Cellular transforming genes in cancer.
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Animals↗
Biomedical subjects
G M Cooper
Publications and source records attributed to G M Cooper.
Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas.
Two lung and two colon carcinoma cell lines of human origin, which contained the same activated rasK transforming gene, expressed abnormal species of p21 that were distinct from the p21 proteins expressed in normal human cells and other human carcinomas. The abnormal species of p21 expressed by three of these cell lines were indistinguishable from each other, but differed from the abnormal p21 expressed by one lung carcinoma cell line. NIH cells transformed by DNAs of these carcinomas expressed the same abnormal p21 species, indicating that these abnormal proteins were encoded by the activated rasK genes detected by transfection. These results indicate that transforming activity of rasK genes in human lung and colon carcinoma cell lines is activated by mutations which alter the structure of their gene products, and that activation of rasK genes can result from different molecular alterations in different individual neoplasms.
Carcinoma↗
Transforming genes of neoplasms.
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Animals↗
Does obesity affect recovery? A study using intravenous methohexitone and Althesin for short procedures.
One hundred and twenty unpremedicated patients, scheduled for minor gynaecological procedures, were randomly allocated to receive Althesin or methohexitone to supplement N2O and O2 anaesthesia. Patients were assessed as thin, medium or fat according to the degree of obesity as measured by skinfold calipers. The range of mean times for the patients to open their eyes was 3.1-4.0 minutes, to be orientated was 4.4-6.7 minutes and to perform a manipulative test was 27.7-32.1 minutes. No statistically significant differences were seen in these indices of recovery whether they received Althesin or methohexitone or whether they were thin, medium or fat. A paper and pencil test was also performed. Induction doses of the intravenous agent were calculated on a body weight basis and increments given only in response to movement. The mean total dose of Althesin was decreased from 1.33 mg total steroid/kg for thin patients to 1.06 mg total steroid/kg for fat patients (p less than 0.01). The mean total dose of methohexitone was decreased from 3.4 mg/kg for thin patients to 2.9 mg/kg for fat patients which was not significant.
Adolescent↗
The effect of age on recovery. A comparison of the kinetics of thiopentone and Althesin.
Eighty unpremedicated patients undergoing dilatation and curettage were randomly allocated to receive induction of anaesthesia with either Althesin or thiopentone prior to maintenance with nitrous oxide, oxygen and halothane. Patients in each group were divided into those under 50 years ('young') or over 50 years ('old'). Recovery was assessed by the time taken to opening their eyes, to give correct date of birth and to achieve their baseline ability of manipulative skill with a children's post box toy. There was no difference in the time taken to open eyes or give correct birth date whether the patients received Althesin or thiopentone, or whether they were 'young' or 'old'. An age-related difference emerged with the post box test in patients who had received thiopentone, the older patients recovery time being increased from 28.5 minutes to 45.1 minutes. There was no difference between the old and young patients who received Althesin in the time taken to complete the post box test.
Adolescent↗
Alfentanil and recovery.
Forty patients were given alfentanil 8 micrograms/kg as a supplement to either methohexitone or Althesin anaesthesia. Satisfactory anaesthesia and recovery were seen in all patients. Testing revealed very rapid recovery of psychomotor function. There were no differences between the two groups.
Adjuvants, Anesthesia↗
Effect of alfentanil and fentanyl on recovery from brief anaesthesia.
One hundred female patients were allocated randomly to receive either no analgesic supplementation to methohexitone, nitrous oxide in oxygen anaesthesia, or supplements of fentanyl 1.5 micrograms kg-1 or alfentanil 8, 12 or 16 micrograms kg-1. No differences were seen in the time to recover consciousness, regain orientation or manipulate shapes into a box. Analgesic supplementation resulted in a decrease in the requirement for methohexitone, and improved operating conditions. Some patients in each group who received fentanyl or alfentanil became apnoeic for more than 30 s duration. The duration of apnoea increased with larger doses of alfentanil.
Adolescent↗
Activation of a cellular transforming gene in tumours induced by Abelson murine leukaemia virus.
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Abelson murine leukemia virus↗
Standard intravenous regional analgesia.
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Adolescent↗
Cellular transforming genes.
Cellular genes potentially capable of inducing oncogenic transformation have been identified by homology to the transforming genes of retroviruses and by the biological activity of cellular DNA's in transfection assays. DNA's of various tumors induce transformation with high efficiencies, indicating that oncogenesis can involve dominant genetic alterations resulting in activation of cellular transforming genes. The identification and characterization of cellular transforming genes and their possible involvement in naturally occurring cancers, is discussed.
Animals↗
[The sick cilia syndrome].
The incidence of bronchiectasis should decrease because of improved immunization, but certain defects would still cause the malady. Fifteen consecutive patients with bronchiectasis were examined for ciliary defects by examining the nasal mucosae with an electron microscope and measuring the clearance of technetium-99m from the lung with a gamma camera. Three patients were found to have defects. Compound cilia, disorganization of the tubular structure, vacuolization and deficient inner dynein arms were observed. In one patient a loss of cell membranes which returned to normal after 4 months, was observed. Ciliary abnormalitites can either be anatomical or physiological and 'sick cilia' should be considered as a cause of bronchiectasis.
Bronchiectasis↗
Transforming genes of chicken bursal lymphomas.
Bursal lymphomas of chickens infected with lymphoid leukosis viruses contain at least two distinct activated transforming genes: 1) a c-myc gene activated by integration of viral DNA and 2) a cellular gene, not linked to viral DNA, which efficiently induces transformation of NIH 3T3 cells. Since lymphomagenesis by lymphoid leukosis viruses appears to be a multistep process, it is possible that activation of these two different genes occurs at different stages of the disease. The bursal lymphoma transforming gene detected by transfection has been isolated by molecular cloning. Hybridization analysis indicates that this gene is homologous to normal chicken DNA sequences.
Animals↗
Stage-specific transforming genes of human and mouse B- and T-lymphocyte neoplasms.
DNAs of 20 B- and T-lymphocyte neoplasms of human and mouse origin induced transformation of NIH/3T3 cells with high efficiencies, indicating that these neoplasms contained activated transforming genes that were detectable by transfection. Analysis of the susceptibility of the transforming activities of lymphocyte-neoplasm DNAs to digestion with restriction endonucleases indicated that the same or closely related transforming genes were activated in independent neoplasms representative of the same stage of normal cell differentiation. However, different transforming genes were activated in neoplasms representative of different stages of normal B- and T-lymphocyte differentiation. These results indicate that specific transforming genes are activated in neoplasms of discrete stages of differentiation within these cell lineages.
Animals↗
Identification of an antigen associated with transforming genes of human and mouse mammary carcinomas.
Sera from tumor-bearing mice immunoprecipitated a 86,000-dalton glycoprotein from extracts of NIH cells transformed by human mammary carcinoma DNA. This antigen was not immunoprecipitated from extracts of NIH 3T3 cells, spontaneously transformed NIH cells, NIH cells transformed by normal human DNA, NIH cells transformed by human bladder carcinoma DNA, or NIH cells transformed by Rous sarcoma virus DNA. In addition, sera from mice bearing tumors induced by NIH cells transformed by either normal human DNA or human bladder carcinoma DNA did not immunoprecipitate this antigen from extracts of NIH cells transformed by human mammary carcinoma DNA. However, this antigen was immunoprecipitated by sera from mice bearing tumors induced by NIH cells transformed by mouse mammary carcinoma DNAs and from mice bearing primary mammary carcinomas. These results indicate that this glycoprotein represents an antigen that is specifically associated with expression of the transmissible transforming genes of human and mouse mammary carcinomas.
Animals↗
Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses.
Blot hybridization analysis indicated that NIH 3T3 mouse bladder transformed by high molecular weight DNAs of a human bladder and a human lung carcinoma cell line contained new sequences homologous, respectively, to the transforming genes of Harvey (rasH) and Kirsten (rasK) sarcoma viruses. The unique ras sequences were present in multiple independent NIH cell lines transformed in both primary and secondary transfection assays and corresponded to ras sequences normally present in human DNAs. The ras gene product was expressed in NIH cells transformed by bladder carcinoma DNAs and in the human bladder carcinoma cell lines at levels 2- to 4-fold greater than the level observed in nontransformed NIH 3T3 cells. These results indicate that the transforming genes of these human tumor cell lines are the cellular homologs of two retroviral transforming genes.
Animals↗
Recovery from day-case anaesthesia. Comparison between methohexitone, Althesin and etomidate.
One hundred unpremedicated patients, undergoing short gynaecological procedures, were randomly allocated to receive one of three i.v. hypnotic agents (methohexitone, Althesin and etomidate) alone or in combination with fentanyl, to supplement 66% nitrous oxide in oxygen. Recovery was assessed by the time patients took to open the eyes, to give correct date of birth, to achieve a certain level of manipulative skill with a children's post-box toy, and to perform a paper and pencil test. Satisfactory operating conditions were not obtained using etomidate alone. Administration of methohexitone alone resulted in a more rapid initial awakening than Althesin alone (P less than 0.05) and the administration of fentanyl with methohexitone reduced the total dose given of the latter (P less than 0.01). Administration of fentanyl with Althesin or methohexitone did not significantly prolong the "post-box" recovery time. Side-effects were less common with Althesin, with or without fentanyl and etomidate with fentanyl was associated with the greatest frequency of complications.
Adolescent↗
The fibrinolytic effects of anaesthesia.
The fibrinolytic effects of six different anaesthetic agents were studied in 36 patients undergoing abdominal hysterectomy. Fibrinolytic activity was measured by dilute whole blood and euglobulin clot lysis times. Concentrations of plasminogen, fibrinogen and fibrin degradation products were also determined. Significant enhancement of fibrinolytic activity, measured as a decrease in clot lysis time, was seen during anaesthesia and surgery with all agents studied. Halothane produced the least effect and the greatest increase in fibrinolytic activity was seen during trichloroethylene anaesthesia. Lumbar extradural anaesthesia also consistently produced enhancement of fibrinolysis. The reasons for these results and their clinical implications are discussed.
Adult↗
Laparoscopy--a stressful procedure.
The metabolic and hormonal response to laparoscopy was investigated in 22 patients, in whom nitrous oxide-oxygen anaesthesia was supplemented with either 150 micrograms fentanyl or an Althesin infusion. There were significant increases in plasma cortisol (p less than 0.05) from 303 to 458 mmol/litre and prolactin from 1869 to 3918 mU/litre (p less than 0.01) at the end of laparoscopy in both groups of patients; these were sustained during the first hour of the recovery period. The blood glucose concentration increased significantly (p less than 0.05) from 4.48 to 5.28 mmol/litre at the end of laparoscopy in the Althesin patients and remained increased 1 hour postoperatively at 5.54 mmol/litre (p less than 0.01). The blood glucose concentration increased significantly (p less than 0.05) from 4.43 to 5.36 mmol/litre in the fentanyl patients only during the recovery period. There was no significant difference between the metabolic and hormonal changes observed with the two anaesthetic techniques.
Adult↗