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Biomedical subjects

H Thornton

Publications and source records attributed to H Thornton.

At least 19 recordsLinked to original sources

Clinical trials--a brave new partnership?

The need for informed consent is considered from the patient's viewpoint by an examination of the shortcomings of the UK Ductal Carcinoma In Situ (DCIS) trial and its failure satisfactorily to accrue both profession and patient. The impersonal, negative aspects of the informed consent process in the research situation are contrasted with the positive benefits of confidence fostered by the traditional doctor/patient relationship. The need for new research with a partnership between patient and profession, the necessity for rigorous re-assessment of treatments and care both within and outside of trials to avoid waste by the perpetration of unnecessary treatments together with the need for evaluation of the efficacy of treatments employed outside of trials, especially in 'new' conditions, to foster progress and maintain public confidence in the profession, is advocated.

Breast Neoplasms

A sacrifice for others? Ethical dilemmas surrounding the UK randomised trial for the management of screen-detected ductal carcinoma in situ of the breast.

Asymptomatic ductal carcinoma in situ (DCIS) is a noninvasive breast lesion for which an effective treatment has yet to be ascertained. Women diagnosed with DCIS are therefore given the choice of either participating in a trial or choosing their own treatment. This raises a series of ethical dilemmas for both the patient and community health team.

Breast Neoplasms

Follow-up of postsecondary-age rural learning disabled graduates and dropouts.

This article reports the dropout rates, basic skills competency levels, and employment status of a group of semi-rural learning disabled postsecondary-age youth and a control group of nonlearning disabled same-age peers. Findings indicated significantly higher dropout rates and significantly lower basic skills competency levels among learning disabled youth. Learning disabled graduates and dropouts were not different in how they fared in the employment market for the group, nor were they different compared to peers. Educational implications of these findings and future suggestions for follow-up research are discussed.

Achievement

Oncogenes in laryngeal cancer: serial passage of transformed cellular DNA.

DNA originally extracted from squamous cell cancer of the larynx has been serially passaged through transformed populations of NIH/3T3 mouse fibroblasts. The transformed foci were then harvested, cloned to volume, and incubated with a fresh population of NIH/3T3 cells in a second passage. Transforming efficiencies were enhanced by serial passage. In addition, Southern Blot analysis of the transformed foci revealed hybridization between transformant DNA and human probe DNA from the Alu family of conserved human DNA sequences. In the first passage this hybridization took the form of diffuse homology throughout the entire molecular weight distribution. The second-passage DNA showed "narrow bands" indicating the possibility that an oncogene has been identified in laryngeal cancer and that serial passage has eliminated contaminating human sequences. Repetitive transfection in third- and fourth-passage studies is now being completed.

Animals

Oncogenes: their presence and significance in squamous cell cancer of the head and neck.

DNA extracted from squamous cell carcinomas of the larynx and tongue has been shown to contain cellular transforming genes characterized by their ability to transform mouse fibroblasts into malignant foci of cells which, when subsequently cloned and grown to volume, have been found to contain human DNA sequences. This DNA has been serially passaged through subsequent populations of NIH/3T3 mouse fibroblasts. Higher malignant transformation efficiencies have been observed and reported with serial passage. Of greater significance is the repeated identification of oncogenes of identical characteristics on electrophoretic radioisotope analysis.

Carcinoma, Squamous Cell

Identification of adenovirus 12-encoded E1A tumor antigens synthesized in infected and transformed mammalian cells and in Escherichia coli.

A 16-amino acid peptide, H2N-Arg-Glu-Gln-Thr-Val-Pro-Val-Asp-Leu-Ser-Val-Lys-Arg-Pro-Arg-Cys-COOH (peptide 204), targeted to the common C-terminus of human adenovirus 12 (Ad12) tumor antigens encoded by the E1A 13S mRNA and 12S mRNA, has been synthesized. Antibody prepared in rabbits against peptide 204 immunoprecipitated two proteins of apparent Mr 47,000 and 45,000 from extracts of [35S]methionine-labeled Ad12-early infected KB cells and a 47,000 protein from extracts of the Ad12-transformed hamster cell line, HE C19. Immunoprecipitation analysis of infected and transformed cells labeled with 32Pi showed that both major Ad12 E1A T antigens are phosphoproteins. Immunofluorescence microscopy of Ad12-early infected KB cells with antipeptide antibody showed the site of E1A protein concentration to be predominantly nuclear. E1A proteins were detected by immunofluorescence at 4 to 6 h postinfection and continued to increase until at least 18 h postinfection. Antipeptide 204 antibody was used to analyze the proteins synthesized in Escherichia coli cells transformed by plasmids containing cDNA copies of the Ad12 E1A 13S mRNA or 12S mRNA under the control of the tac promoter (D. Kimelman, L. A. Lucher, M. Green, K. H. Brackmann, J. S. Symington, and M. Ptashne, Proc. Natl. Acad. Sci. U.S.A., in press). A major protein of ca. 47,000 was immunoprecipitated from extracts of each transformed E. coli cell clone. Two-dimensional gel electrophoretic analysis of immunoprecipitates revealed that the T antigens synthesized in infected KB cells, transformed hamster cells, and transformed E. coli cells possess very similar molecular weights and acidic isoelectric points of 5.2 to 5.4.

Adenoviruses, Human

Survival after extended resection for locally advanced carcinomas of the colon and rectum.

Two hundred and fifty five patients were treated surgically for adenocarcinoma of the colon or rectum on the Surgical Unit at Westminster Hospital in the years 1962-78. After 13 patients had been excluded on the grounds of inadequate data, 57 of the remaining 242 had tumours which, at laparotomy, were firmly adherent to neighbouring organs or the abdominal wall. These 'locally advanced' tumours were treated by an extended en-bloc resection of the tumour and neighbouring organs. The operative mortality after extended resections was higher than after standard resections, but subsequent survival did not differ significantly from survival after standard excisions for tumours of the same Dukes' stage. Histological examination of the neighbouring organs included in the extended resections confirmed direct tumour spread in only 33%.

Adenocarcinoma

Oncogenes: preliminary studies in head and neck cancer.

DNA has been extracted from squamous cell carcinomas of the larynx, base of tongue, and nasopharynx. These tumors were excised from patients at the St. Louis University Medical Center and processed at the Institute for Molecular Virology of the St. Louis University Medical Center. NIH/3T3 cells were transfected with the DNAs from these cancers. Malignant, transformed foci of NIH/3T3 cells have been observed. These foci have been cloned and grown in quantity. The cloned foci have been injected into nude mice with the production of highly malignant sarcomas. DNA extracted from these sarcomas has shown homology with human DNA on hybridization analyses of both nasopharynx and tongue cancer. Further hybridization studies are being conducted on the larynx cancer-induced sarcomas and on the DNAs taken from the original transformed foci of NIH/3T3 cells transfected with squamous cell cancers of the larynx, nasopharynx, and tongue base. Our preliminary results indicating the presence of human sequences in the mouse sarcomas support the hypothesis that human cellular transforming gene(s) may be present in the DNA isolated from the head and neck cancers. Additional studies will include repetitive retransfection of NIH/3T3 cells, molecular cloning of putative oncogenes, and DNA sequence analysis of the cloned oncogenes. It is hoped that identification of putative oncogene sequences will result in the identification of the proteins coded for by the specific nucleotide sequences responsible for malignant cellular transformation by DNA extracted from head and neck tumors.

Animals

Results and prognostic factors in salvage surgery for squamous carcinomas of the tongue.

Fifty-six patients who had undergone salvage surgery for residual or recurrent squamous carcinomas of the tongue between 1967 and 1977 were reviewed. Failure to obtain operative clearance led to certain local recurrence. The tongue or cervical lymph nodes were involved in 27 of the 28 patients who died with recurrent tumour. The overall age-corrected actuarial postoperative survival was 45.1 per cent at 2 years and 35.3 per cent at 5 years. Survival was reduced in women and patients aged over 60 years at operation, and in patients whose tumors were at first biopsy moderately or poorly differentiated, classified as stage III or IV at initial presentation or preoperatively, or recurred within 6 months of completing primary treatment.

Actuarial Analysis