Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms.
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Animals↗
Biomedical subjects
G M Cooper
Publications and source records attributed to G M Cooper.
Integration of Rous sarcoma virus DNA during transfection.
We have investigated the organization and integration sites of Rous sarcoma virus (RSV) DNA in NIH 3T3 mouse cells transformed by transfection with unintegrated and integrated donor RSV DNAs. RSV DNAs of different cell lines transformed by unintegrated donor DNA were flanked by different cellular DNA sequences, indicating that RSV DNA integrates at multiple sites during transfection. The RSV genomes of cells transformed by transfection were colinear with unintegrated RSV DNA, except that deletions within the terminal repeat units of RSV DNA were detected in some cell lines. These results suggested that the terminal repeat sequences of RSV DNA did not necessarily provide a specific integration site for viral DNA during transfection. In addition, cell lines transformed by integrated RSV DNAs contained both the RSV genomes and flanking cellular sequences of the parental cell lines, indicating that integration of integrated viral DNA during transfection occurred by recombinational events within flanking cellular DNA sequences rather than at the terminal of viral DNA. Integration of RSV DNA during transfection thus appears to differ from integration of RSV DNA in virus-infected cells, where the terminal repeat units of viral DNA provide a highly specific integration site. Integration of donor DNA during transfection of NIH 3T3 cells instead appears to proceed by a pathway which is nonspecific for both donor and recipient DNA sequences.
Animals↗
Molecular cloning and characterization of the chicken gene homologous to the transforming gene of Rous sarcoma virus.
Four molecular clones containing DNA homologous to the Rous sarcoma virus transforming gene (src) have been isolated from a random library of normal chicken DNA. The four clones are distinct overlapping isolates, which together span approximately 33 kb of cellular DNA. The clones locus appears to represent the major region of chicken DNA homologous to src, since src-containing restriction fragments of this locus account for the fragments detected by hybridization of src-specific probe to restriction digests of total chicken DNA. Analysis of the cloned chicken src locus by restriction and heteroduplex mapping indicates that the locus contains 1.6-1.9 kb of DNA homologous to the viral src gene. The chicken DNA sequences homologous to viral src are interrupted by five or six nonhomologous regions, totaling approximately 6 kb, which presumably represent introns in the cellular src gene.
Animals↗
Transforming activity of human tumor DNAs.
High molecular weight DNAs of 26 human tumors and tumor cell lines were assayed for the presence of transmissible activated transforming genes by transfection of NIH 3T3 mouse cells. DNAs of two bladder carcinoma cell lines induced transformation with high efficiencies (approximately 0.2 transformant per microgram of DNA), whereas DNAs of the other tumors studied lacked detectable transforming activity. These findings suggest that dominant mutations or gene rearrangements can result in the activation of cellular transforming genes in some human tumors.
Animals↗
Activation of related transforming genes in mouse and human mammary carcinomas.
High molecular weight DNAs of five tumors induced by mouse mammary tumor virus (MMTV), two mouse mammary tumors induced by a chemical carcinogen, and one human mammary tumor cell line (MCF-7) were assayed for the presence of transmissible activated transforming genes by transfection of NIH 3T3 mouse cells. DNAs of all five MMTV-induced tumors, one chemical carcinogen-induced tumor, and the human tumor cell line induced transformation with high efficiencies (approximately 0.2 transformant per micrograms of DNA). NIH cells transformed by DNAs of MMTV-induced tumors did not contain exogenous MMTV DNA sequences, indicating that MMTV-induced mammary carcinomas contained activated cellular transforming genes that were not linked to viral DNA. The transforming activities of DNAs of all five MMTV-induced tumors, the chemical carcinogen-induced mouse tumor, and the human tumor cell line were inactivated by digestion with the restriction endonucleases Pvu II and Sac I, but not by BamHI, EcoRI, HindIII, Kpn I, or Xho I. These results indicate that the same or closely related transforming genes were activated in six different mouse mammary carcinomas, induced by either MMTV or a chemical carcinogen, and in a human mammary carcinoma cell line.
9,10-Dimethyl-1,2-benzanthracene↗
Fentanyl and the metabolic response to gastric surgery.
The effect of the supplementation of nitrous oxide-oxygen anaesthesia with either 50 micrograms fentanyl/kg body weight or 0.5-1.0% halothane on the metabolic and hormonal response to gastric surgery was investigated in 16 patients. Those patients who received fentanyl showed a significant decrease (p less than 0.05) in the hyperglycemic response to surgery after 30 and 90 minutes and a significant decrease (p less than 0.05) in the plasma cortisol response after 30 minutes. Profound respiratory depression occurred at the end of surgery in all patients who were given fentanyl. This required the intravenous administration of naloxone and careful supervision in the early postoperative period. It is concluded that the transient metabolic and endocrine benefits produced by fentanyl do not compensate for the severe respiratory problems postoperatively and thus 'high-dose fentanyl' cannot be recommended for upper abdominal surgery.
Alanine↗
Studies on premedication and ventilatory responses to minaxolone.
The effect of three premedications on induction, maintenance and recovery characteristics of minaxolone as a supplement to nitrous oxide and oxygen anesthesia were studied in 70 patients. Morphine and atropine premedication provided superior operative conditions with fewer side-effects when compared with atropine alone or diazepam and atropine. Recovery was significantly longer after minaxolone compared with a similar group of patients given Althesin. The ventilatory responses to the induction of anesthesia with minaxolone were measured in 25 patients. All patients showed an increase in respiratory frequency and a decrease in tidal volume. This effect was most marked in the group premedicated with diazepam and atropine.
Adult↗
Transforming genes of neoplasms induced by avian lymphoid leukosis viruses.
Oncogenic avian retroviruses can be classified into three groups: sarcoma viruses, acute leukaemia viruses and lymphoid leukosis viruses (LLVs). Sarcoma and acute leukaemia viruses transform fibroblasts and/or haematopoietic cells in culture and induce tumours with short latent periods in infected birds. In contrast, LLVs do not transform cells in vitro and require long latent periods before formation of neoplasms in vivo. The most frequent neoplasm induced by LLVs is malignant lymphoma of the bursa of Fabricius, but LLVs also induce other neoplasms, including sarcomas, nephroblastomas and erythroblastosis. The genomes of both sarcoma and acute leukaemai viruses contain specific genes responsible for viral oncogenicity, whereas the genome of LLVs apparently includes only genes required for virus replication. The genetic basis for the low oncogenic potential of LLVs is therefore obscure. The present experiments indicate that LLV-induced tumours contain transforming genes that can be detected by transfection of NH 3T3 mouse cells. These transforming genes are not linked to LLV DNA sequences, suggesting that oncogenesis by LLVs may result from indirect activation of cellular transforming genes.
Alpharetrovirus↗
Transforming activity of DNA of chemically transformed and normal cells.
DNA fragments of chemically transformed and normal avian and murine cells induce transformation of NIH 3T3 mouse cells with low efficiencies. High molecular weight DNAs of cells transformed by DNA fragments induce transformation with high efficiencies in secondary transfection assays. It thus seems that endogenous transforming genes of uninfected cells can be activated and efficiently transmitted by transfection. These results are consistent with the hypothesis that normal cells contain genes that are capable of inducing transformation if expressed at abnormal levels.
Animals↗
Beta-adrenergic blockade and the metabolic response to surgery.
The effect of the administration of propranolol 0.15 mg per kg body weight i.v. on the metabolic response to pelvic surgery was compared with results in similar patients who had not received propranolol. The only significant difference between the two groups was a lower plasma insulin concentration in the beta-blockade patients after 60 and 90 min of surgery. The glycaemic response to surgery was unimpaired in the propranolol-treated patients and there were no adverse haemodynamic effects. We conclude that beta-adrenergic blockage is unlikely to have deleterious metabolic effects on healthy patients.
Adult↗
4-aminopyridine fails to induce porcine malignant hyperthermia.
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4-Aminopyridine↗
Transformation of NIH-3T3 mouse cells by avian retroviral DNAs.
NIH-3T3 cells were found to be transformable by RSV DNA in the absence of progeny virus production. Cells transformed by intact RSV DNAs contained rescuable RSV genomes that were integrated into cellular DNA and were colinear with unintegrated RSV DNA. NIH-3T3 cells were also transformable by subgenomic fragments of RSV DNA, synthesized in vitro or generated by restriction endonuclease digestion of intracellular RSV DNA. These cells did not contain rescuable RSV genomes but did contain RSV DNA fragments that efficiently induced transformation of NIH-3T3 cells in secondary transfection assays. Further analysis of the RSV DNA sequences present in these cells and transformation assays of defined fragments of RSV DNA may contribute to the elucidation of the sequences required for expression of the src gene of RSV. DNAs of the avian acute leukemia viruses MC29 and AEV also induced transformation of NIH-3T3 cells. The use of these cells as recipients may thus provide a system suitable for functional analysis of the transforming genes of avian leukemia viruses as well as sarcoma viruses.
Animals↗
Minaxolone or Althesin supplemented by nitrous oxide. A study in anaesthesia for short operative procedures.
Minaxolone citrate, a new water-soluble steroid intravenous anaesthetic, has been compared with Althesin as an induction agent and subsequently intermittently supplemented by nitrous oxide and oxygen alone for anaesthesia for short surgical procedures. Short term recovery following Minaxolone was significantly slower than after Althesin, but 1 h after the end of anaesthesia, no differences could be detected between the two groups of patients. Minaxolone, given by intravenous increments to supplement nitrous oxide following an induction dose of 0.5 mg/kg, appears to provide satisfactory anaesthesia for short surgical procedures.
Adult↗
Transfection by DNAs of avian erythroblastosis virus and avian myelocytomatosis virus strain MC29.
Chicken embryo fibroblasts and NIH 3T3 mouse cells were transformable by DNAs of chicken cells infected with avian myelocytomatosis virus strain MC29 or with avian erythroblastosis virus. Transfection of chicken cells appeared to require replication of MC29 or avian erythroblastosis virus in the presence of a nontransforming helper virus. In contrast, NIH 3T3 cells transformed by MC29 or avian erythroblastosis virus DNA contained only replication-defective transforming virus genomes.
Alpharetrovirus↗
Integration, expression, and infectivity of exogenously acquired proviruses of Rous-associated virus-O.
We investigated the integration sites, infectivities, and expression of Rous-associated virus-0 (Rav-0) DNAs in exogenously infected turkey and chicken cells. Restriction endonuclease analyses of the DNAs of RAV-0-infected cells indicated that unique integration sites of RAV-0 DNA were detectable in clones of RAV-0-infected cells but not in mass-infected cell cultures. In addition, the sites of integration of RAV-0 DNA differed in each of the seven clones of RAV-0-infected cells examined. Thus, endogenous RAV-0 proviruses appeared to integrate at multiple sites in cellular DNA, which were distinct from the sites of integration of endogenous RAV-0 genomes. Since exogenous RAV-0 proviruses are expressed at 10(3)- to 10(4)-fold-higher levels and are 10(3)- to 10(4)-fold more infectious in transfection assays than the endogenous RAV-0 genome of uninfected V+ chicken cells, these results are consistent with the hypothesis that transcription of the endogenous RAV-0 genome is regulated by flanking cellular DNA sequences. Although all RAV-0-infected cells contained infectious RAV-0 DNA and produced high titers of RAV-0 compared with uninfected V+ cells, different clones of RAV-0 infected chicken cells differed by as much as 30-fold in their levels of virus production. The infectivity of the DNA of each clone of RAV-0-infected cells correlated with the amount of virus produced by that clone. However, these differences did not appear to be correlated either with the number of exogenous RAV-0 proviruses in different clones or with the infectivity of RAV-0 produced by different clones, indicating that differences either in modification of RAV-0 DNAs or in the cellular sequences flanking exogenous RAV-0 DNAs were responsible for the observed differences in expression and infectivity.
Animals↗
Early clinical evaluation of minaxolone: a new intravenous steroid anaesthetic agent.
Minaxolone has been used for the induction and maintenance of anaesthesia in 60 patients undergoing minor surgical procedures. With nitrous oxide as the only supplement, satisfactory conditions were obtained in 56 patients. Patient acceptance was high.
Adult↗
Epidural analgesia and the metabolic response to surgery.
The effect of epidural blockade on the metabolic and hormonal responses to pelvic surgery was investigated in 14 female patients. Central venous blood samples were collected every 30 minutes and analysed for free fatty acids, glycerol, beta-hydroxybutyrate, acetoacetate, glucose, lactate, pyruvate, cortisol and growth hormone concentrations. There was no change in fat and glucose metabolism except for a transient decrease in lipolysis after 30 minutes of surgery. Cortisol and growth hormone values were significantly increased (p less than 0.01) after 60 minutes. A small but statistically significant increase in blood lactate concentration was observed (p less than 0.01) and the concept of a "metabolic V/Q" abnormality is postulated to explain the lacticacidaemia.
Adult↗
Transfection by exogenous and endogenous murine retrovirus DNAs.
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Animals↗