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C Geisler

Publications and source records attributed to C Geisler.

At least 91 records · Page 5Linked to original sources
PubMed1989

Failure to synthesize the human T-cell CD3-zeta chain and its consequence for the T-cell receptor-CD3 complex expression.

The T-cell antigen receptor is composed of two variable chains (alpha and beta, termed TcR) which confer ligand specificity, and four constant chains (gamma, delta, epsilon, and zeta, collectively termed CD3) whose functions are not fully understood. To explore the role of the individual CD3 components, the human T-cell tumour line Jurkat was chemically mutagenized followed by negative selection with F101.01 (a monoclonal antibody against the TcR-CD3 complex), and cloning. Growing clones were analysed for TcR-CD3 expression by immunofluorescence. One clone, J79, was found to express greatly diminished levels of TcR-CD3. This clone produced all the TcR-CD3 components except the CD3-zeta, as demonstrated by metabolic labelling and immunoprecipitation followed by one- and two-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis. These data indicate that the CD3-zeta determines the normal intracellular fate of the TcR-CD3 complex, and that the CD3-zeta is necessary for the intracellular transport and expression at the cell surface of the TcR-CD3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor.

Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected. A thymic biopsy specimen showed severe abnormalities of both the thymic lymphoid and epithelial component with abortive medullary differentiation and almost an entire lack of Hassall's corpuscles. This patient represents a case of primary immune deficiency syndrome not previously described. Thymic deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Identification of alpha beta and gamma delta T cell receptor-positive cells.

Two lineages of T lymphocytes bearing the CD3 antigen can be defined on the basis of the nature of the heterodimeric receptor chain (alpha beta or gamma delta T cell receptor (TCR) expressed. Precise identification of alpha beta and gamma delta TCR+ cells is essential when studying the tissue distribution and function of these different T cells. In immunofluorescence studies gamma delta TCR+ cells have been identified as CD3+WT-31- or CD3+CD4-CD8- cells. However, this may not be the optimal procedure because gamma delta TCR+ cells are weakly WT-31+, and some are CD8+. The aim of this study was to evaluate a panel of monoclonal antibodies (MoAb) directed against different chains of the TCR-T3 complex for a more precise identification of alpha beta+ and gamma delta TCR+ cells in flow cytometric studies. We found that the MoAb anti-Ti-gamma A and delta-TCS-1, recognizing the TCR-gamma and the TCR-delta chain respectively, only reacted with a subpopulation of gamma delta TCR+ cells, whereas another TCR-delta chain recognizing MoAb anti-TCR-delta 1 reacted with all gamma delta TCR+ cells. All MoAb reported to belong to the CD3 group reacted with both alpha beta TCR+ and gamma delta TCR+ cells as expected. Our results indicate that all gamma delta TCR+ cells can be identified with the MoAb anti-TCR-delta 1. Because no MoAb recognizing the TCR-alpha or TCR-beta chains at the cell surface of intact cells are yet available, we suggest that alpha beta TCR+ cells could be identified as CD3+ anti-TCR-delta 1-cells.

Antibodies, Monoclonal↗
PubMed1988

Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules.

Recent investigations have demonstrated that the primary mixed lymphocyte reaction (MLR) is dependent on certain accessory molecules, e.g. CD4 and LFA-1. We have compared the requirements of the primary MLR and the responses of alloreactive, primed lymphocytes (PL) by inhibition studies using monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c-reactive MoAb significantly inhibited the primary MLR (inhibition = 25%, P less than or equal to 0.01; 48%, P less than or equal to 0.01 and 13%, P less than or equal to 0.05, respectively) but these MoAb did not inhibit the primed lymphocyte reaction (PLR). The CD11b-reactive MoAb had no significant influence on either of the responses. CD2- and CD4- reactive MoAb significantly inhibited both primary MLR (greater than 80%, P less than or equal to 0.01) and to a lesser extent the PLR (40-65%, P less than or equal to 0.01). A MoAb reactive with IL-1 beta inhibited the primary MLR (38%, P less than 0.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data indicated that PL seemed neither to bind exogenous IL-1 (as opposed to CD4+ PBMC) nor to possess membrane-bound IL-1. The differences between 'virgin' and primed, allogeneic T-cell responses indicate that profound changes in the functional capability of the responding T-cell population take place during the bulk expansion. The results indicate that during repeated priming with alloantigen and bulk expansion, the proliferative response of T lymphocytes becomes independent of (i) the interaction with the CD11 adhesion molecule(s), (ii) the CD5 molecule, and (iii) the cytokine IL-1 beta.

Antibodies, Monoclonal↗
PubMed1988

Characterization and expression of the human T cell receptor-T3 complex by monoclonal antibody F101.01.

A murine monoclonal antibody (MoAb) F101.01 reacting with the T cell receptor (TCR)-T3 complex is presented. Immunohistological studies showed that F101.01 specifically stains T-zone lymphocytes in lymph nodes, tonsils, and splenic tissue. Two-colour immunofluorescence and flow cytometry demonstrated co-expression of the antigen defined by F101.01 and the pan-T cell antigens defined by CD2, CD3, CD5, and CD7 antibodies. Cells stained with CD4 and CD8 antibodies were both included in the F101.01-positive population, whereas CD16-positive natural killer cells (NK), B cells (CD19 and CD20), and myeloid cells (CD13 and CD33) were excluded. The target antigen of F101.01 co-modulated with the CD3-defined antigen (T3) and the TCR recognized by the MoAb WT-31. CD3 antibody and WT-31 both blocked binding of F101.01. F101.01 precipitated the TCR-T3 complex from lysates of 125I-labelled peripheral blood mononuclear cells (PBMC) and HPB-ALL, when the lysate was prepared with a detergent (digitonin) that conserves the TCR-T3 complex. FACS analysis of T cells from a patient with a T cell immunodeficiency demonstrated that delta-TCS-1-CD3+CD4+ and delta-TCS-1-CD3+CD8+ cells were brightly F101.01+, whereas a large subpopulation of delta-TCS-1+CD3+CD4-CD8- cells were weakly F101.01+. We conclude that F101.01 recognizes a conformational epitope of the TCR-T3 complex and that it reacts with the alpha beta TCR-T3 and the gamma delta TCR-T3 complexes with different intensities.

Antibodies, Monoclonal↗
PubMed1988

CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): preliminary results of a randomized multicenter study.

Five hundred and fifty consecutive patients with newly diagnosed B-CLL have been registered and classified in a Danish multicenter study. The study includes a protocol for primary treatment of patients in stage B or C (at diagnosis or after demonstrated progression), below 76 years of age, and without complicating serious disease. Until now 144 such patients have been randomized to either prednisolone (PRD) plus chlorambucil (CLB) 5 days every 4 weeks or monthly intensive CHOP treatment. Twenty-nine percent of the treated patients achieved CR on PRD + CLB versus 63% on CHOP (p less than 0.005). No response was found in 29% versus 18%, respectively (NS). A significant difference in survival between patients achieving CR, PR and NR was also demonstrated, whereas to date no difference in survival could be demonstrated between the two regimens. The toxicity was limited, and only 2 treatment-related deaths occurred in approximately 700 CHOP treatment series.

Adult↗
PubMed1988

The CLL2 study: preliminary results of flow cytometry immunophenotyping in the first 500 patients.

In the period 1984-1987, 500 consecutive, newly diagnosed patients with chronic lymphocytic leukaemia (CLL) have been registered in the still open Danish CLL2-study. As part of patient work-up, the immunological phenotype was established in all patients by immunofluorescence microscopy, and in 458 patients also by flow cytometry, with a panel of polyclonal and monoclonal antibodies. The majority of cases exhibited a CD5-pos, SmIgMD-pos phenotype with faint SmIg-fluorescence, and there is as yet no significant difference in survival between SmIgD-pos and SmIgD-neg cases. Seventy cases were FMC7-pos, a marker associated with a higher B-cell differentiation, and this was significantly correlated with stronger SmIg fluorescence intensity and splenomegaly (Rai stage II). The survival of the FMC7-pos patients was not significantly different from that of the FMC7-neg. Thus, in this preliminary phenotype analysis of the first 500 patients in the CLL2 study, no important prognostic subgroups were detected, although this might be due to the still short observation time (median observation time 532 days).

Denmark↗
PubMed1987

Reduction of the number of immunocompetent cells in the acute stage of herpes zoster.

Circulating and in situ mononuclear cell subsets were phenotypically characterized during both the acute and convalescent phase of herpes zoster infections in 14 patients. In peripheral blood a significant reduction in the absolute number of Leu 4+ T cells, Leu 2a+ suppressor/cytotoxic T cells, Leu 3a+ helper/inducer T cells, Leu 7+ killer cells, and B1+ B cells were found during the acute stage compared to convalescents and normal controls. In contrast no change in the absolute number of MO2+ monocytes was seen in the acute stage of the disease. During convalescence a return to normal values in the lymphocyte subsets and killer cells was seen within 1-2 months after the initial disease presentation. In skin biopsy specimens from 4 of the 14 patients with active herpes zoster lesions the cellular infiltrate consisted of T cells (Leu 4+) the majority being helper/inducer T cells (Leu 3a+). Most of the cells expressed HLA-DR (Ia) antigens and were according to this in an activated state. The observed changes in effector and regulatory cell numbers may have implications for the acquisition of Varicella-zoster virus infections, the immune deficiency state associated with the disease, and/or the immune response to resolve the infection.

Aged↗
PubMed1987

Hypereosinophilia in a patient with acute lymphoblastic leukemia.

A case of a coincident acute lymphoblastic leukemia and marked eosinophilia is presented. The clinical and pathological features of this case are discussed with special emphasis on the hypereosinophilic syndrome versus secondary hypereosinophilia that can be found to accompany ALL. Special immunological studies may be helpful in the diagnostic procedures.

Adult↗
PubMed1986

Simultaneous presence of translocations t(14;18) and t(2;8) in a case of chronic lymphocytic leukemia.

We report a patient with classical chronic lymphocytic leukemia of IgM kappa phenotype and a stable clinical course, in which repeated chromosome analyses of blood lymphocytes revealed the coexistence of t(14;18), a marker often associated with follicular low grade lymphocytic lymphomas, and t(2;8), a variant of the t(8;14) typically seen in Burkitt's lymphoma. Both these translocations involve immunoglobulin gene regions, the t(2;8) being almost always found in patients with kappa light chain restriction. However, in an EBV-immortalized cell line of this patient, most karyotypes contained t(14;18) alone, without the t(2;8). This suggests that t(14;18) was the primary cytogenetic event, and that t(2;8) evolved subsequently. As a secondary cytogenetic event, the t(2;8) may not share the grave clinical consequences of a primary t(2;8) as seen in Burkitt's lymphoma and related disorders.

Aged↗
PubMed1986

The use of subliminal psychodynamic activation in the study of repression.

Female undergraduates (N = 33) selected for the presence of high sexual guilt were divided into two groups. One group evidenced a high degree of personality development from which it was inferred that they were prone toward (a) the use of repression rather than more primitive defenses and (b) oedipal rather than preoedipal conflict. The second group evidenced a lesser degree of personality development, and hence the above inferences did not apply. The subliminal psychodynamic activation method was used with both groups to investigate the effects on repression of intensifying and diminishing unconscious conflict over sexual wishes. Subjects were exposed to the verbal stimuli "LOVING DADDY IS WRONG" (conflict intensifying), "LOVING DADDY IS OK" (conflict reducing), and "PEOPLE ARE WALKING" (neutral control), each accompanied by a congruent picture both before (in one condition) and after (in another) a recall test of both neutral and sexual material. The conflict-reduction condition did not affect memory of the passages, but the conflict-intensification condition did for the group with the greater degree of personality development, when this condition was presented before the material to be remembered, and for the recall of neutral passages. The special conditions necessary for demonstration of repression are viewed as shedding light on why it has previously been difficult to show evidence of repression in laboratory experiments.

Conflict, Psychological↗
PubMed1986

The bone marrow histological pattern has independent prognostic value in early stage chronic lymphocytic leukaemia.

The initial diagnostic bone marrow specimens from 90 consecutive, untreated patients with chronic lymphocytic leukaemia were examined for the pattern of lymphocytic infiltration in relation to clinical stage (International Workshop System) and survival. Three non-diffuse (interstitial, nodular, mixed nodular-interstitial) and one diffuse pattern were recognized. Generally, the bone marrow patterns correlated well with clinical stage: a non-diffuse pattern prevailed in early, and a diffuse pattern in later stages. However, with a Cox analysis of the covariate effect of clinical stage and bone marrow pattern on survival, the bone marrow pattern was shown to have independent prognostic significance in the early stage A in which a diffuse pattern carried a fourfold increase in death rate as compared to a non-diffuse pattern. These high risk patients could not be identified by the Rai substages of the International Workshop System.

Aged↗
PubMed1985

An enzyme-linked immunosorbent assay for autoantibodies against the nuclear protein Scl-70.

This paper describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of autoantibodies against the nuclear protein Scl-70. The isolation of Scl-70 from rat livers and the conditions for the ELISA are described. Compared with the already established double diffusion in gel for detection of anti-Scl-70 antibodies this ELISA has advantages.

Absorption↗
PubMed1985

Lymphocyte subsets in patients with compositae oleoresin dermatitis and increased UVA sensitivity during treatment with azathioprine.

Four patients with severe contact dermatitis resulting from compositae oleoresin were found to have increased sensitivity to ultraviolet light. All showed a clear reduction of Leu-3a-positive lymphocytes (T helper/inducer cells) and cells expressing the Ia phenotype in their blood. The numbers of T suppressor/cytotoxic (Leu 2a) lymphocytes, monocytes and B lymphocytes were within the normal range. Treatment with azathioprine (150 mg daily) improved the eczema. The number of Leu-3a-positive lymphocytes normalized during therapy, but the number of Ia-positive cells did not.

Aged↗
PubMed1985

Sézary syndrome: phenotypic and functional characterization of the neoplastic cells.

Phenotypic properties of the neoplastic cells in skin, blood and lymph node specimens from 5 patients with the Sézary syndrome were examined by immuno-enzymatic and -fluorescence labelling of cells and tissue sections with a monoclonal antibody panel. In 3 cases, the in vitro functional properties of the neoplastic cells (isolated from blood specimens) were also analysed using a reverse plaque-forming cell assay. 3 different immunological categories were identified as follows: T-helper/inducer neoplasms (3 patients); T-suppressor/cytotoxic neoplasms (1 patient); and neoplastic T-cells demonstrating characteristics consistent with a concept of their derivation from inducible suppressor T-cells (1 patient). These data provide conclusive evidence that Sézary syndrome is heterogeneous with respect to the immunological characteristics of the neoplastic cells.

Aged↗
PubMed1985

Naproxen has greater antipyretic effect on Hodgkin's disease-related fever than no other tumours or infection.

In 28 febrile patients with malignant lymphoma or leukaemia, the hourly temperatures were recorded following an oral dose of 125 mg naproxen (50% of normal single adult analgesic dose). 15 patients had clinical infection, and 13 had fever secondary to their malignant disease. Compared to controls, there was no significant antipyretic effect of 125 mg naproxen in infected patients, whereas this small dose in patients without infection had a significant effect. In the uninfected patients, the antipyretic effect was significantly more marked in fever related to Hodgkin's disease than to non-Hodgkin lymphoma or leukaemia. This selective antipyretic effect of a prostaglandin-synthesis inhibitor in tumour-related fever, especially in Hodgkin's disease, is unexplained but may be useful in the palliative treatment of patients with advanced disease.

Anti-Inflammatory Agents, Non-Steroidal↗