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Biomedical subjects

M Gramatzki

Publications and source records attributed to M Gramatzki.

At least 73 records · Page 4Linked to original sources
PubMed1987

Early T cell differentiated chronic myeloid leukemia blast crisis with rearrangement of the breakpoint cluster region but not of the T cell receptor beta chain genes.

Early T cell differentiation is described in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis, supporting multi-lineage differentiation potential of CML precursor cells. In the absence of myeloid markers, strong positivity for terminal deoxynucleotidyl transferase (TdT) and reactivity with T cell antibody 3A1, but lack of more mature T cell antigens, provided evidence for immature T cell differentiation. Molecular analysis of the breakpoint cluster region (bcr) in chromosome 22 revealed a rearrangement and thus confirmed the CML origin of the early T cell blasts. T cell receptor beta chain sequences were found in germline configuration and therefore suggest a very immature stage of T cell differentiation in the CML blasts.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Intralymphatic interleukin 2 treatment in patients with acquired immunodeficiency syndrome: preliminary experience in three cases.

Patients with opportunistic infections during the course of acquired immunodeficiency syndrome (AIDS) were analyzed for cellular immune functions and found to be severely immunocompromised. In particular, interleukin 2 (IL 2) production appeared to be defect not only qualitatively but also quantitatively. In some of these patients, exogenous IL 2 improved immune response in vitro. Intralymphatically administered highly purified natural IL 2 was given repeatedly (over a time period of ten days) to three of these patients. In two cases, such a treatment course was repeated later. Clinical response - at least in some patients - appeared to be of temporary benefit. Shortly after termination of IL 2 application in two patients an increase of lectin responsiveness as well as improved reactivity in skin testing was noted, encouraging further exploration of IL 2 as an immunostimulatory drug in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Current results of a multicenter trial in multiple myeloma.

257 untreated myeloma patients (stage II and III) were studied in a multicenter trial. The patients were randomized and received MP or VCMP therapy. No differences in remission rate could be found in both therapy arms. After successful remission induction those patients without maintenance therapy relapsed significantly earlier than those patients receiving maintenance therapy. In pilot studies an etoposide therapy was found ineffective and a multidrug therapy (VBAMDex) could induce high remission rates in high risk and pretreated patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Intraarticular T lymphocytes in monoarticular and oligoarticular inflammatory joint diseases. Normal subset distribution and less numbers of activated T cells indicate major differences as compared to rheumatoid arthritis.

T lymphocyte subpopulations and the expression of T cell activation antigens were determined in peripheral blood, synovial fluid and/or synovial tissues of patients with recurring monoarticular arthritis and patients with HLA-B27 associated oligoarthritis in comparison to patients with rheumatoid arthritis (RA). In individuals with monoarthritis or oligoarthritis, there was a normal T cell subset distribution, both in peripheral blood and in intraarticular sites, with only a small number of T cells bearing Ia antigens. This was in marked contrast to the patient group with RA that demonstrated a significantly decreased ratio of T helper/inducer to T suppressor/cytotoxic cells in addition to large numbers of Ia+ T cells in intraarticular sites. The expression of the Tac antigen was similar in all disease groups.

Adolescent↗
PubMed1985

Hand-mirror variant of acute lymphoblastic leukemia. Evidence for early T-cell lineage in two cases by evaluation with monoclonal antibodies.

Lymphoid cells from two patients with hand-mirror variant of acute lymphoblastic leukemia (ALL) were studied with various monoclonal antibodies in attempts to determine their derivation and differentiation. The predominant feature of the malignant bone marrow cells was strong reactivity with antibody 3A1, which stains the majority of normal T-cells and is apparently present on all T-ALL cells. In addition, a less intense binding was observed with antibody 4F2, which reacts with activated or rapidly dividing cells, and antibody 10.2, which reacts with all thymocytes and most peripheral T-cells. Most other antibodies with a wide variety of specificities were not reactive or, in the case of a few anti-T-cell antibodies showed, by fluorescence-activated cell sorter analysis only weak staining on some cells. Sequential bone marrow studies in one patient, before and during treatment with chemotherapy, revealed a reduction of 3A1-positive cells, concordant with a decrease of malignant cells in the marrow. When involved lymph nodes, peripheral blood, or marrow were studied, similar reactivity patterns were found in all locations. The data obtained suggest that in both patients with hand-mirror variant of ALL, the malignant lymphoid cells were immature cells of early T-lymphocyte lineage. The relation of phenotype by monoclonal antibody analysis to hand-mirror morphologic type and biologic function is discussed.

Adolescent↗
PubMed1985

Total lymphoid irradiation in patients with refractory rheumatoid arthritis.

Eleven patients with rheumatoid arthritis that had been refractory to conventional drug therapy were treated with total lymphoid irradiation (TLI). Followup continued for 6 months in 9 patients, 12 months in 6 patients, and 24 months in 3 patients. At 6 and 12 months post-TLI, a significant improvement in clinical disease activity was demonstrated. Side effects noted during TLI included fatigue, nausea, diarrhea, and vomiting. One patient died of cardiorespiratory arrest, 2 patients died of kidney failure secondary to generalized amyloidosis, and 1 patient died of septic shock secondary to a multilocular septic arthritis. One patient experienced 2 episodes of septic arthritis; 2 patients manifested delayed wound healing. Immunologic assessments showed consistent lymphopenia in all patients. T lymphocyte subsets decreased after TLI, and showed a transient increase at 6 months post-TLI. The suppressed mitogen responsiveness, which was noted 2 months after irradiation, was found to increase almost to the pre-TLI levels at 12 months. The observed increase in morbidity and mortality after TLI is evidence that discourages the use of this therapeutic technique, at least in its present form.

Antigen-Antibody Complex↗
PubMed1985

Characterization of cell lines enhancing IL-2 production by human phytohemagglutinin-stimulated lymphocytes.

Certain cell lines were found to significantly enhance IL-2 production by phytohemagglutinin-stimulated T lymphocytes, and the mechanisms involved in mediating such an enhancement have been studied. All B-lymphoblastoid cell lines (B-CL) tested had an enhancing capability, even lines which were immature, surface immunoglobulin negative, or negative for EBV-associated antigens or Fc receptors. Furthermore, a B-CL lacking HLA-A, B, and C, antigens as well as a HLA-DR-deficient mutant line enhanced IL-2 production. Autologous B-CL as well as allogeneic lines were able to augment IL-2 production. Cell lines from patients with T-cell acute lymphoblastic leukemia did not stimulate, while more mature, DR-positive T-cell lines did. Although all HLA-DR positive cell lines, regardless of their derivation, provided enhancement, several lines of evidence, including blocking experiments with anti-DR antibodies, indicated that the reaction was not HLA-DR mediated. The enhancing determinant(s) appeared to be cell associated since CL supernatants were ineffective, and it may serve as an important additional signal to the preactivated IL-2-producer T-cell.

B-Lymphocytes↗
PubMed1985

Pulmonary sarcoidosis associated with acquired humoral and cellular immunodeficiency.

A previously healthy 27-year-old man with class II pulmonary sarcoidosis developed severe humoral immunodeficiency within the course of the disease with an IgG of less than 250 mg/ml and undetectable levels of IgA and IgM. Repeated skin tests were negative for seven common recall antigens. Cellular blood test demonstrated normal numbers of B cells and slight T-cell lymphopenia with a normal T-helper/suppressor subset distribution (ratio 1.6). In contrast, parallel examination of the bronchial alveolar lavage fluid (BAL) demonstrated highly elevated numbers of T cells with a subset ratio of 3.1 and significant numbers of activated T cells as revealed by the expression of Ia and Tac antigens. Functional in vitro assays showed a greatly decreased mitogenic response of blood T cells and diminished production of immunoglobulins. These data indicate that, despite a severely depressed systemic humoral and cellular immune system, T-cell activation can take place at the inflammatory site, potentially causing the lesions characteristic of sarcoidosis.

Adult↗
PubMed1985

Cultured T cells from patients with T cell chronic lymphocytic leukemia demonstrate a normal phenotype.

Peripheral blood mononuclear cells from eight patients with the rare T-cell form of chronic lymphocytic leukemia were isolated and cultured with Interleukin-2 (IL-2). In all but one case, cultured T-cells (CTC) were established. Various culture conditions were tested for their effectiveness; feeder layers proved valuable for expanding the cultures to large volumes. The CTC remained IL-2 dependent. Analysis of surface determinants on these CTC showed a polyclonal proliferation of T-cells. The distribution of subset markers in the patients' CTC population had completely changed in comparison to the "fresh" peripheral blood cell population but was similar to CTC initiated from healthy donors. Our data suggest that the patients' few contaminating normal T-lymphocytes expanded in culture, while the malignant cells were unresponsive to IL-2. This conclusion is supported by growth characteristics and morphology of the CTC.

Antigens, Surface↗
PubMed1985

IgE-containing circulating immune complexes in Churg-Strauss vasculitis.

In five patients with vasculitis, hypereosinophilia, and elevated serum IgE levels a diagnosis of Churg-Strauss syndrome was established. To identify a possible role of IgE in pathogenic mechanisms leading to the vasculitis, we performed a sequential precipitation of the patients' sera with different concentrations of polyethylene glycol (PEG) 6000. Using a radio immunosorbent test, we tested the precipitates obtained for IgE. Considerable amounts of IgE were traced in the serum precipitates of all patients, especially after the second precipitation step (4.0% PEG). In contrast, no IgE-containing precipitates were detectable in sera from patients with different allergic diseases and high IgE serum levels. Together with an increase in C3d serum levels and the failure to demonstrate C1q-binding material in patients' sera, these data suggest the involvement of IgE-containing immune complexes in the pathogenesis of Churg-Strauss vasculitis, activating the complement via the alternate pathway.

Antigen-Antibody Complex↗
PubMed1984

Preservation of the helper and suppressor/cytotoxic T-lymphocyte phenotype in continuous culture.

The objective of the present investigation was to culture helper or suppressor/cytotoxic T cell subsets after extensive purification in interleukin 2-containing medium to determine whether phenotype changes for OKT4/91d6- or OKT8/Leu-2a-defined antigens do occur with prolonged culture. Repeated and sequential analysis of such polyclonally activated cultured T cells documented stability of the OKT4/91d6+ and OKT8/Leu-2a+ phenotype. Both populations could be considerably expanded in culture. However, mixing experiments revealed a growth advantage of the OKT8/Leu-2a+ subset. A significant number of cells expressing both phenotypic markers was not detectable. While cultured T cells promoted on interleukin 2 were stable for expression of these functionally important differentiation markers, additional studies on activation antigens revealed high numbers of Tac+ cells at an early time of culture and decreasing numbers during further incubation. The expression of Tac antigen preceded the exponential expansion of the culture. In contrast, the number of cells bearing Ia determinants steadily increased with prolonged culture.

Antibodies, Monoclonal↗
PubMed1984

Rheumatoid non-lymphoid synovial cells and the induction of mixed leukocyte reactions. Low-density preparations containing Ia+ macrophages and dendritic cells are less stimulatory than peripheral blood non-T cells.

Interactions of autologous or allogeneic T cells with non-lymphoid synovial cells were investigated to study the mechanisms of T-cell activation in rheumatoid arthritis. The synovial cell fraction obtained by Percoll gradients contained an average of 31% cells positive for monocyte antigens and 62% intensely Ia-positive cells. Tissue cultures demonstrated large numbers of cells with a dendritic morphology. Mixed leukocyte reaction (MLR) cultures between these synovial cell preparations and autologous or allogeneic peripheral blood T cells as responder cells revealed low T-cell responsiveness with an average of 3900 dpm or 17 800 dpm, respectively, in contrast to 16 900 dpm or 79 600 dpm, using rheumatoid peripheral blood non-T cells (P less than 0.01), despite equivalent amounts of Ia antigens on both stimulator populations, as determined by cell-sorter analysis. The addition of indomethacin to these synovial cell/T cell co-cultures resulted in an enhancement of T-cell responsiveness; however, this increase did not reach statistical significance due to large test variations. Co-cultures of non-lymphoid synovial cells and PHA-stimulated autologous T cells induced a marked inhibition of T-cell proliferation that could partially be reversed by the addition of indomethacin. The reduction of monocyte-antigen-positive cells by depletion of iron phagocytic cells did not result in a significant enhancement of T-cell responsiveness. These data demonstrate that the majority of non-lymphoid synovial cells, despite the presence of large amounts of Ia-antigens, are not potent inducers of T-cell proliferation and strong suppressing cells in polyclonal T-cell activation. These effects do not appear to reside in the macrophage fraction alone and can only partly be attributed to the action of prostaglandins.

Arthritis, Rheumatoid↗
PubMed1984

Dissociation of helper/inducer T-cell functions: immunodeficiency associated with mycobacterial histiocytosis.

Mycobacterial histiocytosis is a generally fatal disease characterized by abundant amounts of undigested atypical mycobacteria present within tissue macrophages that diffusely infiltrate the affected lymph nodes. The immune functions of a 22-year-old man with infection due to Mycobacterium avium were investigated. Although the patient had a marked increase in serum immunoglobulin levels and detectable antibodies toward mycobacterial antigens, he had no cellular response to these antigens both in vivo and in vitro. There was an elevated proportion of blood cells with the helper/inducer (T4+) phenotype, but these cells showed a markedly decreased response to several T-cell mitogens, as well as to autologous and allogeneic cells. The patient's lymphocytes produced diminished amounts of immune interferon, and there was no detectable interleukin 2 (IL-2) activity after stimulation with phytohemagglutinin (PHA). The proliferative response of T4+ cells to pokeweed mitogen (PWM), however, was normal; 47% of these cells bore the Tac antigen, and the production of IL-2 using PWM was within the normal range. No phenotypical or functional abnormalities were found in peripheral blood monocytes. These findings suggest a dissociation of helper/inducer T-cell functions with intact B-cell help, but an impaired ability to activate tissue macrophages or to produce immune mediators.

Adult↗