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Biomedical subjects

D R Fisher

Publications and source records attributed to D R Fisher.

At least 91 records · Page 5Linked to original sources

The microdosimetry of lymphocytes irradiated by alpha-particles.

Although the concept of absorbed dose is commonly used in radiation biology as a parameter for comparing the toxic effect of different levels of radiation on a system, there are situations where the absorbed dose by itself is inadequate, and additional dose distribution information is required to explain the observed biological effects. A good example is the irradiation of cells by alpha-particles. This paper reports the use of internal microdosimetry techniques to reinvestigate the dosimetry to two very similar experiments with apparently contradictory dose-response results. Yields of dicentric chromosome aberrations induced in human blood lymphocytes following in vitro exposure to dissolved americium or plutonium at two separate laboratories produced linear dose-response functions, but the slopes of the best-fit straight lines differed by a factor of 12. Our microdosimetric analysis showed the results of one experiment to be inconsistent with a uniform distribution of activity. It also showed that the difference in slope could be attributed to differences in particulate size and spatial distribution as a result of dissimilarities in procedures used for preparing the actinide solutions.

Alpha Particles↗

Computed tomographic mammography using a conventional body scanner.

The technique for computed tomographic (CT) examination of the breasts using a conventional body scanner is described, and experience with 67 patients is reported. In the diagnosis of both malignant and benign breast lesions, the results with a body scanner were equal to those of a dedicated CT/M mammographic unit. Although the CT study of the breast cannot replace conventional mammography in screening or in routine diagnostic workup, the unique capability of demonstrating both anatomic changes and increased iodide concentration in a cancer provides many advantages over conventional mammography. CT mammography appears to have the capability to detect breast cancers that are occult to other methods. Indications for a CT study of the breasts are: (1) clinically suspected breast cancer, especially with a mammographically occult lesion; (2) questionable mammographic findings, including microcalcifications, tumor shape, architectural distortion, and uncertain lesion location; and (3) evaluation of postbiopsy or postlumpectomy breast cancers when a primary irradiation therapy is contemplated. Breast CT also appears to be a valuable diagnostic tool in searching for a second primary breast cancer, follow-up study of postirradiation of breast cancer, followup study for postmastectomy patients, and screening procedure for genetically high-risk patients, especially those with dense breasts.

Adult↗

Ca-DTPA-induced fetal death and malformation in mice.

Increased fetal mortality and congenital malformation were induced in mice by Ca-DTPA, a chelate widely used for the removal of internally deposited plutonium in human beings. Mated C57BL/Do female mice were given five daily injections of 720-2,880 mumol/kg Ca-DTPA during early, mid, or late gestation. Damage probably occurred as a result of the depletion by Ca-DTPA of zinc and manganese, trace elements essential to growth and development. By extension, it seems likely that Ca-DTPA could damage human fetuses. A much safer chelate, Zn-DTPA, is recommended for the treatment of accidental plutonium contamination.

Abnormalities, Drug-Induced↗

Letter: Immunoblasts.

Explore the source record for details and available documents.

Antibody-Producing Cells↗

Leukemic mitochondria. III. Acute lymphoblastic leukemia.

Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic lymphoblasts in 6 patients with acute lymphoblastic leukemia. Similar studies were performed on lymphoblasts from lymph nodes obtained from 10 surgical patients without nodal diseases. Significant quantitative differences between normal and leukemic mitochondria were not observed except for a difference in mitochondrial area per cell (P less than 0.05). This was not significant lacking, qualitative diffecrences were observed. These abnormalities included rare giant mitochondria, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and nucleus during interphase. Fifty-three percent of the leukemic lymphoblasts contained polyribosomes, as compared to 25% of the normal lymphoblasts. The cells with the polyribosomes contained the giant mitochondria. The leukemic lymphoblasts had an appearance similar to transformed lymphocytes resulting from an immunologic stimulus. This suggests that acute lymphoblastic leukemia may be a disease which is associated with an immunologic response. From the available ultrastructural and biochemical data, it would seem that the leukemic lymphoblast is a product of an abnormal metabolism which affects its ability to differentiate. These ultrastructural findings seem to indicate the need for biochemical investigation of leukemic mitochondria. (Am J Pathol 78:49-58, 1975

Adolescent↗

Leukemic mitochondria. I. Acute myeloblastic leukemia.

Quantitative and qualitative electron microscopic studies were performed on the mitochondria of leukemic myeloblasts in 3 patients with myeloblastic leukemia and in 3 patients with myelomonoblastic leukemia. In addition, to confirm the presence of virus-like particles within mitochondria and better understand the interaction between the virus and mitochondrion, a rat embryo tissue culture infected with MSV-MLV (Moloney sarcoma virus-Moloney leukemia virus) was selected for detailed electron microscopic examination. Significant quantitative differences between normal and leukemic human mitochondria were not observed. However, qualitative abnormalities were found in the human leukemic mitochondria and in the tissue culture material. These abnormalities included variable forms of the leukemic mitochondria (twisted, tear-drop and irregular shapes), fewer cristae, disrupted mitochondria with virus-like particles, smaller granules in greater abundance, mitochondrial DNA, and contact between the mitochondrion and the nucleus. The tissue culture material revealed similar changes, but showed more virus particles which were located outside the cells, in intracytoplasmic sacs and within the mitochondria. In addition two striking features were observed in the tissue culture material not seen in the human material: a) Budding from the outer mitochondrial membrane into the mitochondrial matrix and b) virus particles attached to the cristae. Since mitochondria are important organelles in the glycolytic-oxidative phosphorylation pathways, perhaps all of us engaged in cancer research should take a closer look at the Warburg effect and carefully consider extranuclear factors operating in oncogenesis.

Adolescent↗

Acute leukemic cells. Qualitative and quantitative electron microscopy.

Quantitative and qualitative electron microscopic studies were performed on the leukemic cells of 3 patients with stem cell leukemia, 6 patients with acute lymphoblastic leukemia, 7 patients with acute monoblastic leukemia, 3 patients with acute myeloblastic leukemia and 7 patients with acute monomyeloblastic leukemia. Significant quantitative differences were noted between some of the leukemic cells in heterochromatin:euchromatin ratios, cell size, granules per cell, amount of endoplasmic reticulum and the number of polyribosomes. Qualitative abnormalities which were found in some cells of all the leukemic groups were observed. These abnormalities included nuclear pockets, deep nuclear indentations (usually not the stem cell), nucleosomes, dilated perinuclear spaces, centrioles located in nuclear pockets (not in the stem cell or lymphoblast), accumulation of microfibrils (greatest in the monoblast and myeloblast), disrupted mitochondria with virus-like particles (none in stem cells), smaller granules and mitochondrial DNA, glycogen, and myelin whorls. The presence of the smaller granules in disrupted mitochondria and the resulting clear areas is probably related to the deranged carbohydrate metabolism of these cells. The presence of virus-like particles within mitochondria may be extremely important, but requires much more investigation. Some of the above findings may offer clues to further investigation of the acute leukemic cell.

Acute Disease↗