Showing papers by "University of Düsseldorf published in 1990"

Control of coronary vascular tone by nitric oxide.

Abstract: A specific difference-spectrophotometric method was used to measure nitric oxide (NO) release into the coronary effluent perfusate of isolated, constant-flow-perfused guinea pig hearts. Authentic NO applied into the coronary circulation decreased vascular resistance dose dependently and enhanced coronary release of cyclic GMP (cGMP) fivefold. Increasing oxygen tension in aqueous solutions from 150 to 700 mm Hg decreased NO half-life (5.6 seconds) by 32%. During single passage through the intact coronary system, 86% of the infused NO was converted to nitrite ions. Oxidation of NO was more than 30 times faster within the heart than in aqueous solution. Endogenously formed NO was constantly released into the coronary effluent perfusate at a rate of 161 +/- 11 pmol/min. The NO scavenger oxyhemoglobin and methylene blue increased coronary resistance and decreased cGMP release (basal release, 342 +/- 4 fmol/min), whereas superoxide dismutase reduced coronary resistance. L-Arginine (10(-5) M) slightly decreased coronary perfusion pressure and enhanced release of cGMP. NG-Monomethyl L-arginine (10(-4) M) reduced basal release of NO and cGMP by 26% and 31%, respectively, paralleled by a coronary vasoconstriction. Bradykinin in the physiological range from 5 x 10(-11) M to 10(-7) M dilated coronary resistance vessels, which was paralleled by the release of NO and cGMP. Onset of NO release preceded onset of coronary vasodilation in all cases. Upon stimulation with bradykinin, amounts of endogenously formed NO were within the same range as the dose-response curves for exogenously applied NO both for changes in coronary resistance and cGMP release. Acetylcholine (10(-5) M), ATP (10(-5) M), and serotonin (10(-8) M) increased the rate of NO and cGMP release, resulting in coronary vasodilation. Our data suggest the following: 1) NO, the most rapidly acting vasodilator presently known, is metabolized within the heart mainly to nitrite and exhibits a half-life of only 0.1 second; 2) in the unstimulated heart, basal formation of NO may play an important role in setting the resting tone of coronary resistance vessels; 3) the kinetics and quantities of NO formation suggest that NO is causally involved in the bradykinin-induced coronary vasodilation; and 4) amounts of NO formed within the heart stimulated with ATP, acetylcholine, and serotonin are effective for vasodilation.

Protective systems against active oxygen species in spinach: response to cold acclimation in excess light.

Abstract: Spinach (Spinacia oleracea L.) plants were acclimated to 1° C or maintained at 18° C under the same light regime (260–300 μmol photons·m−2·s−1). The cold acclimation led to several metabolic and biochemical changes that apparently include improved protection of the photosynthetic apparatus against active oxygen species. In particular, cold-acclimated leaves exhibited a considerably higher ascorbate content and significantly increased activities of superoxide dismutase, ascorbate peroxidase, and monodehydroascorbate reductase in the chloroplasts. The level of dehydroascorbate reductase did not alter. Catalase activity decreased. The photosynthetic pigment composition of cold-acclimated spinach was characterized by increased levels of the xanthophylls lutein + zeaxanthin and violaxanthin. The observed changes are discussed in terms of their possible relevance for plant resistance to photoinhibition at chilling temperatures.

Ultradifferentiable functions and Fourier analysis

Abstract: Classes of non-quasianalytic functions are classically defined by imposing growth conditions on the derivatives of the functions. It was Beuding [1] (see Bjorck [2]) who pointed out that decay properties of the Fourier transform of a compactly supported function can be used for this purpose equally well. In the present article we modify Beuding's approach. More precisely, we call w: [0,00[--+ [0, oo[ a weight function if w is continuous and satisfies

Cortical and subcortical glucose consumption measured by pet in patients with huntington's disease

Abstract: In 23 patients with moderate to severe Huntington's disease (HD) and 21 normal volunteers, the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in the cerebellum, thalamus, striatum, and cortex using positron emission tomography and the 18F-deoxyglucose method. In contrast to previous reports, rCMRGlc was reduced not only in the striatum, but also in the cerebral cortex of patients with HD as compared with normal subjects. No significant difference between HD patients and normal subjects was found for thalamic and cerebellar rCMRGlc. To investigate the relationship between the clinical status and rCMRGlc, correlation coefficients for the clinical data were calculated for absolute values of rCMRGlc and for cerebellar ratios (CR) of rCMRGlc. The duration of chorea correlated significantly only with the absolute values of frontoparietal and temporo-occipital rCMRGlc and with the CRs of most cortical regions evaluated. The severity of chorea correlated significantly only with lentiform nucleus rCMRGlc. The severity of dementia correlated significantly only with the frontoparietal and temporo-occipital rCMRGlc, the CRs of most cortical regions, and the CR for the caudate nucleus. The degree of disability correlated significantly with the CRs of all regions evaluated except the occipital and the superior frontal cortex. It appears from this study that there is a reduction not only for the striatum but also for cortical rCMRGlc in patients with manifest HD, and that the cortical reduction of rCMRGlc contributes to the severity of clinical symptoms in these patients. This challenges the concept that dementia in HD is of purely subcortical origin.

Isolation and characterization of the Pichia stipitis xylitol dehydrogenase gene, XYL2, and construction of a xylose-utilizing Saccharomyces cerevisiae transformant.

Abstract: A P. stipitis cDNA library in lambda gt11 was screened using antisera against P. stipitis xylose reductase and xylitol dehydrogenase, respectively. The resulting cDNA clones served as probes for screening a P. stipitis genomic library. The genomic XYL2 gene was isolated and the nucleotide sequence of the 1089 bp structural gene, and of adjacent non-coding regions, was determined. The XYL2 open-reading frame codes for a protein of 363 amino acids with a predicted molecular mass of 38.5 kDa. The XYL2 gene is actively expressed in S. cerevisiae transformants. S. cerevisiae cells transformed with a plasmid, pRD1, containing both the xylose reductase gene (XYL1) and the xylitol dehydrogenase gene (XYL2), were able to grow on xylose as a sole carbon source. In contrast to aerobic glucose metabolism, S. cerevisiae XYL1-XYL2 transformants utilize xylose almost entirely oxidatively.

Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers.

Abstract: Singlet molecular oxygen (1O2) has been shown to be generated in biological systems and is capable of damaging proteins, lipids and DNA. The ability of some biological antioxidants to quench 1O2 was studied by using singlet oxygen generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The carotenoid lycopene was the most efficient 1O2 quencher (kq + kr = 31 x 10(9) M-1 s-1). Tocopherols and thiols were less effective. The singlet oxygen quenching ability decreased in the following order: lycopene, gamma-carotene, astaxanthin, canthaxanthin, alpha-carotene, beta-carotene, bixin, zeaxanthin, lutein, bilirubin, biliverdin, tocopherols and thiols. However, the compounds with low quenching rate constants occur at higher levels in biological tissues. Thus, carotenoids and tocopherols may contribute almost equally to the protection of tissues against the deleterious effects of 1O2. The quenching abilities of carotenoids and tocopherols were mainly due to physical quenching. In case of some thiols chemical quenching also plays a significant role. Carotenoids and tocopherols have been reported to exert a protective action against some types of cancer.

Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation

Abstract: Sunlight is a well-established factor in the induction and exacerbation of lupus erythematosus. Although experimental reproduction of lupus erythematosus lesions with wavelengths shorter than 320 nm was demonstrated previously, the effect of wavelengths longer than 320 nm was not investigated adequately. In this study we show that the action spectrum of lupus erythematosus reaches into the UVA region. A total of 128 patients with lupus erythematosus underwent phototesting with the use of polychromatic UVB and long-wave UVA. Subsets of the disease consisted of discoid lupus erythematosus (n = 86), subacute cutaneous lupus erythematosus (n = 22), and systemic lupus erythematosus (n = 20). Skin lesions clinically and histologically compatible with lupus erythematosus were induced in 64% of patients with subacute cutaneous lupus erythematosus, 42% of patients with discoid lupus erythematosus, and 25% of patients with systemic lupus erythematosus. The action spectrum of the induced lesions was within the UVB range in 33% of patients, in the UVA range in 14%, and in the UVB and UVA range in 53%. In positive test reactions patchy dark erythema and urticarial plaques developed within a few days. In some patients typical discoid lesions persisted for months.

Evidence for abnormal platelet glycoprotein expression in diabetes mellitus.

Abstract: In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54,100 x 1.27 +/- 1 vs. 39,100 x 1.3 +/- 1 GPIIB/IIIA: 77,500 x 1.3 +/- 1 vs. 62,700 x 1.3 +/- 1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0.52 +/- 0.07; r (diabetic) = 0.46 +/- 0.1). Additionally, von Willebrand factor-related antigen (vWF: AG) was increased to 129% x 1.3 +/- 1 in diabetics vs. 111% x 1.4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0.38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone-marrow megakaryocyto- thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.

Premotor cortex and conditional motor learning in man

Abstract: The role of premotor cortex (PMC) in conditional motor learning tasks in man was investigated. Patients with PMC lesions had to learn to associate 6 different visual, tactile or auditory stimuli with 6 different arm movements which were previously rehearsed (Task A). A comparative task involved an association between the same set of sensory stimuli and 6 spatial locations (Task B). Patients with PMC lesions were only impaired when they had to recall a movement from memory on the basis of a sensory cue (Task A), but not for an association involving spatial location (Task B). This indicates that the PMC plays a role in sensory conditional motor learning.

Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: effects on pulmonary capillary pressure and ventilation-perfusion distributions.

Abstract: Nine patients who had developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2) (12.5-35.0 ng.kg-1.min-1). Whether PGI2 might decrease the pulmonary capillary pressure (PCP) obtained by analysis of the pulmonary artery occlusion pressure decay curve and improve systemic oxygen delivery was examined. Gas exchange alterations induced by PGI2 were analyzed by using the multiple inert gas elimination technique. PGI2 reduced the pulmonary artery pressure from 35.6 to 28.8 mmHg (P less than 0.001) and the PCP from 22.9 to 19.7 mmHg (P less than 0.01) without changing the contribution of the pulmonary venous resistance to the total pulmonary vascular resistance. The cardiac index increased from 4.2 to 5.7 1.min-1.m-2 (P less than 0.001) due to both increased stroke volume and heart rate. Despite a marked deterioration of ventilation-perfusion (VA/Q) matching with increased true intrapulmonary shunt flow from 28.6% to 38.6% (P less than 0.01) of the cardiac output, the PaO2 was unchanged due to increased mixed venous oxygen content indicated by an augmented mixed venous PO2 (from 37.0 to 41.9 mmHg, P less than 0.01). This caused a 35% (P less than 0.001) increase of the systemic oxygen delivery rate. Thus, short-term infusions of PGI2 reduced PAP and PCP without deleterious effects on arterial oxygenation in patients with ARDS. Hence, PGI2 may be useful to lower pulmonary vascular pressures in patients with ARDS.

Variation of perisylvian and calcarine anatomic landmarks within stereotaxic proportional coordinates.

Abstract: This investigation describes the variability in location of functionally important persylvian landmarks and of the calcarine sulcus within the Talairach stereotaxic grid, a system frequently used for cortical localization in functional images. Twenty healthy volunteers (40 hemispheres) had MR imaging under stereotaxic conditions. Outlines of the following structures were directly identified on sagittal 5-mm MR sections and marked on individual proportional grid overlays: inferior central sulcus, inferior precentral sulcus, inferior postcentral sulcus, anterior ascending ramus and posterior rami of the sylvian fissure, superior temporal sulcus, and calcarine sulcus. Maximal variation zones for these landmarks were defined by superimposition of the standardized individual data on a standard stereotaxic grid. The sulcal variation zones measured 1.5-2.0 cm. The findings indicate that macroanatomic individuality in the cerebral surface cannot be accounted for adequately by proportional coordinates, and that this method does not allow precise definition of anatomically based regions of interest for functional imaging. Instead, MR mapping of the individual sulcus pattern should be used to generate brain templates.

Carotid artery disease assessed by color Doppler flow imaging: correlation with standard Doppler sonography and angiography.

Abstract: Carotid artery disease was assessed in 180 patients by means of color Doppler flow imaging. Color Doppler findings in 360 carotid arteries were compared with the results of standard Doppler sonography, and color Doppler findings in 60 bifurcations were compared with the results of intraarterial angiography. The sensitivity of color Doppler for the detection of carotid disease was 100% when compared with angiography. The accuracy of color Doppler in classifying minor (40-60%), moderate (61-80%), and severe (81-90%) stenosis ranged from 91.3% to 97.8% vs standard Doppler sonography, and from 91.7% to 95.8% vs angiography. Whereas all occlusions were identified correctly by both color Doppler and angiography, four pseudoocclusions of the carotid artery were misdiagnosed as occluded. Characteristic features providing reliable criteria of the degree of stenosis are (1) intensity, extent, and duration of color fading; (2) postprocessed systolic peak frequency; (3) plaque extent on serial sonograms; and (4) poststenotic flow patterns. Display of hemodynamic disturbances induced by less pronounced plaques showed highly variable patterns that could not be anticipated from the plaque morphology alone. Thus, color Doppler preserves the advantages of standard Doppler and duplex sonography but provides additional information about otherwise anechoic necrotic and thrombotic material that often causes cerebral embolisms. With atherogenesis, repair mechanisms may be sustained or progression be stopped by reducing the risk factors and instituting medical treatment; thus, the application of this noninvasive technique is important.

Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86).

Abstract: In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.

T cell activation in Guillain‐Barré syndrome and in MS: Elevated serum levels of soluble IL‐2 receptors

Abstract: Guillain-Barre syndrome (GBS), chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS) are disorders with presumed immunopathogenesis. To obtain evidence for T cell activation, we determined serum concentrations of soluble interleukin-2 receptors (sIL-2 R) in 50 patients with GBS, 24 with CIDP, and 54 with MS. Both in GBS and clinically active MS sIL-2 R levels were markedly increased compared with those in patients with other neurologic diseases. Four of 24 CIDP patients had abnormally increased sIL-2 R concentrations. sIL-2 R concentrations decreased with clinical improvement in serial samples taken from GBS patients, but were not otherwise correlated with disease severity. These data establish that T cells are activated in GBS and some patients with CIDP, and corroborate earlier evidence that activated T cells are circulating in the blood of MS patients.

Reduction of acetophenone to R (+)-phenylethanol by a new alcohol dehydrogenase from Lactobacillus kefir

Abstract: A new alcohol dehydrogenase catalysing the enantioselective reduction of acetophenone to R(+)-phenylethanol was found in a strain of Lactobacillus kefir. A 70-fold enrichment of the enzyme with an overall yield of 76% was obtained in two steps. The addition of Mg2+ ions was found to be necessary to prevent rapid deactivation. The enzyme depends essentially on NADPH and was inactive when supplied with NADH as the coenzyme. Important enzymological data of the dehydrogenase are: K m (acetophenone) 0.6 mM, K m (NADPH) 0.14 mM, and a pH optimum for acetophenone reduction at 7.0. Addition of EDTA leads to complete deactivation of the enzyme activity. Added iodoacetamide or p-hydroxymercuribenzoate cause only slight inhibition, revealing that the active centre of the enzyme contains no essential SH-group. Besides acetophenone several other aromatic and long-chain aliphatic secondary ketones are substrates for this enzyme. Batch production of phenylethanol was examined using three different methods for the regeneration of NADPH: glucose/glucose dehydrogenase, glucose-6-phosphate/glucose-6-phosphate dehydrogenase, and isopropanol.

Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve.

Abstract: A cDNA clone containing the entire coding region of rat apolipoprotein D (Apo D) was isolated from a cDNA library of regenerating sciatic nerve by differential hybridization Only small amounts of Apo D mRNA were detected in noninjured mature nerve Moderately increased levels of Apo D transcripts were found in transected nerves, which were prevented from regeneration by ligation In contrast, in regenerating crushed nerve, the steady-state level of Apo D mRNA transiently increased at least 40-fold above control levels at the time when axons from the proximal stump grow into the distal nerve segment Using transverse sections and primary cell cultures from regenerating nerve, Apo D transcripts could be localized by in situ hybridization in endoneurial fibroblasts but not in Schwann cells, macrophages or perineurial and epineurial cells Apo D protein (Mr 328 kd) was secreted and accumulated in the endoneurial extracellular space where it could be detected in lipoprotein fractions by immunoblotting using established antibodies to human Apo D High level expression of Apo D mRNA seems to be a novel regeneration-associated molecular event of endoneurial fibroblasts indicating a function for Apo D and fibroblasts in nerve repair

The role of interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.

Abstract: The role of interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon-gamma markedly augmented both myelin-induced and T-cell line-mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon-gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon-gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon-gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.

How effective is cushioned therapeutic footwear in protecting diabetic feet? A clinical study.

Abstract: Therapeutic footwear with cushioned insoles was supplied to 50 diabetic patients with severe peripheral neuropathy and/or peripheral vascular disease (age 59(SD 12) years, known duration of diabetes 17(7) years), 36 of whom had a history of foot ulceration. A follow-up examination was carried out 25(14) months later, except in 8 patients who died from conditions unrelated to their foot lesions, and 1 patient who died from sepsis due to upper limb amputation. Among the surviving 41 patients, intercurrent foot lesions during follow-up occurred in significantly fewer (42 %) of the 26 who had worn the shoes regularly than of the 15 who had worn the shoes irregularly (87 %, p < 0.01). At follow-up, only 15 % of the 41 patients were being treated for foot-lesions, compared with 78 % of these 41 patients before cushioned shoes were provided. It is concluded that the availability of therapeutic shoes with cushioned insoles for diabetic patients at risk of foot lesions decreases the morbidity due to the diabetic foot syndrome.

Ethanol formation in adh0 mutants reveals the existence of a novel acetaldehyde-reducing activity in Saccharomyces cerevisiae.

Abstract: A strain of Saccharomyces cerevisiae has been constructed which is deficient in the four alcohol dehydrogenase (ADH) isozymes known at present. This strain (adh0), being irreversibly mutated in the genes ADH1, ADH3, and ADH4 and carrying a point mutation in the gene ADH2 coding for the glucose-repressible isozyme ADHII, still produces up to one third of the theoretical maximum yield of ethanol in a homofermentative conversion of glucose to ethanol. Analysis of the glucose metabolism of adh0 cells shows that the lack of all known ADH isozymes results in the formation of glycerol as a major fermentation product, accompanied by a significant production of acetaldehyde and acetate. Treatment of glucose-growing adh0 cells with the respiratory-chain inhibitor antimycin A leads to an immediate cessation of ethanol production, demonstrating that ethanol production in adh0 cells is dependent on mitochondrial electron transport. Reduction of acetaldehyde to ethanol in isolated mitochondria could also be demonstrated. This reduction is apparently linked to the oxidation of acetaldehyde to acetate. Preliminary data suggest that this novel type of ethanol formation in S. cerevisiae is associated with the inner mitochondrial membrane.

Clinical use of the magnetic stimulator in the investigation of peripheral conduction time.

Abstract: The application of rapidly changing magnetic fields (magnetic stimulation) over the neck or lower back elicits EMG responses in the muscles of the arm or leg respectively. Such responses have stable onset latencies but their amplitudes vary depending on the position of the coil over the neck or lower back. Supramaximal responses could not be obtained. Comparison of onset latencies with estimates of peripheral conduction time using a conventional F-wave technique suggest that the site of excitation of the motor axons is about 1.3 msec conduction time distal to the cervical motoneurons and 3 msec distal to the lumbosacral motoneurons. Response configuration after paravertebral magnetic stimulation was similar to that of the standard electrically evoked M-wave in the small hand muscles but not in lower limb muscles. Responses in lower limb muscles after paravertebral magnetic stimulation may consist of additional F-wave and H-reflex components. The possible clinical role of paravertebral magnetic stimulation in the investigation of peripheral and central motor pathways is discussed in the light of these findings.

Trends and future prospects of aqueous two-phase extraction.

Abstract: Aqueous two-phase systems form the basis for an extraction technology of proteins. Trends in the development of the technology are reviewed and discussed with regard to future applications.

Cis- and Trans-isomeric fatty acids in plasma lipids of newborn infants and their mothers.

Abstract: The proportionate fatty acid composition of plasma lipids was determined by high-resolution gas-liquid chromatography in 30 pairs of mothers and their term infants at the time of birth. Trans-fatty acids were found at similar percentage levels in maternal and infantile plasma, evidence for the first time of their placental permeability. In umbilical plasma, linoleic and alpha-linolenic acids contributed markedly smaller portions to total fatty acids, in contrast to clearly higher proportions of their long-chain polyunsaturated metabolites (LCP). Significantly larger percentage values in cord than in maternal plasma were found for those LCP that are structural components of brain lipids, which may reflect a discriminating placental transport mechanism for certain physiologically important LCP.