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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 307 records · Page 17Linked to original sources

[Changes in the blood picture in hyperthyroidism].

On the basis of a retrospective study about 276 clinically and paraclinically ascertained cases of hyperthyroidism in 34% of the patients above all mild anaemias could be proved which under thyreostatic therapy with thiamazol which after repeated incidence of an euthyroid metabolic situation vastly normalized themselves also without an anaemia-specific additional medication. Leukocytopenias (5.8%) and thrombocytopenias (3.3%) had only a low frequency in untreated hyperthyroidism. Nevertheless an unequivocal parallelity of the haematologic changes was to be observed in erythro-, granulo- and thrombopoiesis. There was a clear correlation between the activity of hyperthyroidism, measured at the T3- or T4 level, and anaemia and haemocytopenia, respectively. Lacking substance deficiency conditions and signs of haemolysis let us first of all think of a causal thyrotoxic bone-marrow damage on account of the dependence of the haematologic changes on the activity of hyperthyroidism and their immediate influencibility by aimed thyrostatic therapy. A relatively low dosed thiamazol therapy has influence on haematopoiesis and peripheral blood picture only at a very small percentage, in which cases the changes mostly are fully reversible. Thereby the initial haematologic situation before the therapy does not provide any predictability for perhaps appearing haematotoxic or allergic side-effects under thyreostatic treatment. The thiamazol therapy does not show any recognizable side-effects in the dosage administered on the investigated leukocytic functions agglomeration, adhesion and phyagocytosis. Only for the adhesion of leukocytes was proved a significant functional disturbance of leukocytes, which was, however, reversible with normalization of metabolism and with high probability was also directly thyreotoxically induced.

Adolescent↗

Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines.

Staphylococcal enterotoxin A (SEA) is a potent polyclonal T cell activator. Its activating effect is entirely dependent upon its binding to accessory cells. Monocytes, B cells, and B lymphomas can bind SEA and support activation of T cells. We have earlier found that Raji cells are particularly efficient as accessory cells for SEA-induced T cell proliferation. In the present investigation we have used this cell line for the isolation and characterization of the membrane molecule to which SEA binds. Flow cytometric analysis of cells dually stained with SEA and anti-HLA-DR mAb showed that the amount of bound SEA was proportional to the HLA-DR expression. Electrophoresis of detergent extracts of Raji cells revealed one distinct SEA-binding band with a Mr of 60 to 65 kDa. This band had the same electrophoretic mobility as the MHC class II molecules. A mAb (G8) with the ability to block SEA binding to Raji cells was established. This mAb was shown to bind to the HLA-DR molecule. Both the G8 mAb and an anti-HLA-DR mAb 9-49 inhibited SEA binding to accessory cells and also inhibited SEA-induced, but not PHA-induced, T cell proliferation and production of IL-2. Immunoprecipitation with specific anti-HLA-DR and anti-HLA-DQ mAb demonstrated that SEA binds to the HLA-DR molecule but not to the HLA-DQ molecule. Binding SEA to Raji cells followed by cross-linking and detergent solubilization of cell membranes, electrophoresis, and Western blotting resulted in two SEA-containing bands corresponding to a Mr of 90 and 105 kDa, respectively. Both these bands also contained the HLA-DR molecule and their appearance could be blocked by preincubation of the Raji cells with the G8 mAb. Collectively the results show that the HLA-DR molecule is the main functional molecule for binding of SEA to accessory cells and that this binding of SEA to HLA-DR is a necessary requirement for SEA-induced T cell activation.

Antibodies, Monoclonal↗

Proliferation of human CD4+45R+ and CD4+45R- T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R- T cells.

Recombinant IL-2 (rIL-2) and IL-4 (rIL-4) promote proliferation of human CD4+ T cells activated in the presence of PHA, TPA or OKT-3 monoclonal antibody (MAb), whereas the production of interferon-gamma (IFN) can be induced only by rIL-2. rIL-4 induced strong proliferative responses both in accessory cell independent assays and in the presence of autologous monocytes, but has failed to induce IFN production in any of these systems. The ability of rIL-2 to induce IFN production was strongly enhanced by the addition of monocytes, although a similar proliferative response was recorded in the absence or presence of monocytes. The MAb anti-Tac inhibited the proliferative response and the production of IFN by CD4+ T cells activated in the presence of rIL-2, whereas the proliferative response to rIL-4 was unaffected. CD4+45R+ and CD4+45R- T helper cell subsets proliferated in response to both IL-2 and IL-4. A kinetic analysis demonstrated that the production of IFN throughout a five day activation period was restricted to stimulation of CD4+45R- T cells with rIL-2. This report clearly demonstrates a dissociation of IFN production and T cell proliferation in man. While proliferation can be induced by both IL-2 and IL-4 in both the helper T cell subsets studied, IFN production was induced only in the CD4+45R- subsets and only in response to IL-2.

Antigens, Differentiation, T-Lymphocyte↗

Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial.

We studied the effect of ursodeoxycholic acid on 18 women and 2 men with primary biliary cirrhosis, mainly stages I and II. After a 3-mo observation period, patients were randomized to a 9-mo treatment period with ursodeoxycholic acid, 10 mg/kg.day, or placebo. Two patients on placebo left the study. In all patients on ursodeoxycholic acid, mean values of serum glutamate dehydrogenase, aspartate and alanine aminotransferases, alkaline phosphatase, and gamma-glutamyl transpeptidase fell significantly by 48%-79% after 18-24 wk; 7 of 10 showed a mean decrease of 35% in immunoglobulin M after 24 wk. Prothrombin time, serum bilirubin, albumin, the antipyrin breath test, and plasma disappearance of indocyanine green were normal initially and did not change. Total serum bile acid concentrations increased; ursodeoxycholic acid became the predominant bile acid. No significant improvement occurred in the placebo group. Hepatic histology improved in 6 patients of the ursodeoxycholic acid group but deteriorated in 4 patients receiving placebo. In studies with erythrocyte membranes, changes in electron spin resonance revealed that ursodeoxycholic acid was less toxic than chenodeoxycholic or deoxycholic acid, and coaddition of ursodeoxycholic acid prevented their toxic effect.

Deoxycholic Acid↗

Evidence for apical sodium channels in frog lung epithelial cells.

To reveal the mechanism of Na+ transport across Xenopus lung epithelium, we recorded short-circuit current (Isc), transepithelial resistance (Rt), and current noise spectra while the isolated lung tissues were mounted in an Ussing-type chamber. Mean values of Isc and Rt obtained while the tissue was bilaterally incubated with NaCl-Ringer solution were Isc = 11.57 +/- 1.19 microA.cm-2 and Rt = 0.82 +/- 0.07 k omega.cm2. Amiloride added to the mucosal (apical) side depressed Isc by 61 to 99%. Ouabain abolished Isc totally when added to the basolateral compartment. Adenosine 3',5'-cyclic monophosphate (cAMP), epinephrine, and a variety of other compounds did not alter Isc significantly. Transepithelial depolarization with serosal KCl solution reduced Isc to 6.22 +/- 1.37 microA.cm-2. Amiloride-sensitive current and the kinetics of amiloride interaction were not significantly affected by depolarization. Fluctuation analysis of Isc in the presence of amiloride revealed a Lorentzian component in the power density spectrum indicating apical Na+ channels. Assuming pseudo-first order kinetics, we calculated single channel currents (iNa) and channel density (M): iNa = 0.29 +/- 0.04 pA and M = 0.24 +/- 0.04 micron 2. Our results show that the route for Na+ transport through lung epithelial cells follows the classical Koefoed-Johnson-Ussing model for tight epithelia.

Amiloride↗

Establishment and characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice.

Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. Growth kinetics, immunohistology and karyotypes were established. One tumor showed a distinct change in its karyotype after only two passages in nude mice; by contrast, no change of immunophenotype occurred during and after in vivo passaging. Treatment of this glioma as xenograft in nude mice revealed a high sensitivity towards single agent treatment with BCNU. In view of the cytologic aberrations, however, this result should be interpreted cautiously with regard to the clinical situation.

Animals↗

Pigment gallstone dissolution in vitro. Solubilization of brown bilirubinate and black polybilirubinate stone material by buffered solvents containing ethylenediaminetetraacetic acid, bile salts, and reducing thiols.

The efficacy of a buffered 1% ethylenediaminetetraacetic acid (EDTA)-2Na solution (pH 9.2) in solubilizing carefully pulverized material from brown bilirubinate and black polybilirubinate pigment stones can be intensified stepwise by admixtures of detergents and mucolytic active thiols. Solubilization effects were quantified either photometrically by measuring the dissolved calcium bilirubinate or gravimetrically by measuring the total weight loss of solids after a defined incubation period. Maximum effects were achieved when using a buffered solvent with 1 g/dl disodium-EDTA, 1 g/dl sodium taurocholate (NaTCA), and 2 g/dl N-acetylcysteine (NAC). Whereas admixtures of NAC enhanced the solubilization of brown bilirubinate stone material additionally by an average of 21.3% (related to the effect of an EDTA/NaTCA-containing solvent), black polybilirubinate material responded rather poorly and inconsistently to NAC (mean, 8.4 +/- 11.7%).

Bile Acids and Salts↗

[The frequency of anemia in pregnancy and the effect of Folicombin].

During pregnancy in 151 of 500 pregnant women at last once a decrease of hemoglobin below 7.5 mmol/l could be detected. 25.8 per cent of the anemias have been found in the first trimester, 58.3 per cent in the second one and only 15.9 per cent in the third one. Older women, multiparae and women with infections of urinary tract had an elevated risk of anemia. Weight increase was lower in anemic pregnants than in non-anemic ones. In 85.8 per cent we observed a remission by early treatment with folicombin (iron and folic acid). Only 14.2 per cent of the anemias remain refractory against treatment. The frequency of anemia in our group of 8.6 per cent was considerably below of that of untreated ones. Additionally the small portion of severe anemias of 2.6 per cent underlines the value of an early treatment of pregnancy anemia using a combination of iron and folic acid.

Adolescent↗

Race and the shaken baby syndrome: experience at one hospital.

At Children's Hospital of Michigan there seemed to be a disproportionate number of white infants with shaken baby syndrome (SBS) relative to the proportion of white infants in our physically abused population. All reports of suspected child abuse on children less than or equal to 18 months from Children's Hospital from 1980-1985 were reviewed. The total number of abused children 18 months or younger was 545 (447 black, 87 white, 1 unknown). There were 20 children in the SBS group. Eight of 87 (9%) of white abused infants had SBS compared with 12 of 447 (2.7%) of black abused infants. The occurrence of SBS in white abused infants was disproportionately higher than in blacks. This finding has not been previously reported. Before generalizations can be made, additional data must be obtained.

Black or African American↗

[Comparison of patients with congenital abnormalities, intrauterine growth retardation and developmental delay in relation to the pre- and perinatal period].

There are substantial differences in the family history, the history of pregnancy and delivery and the course in the first week of life of patients with congenital malformations and patients with developmental or intrauterine growth retardation. Patients with malformations demonstrate a high degree of relatives with malformations; in contrast problems in pregnancy, delivery and postnatal development are less pronounced. Mothers of children with intrauterine growth retardation present with a history of early abortion, prematurity, bleeding, toxemia of pregnancy and tobacco abuse. These children present a great number of problems during the first week of life. Patients with mental retardation present with a history of previous abortion prematurity and tobacco and alcohol abuse during pregnancy. These children also present with significant morbidity in the first week of life. The history of these children discloses an unusual number of siblings with death in early life.

Austria↗

Purification and characterization of DNA polymerase alpha from plasmodia of Physarum polycephalum.

DNA polymerase alpha from Physarum polycephalum has been purified from freshly harvested microplasmodia. An inhibitory activity was removed by precipitation with poly(ethyleneimine) and interfering type-beta-like DNA polymerase by chromatography on phosphocellulose. The preparation was free of endonucleases and exonucleases. The DNA-polymerizing polypeptide had a molecular mass of 140 kDa by polyacrylamide gel electrophoresis under denaturing conditions. It was contained in purified samples and in crude cell extracts. Peptides of smaller size that reacted with antibodies against this protein were generated during purification and prolonged standing. Molecular sizing under non-denaturing conditions resulted in high-molecular-mass forms. The type of isolated DNA polymerase was established on the basis of inhibition and template-primer utilization experiments underlying the classification of DNA polymerases from higher eucaryotes. The majority of the DNA-polymerizing activity was contained in the cell nucleus fraction and was inhibited by aphidicolin. The isoelectric point (pI) was 6.7 +/- 0.2, the pH optimum at pH 6.8, and the temperature optimum at 40 degrees C. Monovalent salts, Li+, Na+, NH+4, K+, were inhibitory except for small activation maxima at 10 mM, 75 mM and 100 mM in the case of Na+, NH+4 and K+ respectively. The bivalent cations Mg2+ and Mn2+ had broad activity maxima at 3-20 mM concentrations, which were shifted to 0.05-0.1 mM in the case of Mn2+ and synthetic DNA homopolymers. The numbers of molecules of DNA polymerases in Physarum nuclei were calculated and compared with the established number of replicons in plasmodia and with the number of molecules of DNA polymerases in higher eucaryotes.

Cell Nucleus↗

A human glioblastoma line with karyotypic nullisomy 13 containing several chromosome 13-specific sequences.

Using a biochemical approach (evaluation of esterase D activity) and recombinant DNA techniques (in situ and filter hybridization with specific DNA probes) a glioblastoma cell line with karyotypical nullisomy 13 was shown to contain several chromosome #13-specific sequences. They were assigned to a marker chromosome. This finding suggests that cytogenetic descriptions of deletions or chromosome losses will gain considerable power of the statement when supplemented by molecular analysis, particularly since, by now, DNA probes have been accumulated for all chromosomes and all their subfragments.

Chromosome Banding↗

Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells.

Staphylococcal enterotoxin A (SEA) activates human T cells at extremely low concentrations corresponding to 1 to 5 molecules/T cell. SEA, in contrast to other polyclonal activators, is absolutely dependent on accessory cells to interact with and activate T cells. Only cells that can bind SEA can act as accessory cells. Monocytes, B cells, and B lymphomas have these properties. Cells of the EBV-transformed B lymphoma Raji are particularly efficient as accessory cells. T cells do not bind soluble SEA. Probably the SEA molecule has to be attached to the accessory cell to become mitogenic. It is presently not known whether the T cell recognizes a molecular complex between the SEA molecule and the putative receptor moiety on the accessory cell or the SEA molecule itself modified by its binding to the accessory cell.

Antigen-Presenting Cells↗