PubMed Health⌕ Search

Biomedical subjects

E König

Publications and source records attributed to E König.

At least 19 recordsLinked to original sources
PubMed1989

Duplication and transcription of procyclin genes in Trypanosoma brucei.

The genes encoding procyclin, the major glycoprotein expressed on the surface of procyclic forms of Trypanosoma brucei, comprise a multigene family. It has previously been demonstrated that procyclin genes in cloned trypanosome strains from Kenya and Uganda show restriction fragment polymorphisms. A detailed study of the Kenyan strain 227 has revealed that procyclin genes are arranged in tandem at 3 distinct loci (Pro A, B and C) and that the polymorphism is due to the duplication of 1.3 kb in the Pro A locus, which has generated an additional procyclin gene. Northern blot analysis has shown that at least 2 loci are transcribed and that a minimum of 3 procyclin genes are expressed within a cloned line. The transcription of procyclin genes is resistant to 1 mg ml-1 alpha-amanitin, whereas that of the 5' flanking gene in the Pro A locus is sensitive. This observation suggests that the two genes form part of separate transcription units with a promoter between them.

Amanitins↗
PubMed1989

The influence of endothelium on glyceryl trinitrate induced relaxation in corresponding arteries and veins of the rabbit.

Glyceryl trinitrate (GTN) induced relaxation was investigated in preparations of corresponding femoral arteries and veins from rabbits containing the intact endothelium in comparison to denuded vessels. Either vascular rings (app. 5 mm segments) or helical cut strips were isotonically mounted in organbaths (37 degrees C, Krebs-Henseleit-buffer). Vessels were precontracted with their specific EC-50 of norepinephrine. Cumulative concentration response curves for GTN were evaluated. Arteries and veins were dilated in a concentration dependent manner in the range of 1 nmol/l to 0.1 mmol/l. V.femoralis was the most sensitive vessel with an EC-50 of 10 nmol/l. There was no significant difference in the sensitivity of veins with or without endothelium. In contrast to this, for half-maximal relaxation of A. femoralis 2-3 orders of magnitude higher concentrations were necessary, depending on the presence of endothelium. The concentration ratio artery/vein (A/V) amounted to 800 in normal vessels, 100 in denuded vessels, resp. indicating that for half-maximal relaxation of endothelium containing arteries significant higher concentrations were needed. By preincubation for 60 min with the EC-90 of GTN in arteries, as well as in veins, tolerance could be induced independently of the presence of endothelium. However, veins were more affected than arteries, but tolerant veins were still more sensitive to GTN than tolerant arteries. This was true both for preparations with and without endothelium (A/V = 70 in normal vessels, 20 in denuded vessels, resp.). Moreover, the endothelial dependence of arterial relaxation was attenuated. Treatment of the tolerant vessels with cystein (1 mmol/l) did abolish the GTN-tolerance in veins but not in arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Frequent association of idiopathic myelofibrosis with plasma cell dyscrasias.

In a retrospective analysis of 199 cases of myeloproliferative diseases a concomitant plasma cell dyscrasia was found in three out of 46 patients with idiopathic myelofibrosis. Chronic myeloid leukemia, polycythemia vera or unclassifiable myeloproliferative disorders were in no case associated with monoclonal gammopathy. One patient with idiopathic myelofibrosis had primarily coexistent IgG-lambda paraproteinemia and increasing osteolytic lesions; histologic evidence of multiple myeloma, however, was insufficient. In the second patient the interval between diagnosis of idiopathic myelofibrosis and IgG-kappa paraproteinemia was 11 years. After a stable period of 9 years' duration the paraprotein level rapidly increased, associated with depression of normal background immunoglobulins and progressive bone marrow failure. The exact nature of this patient's malignant plasma cell dyscrasia remained uncertain. In the third case benign monoclonal gammopathy of the IgM-lambda type was diagnosed 13 years after idiopathic myelofibrosis. A review of the literature confirms a remarkably high incidence of monoclonal gammopathies in idiopathic myelofibrosis. Benign monoclonal gammopathy seems to occur in at least 8% of the patients while only a few cases of concomitant multiple myeloma have been reported. It may be speculated that plasma cell dyscrasias in idiopathic myelofibrosis reflect involvement of the lymphoid lineage in the neoplastic stem cell disorder.

Female↗
PubMed1988

Stimulation of coronary vascular PGI2 by organic nitrates.

The present study summarizes recent investigations in our laboratory, demonstrating that a number of organic nitrates, including glyceryltrinitrate, isosorbide dinitrate, isosorbide-2-mononitrate and the novel nitrate teopranitol stimulate the release of a prostacyclin (PGI2)-like antiplatelet activity from isolated bovine coronary arteries and veins. In bioassay experiments this increase amounted to 50 to 200% of control. Evidence for nitrate induced PGI2 stimulation is presented by inhibition of its formation by indomethacin and dexamethasone, the demonstration of inhibition of thrombin induced thromboxane generation of washed platelet suspensions by nitrate stimulated vessel incubates and an enhanced accumulation of the hydrolysis product of PGI2, 6-oxo-PGF1 alpha, in incubates of teopranitol stimulated vessels. This action is obtained at nanomolar, i.e. therapeutic concentrations of the compounds and requires the presence of free nitro group(s) at [exo] position of the isohexide molecule. There was no correlation between PGI2 release and the relaxing action of the nitrates on isolated vessel strips. The inhibitor of cyclic GMP accumulation, methylene-blue, also blocked the generation of the antiplatelet activity by glyceryltrinitrate and teopranitol. Recent evidence suggests that cGMP accumulation via intermediate nitrogen oxide (NO) production mediates the vascular effects of organic nitrates. Since NO is also a potent antiplatelet agent, it is concluded that a nitrate stimulated PGI2 release associated with or mediated by NO formation might explain the antiplatelet actions of organic nitrates in vitro and ex vivo.

Animals↗
PubMed1988

The Chirp Train Streaming test. A clinical approach to auditory selectivity and listening.

Traditionally, the auditory system is considered as capable, primarily, of frequency and temporal analysis. We introduce a new test, the CTS test, using tone glides (chirps), which takes into account the ability of the auditory system to form perceptual streams. Based on Békésy tracking, the test gives an auditory selectivity index, the streaming index or STIN. The STIN value together with the tracking pattern provide insight into the nature and cause of the patient's listening problems. In this paper, we use the STIN to develop a working hypothesis about the role of middle-ear silent mucosal metaplasia in presbyacusis. The test is described in detail, and the results for 560 patients (1,109 ears) are given. The validity, reliability, limitations, and interpretation of the test are discussed.

Adolescent↗
PubMed1987

Lupus anticoagulant associated syndrome in benign and malignant systemic disease--analysis of ten observations.

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1987

Congestive heart failure due to mitochondrial cardiomyopathy in Kearns-Sayre syndrome.

Despite extensive analysis of the ultrastructural changes in skeletal muscle fibers in chronic progressive external ophthalmoplegia (CPEO), similar changes in the heart muscle fibers of patients with cardiac involvement in CPEO, called Kearns-Sayre syndrome, have not been described in detail. We report the clinical long-term course in a patient with Kearns-Sayre syndrome in whom mitochondrial cardiomyopathy was suspected in vivo and was confirmed at autopsy as the underlying cause of severe dilative cardiomyopathy. Enlarged, abnormally structured, excessively augmented mitochondria and loss of myofibrils could be shown both in skeletal and heart muscle cells.

Adult↗
PubMed1987

Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers.

Coadministration of captopril has been shown to increase serum digoxin concentration. The effects of ramipril, a new angiotensin converting enzyme inhibitor, on serum digoxin concentration after multiple dosing were studied in 12 healthy volunteers. All subjects were receiving steady-state digoxin medication (0.5 mg daily), and ramipril (5 mg daily) was coadministered for 14 days. Serum digoxin concentration was measured repeatedly before, during and up to 1 week after ramipril coadministration at 8 a.m. (trough values) and on selected trial days at 11 a.m., 3 hours after the morning medication. Simultaneously, blood levels of ramipril and its active metabolite diacid were determined. Volunteers were followed closely for side effects and for changes in blood pressure, heart rate and electrocardiogram. Safety pharmacology included serial determination of sodium, potassium, serum glutamic oxaloacetic transaminase, creatinine and a full blood count. Mean serum digoxin concentration was not significantly influenced by ramipril coadministration with trough levels of 0.90 +/- 0.24 before, 0.93 +/- 0.38 during and 0.82 +/- 0.33 ng/ml after ramipril medication. The increase in serum digoxin concentration 3 hours after the morning dose was also not significantly affected by ramipril. Serum levels of ramipril and its diacid showed a wide range of variation. Mean serum potassium increased by 0.3 mmol/liter during ramipril coadministration with development of symptomless hyperkalemia (6.0 mmol/liter) in 1 subject. The only other side effect possibly related to ramipril was a dry cough in 1 subject. Both drugs were well tolerated. Ramipril showed no significant influence on serum digoxin levels in healthy volunteers.

Adult↗
PubMed1987

Relative and absolute numbers of human lymphocyte subpopulations. A comparison of immunofluorescence microscopy and flow cytometric methodologies with special reference to precision and reference values.

Lymphocyte subpopulations were determined in blood samples from blood donors (40 women and 45 men) using immunofluorescence microscopy and flow cytometric methodologies. The study demonstrates the value of both methods for the enumeration of lymphocyte subpopulations. The advantages of employing an automated flow cytometer system are better precision and speed. The automated systems require a large initial technical and financial burden and are therefore probably destined to be reserved for the larger laboratory. There is a need for an adequate lymphocyte standard which shows little variation between aliquots and can be used for interlaboratory comparisons.

Adolescent↗
PubMed1987

Defibrotide is equipotent to urokinase in stimulating arterial and venous thrombolysis.

The action of iv. defibrotide (100 mg/kg bolus injection, followed by 30 mg/kg x h) on arterial and venous thrombus formation was studied in rabbits and compared with iv. urokinase (4,000 IU/kg bolus injection, followed by 1,500 IU/kg x h). In comparison with saline treated controls, defibrotide reduced the thrombus weight by 43% in veins and 76% in arteries (P less than 0.01), while urokinase reduced the thrombus weight by 50% in veins and 71% in arteries. The data suggest a potent thrombolytic activity of defibrotide which is comparable to that of urokinase.

Animals↗
PubMed1987

Different sensitivities of arteries and veins to glyceryltrinitrate-induced relaxation and tolerance: an "in vitro" study on isolated vessels from rabbits.

Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxation (EC-10) were different in arteries (2 X 10(-8) mol/l) and in veins (2 X 10(-9) mol/l), indicating a higher sensitivity of veins than of arteries to low concentrations of GTN. After induction of GTN-tolerance (60 min preincubation with EC-90) the arterial vessels revealed a monophasic concentration response curve (EC-10: 10(-6); EC-50: 10(-5) mol/l). The relaxation at the lower concentration range was abolished (shift to the right at lower GTN-concentration). On the other hand, in veins the concentration-response curve was completely shifted to higher concentrations (EC-10: 10(-8) mol/l) and the high sensitivity component was diminished to 50%. However, the enhanced sensitivity of veins in comparison to arteries was preserved. 10(-3) mol/l cystein was unable to affect tolerance in arteries, but partially reversed the development of tolerance effects in veins. Moreover, 10(-6) mol/l indomethacin could mimic GTN-tolerance in arteries but not in veins. Thus, relaxation as well as tolerance induced by GTN, seem to be mediated at least by 2 different mechanisms. Only in arteries the prostaglandin system appears to be involved. On the other hand depletion of SH-groups seems to play a major role in veins in agreement with the hypothesis of Ignarro et al. (1981).

Animals↗
PubMed1986

[Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas].

The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗
PubMed1986

Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia.

A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.

Adult↗