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Biomedical subjects

S Thierfelder

Publications and source records attributed to S Thierfelder.

At least 163 records · Page 9Linked to original sources
PubMed1977

Hematologic and immunologic studies in dogs given nitrogen mustard (hn3).

Hematologic and immunosuppressive effects of single doses of nitrogen mustard (HN3) were evaluated in 20 dogs. HN3 caused profound depression of peripheral blood counts in all animals. Recovery of total white blood cell counts in dogs surviving the acute gastrointestinal toxicity of HN3 was complete by day 15. Recovery of platelet and lymphocyte counts to initial levels took a more prolonged course. Granulopoietic progenitor cells (CFU-C) in the bone marrow were assayed by an in vitro culture system. Concentrations of CFU-C were markedly decreased one day after HN3-treatment, but showed at near-lethal doses rapid restoration to normal values within 4 to 7 days. Cellular immune function of HN3-treated dogs was impaired for prolonged periods as indicated by the reduced capacity of canine lymphocytes to proliferate in vitro in response to stimulation with mitogens. Humoral immune function was similarly affected as determined by the depressed and delayed antibody formation against an intravenous challenge with sheep red blood cell. In conclusion, our results suggest a different effect of HN3 on lymphoid and myeloid precursor cells.

Animals↗
PubMed1977

Evidence for monoclonal proliferation in prolymphocytic leukemia of T-cell orgin. A cytogenetic and Quantitative immunoautoradiographic analysis.

B- and T-cell markers were studied in a patient with prolymphocytic leukemia, a rare variant of chronic lymphocytic leukemia. Thymus-derived features were identified on the membrane of the neoplastic lymphocytes using the following cellsurface markers: Heterologous T-cell antigen, sheep erythrocyte receptor, surface immunoglobulin, complement receptor, Fc receptor and mouse erythrocyte receptor. Cytogenetic studies of leukemic cells from unstimulated and mitogen-stimulated cultures revealed a consistent karyotype characterized by marker chromosomes and a decreased chromosome number, whereas chromosomal analysis of hair root cells yielded a normal karyotype. A uniform expression of T-cell antigens measured on single leukemic cells by quantitative microphotometric immunoautoradiography correlated with the cytogenetic findings which are compatible with a descent from one progenitor cell.

Aged↗
PubMed1977

Immunohistochemical identification of T-and B-lymphocytes delineated by the unlabeled antibody enzyme method. II. Anatomical distribution of T- and B-cells in lymphoid organs of nude mice.

Tissue sections of the spleen, lymph nodes, and Peyer's patches were examined using an immunohistochemical demonstration of T- and B-lymphocytes in athymic homozygous nude mice possessing a known 1-5% of T-lymphocytes. Some of the few lymphocytes in the tyhmus-dependent periarteriolar zone of the spleen white pulp, the paracortex of lymph nodes and interfollicular area of Peyer's patches, were identified as T-lymphocytes. Also, singular T-lymphocytes occur in the thymus-independent marginal zone of the spleen white pulp, cortex and medulla of lymph nodes, as well as the follicular and subepithelial zones of Peyer's patches. These results indicate that the decreased numbers of T-cells in nude mice are found preferably in thymus-dependent regions, and to a smaller degree may recirculate in a similar way as in normal mice.

Animals↗
PubMed1977

Transplantation of syngeneic bone marrow incubated with leucocyte antibodies. I. Suppression of lymphatic leukemia of syngeneic donor mice.

"Antileukemic autotransplantation" an approach to eradicate by antibodies residual leukemia in the bone marrow taken during remission and regrafted in relapse is proposed and is the basis of investigations on the elimination of leukemic cells transferred to syngeneic mice. Rabbit antiserum against mouse T cells killed over 99% of cells when incubated with 10-5 lymphocytes of a T cell AKR/J leukemia transferred subsequently to syngeneic hosts. Seventy-five per cent of the recipients of antibody-coated and complement-treated leukemic cells survived the observation period of 80 days. Recipients conditioned with 800 R and given syngeneic bone marrow mixed with 10-5 leukemic cells died within 11 days, while 40% survived the observation period of 100 days without leukemia if the leukemic bone marrow had been preincubated with anti-T cell globulin (ATCG) and complement. A detrimental effect of ATCG on normal T cells could only be demonstrated in thymectomized, irradiated recipients of syngeneic ATCG-treated marrow. These mice did not reject H-2-incompatible skin grafts in contrast to the controls without ATCG or without thymectomy. ATCG thus inhibited leukemic lymphocytes while sparing stem cells for hemopoietic reconstitution. At the same time it did not interfere with the recovery of cellular immunity after bone marrow transplantation.

Animals↗
PubMed1977

Anatomical distribution of T and B lymphocytes identified by immunohistochemistry in the chicken spleen.

Antisera against chicken bursal and thymic lymphocytes were raised in rabbits. They were made specific for the target T or B cells by appropriat absorption and then used for immunohistochemical identification of T and B lymphocytes in tissue sections of chicken spleen, applying the unlabeled antibody enzyme method. Lymphocyte reacting with anti-chicken-thymus globulin predominated in the periarteriolar lymphatic sheaths and in the red-pulp cords. A few of these lymphocytes were localized between the periellipsoid lymphatic tissue and in germinal centers. The periellipsoid lymphocytes around the Schweigger-Seidel sheaths consisted of lymphocytes positive with anti-chicken-bursa-cell globulin. The majority of lymphocytes in the germinal centers were labeled also by anti-chicken bursa-cell globulin. Age-dependent changes in the anatomical localization of T and B lymphocytes are described between late embryonic development and an age of 2 years. The different conditions of avian and mammalian T and B cell distribution in the spleen were considered.

Aging↗
PubMed1977

Specific absorbed antithymocyte globulin for incubation treatment in human marrow transplantation.

The experimental data show that absorption of ATG with liver-kidney homogenate and CLL and LCL cells stepwise removed the hemopoietic toxicity, whereas the specific activity against T lymphocytes remained. Although the mode of action of absorbed ATG could not be tested in the first clinical case, the successful experiments in rodents together with the fact that the incubation treatment was tolerated by the patient may provide a new way of preventing fatal GVH reactions in man.

Animals↗
PubMed1977

Other mammalian histocompatibility systems. Skin graft rejection and graft-versus-host reaction across I-subregion differences: are there many more than three H loci within the H-2 complex?

The data confirm an earlier finding by Klein et al. that the I region harbors a strong histocompatibility locus, which by exclusion might be assigned to the IA subregion. In addition, it appears that intercalated between the IA subregion and S region there is a minor H locus since (DBA/2 X 4R)F1 rejects skin of 2R in a chronic fashion. In another combination, HTT versus 7R, which differs for the IC, S, and G regions but may also differ for genes between the D and TL locus, a similar chronic rejection pattern was observed indicating minor H gene(s) within or closely linked to the H-2 complex. The data reported here are in concordance with very recently published results by Klein et al..

Animals↗
PubMed1977

Antilymphocytic antibodies and marrow transplantation. V. Suppression of secondary disease by host-versus-theta-graft reaction.

An approach to block secondary disease was investigated in mice sensitized against the Th-1.1 (theta-AKR) alloantigen on the marrow donor's T cells. To avoid a concomitant sensitization against the donor's histocompatibility antigens, prospective marrow recipients were sensitized against thymocytes of a third-party strain sharing the donor's Th-1 alloantigen but not his histocompatibility antigens. Advantage was taken of the fact that rats carry a Th-1.1-like theta-antigen which induces anti-Th-1.1 antibodies in Th-1.2 mice. CBA/J and (C57BL/6 x CBA)F1 Th-1.2 mice were sensitized against rat thymocytes and tranfused with spleen and bone marrow of AKR/J Th-1.1 after irradiation with 800 to 900 R. Although unsensitized recipients died within 3 weeks of acute secondary disease, sensitized mice survived the observation period of 50 days as chimaeras. Sensitized recipients were killed by the transplantation of spleen cells from congenic AKR/Cum carrying the Th-1.2 antigen. The host-versus-theta-graft approach suppressed secondary disease following H-2-compatible and -incompatible marrow grafts. Its hemopoietic and Tcell chimaeras tolerated skin grafts of the donor strain while rejecting third-party skin grafts.

Animals↗
PubMed1977

Effects of busulfan (BU) on hemopoiesis and immune reactivity in dogs.

Hematologic and immunosuppressive effects of BU were evaluated in 21 dogs. Twenty to 30 mg BU/kg produced severe but in most cases reversible myelotoxicity. All animals given 40 mg BU/kg died of marrow failure which was consistently reversed by the infusion of autologous marrow. Granulocytic progenitor cells (CFU-C) in the bone marrow of BU-treated dogs were severely depressed by day 7 after drug administration and in surviving animals showed only slow recovery to normal values. Cell-mediated immunity as determined by the in vitro reactivity of lymphocytes was normal after stimulation with T-cell mitogens (PHA, ConA), but impaired after stimulation with B-cell mitogens (PWM, SpA). Antibody formation against sheep red blood cells was not suppressed by BU-treatment.

Animals↗
PubMed1977

In vitro and in vivo immune response to specific antigens in canine marrow graft recipients.

Cellular and humoral immune reactivity to primary and secondary challenge with tetanus toxoid, diphtheria toxoid and keyhole limpet hemocyanin was studied in normal dogs and canine bone marrow chimeras prepared for marrow grafting by lethal doses of cyclophosphamide. Short-term chimeras (less than 100 days postgrafting) showed general impairment of immune function as indicated by marked depression of skin test reactivity, lymphocyte blastogenesis in vitro and antibody formation. Long-term chimeras (more than 100 days post-grafting) demonstrated gradual improvement of immunologic capacity related to the stage of postgrafting. Prolonged immunoincompetence was suggested by decreased lymphocyte proliferation in vitro in response to stimulation with tetanus and diphtheria toxoids and by incomplete conversion from 19S to 7S antibody synthesis. Lymphocyte blastogenesis to specific antigens may prove a useful parameter for the in vitro evaluation of defects in cell-mediated immunity following allogeneic bone marrow transplantation. Our findings of prolonged immunodeficiency in the preclinical canine model point out the necessity for vigilance in early detection and treatment of infection and underline the importance of approaches aimed at accelerating immunologic reconstitution.

Animals↗
PubMed1977

Myeloid membrane markers. I. Expression of marker antigens specific for murine granulocytes and their precursor cells.

Bone marrow cells were investigated by immunoelectromicroscopy and by quantitative photometric immunoradioautography with a rabbit antiserum against murine bone marrow cells. The serum was absorbed with murine spleen, liver and thymus cells until it no longer reacted with thymocytes and lymph node cells in a quantitative complement fixation test. The antiserum stained granulopoietic but not erythropoietic or lymphopoietic cells. The density of the myeloid antigen on single cells increased with the differentiation from immature to mature granulopoietic cells. While the increase of label was statistically not significant at the level of differentiation from promyelocyte to myelocyte and metamyelocyte to band neutrophil, there was a remarkable gain of label from myeloblast to promyelocyte and from band neutrophil to segmented neutrophil. This was evident under the electron microscopy using peroxidase-labeled antibodies and could be measured quantitatively with photometric immunoradioautography using 125I-labeled antibodies.

Absorption↗
PubMed1976

[Use of specific anti-T-lymphocyte globulin (sATG) for the diagnosis of lymphoproliferative diseases (author's transl)].

Difficulties in the production of specific antisera against T-lymphocytes could be overcome by a stepwise absorption and purification procedure of anti-human thymocyte serum. Specific anti-T lymphocyte globulin (sATG) reacted with thymocytes, thymus-derived lymphocytes and a lymphoblastoid cell line of T-cell type whereas no activity was found against lymphoblastoid cell lines of B-cell type. Five chronic and three acute lymphatic leukemias were characterized using sATG in the cytotoxic test, electron microscopy, complement fixation test and quantitative immunoautoradiography, and compared with lymphocyte populations of normal individuals. Three chronic lymphatic leukemias with low numbers of spontaneous rosettes and high percentages of membrane-Ig-positive lymphocytes showed only few T-cell-antigen-positive lymphocytes and were therefore classified as B-cell leukemias. The cells of two chronic lymphatic leukemias with high numbers of spontaneous rosettes carried T-cell-antigen. The T-cell-antigen concentration, however, was lower than that of normal peripheral blood T-lymphocytes. The T-cell nature of two acute lymphatic leukemias with high numbers of spontaneous rosettes was confirmed by a positive reaction of the cells with sATG. In one case of acute lymphatic leukemia most leukemic cells carried T-cell-antigen although these cells did not form spontaneous rosettes. In the first two cases the T-cell-antigen concentration on the cell surface exceeded that of normal blood-T-lymphocytes, in the latter case it was slightly below that. The advantages of the characterization of leukemias with sATG in comparison with the spontaneous rosette formation and the relevance for prognosis are discussed.

Antilymphocyte Serum↗