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Biomedical subjects

E Neumann

Publications and source records attributed to E Neumann.

At least 109 records · Page 6Linked to original sources

Tissue specificity of the initiation of immunoglobulin kappa gene transcription.

The transient transcription of a rearranged mouse immunoglobulin kappa gene was studied in a monkey fibroblast cell line. The gene was inserted into an SV40 expression vector and the calcium phosphate coprecipitation method was used for transfection. The transcripts were correctly spliced; transcription, however, was initiated within the vector and not at the correct site 23-26 bp upstream of the gene, irrespective of the length of the upstream sequences (90, 160, 370, and 870 bp) in the plasmid constructs. In contrast, accurately initiated transcripts were observed when a plasmid containing the kappa gene with 870 bp of its upstream sequence was introduced into a lymphoid cell line; the plasmid was constructed from the pSV2-gpt vector and the electric impulse method was used for gene transfer in most experiments. Tissue-specific expression of kappa light chain genes in lymphoid cells is known to depend on the presence of an enhancer element in the J-C intron. The results reported in this paper suggest that the sequence elements pd and dc which are located upstream of the leader gene segment also act in a tissue-specific manner and that it is the initiation of transcription which is a tissue-specific event.

Animals↗

Giant papillary conjunctivitis following cataract extraction.

Out of a series of 600 cataract extractions, 14 patients were found to have giant papillary conjunctivitis (GPC) due to 10-0 nylon sutures. When renewed conjunctival irritation appears weeks or months after surgery, GPC should be suspected and confirmed by eversion of the upper eyelid at the slit lamp. Free edges of protruding corneoscleral nylon sutures should be looked for. Signs and symptoms of GPC disappear within one to four weeks after removal of the offending suture.

Aged↗

Range and clinical significance of the number of myeloid-committed stem cells in the blood of patients with acute leukaemia in remission.

Circulating granulocyte/macrophage progenitor cells (CFU-GM) were assayed serially during remission in 17 patients with acute leukaemia (9 ALL, 8 AML). In patients with ALL receiving cyclophosphamide, 6-mercaptopurine and methotrexate, CFU-GM numbers were significantly lower than in normal individuals; cycles of 'reinduction' chemotherapy (vincristine, prednisolone) caused a 10-fold increase in CFU-GM per ml of blood. In 2 ALL patients a substantial increase in CFU-GM numbers preceded the morphologically detectable relapse. In patients with AML receiving repeated courses of cytosine-arabinoside and 6-mercaptopurine, circulating CFU-GM were likewise reduced. In 6 patients who relapsed, a further reduction of CFU-GM was seen. A complete absence of circulating CFU-GM was observed in 10 of the 23 investigations performed within 6 weeks prior to the morphologically detectable relapse, while such a 'zero'-growth occurred in only 1 of 54 experiments performed during stable remission. In summary, in patients with ALL in remission, circulating CFU-GM are increased following treatment with vincristine and prednisolone. In patients with AML, declining numbers of circulating CFU-GM may predict an imminent relapse.

Acute Disease↗

[Morphometric analysis of the dorsal lateral geniculate body of the laboratory mouse and microphthalmic variants].

The dorsal lateral geniculate nucleus (dLGN) of the mouse (strain 944 with microphthalmus syndrome, P. Hertwig 1942) has been morphometrically investigated. The eyes of the gray littermates develop normally (control animals) while the white littermates show the microphthalmus syndrome (microphthalmic animals). Four male twentyone day old animals were examined. Following perfusion with formaldehyde (diluted 1:4 with H2O) Nissl stained frontal sections were used for classification of neurons. we differentiate between projection neurons (PN) (geniculo-cortical relay neurons) and interneurons (IN). We succeeded in identifying these two cell types using deimpregnated Golgi preparations (Fairén et al. 1977), which were counterstained with methylene blue (0.1%). The neuronal packing density and the ratio PN:IN were conventionally determined using 20 micron thick sections from both control and microphthalmic animals. In both cases this ratio was 12:1 (= 8% IN). Measuring fields distributed in a meander-like manner were selected for estimating the neuronal density. Measuring fields giving equal values were connected. The results show that we can distinguish between 3 regions of dLGN: lateral, medial and caudal. They differ with regard to neuronal packing density, size and structure of the PN. Using 3 micron thick Nissl stained sections from both control and microphthalmic animals the size and structure of PN were automatically determined using the picture processing device "MORPHOQUANT" VEB Carl Zeiss JENA). The distribution pattern of IN is apparently uniform. The microphthalmus syndrome produces a diminished number of pathologically changed retinal fibers. The morphometrically registered findings show that within the dLGN, of the microphthalmus mouse the neuronal packing density increased (diminution of neuropil), the size of PN decreased and their structural density increased (transneuronal dystrophy). Compared with the other parts, the medial part of the dLGN is minimally altered.

Animals↗

ATP-stimulated accumulation of calcium by chromaffin granules and mitochondria from the adrenal medulla.

In the presence of high concentrations of free Ca2+ (10(-5) - 10(-4) M) chromaffin granules and adrenal medullary mitochondria take up large amounts of Ca2+. At low levels of buffered free Ca2+ (less than 10(-8) M), these mitochondria release almost all of their stored calcium, whereas chromaffin granules retain the major part of their calcium pool. In the presence of MgATP and at less than 10(-8) M free Ca2+, the mitochondria do not take up significant amounts of Ca2+. Chromaffin granules, however, under the same conditions, show active MgATP-dependent Ca2+ uptake even at nM-concentrations of free Ca2+. The implications of these results for the calcium metabolism of chromaffin cells are discussed.

Adenosine Triphosphate↗

Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata.

Excitable acetylcholine receptor rich membrane fragments from Torpedo marmorata have been used to measure, in parallel, (1) the permeability response to the fluorescent cholinergic agonist Dns-C6-Cho (in the 0.1 microM to millimolar concentration range) characterized by both the initial rate of Li+ transport and the rate of channel closure using the rapid-mixing quench-flow technique and (2) the kinetics of interaction of Dns-C6-Cho with the acetylcholine receptor sites using the rapid-mixing stopped-flow technique. Analysis of the kinetics of Dns-C6-Cho binding in the millisecond to minute time scale leads to the identification of at least three conformational states of the acetylcholine receptor: a "low-affinity" one (approximately 50 microM) that can be interconverted in the fraction of a second to a transient state of "intermediate affinity" (approximately 1 microM), followed by the final stabilization, in the second to minute time range, of a state of "high affinity" (approximately 3 nM). Comparison of Dns-C6-Cho binding data with the permeability response to the same agonist demonstrates that the binding to the low-affinity conformation(s) of the acetylcholine receptor sites coincides with the triggering of the permeability increase--or "activation"--and the transitions to the intermediate- and high-affinity states with the two-step process of channel closing--or "desensitization". The data are interpreted in terms of a minimum four-state "allosteric" model for the acetylcholine receptor.

Animals↗

T-cell alterations in hemophiliacs treated with commercial clotting factor concentrates.

Various immunological parameters were determined in 46 patients with severe hemophilia A and in 9 patients with severe hemophilia B. All patients were treated over many years with commercial factor VIII or IX concentrates. Patients with severe classic hemophilia had a significantly reduced relative and absolute number of T-helper cells and a significantly increased relative and absolute number of T-suppressor cells. About half of these patients had an inverse T-helper/suppressor cell ratio. Patients with moderate hemophilia A and severe hemophilia B did not show these abnormalities. Hemophiliacs with an inverse ratio had a significantly higher concentration of serum total protein, IgG and IgM. No relationship between the amount of factor VIII concentrate administered, the HLA-type of the patient, the presence or absence of CMV-antibodies, hepatitis markers, thrombocytopenia and abnormal liver function tests to the T-cell abnormalities could be established. Lymphadenopathy was frequently associated with an inverse ratio. Indirect evidence suggests that the alterations of the immune system began in 1979/80.

Acquired Immunodeficiency Syndrome↗

Kinetic scheme for Ca2+-arsenazo III interactions.

Temperature-jump relaxation kinetic studies show that the complex formation between Ca2+ and the metallochromic dye arsenazo III (Ar) is associated with a rapid mode (less than or equal to 10 mus-range) involving both Ca2+ and Na+ of the Na-salt of Ar and a slower mode (approximately 10 ms range) which can be attributed to structural rearrangements in the 1:2 complex CaAr2. The kinetic data suggest the scheme: Ca+2Ar = CaAr+Ar = CaAr2 = CaAr2. The relatively slow rate-limiting step sets a limit for the use of arsenazo III to study the kinetics of Ca2+ processes in cell biology.

Arsenazo III↗

Primary Hodgkin's disease of the lung. Case report and review of the literature.

A patient with primary Hodgkin's disease of the lung is described. Special features of this case were alcohol-induced chest pain as the main presenting clinical symptom and the documentation of the evolution of the pulmonary mass by serial X-rays. Complete remission was achieved by lobectomy and subsequent MOPP-therapy. Since then the patient has been in unmaintained remission for 36 months.

Adult↗

[Bone marrow transplantation for aplastic anemia--initial results in 8 patients].

8 young patients (aged 11 to 23 years) with severe aplastic anaemia received bone marrow grafts from their HLA-identical, MLC-non reactive siblings. All patients had received repeated transfusions previously and had been unsuccessfully treated with corticosteroids (7 out of the 8 patients) and/or anabolic drugs (4 out of the 8 patients). In order to prevent graft rejection 5 patients received donor buffy coat cells after the marrow infusion and 3 patients underwent total body irradiation with 400 rad prior to the marrow transplantation. 5 patients are alive, 3 patients died. Death occurred from Candida septicaemia (day 4 after transplantation), left ventricular failure (day 14) and graft versus host reaction of the gut (day 85). The 5 living patients are in a very good state of health 30 to 166 days after transplantation. 4 patients already have normal blood cell counts. 2 of the surviving patients developed a transient GVH-reaction of the liver. One patient had a mild GVH-reaction of the skin on day 130.

ABO Blood-Group System↗

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↗