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Biomedical subjects

C Ludwig

Publications and source records attributed to C Ludwig.

At least 109 records · Page 6Linked to original sources

Evidence for selection of homogeneously staining regions in a human melanoma cell line.

Cytogenetic analysis of tumor cells from a human malignant melanoma was performed on both the primary tumor colony-forming cells and a cell line (HA-A) established subsequently from the clonogenic population. Chromosome-banding analysis demonstrated identical karyotypic alterations in both the tumor colony-forming cells and the HA-A cell line, documenting their origin from a common precursor. The most distinctive chromosome alterations shared between tumor colony-forming cells and the HA-A cell line were double-minute bodies (DMs) and a homogeneously staining region (HSR) on chromosome 7 at band p22. This represents the first observation of DMs or HSRs in cells from a human malignant melanoma. The frequency of HSR-bearing cells observed in the original tumor was less than 1%, while DM-containing cells were present in greater than 90% of all cells examined. In contrast, serial chromosome harvests at early passage of the HA-A cell line revealed positive selection for HSR-bearing cells with concomitant loss of DM-containing cells after increasing time in vitro. Following the ninth serial passage in vitro, HSRs were observed in 100% of cells with DMs no longer observed in the HA-A cell line. The finding of an HSR-bearing marker in the original tumor sample supports the view that HSRs are not an artifact of in vitro monolayer growth. However, our results demonstrate that the frequency of HSR-bearing cells within established cell lines may reflect in vitro selection and therefore not accurately reflect the frequency of this population in vivo.

Adult↗

[Intact cellular immune response in patients with locally metastasizing breast carcinoma at the time of diagnosis].

Reduced cellular immune response is well documented in patients with advanced breast cancer. To investigate immunocompetence at the time of diagnosis, 104 patients with breast cancer staged according to the TNM classification were studied preoperatively and compared with 95 age matched healthy women. Tests of blood mononuclear leukocytes included lymphocyte and monocyte counts, determination of rosette forming T (SER +) and B (MER +) lymphocytes, T lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin, SBA), lymphocyte transformation tests with PHA and ConA and colony formation of T cells in agar (TL-CFC). Two age groups (A: 30-50, B: 51-70 years) and the different tumor stages (I-IV) were analyzed. Patients and controls did not differ in absolute numbers of lymphocytes, T and B cells. In patients of group B the absolute number of monocytes was slightly increased in stages II and III and significantly in stage IV (p less than 0.025). Similarly, the lymphocyte response to PHA was significantly reduced in stage IV group B only (p less than 0.05). ConA induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age matched controls, in whom T lymphocyte subsets were determined, the relative numbers of T cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or SBA were similar. In conclusion, in breast cancer, at the time of diagnosis, blood T lymphocyte populations and functions are not altered except in elderly patients with disseminated disease. The monocytosis and reduced PHA responsiveness observed in the latter group may be related phenomena.

Adult↗

[OKT-8+ suppressor T-lymphocytes are increased in patients with stable multiple myeloma].

T-lymphocyte subpopulations were studied in 68 patients with monoclonal gammopathies and 27 age-matched healthy controls using the monoclonal antibodies (mAb) OKT-3, OKT-4 and OKT-8. 13 patients had untreated multiple myeloma (MM), 51 had MM and were receiving intermittent pulse chemotherapy or were in remission and followed up without treatment. Four patients had a monoclonal gammopathy of unknown significance (MGUS). Analysis of the data for disease activity demonstrated a significant imbalance of T-lymphocyte subpopulations in patients with stable (plateau phase) MM. In these patients the relative number of cells with suppressor phenotype (OKT-8 positive) was significantly increased (p less than 0.0001) and the relative number of cells with helper phenotype (OKT-4 positive) significantly decreased (p less than 0.0001) when compared with normal controls or patients with active MM. Patients with stable disease also had a significantly higher absolute number of OKT-8 positive cells than patients with active MM (p = 0.04). Additionally, in vitro functional studies showed significant suppression of clonal growth of the human myeloma cell line (RPMI 8226) by a soluble suppressor factor of OKT-8 positive cells from the peripheral blood of healthy donors as well as from bone marrow aspirates of patients with MM. These findings support the hypothesis that T-lymphocyte subpopulations play an important role in the control of proliferation of the myeloma cell clone in patients with low cell mass (stable phase) multiple myeloma.

Adult↗

Monoclonal antibody against a membrane antigen characterizing leukemic human B-lymphocytes.

In the diagnosis of non-Hodgkin's lymphomas, the ready characterization of the neoplastic cell lineage by analysis of cell surface markers is of great importance. We present evidence for the existence of a human B-leukemia-associated antigen recognized by a complement-fixing monoclonal antibody (anti-Y 29/55). A hybridoma was produced by fusing mouse myeloma cells and splenocytes of a mouse immunized against lymphoid cells of a patient with B-cell chronic lymphocytic leukemia. Characterization of anti-Y 29/55-reactive normal and malignant leukocytes was demonstrated by cytolysis and indirect immunofluorescence. This revealed reactivity with an antigen on B-lymphoma cells (11 patients), on leukemic lymphocytes in B-cell chronic lymphocytic leukemia (13 patients), and on malignant cells in hairy-cell leukemia (two patients) but not on leukemic cells of T-cell acute lymphoblastic leukemia (one patient), on T-lymphoma cells (one patient), on cells of acute myeloblastic leukemia (four patients), or of chronic myeloid leukemia (four patients). No specific cytolysis occurred with B- and T-peripheral blood lymphocytes from (a) healthy donors (16 individuals), (b) patient with reactive lymphocytosis (one patient), (c) nonleukemic multiple myeloma (six patients), or (d) Hodgkin's disease (three patients). Surface immunoglobulin-positive, sheep RBC-negative lymphocytes isolated from human spleen (three individuals), tonsils (seven individuals), and lymph nodes (one individual), however, were recognized. It is concluded that leukemic B-cells carry a marker characteristic of nonrecirculating sessile B-lymphocytes.

Adolescent↗

[Determination of leukemic B-lymphoma cells with the monoclonal antibody anti-Y 29/55].

The monoclonal antibody anti-Y 29/55 recognizes a group specific antigen on sessile human B-lymphocytes which do not belong to the recirculating lymphocyte pool. The occurrence of this antigen in malignant NHL, with or without leukemic state, and in other leukemias has been studied. The antigen was expressed on cells of various histologic B-cell types but not on leukemic cells of ALL, T-lymphoma, AML or CML. It is concluded that in malignant B-lymphoma, B-CLL and HCL, cells appearing in blood carry a marker characteristic of virgin or activated sessile B-lymphocytes. Anti-Y 29/55 permits differentiation of such cells from normal recirculating B-cells and other leukemic cells including ALL, AML and CML. In follow-up studies this antibody may be helpful in detecting early leukemic output. B-lymphocytic leukemia may reflect a disproportion between binding sites on the lymphatic reticulum and the neoplastic cells bearing this antigen, which might be involved in binding of B-lymphocytes to the supporting lymphatic reticulum.

Antibodies, Monoclonal↗

[The diagnostic value of T- and B-rosette formation and the unspecific acid esterase in the differential diagnosis of acute and chronic leukemia].

The diagnostic significance of acid non-specific alpha-naphthyl-acetate (ANAE) and of rosette formation of leukemic cells with sheep and mouse erythrocytes was studied in 8 patients with acute myeloic leukemia (AML), in 4 patients with acute lymphatic leukemia (ALL) and in 14 patients with chronic lymphatic leukemia (CLL). ANAE showed typical diffuse cytoplasmic activity in all cases of AML. The enzyme activity was granular in both of the lymphoid malignancies, T-ALL and B-CLL, allowing differentiation from AML but not between B- and T-leukemia cells. Rosette formation with mouse erythrocytes (ME) was diagnostic in all 14 cases of CLL and superior to labeling of surface immunoglobulin (8 of 14 cases positive). ME-rosette forming myeloblasts were detected in 2 of 4 evaluated cases of AML. Rosette formation with sheep erythrocytes (SE), including cytological evaluation of rosette-forming cells, was diagnostic in all cases of ALL (= T-ALL). In 6 of 9 patients with AML, however, rosette formation with SE was observed in a few cells, including myeloblasts with Auer rods. The occurrence of blasts in myeloic leukemia carrying lymphoid cell markers is discussed in the light of recent findings, according to which lymphoblastoid cells may arise in the course of myeloic leukemia requiring antileukemic treatment different from that of AML.

Animals↗

[Tumor stem cell cultures on agar: 1st results].

Hamburger and Salmon have recently developed an in vitro assay for human tumor stem cells which permits formation of colonies of human solid tumors and lymphomas in soft agar. In 50 patients with solid tumors or lymphomas studied by us, tumor colonies grew from effusions and biopsies in 75% of patients (17 of 21) with histologically or cytologically involved specimens. Lymphoid colony growth was obtained in about 25% of specimens (5 of 19) including malignant lymphomas. Conversely, no colony growth was observed in 10 cases where the biopsies or effusions were histologically or cytologically negative. The effect of various conditioned media on tumor growth in agar was investigated. Colony formation of solid tumors was promoted to an especially marked extent by cell-free malignant effusions. This assay yields satisfactory results in solid tumors and appears useful for investigation of different cytotoxic effects of anticancer drugs on the survival of human tumor colony-forming cells.

Agar↗

[Examinations on the behaviour of grampositive and gramnegative bacteria on aluminium foil (author's transl)].

The survival times of Staph. aureus, Strept. faecalis, E. coli, Klebs. pneumoniae, Ser. marcescens and P. aeruginosa were found out on aluminium foil. It was examined whether there exists a dependence on the initial colony count and in mixed cultures a mutual influence of the several species of bacteria. The longest survival times were found among the grampositive cocci. Ser. marcescens and Klebs. pneumoniae could no more be indicated after 19 days in case of initial colony count of log 7.0/cm2; E. coli could no more be shown after 14 days. P. aeruginosa had the shortest survival time. The dependence on the initial colony count was ascertained in 3 different concentrations of bacteria. The highest concentrations showed the smallest reduction of cocci and the longest survival times of Enterobacteriaceae respectively. The middle and lowest initial colony counts showed quicker reduction or shorter survival times. Ser. marcescens was more resistant to drying than Klebs. pneumoniae. The quickest dying rates showed P. aeruginosa without any dependence on initial colony count. In mixed cultures with Staph. aureus or Strept. faecalis survival times of Enterobacteriaceae were longer; the same result gave Klebs. pneumoniae in culture together with Ser. marcescens. The following explanation might be possible: because of the drying resistance of grampositive cocci the total bacteria number in these mixed cultures after several days is higher than in monocultures of E. coli, Klebs. pneumoniae or Ser. marcescens. This protects the Enterobacteriaceae against external influences for a longer time. Therefore it is understandable that the effect increases with the length of duration. The same interpretation could apply to the mixed cultures of Klebs. pneumoniae/Ser. marcescens.

Aluminum↗

Effects of D-600 and its optical isomers on force of contraction in cat papillary muscles and guinea-pig auricles.

1 (--)-D-600 and (+)-D-600 exerted concentration-dependent negative inotropic effects in papillary muscles from cats, the potency of (--)-D-600 being about 100 times greater than that of (+)-D-600. The action was more pronounced at high than at low frequencies of stimulation. Time to peak force, relaxation time and therefore also total duration of contraction were not significantly affected by the drugs. 2 The negative inotropic effects of both drugs were not reversible after washing in drug-free solution for 60 min at all concentrations tested. 3 The same negative inotropic effects were seen in guinea-pig left auricles with the racemic mixture of both isomers. 4 Uptake measurements of D-600-[nitrile-14C] in isolated left auricles of guinea-pigs showed the drug to be accumulated in the myocardial tissue; tissue-medium ratios from 1.25 to 6.0 were found at exposure times from 1 to 100 minutes. Preparations which were loaded first with D-600-[nitrile-14C] for 100 min and then washed in drug-free solution for different times lost up to about 80% of the initial radioactivity, whereas the depression of force of contraction was not reversible. 5 The results show that there are marked quantitative differences between the actions of (--)-D-600 and (+)-D-600 on isometric force of contraction in cat papillary muscles. Although the time course of the uptake of D-600-[nitrile-14C] and the development of the negative inotropy in guinea-pit left auricles were reasonably well related, the magnitude of the negative inotropy does not seem to be dependent on the total tissue concentration once the negative inotropic effect has been fully developed.

Animals↗