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Biomedical subjects

D Lutz

Publications and source records attributed to D Lutz.

At least 109 records · Page 6Linked to original sources

Surface antigens defined by monoclonal antibodies as tumor markers in human leukemia.

The detection of surface-linked antigenic determinants by heteroantisera has greatly contributed to a better understanding of the heterogeneity of benign and malignant hematopoietic cells. The difficulties encountered in rendering these heteroantisera specific for a unique cell surface component have been a major drawback to a more rapid development of immunologic cell typing. With the introduction of hybridoma technology, it became possible to obtain monoclonal antibodies and markedly improve immunologic cell typing. We have, therefore, used this new technology for the production of monoclonal antibodies against human leukocyte surface antigens. This paper describes four cell type-specific monoclonal antibodies, which turned out to be very useful reagents in leukemia diagnosis. One of these antibodies, VIM-D5, is directed against a myeloid cell surface antigen. VIL-A1 is specific for the common acute leukemia associated antigen. VIB-C5 recognizes B-cell differentiation antigen and VIE-G4 is specific for glycophorin A, and thus detects erythroid precursor cells.

Antibodies, Monoclonal↗

[Diagnosis of leukemia with monoclonal antibodies].

The diagnosis and classification of leukaemic diseases is still primarily based on morphological and cytochemical criteria. Interpretational difficulties occur quite frequently, especially in acute leukaemias. Subjective morphological cell-type characterization--which is acquired only after many years of experience--is rather unsatisfactory in the long run. Therefore in order to obtain uniform results in all haematological areas, new methods are needed. In principle, immunological cell-type characterization represents an alternative method. By applying requisite antibodies practically any cell component can be demonstrated and quantitated. Up to recently the major obstacle to a more rapid development of immunological cell typing was the lack of specific antisera, but with the introduction of hybridoma technology it became possible to obtain monoclonal antibodies and thus, markedly improve immunological cell typing virtually overnight. We have, therefore, used this new technology for the production of monoclonal antibodies to human leucocyte antigens. This paper describes six of the cell-type specific monoclonal antibodies obtained, their suitability for diagnostic purposes and the classification of human leukaemias. With the help of these antibodies the majority of human leukaemias can now be typed. Without claiming completeness and in full awareness of the fact that a number of problems remain to be solved, we nevertheless believe that the presented data point to the possibilities opened up by this technology for leukaemia diagnosis in the future.

Animals↗

[Density distribution of human lymphocytes. II. Distribution patterns of malignant lymphocytes and their prognostic significance in patients with non-Hodgkin's lymphoma].

The aim of this study was to investigate the prognostic significance of density distribution profiles in non-Hodgkin lymphomas. Density profiles were evaluated by equilibrium centrifugation on linear polysucrose-metrizoat gradients. Biopsy cells from 44 untreated non-Hodgkin lymphomas in advanced stages according to their density patterns could be classified into one of two distinct groups: Group A lymphomas exhibited high to intermediate densities and resembled normal resting B or T lymphocytes; they showed low spontaneous proliferation and favourable histologies. Group B lymphomas exhibited light densities, resembling activated lymphocytes and frequently revealed high spontaneous proliferation and unfavourable histology. Within a minimal time of observation of 40 months only 28% of the group A but 75% of the Group B lymphomas died. Simultaneously performed surface marker studies excluded the possibility that variable proportions of normal lymphocytes contaminating the lymphoma suspensions are responsible for the two density groups. They rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into denser tumour clones with low spontaneous proliferation. We therefore conclude that analyses of density profiles from non-Hodgkin lymphomas represenmts a promising method for the prognostic classification of this disease.

Animals↗

Correlation of alkylating and mutagenic activities of allyl and allylic compounds: standard alkylation test vs. kinetic investigation.

Thirty-nine allylic and non-allylic compounds have been tested in the standard 4-(p-nitrobenzyl)pyridine (NBP) alkylating procedure and the Salmonella typhimurium mutagenicity assay. Fourteen of these were found directly mutagenic (without addition of S-9 mix activating enzyme system). With twelve of these compounds, a good correlation of alkylating and mutagenic potencies was established; the remaining two do not meet the chemical conditions of the NBP procedure on account of HCl elimination with these two compounds. The other 25 substances were inactive in both systems. The quantitative correlation proved to be almost linear in the lower activity ranges (E approximately 2; revertants/muml approximately 600). The reasons for some deviations from the linear relationship have been analyzed and discussed on the basis of structural features. In addition to the standard alkylation test, a modified NBP-test was performed in order to obtain kinetic data and activation energy values. The results with 6 representative allylic compounds show that the overall correlation is not substantially improved above that of the standard procedure: nonetheless, additional information on reaction characteristics is obtained with some substances.

Alkylating Agents↗

Prognostic significance of lymphocyte density distribution profiles in adult non-Hodgkin lymphomas.

Biopsy material from 24 adults with advanced stages of non-Hodgkin lymphomas (NHL) were examined for the distribution profiles of infiltrating cells following centrifugation to equilibrium on linear density gradients. Seven of these biopsies were predominantly composed of cells with high buoyant densities and 9 further biopsies predominantly of cells with intermediate buoyant densities. Both patterns were associated with favorable histologic features and with low proliferation of lymphoma cells. Intensive polychemotherapy was rarely required to achieve long-lasting disease control; in both groups, only 28% of patients died within a minimal observation period of 40 mo. In 8 biopsies, a predominance of light lymphoma cells was observed. This pattern was frequently associated with unfavorable histology and with high spontaneous tumor cell proliferation. Despite intensive polychemotherapy, rapid disease progression occurred in all cases, leading to death in 75% of the patients within a minimal observation period of 40 mo. Surface marker studies excluded the hypothesis that only the variable proportions of normal lymphocytes contaminating the lymphoma suspensions were responsible for the differences in the density distribution patterns described above; they rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into dense tumor clones with low spontaneous proliferation.

Adult↗

[Clinical studies and immunology in acute myeloid leukemia during chemo-immunotherapy].

14 patients with acute myeloid leukemia were treated with intermittent chemo-immunotherapy for maintenance of remission. At monthly intervals, they received 5 days of cytosine-arabinoside alternately combined with adriamycin or thioguanine or cyclophosphamide or CCNU. Two weeks later, 2 x 10(9) unirradiated allogenic blasts mixed with 5-50 units neuraminidase/ml were injected intradermally. Half the patients who had had many unfavourable prognostic factors at the time of diagnosis relapsed within 15 months (average duration of 1st remission 8 months). This result is comparable with the (past) results of chemotherapy alone. Seven of the patients still in first remission have at present reached an average remission duration of 17 months. Regular variations in the blood cell counts, which depended on chemo- as well as immunotherapy, were observed during the course of remission but not shortly before relapse. The extent to which peripheral lymphocytes could be stimulated varied noticeably from one patient to another and mostly increased with the progress of remission; however, to date no correlation to the clinical course was evident.

Adult↗

[The clinical significance of the Philadelphia chromosome in acute leukaemia (author's transl)].

So-called "Philadelphia-positive acute leukaemias" require varied therapeutic management. Additional chromosome anomalies together with Ph1 indicate an acute transformation of a Philadelphia-positive disease, requiring "non-myelotoxic" treatment and new therapeutic approaches. By contrast, "de novo" acute leukaemias with a Ph1-positive karyotype should be treated with intensive chemotherapy for the induction and maintainance of remission.

Acute Disease↗

Necrotizing myelopathy associated with acute lymphoblastic leukemia. Case report and review of literature.

The clinico-pathological findings are reported of a 16-year-old boy with acute lymphoblastic leukemia who during chemotherapy which included intrathecal Methotrexate developed a transverse cord lesion 5 months before death. Autopsy revealed necrotizing myelopathy of the T8--T10 segments and moderate lymphoblastic infiltration of the cerebrospinal meninges and spinal nerve roots. Neither parenchymal infiltration nor vascular lesions were found. The pathogenesis of this rare lesion associated with acute lymphoblastic leukemia remains obscure.

Adolescent↗

Rapid detection of polyamines in the sera of patients with colorectal carcinoma by liquid ion-exchange chromatography.

The polyamines spermidine and spermine and the diamines putrescine and cadaverine have been determined in their free and unbound state in the sera of patients with colorectal carcinoma. The obtained values were compared with normal control levels. Elevated levels of putrescine and spermidine were found in untreated patients and declined to the control range after surgical and chemotherapeutic treatment. Spermine levels remained unchanged throughout the observation at normal control levels.

Aged↗

[Morphology and index of nucleoli in malignant lymphomas].

The significance of morphology and the number of lymphocyte nucleoli was evaluated by electronmicroscopic sections of malignant lymphomas. It was not only the number and the size of nucleoli which characterized malignant lymphomas differing in histological respect, but above all the different morphology of the nucleoli. The prognostic significance of the nucleolus can be illustrated, if malignant lymphomas of a low grade malignancy with a preponderance of micronucleoli and a low nucleolar index are compared with a significantly higher nucleolar index and markedly increased macronucleoli. These differences are further supplemented by additional morphological properties of nucleoli in malignant lymphomas.

Cell Nucleolus↗