or maintained in a quiescent state in low serum; they appear rounded with long processes and show no sign of contact inhibition. When dexamethasone is present with the growth factor, the cells grow to a high density and are not contact-inhibited; they have the appearance of transformed cells. Addition of insulin or dibutyryl cyclic AMP to the cells results in a morphology similar to that of cells growing in the presence of serum. Addition of growth factor or growth factor plus dexamethasone to cells that have reached confluency in 10% serum and that are clearly contact-inhibited results in the resumption of growth. The final cell density reached is similar to that of cells growing in the presence of 30% serum with daily fluid changes. No contact inhibition is observed in either of these situations.


Glycophorin in lipid bilayers.

Glycophorin in lipid bilayers. Glycophorin, the major glycoprotein of human erythrocytes, has been isolated and reincorporated into lipid vesicles. Freeze-fracture electron microscopy shows the reincorporated glycophorin to occur as small particles in vesicle fracture faces while the etch faces are smooth. The glycoprotein has a tendency to cluster into groups of several particles. Evidence is presented that, although lipids in immediate contact with glycopherin are likely somewhat immobilized, the entire lipid-protein complex has a tendency to occupy fluid regions of the bilayer. Reincorporated glycophorin assumes its proposed conformation in the intact erythrocyte in so far as it penetrates the hydrophobic membrane interior while its N-terminal end with attached carbohydrate residues is exposed to the aqueous compartment and is available as a specific recognition site.


Latent DNA of Epstein-Barr virus: separation from high-molecular-weight cell DNA in a neutral glycerol gradient. Epstein-Barr virus DNA in virus non-productive cells was separated from high-molecular-weight cell DNA by sedimentation through a neutral glycerol gradient after gentle lysis of cells by Pronase and Sarkosyl. The isolated Epstein-Barr virus DNA had a density of 1.716-1.717 g/cm(3) in CsCl equilibrium centrifugation, which is very close to the virus DNA density of 1.718 g/cm(3). The results indicated that the majority of Epstein-Barr virus DNA in virus nonproductive cells is not covalently integrated into high-molecular-weight cell DNA.


Coexistence of several putative neurotransmitters in single identified neurons of Aplysia. By sensitive enzymatic micromethods several putative neurotransmitters were measured in four identifiable neurons of Aplysia californica (R-2, R-14, L-11, and C-1). Serotonin was found in all of these neurons, and octopamine in all but C-1. Acetylcholine has been previously reported to be present in R-2 and L-11. The catecholamines, norepinephrine and dopamine, were not detected in the four cells examined. The possible biological consequence of the presence of several putative transmitters in single identifiable neurons is discussed.


Competitive inhibition of beef heart cyclic AMP phosphodiesterase by cytokinins and related compounds. Two cytokinins and four related analogs, none of which is a cyclic ribonucleotide, have been shown to act as competitive inhibitors of the high K(m) cyclic-AMP phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) activity from beef heart. Weak inhibition of the low K(m) cyclic AMP phosphodiesterase activity was also observed, suggesting a possible mechanism for regulation of intracellular cyclic AMP levels by the exogenously added compounds. In addition to the kinetic data, obtained on the six inhibitors in four different heterocyclic series, 15 other cytokinins and related compounds have been shown to inhibit the high K(m) cyclic AMP phosphodiesterase activity at single concentrations of substrate and inhibitor. Heterocycles such as adenosine and 7-amino-3-methylpyrazolo[4,3-d]pyrimidine, which lack the N-substituent, were inactive as cyclic AMP phosphodiesterase inhibitors. The observed inhibition of cyclic AMP phophodiesterase supports prior observations which implicate exogenously added cytokinins in cyclic AMP metabolism.


Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with poorly differentiated carcinoma of the nasopharynx. A well-differentiated squamous cell carcinoma and three poorly differentiated carcinomas of the nasopharynx were analyzed for the presence of Epstein-Barr virus DNA by hybridization with radioactive complementary RNA. The well-differentiated carcinoma contained no detectable Epstein-Barr virus DNA, whereas the three anaplastic carcinomas contained 41, 16, and 14 viral genome equivalents per cell. The anaplastic carcinomas were heavily infiltrated with lymphocytes and other non-neoplastic cells. All four tumors were successfully passaged in nude (thymusless) mice. Mouse cell admixture in the heterotransplanted tumors was estimated by analysis of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and varied between 25% and 80%. After two passages in nude mice, the carcinoma that was negative for Epstein-Barr virus DNA remained negative, while the three anaplastic carcinomas retained their viral DNA. After correction for mouse cell admixture, the latter tumors were found to contain about 80, 55, and 160 Epstein-Barr virus genome equivalents per human cell. The virus-determined nuclear antigen was localized in the large carcinoma cell clusters in all three mouse-passaged tumors positive for the viral DNA, but other virus-determined antigens were not detected, indicating the absence of virus induction. In contrast to the original tumor biopsies, the nude-mouse-passaged tumors showed virtually no lymphocytic infiltration. It is concluded that the Epstein-Barr virus DNA found in biopsies of human nasopharyngeal carcinomas is localized in the neoplastic cells.


Isolation of a viral polypeptide associated with poliovirus RNA polymerase. Poliovirus-infected HeLa cells were labeled with radioactive methionine or phenylalanine and subjected to a new purification procedure for the viral induced RNA polymerase activity. Detergent-solubilized polymerase activity was purified by precipitation with 2 M LiCl and sedimentation through sucrose gradients. Approximately 0.001% of the incorporated amino acid radio-activity sediments with the peak of polymerase activity. Gradient fractions comprising the polymerase activity peak were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and found to contain predominantly one virus-specific polypeptide. Polyacrylamide gel electrophoresis also reveals that this purified polypeptide migrates with a 58,000 molecular weight noncapsid polio-virus polypeptide.


Plasminogen activator production accompanies loss of anchorage regulation in transformation of primary rat embryo cells by simian virus 40. We have isolated several lines of rat embryo cells transformed by simian virus 40. All these lines are fully transformed with regard to saturation density and serum sensitivity, but they differ greatly in their anchorage dependence, as assayed by efficiency of plating in methyl cellulose suspension. This set of lines reveals a consistent relation of plasminogen activator production to plating efficiency in methyl cellulose. T-antigen-positive transformed lines that synthesize activator grow in methyl cellulose suspension, while T-antigen-positive transformed lines that do not synthesize activator fail to form colonies in suspension. Normal rat embryo cells produce very little plasminogen activator and do not grow in methyl cellulose. Sera that permit high levels of plasmin formation and activity support growth in semi-solid medium better than sera whose plasminogen is activated poorly and/or sera that contain inhibitors to plasmin.


Focal erythrocyte membrane perturbations caused by nitroxide lipid analogues. Three classes of lipoidal nitroxide spin probes reversibly perturb erythrocyte membranes at low concentrations (10(-10)-10(-5) M). This is manifest in (a) decreased osmotic fragility and (b) alterations of surface topology. At bulk phase nitroxide concentrations providing maximal osmotic stabilization, the erythrocytes exhibit a classic echinocyte morphology. At nitroxide concentrations very slightly higher than those yielding minimal osmotic fragility (10(-5)-10(-4) M), the cellus undergo a sphering reaction and lyse. The morphologic sequence seen in intact cells is not observed in erythrocyte ghosts. We suggest that the spin probes initially concentrate in focal domains, which expand into echinocytic protrusions primarily due to localized weakening of membrane cohesion. We propose that cell lysis involves an irreversible breakdown in membrane domain structure.


Viable deletion mutants of simian virus 40: selective isolation by means of a restriction endonuclease from Hemophilus parainfluenzae. Resistance of simian virus 40 (SV40) DNA to cleavage by Hemophilus parainfluenzae II (HpaII) restriction endonuclease has been used as a positive, in vitro selection for mutants lacking the one HpaII endonuclease-cleavage site of wild-type SV40 DNA. Each of 10 viable mutants isolated by this procedure multiplies significantly more slowly than wild-type virus and contains a small deletion (80 to 190 base pairs in size) of the region of the genome that includes the HpaII endonuclease-recognition sequence. These well-defined mutants, having a selective disadvantage for growth, would not have been readily obtained by conventional methods used to screen for viral mutants. Therefore, in certain circumstances, restriction endonucleases are effective reagents for the selection of new classes of mutants. Because these small deletions can be visualized in heteroduplexes, these mutants provide internal markers for mapping other alterations or features of the simian virus 40 genome.


Initiator RNA in discontinuous polyoma DNA synthesis. During replication of polyoma DNA in isolated nuclei, RNA was found attached to the 5' ends of growing progeny strands. This RNA starts with either ATP or GTP and can be labeled at its 5' end with (32)P from beta-labeled nucleotides. Digestion of progeny strands with pancreatic DNase released (32)P-labeled RNA that, on gel electrophoresis, gave a distinct peak in the position expected for a decanucleotide. We believe that this short RNA is involved in the initiation of the discontinuous synthesis of DNA and propose the name "initiator RNA" for it. The covalent linkage of initiator RNA to 5' ends of growing DNA chains was substantiated by the finding that (32)P was transferred to ribonucleotides by alkaline hydrolysis of purified initiator RNA obtained by DNase digestion of polyoma progeny strands synthesized from [alpha-(32)P]dTTP. While initiator RNA was quite homogeneous in size, it had no unique base sequence since digestion with pancreatic RNase of initiator RNA labeled at its 5' end with (32)P released a variety of different [(32)P]oligonucleotides. The switch from RNA to DNA synthesis during strand elongation may thus depend on the size of initiator RNA rather than on a specific base sequence.


Kirromycin, an inhibitor of protein biosynthesis that acts on elongation factor Tu. Kirromycin, a new inhibitor of protein synthesis, is shown to interfere with the peptide transfer reaction by acting on elongation factor Tu (EF-Tu). All the reactions associated with this elongation factor are affected. Formation of the EF-Tu.GTP complex is strongly stimulated. Peptide bond formation is prevented only when Phe-tRNA(Phe) is bound enzymatically to ribosomes, presumably because GTP hydrolysis associated with enzymatic binding of Phe-tRNA(Phe) is not followed by release of EF-Tu.GDP from the ribosome. This antibiotic also enables EF-Tu to catalyze the binding of Phe-tRNA(Phe) to the poly(U).ribosome complex even in the absence of GTP. EF-Tu activity in the GTPase reaction is dramatically affected by kirromycin: GTP hydrolysis, which normally requires ribosomes and aminoacyl-tRNA, takes place with the elongation factor alone. This GTPase shows the same K(m) for GTP as the one dependent on Phe-tRNA(Phe) and ribosomes in the absence of the antibiotic. Ribosomes and Phe-tRNA(Phe), but not tRNA(Phe) or Ac-Phe-tRNA(Phe), stimulate the kirromycin-induced EF-Tu GTPase. These results indicate that the catalytic center of EF-Tu GTPase that is dependent upon aminoacyl-tRNA and ribosomes is primarily located on the elongation factor. In conclusion, kirromycin can substitute for GTP, aminoacyl-tRNA, or ribosomes in various reactions involving EF-Tu, apparently by affecting the allosteric controls between the sites on the EF-Tu molecule interacting with these components.


Cyclic nucleotides and growth control in cultured mouse cells: correlation of changes in intracellular 3':5' cGMP concentration with a specific phase of the cell cycle. The commencement of cell growth following serum addition to quiescent cultures of mouse fibroblasts is preceded by transient changes in intracellular concentrations of cAMP and cGMP. By artificial depletion of the culture medium for different nutrients, cell growth can be reversibly arrested in various phases of the cell cycle. Here it is shown that the major cGMP increases are only observed when cultures which are arrested in the G(0) phase are stimulated to grow or when synchronized growing cells pass through the G(1) phase. In addition to its concomitant decrease, cAMP exhibits rhythmic changes during the cell cycle. This suggests that the increase in cGMP could act as a specific signal for movement of cells out of the G(0) or G(1) phase of the cell cycle by activating the pleiotypic and mitogenic program of the cell.


Demonstration of a genetic factor influencing spontaneous release of a xenotropic virus of mouse cells. There is increasing evidence that mouse cells of different strains contain different numbers and biologic classes of naturally-integrated type-C RNA viruses. The present studies have examined the cellular regulation of one class of virus, xenotropic in host range, which is common to mice of NIH Swiss and NZB strains. This virus is spontaneously released at high level by NZB embryo cells but its production by NIH Swiss embryo cells is below detectable levels. Quantitative analysis of the chronic level of virus release by embryo cell lines established in tissue culture from genetic crosses of NIH and NZB strains has demonstrated the existence of a partially dominant gene influencing virus release. Evidence is presented indicating that this gene may act to provide a factor necessary for expression of a specific class of endogenous virus.


Unscheduled DNA synthesis in the germ cells of male mice exposed in vivo to the chemical mutagen ethyl methanesulfonate. An unscheduled DNA synthesis has been clearly demonstrated in meiotic and postmeiotic germ cell stages of the male mouse after in vivo treatment with a 250 mg/kg dose of ethyl methanesulfonate. The germ cell stages showing unscheduled DNA synthesis range from early to middle meiotic prophase stages through early to middle spermatid stages. The initiation of this synthesis, taken to be repair of chemically damaged DNA in these germ cells, is rapid, beginning within 1 hour after the injection of ethyl methanesulfonate. Unscheduled DNA synthesis has not been detected in the most mature germ cell stages, which give rise to dominant lethal mutations, nor does it occur in germ cell stages where protamine has replaced the chromosomal histones.


A quantal analysis of the synaptic depression underlying habituation of the gill-withdrawal reflex in Aplysia. Habituation, one of the simplest behavioral paradigms for studying memory, has recently been examined on the cellular level in the gill-withdrawal reflex in the mollusc Aplysia and in the escape response in cray-fish. In both cases short-term habituation involved a decrease in excitatory synaptic transmission at the synapses between the sensory neurons and their central target cells. To analyze the mechanisms of the synaptic depression in Aplysia, we applied a quantal analysis to synaptic transmission between the sensory and motor neurons of the gill-withdrawal reflex. Our results indicate that short-term habituation results from a presynaptic mechanism: a decrease in the number of transmitter quanta released per impulse. The sensitivity of the postsynaptic receptor remains unaltered.


Neurosurgical aspects of recurrent meningitis.


Active transport of calcium in inverted membrane vesicles of Escherichia coli. Accumulation of (45)Ca(++) was found to occur in membrane vesicles of E. coli prepared by lysis with a French pressure cell. The uptake occurs by active transport, requiring an energy source. Substrates of the electron transport chain, including D-lactate, reduced phenazine methosulfate, and NADH, stimulated accumulation, but this effect was blocked by the addition of cyanide. ATP could also stimulate accumulation, and this effect was blocked by dicyclohexylcarbodiimide. Uncouplers of oxidative phosphorylation inhibited the accumulation driven by either type of energy source. Accumulation of calcium is rapid, reaching the steady-state plateau within 1 min. Addition of phosphate to the assay buffer results in a prolongation of the reaction, allowing for the time-dependent accumulation of calcium for as long as 30 min. Vesicles prepared by lysis with a French pressure cell exhibit almost no ability to accumulate proline, while vesicles prepared by the method of Kaback transport proline but exhibit little energy-dependent transport of calcium. It is suggested that the accumulation of calcium in these vesicles, which are believed to be inverted, reflects a system that in vivo is responsible for the active extrusion of calcium from the cells.


Expression of murine leukemia virus structural antigens on the surface of chemically induced murine sarcomas. Cultured cells of different chemically-induced C57BL/6N murine sarcomas produced variable amounts of infectious murine leukemia virus (MuLV) and contained proportional amounts of MuLV structural components as determined by radioimmunoassay. Monospecific antisera directed against the major MuLV glycoprotein (gp71), the major internal antigen (p30), and the ribonucleoprotein (p10) were capable of mediating tumor cell lysis in the presence of complement, suggesting that these viral structural components were localized at least in part to the cell surface. Membrane immunofluorescence studies with MuLV p30 antiserum confirmed surface localization. Addition of MuLV p30 polypeptide to normal cells and tumor cells enhanced the cytotoxicity of MuLV p30 antiserum. Studies are presented which suggest that the presence of MuLV structural components on cell surfaces can be independent of virus production and cellular transformation.


Encephalomyocarditis (EMC) virus infection of the femoral artery of newborn mice.


Effect of acute cardiac overload on intramyocardial cyclic 3',5'-AMP: relation to prostaglandin synthesis.


Studies on the characterization of pure submaxillary gland renin.


Effect of dibutyryl cyclic AMP and serum deprivation on the membranes of transformed mouse fibroblasts. A freeze fracture study.


Different sensitivities of type 1 and type 2 Herpes simplex virus to sodium p-chloromercuribenzoate and chlorhexidine gluconate.


Intranuclear binding of hydrocortisone in liver and thymus tissues.


Prudence in orthopedic surgery.

Prudence in orthopedic surgery.


Practical approach to endocrine problems in office practice.


The effect of chronic alveolar hypoxia on lung and serum angiotensin I converting enzyme activity.


Differential effects of two strains of BCG on transplantation immunity to SV40-induced tumors in hamsters.


Mode of action and biological properties of insoluble interferon.


Evidence for chronic viral infections in human arteries.


Parathyroid hormone activation of adenylate cyclase in liver.


The role of the renin--angiotensin system in experimental renal hypertension in dogs.


Some new developments in the field of immunotherapy.


Effects of ions on adrenocorticotropin-sensitive adenylate cyclase of rat adrenals.


Isolation and characterization of an echovirus, possible "prime" strain of echovirus type 12.


Quantitative study on leucine incorporation in multinucleate cells induced by Sendai virus.


Neonatal hyperthyroidism and maturation of the rat hypothalamo-hypophyseal-adrenal axis.


Rhinoviruses: an antigenic study of the prototype virus strains.


Studies on the effect of collagenase and hyaluronidase on glycogen content of isolated rat liver parenchymal cells.


Effect of phenylalanine and p-chlorophenylalanine administration on the development of rat brain 2',3'-cyclic nucleotide 3'-phosphohydrolase.


Acute renal failure in disseminated intravascular coagulation. Experimental studies of the induction and prevention of renal fibrin deposition.


Antiviral activity of selected biguanide derivatives.


Effects of papaverine on smooth muscle and their mechanisms.


Influence of dietary sorbitol on some enzymes linked to glucose metabolism.


Inhibition of phosphodiesterase activity in brain cortical slices from guinea pig and rat.


The effects of ACTH- and vasopressin- analogues on CO2-induced retrograde amnesia in rats.


Central beta-adrenoceptor sites and ouabain action.


The in vitro effect of different substrates and high potassium concentration on the respiratory rate of slices, cell suspension and homogenate of brain.


Involvement of cyclic-AMP in changes of the structuredness of cytoplasmic matrix (SCM).


ESR investigations on radical formation after ultraviolet irradiation of trypsin in various polar and nonpolar media.


Glomus tympanicum and glomus jugulare tumors.


Photosensitization of small peptides by proflavine: an E.S.R. study at low temperature.


Immunofluorescence antibodies in human sera to antigens in cells of a type C virus producing human culture of tumor origin.


Malignant lesions of the ear.

Malignant lesions of the ear.


Oncoduction. A unifying hypothesis of viral carcinogenesis.


Mechanism of cytolysis by thymus-derived lymphocytes. Implications in tumor immunity.


Host immune response to virus-induced tumors. Some recent concepts.


Antigenic analysis of transformed and nontransformed cells from human neoplasms.


Antigenic expression as a determining factor of tumor growth in Gross' virus lymphoma.


Tumor-specific antigens and reexpression of fetal antigens in mammalian cells.


Vaccine production as a unit process.

Vaccine production as a unit process.


Relative DNA contents of fibroblast nuclei after collagenase digestion.


Control of exocrine pancreas secretion in vitro: a review.


Carcinoma of the cervix and herpes hominis (simplex) type 2 virus infection.


Slow potential changes evoked in nucleus medialis dorsalis of the thalamus by stimulation of the amygdaloid nuclear complex.


Uneven distribution of phospholipids in rat liver inner mitochondrial membranes.


Distribution of tumours in Uganda.

Distribution of tumours in Uganda.


Tumours of the female genitalia.

Tumours of the female genitalia.


Malignant tumours of the kidney, bladder and urethra.


Tumours of endocrine glands.

Tumours of endocrine glands.


Tumours of bone and jaw.

Tumours of bone and jaw.


Soft tissue tumours.

Soft tissue tumours.


Childhood tumours.

Childhood tumours.


Metabolic effects of seizures.

Metabolic effects of seizures.


Psychiatric disturbances in endocrine disease: some issues for research.


Histamine induced changes in pulmonary guanosine-3',5'-cyclic monophosphate (cGMP) and adenosine-3',5'-cyclic monophosphate (cAMP) levels in mice following sensitization by Bordetella pertussis and/or propranolol.


Clostridium perfringens (Cl. welchii) in the human gastro-intestinal tract.


Viruses associated with the healthy individual.


The normal microbial flora of the skin.

The normal microbial flora of the skin.


The normal microbial flora of the mouth.


Range of action of the mechanism that repairs damage induced by certain chemical agents in Escherichia coli K-12.


Heterotransplantation of human malignant neoplasms to the mouse mutant nude.


Alteration of cardiac contractility and hemodynamics by phosphodiesterase inhibition.


Cytomegalovirus antigen-antibody complexes in biopsy specimens in renal allograft rejection.


Effect of portacaval shunt on hepatic Krebs-Henseleit enzymes in dogs.


Immunosuppressive plasma factors in transplant recipients with viral infections.


Complete protection of severely damaged kidneys by a silica gel plasma perfusate.


Serum albumin alterations during experimental sepsis.


Cholera toxin as a suppressor of in vivo cell-mediated immunity.


Morphologic evidence of direct innervation of parietal cells in rodent gastric mucosa.


Calcium influx in gastric acid secretion.


Role of cyclic AMP system in humorally stimulated gastric acid secretion.


Immunochemotherapy of hepatoma in rats.

Immunochemotherapy of hepatoma in rats.


Estrogens and development of immobilization osteoporosis in rats.


Lymph flow augmentation secondary to increases in serum calcium.


Neurotrophism in relation to muscle and nerve grafts in rats.


Renin-angiotensin I activity in renin lymph during acute ureteral obstruction.


Action of alpha receptors of sympathetic nervous system on urethra and its vasculature.


Induction of aerobic metabolism by phosphocreatine following hemorrhagic shock.


Deoxycorticosterone inhibits a viral tumor.


Functional aspects of reinnervation of skin grafts.


Development of the trigeminal ganglion.

Development of the trigeminal ganglion.


The inhibition of cancer cell stickness by the methylxanthine derivative pentoxifylline (BL 191).


Contact activation of heparinized plasma.


Stimulation of human platelet adenylate cyclase by prostaglandin D2.


Relaxation of retracted clots: a thrombelastographic study.


Hypouricemic, mentally retarded infant with a defect of 5-phosphoribosyl-1-pyrophosphate synthetase of erythrocytes.


Hepatitis associated antigen in various clinical conditions especially in primary hepatoma and metastatic liver cancer.


The effect of Dianabol on certain cell energy processes in postirradiation disease.


Oxathiol effects on 210Po retention in the dogs' organs.


The nuclear envelope: current problems of structure and of function.


Feedback control mechanisms in micro-organisms and efficiency of growth.


Lipid-protein interactions in the structure of biological membranes.


Progress in and deterrents to orthotopic liver transplantation, with special reference to survival, resistance to hyperacute rejection, and biliary duct reconstruction.


Observations on the influence of ACTH on adrenal cholesterol metabolism.


Some observations on arterial and venous levels of angiotensin II in man.


Biosynthesis, secretion and mechanism of action of parathyroid hormone.


Radiographic diagnosis of joint diseases.


Interpretation of abdominal survey radiographs.


Studies of feline viral rhinotracheitis vaccine.


Virus-induced cell pathology as viewed in the scanning electron microscope.


Placental and fetal manifestations of cytomegalovirus infection.


Evolution and selective reduction of hormonal secretion in the mammotropic pituitary tumor (MtT-F4).


A new look at infectious gastroenteritis.


A simple, kinetic procedure for the optimized determination of the activity of serum glutamate dehydrogenase (EC 1.4.1.2.) with an enzyme analyzer.


Analysis of catecholamines, serotonin and their metabolites by ion pair partition and modern liquid chromatography.


True Arrhenius relationship of human lactate dehydrogenase.


The effect of dilution and substrate repletion on the fluormetric determination of lactate dehydrogenase (LDH) isoenzymes of sera with high LDH activities.


Determination of plasma cortisol by an enzymic fluorometric method.


Preparation of specific solid supports from p-nitrophenyl substituted polyacrylamide gels. Affinity chromatography of cAMP specific enzymes.


Specific coupling of nicotinamide adenine dinucleotide (NAD) to polymer supports.


A comparison of three methods of human plasma low density lipoprotein analysis.


Preparation and properties of an antibody to human low density lipoprotein.


Analysis of metobolites in human biopsies by means of analytical isotachophoresis.


Application of electron spin resonance to the study of alpha-amylase activity.


Circadian rhythm of the renin-angiotensin-aldosterone system.


Liver tumours in CF-1 mice exposed for limited periods to technical DDT.


Studies on electron spin resonance of Cu2+ complexes with nucleosides.


Solubilization of collagen fibrils by human leucocyte collagenase activated by rheumatoid synovial fluid.


The role of cyclic adenosine 3',5'-monophosphate in the synthesis of the enzymess of gamma-aminobutyrate breakdown in Escherichia coli K-12.


The prevalence of hypertension in an unselected population, and the frequency of abnormalities of potassium, angiotensin II and aldosterone in hypertensive subjects.


Borderline hypertension: correlation between the cardiac output and the vascular reactivity to norepinephrine.


A correlation between plasma renin activity and the pressor response to angiotensin II.


On the decrease curve of leukemic cells and the treatment of acute leukemia.


Effect of phytohemagglutinin, basic protein and measles antigen on myo-(2-3H)inositol incorporation into phosphatidylinositol of lymphocytes from patients with multiple sclerosis.


The cerebral copper-protein complexes in hepato-lenticular degeneration studied by means of electron-spin-resonance technique.


Peripheral nerve involvement in leprosy: quantitative histologic aspects.


Chloroquine-enhanced cerebellovascular changes in nutritionally imbalanced chicks.


Problems of the management of insulinomas. Review of 132 cases treated with medical measures.


Primary intracranial adenoid cystic carcinoma (cylindroma). An electron microscopic study.


New linear accelerator for radiation therapy. A preliminary report.


Fast neutron therapy. Past and present.

Fast neutron therapy. Past and present.


Corrections of isodose diagrams for 60Co and 35 MeV electrons at penetration of lung tissue.


Physical aspects on dose planning in treatment of mammary carcinoma.


Radiation dosimetry with exoelectron emitting materials.


Dosimetric investigation of postoperative irradiation of regional lymph nodes in mammary carcinoma.


Individual plastic casts for radiation treatment.


Small gas-tight ionization chambers for absorbed dose control during radiation therapy.


The radionuclide imaging process.

The radionuclide imaging process.


Computerised system for scintigraphy.

Computerised system for scintigraphy.


Spectrum stabilization on a whole body counter with three detectors.


Quantitative evaluation of isotope nephrograms.


Computer evaluation of scintigraphic images.


Computer processing of scintigraphic images.


The mineral content in bone. Measured by means of 27.5 keV radiation from 125I.


Digital stereoscintigraphy.

Digital stereoscintigraphy.


The dot counting method in scintigraphy.


Measurement of the resolution of a gamma camera system.


A new whole body monitoring laboratory.

A new whole body monitoring laboratory.


Transit dose in extracorporeal blood irradiation devices measured by means of thermoluminescence.


Cryosurgery. Principles and application to tonsillectomy.


Dosimetry by extracorporeal irradiation of blood.


Optical data processing. Principles and application to EEG audiometry.


Measuring methods for clinical investigation of the middle ear.


Beta and gamma radiochromatography with spark chambers.


Treatment couch according to the Malmö system.


Safety aspects of modern medical linear accelerators.


Instrument for dose rate measurements in gynaecologic radiation therapy.


Analytic approximation of the dose distribution from a 6 MeV linear accelerator.


Skin doses for electrons in the energy range 10 to 33 MeV. Measurements with thermoluminescence dosimeters.


Depth dose near the surface by fast electron irradiation. Measurements with thermoluminescence dosimetry.


Automation in radiation therapy.

Automation in radiation therapy.


Treatment of Hodgkin's disease by radiation therapy.


A digital electrometer.

A digital electrometer.


Irradiation of the thorax. Comparison between 60Co gamma rays, 6 MeV roentgen rays and 30 MeV electrons.


Radiophysical means for adequate radiation therapy with supervoltage apparatus at Radiumhemmet.


The importance of two independent integrating monitoring systems in medical accelerators.


45 MeV betatron for radiation therapy.

45 MeV betatron for radiation therapy.


The effect of cadmium on catecholamines and angiotensin responses in the dog kidney.


Effect of immunization with fetal cells on adenovirus-12 oncogenesis.


Ultrastructure of the ribonucleoprotein and messenger-like ribonucleic acid of the polyribosomes isolated from Rous sarcoma virus-induced mouse ascites sarcoma cells.


The role of cyclic nucleotide on fetal and neonantal erythropoiesis.


Attempts to isolate virus from human brain tumors.


Epstein-Barr virus (EBV) infections in army recruits.


Advances in penicillin research.

Advances in penicillin research.


An outbreak of arthrogryposis and hydranencephaly syndrome affecting calves in Israel: a retrospective epidemiological study.


Studies of the nicotinic receptor-response mechanism in Torpedo postsynaptic membranes.


Membranes of adrenal medulla: their role in exocytosis.


Binding of ADP and ATP to mitochondrial protein and its possible involvement in the mechanism of oxidative phosphorylation.


Modification of the secretory granule during secretion in the rat parotid gland.


Interactions of membranes, microfilaments, and microtubules in endocytosis and exocytosis.


The molecular organization of the beta granule of the islets of Langerhans.


Molecular basis of enzyme secretion by the exocrine pancreas.


The relation between cholinergic and monoaminergic activity in the caudate nucleus.


The pathology of Parkinsonism: a comparison of degenerations in cerebral cortex and brainstem.


Depigmentation in the nerve cells of the substantia nigra and locus ceruleus in Parkinsonism.


Biochemistry of neuromelanin.

Biochemistry of neuromelanin.


Free radicals in the human nervous system.


Dopaminergic involvement in hypothalamic function: extrahypothalamic and hypothalamic control. A neuroanatomical analysis.


Catecholaminergic control of gonadotropin and prolactin secretion with particular reference to the possible participation of dopamine.


Central noradrenergic neurons.

Central noradrenergic neurons.


The role of brain catecholamines in the regulation of ACTH secretion.


Mechanisms involved in the control of extrapyramidal dysfunctions and in striatal dopamine synthesis.


The use of protoplasts and separated cells in plant virus research.


Remarks on the ultrastructure of type A, B, and C virus particles.


Plant viruses with a multipartite genome.


On the problem of heredity in hypersomnia, narcolepsy and dissociated sleep disturbances.


Trophoblastic disease I.

Trophoblastic disease I.


Trophoblastic disease II. Trophoblastic invasion.


Trophoblastic disease III. Choriocarcinoma and related diseases.


Blood flow through the thyroid gland in rats.


PR aside: initial results from NIMH's service program evaluation studies.


Vinca alkaloids. Experimental and clinical trials.


The role of viruses in congenital defects.


Concomitant Mycoplasma and adenovirus infection in a family.


Radioimmunoassay of alpha-fetoprotein in human serum: clinical value in patients with liver diseases.


Rational use of psychotropic drugs. I. Hypnotics.


Cushing's disease with cure by resection of a pituitary adenoma. Evidence against a primary hypothalamic defect.


Cell surface contributions to the malignant process.


Statistical correlation of uveitis syndromes with virus titers.


Parathyroid hormone stimulation of glucose and urea production in isolated liver cells.


Renal function in dogs with acute selective hepatic venous outflow block.


Facilitation of transmitter release at the mammalian neuromuscular junction.


Effect of parathormone and cyclic adenosine monophosphate on renal bicarbonate reabsorption.


MEPP frequency distribution in rat diaphragm under vitamin E deficiency.


Alterations in pharmacologic receptor activity by dithiothreitol.


Effects of phosphate depletion and parathyroid hormone on renal glucose reabsorption.


Theophylline, cyclic AMP, choleragen, and electrolyte transport by rabbit ileum.


Comparison of the biochemical composition of four preparations of contracting cardiac muscle.


Partial resection of the liver for primary cholangiocarcinoma. Presentation of a successful case.


Inhibition of gastric acid secretion by extract of WDHA tumor.


Enzymatic liberation of myogenic cells from adult rat muscle.


Blood vessel wall characteristics in experimental hypertension.


Conference on the scientific basis of respiratory therapy. Aerosol therapy. Steroid and antibiotic aerosols.


Extra-adrenal retroperitoneal paraganglioma.


Intracellular metabolism of oxygen.

Intracellular metabolism of oxygen.


Accuracy, sensitivity, and specificity of electron spin resonance analysis of mineral constituents of irradiated tissues.


The replication of herpes viruses.

The replication of herpes viruses.


Treatment of shrinkage diseases of the conjunctiva.


Ocular complications in renal transplant patients.


Pheromones as a means of genetic control of behavior.


Genetics of DNA tumor viruses.

Genetics of DNA tumor viruses.


Regulation: positive control.

Regulation: positive control.


Test method for the evaluation of virucidal efficacy of three common liquid surface disinfectants on a simulated environmental surface. The Association of Official Analytical Chemists bacterial use-dilution test for evaluating liquid surface disinfectants was modified to determine the efficacy of three common environmental germicide compounds against representatives of four virus groups. Modifications were made to conform to the Environmental Protection Agency guidelines on virucidal testing procedures. Alterations included: the use of a concentrated tissue culture preparation of virus instead of a standard bacterial culture; HEp-2 tissue culture cells as a visible test system in place of standard nutrient broth; and controls to measure the virus titer end point and the toxicity of the disinfectant to the cell cultures. Comparison of control end points with results from the test proper were the measure of the effectiveness of the germicides against the viruses. Results are described which agree with those based on other methods previously reported.


Recovery of heated Clostridium perfringens type A spores on selective media. The enumeration of Clostridium perfringens spores on sulfite-polymyxin-sulfadiazine agar (SPS), tryptone-sulfite-neomycin agar (TSN), Shahidi-Ferguson-perfringens agar (SFP), tryptone-sulfite-cycloserine agar (TSC), and TSN lacking antibiotics (BASE) was studied. The spores were heated at 105 to 120 C by the capillary-tube method. The media were about equally efficient for the enumeration of heat-activated spores. Efficiency of the media for the recovery of spores surviving heat treatments at ultrahigh temperatures varied as follows: TSC >/= SFP > BASE > SPS > TSN. Greater recovery when survivors were enumerated on TSC or SFP was attributed to germination of injured spores by the lysozyme present in the egg yolk emulsion used in these media. Low recovery of survivors on TSN and SPS was due to both the absence of lysozyme and inhibition of injured spores by the selective agents of these media. Recovery of heated spores was reduced greatly by polymyxin, neomycin, and kanamycin, and slightly by sulfadiazine and D-cycloserine. The addition of lysozyme to SPS or TSN did not improve the percentage of heat-injured spores recovered because the selective agents of these media interfered with the action of lysozyme. The suitability of the selective media for the enumeration of survivors was greatly affected by the presence of certain foods.


Cold shock lethality and injury in Clostridium perfringens. Several observations have been made in regard to cold shock lethality of Clostridium perfringens: (i) loss of viability was not consequence of exposure of the cells to air; (ii) stationary-phase cells were much more resistant to cold shock at 4 C than exponential-phase cells; (iii) at 4 C 96% of an initial population of exponential-phase cells was killed upon cold shock and 95% of the remaining population was killed within 90 min of continued exposure at 4 C; (iv) the minimal temperature differential for detectable cold shock lethality was between 17 and 23 C, and the maximum beyond which lethality was not appreciably increased was between 28 and 33 C. Up to 75% of viable cold-shocked cells were injured, as demonstrated by cold shocking late exponential-phase cells at 10 C and using differential plating procedure for recovery. Repair of injury was temperature dependent, and occurred in a complex medium and 0.1% peptone but not water. Nalidixic acid, chloramphenicol, and rifampin did not inhibit repair of injury.


Simplified method for the preparation of silica gel media. A simplified and reliable method for the preparation of a variety of silica gel media is described. The growth of common microorganisms on these media was examined.


Chemical disinfection of holding-tank sewage. A number of chemical disinfectants were evaluated for their bactericidal and virucidal effectiveness in holding-tank sewage. It was found that the disinfection efficiencies of formaldehyde, benzalkonium chloride, cetylpyridinium chloride, and methylene blue were markedly improved if the pH of the sewage was raised from 8.0 to 10.5. When formaldehyde, benzalkonium chloride, and methylene blue were tested with either 2-week holding times with no sewage additions or 10-day holding times with daily sewage additions, disinfection effectiveness was maintained as long as the sewage pH was kept at 10.5 and the disinfectant concentration was kept at 100 mg/liter or more. Calcium hypochlorite, zinc sulfate, and phenol were found to be relatively ineffective disinfectants for holding-tank sewage.


Response of ligated intestinal loops in chickens to the enterotoxin of Clostridium perfringens. Approximately 45-cm length of jejunoileum of 7-week-old chickens was found to be responsive and suitable for testing the enterotoxin of Clostridium perfringens by the ligated intestinal loop technique. Injections of 20 to 30 mug of enterotoxin per loop caused positive response of fluid accumulation. Chickens were found to be more convenient and economical for this purpose than other laboratory and domestic animals.


Persistence of enteroviruses in lake water. Two enteroviruses were inactivated more rapidly in a lake than in sterile lake water; then their coat proteins were degraded and, perhaps, used by microorganisms.


The effect of Zn2+ ions on mitochondrial electron transport.


Partial specificity of low-molecular weight RNA that stimulates RNA synthesis in various tissues.


The effect of essential amino acid deprivation on macromolecular synthesis and nucleotide pool sizes in Neurospora crassa.


Alterations in glucose metabolism in chick embryo cells transformed by Rous sarcoma virus. Transformation-specific changes in the activities of key enzymes of the glycolytic and hexose monophosphate shunt pathways.


Occurrence of initiation factor 2 in the postribosomal fraction and identification of an initiation inhibitor as elongation factor G.


Concanavalin A and wheat germ agglutinin receptor activity of sialoglycopeptides isolated from the surface of Novikoff hepatoma cells.


Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase and cytochrome b5 as electron carriers in NADH-supported cytochrome P-450 -dependent enzyme activities in liver microsomes.


Absence of high-affinity adenosine 3',5'-monophosphate binding sites from the cytosol of three hepatic-derived cell lines.


D2O effects on association behavior and binding properties of phospho- and dephospho-cytoplasmic malic dehydrogenase.


Mechanism of aromatic hydroxylation. Properties of a model for pyridine nucleotide-dependent flavoprotein hydroxylases.


Resonance Raman spectra of the b- and c-type cytochromes of succinate-cytochrome c reductase.


Properties of purified kidney microsomal NADPH-cytochrome c reductase.


Structural implications derived from the analysis of electron paramagnetic resonance spectra of natural and artificial copper proteins.


Calcium-dependent cyclic nucleotide phosphodiesterase from glial tumor cells.


Pharmacological receptors and the control of cell function.


Modulation of trigeminal reflexes during the REM state in brain transected cats.


Paget's disease of the breast.

Paget's disease of the breast.


Studies on a gram-positive hydrogen bacterium, Nocardia opaca 1 b. III. Purification, stability and some properties of the soluble hydrogen dehydrogenase.


Advances in lipoprotein research. Biochemical and clinical aspects.


A phototrophic gliding filamentous bacterium of hot springs, Chloroflexus aurantiacus, gen. and sp. nov.


Characterization of amino acid pools in the vacuolar compartment of Saccharomyces cerevisiae.


Linkage of the Salmonella typhimurium chromosomal loci encoding for the cytochrome-linked L-alpha-glycerophosphate dehydrogenase and amylomaltase activities.


Drug and sociotherapy in the aftercare of schizophrenic patients. III. Adjustment of nonrelapsed patients.


Drug and sociotherapy in the aftercare of schizophrenic patients. II. Two-year relapse rates.


Regulation of biosynthesis of aspartate family amino acids in the photosynthetic bacterium Rhodopseudomonas palustris.


Sleep amphetamine effects in MBDS and normal subjects.


A simple method for the quantification of 140S particles of foot-and-mouth disease virus (FMDV).


Complement-requiring neutralizing antibodies in cattle to infectious bovine rhinotracheitis virus.


Analysis of minimal functions of simian virus 40. IV. Oncogenic transformation of syrian hamster kidney cells in vitro by beta-propiolactone inactivated sv40.


Varicella virus isolation from spinal ganglion.


Inhibition of giant cell formation by Compound 48-80 after infection with herpesvirus hominis. III. Binding of tritium-labelled Compound 48-80 to normal and infected cells and its action upon phosphatidyl-choline-biosynthesis.


Study of poliovirus multiplication in different animal species using photosensitized virus strains.


The properties of intracellular paramyxovirus ribonucleoprotein in a nonpermissive system.


Improvement of methods for intratypic differentiation of polioviruses. I. Agar gel diffusion precipitation test with repeated addition of antigens for differentiation between wild and vaccine polioviruses type 1 and 2.


Herpes simplex viruses types 1 and 2. Type and strain specific characteristics affecting virus plaque formation.


Inhibition of giant cell formation by Compound 48-80 after infection with herpesvirus hominis. IV. Compound 48-80, an inhibitor of choline kinase activity.


Improvement of methods for intratypic differentiation of polioviruses. II. Use of strain-specific antisera cross-adsorbed with antigens of heterologous strains in agar gel diffusion precipitation test for differentiation between wild and vaccine strains of poliovirus typess 1,2 and 3.


Improvement of methods for intratypic differentiation of polioviruses. III. Neutralization test with cross-adsorbed sera for differentiation between wild and vaccine strains of polioviruses.


Properties of SV40 rescued from actinomycin D-sensitive and actinomycin D-resistant transformed hamster cells. I. Lytic infection.


Subependymal germinolysis.

Subependymal germinolysis.


The thrombotic syndrome associated with carcinoma. A clinical and neuropathologic study.


Regulation of lactate dehydrogenase activity in Actinomyces viscosus by adenosine-5'-triphosphate.


Letter: Aerosol administration of the SA-2 vaccine strain of infectious laryngotracheitis virus.


Karyometric studies of thioacetamide-induced hepatomas.


Hepatic parenchyma weight changes in the presence of primary and secondary tumors of the liver: a morphometric study.


Structure and function of the stimulated adrenal cortex. 2. Early effects of ACTH on the ultrastructure of the zona fasciculata in dexamethasone--treated rats.


Concentration of elongation factor 2 in rat skeletal muscle during protein depletion and re-feeding. Rat skeletal-muscle elongation factor 2 was assayed by causing it to react with NAD(+) by using fragment A of diphtheria toxin as the catalyst. Dietary protein restriction decreased the concentration of elongation factor 2 in homogenates of whole muscle. These decreases paralleled a decline in muscle RNA so that the number of molecules of elongation factor 2 per ribosome appeared to be independent of the diet. We conclude that elongation factor 2 is probably not the factor limiting the rate of muscle protein synthesis and is not responsible for the fall in the protein-synthetic rate in vivo observed in the muscles of animals whose dietary protein intake is inadequate.


The effect of energization on the apparent Michaelis-Mentne constant for oxygen in mitochondrial respiration. Lineweaver-Burk plots of 1/v against 1/[O(2)] for rat liver mitochondrial respiration with succinate or ascorbate+NNN'N'-tetramethyl-p-phenylenediamine as substrates are non-linear. In state 3u (uncoupled by trifluoromethoxycarbonyl cyanide phenylhydrazone) such plots tend to be concave upward, whereas in state 4 (energized) the plots were concave downward. The apparent K(m) for oxygen is larger in state 4 than in state 3u, despite the higher turnover in the latter system. It is postulated that at least one reversible reaction occurs between cytochrome c and cytochrome c oxidase, whose rate is increased on energization (reversed electron transfer); a model including such a reaction is proposed which accounts semiquantitatively for the observations.


Metabolism of dihydrotachysterol and 5,6-trans-cholecalciferol in the chick and the rat. Dihydrotachysterol and 5,6-trans-cholecalciferol are biologically active analogues of cholecalciferol (vitamin D) with a similarity in steric structure to 1,25-dihydroxycholecalciferol, the active form of the vitamin. The question arises as to the nature of the active form of these analogues. High specific radioactivity (14)C- and (3)H-labelled forms of dihydrotachysterol and 5,6-trans-cholecalciferol and its 25-hydroxy derivative were synthesized and their metabolism was studied in chicks and rats. All these steroids were very rapidly metabolized compared with cholecalciferol; 20% of the dihydrotachysterol dose was excreted in bile in the first 24h, about 50% as a carboxylic acid derivative. Although polar metabolites were detected in tissues, no 1-hydroxy form was observed. Larger proportions of the parent steroid and its 25-hydroxy metabolite were detected in tissues compared with cholecalciferol, but no single metabolite was detected at the intracellular site of action of cholecalciferol. It is suggested that analogues of cholecalciferol will be biologically active if they possess a hydroxyl group in the same steric position as that at C-1 of cholecalciferol, with the greatest activity shown by those that also have a C-25 hydroxyl group. The implication of these findings for the chemical features necessary for binding to receptor proteins are briefly discussed.


A new method for the preparation of uniformly 14C-labelled compounds by using Anacystis nidulans. 1. Growth conditions were devised which enabled Anacystis nidulans to be grown on high specific radioactivity (14)CO(2) (at over 98% isotopic abundance of (14)C) in a closed system with greater than 85% substrate utilization. 2. The DNA and RNA content of A. nidulans was estimated by various methods and compared with that of Chlorella pyrenoidosa. 3. A procedure was developed for the quantitative extraction and separation of the DNA and RNA from A. nidulans. 4. The fractionation and analysis of the DNA and RNA includes methods for the preparation of the uniformly (14)C-labelled deoxyribonucleoside monophosphates and the uniformly (14)C-labelled ribonucleoside monophosphates. 5. The base 6-methylaminopurine was identified as a component of the DNA. 6. The preparation and total yield of uniformly (14)C-labelled amino acids from A. nidulans are also briefly described. The results are discussed in relation to the use of other micro-organisms for the preparation of compounds labelled with (14)C.