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Biomedical subjects

G Harris

Publications and source records attributed to G Harris.

At least 163 records · Page 9Linked to original sources

Reaction time and mild mental retardation: high speed scanning reexamined.

When observers judge whether a probe is contained within a small positive set, reaction time (RT) increases linearly with set size (Sternberg, 1969b). Slope and intercept of the function relating RT to positive set size are believed to reflect durations of different processing stages. As results of several investigations suggested inverse slope/intercept relationships, however, studies using "high-speed scanning" tasks to compare retarded with nonretarded individuals were reexamined. When slope was correlated with points along the RT function (intercept, Positive Set Sizes 1, 2, and 4), results showed no interdependencies for nonretarded adults. Slope and intercept were negatively correlated for retarded and nonretarded adolescents, whereas slope and Positive Set Size 1 values apparently were unrelated. These results seem to contradict theoretical expectations, and specification of processing stages where efficiency varies across populations may not be possible based on results from high speed scanning tasks.

Adolescent↗

Human tumor cloning: feasibility and clinical correlations.

The human tumor cloning system is a soft agar technique which allows the growth of human tumors in vitro. We report here our experience with culturing 2,365 patients' tumors in the system. Overall 1,844 (78%) have formed colonies in vitro. However, only 51% have formed greater than or equal to 30 colonies per 500,000 cells plated. Despite the limitations of inadequate growth for some tumors there are a number of clinical applications for the system, which are reported here. These include: (1) Use of the system to predict for sensitivity of an individual patient's tumor to a particular chemotherapeutic agent; (2) screening new anticancer agents to predict for in vivo activity; 3) monitoring patients' bone marrows for tumor involvement; and (4) use of the number of colonies which form in the assay as a prognostic factor for survival. All of these clinical applications are in their infancy of development and will require carefully designed prospective trials to determine the final place of the human tumor cloning system in the practice of clinical oncology.

Agar↗

The response of rabbit spleen explants to ionizing radiation.

Explants of rabbit spleen, responding to sheep erythrocytes in vitro, were exposed to ionizing radiation at different times in culture. Radiation was found to depress the development of specific haemolysin-producing cells (PFC) at subsequent times, while cells already engaged in haemolysin production were relatively resistant to radiation. The depressing effects of radiation on PFC was most marked at times when the rate of increase of PFC was highest. Recovery from low doses (less than 2 Gy) occurred while higher doses of radiation had persistent depressing effects on the level of PFC. Assessment of synthesis of other macromolecules in these irradiated cultures showed that protein synthesis was highly resistant and DNA synthesis was sensitive like the immune response. Irradiation in hypoxic conditions showed that this protected the tissues from damage by radiation and there were also indications of enhancement of repair of this damage. Finally it was found that the results obtained with these cultures correlated well with previous studies of intact mice.

Animals↗

Mode of action of methylating carcinogens: comparative studies of murine and human cells.

Murine and human cells (mainly lymphocytes) were ethylated in vitro with either N-[14C]methyl-N-nitrosourea (MNU) or di[14C]methyl sulphate (DMS) and the extents of methylation of DNA at O-6 and N-7 of guanine and N-3 of adenine were determined. The cytotoxic action of MNU was also compared with that of DMS, as assessed by their effects on cell division following stimulation of these lymphocytes in culture by concanavalin A (Con A). The overall extent of methylation of the DNA of human cells was about 70% of that of murine cells after exposure to MNU and DMS. Mouse cells, responding to Con A in culture, were found to be much more sensitive to both agents than could be accounted for by these differences in overall extent of methylation of the DNA. Significant differences were found between cells in their ability to rapidly remove O6-methylguanine from DNA. Normal human lymphocytes were always proficient, but some human lymphoid lines were deficient in this respect, while all the murine cells tested were deficient, as found in vivo for mouse lymphoid tissues. No correlation has yet been found between the susceptibility of various mouse strains to the carcinogenic action of MNU and their ability to remove methylated bases from DNA. The cytotoxicity studies, showing that normal human lymphocytes were relatively more resistant than murine cells to methylation by both MNU and DMS, suggested that the ability to remove O6-methylguanine (which is produced in a very low proportion by DMS) was not of prime importance in conferring resistance in this type of assay.

Animals↗

The acute effects of ionizing radiation on DNA synthesis and the development of antibody-producing cells.

Ionizing radiation inhibited the development of specific haemolysin-producing cells (PFC) and depressed the incorporation of (3H) thymidine by rabbit spleen explants responding to SRC in the culture medium. In contrast to these effects, the rates of incorporation of precursors for protein and RNA synthesis were much less affected. The depression of (3H) thymidine incorporation was found to result from a quantitative reduction of new DNA synthesis, without any change in the proportion of labelled cells, at any time after irradiation. The DNA synthesis occurring in these cells preparing to develop antibody-producing capacity was thus radio-sensitive, but the exact nature of the defect resulting from exposure to radiation requires further study.

Animals↗

The effect of ethidium bromide on the response of spleen explants of primed rabbits to sheep red cells (SRC).

Ethidium bromide (EB) selectively inhibited the response of cultured spleen explants from primed rabbits to SRC. This was particularly so with exposure to relatively high concentrations of the drug for short periods at any time in culture. It was concluded that the likeliest target for the action of EB was the DNA of the cell. The exact nature of this target has not yet been elucidated, but the selectivity and persistence of the inhibition of the development of PFC, as well as lack of morphological evidence of mitochondrial damage suggested DNA of nuclear origin. The prevention, by EB, of increases in the labelling index of cells migrating from explants pre-labelled with [3H]-thymidine, further suggested that, as a result of intercalation with the drug, transfer of DNA, of an episomal nature, was being prevented and that this intercellular exchange was important for the immune response.

Animals↗