Noncoding nucleotide sequence in the 3'-terminal region of a mouse immunoglobulin kappa chain messenger RNA determined by analysis of complementary DNA.
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Biomedical subjects
Publications and source records attributed to J Jackson.
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We have shown that three types of copper-binding ligands, thiosemicarbazones, 8-hydroxyquinolines, and isonicotinic acid hydrazide and their copper complexes, inactivate the transforming ability of RSV and inhibit its RNA-dependent DNA polymerases. Three other compounds, 2-pyridine thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone, and diphenyl thiocarbazone inhibit transformation by RSV intracellularly. Most but not all of these compounds bind to nucleic acids in the presence of copper, which may be important in their mode of action.
Several, structurally different, copper-binding ligands can inhibit the RNA-dependent DNA polymerase of Rous sarcoma virus (RSV) and can inactivate the ability of the virus to malignantly transform chick embryo cells. These ligands include the anti-microbial agents, thiosemicarbazones, 8-hydroxyquinolines, isonicotinic acid hydrazide, and others. Many of these compounds bind to DNA and RNA in the presence of copper, which may play a role in their anti-viral activity. However, not all agents active against RSV bind to nucleic acids and not all ligands that bind to nucleic acids are active against RSV. Some copper-binding ligands are neither active against RSV, nor bind nucleic acids. It appears that there is no simple relationship between the anti-viral activity of copper-binding ligands and their nucleic acid-binding ability. The biological importance of thiosemicarbazone-copper complex binding to nucleic acids is supported by the observation that treatment of intact RSV virions with the complex causes the genome 70S RNA to sediment abnormally in velocity sucrose gradient analysis.
Hypotheses were derived from assumptions inherent in two contrasting conceptions of a treatment environment, attitudinal and ecological. Research was conducted in two different British mental hospitals, using scales from the OMI and the CTE. As predicted, the OMI scales were related only to staff attributes and did not discriminate among environments of institutions or units that differed in program, philosophy, organization, or type of patients. CTE scales distinguished between hospital treatment environments and wards. There was slight evidence that observed attributes influenced ecological measures of the objective treatment environment, or that staff ideology had any substantial impact upon treatment environments.
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Kethoxal bis (thiosemicarbazone) (KTS) inhibited replication of, and plaque formation by, vesicular stomatitis virus (VSV) in chick embryo cells. No other thiosemicarbazones tested were effective. Virus-specific m-RNA and protein synthesis were inhibited by KTS. However, virion RNA-dependent RNA synthesis was not inhibited by the drug. Treatment of VSV virions directly with KTS produced enhancement, rather than inactivation, of plaque formation. KTS inhibited cellular DNA and RNA synthesis by 67 and 25% respectively. Since cellular DNA and RNA synthesis are not required for VSV replication, the inhibition of these processes is probably unrelated to the antivirial activity of KTS. Cellular protein synthesis was inhibited 24% by KTS. Unexpectedly, synthesis of four proteins was induced in KTS-treated uninfected cells.
A large body of data on segregating families is used to generate specific recurrence risks conditional on sex and birth order for the best-fitting model of polygenes plus maternal effect. The method is general for diseases of complex inheritance, and lies within the competence of any serious genetic clinic. The question of whether consultees demand as much specificity should be subordinate to the question of whether counsellors are justified in providing less.
A method for diagnosing pregnancy in the guinea pig by manual palpation was developed. Using this technique, pregnancy was detected between the 15th and 30th day of gestation with 98% accuracy. The 2% error consisted of animals that were pregnant but diagnosed as nonpregnant. Common mistakes that led to diagnosing nonpregnant animals as pregnant were: (1) palpation of fecal pellets; (2) palpation of left kidney; and (3) palpation of the sartorius muscle. Common errors that led to diagnosing pregnant animals as nonpregnant were: (1) failure to search the entire abdomen; (2) too close apposition of thumb and forefingers while searching the abdomen; and (3) failure to deprive animals of feed before palpation.
This report documents a case of dentin dysplasia Type I in a 17-year-old boy and two members of his family. The clinical, radiographic, histologic, and ultrastructural findings indicate that this condition is distinct from other heritable defects of dentin. The entity is transmitted as an autosomal dominant trait and is characterized by teeth which have a normal color and exhibit pulpal obliteration, short roots, periapical radiolucencies, and spontaneous exfoliation. Our ultrastructural findings in agreement with those reported by Sauk and associates.
8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of "concentration quenching" was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity.
Seven cases of congenital deafness and an autosomal recessive pedigree pattern were observed in an inbred kindred. Three of the cases also had vitiligo, and there were 2 other cases of vitiligo in this kindred. The vitiligo also appeared to have an autosomal recessive inheritance pattern.
Four cases of Engelmann disease were observed in a dominant inheritance pattern in a family of St. Landry Mulattoes. In the youngest sibship, one of the cases also had tumoral calcinosis. Another sib had only tumoral calcinosis, though some findings suggested that this sib may also have had Engelmann disease. All 3 of the younger sibs had snow-capped teeth. It is suggested by this family that snow-capped teeth may be part of the syndrome of Engelmann disease.
The effects of standardized aerobic and anaerobic exercise intensities on intraocular tension, blood lactate, and pH were studied. Intraocular tension decreased rapidly at all exercise intensities. The absolute lowest level of intraocular tension reached with aerobic and anaerobic exercise levels varied by only 1.5 mm. Hg and this difference was not statistically significant. Blood lactate and pH changes correlated with intraocular tension changes at anaerobic exercise levels, but not at aerobic exercise levels. These findings associated with aerobic exercise have not been previously reported. It is suggested that parameters other than the decrease in blood pH and the increase in blood lactate are responsible for most of the decrease in intraocular tension associated with dynamic exercise.
Regulation of isoleucine, valine, and leucine biosynthesis and isoleucyl-, valyl-, and leucyl-transfer ribonucleic acid (tRNA) synthetase formation was examined in two mutant strains of Escherichia coli. One mutant was selected for growth resistance to the isoleucine analogue, ketomycin, and the other was selected for growth resistance to both trifluoroleucine and valine. Control of the synthesis of the branched-chain amino acids by repression was altered in both of these mutants. They also exhibited altered control of formation of isoleucyl-tRNA synthetase (EC 6.1.15, isoleucine:sRNA ligase, AMP), valyl-tRNA synthetase (EC 6.1.1.9, valine:sRNA ligase, AMP), and leucyl-tRNA synthetase (EC 6.1.1.4, leucine:sRNA ligase, AMP). These results suggest the existence of a common element for the control of these two classes of enzymes in Escherichia coli.
The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin beta-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity. Two cations, Cu(++) and Hg(++), can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism between N-methyl isatin beta-thiosemicarbazone and Cu(++) occurs, since treatment of the virus with a low dose of either N-methyl isatin beta-thiosemicarbazone or Cu(++) has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions. Several cations (Ag(+), Co(++), Zn(++), Cd(++), and Ni(++)) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.
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