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Biomedical subjects

S E Shackney

Publications and source records attributed to S E Shackney.

At least 73 records · Page 4Linked to original sources

Rapid grain and cell counting for cell kinetic studies.

A commercially available bacterial colony counter has been adapted for the counting of radioautographic grains over individual cells in smears and for the counting of cells in histologic sections. For radioautographic grains, the correlation coefficients between counts obtained visually by 2 observers and between counts obtained visually and with the use of the instrument were similar (r=0.999 and r=0.998, respectively). The instrument counts were obtained more rapidly than the visual counts and were associated with less observer fatigue. Even though the performance of the instrument in counting cells in mouse bone marrow sections was less accurate than that in counting radioautographic grains, a good estimation of marrow cell number was obtained (r=0.968). Data on bone marrow cellularity were obtained far more rapidly than those with semiquantitative methods.

Autoradiography↗

Lethal and sublethal effects of hydroxyurea in relation to drug concentration and duration of drug exposure in sarcoma 180 in vitro.

The lethal and sublethal effects of hydroxyurea were studied in Sarcoma 180 in vitro in relation to drug concentration and drug exposure duration using cloning methods, radioautography, and flow microfluorometry. It was shown that postperturbation changes in radioautographic labeling intensity reflected real changes in the rate of DNA synthesis in individual cells. The data suggest that both the lethal and sublethal effects of hydroxyurea are dependent on the rate of DNA synthesis. These findings have important implications for the interpretation of DNA content distributions under perturbation conditions and for the development of drug treatment regimens that are based on cell kinetics.

Animals↗

The effects of colcemid on mouse bone marrow.

Following Colcemid administration, mitoses accumulate preferentially in the subendosteal region of the bone marrow of the mouse. This finding suggests that the most rapidly proliferating cells are localized to the subendosteal region, and complements previous radioautographic studies which have demonstrated a corresponding labelling gradient in the marrow. Quantitative estimates of cell cycle time by the stathmokinetic method were precluded by the presence of significant Colcemid induced interphase cell loss. Colcemid also affected cell differentiation in the marrow. Following Colcemid administration there was a fall in mature granulocytes in the marrow, and a concommitant rise in marrow megakaryocytes.

Animals↗

The effects of colcemid on hematopoiesis in the mouse.

Colcemid was found to induce a dose and schedule dependent marrow magakaryocytosis and peripheral thrombocytosis. The response could be divided into early and late components. The early component appears to have been due to a direct stimulatory effect, probably by enhancement of endoreduplication in metaphase arrested megakaryocyte precursors. The ealy stimulatory response was blunted on toxic drug schedules. In contrast, the late component of the thrombopoietic response was demonstrated best on the most toxic drug schedules. It coincided temporally with the reactive restoration of the mononuclear marrow and blood cell elements, respectively. Thus, the late component appears to be a nonspecific rebound phenomenon. On comparing the thrombopoietic properties of Colcemid with those of the vinca alkaloids in experimental systems, the former appears to have a more favorable therapeutic index. The data suggest that colchicine and its derivatives may be useful agents in the treatment of clinical thrombocytopenic states.

Animals↗

Role of radioautographic studies in clinical investigative oncology and chemotherapy.

Three clinical areas are identified in which radioautographic studies may be of practical usefulness. First, human tumors can be classified according to the predominant pattern of DNA synthesis in the slowly proliferating cell fraction. This classification scheme groups carcinoma of the breast and ovary together, melanoma and carcinoma of the lung together, and places acute adult leukemia in a separate class. If there are correlations between kinetic characteristics and drug response behavior, this classification scheme may simplify the clinical study of new drugs and drug combinations. Second, changes in the labeling index (LI) and/or cell labeling intensity may serve as useful guides in drug scheduling. There are circumstances where changes in cell labeling intensity may be more reliable than changes in the LI. Third, cell morphology, population kinetics, and clinical course may all be correlated in certain human tumors, particularly the lymphomas. Supporting evidence in Sézary's syndrome is presented.

Acute Disease↗

The radioautographic transfer function and its implications for radioautographic methodology.

A function was developed to relate the radioautographic detectability of tritiated thymidine to its incorporation into nuclear DNA under various experimental and specimen processing conditions. The implications of this function for the interpretation of cell kinetic studies were outlined, and its implications for radioautographic methodology were discussed. The standardization of radioautographic methods for facilitation of comparisons of data obtained from different sources under dissimilar experimental conditions was discussed.

Autoradiography↗

Kinetic-microarchitectural correlations in the bone marrow of the mouse.

Transverse histologic sections of bone marrow obtained from mice that were sacrificed by perfusion fixation at intervals following tritiated thymidine injection were studied by means of radioautography. A kinetic gradient was demonstrated across the marrow section, with the highest proliferative rate in the subendosteal region. Megakaryocytes were shown to originate from the rapidly proliferating subendosteal cells. The immediate proliferating precursors of mature granulocytes were slowly proliferating cells found predominantly in the central region of the marrow. It was concluded that in the steady state there must be a migration of cells from the subendosteal region to the central region with concomitant growth retardation of the migrating cells.

Animals↗

Multicompartment analysis of cell proliferation and cell migration in the Sezary syndrome.

Serial radioautographic data obtained in two patients with Sezary syndrome following intravenous tritiated thymidine administration were analysed using multicompartment kinetic models. In both patients, the grain count halving time in the cutaneous Sezary cell compartment was too long to account for the grain count halving rate observed in the peripheral blood. This implies that some proliferating cell compartment other than the skin is primarily responsible for producing the Sezary cells that circulate in the peripheral blood. In both patients, the cell compartment that served as the source of circulating Sezary cells consisted of 5-6 X 10(11) cells (500-600 g of tumor) with an average cell cycle time of 3-4 days. By comparison, the cutaneous Sezary cell compartment was estimated to contain 2.2-4.6 X 10(12) cells (2.2-4.6 kg of tumour) with an average cell cycle time of 7-70 days. While this study does not permit direct anatomic localization of the primary site of Sezary cell production, the properties of this compartment that can be deduced from the available data suggest the lymph nodes as likely candidates. Thus, the Sezary syndrome may well be a true lymph node malignancy with prominent cutaneous manifestations.

Autoradiography↗