[Work environment. Violence is not a private affair].
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Biomedical subjects
Publications and source records attributed to J B Christensen.
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Colonoscopy is a common procedure, usually performed in a hospital setting. Hospital backup is desirable for high-risk patients, but the cost to benefit ratio may be unnecessarily high for low-risk patients. The demand for colonoscopic examinations is escalating, and cost containment has become an important issue. One way to reduce the cost is to eliminate the hospital component by performing the examination in the office. Over the past two and a half years, colonoscopy was performed on selected patients in the authors' office. Five hundred fifty-four office colonoscopies were performed to date, including biopsy or polypectomy in 348. Basic principles of safe intravenous sedation and colonoscopy were followed strictly. The cecum was reached in 92 percent of cases, and no significant complications were encountered. Office colonoscopy is a safe alternative to hospital colonoscopy. It confers significant cost savings to the patient and allows more efficient use of the physician's time.
The viability, p53 binding, and SV40 origin binding of a series of SV40 large T antigen point mutants, which map to the amino terminal one-third of the molecule, were examined. Two mutants which yield small plaques were found to have altered kinetics of replication upon infection of permissive cells. Mutants which did not bind to the origin of replication were not able to replicate, but the reverse was not always true. Replication defective mutants which bound the SV40 origin were found; these map both inside and outside of the origin binding domain. All the transformation defective mutants bound the cellular protein, p53.
Twenty-five consecutive patients with lung tumors were classified according to the presence of metastases by the use of 57Co-Bleomycin scintigraphy. Twenty-two of the tumors were visualized but metastatic spread to hilar lymph nodes was not detected. Reliable separation of central tumors with and without growth into neighbouring organs was not possible. Mediastinal uptake was found in eight cases but only a part of these could be verified by operation. The method can contribute to the evaluation of lung tumors and can be helpful to avoid some unnecessary thoracotomies.
When SV40 infects mouse cells, it does not replicate but instead causes neoplastic transformation of a small percentage of the cells. It is unknown, however, what happens to the virus in those cells that do not become transformed. We introduced SV40 into mouse cells by nonselective means, either by cotransfection of SV40 DNA with a selectable marker or by random cloning of SV40-infected cells. We analyzed the fate of viral DNA sequences, expression of T antigens, and transformation properties of these cells. We found that, upon infection, viral DNA integration occurs at a frequency that is at least 10-fold higher than the frequency of transformation. The majority of these cells are not transformed due to lack of expression of T antigen. One cell line which expresses a truncated T antigen is not transformed. We have mapped the viral sequences in the genome of these cells and find that integration in the large T intron is probably responsible for the defect. Lack of transformation can therefore be attributed to both cellular and viral factors, namely, introduction of viral DNA into cells that are resistant to transformation or integration of viral DNA in such a way that T antigen expression is prohibited.
In a 22-year period from 1962 to 1984, 51 patients with malignant lung disease had a sleeve resection performed. In 33% of the patients, pneumonectomy was contraindicated because of limited lung function. The operative mortality was 8%. Six per cent of the patients developed complications after the operation. The 5-year survival of the total group of patients was 30%. Patients with lesions classified as stage 1 and stage 2 had the best prognosis, with a 5- and 10-year survival of 43.5% and 27%, respectively. In patients classified as stage 3 and stage 4, the 5- and 10-year survival was 20%. A postoperative measurement of regional ventilation and perfusion indicated that the function of the remaining lung was presumably undisturbed by the operation. Also, the vital capacity and FEV 1 were only minimally reduced as a result of the operation. The amount of functional lung tissue spared by the operation compared to pneumonectomy was estimated to 39%. Because of these functional results and the promising 5-year survival figures, we suggest that sleeve lobectomy should be the operation of choice for tumors localized to the upper lobe orifice involving the main bronchus.
Non-traumatic spontaneous rupture of the urine bladder is a rare occurrence. The clinical features of three cases are reported. Although admitted as abdominal emergencies there was a considerable delay in operative treatment in two patients. The reasons are discussed.
In two patients with persisting pancreatic fistula not responding to conventional treatment, definitive closure of the fistula was achieved when somatostatin was added to the treatment.
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In an attempt to identify cellular genes that might be involved in simian virus 40 (SV40) transformation, we have set out to isolate cells which express T antigen but are not transformed. SV40 DNA and the herpes simplex virus thymidine kinase gene were cotransfected into tk- 3T3 fibroblasts. Of 72 colonies screened that were resistant to hypoxanthine-aminopterin-thymidine, 57 were T antigen positive as judged by immunofluorescence. One of these lines, A27, had a normal growth phenotype in monolayer overgrowth and soft agar assays. It contained intact SV40 sequences that could be rescued by fusion to permissive cells. This rescued virus was fully capable of transforming nonpermissive cells to the same extent as did wild-type virus. The A27 cells, however, were not transformable by infection with SV40 or by transfection of SV40 DNA. It is likely that these cells were altered in a cellular function required for the establishment of the transformed state.
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The roles of the large T and small t antigens of simian virus 40 in cellular DNA synthesis and cell division were analyzed in BALB/c 3T3 mouse cells transformed by wild-type, temperature-sensitive A (tsA), or tsA-deletion (tsA/dl) double mutants. Assessment of DNA replication and cell cycle distribution by radioautography of [3H]thymidine-labeled nuclei and by flow microfluorimetry indicate that tsA transformants do not synthesize DNA or divide at the restrictive temperature to the same extent as they do at the permissive temperature or as wild-type transformants do at the restrictive temperature. This confirms earlier studies suggesting that large T induces DNA synthesis and mitosis in transformed cells. Inhibition of replication in tsA transformants at the restrictive temperature, however, is not complete. Some residual cell division does occur but is in large part offset by cell detachment and death. This failure to revert completely to the parental 3T3 phenotype, as indicated by residual cell cycling at the restrictive temperature, was also observed in cells transformed by tsA/dl double mutants which, in addition to producing a ts large T, make no small t protein. Small t, therefore, does not appear to be responsible for the residual cell cycling and plays no demonstrable role in the induction of DNA synthesis or cell division in stably transformed BALB/c 3T3 cells. Comparison of cell cycling in tsA and tsA/dl transformants, normal 3T3 cells, and a transformation revertant suggests that the failure of tsA transformants to revert completely may be due to leakiness of the tsA mutation as well as to a permanent cellular alteration induced during viral transformation. Finally, analysis of cells transformed by tsA/dl double mutants indicates that small t is not required for full expression of growth properties characteristic of transformed cells.
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