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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    OR spectrum 14 (1992), S. 149-160 
    ISSN: 1436-6304
    Schlagwort(e): Lineare Programmierung ; logische Aussagen ; Binärvariablen ; Modellgenerator ; Linear programming ; predicates ; binary variables ; model generator
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Mathematik , Wirtschaftswissenschaften
    Beschreibung / Inhaltsverzeichnis: Summary We introduce in the field of formulating logical predicates in addition to linear programs. The error prone process of developing linear constraints including binary variables (“auxilliary formulations”) to accomplish this leads us to discuss the possibilities and capabilities of model generation. Based on Williams [12] we develop the formulae apparatus and discuss formulation and design problems for the development of our model generator now being implemented.
    Notizen: Zusammenfassung Wir geben eine Einführung in das Gebiet der Formulierung logischer Aussagen ergänzend zu Linearen Programmen. Der dazu notwendige, fehlerträchtige Prozeß der Aufstellung linearer Restriktionen unter der Verwendung von Binärvariablen („Ersatzformulierungen“) führt uns dazu, die Möglichkeiten und Fähigkeiten eines Modellgenerators für diesen Zweck zu diskutieren. Auf der Grundlage von Williams [12] entwickeln wir den Formelapparat und erörtern Formulierungs- und Entwurfsprobleme für die Entwicklung unseres sich jetzt in der Implementationsphase befindlichen Modellgenerators.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-1440
    Schlagwort(e): Angiotensin II ; Insulin ; Smooth muscle cell ; Vascular
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 × 10−10–1.7 × 10−6 M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin 11 induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin 11. In conclusion, insulin is able to enhance angiotensin 11 induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-1440
    Schlagwort(e): Na+/H+ antiport ; Hypertension ; Diabetic nephropathy ; Hereditary factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistantly observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9±2.4/78.4±1.5 mmHg; group 2, 113.9±3.6/76.1±1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43±0.43 10−3·s−1 in control subjects and was markedly elevated in EH (28.38±0.62 10−3·s−1 P〈0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54±0.57 10−3·s−1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2(26.95±0.73 10−3. s−1 ; P〈0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 72 (1994), S. 874-877 
    ISSN: 1432-1440
    Schlagwort(e): Bartter's syndrome ; Cardiovascular remodeling ; Diastolic dysfunction ; Intima/media complex
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In a 56-year-old normotensive white male subject with a 12-year history of hypokalemic alkalosis, hyperreninemia, and aldosteronism, the diagnosis of Bartter's syndrome was established on the basis of an impaired maximal renal diluting capacity and decreased distal fractional chloride absorption [CH2O/(CH2O + CCl)]. Negative urine analysis for diuretics suggested that this renal tubular defect was not secondary to diuretic (ab)use. In this normotensive patient with hyperreninemia and secondary aldosteronism, significant cardiovascular remodeling could be observed. Thus, in spite of normal arterial blood pressure and normal left ventricular systolic function (ejection fraction 〉 70%), impaired left ventricular diastolic function was observed using pulsed-wave Doppler echocardiography. Moreover, duplex analysis of the common carotid artery revealed significant intima-media hypertrophy with an average intima-media diameter of 0.9 mm (normal ≤ 0.6 mm). Also, forearm venous occlusion plethysmography revealed an abnormally high minimal forearm vascular resistance following a 10-min period of forearm ischemia handgrip exercise suggesting remodeling within the peripheral arterioles. Thus, in a patient with Bartter's syndrome and activated neurohormonal systems such as the renin-angiotensin system, cardiac and vascular remodeling can be observed in the absence of hypertension. In analogy to the results of experimental studies showing that angiotensin II and noradrenaline act as growth factors on cardiac and vascular cells, cardiovascular remodeling present in our patient with Bartter's syndrome may be explained by increased activity of angiotensin II and/or noradrenaline.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-1440
    Schlagwort(e): Angiotensin II ; Diltiazem ; Mitogenic effect ; Nifedipine ; Platelet-derived growth factor ; Vascular smooth muscle cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 μM did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 μM, while no significant influence was seen with concentrations from 10 nM up to 1 μM. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 70 (1992), S. 710-710 
    ISSN: 1432-1440
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-1440
    Schlagwort(e): Arterial Hypertension, structural changes ; Arteriolar hypertrophy and hyperplasia ; Na+/Li+-exchange ; Na+/H+-antiport ; Phosphatidylinositol metabolism ; Growth factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The most common haemodynamic abnormality in human essential hypertension is an increase in systemic vascular resistance. Morphologic substrate for increased flow resistance is a narrowing of the lumen of arteriolar resistance vessels. During the course of essential hypertension, this is associated with an increase in wall (mainly media) thickness due to hypertrophy and hyperplasia of vascular smooth muscle cells. In contrast to concepts interpreting media thickening strictly as structural adaptation to increased perfusion pressure, various lines of evidence also point to pressure independent factors. In this context, extracellular factors such as “growth factors” as well as alterations in the activity of intracellular messenger systems must be considered. Recent studies suggest that substances generally known to act as vasoconstrictors such as angiotensin II, noradrenaline and arginine-vasopressin may also stimulate vascular smooth muscle cell growth and proliferation. Intracellular messenger systems with possible significance in the response to trophins and/or mitogens of vascular smooth muscle cells are phospholipase C, protein kinase C and the Na+/H+-antiport. These systems have been demonstrated to be altered in hypertension supporting the concept that one endogenous factor in human essential hypertension with pathophysiological significance, at least in a subgroup of patients, may be an enhanced reactivity of vascular smooth muscle cells to trophic and mitogenic stimuli. In this context, intracellular messenger systems such as phospholipase C, protein kinase C and/or the Na+/H+-antiport may play an important pathophysiological role.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 72 (1994), S. 519-521 
    ISSN: 1432-1440
    Schlagwort(e): Iron-deficiency anemia ; Celiac disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report on a 40-year-old woman with a 2-year history of iron-deficiency anemia of unknown origin. Repeated endoscopic investigations in the past had revealed no abnormality of the gastrointestinal system on macroscopic examination. Oral iron supplementation was shown to have no effect on serum iron levels and had no influence on the anemia. Upper gastrointestinal endoscopy performed at our hospital confirmed normal macroscopic findings. However, jejunal biopsies revealed subtotal villous atrophy of the mucosa of the small intestine. A strict gluten-free diet led to an increase in serum iron, resolution of the anemia, and restitution of normal mucosal architecture. Thus iron-deficiency anemia may be the lone manifestation of celiac disease.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1440
    Schlagwort(e): Cell volume regulation ; Hypertonicity ; Lymphocytes ; Na+/H+ antiport ; Saline infusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The Na+/H+ antiport is a membrane transport protein that extrudes intracellular protons in exchange for extracellular sodium. Some details of its physiological and pathophysiological role remain poorly defined. Experimental evidence suggests that the antiporter is involved in the regulation of cell volume. In the present study, we therefore investigated the activity of the lymphocyte Na+/H+ antiport in nine healthy volunteers following acute hypertonic (2.5%) saline infusion (4 mmol NaCl/kg over 120 min). Antiport activity was measured after acidifying the cells with Na+ propionate (5–40 mM) using the fluorescent dye bis-carboxyethyl carboxyfluorescein. Hypertonic saline induced significant increases in plasma osmolality (308.4±2.3 vs. 293.5±2.7 mOsm/kg; P〈0.01), serum Na+ (150.8±3.7 vs. 138.9±0.5 mmol/kg; P〈0.01), and Cl− concentrations (118.0±3.9 vs. 101.1±1.0 mmol/kg; P〈0.01). Extracellular hypertonicity was followed by a stimulated activity of the lymphocyte Na+/H+ antiport with an increase in the apparent V max values from 2.44±0.16 to 3.27±0.34 10−3 s−1 (P〈0.01) and a slight rise in pK from 6.81±0.03 to 6.87±0.03 (P〈0.05) after hypertonic saline. In addition to antiport activation, cytosolic alkalinization was observed with cytosolic pH values averaging 6.90±0.02 before and 6.99±0.02 (P〈0.01) after hypertonic saline. Our results show for the first time that acute extracellular hypertonicity in man due to hypertonic NaCl loading is associated with a stimulated lymphocyte Na+/H+ antiport activity and cytosolic alkalinization.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-1440
    Schlagwort(e): Na-K-ATPase ; Ouabain ; Natriuretic hormone ; Intracellular electrolytes ; Peripheral vascular resistance ; Cardiac function ; Hypertension ; Calcium entry blockade ; Human studies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 µg ouabain/kg body weight inhibited red blood cell (RBC) — Na-K-ATPase by 49% which was accompanied by a significant increase in RBC — ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vaso-constriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase — in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion — may play a role in the pathogenesis of human arterial hypertension.
    Materialart: Digitale Medien
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