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T Tscherning

Publications and source records attributed to T Tscherning.

15 recordsLinked to original sources
PubMed1995

[Problem-based medical teaching].

A possible method of improving teaching at faculties of Health Sciences is the so-called problem-based teaching method. A student is presented with a (clinical) medical case, which is to be investigated. By means of this method, the student himself will, under guidance, formulate his individual lack of knowledge, goals, priorities, methods, and evaluation. Educational observations show that the learning process is better when the problem-solving takes place among a group of students. A tutor acts as a catalyst for the process and gives feed-back through the problem-solving. He is therefore not an intermediary of knowledge to the group, but primarily refers the student to literature or knowledge experts at the faculty. International studies have not proven any unequivocal improvement in the students' ability to pass exams or to work as doctors, but both teachers and students seem to be more satisfied with the teaching method, which has stimulated the wish to study. The use at other faculties has not caused any large increase in expenditures. This should result in an increased use of problem-based teaching in medical education.

Denmark↗
PubMed1995

[Pyomyositis].

A 49 year old man with a palpable femoral tumor was examined by ultrasonography, CT and MRI within five days. Ultrasonography and CT indicated a solid malignant tumor, whereas MRI showed high signal intensity throughout the medial vastus muscle on T2-weighted images and centrally localized areas with low signal intensity on T1-weighted images indicative of pyomyositis. This diagnosis was immediately confirmed at surgery. Prompt diagnosis of pyomyositis is of utmost importance since it can rapidly develop into a life-threatening condition. The present case demonstrates the superiority of MRI in this clinical entity, whereas ultrasonography and CT may be misleading in the early stage.

Diagnosis, Differential↗
PubMed1994

The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils.

The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro-urokinase (pro-uPA) and facilitates its conversion to enzymatically active urokinase (uPA). uPA in turn activates surface-bound plasminogen to plasmin, a process of presumed importance for a number of biologic processes including cell migration and resolution of thrombi. We have previously shown that uPAR is expressed on the plasma membrane of circulating neutrophils, and we now report that stimulation with phorbol myristate acetate (PMA), FMLP, or tumor necrosis factor-alpha results in a rapid increase in the expression of uPAR. This process is accompanied by an increased cell-associated plasminogen activation after preincubation of neutrophils with pro-uPA in vitro. By subcellular fractionation of unstimulated neutrophils, 50% of uPAR is recovered in fractions containing latent alkaline phosphatase, corresponding to an intracellular compartment of easily mobilizable secretory vesicles distinct from both primary and specific granules, whereas the remaining 50% of uPAR is associated with a compartment eluting close to the specific granules. In contrast, the ligand pro-uPA is primarily (approximately 80%) found in the specific granules, but small amounts of pro-uPA/uPA (approximately 20%) coelute with latent alkaline phosphatase. Stimulation of neutrophils with FMLP results in translocation of uPAR as well as of pro-uPA from the secretory vesicles, whereas stimulation with PMA is required to translocate material from specific granules. Flow cytometry of neutrophils saturated with exogenous diisopropyl fluorophosphate-uPA shows a large excess (approximately 90%) of unoccupied uPAR on resting as well as FMLP- and PMA-stimulated neutrophils, suggesting a possible role for exogenous pro-uPA in providing neutrophils with a potential for plasminogen activation. These processes may be important for neutrophil extravasation and migration through extracellular matrix and for the contribution of neutrophils to resolution of thrombi.

Biological Transport↗
PubMed1993

Selective engraftment of memory CD4+ T cells with an unusual recirculation pattern and a diverse T cell receptor-V beta repertoire into scid mice.

Young (H-2d, Ld+) severe combined immunodeficiency (scid) mice were injected intravenously with 10(5) CD4+CD8- T cells purified from spleen, thymus or lymph nodes (LN) of dm2 (H-2d, Ld-) donor mice. In the immunodeficient recipients, the lymphoid compartment in the splenic white pulp was repopulated with donor-type T cells and cellularity in the red pulp was increased. In addition, donor-type CD4+ T cells repopulated the peritoneal cavity, mesenteric LN and the lamina propria of the small intestine of scid mice, but were undetectable in thymus and peripheral (inguinal, axillary) LN. Histological examination of repopulated mesenteric LN showed expanded subcapsular sinuses, repopulated cortical areas, but poorly developed high endothelial venules (HEV) indicating deficient blood-LN lymphocyte recirculation. The engrafted CD4+ T cell population had the surface phenotype of memory T cells (CD44/Pgp-1high CD45RB(low) and expressed the Peyer's patch HEV-specific homing receptor CD49d (LPAM-1), but not the LN HEV-specific homing receptor LECAM-1. The CD4+ T cell population in spleen and mesenteric LN of transplanted scid mice displayed a diverse T cell receptor-V beta repertoire. Transfer of titrated numbers (10(3), 10(4), 10(5) cells per mouse) of CD4+ T cells into scid mice established donor-type T cell populations with this unusual homing pattern in all recipients. Repeated serial transfers of dm2 CD4+ T cells through young scid mice revealed an extensive in vivo expansion potential of transferred cells for > 18 months. The experimental system described represents an in vivo model to study the functional competence and the differentiation potential of a murine memory CD4+ T cell subset.

Animals↗
PubMed1993

Regulatory effects in vitro by thymic medullary epithelial cells on TCR transgenic T cells specific for male H-Y antigens.

To evaluate the ability of thymic epithelial cells (TEC) to influence growth and differentiation of antigen specific T cells, we have used female transgenic (TG) mice expressing a receptor on the majority of their T cells for the male (H-Y) antigen in the context of H-2Db antigens. Male or female TEC expanded in serum-free medium were co-cultured with female TG thymocytes. FAC-Scan analysis after 3 days of co-culture did not indicate any selective deletion of subpopulations induced by male TEC. In contrast, the presence of TEC in TG thymocyte cultures led to increased proliferation, irrespective of the type of TEC and stimulus used. Limiting dilution (LD) proliferation analyses, using irradiated male spleen cells as stimulator cells, showed increased clonability of CD4-CD8+ cells, but reduced clonability of CD4-CD8- thymocytes, in the presence of both male and female TEC. Clones from the LD cultures were expanded for several weeks. Expanded clones all expressed the v beta 8.2+ TG TCR. One-half of the expanded TG CD8+ T cell clones obtained from LD cultures exhibited H-Y specific proliferation, and the majority of clones showed antigen-specific IL-3 secretion. Expanded clones did not develop into a cytotoxic machinery in the present culture system.

Animals↗
PubMed1993

Veto suppression: the peripheral way of T cell tolerization.

Cells with veto activity induce a state of tolerance in T cell precursors with specificity for antigen determinants expressed on the surface of the veto-active cell. This state of tolerance is not strictly defined, but results in altered responses to specific antigen, such as decreased proliferation, decreased development of cytotoxicity and secretion of interleukins, down-regulated ability to reject grafts and expression of T cell and IL-2 receptors. Both clonal anergy and clonal deletion has been shown to operate in vetoed T cells. Veto-induced tolerance can be established in vitro and in vivo for both MHC class I and II as well as minor histocompatibility antigens. The most powerful veto activity is present in mature activated cytotoxic CD8+ T cells, but other cells including noncytotoxic cells are also capable of acting as veto cells. Thus it appears that veto activity per se is not confined to a certain cellular entity, but rather reflects a constitutively expressed immunoregulatory capability inherent to a broad array of activated T cell and non-T cell categories with their own distinct functions not related to their eventual veto activity.

Animals↗
PubMed1993

T-cell activation. V. Anti-major histocompatibility complex class I antibody-induced activation and clonal abortion in Jurkat T-leukaemic cells.

We have studied activation-induced changes in intracellular calcium [Ca2+]i, interleukin-2 (IL-2) secretion, and clonal abortion of the human leukaemic T-cell line Jurkat and three T-cell receptor (TcR)/CD3 receptor negative clones deficient for the TcR alpha, TcR beta and CD3 gamma chains respectively, as well as three transfectant clones reconstituted with the appropriate TcR/CD3 cDNA. For activation, the cells were exposed to anti-TcR/CD3, anti-CD2 and anti-major histocompatibility complex (anti-MHC) class I monoclonal antibodies (mAb) respectively. Cellular activation by these mAb leading to an increased IL-2 secretion was preceded by a rise in [Ca2+]i and was relatively dependent on the expression of the a TcR/CD3 complex. In contrast, anti-MHC class I mAb-induced clonal abortion in Jurkat T cells may occur without previous fluctuations in [Ca2+]i and appeared to be independent of TcR/CD3 expression. The present observation suggest the existence of different secondary messenger systems operating in Jurkat cells following activation via the TcR/CD3, CD2 and the MHC class I pathways, respectively.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

H-2 class I Ld antigen positively selects different TCR V beta gene products in CD8+ and CD4+ T cells.

Expression of CD4+ or CD8+ determinants and ten different TCR V beta genes was analysed by two-colour flow cytometry in lymph node cells (LNC) of BALB/c and dm2 (a BALB/c Ld loss mutant) mice. TCR V beta 14 expression of CD8+ T cells and TCR V beta 7 and 14 of CD4+ T Cells were significantly more frequent in BALB/c than in dm2 LNC, whereas no differences were observed in the frequency distribution of TCR V beta+ CD4-CD8- double negative LNC from BALB/c versus dm2 mice. These results represent the first published evidence for positive selection of particular TCR V beta genes by individual MHC class I molecules in non-manipulated mice.

Animals↗
PubMed1991

CD3+ T cells in severe combined immunodeficiency (scid) mice. IV. Graft-vs.-host resistance of H-2d scid mice to intravenous injection of allogeneic H-2b (C57BL/6) spleen cells.

Intraperitoneal injection of 2 x 10(7) nonfractionated spleen cells (SC) from C57BL/6 (B6, H-2b) mice into completely allogeneic immunodeficient H-2d scid mice induced clinical and histological signs of acute graft-vs.-host disease (GVHD), with all transplanted severe combined immunodeficiency (scid) mice dying in the 3rd week post-transfer. In contrast four out of five scid mice survived for greater than 7 weeks after intravenous (i.v.) injections of equal numbers of B6 SC. Intravenously allotransplanted scid mice analyzed in the 8th week post-transfer had engrafted donor-type CD4+ and CD8+ T cells in the spleens but showed no clinical or histological evidence of GVHD. i.v. injection of 10(7) or 10(6)O B6 SC engrafted allogeneic T cells in spleens of scid recipients; in contrast, i.v. injection of 10(5) nonfractionated B6 SC or 3 x 10(5) cell sorter-purified, naive or anti-H-2d-primed splenic CD4+ or CD8+ B6 T cells led to rejection by young scid recipient mice. B6 T cells engrafted into spleens of scid mice after i.v. injection showed proliferative anti-host alloreactivity in vitro. No cytotoxic reactivity against host-type alloantigens was found in standard 4-h 51Cr-release assays. These data demonstrate that allogeneic T cells injected i.v. into immunodeficient scid mice are partially tolerized against host-type alloantigens.

Animals↗
PubMed1991

Veto-like down-regulation of T helper cell reactivity in vivo by injection of semi-allogeneic spleen cells.

Injection of semiallogeneic (C57BL/6 X BALB/c) F1 MHC class II expressing spleen cells into C57BL/6 mice leads to a clonal deletion or anergy of recipient CD4+ T helper cells with specificity for the allogeneic MHC class II molecules on the injected cells whereas reactivity against third party allogeneic cells is not influenced. These observations were based on analyses in the recipient mice of proliferating CD4+ T cells in mixed lymphocyte reactions (MLR), limiting dilution (LD) cultures and measurements of IL-2 and IL-3 secretion.

Animals↗
PubMed1991

T-cell activation. IV. Evidence for a functional linkage between MHC class I, interleukin-2 receptor, and interleukin-4 receptor molecules.

The aim of the present work was to study regulatory interactions between MHC class I molecules and the interleukin (IL)-2, IL-3, and IL-4 receptors and functional interactions between the receptors for IL-2 and IL-4. Our major observations were: (1) quiescent splenic T cells exposed to specific anti-MHC class I antibodies become responsive to IL-2 and IL-4 stimulation; (2) T-cell clones (CTLL-2 and HT-1) grown at high cell density or low IL-2 concentrations become refractory to IL-2 and IL-4 stimulation. After exposure to anti-class I antibodies the refractory cells recover responsiveness to lymphokine-induced proliferation; (3) IL-2 receptor expression is non-inducible in class I-negative T-lymphoma cells, but is inducible following class I gene transfection of the cells; (4) exposure of T-cells and clones to IL-2 receptor antibody increases the responsiveness to IL-4 stimulation; (5) IL-2 and IL-4 act synergistically at low and substimulatory lymphokine levels; and (6) IL-3 responsiveness of hemopoietic cells is not influenced by exposure to anti-MHC class I antibody. It is concluded that class I molecules are of importance for the functional expression of the receptors for IL-2 and IL-4 and that these receptors are functionally interrelated.

Animals↗
PubMed1991

CD3+ T cells in severe combined immunodeficiency (SCID) mice. V. Allogeneic T cells engrafted into SCID mice do not induce graft-versus-host disease in spite of the absence of host veto and natural suppressor cell activity.

Intravenous injection of 10(6) to 10(7) non-fractionated spleen cells (SC) from C57BL/6 (B6, H-2b) mice into completely allogeneic, immunodeficient H-2d severe combined immuno deficiency (scid) mice leads to engraftment of allogeneic donor T cells. Mice analysed in the tenth week posttransfer had engrafted donor-type CD4+ and CD8+ T cells in the spleens but showed no clinical evidence of graft-versus-host disease (GVHD). Transfer of allogeneic T cells engrafted in scid recipients did not induce GVHD upon i.v. injection into secondary scid recipients and lead in most recipients to engraftment of a pure CD4+ T-cell population. Experiments were carried out to investigate the reason(s) for the lack of GVHD in recipient scid mice, i.e. the presence of allotolerance in the engrafted donor T cells. Scid spleen cells (SC) efficiently stimulated alloreactive responses of B6 T cells: scid SC stimulated H-2d-specific cytotoxic responses in a B6 anti-scid mixed lymphocyte culture in vitro, and scid SC injected i.v. into B6 mice efficiently primed splenic cytotoxic lymphocyte precursors against H-2d alloantigens. Moreover when assayed in vitro, no veto activity or natural suppressor activity was detectable in scid SC. These data demonstrate that tolerizing mechanisms currently believed to operate in vivo can not explain the fact that allogeneic T cells injected i.v. into immunodeficient scid mice become tolerized against host-type alloantigens. Our results are discussed in the light of clinical experience of allogeneic T-cell transfer in scid infants.

Animals↗
PubMed1990

Inhibitory effect of mycoplasma-released arginase. Activity in mixed-lymphocyte and tumour cell cultures.

Non-fermenting mycoplasma species deplete culture media for arginine through arginase activity linked to their arginine deiminase pathway, resulting in proliferation arrest and cell death in mycoplasma-contaminated cell cultures. The presence of only 2-3 Mycoplasma (M.) arginini-contaminated T cells in a one-way allogeneic mixed-lymphocyte culture (MLC) significantly inhibits development of cytotoxic T-cell activity. Likewise, strong degrees of inhibition are observed after addition of nanogram doses of M. arginini extracts (MAE) to MLC or cell proliferation cultures. M. arginini-induced cell inhibition can be reversed by addition of excess arginine to the culture medium. Antisera raised against non-fermenting, but not against fermenting, mycoplasma species block the inhibitory effect of MAE. SDS-PAGE separation of MAE disclosed a broad band at 60 kDa which contained arginase activity when assayed in MLC and cell proliferation culture. SDS-PAGE followed by western blotting and reaction with antisera raised against non-fermenting mycoplasma species demonstrated a band at 43 kDa common for these micro-organisms.

Animals↗