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Biomedical subjects

D E Harrison

Publications and source records attributed to D E Harrison.

At least 145 records · Page 8Linked to original sources
PubMed1976

Population of lymphoid tissues in cured W-anemic mice by donor cells.

The percentages of donor cells in lymphoid organs of cured W-anemic mice were determined by using donors with the T6 chromosome marker. W-anemic recipients of two different genotypes were cured by marrow or spleen grafts from histocompatible normal T6/T6 or T6/+ donors. After 2 to 10 months, almost all proliferating cells in the thymuses and marrows, and approximately 75% in the spleens of cured mice were of donor type. However, only 30-40% of the proliferating cells in recipient lymph nodes and 10-20% in their Peyer's patches were of donor type. Percentages of donor cells in marrows and spleens remained high hemopoietic cell division was stopped by injections of erythrocytes. All tissues were slightly less repopulated by donor cells in W-anemic recipients cured by spleen cells compared with those cured by marrow cells. These results were not altered by matching recipients and donors to avoid possible graft versus host reactions, or by removing the thymus of a recipient before it was cured. The fact that the repopulating cells are not all donor type suggests that there are at least two classes of precursor cells that populate the immune system of W-anemic mice, and that not all classes are derived from the grafted cells. Cured W-anemic mice may provide a unique system in which different types of precursor cells of the lymphoid system can be distinguished.

Anemia, Macrocytic↗
PubMed1976

Avoidance of graft versus host reactions in cured W-anemic mice.

Graft-versus-host reactions of parental cells in F1 hybrids were studied with two unrelated inbred strains of mice that differed at the mouse histocompatibility locus. W-anemic F1 recipients were compared with lethally irradiated normal F1 recipients. Both sets of recipients were populated by marrow and spleen cell grafts from parental and F1 donors. Most W-anemic F1 recipients were cured by parental and F1 cell grafts (except B6 spleen). Even after 13 to 18 months, they showed little or no effect from GVH reactions. Lethally irradiated normal F1 recipients tolerated parental marrow grafts almost as well, but gave dramatically different results with parental spleen grafts. Seventy-nine of 80 irradiated F1 recipients of parental spleen grafts died within 1 month. Unlike lethally irradiated recipients, W-anemic recipients have substantial numbers of their own cells along with the donor cells in their lymphoid tissues. These F1 lymphocytes may interact with parental lymphocytes in vivo to restrain reactions against F1 allogeneic antigens.

Anemia, Macrocytic↗
PubMed1975

Normal function of transplanted marrow cell lines from aged mice.

Transplantation experiments indicated that losses with age in erythrocyte production were not intrinsically timed within marrow cell lines. In most cases marrow cell lines from old donors functioned as well as those from young donors after transplantation into either W/W-v anemic or lethally irradiated normal recipients. After normal marrow cells had been serially transplanted into successive W/W-v mice 5 times, both old and young cell lines began to fail; the old cell lines had produced erythrocytes normally for 77 to 84 mo. Transplanted old and young control marrow cell lines, identified by T6 chromosomes, saved the lives of lethally irradiated recipients; the oldest cell lines functioned normally for 54 mo. The hypothesis is suggested that senescence of an organism is caused by intrinsically timed functional declines in only a few vital cell types. In transplantation experiments to identify these cell types, four criteria--function, identification, control, and health--should be met. The marrow transplantation experiments led to and illustrate the hypothesis and the four criteria.

Aging↗
PubMed1975

Defective erythropoietic responses of aged mice not improved by young marrow.

Defective responses to severe bleeding in 25-mo.-old C57BL/6J mice were not improved by injections of 8-mo.-old marrow cells. Such injections greatly improved responses of genetically anemic W/W-v mice that have defective erythropoietic stem cells. Apparently the defective responses of old mice were not intrinsic to their erythropoietic stem cells.

Aging↗
PubMed1975

Molar growth yields, respiration and cytochrome patterns of Beneckea natriegens when grown at different medium dissolved-oxygen tensions.

The effect of medium dissolved-oxygen tension on the molar growth yield, respiration and cytochrome content of Beneckea natriegens in chemostat culture (D 0-37 H-1) was examined. The molar growth yield (Y), the specific rate of oxygen (qo2) and glucose consumption, and the specific rate of carbon dioxide evolution were independent of the dissolved-oxygen tension above a critical value (greatest than 2 mmHg). However, the potential respiration rate increased with reduction in the dissolved-oxygen tension at values of the dissolved-oxygen tension well above the critical value. Changes in the cytochrome content occurred at dissolved-oxygen tensions well above the critical value. An increase in cytochrome c relative to cytochrome b was observed as the dissolved-oxygen tension was decreased. Reduction of the dissolved-oxygen tension to less than I mmHg caused a switch to fermentative metabolism shown by the apparent rise in YO2 and decrease in the molar growth yield from glucose. At this point the potential respiration rate (qO2) increased to its highest value, while the cytochrome pattern reverted to that observed at dissolved-oxygen tensions above 96 mmHg. There appeared to be no correlation between cytochrome content, potential qO2, in situ qO2, and cyanide sensitivity of the organism at various dissolved-oxygen tensions.

Cyanides↗
PubMed1975

Normal function of immunologic stem cells from aged mice.

Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases: 1) Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. 2) If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37% of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinisically timed in the precursor cell lines that populate the immune system.

Age Factors↗
PubMed1973

Normal production of erythrocytes by mouse marrow continuous for 73 months.

Marrow cell transplants from old and young control donors were carried in genetically anemic W/W(v) recipients whose anemias were cured by successful transplants. After maximum of 36 months and four serial transplants, marrow cell lines from both old and younger control donors continued to produce erythrocytes normally. The oldest marrow cell lines had produced erythrocytes normally for 73 months. NORMAL ERYTHROCYTE PRODUCTION WAS DEMONSTRATED BY: (1) cure of the anemia in W/W(v) recipients, (2) normal rather than delayed recovery rate of cured recipients after severe bleeding, and (3) normal rather than ineffective response of cured recipients to erythropoietin. Hemoglobin patterns, tested in cured W/W(v) recipients after the first transplantation, showed that at least 90% of the circulating erythrocytes were of the donor type even in donor lines that had produced erythrocytes continuously for 45 months and were recovering from severe bleeding. Concentrations of cells capable of forming macroscopic spleen colonies were more than two orders of magnitude higher in W/W(v) mice cured by old or younger marrow than in uncured W/W(v) mice. Nevertheless, colony-forming unit concentrations declined slowly with successive transplants, and the decline seemed more pronounced at the fourth transplant in old than in younger cell lines.The hypothesis is suggested that senescence is caused by declines in function of only a few vital cell types. The system for comparing old and younger marrow cell lines offers a model for experiments to test this hypothesis and to identify the cell types whose decline causes aging.

Anemia↗