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W Heit

Publications and source records attributed to W Heit.

At least 73 records · Page 4Linked to original sources
PubMed1983

[Properties of Hodgkin cell lines. Possible significance for pathophysiology and clinical medicine].

In the last three years, five permanently in-vitro growing cell cultures with malignant properties were established from tumour material of patients with histologically confirmed Hodgkin's disease. Four cell lines have been maintained in culture. L 428 had identical characteristics in every respect with Hodgkin and Sternberg-Reed cells, tested in-vivo on biopsy tissue. The other lines--L 538, L 540 and L 591 - had certain characteristics of Hodgkin and Sternberg-Reed cells with a number of markers, but were not fully congruent. All lines reacted with a heterologous antiserum against L 428, which selectively cross-reacted with Hodgkin and Sternberg-Reed cells in fresh biopsies. Two sublines, L 428 KS and L 428 KSA, were established from L 428 by modifying the culture medium. Tests on L 428 KS cells with conventional methods and with monoclonal antibodies demonstrated that this line carried antigens of myeloid cells; however, it could not be definitely placed into any haematopoetic line. Conditioned medium of L 428 and its sublines showed CSF activity (colony-stimulating factor) and suppression of cell-mediated cytolysis.

Acid Phosphatase↗
PubMed1983

Production of colony-stimulating factors by Hodgkin cell lines.

This work was performed with L 428, a cell line established in 1978 from a patient with Hodgkin's disease. These in vitro cells represent counterparts of in vivo Hodgkin and Sternberg-Reed cells. L 428 and its derived sublines produce a significant amount of colony-stimulating factor (CSF) compared to standard preparations of CSF (fetal liver conditioned medium). Hodgkin-cell-derived conditioned medium, tested in cord-blood assays and in semi-solid agar systems, induced myeloproliferation predominantly. Production of CSF is independent of fetal calf serum concentration in the cultures. L 428-conditioned medium could provide an excellent source for characterization and purification of granulocyte CSF.

Cell Line↗
PubMed1983

Hodgkin's disease cell lines: characteristics and biological activities.

In the last 4 years we have established five long-term cultures from tumor material of Hodgkin's disease. The in vitro cells have malignant characteristics and represent the in vivo Hodgkin- and Sternberg-Reed-cells as shown by the identity of multiple properties. Common immunological, functional, and morphological assays did not characterize the in vitro cells as a known cell type of lymphoid, myeloid, or monocytoid tissue. The in vitro Hodgkin's disease cells are biologically active by producing factors involved in regulation and promotion of immunological response and granulopoiesis. The relevance of the findings for pathogenesis and clinical appearance of Hodgkin's disease is discussed.

Antibodies, Monoclonal↗
PubMed1982

[Drug induced agranulocytosis].

Drug-induced agranulocytosis comprises a severe selective neutropenia in a hypersensitive individual. The compelling problem in a single case to determine the etiology of agranulocytosis results from multiple drug consumption, use of composed preparations and the unknown relative risk of most of the incriminated drugs. Immune and toxic mechanisms may be involved, however, the underlying pathomechanism does not correlate with typical hematological and clinical features of agranulocytosis. Prognosis is associated with the infectious state of the patient and the duration of the neutropenic phase which reflects the degree of impairment of bone marrow hemopoiesis. After withdrawal of all potentially hazardous drugs treatment of agranulocytosis follows the therapeutical approach in severe neutropenias due to cytostatic drug exposure.

Agranulocytosis↗
PubMed1982

Characteristics of Hodgkin's disease-derived cell lines.

In the last 3 years we were able to establish five long-term in vitro cell cultures from biopsy specimens taken preterminally from four patients with histologically proven Hodgkin's disease (nodular sclerosing type, clinical stage IVB). Four of the lines are continuously proliferating in vitro; one culture stopped growth for unknown reasons after 7 months. When culture conditions were modulated, the first culture, L 428, gave rise to two sublines: L 428 KS, after adaptation to calf serum, and L 428 KSA, permanently growing as an adherent monolayer line after treatment with a phorbol ester (12-O-tetradecanoylphorbol-13-acetate) for 3 weeks. Cell-marker analysis by conventional means (SIg, cIg, rosette formation, Epstein-barr virus reactivity, cytochemistry, phagocytosis, and lysozyme production) and with monoclonal antibodies directed against various human lymphoid, myeloid, and monocytoid antigens showed that the tested cell lines are clearly different from all hitherto described hematopoietic lines; they most likely represent a cell type resembling an early myeloid-monocytoid progenitor cell. Conditioned medium of the L 428 cells and its two sublines showed colony-stimulating factor activity and suppression of spontaneous cell-mediated cytolysis of L 428 KS and K 562 cells.

Adult↗
PubMed1982

Extrarenal erythropoietin production by macrophages.

Murine bone marrow and adherence-separated spleen cells cultured on hydrophobic, gas-permeable Teflon foils (petriperm dishes) can be shown to synthesize and secrete erythropoietin (Epo) and colony-stimulating activity (CSA) simultaneously into the surrounding medium. The Epo activity in the supernatants of primary cultures as measured by the fetal liver erythroid colony-forming technique, from adherent and nonadherent spleen cells, increases over the first 7 days in culture, followed by a plateau until 14 days. Use of the macrophage-specific cytotoxic agent, crystalline silica, as a tool to release residual Epo contained in these cells produces a similar time-Epo activity curve to that found in the primary supernatants. This, together with functional and morphological examination of the cells, indicates that macrophages are responsible for this activity. The total Epo activity released from adherent and nonadherent spleen cells at plateau levels was estimated to be 25 mU/ml culture/day. Weekly subcultivation of bone marrow and adherence-separated spleen cells initiated from primary cultures demonstrated a massive increase in both Epo activity and CSA above that obtained for the primary cultures. Subcultivation could be continued for at least 6 wk. These results, together with the reversible inhibition of Epo and CSA production by cycloheximide, demonstrate that these molecules are synthesized by the macrophage. The evidence supports the hypothesis that the macrophage is involved not only in extrarenal Epo production, but also in the possible short-range regulation of hemopoiesis.

Animals↗
PubMed1981

Release of erythropoietin from macrophages by treatment with silica.

An erythropoietic stimulating factor (ESF) can be shown to be released from preincubated macrophage-containing cell suspensions from mice by the macrophage-specific, cytotoxic agent, silica. A concentrated silica-treated spleen cell supernatant containing ESF is shown to cause a dose-dependent increase in 59Fe incorporation into red blood cells using the in vivo polycythemic mouse bioassay. The ESF from the same supernatant can also be neutralized by anti-erythropoietin. A second concentrated supernatant fractionated using wheat germ lectin-Sepharose 6MB and compared to either unfractionated or fractionated step III erythropoietin (Ep), tested in vitro using the erythroid colony-forming technique and 12-day fetal liver as target cells, indicates parallelism of all linear dose-response lines. This, together with the in vivo data, strongly suggests that the ESF released from macrophages treated with silica is, in fact, Ep. Substituting Ca2+ ions for fetal calf serum in the preincubation procedure results in the same activity being released compared to the presence of 1% or 20% fetal calf serum.

Animals↗
PubMed1980

An erythropoietic stimulating factor similar to erythropoietin released by macrophages after treatment with silica.

An erythropoietic stimulating factor (ESF) can be detected in the supernatant from fetal liver and adult bone marrow and spleen cells when preincubated with the macrophage-specific cytotoxic agent, silica. Stimulation is observed in 12-day fetal liver CFU-E cultures in the absence of added erythropoietin (Ep). The concentration of ESF in the supernatant added to CFU-E cultures is dependent on the preincubated cell dose and the volume added. The stimulating activity is abolished when mice are hypertransfused and increased above normal values when mice are bled. A concentrated silica-treated spleen supernatant was able to stimulate erythropoiesis in the polycythemic mouse bioassay. It is concluded that the ESF is similar, if not identical, to Ep.

Anemia↗
PubMed1980

The effect of actinomycin D on hemopoiesis. I. Short-term effects.

The effect of in vivo administration of actinomycin D (Act D) on the hemopoietic precursor compartments and, in particular, the BFU-E, CFU-E, and erythroblast populations was investigated over a 6-day period. Daily injections of mice with 15 microgram/kg, 30 microgram/kg, and 60 microgram/kg Act D showed a dose-dependent effect. The highest dose caused an almost complete eradication of CFU-E as well as the morphologically identifiable erythroblasts. There was no appreciable reduction in BFU-E, GM-CFU, and CFU-S. These observation indicate that Act D interferes with erythropoiesis by selectively inhibiting the CFU-E compartment. The effects are not due to altered sensitivity to erythropoietin as dose response curves were similar for control and Act D-treated cells. Although a considerable reduction in CFU-E is observed and approximately 20-30% of nucleated cells are lost from the small size region, there is no displacement in the velocity sedimentation profiles either from the remaining CFU-E and nucleated cell populations or the BFU-E and GM-CFU populations.

Animals↗
PubMed1980

Endotoxin-induced changes in the interrelationship of density subpopulations of granulocyte-macrophage progenitor cells.

Progenitor cells of in vitro colonies of granulocytes and/or macrophages (CFU-s'c) constitute a functionally heterogeneous population reflected by differences in their bouyant density. The interrelationship of density subpopulations of murine (CFU-c, obtained by isopycnic centrifugatiuon of bone marrow cells in continuous albumin density gradients, was examined in perturbed states induced by endotoxin injection. Femoral bone marrow CFU-c's were investigated at daily intervals for 3 days after injection of endotoxin. A distinct difference was found between the changes in CFU-c when detected in vitro with MLCM and HU as the sources of CSF. After 1 day, there was a reduction in the number of CFU-c's, in particular by those CFU-c's of low density (< 1.07 gm/cm3) that are detectable in vitro with CSFMLCM and that form predominantly granulocytic colonies. This was followed on day 2 by the reappearance of this subpopulation. In contrast, those CFU-c's detectable with CSFHU and forming predominantly macrophage colonies were characterized by a high modal density (> 1.075 gm/cm3). Their numbers decreased on day 1, increased by day 2, and further increased above control levels by day 3 when they were characterized by a very high mean modal density of 1.087 gm/cm3. These results indicate that the different types of CSF detect subpopulations of CFU-c's that differ in differentiation potential and perhaps constitute a hierarchy in the myelopoietic pathway.

Animals↗
PubMed1980

[In vivo synthesis of cartilage after transplantation of chondrocytes in animal experiments (author's transl)].

Long-term results after cartilage transplantation are not satisfactory owing to poor viability of the chondrocytes. In vitro experiments with isolated fetal and neonatal rabbit chondrocytes revealed a much better proliferative ability compared with adult cartilage derived cells. Cryopreservation of cell suspensions did not decrease the proliferative ability. In in vivo experiments, cultured neonatal, fetal, and cryopreserved rabbit chondrocytes were tested in transplants and compared with cell-free controls or radiated chondrocytes. These chondrocytic transplants showed good viability and seemed to synthesize cartilage matrix, which could be stained with safranin, whereas only fibrous tissue was found in controls.

Animals↗