Search PubMed⌕ Search

Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 343 records · Page 19Linked to original sources
PubMed1994

Mast cell growth factor enhances multilineage hematopoietic recovery in vivo following radiation-induced aplasia.

Based on in vitro studies, mast cell growth factor (MGF; also known as steel factor, stem cell factor, and c-kit ligand) has been implicated as an important hematopoietic regulator, especially in the presence of additional hematopoietic cytokines. Since hematopoietic regeneration follows sublethal radiation-induced hematopoietic injury and is thought to be mediated by endogenously produced cytokines, the ability to accelerate recovery from radiation-induced hematopoietic hypoplasia was used to evaluate in vivo effects of MGF administration. Female B6D2F1 mice were exposed to a sublethal 7.75-Gy dose of 60Co radiation followed by subcutaneous administration of either saline or 100, 200, or 400 micrograms/kg/d recombinant murine MGF on days 1 to 17 postirradiation. Recoveries of bone marrow and splenic spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming cells (GM-CFC), and peripheral white blood cells (WBC), red blood cells (RBC), and platelets (PLT) were determined on days 14 and 17 during the postirradiation recovery period. MGF accelerated hematopoietic recovery at the 100 and 200 micrograms/kg/d doses. The 100 micrograms/kg/d dose accelerated recovery of only GM-CFC, while the 200 micrograms/kg/d dose accelerated CFU-S, GM-CFC, WBC, and PLT recoveries. In contrast, hematopoietic recovery was delayed in mice receiving the 400 micrograms/kg/d dose. These studies demonstrate the in vivo dose-dependent ability of MGF to accelerate multilineage hematopoietic regeneration following radiation-induced hematopoietic hypoplasia. They also document detrimental effects of providing "supraoptimal" doses of this growth factor and suggest caution in dose-escalation trials in humans.

Animals↗
PubMed1994

[Hodgkin lymphomas ar negative with regard to bcl-2/JH gene rearrangement, but partly express BCL-2 protein: analysis of 83 cases from the German Hodgkin Trial].

Conflicting data on the presence of bcl-2/JH gene rearrangement and BCL-2 protein expression in Hodgkin's disease (HD) have been reported. To find out the reason for these differences, well characterized cases from the German National Trial were examined by PCR for the bcl-2 gene rearrangement and immunohistochemically for BCL-2 protein expression. No bcl-2/JH rearrangement could be detected among the HD analyzed from paraffin sections, as well as another 24 cases of HD investigated in fresh tissue. Contrasted with this, immunohistochemistry demonstrated BCL-2 protein expression in all types of HD. In conclusion, our results suggest that the bcl-2/JH gene rearrangement does not play a role in HD, but BCL-2 protein is frequently expressed by RS/H cells of non-lymphocyte predominance subtypes.

Antigens, CD↗
PubMed1994

[Prognosis in endoscopic perforans vein excision in postphlebitic syndrome].

In the presence of leg ulcer endoscopic treatment is particularly indicated as it permits reliable diagnosis and treatment of incompetent perforator veins from a small incision away from the contaminated zone. Lately 3 surgeons have developed special instruments for this type of endoscopy. Hauer was the 1st to develop a specialized technique with the Wolf Company. He uses an angulated optic system and a double cautery clamp. It permits excellent vision. Sattler works with a Storz thoracoscope and specially built instruments controlled by a monitor. This means agreeable and motivating handling. Fischer uses direct vision through a Wolf or similar endoscope shaft and a set of instruments produced by Storz and Ulrich Co for him for swift, simple and reasonable treatment. Each surgeon will chose his method on the ground of his education, his special liking and his set up.

Endoscopes↗
PubMed1994

Three-dimensional reconstruction of histologic structures in human bone marrow from serial sections of trephine biopsies. Spatial appearance of sinusoidal vessels in primary (idiopathic) osteomyelofibrosis.

Computer-based three-dimensional (3D) reconstruction of histologic features permits the assessment of the spatial arrangement of complex structures and has the additional advantage of demonstrating aspects that may be obscured in conventional, two-dimensional evaluations. Until now the spatial appearance of histotopographic details in human bone marrow has not been investigated. In the present study we explored the use of 3D visualization techniques to determine the configuration of sinusoidal vessels and surrounding megakaryocytes in osteomyelofibrosis. Up to 34 serial sections were cut from each trephine biopsy block and stained sequentially by monoclonal antibodies against collagen type IV and megakaryocytes (CD61-Y2/51) to discriminate relevant structures selectively and with high contrast. Images were digitized, and contours were traced manually. A new fast and graphically interactive software package for the reconstruction of 3D objects employing a low-cost personal computer was developed. The system allows reconstructions from any serial image in solid model form using a fast triangulation algorithm. 3D reconstruction emphasizes the close spatial relationship between sinus walls and megakaryocytes in this disorder and exhibits enhanced vascularity with a complex 3D meshwork of branching and tortuous sinusoidal vessels. Furthermore, an increase in luminal distention and aberration from normal shape could be observed. Large and ameboid megakaryocytes were frequently found adjacent to the abluminal surface of the sinus. The method described permits more elaborate insight into the complex topographic relationship of these two morphologic features in human bone marrow and may stimulate applications to other interesting specimens that warrant 3D visualization.

Biopsy↗
PubMed1994

[Invaginative stripping in surgery of varicose veins].

Invaginative stripping helps to reduce invasivity in varicose vein surgery. It therefore meets increasing interest. With this procedure however the saphenous vein sometimes tears off. This can be prevented in part of these cases by cutting the branches of the saphenous vein during stripping by means of the "sikkle" (Fig. 2). If it does not work then the remaining parts of the saphenous vein must be stripped in the conventional manner with a stripper head. However how can the stripper be introduced again into the stripper canal? One end of the tie which is used to knot the saphenous vein to the stripper is left long. In this way the long end of the tie remains in the stripper canal after invaginative stripping. This tie then can be used to pull another stripper into the stripper canal. In order to prevent the tip of the stripper to be caught in the subcutaneous tissue a special tip is used which we call "dolphin" (Fig. 5). It is a fish-shaped gadget with a mouth or a hook on one side for the tie and a thread at the other side for the thread of the stripper. Another possibility is to pull a second stripper after the first one by means of the "torpedo" (Fig. 3) whenever invaginative stripping is intended. The second stripper then can be used for conventional stripping if necessary.

Humans↗
PubMed1994

Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells.

The effect of histamine on the phosphoinositide turnover and intracellular free calcium activity [Ca2+]i was examined in human glomerular epithelial cells in culture. Addition of histamine to glomerular epithelial cells resulted in formation of inositol phosphates in a time- and dose-dependent manner. A transient maximum of inositol trisphosphate (InsP3) was observed within 10 s. Stimulation of protein kinase C by short-term pretreatment (15 min) of glomerular epithelial cells with phorbol 12-myristate 13-acetate caused a dose-dependent inhibition of the histamine-induced inositol phosphate accumulation. The baseline of [Ca2+]i in the cells was 115 +/- 2.7 nmol/l (n = 103). Histamine (ED50: approx. 2 x 10(-7) mol/l) caused a rapid and transient increase in [Ca2+]i as detected by fura-2 microfluorimetry studies. In a calcium-free extracellular solution the rapid increase of [Ca2+]i was still present. The H1 receptor antagonist mepyramine (IC50: approx. 8 x 10(-9) mol/l) inhibited the histamine (10(-6) mol/l) response on [Ca2+]i. Cimetidine, a potent H2 receptor antagonist, showed no effect. This data indicates that H1 receptor activation causes hydrolysis of phosphatidylinositol 4, 5-bisphosphate by phospholipase C activation, and consecutive mobilization of intracellular calcium. Since histamine is a mediator of inflammation, antigen response and cellular injury, these findings could be of importance for the understanding of glomerular epithelial cell pathology.

Calcium↗
PubMed1994

Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction.

A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage.

Aged↗
PubMed1994

An unusual pattern of lymph node involvement in mycosis fungoides simulating neoplastic follicles.

We describe an unusual pattern of lymph node involvement in a case of mycosis fungoides. The neoplastic proliferation formed pale nodules composed of small, irregular lymphoid cells, features that, on routine paraffin sections, suggested neoplastic follicles and a B-cell phenotype. The correct diagnosis was established by immunohistochemical studies that demonstrated a T-cell phenotype. Polymerase chain reaction for rearrangement of the T-cell receptor gamma gene confirmed that the proliferation was monoclonal. This case demonstrates that both architectural pattern and cytologic features may be unreliable in predicting immunologic phenotype. Immunologic marker studies and careful attention to the clinical history are vital to classify lymphoproliferative disorders correctly.

Aged↗
PubMed1994

Bioavailability of iron from oral ferric polymaltose in humans.

The bioavailability or iron from iron(III)hydroxide polymaltose complex (ferric polymaltose, Fe-PM) was studied in human volunteers with normal or depleted iron stores as well as in patients with iron deficiency anemia. From an oral iron dose of 100 mg neutron activated Fe-PM, starved subjects with depleted iron stores absorbed significantly less (p < 0.003) 59Fe (3.91 +/- 2.24%, mean +/- SD) as compared to the reference, aqueous 59Fe(II) ascorbate solution (13.8 +/- 6.19%). Using non-radiolabeled, commercial Fe-PM no postabsorptive serum iron increase was found after oral Fe-PM (100 mg Fe dosage) in a group of 7 patients with haemorrhagic or posthaemorrhagic iron deficiency anemia. In addition, almost no haemoglobin increase was observed in 9 patients during a 4-weeks treatment period when given Fe-PM (100-300 mg Fe/d) on empty stomach, whereas subsequent treatment with ferrous sulfate (100-200 mg Fe/d) was therapeutically effective (0.15-0.23 g/dl Hb-increase/d). When given 100 or 300 mg Fe/d Fe-PM together with meal, 3 out of 6 patients showed a higher iron utilization rate (3.4-11.9%/d) than given without meal (0.5-7.5%/d). In vitro incubation studies demonstrated that Fe-PM is very stable at neutral pH. A small release of iron from the high molecular weight complex was found only at low pH (< 2). However, high amounts of ionic iron were measured in the reaction tubes after incubating solutions of Fe-PM together with ascorbic acid. This finding could explain the somewhat higher bioavailability of Fe-PM when given with vitamin C containing meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Active uptake of serotonin as viability parameter of stored platelets.

The platelet-plasma serotonin (5-HT) exchange in different apheresis products and platelet concentrates (PCs) from buffy coats was studied for quality control over a period of 7 days. In PCs with steadily decreasing pH due to inappropriate gas exchange the platelet 5-HT concentration increases significantly (> 10% positive netto uptake) during the 1st day of storage. Thereafter platelet serotonin drops rapidly with t1/2 = 1 day at pH < 6.5, but platelet counts were constant and 5-HT uptake was inhibited concomitantly. Plasma 5-HT increases as pH decreases. This can be enforced by competitive inhibition of serotonin uptake due to imipramine which also moderates the total 5-HT loss. However, in PC with stable pH the operative 5-HT pump keeps steady-state conditions. The efficacy of the transmembrane uptake mechanism can be adequately monitored by the assessment of the 5-HT platelet/plasma ratio as a new platelet viability parameter.

Blood Platelets↗
PubMed1994

Screening for hereditary hemochromatosis in prospective blood donors.

Prospective blood donors (n = 1,265, mean age 26 years) were screened for elevated serum ferritin and serum iron. Final diagnosis for hereditary hemochromatosis was made by liver iron concentration (noninvasive biomagnetometry), transferrin saturation, and 59Fe absorption in 3 male subjects. This preliminary result confirms for the first time the current frequency estimation of homozygous hemochromatosis (0.2-0.6%) in a group of young North-Germans.

Adult↗
PubMed1994

[Enzyme immunoassay for the determination of serotonin in stored platelet concentrates].

A new enzyme immunoassay (EIA) was applied on measurements of serotonin (5-HT) in stored platelet concentrates (PC). PC were prepared by apheresis of two separators (Cobe, Fresenius) or from buffy coats and stored for a period of 7 days at 22 degrees C and agitating. Measurements were done in pellets and suspension medium (plasma). Detection of 5-HT was specific and sensitive within the bounds of 2 and 1,000 ng/10(9) PLT.

Blood Component Removal↗
PubMed1993

Purification and characterization of heterogeneous pluripotent hematopoietic stem cell populations expressing high levels of c-kit receptor.

Mouse pluripotent hematopoietic stem cells (PHSC) were fractionated based on size and density using counterflow centrifugal elutriation (CCE). These heterogeneous PHSC populations were further enriched by subtraction of cells with lineage-specific markers (Lin-) followed by positive sorting for c-kit expression. The cells were characterized for their functional and biochemical properties. We defined a subpopulation of c-kit-positive cells that expressed high numbers of c-kit receptors (c-kitBR). One hundred c-kitBR cells from either low- or higher-density fractions were sufficient to repopulate the lymphohematopoietic system in WBB6F1-W/Wv (W/Wv) recipients, whereas no PHSC were found in cells with low (c-kitDULL) or no (c-kitNEG) c-kit expression. Lin- c-kitBR cells were separated into RhoDULL and RhoBR subsets based on their ability to efflux rhodamine 123 (Rho). The PHSC were concentrated in Lin- c-kitBR RhoDULL cells and the number of Lin- c-kitBR RhoBR cells correlated directly with the number of day 12 colony-forming unit-spleen (CFU-S12) in each fraction. We were not able to enrich further for PHSC using monoclonal antibodies to the cell-surface markers AA4.1 or CD4, which have been used by others to isolate PHSC. The small, low-density Lin- c-kitBR subset contained PHSC and few CFU-S12. This enabled us to assay PHSC for expression of the flk-2 gene, which encodes a tyrosine kinase receptor present on fetal liver PHSC. Purified RNA from the low-density Lin- c-kitBR subset did not contain flk-2 mRNA. We suggest that AA4.1, CD4 and flk-2 are expressed as stage-specific markers on PHSC in cell cycle.

Animals↗
PubMed1993

Purification and properties of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum.

N5-Methyltetrahydromethanopterin:coenzyme M meth-yltransferase is an integral membrane protein found in methanogenic archaea. It catalyzes an energy-conserving step in methane formation from CO2 and from acetate. The enzyme from Methanobacterium thermoautotrophicum (strain Marburg) has been purified 30-fold to apparent homogeneity. The purified enzyme had an apparent molecular mass of 670 kDa and was composed of seven different polypeptides of 34 kDa, 28 kDa, 24 kDa, 23 kDa, 21 kDa, 13 kDa, and 12 kDa. The N-terminal amino acid sequences of these polypeptides were determined. The native 670-kDa enzyme was found to contain 7.6 mol 5-hydroxybenzimidazolyl cobamide/mol, 37 mol non-heme iron/mol and 34 mol acid-labile sulfur/mol. Cobalt analyses after sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that the corrinoid was bound to the 23-kDa polypeptide. The apparent molecular masses of the polypeptides given above were determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis without boiling the samples prior to analysis. When the samples were boiled, as is usually done, the 23-kDa polypeptide changed its apparent molecular mass to 33 kDa and the 21-kDa, 24-kDa, and 28-kDa polypeptides formed aggregates. The specific activity (apparent Vmax) of the purified methyltransferase preparation was 11.6 mumol.min-1.mg protein-1. The apparent Km for N5-methyltetrahydromethanopterin was 260 microM and that for coenzyme M was 60 microM. The preparation was absolutely dependent on the presence of Ti(III) for activity. ATP enhanced the activity 1.5-2-fold.

Amino Acid Sequence↗
PubMed1993

Determination of methylmercury in fish samples using GC/AA and sodium tetraethylborate derivatization.

A simple technique is described for the rapid determination of methylmercury in fish tissue. Following simple dissolution in methanolic KOH solution, aqueous phase ethylation by derivatization with NaB(C2H5)4, cryogenic trapping on a packed chromatographic column, and GC separation, volatile mercury species are detected by atomic absorption spectrometry. Absolute detection limits are 4 pg of Hg for CH3Hg+ and 75 pg of Hg for labile Hg2+. Concentration detection limits for this optimized procedure are 4 ng of Hg for CH3Hg+ and 75 ng of Hg for labile Hg2+ per gram of pulverized dried fish tissue. Analysis of standard reference materials demonstrates the accuracy, precision, and reproducibility of the analytical method.

Animals↗