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Biomedical subjects

K W Sell

Publications and source records attributed to K W Sell.

At least 19 recordsLinked to original sources

Defective transient endogenous spleen colony formation in S1/S1d mice.

WCB6F1 mice of the genotype S1/S1d did not form transient 5-day endogenous spleen colonies following midlethal irradiation, either spontaneously or in response to postirradiation bleeding. Their hematologically normal (+/+) littermates produced colonies equivalent in number and morphologic type to a normal strain (D2B6F1), as evaluated by both macroscopic and microscopic criteria. Bone marrow cells from S1/S1d mice, when transplanted into lethally irradiated +/+ mice, were able to generate equivalent numbers of transient endogenous spleen colonies (TE-CFUs), as compared to that obtained when syngeneic +/+ marrow cells were injected into lethally irradiated +/+ recipients. A defective growth of an early class of hematopoietic progenitor cells, resulting in the clinical course of the S1/S1d anemia is suggested and confirms previous reports on the microenvironmental nature of this abnormality.

Anemia

Loss of lymphocyte chalone activity in mice with autoimmune disease.

Lymphocyte chalone from the spleens of old BALB/c, young BALB/c and young NZB mice caused significant suppression of the proliferative response of BALB/c and NZB spleen cells to T and B mitogens, whereas lymphocyte chalone from old NZB spleen did not suppress. Lymphocyte chalone from young and old NZB mice was tested using different ages of NZB/NZW responding spleen cells; at all ages concanavalin A- and lipopolysaccharide-induced proliferation was suppressed less by the chalone from old NZB mice than from that of young NZB mice. The responding NZB/NZW cells were suppressed equivalently at all ages studied. The basis for the loss of lymphocyte chalone activity in old NZB mice remains unknown; however, it appears likely that this event has a role in the disturbance of the negative feedback control system which contributes to NZB autoimmune disease.

Aging

Use of attenuated sporozoites in the immunization of human volunteers against falciparum malaria.

Three human volunteers were successfully protected against sporozoite challenge by immunization with attenuated sporozoites of the Tamenie strain of Plasmodium falciparum from Ethiopia. The immunizing sporozoites were attenuated by exposing infected Anopheles stephensi mosquitos to X-rays at a dose of at least 120 Gy (12 000 rad). These irradiated, infected mosquitos were allowed to feed upon volunteers, thereby inoculating sporozoites into their blood stream. During the 10- to 38-week period of immunization, volunteers were exposed 6-8 times, at irregular intervals, to a total of 440-987 irradiated infected mosquitos. Protection against challenge by nonirradiated infected mosquitos lasted for at least 8 weeks, but not 16 weeks, after the last immunization with irradiated sporozoites. By contrast, volunteers who were exposed to a total of 200 or fewer irradiated infected mosquitos on 2-4 occasions were not protected upon challenge. Immunization by a sufficient number of irradiated mosquitos infected with the chloroquine-sensitive Tamenie strain from Ethiopia also protected against challenge with the chloroquine-resistant Marks strain of P. falciparum from Viet Nam. The results obtained in these studies suggest that immunization with attenuated sporozoites may be a useful method of protecting small groups of nonimmune individuals living in endemic areas. These findings should encourage further efforts to develop a sporozoite vaccine against human malaria.

Adult

Characterization of the immunosuppressive state during Schistosoma mansoni infection.

Analysis of a murine model of schistosomiasis revealed that both the thymus (T)- and bursa (B)-derived compartments of the immune system are modified during acute infection. The functional capacity of T and B lymphocytes to respond to mitogenic stimuli and the humoral response to thymus-dependent (SRBC) and thymus-independent (DNP-Ficoll) antigens are severely depressed. In addition, it was found that suppressor cells capable of inhibiting the response of normal lymphocytes to SRBC arise during acute infection. Although the splenic frequency of T (theta) and B (Ig+) cells remained constant during chronic infection, quantitative changes were detected in each population. In the T cell pool there was a decrease in the percentage of Ly-1+ cells and a concomitant increase in Ly-1+, 2+, 3+, cells, whereas the B cell pool showed a progressive loss of complement receptor-bearing lymphocytes, which apparently was the result of inactivation of surface complement receptor by a serum factor specifically found in infected mice. Characterization of the serum factor strongly suggests it is an immune complex. Thus, it appears that both suppressor cells and immune complexes contribute to changes noted in the immune system during acute schistosomiasis. Additional studies carried out in mice after unisexual infection revealed that egg production is not a necessary prerequisite for several of the immunologic phenomena associated with acute schistosomiasis.

Animals

Distribution of Lyb-4.1 and other membrane antigens on murine lymphoid tumors.

The distribution of membrane antigens on 6 DBA/2-derived tumors (L1210, L5178Y, P815, ABLS 11, ABLS 12, and ABLS 13) was studied by direct cytotoxicity and quantitative absorption assays. Lyb-4.1 antigen was found solely on the L1210 tumor. Iad antigens were absent from all tumors, and H-2Kd and H-2Dd antigens were present on all tumors. Immunoglobulin was adsorbed to the ascites tumors and lost after 3 days or more in tissue culture. These studies were performed to characterize the distribution of DBA/2 membrane antigens on DBA/2-derived tumors as a base line for functional and chemical studies with these tumors and with their solubilized proteins.

Animals

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

Detection of B cell antibodies in renal transplant recipients.

A retrospective study for the presence of lymphocytotoxic antibodies was performed on sera collected from 119 kidney graft recipients. Sera that had been collected on days 12 to 19 post-transplant were tested for cytotoxic reactions against a panel of human peripheral blood lymphocytes from 60 unrelated donors and 37 to 47 cultured human lymphoid cell lines (LCL). Forty-nine sera were negative against peripheral blood lymphocytes but contained cytotoxic antibody against cells on the LCL panel. Several sera were tested on E rosette-purified peripheral blood lymphocyte B cells and T cells from five donors whose LCL had also been tested. LCL appeared to be more sensitive to cytotoxic reactions than their B cell counterparts and may identify additional specificities which may not be related to the B cell alloantigenic system. Mixed lymphocyte culture blocking experiments were carried out against all combinations of these five cells. Some sera showed reactions of identity for B cells and LCL, and blocked the appropriate stimulator cells in mixed lymphocyte culture. Two sera that were positive for LCL but negative for B cell blocked only responder cells in the mixed lymphocyte culture.

Antibodies

Cellular immunity to cytomegalovirus in a patient following bone marrow transplantation.

Cell-mediated immunity to cytomegalovirus (CMV) was studied in a bone marrow transplant patient with evidence of active CMV infection. The lymphocytes from this patient were found to specifically recognize and respond in vitro by transformation to CMV-infected Wistar-38 fibroblasts and by production of macrophage migration inhibition factor to CMV antigen. In addition, plasma and spinal fluid from the patient were found to contain blocking factor that specifically inhibited the lymphocyte response in the above assays. Biochemical, biophysical, and immunological studies indicate that the blocking factor may be an antigen-antibody complex.

Adolescent