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M Uppenkamp

Publications and source records attributed to M Uppenkamp.

49 records · Page 3Linked to original sources
PubMed1988

Diagnostic interpretation of T gamma gene rearrangement: effect of polyclonal T cells.

Rearrangement of the T gamma gene, which encodes one chain of the second T-cell receptor, is an early event in the development of T lymphocytes. In contrast to the T-cell receptor beta chain gene, the T gamma gene contains a very limited V region gene repertoire, accounting for only 8 to 10 rearranging V gamma genes. As a consequence of the limited number of V gamma genes, only seven or eight nongermline restriction fragments are displayed, even by highly polyclonal T cells. Here, we demonstrate that T gamma gene analysis produces a picture of pseudoclonality among polyclonal T lymphocytes accompanying B-cell lymphoma, T-cell lymphoma, and Hodgkin's disease. As little as 10% contamination by polyclonal T lymphocytes is sufficient to detect rearrangements in both clinical samples and in a controlled sensitivity assay. Conversely, polyclonal T cells were found to obscure T-cell clones when polyclonal T cells represented as little as 30% of total cells. We conclude that, due to the unusual genomic structure of the T gamma gene, rearrangement analysis of the T gamma gene carries a significant limitation as a marker of clonality and lineage.

B-Lymphocytes↗
PubMed1987

Limited diversity and selection of rearranged gamma genes in polyclonal T cells.

The role of a T gamma gene product in the immune response is not known. To investigate the participation of the T gamma gene in functional T cells, we estimated its variable (V gamma) gene diversity among mature polyclonal T cells and assayed for in vivo selection of rearranged V gamma genes during the immune response. In this study, we present evidence that functionally mature, normal human T cells have rearranged their T gamma genes but display a limited range of gene rearrangement choices. In contrast to clonal T cell neoplasms, an invariant array of seven T gamma gene rearrangements was found to be proportionately distributed within normal polyclonal T cell populations, as well as in benign polyclonal T cell proliferations incited by a wide variety of pathological conditions. Findings presented here indicate that the likelihood of rearrangement of each human V gamma gene may be fixed. Lack of selection of V gamma genes during the mature T cell immune response implies a limited role of any single V gamma gene at this stage of T cell development.

Antibody Diversity↗
PubMed1987

Rearranged antigen receptor genes in Hodgkin's disease.

Despite intensive efforts using a wide variety of approaches, the cellular lineage and clonality of the abnormal cells of Hodgkin's disease have remained an enigma. In the present study, cell separation techniques that enriched for Reed-Sternberg cells and their variants were used to generate sufficient percentages of abnormal cells to allow detection of rearrangements in these cell fractions. DNA from the involved tissues of eight Hodgkin's disease patients was subjected to Southern blot analysis to detect rearrangements of T cell antigen receptor genes and immunoglobulin genes. Immunoglobulin gene rearrangements were found in three of five cases in which Reed-Sternberg cells and their variants were enriched by cell separation techniques to cell frequencies greater than 1%. Rearrangements of immunoglobulin heavy chain genes occurred in two cases, and a lambda light chain gene rearrangement occurred in a third case. Rearrangements were not detected in lymphocyte fractions or in unseparated cells prepared from the same tissues. The putative Hodgkin's cell line, L428, also contained rearrangements of immunoglobulin heavy and kappa and lambda light chain genes and, in addition, harbored a single T cell receptor beta gene rearrangement. These findings indicate that Reed-Sternberg cell-enriched fractions contain clonal cell populations and provide a lead, at the molecular genetic level, to a possible lymphoid derivation of the Reed-Sternberg cell.

Antigens, Surface↗
PubMed1987

Development of T3/T cell receptor gene expression in human pre-T neoplasms.

Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia.

A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.

Adult↗
PubMed1985

[High-dose cytarabine treatment: a promising therapy modality in acute resistant myeloid leukemias in recurrence].

High dose Cytarabin in relapsed and refractory acute leukaemia. High dose cytarabin can be very effective for the treatment of acute leukaemia resistent to conventional cytarabin doses. Therefore 10 patients (6 males, 4 females) with ages ranging from 18 to 58 years (median: 34 years) refractory to conventional induction therapy were treated with 1 hour infusions of high dose cytarabin (3 g/m2 q 12 h for 6 days) 2 patients got additional 20 mg/m2 doxorubicin on days 7 to 9. According to this treatment, in 5 of the 10 patients complete remissions could be achieved. Without further treatment 3 patients relapsed after 4, 7 and 15 months leading to death in 2 or 3 months. 19 months after treatment 1 patient is in complete remission, though demonstrating meningosis leukaemica 5 months after high dose cytarabin. Another patient relapsed 14 months after high dose cytarabin, reaching another complete remission after treatment according to a ALL/AUL protocol [7]. 2 patients died in bone marrow aplasia and 2 patients did not show any response, dying 11 months after high dose cytarabin application. All patients demonstrated vomiting, nausea, diarrhea and allopecia. Bone marrow was profoundly depressed in all patients with severe granulocytopenia and thrombocytopenia for periods from 7 to 34 days. 3 to 5 days after the end of high dose cytarabin therapy 3 patients developed acute ceratitis and 2 patients conjunctivitis. 3 patients showed erythrodermia of their skin with epidermolysis in 2 of these patients.

Adolescent↗
PubMedDate not supplied

Rearranging antigen-receptor genes in enriched Reed-Sternberg cell fractions of Hodgkin's disease.

Molecular genetic analysis of rearranging antigen-receptor genes in non-Hodgkin's lymphomas has revealed the clonality and lineage in the majority of cases. In an analogous approach, we sought to apply gene rearrangement analysis to Hodgkin's disease to understand better the clonality and origin of this disorder. However, the putative neoplastic cell of Hodgkin's disease, the Reed-Sternberg cell and its variants, is extraordinarily rare in most cases of Hodgkin's disease. On the average, Reed-Sternberg cells and variants represent 0.1 per cent of total cell suspensions of nodular sclerosing Hodgkin's disease. As this frequency is below the minimum threshold of sensitivity of the Southern blot assay, we attempted to enrich for Reed-Sternberg cells before DNA extraction and analysis. Using either elutrition or Percoll density gradient centrifugation, we were able to enrich the percentage of Reed-Sternberg cells and variants to above 1 per cent in five cases of nodular sclerosing Hodgkin's disease. In three of these cases, immunoglobulin gene rearrangements were identified, but no T cell receptor gene rearrangements were seen. No rearrangements were detected in unseparated cells or in the Reed-Sternberg cell-depleted fractions. In addition, the L428 Hodgkin's disease cell line was found to have one rearranged and one deleted heavy-chain gene, a rearranged kappa gene, a rearranged lambda gene, and a single rearranged beta allele. No rearrangements of the T gamma gene were found in L428. Taken together, these findings indicate that clonal cell populations are present in Hodgkin's disease and suggest the possibility of a clonally expanded lymphoid cell in this disorder.

Genes, Immunoglobulin↗
PubMedDate not supplied

Molecular analysis of an ataxia telangiectasia T-cell clone with a chromosomal translocation t(14;18)--evidence for a breakpoint in the T-cell receptor delta-chain gene.

We established a clonal T-cell line with a reciprocal chromosomal translocation t(14;18)(q11;q23) from a patient with ataxia telangiectasia (AT) and T-cell chronic lymphocytic leukemia (T-CLL). The tumor cells and the derived T-cell line were compared with respect to phenotype, karyotype, and rearrangement pattern. Restriction fragment analyses of the T-cell receptor (TCR)-delta gene, which is located within the TCR-alpha gene on chromosome 14q11, indicated that the breakpoint is located within the TCR-delta locus, splitting the TCR-delta gene between the variable and joining segments. This specific chromosomal translocation was only detected in the derived T-cell line and may be involved in the genesis of T-cell malignancies in AT.

Ataxia Telangiectasia↗
PubMedDate not supplied

Infection by Alcaligenes xylosoxidans subsp. xylosoxidans in neutropenic patients.

Alcaligenes xylosoxidans subsp. xylosoxidans (A. x. xylosoxidans) is a nonfermenting gram-negative peritrichous rod and opportunistic pathogen. The organism is frequently found in an aqueous environment. In the past few years, nosocomial infections caused by A. x. xylosoxidans have become more evident. The literature suggests that systemic infections are severe and often lethal and an optimal antibiotic therapy is not well established. This report describes nosocomial infections in 11 patients of a hematology ward over a 2-month period. Primary infection occurred during the neutropenic phase after cytotoxic chemotherapy. Reinfection spread from central venous catheters that had been implanted before the first infection. The bacteremia was successfully treated by imipenem. None of the 11 patients died from the bacteremia, but 3 died of their underlying diseases. Despite an intensive search for the source, the route of infection remained uncertain. Nosocomial infections by A. x. xylosoxidans are of growing importance in high-risk patients. Although the source of infection often remains unknown, infection seems to originate from contaminated solutions. Treatment with imipenem and the removal of central venous catheter systems successfully eliminated A. x. xylosoxidans, which adheres to plastic material.

Adolescent↗