Biomedical subjects
Publications and source records attributed to D W Ross.
Dyserythropoiesis, a qualitative abnormality of erythrocyte production, is described in a patient with hairy cell leukemia (leukemic reticuloendotheliosis). The development of a second population of circulating RBCs with a mean corpuscular volume of 154 cu mu suggests the emergence of an abnormal clone of marrow erythrocyte precursors.
Automated flow cytochemistry is a new technology which when applied to the problem of the white cell differential in leukemic patients extends the quantitative measure of both leukemic and nonleukemic cells over a greater range of concentrations. The Technicon Instruments Corporation, Hemalog-D automated white cell differential counter was employed in an investigation of leukemic patients with the following results: (a) There is an improvement in the diagnostic accuracy of subclassifying leukemias because of the use of cytochemistry. (b) Automated cytochemistry has increased sensitivity for the detection of both leukemic blasts and mature neutrophils in leukopenic patients, thus aiding in the distinction between early remission and persistent leukemia. (c) The increased precision of the differential demonostrates a linear correlation between the kinetics of different cell types not previously noted.
A dichotomy exists in the characterizations of the histogenesis of Hodgkin's disease. The Reed-Sternberg cell has been shown to possess functional properties both of lymphocytes and of mononuclear phagocytes. The majority of ultrastructural studies support the lymphocytic origin although a conflicting report describes some features of "histiocytic" cells [9]. In our study of four cases of Hodgkin's disease, the Reed-Sternberg cells contained a well-developed Golgi, moderate numbers of free polyribosomes and smooth and rough endoplasmic reticulum, variable numbers of lysosomes, lipid droplets, glycogen, fibrillar bodies, and irregular cytoplasmic processes. The number, size, and organization of cytoplasmic organelles are more consistent with a mononuclear phagocyte than a transformed lymphocyte and are similar to those seen in monoblastic leukemias. These findings support the concept of the derivation of the Reed-Sternberg cell from a monocyte-macrophage.
The use of electronic pulse spectroscopy to determine the volume distribution of a white blood cell fraction isolated by sedimentation from anticoagulated whole blood permits a rapid quantitative measure of size and dispersion of white blood cells in suspension. In patients without apparent hematologic diseases the white cell volume distribution presents as a broad peak. In patients with a large percentage of circulatory malignant cells, a single narrow volume peak is observed in acute leukemias and a broad and sometimes bimodal curve is observed in chronic leukemias. The volume of the leukemic cells is observed to shift in vivo after the start of effective chemotherapy as was predicted on the basis of a tissue culture model. The prognostic significance of the white cell volume distribution in leukemia and the use of a shift in size of leukemic cells after the start of therapy as a means of monitoring therapy are discussed.
An optical polarizing microscope with a good coefficient of extinction permits the visualization of the cytoplasmic fibrillar body in living preparations and smears of leukemic cells (human leukemias and the L 5222 experimental leukemia). These inclusions are not visible by phase contrast microscopy nor in fixed and stained smears. The detection in living cells of fibrillar bodies makes it possible to study directly the conditions for their formation and their reaction to the effect of certain drugs.
The effects of various chemotherapeutic agents on the volume of Chinese hamster V79 fibroblasts and murine lymphoma L5178Y cells were studied by electronic volume spectroscopy. Cells arrested in the division cycle by a chemotherapeutic block continued to grow in volume resulting in abnormally large cells unable to reduce their volume by cell division. This was observed in cells treated with colcemid, vinblastine, excess thymidine, hydroxyurea, ARA-C, 5-fluorouracil, actinomycin-D and bleomycin, but not with puromycin or cycloheximide. Increase in cell volume of blocked cells was correlated with a decrease in cell survival as measured by clonogenic ability. The results suggest the possibility of volume spectroscopy for a rapid in vitro test to determine tumor sensitivity to chemotherapeutic agents and the in vivo monitoring of response to chemotherapy. Mechanisms for increased cell kill by a second agent acting selectively on enlarged cells are considered.
A method is described whereby about 100 litres of plasma containing 10-50 IU/ml tetanus antitixin was obtained, from which were prepared 5000 X 250 IU doses of human antitetanus immunoglobulin. Of 40 blood donors who received a booster injection of tetanus vaccine BP, 33 were plasmapheresed each week over a 10-12 week period starting three weeks after the injection. Twenty-two of these donors provided 90% of the total plasma, the antitoxin content of which averaged 23.6 IU/ml over the 10-12 week period.
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The increase in cell volume (from electronic cell sizing) and the apportionment of this volume amongst the nuclear, cytoplasmic, and mitochondrial subcellular compartments (from electron microscopy) were studied throughout the cell division cycle in partially synchronized cultures of Chinese hamster V79-S171 cells. Average whole cell volume was found to increase smoothly, consistent with the doubling in one generation of individual cell volume. Nuclear size increased in like fashion. Mean total mitochondrial volume and number of mitochondria per cell both showed a different kind of variation, most notably a significant decrease in G(1) and G(2) as compared with mid S. These results are therefore counter to a model of simple doubling of mitochondria either synchronously with the cell division cycle or asynchronously. Absolute mean values per cell for log phase Chinese hamster cells were also determined, as follows: whole cell volume, 710 mu(3); nuclear volume, 190 mu(3); total mitochondrial volume, 37.5 mu(3); number of mitochondria per cell, 90.
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The increase of cell volume as a function of time was studied throughout the generation cycle in synchronous cultures of Chinese hamster cells using a Coulter aperture and a multichannel analyzer calibrated against known cell volumes. The experimental results were compared to a mathematical model of cell volume increase which considered the effect of the distribution of individual cell generation times on the progress of the population. Several modes of volume increase, including linear and exponential, were considered. The mean volume vs. time curve was rounded at the ends of the cycle even when linear growth was assumed. The experimental results show that cell volume increased in a smooth fashion as a function of time, with no discontinuities in rate detectable at periods when cells may have been undergoing metabolic shifts as, for example, through the phases associated with DNA synthesis, G(1), S, G(2). A statistical test on the comparison of the modal cell volume vs. time data to the predictions of linear and exponential growth models accepted both hypotheses within the resolution of these experiments. However, exponential growth was favored over linear growth in one cell line. Volume dispersion was almost constant with time in both sublines which is also consistent with exponential growth. Limitations of the electronic technique of volume measurement and indications for future experiments are discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.