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L L Sensenbrenner

Publications and source records attributed to L L Sensenbrenner.

At least 73 records · Page 4Linked to original sources

Engraftment of bone marrow transplants in W anemic mice measured by electronic determination of the red blood cell size profile.

Defective stem cells of WBB6F1-W/Wv mice produce macrocytic red blood cells (RBCs); stem cells of WBB6F1-+/+ mice produce normocytic RBCs. Utilization of the Coulter counter channelyzer permitted good dissociation between the size distribution of populations of +/+ and W/Wv RBCs. Peaks (mean cell volumes) for +/+ and W/Wv RBCs have been determined to be between the 30th and 40th channel and 50th and 60th channel, respectively. Variability of profiles for individual mice of both genotypes did not exceed the variability of separate determinations of the same cell suspension from a single mouse. Admixture (approximately 15%) of either type of erythrocytes could be quantitatively detected by this method. One week after transplant of 10(7) +/+ marrow cells into W/Wv recipients, 25% of donor type erythrocytes were detected. Eighteen days post-graft, concentration of +/- normocytes exceeded the concentration of macrocytes in the W/Wv recipients' circulation. Approximately 45 days post-transplant, the proportion of macrocytes decreased below the 10% detectable level. Calculation of the daily RBC production rate during repopulation and estimation of the number of RBCs produced by a single hematopoietic colony were determined. The RBC size profile was found to be a convenient method for studying the effect of implantation of W/Wv marrow into lethally irradiated +/+ mice. This method proved suitable for repetitive determination of the size population in individual transplanted mice.

Anemia↗

Adverse effects of nutritional deprivation on transplanted hematopoietic cells.

We studied the effect of food deprivation on hematopoietic reconstitution of B6D2F1 mice given 900 rad total body irradiation followed by 2 x 10(5) syngeneic bone marrow cells. Animals deprived of food from the day of cell transfer to the day of sacrifice were compared to control animals allowed ad libitum laboratory chow. The body weight of food deprived mice decreased by 36% on day 7 as compared to a 9% decrease in fed controls. The mean number of nucleated cells/femur on day 7 was only 22% of that found in fed controls. The spleen weight in the experimental animals was only 48% of that in the controls. Food deprived animals showed complete suppression of macroscopic hematopoietic spleen colony formation. Both marrow and spleen from the primary recipients, when studied for content of CFU-s in secondary ad libitum fed recipients, showed that food deprived animals had less than 25% of the number seen in controls. A third group of animals receiving vitamin supplements and small amounts of dextrose, but no protein, showed hematopoietic suppression similar to that seen in the totally food deprived mice.

Animals↗

Induction of partial chimerism in nonirradiated B-lymphocyte-deficient CBA/N mice.

Nonirradiated B-lymphocyte-deficient CBA/N mice given T6T6 chromosome-marked normal CBA/CaHN spleen cells became lymphoid chimeras exhibiting donor-type mitoses. Normal CBA/CaHN recipients did not exhibit significant numbers of donor-type mitoses. The lymphoid cell chimerism in the CBA/N host appeared in spleen, lymph nodes, and Peyer's patches, but not in marrow or thymus. Stimulation of CBA/N-recipient spleen cells in vitro suggested that the chimerism involved donor T6T6 cells which were responsive to the B-lymphocyte mitogen, lipopolysaccharide, but not to the T-lymphocyte mitogen, phytohemagglutinin. These data indicate that stable, long-term chimerism of a specific class of lymphocytes is possible in nonirradiated, B-lymphocyte-deficient CBA/N mice.

Animals↗

Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells.

A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality [45, X, -X, t(8;21) (q22; q22)] was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.

Adult↗

Recovery of hematologic competence without engraftment following attempted bone marrow transplantation for aplastic anemia: Report of a case with diffusion chamber studies.

An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusion. Although subsequent karyotyping showed that engraftment was not achieved, prompt hematologic recovery ensued by the third week post-transplant. Diffusion chamber culture of the patient's bone marrow stroma, obtained prior to cyclophosphamide therapy, was carried out. A prompt increase in the number of cells in the chambers was observed. A differential cell count of the contents was similar to that seen when normal bone marrow is cultured in a similar manner.

Adolescent↗

Growth and differentiation of normal and leukemic human bone marrow cells cultured in diffusion chambers.

Bone marrow from healthy, normal volunteers and patients with acute myelocytic leukemia was cultured in diffusion chambers implanted into cyclophosphamide pretreated mice. Chambers were removed at regularly scheduled intervals over a period of 28 days. Total and differential cell counts were then done on the contents of each chamber. Normal human bone marrow showed an orderly pattern of growth and differentiation which was not found with leukemic bone marrow. Monocytes and macrophages were the predominant cell types in the diffusion chambers filled with normal marrow after day 10 of culture. Although leukemic specimens showed predominantly leukemic cells, a few mature polymorphonuclear leukocytes could be found throughout the entire culture period. Questions about the nature of the defect in acute myelocytic leukemia and the significance of the in vivo culture system are discussed. The results of these studies are compared and contrasted with studies of a similar type.

Animals↗

Mitigation of Graft-versus-host disease in mice with xenogeneic antithymocyte serum and complement.

In vitro treatment of parental C57BL/6 lymphohematopoietic cell grafts with unabsorbed guinea pig anti-mouse thymocyte serum (ATS) and guinea pig complement (GPC), prior to inoculation into lethally irradiated B6D2F hybrid hosts, has proven to be of value in terms of mitigating graft-versus-host disease (GvHD). However, the beneficial effect of such a pregrafting procedure is limited to the prevention of acute GvHD. The late GvHD remains a continuing problem, and is probably due to the graft-versus-host activity (GvHA) of newly produced nontolerant lymphocytes from lymphoid precursors resistant to ATS. Possible ways to render these precursors sensitive to ATS and complement are discussed. The potential significance of thymic hormones and cyclic AMP in achieving this is emphasized.

Animals↗

Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

Animals↗