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Biomedical subjects

E Thiel

Publications and source records attributed to E Thiel.

At least 253 records · Page 14Linked to original sources
PubMed1987

Phenotypic modulation of chronic lymphocytic, prolymphocytic, and lymphoplasmacytic leukemia cells by TPA: induction of TRAP isoenzyme 5 and HD6 (CD22) antigen and enhancement of IgM messenger RNA.

B-cell neoplasias such as CLL can be viewed as models of monoclonal populations restricted within discrete ranges of B-cell maturation. It is unknown whether other B-cell leukemias such as prolymphocytic leukemia (PLL), lymphoplasmacytoid immunocytoma (IC), and hairy cell leukemia (HCL) involve different B lineages or are malignant variants of B cells in successive stages of development along the same lineage. Therefore in vitro maturation was induced with the phorbol ester TPA in leukemic cell samples from 10 CLL, 4 PLL, and 4 IC patients. Morphologically, both plasmacytic and hairy cell-like phenomena were induced. The latter unexpected finding was confirmed by reaction with HD6 (CD22) antibody which stains HCL but is unreactive with plasma cells, multiple myeloma, and CLL cells. Tartrate-resistant acid phosphatase was demonstrated in TPA-cultured CLL, PLL, and IC cells, and the same isoenzyme band as in HCL was revealed by isoelectrofocusing. On the other hand, an increase of IgM messenger RNA was detected in up to 20% of the cells in CLL cultures by single-cell in situ hybridization with fluoro-chrome-labeled DNA probes. An abundance of IgM messenger RNA characterizes lymphoplasmacytoid cells as found in IC. Our data demonstrate that CLL, PLL, and IC can be induced to realize a common genetic program which bears characteristics of HCL indicating that these four entities are more closely related than previously thought.

Acid Phosphatase↗
PubMed1987

Analyses of phenotype and genotype in acute lymphoblastic leukemias at first presentation and in relapse.

As a clue to the cellular origin of leukemic populations in relapse we analyzed 11 cases of acute lymphoblastic leukemia (ALL) by immunological and molecular genetic approaches. Blast cells obtained from both initial diagnosis and relapse were immunophenotyped using a variety of monoclonal antibodies; simultaneously we hybridized Southern blots of respective cell samples to immunoglobulin (Ig) heavy and light chain as well as to T-cell receptor beta-chain (T beta) sequences. While similar phenotypes were observed in both states of nine cases, comparison of Ig gene rearrangements revealed clonal variations, ie, appearance of an evoluted or novel leukemic cell clone in relapse beside identical leukemic populations in both states. One pre-T (ALL) patient, presenting with germline configuration of T beta gene sequences at diagnosis, exhibited a rearrangement of T beta gene sequences in recurrent disease. Another patient displayed T-ALL phenotype and T beta gene rearrangement at diagnosis but relapsed with a very immature phenotype and germline configuration for T beta sequences. Our results emphasize the value of molecular analyses in order to unravel the nature of leukemic relapse.

Acute Disease↗
PubMed1987

Monoclonal antibodies detecting plasminogen activators on the membrane of leukemic lymphoid cells of T-cell origin.

The specificities of six monoclonal antibodies produced against plasminogen activator of the human Bowes melanoma cell line are described. They have been used to detect membrane-bound plasminogen activator on cultured human lymphoid cell lines and in neoplastic human lymphocytic and myeloid cells of leukemic patients. These studies indicate that only certain phenotypic subsets of the T-cell lineage derived from patients with chronic lymphocytic leukemia or with Szezary syndrome express plasminogen activator on their surface membrane.

Animals↗
PubMed1986

[Comparison of CHOP and COP-BLAM chemotherapy in highly malignant non-Hodgkin's lymphoma].

The course of disease in 61 consecutive patients with non-Hodgkin lymphoma of high grade malignancy, treated between 1979 and 1985 with either CHOP or COP-BLAM regimen, was analysed retrospectively. Both groups showed a highly similar distribution of prognostic variables. COP-BLAM treatment resulted in significantly more complete remissions (23 of 27) than CHOP (11 of 29, P = 0.001). Life expectancy was, therefore, considerably higher in the COP-BLAM treated group. The mean observation period, however, was longer for CHOP-treated patients (37 vs. 30 months. The higher remission rate of the COP-BLAM regimen was not compromised by a substantial increase in toxicity; no therapy-related death was observed. Thus, the COP-BLAM regimen appears to be superior in inducing complete remissions in aggressive non-Hodgkin lymphoma. Actual survival curves suggest that this corresponds to an increased proportion of cured patients, but longer follow-ups are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Simultaneous demonstration of two antigens on single T cells using antibodies with contrasting labels.

We describe a double labeling method for the discrimination of 2 antigens on single cells. It consists of a combination of 3H-immunoautoradiography and immunocytochemistry applied to cells previously fixed on poly-L-lysine (PLL)-coated multispot slides. The method has been applied to various mouse cells contemporaneously labeled with 2 different monoclonal antibodies. In order to distinguish the attached antibodies unambiguously, they were labeled with contrasting markers. One of the antibodies was marked with tritium blackening the photographic film that covers the slide. The other was detected with the peroxidase-anti-peroxidase (PAP) method forming a reddish precipitate. The contrast between the reddish reaction product of the PAP-labeled antibody and the black silver grains allows cells, specifically labeled with both antibodies, to be distinguished from cells labeled with only one or neither of the antibodies. Tritium-labeled antibodies were introduced because of their advantage over antibodies labeled with iodine in the closer localization of the silver grains to the bound antibody and their much longer halflife (60 days versus 12 years). In this study we applied a tritium-labeled anti-Thy-1.1 together with anti-Lyt-1 monoclonal antibody for studying the distribution of the corresponding antigens on lymphocytes in the mouse thymus and lymph node cells.

Animals↗
PubMed1986

Homogeneously staining chromosomal region in a case of erythroleukaemia.

Cytogenetical analysis of bone marrow and peripheral blood cells in a case of erythroleukaemia revealed a complex karyotype with a stemline of 44 chromosomes. 1 marker chromosome bearing a homogeneously staining region (hsr) was found in each of the aneuploid cells examined. The hsr was localised to the chromosome regions 15q12 and 15p12. The possible function of amplified DNA sequences and the relationship of hsr to cell proliferation are discussed.

Aged↗
PubMed1986

Frequency and clinical significance of DNA aneuploidy in acute leukemia.

Analyses of the cellular DNA content were carried out in 446 patients with newly diagnosed acute myeloid (AML) and lymphoblastic (ALL) leukemias in order to assess the frequency of DNA aneuploidies and its relation to immunologic and morphologic subtypes as well as its prognostic relevance. Based on high resolution FCM analyses and standardized reference measurements, DNA aneuploidies were identified at a similar frequency in children and adults with AML (38.0% and 40.0%) and ALL (40.0% and 37.4%). In AML aneuploid DNA stemlines were significantly less frequent in FAB-M 1 cases as compared to the other morphologic subtypes (p less than 0.05), whereas the degree of DNA aneuploidy was significantly lower in M 1 and M 2 leukemias as compared to the M 4 and M 5 subgroups (p less than 0.05). In ALL non-T/non-B and C-ALL revealed a higher frequency of DNA aneuploidies than T- and Null-ALL cases (p less than 0.05). No differences in the response to induction therapy were found between patients with and without DNA aneuploidy in children or adults with AML or ALL. In the childhood ALL trial BFM 79/81, however, a significantly higher frequency of long term remissions was observed in children with DNA aneuploidy (0.91 versus 0.66 at five years, p = 0.053). A similar though not significant tendency was also revealed from the AML studies BFM 78 in children and 78/81 in adults. In the subsequent studies these differences could not be confirmed at present, possibly because of the considerably shorter observation time.

Adult↗
PubMed1986

[Leukemia cell analysis in the diagnosis of ALL/AUL: clinical value of currently available methods].

After morphology and cytochemistry, immunological leukemic cell diagnosis became a generally available method by the development of monoclonal antibodies. Besides an otherwise not possible classification of nonmyeloid leukemias according to T- or B-differentiation status, precision and standardization of leukemia diagnosis is accomplished by immunodiagnostic means in an experimental way, an important point for therapy studies. In children, the common ALL--a precursor B-ALL type--was prognostically more favorable than the T-ALL which differs also in clinical appearance and in prognostic factors. In adults, however, T-ALL had a better prognosis than common ALL in a prospective trial. The heterogeneous Null-ALL which makes up 23% of ALL in adults and 5% in children, was the prognostically most unfavorable form besides the rare B-ALL (1-2%), the immunophenotype being an independent prognostic variable. Immunodiagnostic means are therefore of utmost clinical importance compared to other methods such as cytogenetic and electron microscopy that are not performable in a corresponding extent.

Adult↗
PubMed1986

Induction of features characteristic of hairy cell leukemia in chronic lymphocytic leukemia and prolymphocytic leukemia cells.

In vitro maturation was induced with 12-O-tetradecanoylphorbol-13-acetate in leukemic cell samples from patients with chronic lymphocytic leukemia (n = 10) and prolymphocytic leukemia (n = 4). The cells were studied for morphology, for immunological markers using the fluorescence activated cell sorter, and for acid phosphatase isoenzymes using both cytochemistry and isoelectrofocusing. Morphologically the induced changes included appearance of cells with an excentric nucleus and basophilic cytoplasm and eventually of cells with many fine cytoplasmic projections ("hairs"). Analysis of immunological markers by flow cytometry revealed that the monoclonal antibody defined cell surface molecule HD6 (CD22), which is strongly expressed on hairy cell leukemia (HCL) but absent from plasmacytoma and plasma cells, can be induced or enhanced in the leukemic samples. In the study of acid phosphatase isoenzymes using cytochemistry we observed the induction of the tartrate resistant isoenzyme. Further, using isoelectrofocusing we could demonstrate the induction of the same band of tartrate resistant acid phosphatase with an isoelectric point of 9.0-9.7 as detected also in HCL. This particular isoenzyme is considered characteristic of HCL but is absent in plasmacytoma. Our data demonstrate that chronic lymphocytic leukemia and prolymphocytic leukemia cells can be induced to realize a common genetic program which bears characteristics of HCL, indicating that these three entities are much more closely related than previously thought.

Acid Phosphatase↗
PubMed1985

[Cutaneous Kaposi sarcoma in chronic lymphatic leukemia].

A classical Kaposi sarcoma, a tumor appearing sporadically mainly in elderly males, occurred in its typical cutaneous location in a male aged 67 years. Routine laboratory investigations revealed a marked leucocytosis which, with the aid of a bone-marrow biopsy and immunocytological methods, could be attributed to a hitherto undetected chronic lymphatic B-cell leukaemia.

Aged↗
PubMed1985

[Rhino-cranial mucormycosis in acute leukemia].

The diagnosis of acute lymphatic non-T-non-B leukaemia of common ALL type was confirmed in a 22-year-old woman. Cytostatic treatment brought full remission for 21/2 years. Renewed cytostatic treatment for recurrence brought about a mucormycosis in the mid-face region during a period of protracted agranulocytosis, despite antibiotic prophylaxis with ketoconazole and cotrimoxazole. The causative mucor organism was demonstrated in smears and biopsy material. The infection was successfully treated with i.v. amphotericin B and débridement of the affected tissue. There remained large tissue defects in the region of gum, nose, upper lip and right oral cavity. Previously the mortality rate of mucormycosis in the course of leukaemia was 100%.

Adult↗
PubMed1985

In-vitro induction of some features of hairy cell leukemia in chronic lymphocytic leukemia and immunocytoma cells.

In an attempt to induce in vitro differentiation we exposed cells from patients with chronic lymphocytic leukemia (CLL) and with immunocytoma (IC) to 12-0-tetra-decanoylphorbol-13-acetate (TPA) at 160 nM. After 3 to 5 days of culture cells became enlarged and the CLL cells developed a basophilic cytoplasm with an excentric nucleus. In some instances cells with many fine projections were seen. We then employed the monoclonal antibody (MAB) HD 6, which was generated against hairy cell leukemia (HCL) cells and reacts most strongly with such cells but is unreactive with plasmocytoma cells and with most CLL cells. TPA treatment induced a greatly enhanced HD 6 binding in CLL and IC cells compared to controls as demonstrated by indirect immunofluorescence. Cytochemical studies revealed that at the same time an acid phosphatase was induced, which was found to be tartrate-resistant in every instance tested. Thus, several features of HCL can be induced in CLL and IC demonstrating the close relatedness of these entities.

Cell Differentiation↗
PubMed1985

Quantitation of antibody uptake on A group erythrocytes using immunoautoradiography and monoclonal IgM anti-A.

The number of antibody molecules on individual erythrocytes was counted in A1, A2, A3 B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A1. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A1 greater than A2 greater than Ax greater than A3B. When compared to the average for total A1 adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A1 adult red cells was 5.6 +/- 3 X 10(4), while A2 had 0.85 +/- 0.35 X 10(4) molecules, thus showing a significant quantitative variation.

ABO Blood-Group System↗
PubMed1985

Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias.

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.

Aclarubicin↗