Specific photoaffinity labeling of the adenosine 3':5'-cyclic monophosphate receptor in intact ghosts from human erythrocytes. [(3)H]N(6)-(Ethyl 2-diazomalonyl)-adenosine 3':5'-cyclic monophosphate is incorporated into intact ghosts from human erythrocytes on photolysis at 253.7 nm. Incorporation is blocked in the presence of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and does not occur in the absence of irradiation. Sodium dodecyl sulfate disc gel electrophoresis of solubilized ghosts shows that one protein is labeled. The position of this protein on the gel corresponds exactly to that previously found. [J. Biol. Chem. 247, 8145 (1972)] for the endogeneous protein substrate of the endogenous, cyclic AMP-dependent, protein kinase.


In vitro translation of oogenetic messenger RNA of sea urchin eggs and picornavirus RNA with a cell-free system from sarcoma 180. A cell-free protein-synthesizing system prepared from mouse sarcoma 180 was characterized by use of RNA from mengo virus and sea urchin egg. In the presence of exogenous mammalian transfer RNA, total sea urchin egg RNA and mengo RNA direct incorporation of [(3)H]leucine into acid-insoluble material. The system is extremely efficient in that a stimulation of 100-times over background can be obtained. Studies with formylmethionyl-transfer RNA, as well as with inhibitors of initiation, indicate that multiple initiation occurs; further, 85-90% of all chains made in vitro are subsequently released from ribosomes. An average translation time of 3.5 min was determined with messenger RNA of sea urchin egg, and product analysis indicates that high-molecular-weight products (greater than 50,000 molecular weight) are being made in vitro. Sequences of sea urchin egg RNA containing poly(A) act as messenger RNA.


Direct evidence of the C-like form of sodium deoxyribonucleate. From infrared linear dichroism studies, direct evidence is given for a new Na DNA form, which is similar to the C form of Li DNA. This C-like form in Na DNA occurs under conditions of very low NaCl content (at high relative humidity), high NaCl content (at low relative humidity), and low G + C content of the DNA (at low relative humitiy). The C form of Li DNA was originally discovered by x-ray diffraction, but has not previously been characterized by infrared spectroscopy. The C form is primarily characterized by the orientation of the O2- -O3 line of the phosphate group, which is about 48 degrees (+/-2 degrees ) with respect to the helical DNA axis and which is different from that of the B and A forms. Na DNA molecules rich in A + T may entirely or partially adopt the C form at low relative humidity. Since from infrared evidence, the C-like form is found not only in Li DNA at low relative humidity but also in Na DNA under different conditions, the C form may be biologically important. A possible role for recognition by proteins is suggested.


Altered growth behavior of malignant cells associated with changes in externally labeled glycoprotein and glycolipid. By use of galactose oxidase (EC 1.1.3.9), followed by reduction with tritiated sodium borohydride, the surface structures of transformed 3T3 and NIL cells, under ordinary growth conditions, were characterized by (i) deletion of the normally existing glycoprotein label and (ii) appearance or increase of a new glycoprotein label. NIL cells had a galactoprotein label with molecular weight 200,000 that was deleted in NIL cells transformed by polyoma virus. 3T3 cells had a glycoprotein label with molecular weight of 30,000 that was lost after transformation. Glycoproteins of transformed 3T3 cells, with molecular weight 105,000, and those of transformed NIL cells, with molecular weight 85,000, were not labeled in normal confluent cells, but became labeled after trypsin treatment. The label in glycolipids was quantitatively different in normal and transformed cells. The labeling pattern in glycoprotein and glycolipids of transformed NIL and 3T3 cells became similar to that of nontransformed cells when contact responses of transformed cells became conspicuous when cells were cultured in the presence of dextran sulfate or dibutyryl cyclic adenosine monophosphate, or in medium in which glucose was replaced with galactose.


Inhibitory action of Ruthenium red on neuromuscular transmission. The effect of Ruthenium Red on synaptic transmission was examined at isolated junctions of the frog, by conventional methods for stimulation and intracellular recording. Ruthenium Red (2.5-10.0 muM) reduces the synaptic potential to subthreshold levels. An analysis of this phenomenon shows that the main action of Ruthenium Red is on the presynaptic nerve terminal where it decreases the number of quanta of transmitter liberated by the nerve impulse. It has the following additional effects: a reduction in the amplitude of the spontaneous miniature end plate potentials; an increase in their frequency; and an increase in delayed release of transmitter after a nerve impulse. Some of these results are discussed in terms of the known inhibitory action of Ruthenium Red on calcium transport across mitochondrial membranes.


Nuclear binding of steroid receptors: comparison in intact cells and cell-free systems. In regulating gene expression in mammalian tissues, steroid hormones bind to cytoplasmic receptors and the resulting complex associates with the nucleus. In an attempt to study this nuclear association under more precisely controlled conditions, we examined the binding of receptor-[(3)H]steroid complexes to isolated nuclei. Two systems were used: the glucocorticoid-responsive hepatoma cell and the estrogen-sensitive immature rat uterus. Cell-free nuclear binding resembles that observed in the intact cell; it requires the receptor-steroid complex in the appropriate form ("active" complex); it is of high affinity; and it appears to involve about 4000 nuclear acceptor sites per haploid genome. Furthermore, whether binding occurs in intact cells or in cell-free extracts, complexes dissociate from nuclei at similar rates, and the ability of NaCl to extract either type of nuclear-bound complex and the sedimentation velocities of the extracted complexes are identical. Despite these similarities, acceptor sites detected in isolated nuclei differ from those of intact cells, since in neither hepatoma cells nor in the uterus do complexes bound to the nuclei of intact cells prevent further cell-free binding. We conclude that receptor-steroid complexes bind to acceptor sites in isolated nuclei that are chemically similar to, but topographically different from, those of the intact cell.


Regulation of hepatic glycogen synthesis during fetal development: roles of hydrocortisone, insulin, and insulin receptors. In fetal rat liver in utero, an increase in glycogen and the glycogen synthetic enzyme glycogen synthetase (EC 2.4.1.11) occurs between gestational days 17 and 19. We used an organ culture system for finding the stimulus for increased enzyme activity and defining the relationship of this increase to glycogen synthesis. In fetal-liver explants from an earlier period (gestational day 16), hydrocortisone causes an elevation in total glycogen synthetase activity. This effect, which can be blocked by actinomycin D, is strikingly similar in time course and magnitude to the normal increase in utero. However, in order for glycogen synthesis to proceed after hydrocortisone increases glycogen synthetase levels, insulin is required. Unlike hydrocortisone, insulin does not increase total glycogen synthetase; it appears to act by converting the b or phospho form of synthetase to the a or dephospho form. Insulin alone does not stimulate glycogen synthesis in explants from 16-day fetal liver, although no defect in insulin binding was demonstrable. These findings support the hypothesis that the increase in liver-glycogen synthesis during the last trimester requires glucocorticoids for the developmental induction of glycogen synthetase and insulin for activation of the enzyme.


Thyroid hormone action in cell culture: domonstration of nuclear receptors in intact cells and isolated nuclei. Triiodothyronine and thyroxine induce a 3-fold increase in the rate of growth of GH(1) cells in culture. To study further the action of these hormones, we examined the binding of [(125)I]triiodothyronine and purified [(125)I]thyroxine to cellular fractions after incubation with intact cells in serum-free medium. High-affinity, low-capacity binding sites for the hormones were demonstrated in nuclear but not in mitochondrial or cytosol fractions. Chromatographic analysis of the bound nuclear radioactivity from cells incubated with [(125)I]thyroxine demonstrated 97% thyroxine, 1% iodide, and 1% triiodothyronine. Apparent equilibrium dissociation constants, determined by Scatchard analysis, were 29 pM for triidothyronine and 260 pM for thyroxine. The maximal binding capacity was identical for both hormones, with about 5000 sites per cell nucleus. [(125)I]Thyroxine binding was competitively inhibited by triiodothyronine. These data suggest that triiodothyronine and thyroxine interact with identical nuclear receptors, and that conversion of thyroxine to triiodothyronine may not be a prerequisite for biologic activity. Similar high-affinity, low-capacity nuclear binding sites were also demonstrated by incubation of [(125)I]triidothyronine directly with isolated nuclei. Incubation of cells with increasing concentrations of nonradioactive triidothyronine results in a subsequent increase in binding when [(125)I]triiodothyronine is then incubated directly with isolated nuclei. This result suggests that nuclear receptors are not fixed, but increase after exposure of intact cells to hormone. This increase in nuclear receptor content may result from the transfer of an unstable cytosol receptor to the nucleus.


Isolation of defective mutant of avian sarcoma virus. A colony of transformed cells was isolated from chick-embryo cells infected with a stock of nondefective Schmidt-Ruppin strain of Rous sarcoma virus. The virus recovered from this colony was a stable defective mutant very similar to the Bryan strain of Rous sarcoma virus in the following characteristics: (i) noninfectiousness of virus particles released from transformed cells that lack helper factor; (ii) formation of infectious pseudotypes by coinfection with avian leukosis virus or by interaction with endogenous-helper factor in chicken cells; (iii) ability of the noninfectious form of virus to transform chick-embryo cells in the presence of ultraviolet light-inactivated Sendai virus; (iv) absence of glycoprotein in the noninfectious form; (v) failure to produce nondefective virus by recombination with avian leukosis virus; and (vi) segregation of polymerase-negative virus. The morphology of transformed cells is characteristic of those infected by the Schmidt-Ruppin strain. The demonstration of segregation of such a defective virus from nondefective sarcoma virus and failure to detect revertants of this mutant suggest that the deletion of some genes may be involved in this mutation.


Requirement of a phage-induced 5'-exonuclease for the expression of late genes of bacteriophage T5. Amber mutants of bacteriophage T5 defective in gene D15, which codes for a 5'-exonuclease, do not express late genes. Electrophoretic separation in sodium dodecyl sulfate-polyacrylamide gels of the proteins induced by this mutant in nonpermissive Escherichia coli show a virtual absence of late proteins. Synthesis of lysozyme and serum-blocking power is very low whereas the extent of synthesis of an early enzyme, deoxyribonucleoside monophosphokinase, is similar to that in wild-type infections. It is proposed that one requirement for the expression of late T5 genes is the introduction of gaps or nicks in the T5 DNA so that late transcription can occur.


In vitro transcription of the viral-specific sequences present in the chromatin of cells transformed by simian virus 40. Separated strands of simian virus 40 (SV40) DNA fragments were used in hybridization experiments to study the RNA transcribed by Escherichia coli RNA polymerase from the chromatin of cells transformed by SV40. The template activity of chromatin of the transformed cell line 11A8 (mouse-embryo cells) examined is about 17% that of purified DNA, suggesting that most of the chromatin DNA is repressed by chromosomal proteins. The SV40-specific RNA present in the RNA transcribed in vitro from 11A8 chromatin hybridizes specifically with the minus strand of SV40 DNA. Little or no reaction occurs with the plus strand of viral DNA. The SV40-specific RNA transcribed in vitro from chromatin of transformed cells shares sequences with the RNA produced during the early phase of SV40 lytic infection, and is similar to that present in the 11A8 cell line in vivo. Although the influence of chromosomal proteins on this pattern of transcription was not definitely determined, preliminary evidence indicates that an asymmetric pattern of transcription may also occur when 11A8 DNA is transcribed by E. coli RNA polymerase.


Bone morphogenesis in implants of insoluble bone gelatin. Insoluble bone gelatin with inclusions of insoluble noncollagenous protein produces new bone when implanted in muscle in allogeneic rats. The implanted residue provides the milieu for expression of bone morphogenetic potential of migratory mesenchymal cells. Neutral buffer solutions activate endogenous enzymes that degrade components essential for cell interactions and differentiation of bone. Chloroform-methanol either denatures or extracts constituents responsible for degradation. Insoluble bone gelatin produces new bone after extraction at 2 degrees with neutral salts, 0.5 M EDTA, 0.1 M Tris.HCl, 4 M urea, 0.5 M hydroxylamine, and 10 M KCNS, as well as after limited digestion with pepsin or collagenase, but not after extraction with 5 M guanidine, 7 M urea, water saturated with phenol, or after alkali hydrolysis with 0.1 N NaOH. The specific activity of cell populations interacting with insoluble bone gelatin suggests that a chemical bond between collagen and a noncollagenous protein or part of a protein, cleaved by a neutral proteinase, controls the bone morphogenetic reaction.


Cytochrome c: observation of numerous single-carbon sites of the reduced and oxidized species by means of natural-abundance 13C nuclear magnetic resonance spectroscopy. Proton-decoupled, natural-abundance (13)C nuclear magnetic resonance spectra (obtained at 15.18 MHz by the Fourier transform method) of aqueous ferrocytochrome c, ferricytochrome c, and mixtures of both species were recorded. The 18 nonprotonated aromatic carbons of amino-acid residues and the 16 nonprotonated aromatic carbons of the heme yielded 22 narrow single-carbon resonances and 6 narrow two-carbon resonances in the spectrum of ferrocytochrome c. Only some of these resonances were detected in the spectrum of ferricytochrome c. Fast electron transfer between ferrocytochrome c and ferricytochrome c produced chemical exchange effects in spectra of mixtures of the two species: 16 nonprotonated aromatic carbons yielded narrow exchange-averaged resonances as a consequence of their small natural linewidths in both redox states and the small changes in their chemical shifts (relative to the reciprocal of the lifetime between electron exchange) when going from the reduced to the oxidized species. These peaks were assigned to carbons situated far from the iron atom. Their fast exchange behavior was used to establish a one-to-one correspondence between resonances in spectra of the two redox states. The other 18 nonprotonated aromatic carbons yielded exchange-broadened resonances as a consequence of large chemical-shift differences between the diamagnetic and paramagnetic species, and/or large paramagnetic broadening of the resonances of ferricytochrome c. We assigned these resonances (only one of which was identified in the spectrum of ferricytochrome c alone) to carbons that are near the iron atom: C(zeta) of Tyr 67, C(gamma) of His 18, and the 16 nonprotonated carbons of the porphyrin ring. Tentative specific assignments for C(zeta) of Tyr 67 (in the spectra of both redox forms) and for C(zeta) of His 18 (in the spectrum of ferrocytochrome c) are also presented.


Regulation of nucleoside cyclic 3':5'-monophosphate phosphodiesterase activity from rat brain by a modulator and Ca2+. Gel filtration of the 40,000 rpm supernatant fraction of a homogenate of rat cerebral cortex on a Sepharose 6B column yielded two fractions: fraction II with the "Ca(2+) plus Mg(2+)-dependent" phosphodiesterase activity and fraction III containing its modulator. The activity of fraction II was stimulated by micromolar concentrations of Ca(2+) and the modulator when present together; the modulator stimulated the activity of fraction II only when the Ca(2+) concentration was above a threshold value (about 2 muM with 0.4-1 muM substrate), and the stimulatory effect of Ca(2+) was dependent upon the presence of the modulator. A possibility is discussed that the modulator may reversibly bind to the enzyme, which by itself is inactive, to form an active enzyme-modulator complex and that Ca(2+) stimulates the activity of phosphodiesterase by shifting the equilibrium between these three species towards the formation of the active enzyme-modulator complex. Although fraction II hydrolyzed both cyclic AMP and cyclic GMP, hydrolysis of the latter was more significantly influenced by Ca(2+) and the modulator than that of the former, and the "Ca(2+) plus Mg(2+)-dependent" phosphodiesterase is likely to be a cyclic GMP enzyme. This conclusion is based on the following evidence: (a) Ca(2+) stimulated hydrolysis of cyclic GMP by fraction II more than that of cyclic AMP. (b) In the presence of Ca(2+) and the modulator, fraction II hydrolyzed cyclic GMP about 8 times faster than cyclic AMP when incubated with 0.4 muM substrate. (c) Half-maximal stimulation of hydrolysis of cyclic GMP was attained at a lower concentration of Ca(2+) (4 muM) than that of cAMP (8 muM). (d) Increase in the concentration of Ca(2+) from 0.06 muM to 12 muM in the presence of the modulator caused a decrease in the K(m) value of cyclic GMP hydrolysis by fraction II from 20 muM to 2 muM accompanied by 4-fold increase in the V(max) value. Under similar conditions, there was only a slight decrease in the K(m) value of cylic AMP hydrolysis (90 muM --> 50 muM), although the V(max) value increased 7-fold. The anomalous shape of the kinetic plot of cyclic GMP hydrolysis became linear when the Ca(2+) concentration was increased in the presence of the modulator. The modulator seems to be a protein, but it is heat stable. It is probably identical to the protein activator of phosphodiesterase first described by Cheung.


In vitro synthesis of RNA that contains polyadenylate by virion-associated RNA polymerase of vesicular stomatitis virus. The RNA synthesized in vitro by the virion-associated RNA-instructed RNA polymerase of purified vesicular stomatitis virus contains polyadenylate sequences. These have been demonstrated by their partial resistance to pancreatic and T(1) ribonucleases and their capacity to bind to poly(U) filters and oligo(dT)-cellulose. The polyadenylate sequences range in apparent size from 50 to 200 bases, similar to the size of the poly(A) in mRNA from vesicular stomatitis virus-infected cells. Possible mechanisms of polyadenylylation of the in vitro RNA product are discussed.


Ribonucleic acid components of murine sarcoma and leukemia viruses. Defective Kirsten murine sarcoma virus was present as leukemia virus pseudotype [Ki-MSV(MLV)] in a 10- to 100-fold excess over its helper, Kirsten murine leukemia virus (Ki-MLV), when the two viruses were propagated in an NRK rat cell line. The s(omega,20) of the fastsedimenting RNA complex of Ki-MLV and of Ki-MSV-(MLV) was 62 S and 55 S, respectively. Gel electrophoresis in buffered aqueous or formamide solution of the dissociated 62S RNA complex of Ki-MLV showed a single major peak of molecular weight about 2.5 x 10(6). Dissociated 55S RNA of Ki-MSV(MLV) was resolved into a major component with a higher electrophoretic mobility than that of Ki-MLV RNA and molecular weight about 2.3 x 10(6). Occasionally, a minor component with the same electrophoretic mobility as Ki-MLV RNA was observed in Ki-MSV(MLV) RNA; it is thought to be the RNA of Ki-MLV present as helper virus in our stocks of Ki-MSV(MLV). The RNA of an endogenous rat C-type RNA virus was electrophoretically different from both Ki-MLV RNA and Ki-MSV(MLV) RNAs. Oligonucleotide fingerprinting of the RNAs digested with RNase T1 indicated that the RNAs of Ki-MSV(MLV) and Ki-MLV are different. However, the extent of the difference between the two RNAs could not be estimated by this method. The heat-dissociated 50-70S RNAs of two other defective murine sarcoma-leukemia viruses; Harvey-MSV(MLV) and Moloney-MSV(MLV) and of defective spleen-focus-forming Friend virus were resolved electrophoretically into two components. The larger components had the same electrophoretic mobility as the RNA of Ki-MLV or Moloney MLV. The smaller were not present in leukemia virus. It is suggested that the small RNA components of the two murine viruses and of Friend virus represent specific genetic information of these replication-defective transforming viruses. Possible relationships between the RNAs of murine leukemia viruses and replication-defective murine sarcoma and Friend viruses are discussed.


Electron transport-linked compared with proton-induced ATP generation in Thiobacillus novellus. The apparently soluble electron-transport system, that does not sediment when centrifuged at 144,000 x g or 300,000 x g for 3 hr, catalyzes oxidative phosphorylation with an efficiency comparable to that of an intact mitochondrial system. While the proton-induced phosphorylation occurs in whole cells, crude cell-free extracts, and supernatants from low-speed centrifugation, it does not occur in either the 144,000 or 300,000 x g supernatant fractions. The data show that oxidative energy can be conserved as ATP under conditions that are incompatible with the basic postulate of the chemiosmotic hypothesis.


Role of cyclic 3':5'-adenosine monophosphate in the early transport changes induced by serum and insulin in quiescent fibroblasts. Serum or insulin added to quiescent mouse-embryo fibroblasts produced rapid increases in the rate of transport of uridine and phosphate and a decrease of the intracellular concentration of cyclic AMP. Incubation of the cells with prostaglandin E(1), theophylline, or both prevented the increase in uridine transport produced by serum or insulin. Prostaglandin E(1) was more effective than prostaglandins E(2) and B(1). Kinetic experiments showed that the addition of prostaglandin E(1) and theophylline causes the uridine transport rate to return to the basal level within 5 min; the rate rose rapidly after their removal. Similar effects were obtained when insulin was used instead of serum. Associated with these transport changes were significant variations in the levels of cyclic AMP. An inverse correlation between the changes in uridine transport and those in cyclic AMP concentration was shown under various experimental conditions. In contrast to the effects observed with uridine transport, phosphate uptake was only slightly affected by changes in the endogenous level of cyclic AMP. We propose that at least two different sorts of membrane changes are rapidly initiated by serum, one under cyclic AMP control and the other not related to this nucleotide.


Assignment of the T-antigen gene of simian virus 40 to human chromosome C-7. Hybrid cell clones between mouse cells deficient in thymidine kinase (EC 2.7.1.21) and two different human cell lines transformed by simian virus 40 (SV40) and deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were examined for SV40 tumor (T) antigen(s). Concordant segregation of the gene(s) for SV40 T antigen and human chromosome C-7 was observed in these hybrids. The human chromosome C-7 which contains the gene(s) for SV40 T antigen is preferentially retained by the majority of the hybrid clones tested. When hybrid clones positive and negative for SV40 T antigen, derived from the fusion of SV40-transformed Lesch-Nyhan fibroblasts with mouse cells, were fused with CV-1 permissive cells, SV40-specific V antigen was observed only in the cultures derived from fusion of the hybrid clones positive for T antigen. This result indicates a linkage relationship between human chromosome C-7, SV40 T-antigen gene(s), and SV40 genome(s) integrated in the human transformed cells.


Changes in membrane structure associated with cell contact. Ultrastructural analysis of 3T3 fibroblasts by freeze-cleavage has demonstrated significant changes in cell-membrane structure associated with cell-to-cell contact and malignant transformation. These changes consist of a rearrangement and redistribution of intramembranous particles on the membrane fracture faces exposed by freeze-cleavage. The results show that noncontacted 3T3 cells in low density contain randomly distributed intramembranous particles. With the development of cell-to-cell contacts during the logarithmic phase of growth however, a pronounced aggregation of intramembranous particles is seen. A direct correlation between the degree of cell contact and the percentage of cells showing intramembranous-particle aggregation has been established. By contrast, transformed SV3T3 and SP3T3 cells show no evidence of intramembranous-particle aggregation even at cell densities where cell-to-cell contact is extensive. In view of recent reports that intramembranous particles represent foci of interaction between certain intrinsic membrane proteins and lipids, we propose that cell-to-cell contact of nontransformed 3T3 cells may initiate a change in the distribution of intrinsic membrane proteins associated with intramembranous particles and that these changes may influence control of cell proliferation.


Changes in rabbit-liver lysosomes and fructose 1,6-bisphosphatase induced by cold and fasting. Exposure of rabbits to cold or fasting results in marked increases in the number and size of liver lysosomes, associated with increases in the total and "free" proteolytic activity. Changes in lysosomal morphology also indicate increased activity and fragility. These effects of cold and fasting are correlated with decreases in the levels of liver fructose bisphosphatase (EC 3.1.3.11) activity and changes in the molecular properties of the purified enzyme, including the loss of a small peptide containing the only tryptophan residue in the peptide chain.


Infectious DNA from herpes simplex virus: infectivity of double-stranded and single-stranded molecules. The infectious units in native and alkalidenatured preparations of DNA of herpes simplex virus were characterized with respect to their sensitivity to Neurospora crassa endonuclease, their sedimentation properties in high-salt, neutral sucrose gradients, and their sensitivity to hydrodynamic shearing forces. Infectious molecules in native preparations were resistant to N. crassa endonuclease, sedimented at 56 S, and were highly sensitive to shearing forces. After alkaline denaturation, infectious molecules became sensitive to the N. crassa enzyme, sedimented at 200 S, and were relatively resistant to shear. We conclude that both intact duplex molecules ([unk]100 x 10(6) daltons) and intact single strands ([unk]50 x 10(6) daltons) are capable of initiating productive infection.


In vivo inhibition of growth of two hormone-dependent mammary tumors by dibutyryl cyclic AMP. Growth of hormone-dependent rat mammary tumors was arrested in vivo by N(6),O(2)'-dibutyryl cyclic adenosine 3',5'-monophosphate. Estrogen concentration did not change, but acid ribonuclease activity and synthesis increased during treatment with the dibutyryl cyclic nucleotide, as was shown during tumor regression due to hormonal deprivation. Growth arrest, thus, appears to derive from enhanced tissue catabolism.


Water-soluble contrast media and adhesive arachnoiditis. I. Reinvestigation of nonoperated cases.


Late sequelae following lumbar myelography with water-soluble contrast media.


Streptozotocin diabetes--further studies on the mechanism of depression of nicotinamide adenine dinucleotide concentrations in mouse pancreatic islets and liver.


Effects of some isoquinoline compounds and certain derivatives on brain phosphodiesterase activity.


Biliary excretion of nicotinamide riboside. A possible role in the regulation of hepatic pyridine nucleotide dynamics.


Neural activity in the dorsal hippocampus during paradoxical sleep, slow wave sleep and waking.


Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. IV. Stimulation of the enzyme activity in established cell lines derived from rat or mouse hepatoma and from normal rat liver.


Glial uptake of taurine in the rabbit retina.


Evidence against cyclic adenosine 3',5'-monophosphate (AMP) mediation of noradrenaline depression of cerebral cortical neurones.


Talc injury: changes in glucosamine and leucine incorporation into liver and plasma proteins.


Familial hyperlipoproteinemia and thyroid dysfunction of beagles.


Influences on the structural stability of collagen in relation to ageing.


Increased plasma renin substrate concentration in human malignant hypertension.


Effect of 25-hydroxycholecalciferol (25-HCC) on intestinal absorption of 47Ca in four cases of iatrogenic Cushing's syndrome.


Serum lipids, dietary intakes, and physical exercise in medical students.


Depth-electroencephalograms of chickens in wakefulness and sleep.


Letter: The stability of Clostridium perfringans type D epsilon toxin in intestinal contents in vitro.


Terminal dentistry and the management of the atrophied mandible.


A genetic study of syndactyly in Utah.

A genetic study of syndactyly in Utah.


Alkaline phosphatase levels in canine mammary neoplasia.


Chemical oncogenesis in culture.

Chemical oncogenesis in culture.


Isozymes and cancer.

Isozymes and cancer.


Effect of 5-iodo-2-deoxyuridine, cycloheximide and rivanol on the multiplication of vaccinia and fowlpox viruses in chick embryo fibroblast culture.


Bordetella pertussis infection in Chandigarh.


Variants of vibrio cholerae in Delhi.

Variants of vibrio cholerae in Delhi.


Vitamin D and rickets.

Vitamin D and rickets.


Isolation of Clostridium absonum and its cultural and biochemical properties. A new procedure for isolation of Clostridium absonum was devised. Sixtyseven strains of C. absonum were isolated from 135 soil samples, but no strain of C. absonum could be found from human fecal samples. The lecithinase, hemolysin, and lethal toxin in the culture filtrates of this species exhibited low avidity for C. perfringens type A antitoxin. The three activities were inseparable by the present method of purification. A reinvestigation of biochemical properties revealed that incomplete suppression of lecithinase reaction by C. perfringens type A antitoxin and no fermentation of raffinose, melibiose, and starch are useful criteria to differentiate C. absonum from C. perfringens, and that positive, although weak, gelatin liquefaction and fermentation of trehalose are useful to differentiate it from C. paraperfringens.


Inhibitory and restorative effects of adenine nucleotides on rickettsial adsorption and hemolysis. The adenine nucleotides, adenosine diphosphate, adenosine triphosphate, (ATP), and the methylene-bridge analogues are inhibitors of rickettsial adsorption to and the hemolysis of sheep erythrocytes. Other nucleotides, adenosine monophosphate, cyclic adenosine monophosphate, cytosine triphosphate, and guanosine triphosphate, are without effect. Adsorption and hemolysis require the generation of energy by the rickettsiae which is usually derived from glutamate. When the generation of energy from the metabolism of glutamate is inhibited by arsenite or cyanide, the addition of ATP can supply the energy to restore hemolysis. However, in the presence of the uncouplers, ATP can not restore hemolysis. Even when functioning in a restorative role, ATP still has its inhibitory properties. These results suggest that a high-energy intermediate (X approximately I), rather than ATP itself, is the energy source. The interactions of inhibitory nucleotides suggest that these compounds share a common transport system.


N-terminal aspartate, glycine and serine in poliovirus capsid protein.


The synthesis and substructure of herpesvirus DNA: the distribution of alkali-labile single strand interruptions in HSV-1 DNA.


Fusion of a Rous sarcoma virus transformed human cell line, KC, by RD-114 virus.


Studies on the histamine sensitisation produced in mice by Corynebacterium parvum.


Activation of descending control of the spinocervical tract by impulses ascending the dorsal columns and relaying through the dorsal column nuclei. 1. Micro-electrode recordings were made from axons of the spinocervical tract in unanaesthetized decerebrate cats.2. Orthodromic activation of the dorsal columns and dorsal column nuclei was used to condition responses evoked in spinocervical tract neurones from cutaneous nerves. Such conditioning produced inhibition of transmission through the tract. The inhibition had a time course of 200 msec or more with maximal action at 30-70 msec and was most effective against polysynaptic responses.3. After removal of the cerebellum or section of the cerebellar peduncles the degree of inhibition was reduced but inhibition could still be evoked by activation of the dorsal columns and dorsal column nuclei.4. Transection of the brain stem just rostral to the dorsal column nuclei removed the inhibitory effects although segmental inhibition was not affected.5. It is concluded that impulses ascending the dorsal columns and relaying through the dorsal column nuclei can lead to activation of descending control of the spinocervical tract. Parts of the pathways involved include the cerebellum and the brain stem. It is unlikely that the cells in the dorsal column nuclei which have descending axons are concerned with the control of transmission through the spinocervical tract.


Some effects of preganglionic nerve stimulation on synaptic vesicle populations in the rat superior cervical ganglion. 1. The ;local vesicle population', namely the population of synaptic vesicles lying within a zone 0.25 mum wide adjacent to the presynaptic membrane and expressed as ;vesicles mum(-2)' has been estimated in rat superior cervical ganglia maintained in vitro for 1 h. Ganglia were either unstimulated or stimulated tetanically during the last few minutes of the in vitro period.2. Individual local vesicle populations at synapses in groups of ganglia which had received the same treatment showed an approximately normal frequency distribution.3. The technique of stimulation did not permit fixation during tetanus, but the mean local vesicle population in ganglia fixed a few seconds after 10 Hz tetani of up to 10 min duration were significantly (P < 0.001) higher than the unstimulated control value of 124.0 +/- S.E. 3.2. Ganglia fixed a few seconds after 3 min tetani at 10 Hz had a mean local vesicle population of 155.7 +/- S.E. 5.7, rising slightly but not significantly to 165.0 +/- S.E. 4.3 at 1 min and 163.1 +/- S.E. 5.2 at 2 min after tetanus. Thereafter the mean local vesicle population fell slowly, reaching control level between 10 and 20 min after tetanus.4. In terms of the vesicle hypothesis, the observations suggest that post-tetanic potentiation might arise from a closer clustering of vesicles about release areas resulting in an increase in fractional release. It is suggested that stimulation increased the local vesicle population by promoting vesicle mobilization rather than by altering the size or shape of the presynaptic terminals. The ;mobilizing agent' might be intracellular Ca(2+).5. The results appear to be consistent with those of other workers where experimental conditions and the region in which vesicles were counted were comparable.6. Alternative interpretations for the findings, not involving the vesicle hypothesis, are considered.


Negative inotropic effect of cyclic AMP on the isolated canine heart muscle.


Thymus adenylate cyclase activity during murine leukemogenesis. Activity of thymus adenylate cyclase was more than three times higher in leukemic AKR mice than in nonleukemic AKR mice and CBA mice. Preleukemic AKR mice that had no evidence of leukemia but were expected to soon develop the disease exhibited similarly elevated activities of thymus adenylate cyclase.


The cricopharyngeus muscle. An electrophysiological and neuropharmacological study.


Unit activity of ganglionic and medullary second order neurones in the eel lateral line system.


Effect of feeding protected lipid on the uptake of precursors of milk fat by the bovine mammary gland.


Tumor producing capacity of temperature sensitive mutants of avian sarcoma viruses in chicks.


Studies by electron paramagnetic resonance on the catalytic mechanism of nitrogenase of Klebsiella pneumoniae. The properties and catalytic reactions of the enzyme nitrogenase purified from Klebsiella pneumoniae were studied by electron-paramagnetic-resonance (e.p.r.) spectroscopy at temperatures down to 8 degrees K. The two protein fractions, Kp1 (the iron-molybdenum protein) and Kp2 (the iron protein), were examined alone and in steady-state mixtures and also in pre-steady-state experiments, by using the rapid-freezing method. Kp1 protein in dithionite solution shows a rhombic type of spectrum with g(1) 4.32, g(2) 3.63, g(3) 2.009 at pH6.8 (0 degrees C). Small changes in the spectrum produced by protons (pK=8.7 at 0 degrees C) or by acetylene indicate binding of these oxidizing substrates to this protein fraction. Kp2 protein shows a rhombic spectrum with g(1) 2.053, g(2) 1.942, g(3) 1.865, which integrates to about 0.45 electron/molecule. Binding of ATP, with a dissociation constant of 4x10(-4)m, changes the spectrum to an axial form with g( parallel) 2.036, g( perpendicular) 1.929, thus indicating a conformation change of Kp2 protein. The Kp2 protein spectrum disappears reversibly on cautious oxidation. The signals of both proteins are diminished in their steady-state mixtures, obtained in the presence of ATP and dithionite (with an ATP-generating system and Mg(2+) ions) and with protons, N(2) or acetylene as oxidizing substrate. At the same time as dithionite is consumed in such reactions, the Kp1 protein signal is gradually restored and the Kp2 protein signal diminishes to zero. In rapid-freezing experiments the signals from the two proteins decreased at indistinguishable rates (t((1/2)) about 10ms), then they remained constant. Results are interpreted in terms of a scheme in which reducing equivalents pass from dithionite to Kp2 protein, then, in an ATP-dependent reaction to Kp1 protein, this being finally reoxidized by N(2) or another oxidizing substrate. In this scheme Kp1 protein cycles between its signal-giving state and a very highly reduced signal-free state.


Electrical changes in the membrane in junctional transmission.


Mental health: systems and non-systems.

Mental health: systems and non-systems.


Superoxide dismutase: a contaminant of bovine catalase. Some commercial samples of bovine catalase contain superoxide dismutase activity. Therefore the inhibition of a reaction on the addition of a catalase preparation need not necessarily mean that H(2)O(2) is responsible for the reaction.


The action of bombesin on the kidney of the anaesthetized dog. 1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.


On the pharmacology of ascending, decending and recurrent postsynaptic inhibition of the cuneo-thalamic relay cells in the cat. 1. In cats decerebrated or anaesthetized with pentobarbitone, cells of the middle third of the cuneate nucleus that were excited by tactile stimulation of the ipsilateral forelimb (responding to displacement of hairs, skin or joints) and inhibited by electrical stimulation of the contralateral pyramid, were invariably inhibited by electrical stimulation of the ipsilateral forepaw and the contralateral forelimb nerves.2. In 50% of the cats, the cells were more fully identified by placing electrodes stereotaxically in the contralateral medial lemniscus. Recurrent inhibition was always a concomitant of the antidromic action potential.3. The intensity and the duration of inhibition evoked by all of these pathways was totally resistant to iontophoretic and intravenous strychnine in doses at least 5 times that required to block completely the response of the same cells to iontophoretic glycine and was extremely sensitive to either iontophoretic bicuculline or picrotoxin.4. Although the inhibition was invariably sensitive to intravenous picrotoxin, no significant change occurred in the duration or intensity of the inhibition when bicuculline was administered intravenously (5 or 6 times) as repeated doses of 0.2 mg/kg.5. Postsynaptic inhibition in the cuneate may be mediated by gamma-aminobutyric acid released from the nerve terminals of a common pool of interneurones shared by ascending, descending and recurrent pathways. Since the receptors involved in this pathway are resistant to intravenous bicuculline, they may well be distinct from those responsible for changes in the primary afferent terminal excitability, usually believed to be associated with presynaptic inhibition.


Fate of angiotension I in the total Bufo melanostictus. 1. The effects of angiotensin I and II on the blood pressure of pithed toads and the disappearance of angiotensin I and II in the perfused organs of the toad were studied.2. Angiotensin I was relatively inactive on the blood pressure of pithed toads; it exhibited less than 3% of the pressor activity of angiotensin II.3. Angiotensin I was not converted to angiotensin II during passage through the lungs. There was also no evidence of net conversion during passage through the kidney and hind quarters.4. During passage through the lungs, 33-50% of angiotensin I was removed and 25-50% was removed during passage through the hind quarters. No loss of activity was detected when angiotensin II passed through the kidneys.5. Angiotensin II passed through the lungs and kidneys without loss but 25-50% disappeared during passage through the hind quarters.6. The relatively low pressor activity of angiotensin I together with its lack of conversion to angiotensin II in isolated perfused organs suggest that the converting enzyme is absent in the toad, Bufo melanostictus.


Effect of anti-inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea-pig tissues. 1. Cellular membranes were obtained by centrifugation of homogenates of various human and guinea-pig tissues. These membranes took up added calcium (Ca) when incubated at 25 degrees C for 10 min in histidine buffer at pH 7.4. The uptake of Ca was increased by the presence of adenosine triphosphate (ATP).2. Evidence is presented that the membrane fragments which took up Ca under these conditions were derived from the endoplasmic reticulum.3. The ATP-dependent uptake of Ca by membranes derived from guinea-pig aortic or gastric smooth muscle or from human umbilical arterial muscle was inhibited by indomethacin in a concentration-dependent manner.4. The ATP-dependent uptake of Ca by membranes derived from heart, brain, skeletal muscle or liver of the guinea-pig was not inhibited by indomethacin.5. Endothelial cells were obtained from the lining of the human umbilical vein. Cellular membranes were prepared from the endothelial cells by homogenization and centrifugation. The endothelial membranes took up added Ca in the presence of added ATP and this uptake was inhibited by indomethacin and also by members of a group of pharmacologically-related drugs.


The relation of adenyl cyclase to the activity of other ATP utilizing enzymes and phosphodiesterase in preparations of rat brain; mechanism of stimulation of cyclic AMP accumulation by NaF. 1. A method for measuring the rate of production of (14)C-labelled adenine nucleotides, including cyclic adenosine 3',5'monophosphate (cyclic AMP), from [(14)C]-adenosinetriphosphate (ATP) was developed and used to study the effects of ATP, adenosine diphosphate (ADP) and adenosine 5'-monophosphate (AMP) on the rate of accumulation of cyclic AMP in cell-free preparations of adenyl cyclase from rat brain.2. The mechanism by which NaF increases cyclic AMP accumulation was studied by comparing its effect on adenine nucleotide metabolism with that of an ATP regenerating system.3. ADP and ATP are potent inhibitors of phosphodiesterase (PDE) and it is the sum of the concentrations of these two nucleotides which controlled the rate of destruction of cyclic AMP. The effect of these nucleotides was significant even in the presence of 6.7 mM theophylline; theophylline itself inhibited PDE only 50-60%.4. Fluoride ion had no direct effect on PDE but it inhibited the rate of hydrolysis of ADP and ATP and thus indirectly inhibited PDE. The effect of fluoride ion on cyclic AMP accumulation can be explained, at least in part, by this indirect inhibition of PDE.5. Studies on a more purified preparation of adenyl cyclase clearly demonstrated a direct action of NaF on adenyl cyclase.


Effect of a sulphated glycopeptide on rat gastric acid secretion stimulated by histamine, bethanechol, pentagastrin and dibutyryl cyclic AMP. The antisecretory activity of a semisynthetic sulphated glycopeptide (GLPS) was studied in rats in which the secretion rates of gastric acid were detennined on the perfused stomach preparation. GLPS at 1 mg/kg i.v. reduced the hypersecretory effect of dibutyryl cyclic AMP, histamine, pentagastrin, bethanechol but not of theophylline.


The action of two inhibitors of glutamic acid uptake upon amino acid-induced and synaptic excitations of thalamic neurones.


Modifications of the firing rate of bulbar reticular units (nucleus gigantocellularis) after intra-arterial injection of bradykinin into the limbs.


Electrophysiology of the frontal granular cortex. II. Patterns of spontaneous discharges of impulses of neurons in the cortex through states of sleep and wakefulness in the monkey.


The action of piperidine on cholinoceptive neurons of the snail.


Altered distribution of choline acetyltransferase and acetylcholinesterase activities in the developing rat dentate gyrus following entorhinal lesion.


The efflux of 45CA2+ and (3H)gamma-aminobutyric acid from cate cerebral cortex.


Effect of psychotropic drugs on phosphodiesterase and cyclic AMP level in rat brain in vivo.


The neuronal pathway subserving the pupillary light reflex and its facilitation from cerebellar nuclei.


Burst formation in electrically coupled neurons.


Studies on post-tetanic depression of the dorsal root reflex in the forelimb skin nerves of the cat.


WHO collaborative studies on enterovirus reference antisera; fourth report. This paper summarizes the results of the fourth part of a comprehensive programme undertaken by the WHO International Reference Centre for Enteroviruses and other laboratories for the testing of enterovirus equine antisera prepared for long-term use as reference antisera. The studies were designed to appraise the specificity of the immune serum of horses inoculated with prototype enteroviruses (coxsackievirus types A2, 4, 8, 10, 11, 14-16, 18-21, and 24, and echoviruses E21, 27, 30, 31, and 33). Tests for neutralizing antibody were performed against the homologous viruses and against available regional homotypic strains. Heterotypic tests were performed against reoviruses 1-3, adenoviruses 1-31, and the entire series of enteroviruses (with the exception of enterovirus 68). The homologous geometric mean titre of the 5 echovirus antisera ranged from 3 000 to 10 000; the titre of 1 coxsackievirus antiserum (A24) was only about 400, but the titres of the others ranged from 1 500 to 14 000. All corresponding preinoculation sera were negative. Heterotypic antibody of significant titre was found in 4 antisera: E31 serum against E5 virus, CA8 serum against CA3 virus, CA13 serum against CA18 virus, and CA15 serum against CA2 virus. Information on other heterotypic antibody titres (where found) is recorded for guidance in the use of the sera. The results of homotypic tests with viruses isolated by the collaborating laboratories, though limited in number, were satisfactory.


Differential diagnosis of variola viruses by microfocus assay. Variola virus was identified by means of a method involving the formation of microfoci on microplate cultures of HeLa cells. It was possible to distinguish between variola major and variola minor viruses within 48 h of receipt of the specimens by determining the temperature sensitivity of focus formation.


Poliomyelitis: epidemiology and prophylaxis. 1. A longitudinal epidemiological survey in Kenya. The results of a long-term survey of poliomyelitis in Kenya are reported. Virus was isolated from patients and a limited number of sera were also tested for antibodies. The purpose of the investigation was to elucidate the epidemiological characteristics of the disease and to determine whether epidemics could be predicted. A 3-year rhythm was found in the circulation of type 1 poliovirus, making possible the prediction and hence, on two occasions, the curbing or prevention of epidemics.


Leukocytic enzyme differences between the clinical forms of malnutrition.


Experimental myasthenia gravis, myositis and myocarditis in guinea-pigs immunized with subcellular fractions of calf thymus or calf skeletal muscle in Freund's complete adjuvant.


Macrophage and lymphocyte co-operation in target cell destruction in vitro.


Perspectives in molecular radiation biology. The biophysical approach.


Properties of myeloma immunoglobulin E(Yu). Chemical, fluorescence polarisation and spin-labeled studies.


Different sensitivity of ribonucleic and deoxyribonucleic acid viruses to resistance induced in rabbit cells (RK-13) by polyriboinosinic acid-polyribocytidilic acid. When a continuous line of rabbit kidney cells (RK-13) was exposed to polyriboinosinic acid polyribocytidilic acid [poly(rI).poly(rC)], the cells became resistant to the replication of a ribonucleic acid (RNA) virus, vesicular stomatitis (VSV), but remained susceptible to the replication of two deoxyribonucleic acid (DNA) viruses, pseudorabies and vaccinia. These differences were identical to previous findings with RK-13 cells pretreated with exogenous rabbit interferon. Confirmation is thereby provided that RK-13 cells are deficient in the synthesis of resistance factors active against the DNA viruses tested and that there are separate resistance factors for RNA and DNA viruses in RK-13 cells. The resistance against VSV which developed in RK-13 cells exposed to poly(rI).poly(rC) could be significantly reversed by prior infection with infective vaccinia virus but not by vaccinia inactivated by ultraviolet irradiation or heat.


Induction of interferon in L cells by reoviruses. L cell cultures challenged with reoviruses types 1 and 3 produced little to no detectable interferon under conditions which permitted virus replication and under conditions which prevented replication of a temperature-sensitive mutant strain of reovirus type 3 (ts-1). Ultraviolet-irradiated reoviruses and double-stranded ribonucleic acids extracted from purified reovirus type 3 also induced little to no interferon in L cell cultures. Under similar conditions, MM virus proved to be an effective inducer of interferon. Exposure of L cells to interferon prior to challenge with virus (priming) failed to enhance interferon production upon subsequent challenge with reovirus although priming increased the amount of interferon produced following MM virus challenge. L cell cultures that were challenged with reovirus type 3 and subsequently with either MM or Colorado tick fever viruses produced similar titers of interferon as cell cultures that were challenged with either MM or Colorado tick fever virus alone, respectively. These data show that the presence of production of reovirus type 3 double-stranded ribonucleic acid is not sufficient for induction of interferon in L cell cultures and that additional processes which are required for induction of interferon in L cell cultures are not expressed by reovirus type 3.


Enhanced effect of repeated administration of bacterial vaccine against viral respiratory infection. Administration of a standard bacterial vaccine (SBV) affords some protection against influenza infection in mice if given 4 to 5 h before inoculation of the virus. This effect was enhanced by repeated injections of SBV 7 and 14 days earlier, as measured by the length of survival, mortality rate, development of gross pneumonia, and virus multiplication in the lungs. Serum interferon levels were likewise enhanced by immunization with SBV, which may, at least in part, explain the increased preventive effect.


Physical separation of streptococcal nicotinamide adenine dinucleotide glycohydrolase from streptolysin O. Streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) with a molecular weight of about 55,000 and an isoelectric pH of 8.55 was isolated from crude streptolysin O (SLO) preparations. NADase differed from SLO in size, charge, and immunological behavior. Streptococcal NADase is considered to have no role in the hemolytic process because it has no hemolytic activity; conversely, partially purified SLO showed no NADase activity. The hemolytic activity of crude SLO was completely inhibited by anti-tetanolysin, whereas the NADase activity in the same reaction mixture was unaffected. Experiments involving double diffusion in agar also demonstrated immunological nonidentity of the two proteins.


Electron transfer in gamma-irradiated complexes between aromatic amino acids and DNA derivatives.


Letter: Free radicals in the sugar moiety of x-irradiated DNA.


Letter: E.s.r. of irradiated single crystals of cytosine.


The catecholamines: reappraisal of their use for acute myocardial infarction and the low cardiac output syndromes.


Letter: Multiplicity effect on the survival of ultra-violet-irradiated Herpes simplex virus.


The effects of derivatives of adenosine 3',5'-monophosphate on fluid secretion by the salivary glands of Calliphora.


A simple technique for monitoring the synaptic actions of pharmacological agents.


The action of cobalt ions on neuromuscular transmission in the frog. 1. Cobalt ions, in concentrations of 0.05-2 mM, block neuromuscular transmission in the frog sartorius muscle.2. The reduction in the e.p.p. amplitude produced by Co(2+) is due to a decrease in the amount of transmitter released by a nerve impulse (mean quantum content). This reduction is associated with little change in the resting membrane potential of the muscle fibre or in the mean amplitude of spontaneous m.e.p.p.s.3. The reduction in evoked transmitter release produced by Co(2+) may be antagonized by elevation of the external Ca(2+) concentration. It is suggested that the antagonism between Co(2+) and Ca(2+) is competitive in nature.4. The mean dissociation constant for Co(2+) and its hypothetical membrane complex was found to be 0.18 mM. On this basis, it is concluded that Co(2+) is about 20 times more potent than Mg(2+) in suppressing evoked transmitter release.5. In contrast to the inhibitory action on evoked release, Co(2+) increases spontaneous transmitter release. However, concentrations of Co(2+) 20-60 times greater than those which decrease the e.p.p. amplitude are needed to produce a significant increase in m.e.p.p. frequency.


The composition of maternal plasma and foetal urine after feeding and drinking in chronically catheterized ewes during the last two months of pregnancy. 1. The fluid sacs and bladders of sixteen foetuses in fourteen ewes were catheterized between 81 and 92 days gestational age and the rumens of four ewes were also catheterized.2. Between 95 and 145 days gestational age in forty-six 24 hr experiments hourly samples of maternal plasma and foetal urine were obtained and in fifteen experiments foetal fluid samples were also taken at 4- to 6-hr intervals.3. The osmolality, pH, and concentrations of sodium, potassium, chloride, glucose, fructose and urea were measured on all samples.4. During experiment there was no significant variation in the composition of amniotic or allantoic fluid. Marked changes in osmolality occurred in maternal plasma and foetal urine when ewes drank after feeding, but not in ewes that received water intrarumenally via catheter while feeding or in fasting ewes. Post-prandial changes in maternal plasma osmolality may have altered transplacental water fluxes and as a result foetal plasma volume and osmolality.5. The results suggest that the foetus alters renal water retention by varying antidiuretic hormone (ADH) secretion in response to changes in blood volume and at later gestational ages plasma osmolality as well.6. Post-prandial changes in the [Na(+)]/[K(+)] ratio of foetal urine suggested that foetal adrenocorticotrophin (ACTH) secretion is influenced by variations in foetal blood volume and glucose concentrations.7. The post-prandial changes in foetal urine composition observed here support previous suggestions (Mellor & Slater, 1972) about the role of foetal urine in foetal fluid formation which were based on gestational changes in the composition of foetal fluids and urine sampled once daily during the post-absorptive state.


Growth after adolescence.

Growth after adolescence.


Enzyme aspects of acute intermittent porphyria.


Leukocyte and placental metabolism as indices of fetal malnutrition.


Standardized multisegmental measurements of blood pressure for quantitative evaluation of the circulation in the limbs.


Induced hypertension in the treatment of severe foot ischemia.


Criticism about the use of muscles provided with a testosterone-binding protein to evaluate the miotrophic activity of androgens.


Fluoride uptake from prophylactic dentifrices. I. Methods for measuring fluoride uptake in tooth enamel in vitro and in vivo.


Fluoride uptake from prophylactic dentifrices. II. Some introductory experiments and findings concerning in vitro fluoride uptake in tooth enamel.


Influence of adrenalectomy and beta-methasone on the composition of liver cell membrane.


Studies on (8-14C) adenosine-5'-carboxylic acid ethyl ester. II. Incorporation of radioactivity into nucleic acids of mouse and dog.


Development of second-generation schizonts, gamonts and oocysts of Eimeria bovis in bovine kidney cells.


Inappropriate renin secretion in pregnancy.


In vitro perfusion of the human utero-tubo-ovarian unit.


An improved method for the assay of hydroxylysine.


An enzymatic method for measuring picomole quantities of acetylcholine and choline in CNS tissue.


Improved rapidity and precision in the determination of brain 2',3'-cyclic nucleotide 3'-phosphohydrolase.


A sensitive fluorometric assay for monoamine oxidase activity.


Preparative solvent partition chromatography of butyrylated cyclic AMP analogues.


Effect of cyclic AMP, theophylline and caffeine on the glucose repression of sporulation in Saccharomyces cerevisiae.


Drill biopsy of the breast--a critical analysis.


Regulation in the chemolithotroph Thiobacillus neapolitanus: fructose-1,6-diphosphatase.


Studies on in vitro synthesis and secretion of growth hormone and prolactin. II. Evidence against the existence of precursor molecules.


Cyclic 3',5'-adenosine monophosphate in isolated bone cells. II. Responses to adenosine and parathyroid hormone.


An investigation of progesterone receptors in guinea pig vagina, uterine cervix, mammary glands, pituitary and hypothalamus.


Mechanism of action of gonadotropin. IV. Cyclic adenosine monophosphate-dependent translocation of ovarian cytoplasmic cyclic adenosine monophosphate-binding protein and protein kinase to nuclear acceptor sites.


Calcitonin and the formation of 3',5'-AMP in bone and kidney.


Cholesterol sulfate: some aspects of its biosynthesis and uptake by tissues from blood.


Glucagon and epinephrine activation of adenylate cyclase and glucagon binding in Morris hepatomas.


Transfer ribonucleic acid in hepatoma tissue culture cells. II. Dexamethasone phosphate induction of tRNAphe analyzed under cell-free conditions.


Changes in thyroid ribonucleic acid, ribonucleases and alkaline ribonuclease inhibitor.


Effects of prostaglandin antagonists on the induction of cyclic 3',5'-adenosine monophosphate formation and thyroid hormone secretion in vitro.


Cyclic-AMP and the ocular responses to norepinephrine.


Rescue of the murine sarcoma virus genome from non-producer cells by the RD-114 type C virus.


The effect of long-term exposure to DDT on CF-1 MICE.


Cell-mediated destruction of Rous sarcomas in Japanese quails.


Surface antigen and polypseudopodia in abortive transformation of BHK 21 cells by polyoma virus.


Establishment of continuous lymphoblast cultures from leukocytes of gibbons (Hylobates lar).


Re-exposure of human lymphoblastoid cell lines to Epstein-Barr virus.


Regulation of maltodextrin phosphorylase synthesis in Escherichia coli by cyclic adenosine 3', 5'-monophosphate and glucose. Cyclic adenosine 3', 5'-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3'-AMP, 5'-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, alpha-methyl glucoside, 2-deoxyglucose, and pyridoxal 5'-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase.


Membrane permeability and the loss of germination factor from Neurospora crassa at low water activities. Neurospora crassa conidia incubating in buffer at low water activities (a(w)) release a germination-essential component as well as 260-nm absorbing and ninhydrin-positive materials, regardless of whether an electrolyte or non-electrolyte is used to reduce a(w). Chloroform and antibiotics known to increase cell-membrane permeability have a similar effect. This suggests that membrane damage occurs in media of low a(w) and that an increase in permeability is responsible for the release of cellular components. The damage caused in media of low a(w) is nonlethal in most cases, and the conidia recover when transferred to nutrient medium.


Sporulation of Saccharomyces cerevisiae in the absence of a functional mitochondrial genome. The role of the mitochondrial system during sporulation of Saccharomyces cerevisiae was studied. Addition of ethidium bromide (EthBr) to cells growing in acetate medium resulted in the quantitative (>98%) conversion of the culture to the petite genotype in one generation. The cells were respiratory active (derepressed) but contained no mitochondrial deoxyribonucleic acid (mtDNA) as demonstrated by analytical ultracentrifugation in CsCl. When transferred to acetate sporulation medium, the culture sporulated. Ascus production was only slightly below that of the control culture. Synthesis of mtDNA occurred during sporulation in the control but not in the EthBr-treated culture. Mitochondrial protein synthesis was virtually eliminated in the EthBr-treated culture. Therefore, completely derepressed cells can sporulate without a functional mitochondrial genetic system. When partially repressed cells were treated with EthBr, no ascus formation was observed after transfer to sporulation medium. Control cultures underwent respiratory adaptation in sporulation medium and then sporulated. Extensive derepression of the respiratory system is thus required for sporulation, and this adaptation is dependent on a functional mitochondrial system. Our results suggest that once the cells are fully derepressed no mitochondrial genetic information has to be expressed during meiosis and ascus formation.


Lactose and D-galactose metabolism in group N streptococci: presence of enzymes for both the D-galactose 1-phosphate and D-tagatose 6-phosphate pathways. Group N streptococci possess enzymes for the metabolism of d-galactose through both the d-galactose 1-phosphate pathway (Leloir pathway) and the d-tagatose 6-phosphate pathway.


Germination of yeast spores lacking mitochondrial deoxyribonucleic acid. A population of petite ascospores (mitochondrial deoxyribonucleic acid [mtDNA]-less), produced by brief ethidium bromide (EthBr) mutagenesis prior to transfer to sporulation medium, was used to examine the role of the mitochondrial genetic system on germination and outgrowth in Saccharomyces cerevisiae. Petite ascospores, which are morphologically indistinguishable by phase-contrast microscopy from wild-type spores, germinate and proceed through outgrowth at a rate and extent only slightly less than that of wild-type spores. Both developmental processes occurred in the absence of mtDNA synthesis and measurable cytochrome oxidase activity. These results indicate that neither respiration nor a functional mitochondrial genome are required for germination and outgrowth. The properties of the petite clones were typical of petites formed during vegetative growth. Individual sporal clones differed markedly from each other in suppressiveness. Petite sporal clones which exhibited a high degree of supressiveness also contained a reduced but detectable amount of mtDNA of altered buoyant density. One clone contained a unique mtDNA with a buoyant density higher than that of wild-type mtDNA.


Differential diagnosis of chronic orofacial pain.


Disabling neuropathy associated with thymoma. Reversal by excision.


Letter: Abdominal pain in hyperlipoproteinemia.


The nitroblue tetrazolium reduction test versus conventional hematology in the diagnosis of bacterial infection.


Zoster immune globulin. A further assessment.


Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 4-1974.


Evidence for a junctional effect of lead on neuromuscular function.


About the neurological sequelae of herniated intravertebral disc.


Proceedings: Human leukocyte antigens and ABO blood groups in gestational trophoblastic neoplasms.


Proceedings: Hormonal relations of endometrial cancer.


Proceedings: Xeroradiography of the breast.


Proceedings: Lectin monitored surface changes in transformed and mitotic normal cells.


Proceedings: Genetics and the cancer cell: cell growth regulation.


Proceedings: Tumors of the adrenal cortex and Cushing's syndrome.


Proceedings: Islets of Langerhans.

Proceedings: Islets of Langerhans.


Proceedings: Genetics and the cancer cell: cell genetics and growth of endogenous viruses.


Proceedings: Soft part sarcomas in children--1972.


Proceedings: Survival of lung cancer patients vis-à-vis therapy and cell type.


Proceedings: The national Wilms' tumor study: a progress report.


Proceedings: Carcinoma of the lung at the New York Hospital-Cornell Medical Center (1964-1968).


Proceedings: Immunological investigations on human brain tumor patients.


Proceedings: Chemotherapy of soft-tissue sarcomas.


Synaptic transmission between photoreceptors and horizontal cells in the turtle retina. Low calcium, high magnesium, and cobalt hyperpolarize the horizontal cell membrane and suppress the response to light, but only partially affect the response of receptor cells. These observations are consistent with the interpretation that a depolarizing transmitter is released by photoreceptors in darkness. The hyperpolarizing response to light of the horizontal cells would then result from a reduction in the amount of transmitter released.


High-frequency C-type virus induction by inhibitors of protein synthesis. When inhibitors of protein synthesis are added to BALB/c mouse cells in culture, induction of naturally integrated C-type RNA virus occurs in a high percentage of cells. The action of protein synthesis inhibitors differs from that of halogenated pyrimidines, another class of virus inducers, in their effects on biologically distinguishable viruses. The use of such inhibitors to study integrated virus expression provides a means for studying gene regulation in mammalian cells.


Reduction of ferricytochrome c by some free radical agents. Fast pulse radiolysis and kinetic spectroscopy were used to rapidly generate a variety of free radicals in situ and study their reactions with ferricytochrome c in the time range 10(-6) to 1 second. The radicals included t-butanol, which is inert to ferricytochrome c; malate, lactate, and ethanol, which react with it relatively slowly but are completely utilized in reducing it to ferrocytochrome c; and hydrated electrons and hydrogen atoms, which react with it very rapidly but yield ferrocytochrome c only in part, showing intramolecular consecutive reactions and further attack on the ferrocytochrome c protein. From a detailed comparison between malate and hydrogen atoms it is argued that malate reacts directly and selectively with a specific part of the ferricytochrome c surface while hydrogen atoms react with other parts of the protein too, yielding radicals which in part transfer intramolecularly to yield ferrocytochrome c.


Proton relaxation rates of water in brain and brain tumors. The distribution of relaxation rates of water in "normal" (autopsy) samples of canine and human brain shows considerable overlap with that for brain tumor samples. The following ranges of values for the spin-spin relaxation rates were observed: for normal brain gray matter, 8.6 to 11.3 sec(-1) (mean, 9.5 sec(-1)); for normal brain white matter, 13.3 to 15.7 sec(-1) (mean, 15.5 sec(-1)); for six types of malignant tumor, 4.8 to 13.4 sec(-1) (mean, 9.3 sec(-1)); for five types of benign tumor, 7.1 to 16.4 sec(-1) (mean, 11.5 sec(-1)). Spin-lattice relaxation rates showed a similar pattern. At least two nonexchanging water components with different relaxation rates were indicated by the analysis of the spin-spin relaxation measurements for the white matter samples.


Protein kinase translocation as an early event in the hormonal control of uterine contraction. beta-Adrenergic stimulation with isoproterenol inhibits contractility, increases cyclic adenosine monophosphate (AMP) concentration, decreases the concentration of unsaturated cyclic AMP receptor sites, and increases cyclic AMP-independent kinase in the uterus of ovariectomized rats. The total soluble kinase activity is reduced. The protein kinase activity lost from the cytosol was translocated to the microsomal fraction mostly in a cyclic AMP-independent form, suggesting a particulate substrate for the activated enzyme.


Rapid adiabatic passage EPR of ferricytochrome c: signal enhancement and determination of the spin-lattice relaxation time.


Thyroid optic neuropathy: to decompress or not?


Studies of the metal sites of copper proteins. V. A model compound for the copper site of superoxide dismutase.


Conformational studies on modified proteins and peptides. VII. Conformation of epsilon-prototoxin and epsilon-toxin from Clostridium perfringens. Conformational changes associated with toxicity.


Preparation of photo-affinity probes for the insulin receptor site in adipose and liver cell membranes.


Cholinergic mechanism in the cerebrovascular action of carbon dioxide.


Phosphorylation of surface proteins of HeLa cells using an exogenous protein kinase and (gamma-32P)ATP.


A partially purified membrane protein specific to the brain.


Monoiodinated angiotensins: preparation and characterization by polyacrylamide gel electrophoresis and isoelectric focusing.


Electron nuclear double resonance studies on heme proteins: interaction of the electron spin with the 57Fe3+ nucleus in metmyoglobin and methemoglobin.


Triphosphoinositide phosphodiesterase in a protozoan-Crithidia fasciculata.


Analysis of polar parts of phospholipids. N-demethylation of choline-containing lipids for gas chromatography and mass spectrometry.


Improved conditions for the preservation and extraction of polyphosphoinositides.


The subcellular distribution of polyphosphoinositides in myelinated and unmyelinated rat brain.


Blood group A active ceramide hexasaccharide lacking N-acetylglucosamine isolated from hog stomach mucosa.


The influence of extracellular calcium ion on hormone-activated lipolysis.


The detection of linoleic acid radicals in the anaerobic reaction of lipoxygenase.


Attempts to reverse the effects of disuse in the lateral geniculate nucleus of the cat.


Influence of L-DOPA on transmission in long ascending propriospinal pathways in the cat.


Effects of stimulation of the vestibular labyrinth on intracellular responses of spinal motoneurons in the pigeon.


Restoration of locomotor activity in mice by low L-DOPA doses after suppression by alpha-methyltyrosine but not by reserpine.


Tetrodotoxin resistant electrically excitable responses of receptor cells.


Demonstration of hyper-alpha-lipoproteinemia in three diabetic patients.


The evolution of EEG features in infantile spasms: a prospective study.


The syndrome of inappropriate secretion of antidiuretic hormone (SIADH).


The effect of pertussis adjuvant on antibody production: the need for thymus-dependent lymphocytes.


Isolation and characterization of an adherent, 8-azaguanine resistant variant of the Burkitt lymphoma cell line, Raji.


Enzyme microelectrophoresis of cell colonies.


Acrosomal ATPase in starfish and bivalve mollusk spermatozoa.


Endocytosis in Chinese hamster fibroblasts. Inhibition by glucose.


The brain and sodium homeostasis.

The brain and sodium homeostasis.


Activation of phosphorylase in sea urchin eggs by Ca2+ and cyclic 3'5'-AMP. A possible mechanism of the regulation of its activity at fertilization.


Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion.


Studies of inhibitors of bone marrow colony formation in normal human sera and during a viral infection.


Preferential retention of the human chromosome C-7 in human-(thymidine kinase deficient) mouse hybrid cells.


Identification of N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine and bufotenin by cellulose TLC.


Medical problems in chronic alcoholic men.


Effects of idoxuridine on Herpesvirus hominis encephalitis and disseminated infections in marmosets.


Role of mosquitoes in the spread of smallpox.


Adenovirus vaccines in military recruit populations: a cost-benefit analysis.


Effect of proteolytic enzymes on the infectivity of a number of herpesviruses.


The two sites of penicillin action in Escherichia coli.


Viruses causing common respiratory infection in man. IV. Reoviruses and Adenoviruses.


Xeroderma pigmentosum cell susceptibility to SV40 virus transformation: lack of effect of low dosage ultraviolet radiation in enhancing viral-induced transformation.


On the origin of oligomer forms of polyoma DNA.


Editorial: Role of the megakaryocyte and platelet in the leukemic process in mice and men--a review and hypothesis.


Factors affecting glycogen levels in HeLa cells: prednisolone and adenine nucleotides.


Antibodies to Epstein-Barr virus-related antigens in nasopharyngeal carcinoma. Comparison of active cases with long-term survivors.


Lung cancer in women: present and future trends.


Prevalence of type-C virus and antibodies in normal cats and cats with neoplasia.


Virus-chemical carcinogenesis: a possible viral immunologic influence on 3-methylcholanthrene sarcoma induction.


A new group of oncogenic viruses: reticuloendotheliosis, chick syncytial, duck infectious anemia, and spleen necrosis viruses.


Detection of hamster type-C virus antigens by the passive hemagglutination technique.


Oncogenicity of Herpesvirus ateles in monkeys.


Studies of FBJ osteosarcoma virus in tissue culture. I. Biologic characteristics of the "C"-type viruses.


Oncogenic potential of murine C-type RNA virus passaged directly from naturally occurring tumors of the BALB-cCr mouse.


Comparative characterization of a C-type virus-producing cell line (VSW) and a virus-free cell line (VH2) from Vipera russelli.


Abelson virus activity in mice and rats neutralized with anti-Rauscher virus serum.


Antibodies reacting to Simian virus 40 T antigen in human sera.


Kinetics of nitrosation of the amino acids proline, hydroxyproline, and sarcosine.


Induction of tubular structures in the endoplasmic reticulum of human lymphoid cells by treatment with 5-bromo-2'-deoxyuridine.


Toxic metabolites released from rat hepatoma cells in culture. I. Effects of metabolites of hepatomas on various cells.


Cultivation and characterization of BALB-cfC3H mammary tumor cell lines.


Selection of tumor-host cell hybrids from polyoma virus- and methylcholanthrene-induced sarcomas.


Histopathology of tumor regression after intralesional injection of Mycobacterium bovis. IV. Development of immunity to tumor cells and BCG.


In vivo inoculation of RNA C-type viruses inducing regression of experimental solid tumors.


High resolution autoradiographic study of the kinetics of development of Rous sarcoma virus (Schmidt-Ruppin strain). V. Estimation of the time of synthesis of virus-associated DNA.


Antibody patterns to Herpesvirus saimiri-induced antigens in owl monkeys.


Transplacental effects of 1-ethyl-1-nitrosourea in inbred strains of mice. 3. Association between infectious or subinfectious endogenous type-C RNA tumor virus expression and chemically induced tumorigenesis.


Interactions of early mouse embryos with oncogenic viruses--simian virus 40 and polyoma. I. Ultrastructural studies.


Expression of A- and C-type particles in early mouse embryos.


Oral excretion of Herpesvirus saimiri in captive squirrel monkeys and incidence of infection in feral squirrel monkeys.


Transplantation of chemically induced metastatic mucinous adenocarcinomas of the jejunum and colon in rats.


5'-Nucleotide phosphodiesterase isoenzyme and hepatic cancer in NCI-Mayo Clinic panel sera.


Reassociation kinetics for Epstein-Barr virus DNA: nonhomology to mammalian DNA and homology of viral DNA in various diseases. The number of Epstein-Barr virus (EBV) genomes per cell in established leukocytic lines and tissue specimens has been evaluated by measuring DNA-DNA reassociation kinetics with hydroxyapatite chromatography. Under the proper conditions, this method is sufficiently sensitive to detect EBV DNA in the amount of 0.1 genome per cell. All the samples tested that have been suspected to be without EBV DNA by cRNA hybridization proved negative by this more sensitive specific analysis. These included Hela and Hep2 cells, a negative case of Burkitt's lymphoma, two negative cases of nasopharyngeal carcinoma, and two established human leukocytic lines. Homology tests conducted with single-strand-specific nuclease S1 indicated that the viral DNA from a nasopharyngeal carcinoma and infectious mononucleosis were more than 90% homologous to EBV DNA.


Alteration in tRNA methyltransferase activity in mengovirus infection: host range specificity. The tRNA methyltransferase activity in mengovirus-infected L cells, HeLa cells, and Maden Derby bovine kidney cells has been examined during the course of infection. The first two cell lines yield a productive infection, but have different kinetics of inhibition of host RNA synthesis, whereas the bovine kidney cells are a restrictive host. In infected L cells the enzymes show altered capacity and base specificity throughout the infection. In infected HeLa cells and in infected bovine kidney cells less marked changes were seen. No inhibitors or activators of the enzymes were detected in any of the infected cell lines. Labeling experiments in infected cells indicated that in infected L cells synthesis of RNA was inhibited to a greater degree than was methylation of RNA. The consequence of this would be a hypermethylation of RNA. The methylated derivatives synthesized in infected L cells showed changes in relative proportions. Infection of HeLa cells and bovine kidney cells did not show such marked effects on methylation of RNA.


Cell-free translation of paramyxovirus messenger RNA. Polypeptides corresponding in electrophoretic mobility to virion polypeptides 1, 3, and 5 were made in a reticulocyte cell-free system to which 18S RNA from Sendai virus-infected cells was added. Immune precipitation was used to select relevant polypeptides from endogenous products. The cell-free product corresponding to virion polypeptide 3 (the nucleocapsid structure unit) was the most abundant; its tryptic peptides comigrated electrophoretically with tryptic peptides of polypeptide 3 isolated from virions. Other sedimenting classes of RNA from infected cells were tested; only the 28S fraction showed slight activity. Virion 50S RNA was inactive. These findings support the hypothesis that complementary RNA transcripts of paramyxovirion RNA are the templates for viral proteins.


Structural characteristics and nucleotide sequence analysis of genomic RNA from RD-114 virus and feline RNA tumor viruses. The results of molecular hybridization experiments have demonstrated that the RNA genome of RD-114 virus has extensive nucleotide sequence homology with the RNA genome of Crandell virus, an endogenous type C virus of cats, but only limited homology with the RNA genomes of feline sarcoma virus and feline leukemia virus. The genomic RNAs of RD-114 virus and Crandell virus also had identical sedimentation coefficients of 50S. A structural rearrangement of genomic RNA did not exist within released RD-114 virions, whereas a structural rearrangement of genomic RNA did occur within feline sarcoma virions and feline leukemia virions after release from virus-producing cells.


Strandedness and complementarity of DNA from long-term RNA-dependent DNA polymerase reactions of Soehner-Dmochowski murine sarcoma virus. The DNA product of the endogenously instructed RNA-dependent DNA polymerase reaction of murine sarcoma virus continued to be synthesized for as long as 64 h in the presence of 0.008% Triton X-100. Higher detergent concentrations and actinomycin D inhibited DNA product synthesis. The DNA product from long-term polymerase reactions consisted of small DNA fragments as shown by sedimentation in alkaline sucrose gradients. The enzymatic DNA product was separated into a slow sedimenting fraction and a fast sedimenting fraction by rate-zonal centrifugation. Fast sedimenting DNA was the predominant fraction made in viral polymerase reactions containing 262 mM NaCl. By using a combination of S-1 nuclease and pancreatic RNase A, the amount of single-stranded DNA, double-stranded DNA, and DNA-RNA hybrid present in the slow-sedimenting and fast-sedimenting fractions was determined. Under standard polymerase conditions of 70 mM NaCl, single-stranded DNA was the major form of DNA found in both fractions. In contrast, the prevalent form of DNA made in the presence of 262 mM NaCl was DNA-RNA hybrid. Hybridization studies in which either S-1 nuclease or pancreatic RNase A was used to measure hybrid formation demonstrated not only that the DNA product was complementary in base sequence to the RNA genome, but also that at least 79 to 84% of the RNA genome was transcribed into complementary DNA.


Polyoma pseudovirions. II. Influence of host cell on pseudovirus production. The type of host cell influenced the relative amounts of pseudovirions and polyoma virions produced. The infection of primary mouse embryo cells resulted in the production of particles that were predominantly pseudovirions. Infection of baby mouse kidney or 3T3D cells yielded mainly infectious polyoma virus. The length of time that infection was allowed to continue also affected the amount of pseudovirions relative to polyoma virions. The longer the viral infection was allowed to proceed, the greater the quantity of pseudovirions produced. Pseudovirion production could be correlated with the fragmentation of host cell DNA to a size of approximately 3 x 10(6) daltons. The fragmentation of host cell DNA was much more extensive in primary mouse embryo cells than in the other cell types.


Cell surface antigens associated with murine leukemia virus: definition of the GL and GT antigenic systems. Two new serological specificities were identified on the surface of murine leukemia virus (MuLV)-infected cells by direct and absorption immunofluorescence tests. Both antigens were detected with antisera prepared in rats that were growing transplants of syngenic MuLV-induced leukemias. Antigen G(L) was defined with the AKR leukemia K36 as the test cell; antigen G(T) was defined with the W/Fu leukemia C58(NT)D as the test cell. G(L) and G(T) antigens were serologically and genetically independent of the MuLV-induced Gross and G(IX) cell-surface antigens. G(L) and G(T) antigens were found in normal lymphoid cells of mice from high-leukemic strains, but not in lymphoid tissues of mice from most low-leukemic strains. Tumors and leukemias of mice of low-leukemic strains often were G(L) and G(T) positive. Similarly, infection of normal cells with MuLV resulted in expression of G(L) and G(T). With ferritin-labeled antibody the G(L) and G(T) antigens were observed on virus-free segments of the cell surface. Genetically, G(L) and G(T) antigens were each controlled by two dominant unlinked genes in AKR mice; these same antigens were each controlled by three or more dominant unlinked genes in C58 mice. Penetrance of G(L) and G(T) regulatory genes was dependent upon the Fv-1 genotype of the host. Expression of G(L) antigen was closely associated with virus production, whereas expression of G(T) antigen was less closely associated.


Morphogenesis of poliovirus. II. Demonstration of a new intermediate, the proviron. Poliovirus-infected cells contain a previously unrecognized particle which appears to be an intermediate in virion synthesis and therefore has been named proviron. It sediments at about 125S, contains the three procapsid proteins, VP-0, VP-1, and VP-3, and has 35S viral RNA. It is disrupted both by sodium dodecyl sulfate and EDTA but the RNA resists digestion by ribonuclease. Pulsechase experiments and studies employing the virus-specific inhibitor, guanidine, all indicate that the proviron is formed by combination of newly made RNA with the procapsid. Cleavage of VP-0 to form VP-2 and VP-4 follows formation of the provirion and would be the final step in poliovirus morphogenesis.


Morphogenesis of poliovirus 3. Formation of provirion in cell-free extracts. Formation of an apparent virion precursor, the provirion, can be demonstrated in cytoplasmic extracts of poliovirus-infected HeLa cells.


Simian virus 40-host cell interactions. I. Temperature-sensitive regulation of SV40 T antigen in 3T3 mouse cells transformed by the ts*101 temperature-sensitive early mutant of SV40. BALB/3T3 and Swiss/3T3 mouse cells transformed at permissive temperature (33 C) by the early temperature-sensitive mutant of simian virus 40 (SV40), ts(*)101, exhibited a temperature-dependent modulation of SV40 tumor (T) antigen as assayed by immunofluorescence. The percentage of T antigen-positive nuclei in ts(*)101 transformed cells was reduced at restrictive temperature (39 C) when compared to 33 C and to wild-type SV40 transformed cells at either 33 C or 39 C. The percentage of T antigen-positive nuclei in ts(*)101 transformed cells returned to the 33 C control level when the cells were shifted from 39 to 33 C. The ts(*)101 transformed cells could be superinfected with wild-type, but not ts(*)101, virions at 39 C as assayed by an increase in T antigen-positive nuclei.


RNA-dependent RNA polymerase in nuclei of cells infected with influenza virus. Nuclei purified from chicken embryo fibroblast cells infected with influenza (fowl plague) virus contain an RNA-dependent RNA polymerase. The in vitro activity of this enzyme is insensitive to actinomycin D, and is completely destroyed by preincubation with ribonuclease. Enzyme induction is prevented if cells are treated with actinomycin D or cycloheximide at the time of infection. RNA-dependent RNA polymerase activity increases rapidly in cell nuclei from 1 h postinfection, reaches a maximum at 3 to 4 h, then declines; a similar RNA polymerase activity in the microsomal cell fraction increases from 2 h postinfection and reaches a maximum at 5 to 6 h. The characteristics of the nuclear and microsomal enzymes in vitro are similar with respect to pH and divalent cation requirements. The in vitro products of enzyme activity present in the nuclear and microsomal fractions of cells infected for 3 and 5 h were characterized by sucrose density gradient analysis, and annealing to virion RNA. The microsomal RNA polymerase product contained 67 and 93% RNA complementary to virion RNA at 3 and 5 h, respectively; for the nuclear RNA polymerase product these values were 40% in each case.


Determination of the molecular weight of animal RNA viral genomes by nuclease digestions. I. Vesicular stomatitis virus and its defective T particle. A procedure has been developed for the determination of the weight of animal RNA virus genomes using controlled nuclease digestions and computation of the moles of oligonucleotides obtained from 1 mol of RNA. Using both pancreatic RNase and RNase T(1) to digest viral RNA labeled by (3)H-uridine, (3)H-cytidine, or (3)H-guanosine, the weight of the virion RNA of vesicular stomatitis virus (VSV) is estimated as 3.82 +/- 0.14 x 10(6) whereas that of the VSV-defective T particle is estimated as 1.23 +/- 0.04 x 10(6).


RD 114 virus-specific sequences in feline cellular RNA: detection and characterization. RNA extracted from cat cells contains sequences homologous to RD-114 viral RNA. The sequences are measured by molecular hybridization with a single-stranded DNA probe synthesized by the virion polymerase using the endogenous viral RNA as template. Viral-specific RNA has been detected in all cells of cat origin tested thus far, but not in cells of other animals, except for the virus-producing human rhabdomyosarcoma cell, RD-114. The extent of hybridization of the DNA probe to cellular RNA was equivalent to that obtained with viral 70S RNA indicating that an equal extent of viral specific sequences is present in all cat cells as well as in RD-114 cells. The amounts of this viral RNA reach approximately 100 copies per cell in cat cells, while virus-producing RD-114 cells contain about 1,000 copies per cell. The viral RNA is present in cat cells in two distinct sizes of about 35S and 18S, whereas in RD-114 cells virus-specific RNA is quite heterogeneous in size.


Viruses as precipitants of asthmatic attacks in children.


Letter: Topical application of cyclic AMP in psoriasis.


Letter: Imipramine and enuresis.

Letter: Imipramine and enuresis.


Phenotypic mixing of vesicular stomatitis virus with HVJ (Sendai virus).


Radiological experience with nasopharyngeal masses.


Effect of exogenous oestrogens on minor psychiatric symptoms in postmenopausal women.


Mannosidosis: clinical, fine-structural and biochemical findings in three cases.


Renal function in long-term survivors after treatment for nephroblastoma.


Comparative measurements of enzyme activities and 2,3-diphosphoglycerate in the erythrocytes of newborns with transitory hyperbilirubinaemia.


Adrenal glucocorticoid function in acute viral infections in children.


Cyclic GMP and gastric acid secretion.

Cyclic GMP and gastric acid secretion.


Comprehensive training in forensic psychiatry.


A guide for drug use in depressive disorders.


Determination of sedimentation coefficients of subcellular particles of rat liver homogenates. A theoretical and experimental approach.


Orthophosphate analysis by the Fiske-SubbaRow method and interference by adenosine phosphates and pyrophosphate at variable acid pH.


Adenosine 3',5' cyclic monophosphate assay at 10-15 mole level.


Clinical observations on response to nasal occlusion in infancy.


Determination of 25-hydroxycholecalciferol by combined thin layer and gas chromatography.


Genetic determinants of aminoglycoside resistance in strains of Mycobacterium tuberculosis.


Cellophane perinephritis hypertension and its reversal in rabbits. Effect on plasma renin, renin substrate, and renal mass.


Interrelationship between bacterial histidine decarboxylase activity and concentration of histidine and pyridoxal-5'-phosphate.


Investigations on the effects of diethazine on neuromuscular transmission in the rat.


Glutamine phosphoribosylpyrophosphate amidotransferase.


Adrenergic control of the peripheral circulation in cardiomyopathic hamsters with heart failure.


Protein kinases.

Protein kinases.


The effect of ACTH and cortisone on gastric acid mucosubstances in rats.


The effects of delta8-THC on the EEG, reticular multiple unit activity and sleep of cats.


Analytical studies on ergot alkaloids and their derivatives. I. Separation of ergot alkaloids of the ergotoxine and ergotamine groups by thin-layer chromatography.


Thin-layer chromatographic behaviour of the acetates of some polyfunctional diterpene alcohols of toxicological interest.


Synthesis and enzymic studies of 5-aminoimidazole and N-1-and N6-substituted adenine ribonucleoside cyclic 3',5'-phosphates prepared from adenosine cyclic 3',5'-phosphate.


Lipolytic activity of Met-Arg-His-Phe-Arg-Trp-Gly, a synthetic analog of the ACTH (4-10) core sequence.


Nucleic acid and polyamine synthesis in the rat during short-term protein deficiency: responsiveness of the liver to partial hepatectomy.


Nucleic acid and polyamine synthesis in the rat during short-term protein deficiency: responsiveness of the bone marrow and liver to blood loss.


Potential antidiabetic agents. Pyrazolo(3,4-b)pyridines.


Letter: Minimal pressure neuropathy.

Letter: Minimal pressure neuropathy.


Changes in serum pre-beta-lipoprotein following the feeding of sucrose. A preliminary trial in physically active and inactive young male students.


Alpha-thalassaemia in an Australian family.


Wilms' tumour: increasing hopes for survival.


Transfemoral catheter embolization: a method of treatment of glomus jugulare tumors.


Viremia during parainfluenza type 3 virus infection of hamsters.


Further observations on the attachment of carbohydrate to lipoproteins by rat liver Golgi membranes.


Antagonism of morphine analgesia by adenine, adenosine, and adenine nucleotides.


Changes in phospholipid composition of Micrococcus lysodeikticus during growth.


The calcium-independent stimulation of thymic lymphoblast DNA synthesis by low cyclic GMP concentrations.


Enancement of uptake of Simian virus 40 by nuclei of permissive cells.


Hepatis B virus antigen development in cultured human hepatocytes.


Simplified method for isolation of cytomegalovirus and demonstration of frequent viremia in renal transplant patients.


Studies on the mode of action of dibromopropamidine.


The antitumor effect of interferon in lymphocyte- and macrophage-depressed mice.


Sucrose feeding in man. Effects of substrate incorporation into hepatic triglycerides and phosphoglycerides in vitro and on removal of intravenous fat in patients with hyperlipoproteinemia.


A simple automates fluorometric method for the determination of 2,3-diphosphoglycerate in blood.


Glycolytic enzyme activity of cells infected with adenovirus types 5 and 12.


Ectopic adrenocorticotropin syndrome with prostatic carcinoma.


Molecular forms of glucose-6-phosphate dehydrogenase in liver diseases.


Hepatic and adrenocortical function during cyclophosphamide stoss therapy.


Hidroadenoma of the vulva.

Hidroadenoma of the vulva.


Virion polypeptides and structure of SV40.


The influence of exogenous substrates on the breakdown of alcohol.


Production of equine infectious anemia antigen in a persistently infected cell line.


Preparation of equine infectious anemia virus antigen for immunodiffusion test.


Multiple immobilized enzyme reactors: determination of pyruvate and phosphoenolpyruvate concentrations using immobilized lactate dehydrogenase and pyruvate kinase.


Structural characteristics of hydrated glycerol-and sphingo-lipids. A spin label study.


Electrophoretic studies on three variants of Mengo encephalomyelitis virus.


Synthesis and acid hydrolysis of monophosphate and pyrophosphate esters of phytanol and phytol.