Search PubMed⌕ Search

Biomedical subjects

M Gramatzki

Publications and source records attributed to M Gramatzki.

At least 19 recordsLinked to original sources
PubMed1992

Multiple chromosomal changes and karyotypic evolution in a patient with myelofibrosis.

Several subclones were identified in unstimulated peripheral blood cells from a patient with chronic myeloproliferative disease, which was classified as myelofibrosis by morphologic terms. These subclones were characterized by an unusual number of different karyotype anomalies. Some of the more complex chromosomal rearrangements could be clearly defined by fluorescence in situ hybridization. Chromosome arms involved in clonal aberrations were 1q, 3p, 6p, 7q, 11q, 13q, 15q, 17q, 18p, and 20q. Reconstruction of karyotype evolution was attempted by karyotypic analysis of 100 metaphase spreads each in two separate investigations.

Aged↗
PubMed1992

Treatment of relapsed or refractory adult acute lymphocytic leukemia.

Sixty-six adult patients were treated for relapsing or refractory acute lymphocytic leukemia (ALL). The induction treatment consisted in a (1) first phase with vindesine 3 mg/m2 intravenously (IV) on days 1, 8, and 15; daunorubicin 45 mg/m2 IV on days 1, 8, and 15; erwinia-asparaginase 10,000 U/m2 IV on days 7, 8, 14, and 15; and prednisone 60 mg/m2 orally on days 1 to 21 and a (2) second phase with cytarabine 3000 mg/m2 as a 3-hour infusion two times a day on days 1 to 4 (in patients greater than 50 years of age we used 1000 mg/m2), and etoposide 100 mg/m2 IV on days 1 to 5. Side effects of induction Phase I were predominantly hematologic with subsequent infections. In Phase II, some patients additionally had gastrointestinal, cutaneous, ocular, and hepatic toxicity. Five patients died during Phase I and another died during Phase II. Five of these patients had T-cell ALL. Thirty-four (64%) of 54 patients in their first relapse had a complete remission (CR) with a median disease-free survival (DFS) of 2.9 months. The median overall survival (OAS) was 6.6 months. Seven of 12 patients with primary refractory disease, a second relapse, or relapse after bone marrow transplantation (BMT) had a CR. The CR rate and survival after first relapse was significantly better in patients with a preceding CR of more than 18 months compared with those with a shorter preceding remission. The leukocyte count was a second significant but not independent risk factor. There was a negative correlation between the leukocyte count and the duration of the preceding CR. The duration of the preceding CR was the major prognostic factor for survival in multivariate analysis. Twenty-two patients received BMT. None of nine patients with autologous BMT is alive and disease-free; 5 of 13 who underwent allogeneic BMT are. It was concluded that this treatment efficiently induced remission with tolerable toxicity. The remission duration should be improved by optimized consolidation treatment.

Adult↗
PubMed1991

Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor.

Fc receptors are important effector molecules of neutrophilic granulocytes (polymorphonuclear neutrophils [PMN]), connecting phagocytic cells and the specific immune response. Neutrophils from healthy donors express the low-affinity receptors for IgG Fc gamma RII (CD32) and Fc gamma RIII (CD16), but not the high-affinity receptor Fc gamma RI (CD64). The latter has been found on neutrophils from patients with certain bacterial infections and can be induced in vitro after incubation with interferon-gamma. We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF). PMN from patients receiving rhG-CSF displayed higher cytotoxicity against Daudi lymphoma cells in vitro compared with control patients and with healthy donors. Fab fragments against Fc gamma RII (monoclonal antibody [MoAb] IV.3) inhibited neutrophil-mediated cytotoxicity of healthy donors but not of patients during rhG-CSF therapy. Therefore, expression of Fc receptors by PMN was investigated by flow cytometry and the mean fluorescence intensity (MFI) was compared. After staining with MoAb 32.2 against Fc gamma RL, the median MFI of neutrophils from G-CSF patients (median, 4.78; range, 2.40 to 8.50; n = 5) was significantly higher (P = .002 and P = .001, respectively) than the median MFI of patients not receiving G-CSF (median, 1.23; range, 1.01 to 1.58; n = 6) and the median MFI of healthy donors (median, 1.04; range, 0.67 to 1.12; n = 6). Fc gamma RI disappeared after the discontinuing of the G-CSF injections, but was reinduced during the next treatment cycle with rhG-CSF. The high expression of Fc gamma RI during rhG-CSF therapy correlated with enhanced cytotoxicity. In vitro incubation with rhG-CSF also enhances cytotoxicity, but only minor increments in Fc gamma RI expression were observed. Thus, during in vivo application of rhG-CSF neutrophils acquire an additional potent receptor for mediating tumor cell killing in vitro by induction of the high-affinity receptor for IgG (Fc gamma RI, CD64).

Antibodies, Monoclonal↗
PubMed1991

Monoclonal antibodies EBU-141 (CDw75) and EBU-65 allow reliable distinction between mature and pre-B-cell tumors in suspension and on tissue sections.

Two new monoclonal antibodies, EBU-65 and EBU-141, were raised by immunization with plasma cell line U-266. Both antibodies strongly react with B lymphocytes in immunofluorescent staining as well as on paraffin-embedded sections. More than 200 leukemias and lymphomas were tested, and for both antibodies reactivity was found only with "mature" B-cell tumors but not with precursor B-cell leukemias. None of the non-B-lineage hematolymphatic tumors tested was stained by EBU-141 or EBU-65. A subpopulation of T lymphocytes particularly present in nonmalignant pleural effusions was detected by EBU-65 additionally. Although EBU-141 was clustered as CDw75 and EBU-65 as "unique," a close relationship of the staining pattern was found and both antibodies react with a sialyltransferase. In particular, CDw75 antibody EBU-141 was demonstrated to be very useful for immunophenotyping of B-cell neoplasias, while EBU-65 reacted with most multiple myelomas and a subgroup of "activated"-appearing T cells.

Animals↗
PubMed1990

Melphalan and prednisone (MP) versus vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAM Dex) induction chemotherapy and interferon maintenance treatment in multiple myeloma. Current results of a multicenter trial. The German Myeloma Treatment Group.

277 untreated multiple myeloma patients of stage 1 (n = 33), II (n = 106) and III (n = 138) entered the study. Patients of stage II presenting a progressive tumor (n = 64) initially or during observation (n = 14) were treated with MivP (remissions: 61%). 138 patients of stage III were randomized to receive MivP or VBAMDex treatment. 51% of MivP treated patients responded versus 70% of the VBAMDex group. 71 responders of stage II and III with stable disease were randomized on Ifn-alpha maintenance versus no maintenance treatment. The relapse rate in both groups was 50% after 7 months. 75% survival was greater than 36 months in stage II and 11 months in stage III patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Synovial fluid involvement in null cell acute lymphoblastic leukemia diagnosed with monoclonal antibodies.

Rheumatic symptoms in patients with leukemia are not uncommon. Often they delay correct diagnosis and therapy. We describe a patient presenting with oligoarticular joint disease in whom immunological analysis of synovial fluid (SF) led to the detection of leukemic cells in the joint. Moreover, analysis with a variety of monoclonal antibodies established the diagnosis of acute lymphoblastic leukemia of null cell type with phenotypically identical malignant cells present in the bone marrow, peripheral blood and SF. Our investigations demonstrate that analysis with monoclonal antibodies is helpful in characterizing joint involvement in patients with leukemia.

Acute Disease↗
PubMed1987

Intralymphatic interleukin-2 treatment of a hemophiliac AIDS patient with defective interleukin-2 production.

To improve immune functions in an interleukin-2 (IL-2) deficient hemophiliac AIDS patient suffering from severe Pneumocystis carinii pneumonia, treatment with IL-2 was started in addition to standard antimicrobial therapy. Highly purified IL-2 was administered subcutaneously and then repeatedly intralymphatically in a manner similar to pedal lymphography. No toxicity was observed. The patient temporarily improved clinically as well as with regard to immunological functions. Particularly the in vitro response to phytohemagglutinin (PHA) could partly be restored, and skin tests revealed improved response to recall antigens. These findings indicate that IL-2 can be administered safely and effectively by the intralymphatic route and may--in addition to antibiotics--be of value in AIDS patients with severe opportunistic infections.

Acquired Immunodeficiency Syndrome↗
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↗