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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 289 records · Page 16Linked to original sources
PubMed1995

Megakaryocytes and fibroblasts--interactions as determined in normal human bone marrow specimens.

An in vitro study was performed to investigate possible interactions between megakaryocytes and bone marrow fibroblasts, both obtained from healthy donors. We were able to demonstrate that the proliferation of fibroblasts increased significantly by co-culturing these cells with megakaryocytes for 6 days. Addition of neutralizing antibodies for PDGF and TGF beta 1, caused a significant reduction of fibroblast growth. Inhibition of cell to cell contacts via tissue culture inserts generated a conspicuous impairment of fibroblast proliferation compared with megakaryocyte-fibroblast co-cultures, where contact was allowed. Hence, our findings suggest that a close spatial relationship between megakaryocytes and fibroblasts is needed for the activation of growth in normal human bone marrow. Neighbouring of megakaryocytes and fibroblasts seems to be necessary in order to achieve a certain threshold of local growth factor concentration. Our results are in keeping with the assumption that PDGF and TGF beta 1, are secreted by normal human megakaryocytes in very low concentrations and promote significantly fibroblast proliferation.

Adult↗
PubMed1995

Role of 3'-untranslated regions in the regulation of hexose transporter mRNAs in Trypanosoma brucei.

Trypanosoma brucei is a unicellular parasite that is transmitted from one mammalian host to the next by tsetse flies. The expression of many trypanosome genes is regulated during the life cycle but there is no evidence for developmental control of transcription by RNA polymerase II. T. brucei expresses at least two hexose transporter mRNAs that are developmentally regulated; we show here that specific portions of the 3'-untranslated regions are responsible for the differential expression. Different trypanosome 3'-untranslated regions, from surface protein, phosphoglycerate kinase and aldolase genes as well as the hexose transporter genes, conferred a spectrum of levels of reporter gene expression, and these activities differed between bloodstream forms and the procyclic forms that replicate in the tsetse vector. Experiments with permanently transformed cell lines showed that regulation occurs at the mRNA level. The results suggest that post-transcriptional control of mRNAs in trypanosomatids operates at several levels, and that it will not always be possible to attribute all the regulation to short RNA motifs.

Animals↗
PubMed1995

Monocytoid B-cell reaction associated with peripheral T-cell lymphomas.

Benign monocytoid B-cells (MBCs) proliferation was reported to occur in various lymphoproliferative disorders, but not in peripheral T-cell lymphomas (PTCL). In our review of fifty three nodal-based, low and high grade PTCL, MBCs were identified histologically and immunohistochemically in eight of the cases. They included: chronic lymphocytic leukaemia of T-cell type (n = 1) with multiple MBCs clusters, large cell anaplastic lymphoma (n = 1) showing lymphoma cells within multiple MBCs foci, and PTCL of angioimmunoblastic lymphadenopathy (AILD) type (n = 6) with solitary (n = 4) or multifocal (n = 2) MBCs reaction. Progression from AILD-hyperimmune reaction to PTCL of AILD type could be observed in one case by three consecutive follow-up biopsies. While MBCs proliferation associated with hyperimmune reaction was prominent, in PTCL of AILD type only isolated or small multiple clusters of MBCs were present. In PTCL of AILD type, MBCs seemed to be a residual component of a prior hyperimmune reaction diminishing with progress of the disease. Therefore we assume that the development of PTCL of AILD type from preceding hyperimmune reaction is more common than previously considered. Cytologically, MBCs proliferation associated with PTCL shows two cell types, as described in reactive lymphadenopathies: the common type and the large cell type MBCs.

Adult↗
PubMed1995

Aspergillus nidulans apsA (anucleate primary sterigmata) encodes a coiled-coil protein required for nuclear positioning and completion of asexual development.

Many fungi are capable of growing by polarized cellular extension to form hyphae or by isotropic expansion to form buds. Aspergillus nidulans anucleate primary sterigmata (apsA) mutants are defective in nuclear distribution in both hyphae and in specialized, multicellular reproductive structures, called conidiophores. apsA mutations have a negligible effect on hyphal growth, unlike another class of nuclear distribution (nud) mutants. By contrast, they almost completely block entry of nuclei into primary buds, or sterigmata (bud nucleation), produced during development of conidiophores. Failure of the primary sterigmata to become nucleated results in developmental arrest and a failure to activate the transcriptional program associated with downstream developmental steps. However, occasionally in mutants a nucleus enters a primary bud and this event relieves the developmental blockage. Thus, there is a stringent developmental requirement for apsA function, but only at the stage of primary bud formation. apsA encodes a 183-kD coiled-coil protein with similarity to Saccharomyces cerevisiae NUM1p, required for nuclear migration in the budding process.

Actins↗
PubMed1995

Reactive versus neoplastic monocytoid B-cell proliferations. In situ hybridization study of immunoglobulin light chain mRNA.

To distinguish reactive versus neoplastic monocytoid B-cell (MBC) proliferations, the clonality of MBC was examined in paraffin-embedded tissues by in situ hybridization (ISH) of immunoglobulin (Ig) light chain messenger RNA (mRNA) with sensitive oligonucleotide probes in 26 cases. They included 13 cases of lymphadenitis with MBC reaction and 13 cases of nodal (n = 8) and extranodal (n = 5) monocytoid B-cell lymphoma (MBCL). Two cases represented a composite lymphoma showing a centroblastic-centrocytic and MBCL component. The clonality of MBC infiltrates could be demonstrated in 16 of 26 (61.5%) cases by immunostaining for Ig light chains and in all (100%) cases by ISH. Neoplastic MBC usually expressed a faint-to-moderate light chain restriction of mRNA, whereas some MBC (10% to 30% of total MBCL population) showed a strong positivity irrespective of plasmacytoid differentiation as indicated by Ig immunostaining (present in 9 of 13 cases). Reactive MBC expressed a faint kappa and lambda light-chain mRNA positivity. Five percent to 20% of total reactive MBC showed also a strong positivity for both Ig light chain mRNA, although only a minor part of these cells (7 of 13 cases) expressed polyclonal Ig by immunohistochemistry. These results indicate that (1) both reactive and neoplastic MBC can differentiate into plasma cells; and (2) a relatively high percentage of reactive and neoplastic MBC show a detectable mRNA transcription, but not a corresponding Ig synthesis. Either the Ig detection is not sensitive enough or these cells might be in an early differentiation phase, where the Ig production has not yet started.

Adolescent↗
PubMed1995

Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone.

Total body iron stores including liver and spleen iron were assessed by non-invasive SQUID biomagnetometry. The liver iron concentration was measured in groups of patients with beta-thalassaemia major or other posttransfusional siderosis under treatment with the oral iron chelator deferiprone (n = 19) and/or with parenteral deferoxamine (n = 33). An interquartile range for liver iron concentrations of 1680-4470 micrograms/g liver was found in these patients. In both groups a poor correlation between liver iron and serum ferritin values was observed. Repeated measurements of liver and spleen iron concentrations as well as determination of liver and spleen volume by sonography were performed in six patients under continuous deferiprone treatment for 3-15 months. In this group detailed information was obtained on the whole body iron store (5-36g) and the iron excretion rates (14-34 mg/d) for each patient. As indicated by decreasing liver iron concentrations, five out of six subjects showed a negative iron balance (2-13 mg/d). Conventional measurements of both serum ferritin and urine iron excretion gave fluctuating results, thus being only of limited use in the control of iron depletion therapy. The non-invasive biomagnetic liver iron quantification is a precise and clinically verified technique which offers more direct information on the long-term efficacy of an iron depletion therapy than the hitherto used methods. This technique may be of use in the clinical evaluation of new oral iron chelators.

Adult↗
PubMed1995

Combination of Hodgkin's disease and diffuse large cell lymphoma: an in situ hybridization study for immunoglobulin light chain messenger RNA.

It is not clear whether the rare combination of Hodgkin's diseases with non-Hodgkin lymphomas are true composite lymphomas or differentiation stages of one tumour cell clone. We used in situ hybridization and immunohistochemistry for the demonstration of immunoglobulin light chains in order to investigate the relationship between the two lymphoma components. In three cases of nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma the Hodgkin cells, as well as the tumour cells in the diffuse large B-cell lymphoma, showed the same messenger RNA for one light chain. Thus, using in situ hybridization in nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma in a small number of cases a possible genetic relationship between the two components could be shown. In nodular sclerosis combined with diffuse large B-cell lymphoma, in situ hybridization did not support a common clonal origin of both tumour parts. However, a unique clonal derivation cannot be excluded by the techniques applied.

Hodgkin Disease↗
PubMed1995

Influence of cytokines (IL-1 alpha, IL-3, IL-11, GM-CSF) on megakaryocyte-fibroblast interactions in normal human bone marrow.

The evolution of myelofibrosis accompanying chronic myeloproliferative disorders (CMPDs) is often linked with megakaryopoiesis. However, it is not known whether or to what extent megakaryocytes of normal human bone marrow are capable of stimulating fibroblast growth. For this reason, an in vitro study was performed to elucidate possible cytokine-dependent interactions between megakaryocytes and fibroblasts derived from healthy volunteers. Fibroblast growth was significantly promoted by the presence of megakaryocytes and modulated by additional application of various cytokines. While recombinant human (rh) interleukin (IL)-1 alpha had no obvious effect on fibroblast proliferation, a slight increase was detected on adding granulocyte-macrophage colony stimulating factor (rhGM-CSF). Application of rhIL-3 caused a significant increase in the number of fibroblasts. In contrast, administration of rhIL-11 suppressed the megakaryocyte-dependent growth-promoting effect and co-stimulation with rhIL-3 led to a significant decrease of fibroblast number in comparison to rhIL-3-stimulated co-cultures. Inhibition of cell-cell contact in unstimulated, as well as in rhIL-3-stimulated co-cultured led to a conspicuous impairment of fibroblast growth. A similar effect was observed when neutralizing antibodies directed against platelet-derived growth factor (PDGF) and transforming growth factor (TGF)beta 1 were added to rhIL-3-stimulated cultures. Our findings are in keeping with the assumption that interactions between megakaryocytes and fibroblasts involve in cytokine-mediated functional network regulated by factors such as spatial relationship, cytokine stimulation, and low concentrations of mediators, particularly PDGF and TGF beta. In this complex system rhIL-3 seems to play a crucial role in the promotion of these various interrelationships.

Bone Marrow↗
PubMed1995

Influence of cytokine stimulation (granulocyte macrophage-colony stimulating factor, interleukin-3 and transforming growth factor-beta-1) on adhesion molecule expression in normal human bone marrow fibroblasts.

Interactions between stromal cells or extracellular matrix and hematopoietic cells are important factors for the very complex processes associated with differentiation and maturation in the bone marrow. To elucidate these multifold processes, the expression pattern of various adhesion molecules was studied on enriched fibroblastic populations derived from healthy volunteers. CD44 (homing cell adhesion molecule) and very late activation antigen beta 1 (VLA beta 1; CD29) could be demonstrated on almost all fibroblasts without an alteration following cytokine stimulation. On the other hand, VLA-2 (CDw49b), VLA-3 (CDw49c), VLA-4 (CDw49d), VLA-5 (CDw49e), intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) were only represented by certain cell fractions. In our studies recombinant human granulocyte macrophage-colony stimulating factor failed to alter the expression pattern of these adhesion molecules, whereas recombinant human interleukin-3 (rhIL-3 showed a tendency for downregulation of the VLA antigens except for VLA beta 1. However, recombinant human transforming growth factor-beta 1 (rhTGF beta 1) exerted a reducing effect on the expression of VLA-3 and induced an increase in the VLA-5-positive fraction. In the immunoglobin class VCAM-1 revealed a decrease staining capacity after stimulation with rhTGF beta 1 and rhIL-3. Contrary to this finding, the presentation of ICAM-1 increased after administration of these mediators.

Bone Marrow↗
PubMed1995

CD34+ human hemopoietic progenitor cells of the bone marrow differ from those of the peripheral blood: an immunocytochemical and morphometric study.

CD34+ progenitor cells were harvested from bone marrow and peripheral blood from 10 healthy donors by immunomagnetic isolation and enrichment procedures. The CD34+ cell population was investigated using a battery of enzyme reactions and monoclonal antibodies on cytospin preparations. Additionally, morphometric measurements were carried out and also liquid suspension culture studies were performed to ascertain vitality and stem cell character. More than 95% of the total yield of medullary CD34 progenitors expressed CD45 (LCA), CD43 (MT1) and beta-glucuronidase. Reactivity with CD33 (My9), CD15 (LeuM1), CD38 (Leu17), CD20 (L26) and Ret40f (glycophorin C) was assumed to be in keeping with a transition into more differentiated elements of the various hemopoietic lineages. Morphometric analysis revealed conspicuous heterogeneity of the CD34+ cell population considering size measurements. This finding was in line with the diversities of antigen expression, indicating the more committed nature of CD34+ stem cells derived from the bone marrow in comparison with those progenitors isolated from the peripheral blood. Moreover, proliferation marker staining by PCNA disclosed a positivity in a considerable number of progenitors in contrast to the findings in CD34+ cells that are found in the peripheral blood.

Antibodies, Monoclonal↗
PubMed1995

Microchip implant system used for animal identification in laboratory rabbits, guineapigs, woodchucks and in amphibians.

Traditional methods for animal identification have a number of drawbacks. We evaluated a new system for individual identification using microchip implants in rabbits, guineapigs, woodchucks (Marmota monax) and amphibians (Xenopus laevis, Pleurodeles waltlii). Implantation procedure and long-term observations are described. Microchip implants proved to be a practicable and reliable system for animal identification without obvious adverse effects. The applicability of electronic animal identification in comparison with common methods and with regard to animal welfare and legal aspects is discussed.

Amphibians↗
PubMed1995

Palliative endobronchial brachytherapy for central lung tumors. A prospective, randomized comparison of two fractionation schedules.

AIM OF THE STUDY: Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications. DESIGN: Group 1 received 4 brachytherapies with a dose of 3.8 Gy (at a 10-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a 10-mm depth) at a 3-week interval. At a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results. PATIENTS: Ninety-three patients with advanced cancer were included in the study; 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Karnofsky performance status, and histologic findings. INTERVENTIONS: A mean total irradiation dose of 13.4 +/- 5.2 Gy for group 1 and 13.7 +/- 4.4 for group 2 were applied (calculated at 10 mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth). RESULTS: The 1-year survival rate was 11.4% in group 1 and 20.4% in group 2. No significant difference in survival time was found, but mean survival was longer in group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was comparable in both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%). CONCLUSION: High-dose rate brachytherapy with 2 x 7.2 Gy with a 3-week interval is equivalent to a 4 x 3.8-Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.

Adult↗
PubMed1995

Analysis of antral biopsy specimens for evidence of acquired mucosa-associated lymphoid tissue in HIV1-seropositive and HIV1-negative patients.

BACKGROUND: There is conflicting evidence concerning the prevalence of Helicobacter pylori gastritis in HIV1-infected patients. Furthermore, a possible influence of immunodeficiency on the acquisition of mucosa-associated lymphoid tissue (MALT) in the antral mucosa remains to be elucidated. METHODS: Seventy-seven consecutive HIV1-infected patients (mean age, 40.2 years) were compared in a prospective study with 77 HIV1-negative age-matched patients, using immunohistochemical stainings. RESULTS: In HIV1-infected patients the prevalence of H. pylori gastritis was lower and the inflammatory reaction less pronounced than in controls. Lymphoid follicles and intraepithelial B cells were significantly more often detected in HIV1-negative patients. CONCLUSIONS: Evidence of acquired MALT is only rarely found in HIV1-infected patients. These findings might contribute to the explanation of why low-grade gastric MALT lymphomas have not been reported in HIV1-infected patients so far.

Adult↗
PubMed1995

Characterization of CD34+ human hemopoietic progenitor cells from the peripheral blood: enzyme-, carbohydrate- and immunocytochemistry, morphometry, and ultrastructure.

Following an immunomagnetic isolation and enrichment procedure, CD34+ cells were harvested from the peripheral blood of about 50 healthy donors. A battery of cytochemical staining reactions, monoclonal and carbohydrate-specific antibodies, proliferation markers and lectins was applied on smears and sections from paraffin-embedded pellets. Additionally, a morphometric analysis and ultrastructural investigation was carried out. More than 95% of the total yield of progenitor cells expressed CD34 and CD43 (MT1) and of these about 90% CD45 (LCA) and 25% CD45A (MT2). The CD34+/CD45RA-population was thought to represent very primitive, probably not lineage-restricted stem cells. On the other hand, reactivity with ANAE, CD11c, CD15, CD20, Ret40f, KiM1P, and CD61 (ranging between 1 to 20%) was considered to indicate a transition into more differentiated elements of hemopoiesis. The failure to detect any staining with proliferation markers (Ki-67/MIB 1, PCNA, KiS1) was in keeping with a quiescent status. Carbohydrate antigens revealed a pattern which underlines the fact that the CD34 and CD43 antigens belong to the family of heavily O-glycosylated sialomucins. Blood group antigens which are located at the peripheral regions of mucin-oligosaccharides (H type 2, Lewis, Lewis) could be demonstrated, but not A, B, Sialyl-Lewis and Lewis. Morphometric analysis revealed that CD34+ progenitors were larger than small lymphocytes. Electron microscopy showed a relatively primitive cytoplasmic organization and numerous tiny magnetic beads clustered at the plasma membrane.

Adult↗