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Biomedical subjects

E Neumann

Publications and source records attributed to E Neumann.

At least 127 records · Page 7Linked to original sources

Gene transfer into mouse lyoma cells by electroporation in high electric fields.

Electric impulses (8 kV/cm, 5 microseconds) were found to increase greatly the uptake of DNA into cells. When linear or circular plasmid DNA containing the herpes simplex thymidine kinase (TK) gene is added to a suspension of mouse L cells deficient in the TK gene and the cells are then exposed to electric fields, stable transformants are formed that survive in the HAT selection medium. At 20 degrees C after the application of three successive electric impulses followed by 10 min to allow DNA entry there result 95 (+/- 3) transformants per 10(6) cells and per 1.2 micrograms DNA. Compared with biochemical techniques, the electric field method of gene transfer is very simple, easily applicable, and very efficient. Because the mechanism of DNA transport through cell membranes is not known, a simple physical model for the enhanced DNA penetration into cells in high electric fields is proposed. According to this ' electroporation model' the interaction of the external electric field with the lipid dipoles of a pore configuration induces and stabilizes the permeation sites and thus enhances cross membrane transport.

Animals↗

Single channel gating events in tracer flux experiments. II. Flux amplitude analysis.

Measurement of tracer ion flux from or into a collection of closed membrane structures (CMS) constitutes a broadly applicable technique for studying ion channel gating by specialized gating molecules in biological membranes. The amplitudes for the flux process reflect the overall change in tracer content due to flux during a period in which channels on at least some of the CMS were open. In practice, the attainment of a time-invariant, finite overall tracer content, indicating a cessation of flux, need not imply that flux has reached completion, i.e., that the CMS internal and external tracer concentrations have fully reached equilibrium. Less than maximum flux amplitudes arise when binding of control ligands leads to an inhibition or inactivation of the channel gating molecules prior to a complete equilibration of tracer. Analysis of the dependence of the flux amplitudes on control ligand concentration permits determination of characteristic parameters of the CMS that may vary with the methods of preparation (e.g., the distributions of CMS size and CMS content of gating units). Knowledge of these parameters in turn permits evaluation of the mean single channel flux amplitude contribution, which is functionally dependent on the rate constant ratio (k'eff/ki), where k'eff and ki are, respectively, the effective rate constants for tracer flux and for gating unit inactivation.

Acetylcholine↗

Single channel gating events in tracer flux experiments. III. acetylcholine receptor-controlled Li+ efflux from sealed Torpedo marmorata membrane fragments.

Filter assay measurements of Li+ efflux from acetylcholine receptor-containing vesicular Torpedo marmorata membrane fragments (microsacs) are presented. Techniques are introduced for: (a) inducing a complete emptying of the Li+ content of all microsacs containing one or more functionally intact receptors, and (b) for determining the distribution of internal volumes of the microsacs using filtration with membrane filters of different pore sizes. The flux amplitudes resulting for acetylcholine receptor-controlled Li+ efflux, when receptors are inhibited by alpha-bungarotoxin or inactivated by a neuroactivator-induced desensitization process, were measured. Amplitude analysis was used to determine characteristic parameters of the microsacs that may vary with the technique of preparation (e.g., the distribution in size and receptor content), as well as the mean single channel flux amplitude contribution (e-kt)infinity, which represents the mean reduction of the Li+ content of a microsac due to efflux from a single receptor-controlled channel closing due to inhibition or inactivation of the receptor. The ratio keff/ki was found to lie in the range 0.1 less than keff/ki less than 0.5, where keff and ki are, respectively, the rate constant for Li+-Na+ exchange flux and for the slow inactivation reaction mode of the acetylcholine receptor induced by carbamoylcholine at high concentrations.

Animals↗

Systemic candidiasis complicating bone marrow transplantation in aplastic anemia. Case report.

A 17-year-old male patient with aplastic anemia underwent bone marrow transplantation and succumbed 4 days after marrow infusion from sudden myocardial failure. Fever of unknown origin (FUO) had accompanied the patients course from admission until death. The cause of death was fungus myocarditis, which had escaped detection in vivo, in spite of a daily culture program for bacteria and fungi, and a close monitoring of the patients circulation and ventricular performance. Commonly applied diagnostic criteria for systemic mycosis, such as topical colonization, malfunction of invaded organs and positive fungus cultures failed to provide a timely diagnosis. With regard to the problems in diagnosing systemic mycosis, the potential stem cell toxicity of antifungal drugs and the need for immunosuppressive therapy prior to marrow infusion, we strongly recommend not to start the transplantation procedure unless FUO has been treated successfully.

Adolescent↗

Vaginal involvement in familial benign chronic pemphigus (Morbus Hailey-Hailey).

Vaginal pain over a period of 3 years has been shown to be based on a vesiculo-bullous acantholytic disorder suggesting familial chronic benign pemphigus (Morbus Hailey-Hailey). Local applications of 5 ml 1% hydrocortisone-enterochinol cream resulted in an almost total regression of all the symptoms, including dyspareunia.

Administration, Topical↗

Diminished serum folic acid levels in renal transplant recipients.

Serum folic acid levels were determined by radioimmunoassay in 26 chronic hemodialysis patients, in 52 renal transplant recipients and in 20 healthy controls. In the dialyzed patients, the mean serum folic acid level was 3.37 +/- 1.25 ng/ml and was significantly lower than that of the controls (6.1 +/- 1.38 ng/ml, P less than 0.001). In renal transplant recipients the mean folic acid concentration was 4.09 +/- 1.58 ng/ml and was also significantly decreased (P less than 0.001). 15 (29 per cent) out of 52 renal transplant patients showed serum folic acid concentrations lower than 3.0 ng/ml. Diminished serum folic acid levels were found not only in patients shortly after surgery but also in cases with excellent graft function up to 6 years after transplantation. The highest serum folic acid level was observed in one transplant patient who had taken no azathioprine for 24 months. Macrocytosis was found in 52 per cent of our renal transplant patients. There was no significant difference between the serum folic acid levels of renal transplant recipients with (n = 27) and without (n = 25) macrocytosis; however, serum creatinine levels were significantly lower in cases revealing macrocytosis. Relative folic acid deficiency does not seem to be responsible for macrocytosis after renal transplantation. Macrocytosis was observed only in patients with good graft function treated with azathioprine. Serum vitamin B12 levels were within the normal range in both dialyzed and renal transplant patients.

Adolescent↗

Glycosylated hemoglobins (GHb): an index of red cell survival.

Levels of glycosylated hemoglobins (GHb) are significantly (p less than 0.0005) lower in patients with hemolytic anemia (n = 20; mean = 3.9% +/- 0.1% SD GHb of total Hb) compared to patients with nonhemolytic anemia (n = 20; mean = 7.0% +/- 0.7% GHb) and normal controls (n = 30; mean = 6.7% +/- 0.7% GHb). A curvilinear correlation between GHb and red cell survival is demonstrable (n = 20;r2 = 0.88; p less than 0.001). Determination of GHb may be useful as a screening test for hemolytic anemia and for the evaluation of the degree of hemolysis, provided that diabetes mellitus can be excluded.

Adolescent↗

[Results with MOPP combination chemotherapy in Hodgkin's disease (author's transl)].

50 patients with Hodgkin's disease were treated with MOPP chemotherapy. Therapeutic success depended on previous treatment, stage of disease and histological subtype. Complete remission was achieved in 56%, partial remission in 28% and no response in 16% of the patients. None of the non-responders survived for longer than 2 years. Patients demonstrating partial remissions showed a median survival time of 3 years, whereas 23 out of 28 patients with complete remissions are still alive after 2 to 7 years. The median remission duration in cases of complete remission has not yet been reached, but would, at present, be not less than 48 months, with no patient at risk. 7 out of 9 patients who relapsed are on alternative treatment (ABVD, TNI) and doing well, the 2 remaining patients died in the course of the disease.

Adolescent↗

[Acute leukemia associated with lactic acidosis].

The clinical course and metabolic disturbances in three patients with acute leukemia and severe lactic acidosis (lactic acid concentrations 11.2, 17.0 and 21.0 mmol/l) are described. Circulatory failure could be ruled out as a possible cause of elevated lactic acid. Clinical findings included somnolence, hyperventilation and diffuse abdominal pain. In patients with malignant disease, a number of factors may contribute to elevated lactic acid levels. However, in our cases the excessive lactic acidosis was due to increased production of lactic acid by the leukemic cells, together with impaired hepatic metabolization. The diminished hepatic gluconeogenesis is also documented by a severe hypoglycemia in our patients. The essential step in treatment is early diagnosis of this syndrome and prompt initiation of cytotoxic medication.

Acidosis↗

[Causal therapeutic management of aplastic anaemia (author's transl)].

Aplastic anaemia is characterized by hypoplasia of haemopoietic tissue. The aetiology of aplastic anaemia is multifactorial, the majority of cases being termed "idiopathic" because of lack of discernible noxious agents. Treatment can include stimulation of haemopoietic stem cells or replacement of stem cells by bone marrow transplantation. Some cases show autoimmune-mediated marrow failure and these patients may respond to immunosuppressive therapy. Pathophysiological subclassification of individual cases is necessary to ensure the correct choice of therapy offering the best chance of success, at minimum risk, from amongst a multitude of therapeutic procedures.

Adrenal Cortex Hormones↗

[Prognosis of panmyelopathy: a retrospective study (author's transl)].

45 patients with pancytopenia were admitted and treated at the 1st Department of Medicine, University of Vienna, between 1972 and 1978. Retrospective analysis disclosed a significantly longer survival time in association with a hypercellular bone-marrow smear. These patients showed a higher incidence of remission with cortisone anabolic therapy, but more often developed acute leukaemia as well. The median survival time of patients with pancytopenia and a hypocellular or blank marrow was five months. This group of patients should, therefore, be considered for early bone-marrow transplantation.

Adolescent↗

Spectrophotometric determination of reaction stoichiometry and equilibrium constants of metallochromic indicators. III. Antipyrylazo III complexing with Ca2+ and acetylcholine receptor protein.

Stoichiometries, equilibrium constants and optical extinction coefficients of calcium-antipyrylazo III (An) complexing are determined with the analytical method described in article I of this series. Spectrophotometric Ca titrations of An at the wavelengths 595 and 710 nm indicate overall dissociation equilibrium constants for the complexes CaAn, CaAn2 and Ca2An to be 4.5 x 10(-4) M, 1.1 x 10(-8) M2 and 1.5 x 10(-6) M2, respectively, extrapolated to zero ionic strength. Ca titrations of solutions containing An plus acetylcholine receptor protein give clear evidence that An binds to the protein to a large extent in the presence of Ca2+; furthermore, addition of acetylcholine results in release of protein-bound Ca and An. This is the first reported indication that antipyrylazo III binds to biological material and questions the usefulness of this dye as a Ca indicator in biological systems.

Animals↗

Properties of agarose-encapsulated adsorbents. II. Elimination of endogenous and exogenous phenolic compounds from human serum.

Phenolic compounds derived from the amino acid tyrosine are endogenous toxins, which are believed to be involved in the pathogenesis of hepatic coma. There are also xenobiotic phenolic substances, such as p-hydroxy-acetanilide (paracetamol or acetaminophen), which can lead to serious complications if taken in an overdose. In both cases, a drastic therapeutic measure such as haemoperfusion may be indicated to eliminate the toxin from the blood. In the present work, human serum has been dosed with the phenolic compounds of immediate relevance in exogenous and endogenous intoxication, and the effectiveness of various adsorbent materials for the elimination of the toxins from the serum has been investigated. Resins and charcoal in the native state have been compared with those encapsulated into large agarose beads, a process which improves the haemocompatibility and thus the practicability of the adsorbents. A certain degree of specificity has been observed. Whereas phenolic acids are adsorbed quite effectively onto the strongly basic ion exchange resins of the Dowex 1X type, particularly 1X8 or 2X8, phenol or paracetamol are less effectively eliminated. In contrast to many other classes of toxin, the Amberlite XAD-type resins are ineffective for all the phenolic substances investigated. Charcoal is the most effective adsorber in most cases, particularly when encapsulated in powder form into agarose beads.

Absorption↗

Ion flow gating by the acetylcholine system: kinetics of isolated receptor and esterase and of receptor-mediated ion flux.

1. Basic features of the elementary bioelectric signals such as miniature-endplate-potentials are molecularly interpreted on the basis of relaxation kinetic data of isolated acetylcholine receptor and acetylcholinesterase. Electrophysiological and molecular data suggest an essentially sequential processing of acetylcholine by receptor and esterase. 2. Flux measurements with sealed biomembrane fragments containing acetylcholine receptor show that the ion-transporting conformation of the receptor-channel is a short-lived metastable state. In the presence of neuroactivators the receptors inactivate. The description of the flux-inactivation requires a cyclic reaction scheme similar to the desensitization scheme of KATZ and THESLEFF (1957). 3. The recently introduced concept of integrated flux rate coefficients permits us to derive gating mechanisms from flux data under well-defined experimental conditions: sealed biomembrane vesicles, activator concentration, type of transported ion. 4. With respect to activation and inactivation and the metastability of the ion-conducting conformation, there are fundamental similarities between the axonal Na+ ion channel and the acetylcholine receptor-channel.

Acetylcholine↗