Identification of the water radicals involved in x-ray inactivation of enzymes in solution and determination of their rate of interaction with the enzyme.
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Biomedical subjects
Publications and source records attributed to A Pihl.
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The presentation of understandable and stimulating lectures on difficult scientific and medical issues is in our opinion an art in decline. This disconcerting trend has, however, received little attention. In this essay, we expose the most common fallacies and pitfalls encountered in poor lectures, discuss the underlying reasons why they occur and consider some remedies to improve the situation. The status of oral communication should in our opinion be upgraded. To give a first rate, lucid lecture is an important service to the scientific community and should be recognised as such. When principal speakers at symposia are selected, and when researchers are considered for academic positions, documented proficiency in oral communication should be given more weight than is currently the case. This essay does not purport to be a treatise on rhetoric. We believe that a more efficient approach is to focus attention on the common blunders. This we have done in a provocative manner to invite comments and discussion.
The usefulness of nude rat xenograft systems in immunolocalization studies was investigated using the monoclonal antibody 9.2.27 which binds to melanomas and osteosarcomas. Three human tumors, two melanomas (LOX and FEMX-I) and one osteosarcoma (OHSX), were used. They were established as s.c. xenografts in congenitally athymic (rnu/rnu) nude rats. These serially transplantable tumors showed the same morphology, take rate and growth properties in nude rats as in nude mice. Radiolabeled 9.2.27 F(ab')2 fragments injected i.v. into nude rats were concentrated in s.c. LOX and OHSX xenografts, reaching tumor to blood ratios of up to 30 after 3-4 days. However, the injected antibody failed to concentrate in FEMX-I xenografts, in contrast to previous findings in mice. This discrepancy could be attributed neither to significant differences in in vivo distribution of the labeled antibody nor to the presence of blocking factors in the serum of nude rats. In immunoscintigraphic studies clear images of s.c. LOX tumors were obtained, whereas lung colonies were less well visualized. Biodistribution studies showed a low tumor to blood ratio of about 4 in the latter animals, suggesting a tumor site-dependent variation in homing of labeled antibodies. Radiography was found to be superior to immunoscintigraphy in detecting the lung tumors. The present findings demonstrate that results of immunolocalization studies in nude mice cannot readily be extrapolated to other species. For the purpose of preclinical evaluation of new methods in cancer diagnosis and treatment, tumor xenografts in nude rats may represent a valuable complement to nude mouse models.
Methodological aspects of testing chemosensitivity by the 6-day subrenal capsule (SRC) assay in immunocompetent mice were investigated. Human tumor xenografts, serially transplanted in athymic nude mice, were used as source of material. All drugs were given by the intravenous route. Administration of the drugs on days 1 and 2 gave the same results as when they were given daily for 5 days in equitoxic total doses, and a clear dose-response relationship was demonstrated. High reproducibility was found with different anti-cancer agents when 15 different tumors (4 melanomas, 7 soft tissue sarcomas, 2 colon carcinomas, and 2 lung carcinomas) were tested repeatedly over a period of several years. The tumors examined showed individual chemosensitivity profiles. The same ranking of drugs was found when the results in the SRC assay were compared with those obtained in the sc nude mouse model, using the same tumors (a colon carcinoma and a leiomyosarcoma), supporting the validity of the SRC assay. Altogether, the results strongly support the view that the 6-day SRC assay in immunocompetent mice is a useful method for assessing the response of human tumors to anticancer agents.