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C Hübner

Publications and source records attributed to C Hübner.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Monitoring aortocoronary bypass. A new experimental approach].

Only few data are known concerning haemodynamic parameters and pathomechanisms of small vessels and bypass grafts. No easy-to-use bedside method exists for monitoring. We developed a miniaturised implantable Doppler probe linked to a 20 MHz pulsed Doppler system. In a circulation model and in animal studies we can show the accuracy of this method. We conclude that the implantable pulsed Doppler system is a sensitive method for monitoring the haemodynamics of small vessels.

Animals↗
PubMed1993

Oxidized LDL-induced leukocyte/endothelium interaction in vivo involves the receptor for platelet-activating factor.

Leukocyte adhesion and subendothelial emigration, constant hallmarks of early atherogenesis, have been ascribed to the action of oxidized low-density lipoprotein (oxLDL). Using intravital fluorescence microscopy in the skinfold-chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion in vivo through a mechanism that depends on the generation and/or action of both leukotrienes and superoxide radicals. On the basis of the fact that oxygen radical-catalyzed peroxidation of phospholipids results in the generation of fragments with short sn2 residues, which besides authentic platelet-activating factor (PAF), activate the receptor for PAF on leukocytes and thereby induce leukocyte adhesion, we asked whether pretreatment of hamsters with a specific PAF receptor antagonist (WEB2170; 1 mg/kg of body weight IV, 10 minutes before oxLDL) attenuates leukocyte adhesion after injection of oxLDL (4 mg/kg of body weight IV, oxidized by 7.5 mumol/L Cu2+ for 18 hours at 37 degrees C). We demonstrate herein that in contrast to untreated control animals in which oxLDL elicited rolling and adhesion of circulating leukocytes to the endothelium of venules and arterioles, oxLDL-induced leukocyte adhesion was significantly attenuated in WEB2170-pretreated animals. These changes cannot be ascribed to alterations of microhemodynamic parameters and, hence, wall shear conditions. This finding indicates that oxLDL-induced leukocyte/endothelium interaction involves the PAF receptor, which may function both as a receptor for authentic PAF or for PAF-like lipids that are generated in a free radical-catalyzed peroxidation of phospholipids.

Animals↗
PubMed1993

Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency.

Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity.

Cells, Cultured↗
PubMed1993

Stimulation of leukocyte/endothelium interaction by oxidized low-density lipoprotein in hairless mice. Involvement of CD11b/CD18 adhesion receptor complex.

BACKGROUND: The adhesion of leukocytes to the vascular endothelium has been identified as a constant, early feature of atherogenesis. Using a skinfold chamber model in hamsters for intravital microscopy, we have recently demonstrated the chemotactic and adhesion-promoting action of oxidatively modified low density lipoprotein (oxLDL) in vivo. EXPERIMENTAL DESIGN: In order to rule out a species specificity of the experimental approach, and to investigate the involvement of leukocyte adhesion receptors in oxLDL-induced leukocyte/endothelium interaction, we have adapted the skinfold chamber model to hairless mice. Using intravital fluorescence microscopy, leukocyte/endothelium interaction in a fine striated skin muscle was assessed during the time course after intravenous injection of native human LDL (4 mg/kg body weight) and oxLDL (oxidized in vitro by 7.5 microM Cu2+, 6 hours, 37 degrees C) into control mice and into mice pretreated with either the selective inhibitor of leukotriene biosynthesis MK-886 (20 mumol/kg body weight, intravenously, 10 minutes before oxLDL) or with a monoclonal antibody directed towards the CD11b subunit of the CD11b/CD18 adhesion receptor complex on leukocytes (monoclonal antibody anti-Mac1, 0.5 mg/kg, iv, 10 minutes before oxLDL). RESULTS: We demonstrate in this study that injection of oxLDL (4 mg LDL-cholesterol/kg, intravenously, oxidized by 7.5 microM Cu2+, 6 hours, 37 degrees C), but not of native LDL or LDL-free Cu(2+)-solution, elicits the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules (173 +/- 75 cells/mm2 at 20 minutes after oxLDL, mean +/- SD) and arterioles (119 +/- 74 cells/mm2 at 20 minutes after oxLDL, mean +/- SD) in the mice. OxLDL-induced leukocyte adhesion was entirely prevented by pretreatment of the animals with the inhibitor of leukotriene biosynthesis or with monoclonal antibody anti-Mac-1. CONCLUSIONS: These results demonstrate the involvement of leukotrienes and of the CD11b/CD18 adhesion receptor complex in oxLDL-induced leukocyte adhesion in vivo and rule out a species specificity of this pathophysiologic event.

Animals↗
PubMed1992

Exposure of HIV-infected cells to phospholipid leads to membrane alterations and selective growth retardation.

The effect of exogenous phosphatidylcholine on structure and function of plasma membranes from HIV-1-producing cells and from their non-infected counterparts was determined. The membrane protein composition was not affected by phospholipid treatment. Membrane fluidity and Ca(2+)-permeability were increased in virus-producing cells and in control cells after lipid treatment. The triacylglycerol content of the plasma membranes was increased in virus-producing cells after lipid treatment, whereas the content of phospholipid and cholesterol was not changed. The increased triacylglycerol content was in accordance with a relatively higher rate of [14C]oleic acid incorporation into triacylglycerols of the virus-producing cells after lipid treatment as shown by metabolic labeling. The results suggest that a latent cytopathic effect of HIV-infection becomes manifest if the cells are exposed to exogenous phospholipid and this may open a way to preferentially eliminate HIV-producing cells.

Calcium↗
PubMed1992

Experimental and first clinical experiences with implantable ultrasonic Doppler probes for postoperative bypass control after coronary surgery.

Concerning postoperative bypass hemodynamics after open heart surgery only few data are known. With this new implantable doppler probe we developed an easy-to-use bedside method for monitoring postoperative bypass function after coronary artery bypass grafting. The accuracy of our method is shown by using a circulation model and by animal studies. Furthermore first clinical data are shown which support our conclusion of having found a sensitive method for monitoring small vessels' hemodynamics.

Aged↗
PubMed1992

Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo.

Low density lipoprotein modified by oxidation (Ox-LDL) causes adhesion of leukocytes to the endothelium, a feature common in early atherogenesis. Because leukocyte adhesion under various pathophysiological conditions involves superoxide generation, we explored the possibility that superoxide is likewise involved in leukocyte adhesion in response to Ox-LDL. For our studies, we used the dorsal skin fold chamber model for intravital microscopic observation of leukocyte-endothelium interactions in hamsters. We show here that injection of human LDL (4 mg/kg LDL cholesterol oxidatively modified by incubation in 7.5 microM Cu2+ for 18 hours at 37 degrees C) elicited in control hamsters (n = 7) the rolling and adhesion of circulating leukocytes along the endothelium of arterioles and postcapillary venules. This adhesion was significantly attenuated when hamsters were pretreated with bovine copper-zinc-superoxide dismutase (CuZn-SOD, 0.25 mg/kg, n = 7) or heparin (2,000 IU/kg, n = 7). The CuZn-SOD infusion and the heparin-induced release of extracellular SOD from endothelial cell surfaces to plasma resulted in nearly equal plasma SOD activities. Further inhibition of Ox-LDL-induced leukocyte adhesion could not be achieved by increasing the dose of CuZn-SOD to 5 mg/kg (n = 6). Pretreatment of the hamsters with inactivated CuZn-SOD showed no effect. These results indicate that Ox-LDL stimulates leukocyte adhesion through a superoxide-dependent step, and they indicate a possible mechanism by which antioxidants might inhibit the onset of experimental and clinical atherosclerosis.

Animals↗
PubMed1992

[Muscular strength: an indicator of nutritional status].

A hand dynamometer was used to measure muscle strength in 207 patients admitted to the Gastroenterology service of a general hospital. Validation of international standards in a normal population of both sexes and different ages revealed that our normals perform at the 25% percentile of international values. Results were correlated with other measurements of nutritional status, namely anthropometric measurements, serum albumin level and tuberculin test. Compared to normals, muscle strength was significantly (p < 0.01) lower in patients with body mass index under 19, cutaneous tricipital folding < 85%, brachial circumference < 85%, and serum albumin < 3.5 g/dl. No difference in muscle strength between tuberculin positive or negative subjects was observed. None of the nutritional parameter was helpful to predict complications in patients submitted to surgery. Thus, muscle strength is a useful parameter to evaluate nutritional status but, similar to other measurements, is not predictive of surgical complications.

Adolescent↗
PubMed1991

Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters.

Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury.

Animals↗
PubMed1991

Oxidatively modified human low-density lipoprotein stimulates leukocyte adherence to the microvascular endothelium in vivo.

In vitro studies indicate that oxidatively modified low-density lipoprotein (oxLDL) promotes leukocyte sticking to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we investigated whether systemic administration of human LDL, oxidized by Cu2+, elicited leukocyte/endothelium interaction in vivo. While no effect was seen after injection of native LDL, oxLDL administration resulted in an immediate induction of leukocyte rolling along the microvascular endothelium and subsequent firm sticking to the wall of postcapillary venules as well as arterioles. The presented model may provide an alternative experimental approach to long-term feeding studies with atherogenic diets for the in vivo investigation of leukocyte/endothelium interaction in early atherogenesis.

Adult↗
PubMed1991

Dextran sulphate reduces diphenylhexatriene anisotropy in human peripheral blood lymphocytes: impact on plasma membrane fluidity and HIV-cytopathogenicity.

Cytopathogenicity of HIV and other enveloped viruses is reduced by membrane fluidizing agents and by dextran sulphate (DS). To investigate whether DS exerts its antiviral action via plasma membrane fluidization of host cells, we performed anisotropy measurements on human peripheral blood lymphocytes (PBL) using the fluorescent marker diphenylhexatriene. Anisotropy was decreased in DS-exposed PBL indicating increased fluidity in the hydrophobic membrane interior.

Adult↗
PubMed1991

Dietary fish oil reduces leukocyte/endothelium interaction following systemic administration of oxidatively modified low density lipoprotein.

BACKGROUND: In vitro and in vivo experiments have demonstrated the role of oxidatively modified low density lipoprotein (oxLDL) in eliciting leukocyte/endothelium interaction during early atherogenesis. METHODS AND RESULTS: In the present study we investigated the effect of dietary fish oil on oxLDL-induced leukocyte/endothelium interaction using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters. Hamsters were fed for 4 weeks prior to the experiments with either standard laboratory chow or a diet supplemented with 5% of a fish oil concentrate (18% eicosapentaenoate, 12% docosahexaenoate). The efficacy of the fish oil diet was demonstrated by the incorporation of fish oil-derived omega-3 fatty acids into plasma, leukocyte, and erythrocyte lipids. In control hamsters (n = 7) and fish oil-fed hamsters (n = 7), leukocyte/endothelium interaction was assessed in the time course after intravenous injection of human LDL (4 mg/kg), oxidized by 7.5 microM Cu2+ (6 hours, 37 degrees C). In control hamsters, injection of oxLDL elicited the rolling and sticking of leukocytes to the endothelium of arterioles and postcapillary venules with a maximum 15 minutes after injection (arterioles: from 3 +/- 1 to 91 +/- 25 cells/mm2 at 15 minutes; venules: from 13 +/- 6 to 150 +/- 46 cells/mm2 at 15 minutes; mean +/- SD). This phenomenon was significantly reduced in fish oil-fed hamsters, where 15 minutes after injection of oxLDL leukocyte sticking reached a maximum of only 15 +/- 7 and 20 +/- 5 cells/mm2 in arterioles and postcapillary venules, respectively (p less than 0.01 versus control animals). CONCLUSIONS: The results of the present study suggest that inhibition of leukocyte/endothelium interaction may be one of the mechanisms by which dietary fish oil exerts its protective effects on experimental and clinical atherogenesis.

Animals↗
PubMed1991

Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters.

In vitro studies indicate that oxidatively modified low density lipoprotein (oxLDL) promotes leukocyte adhesion to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters, we studied whether (a) oxLDL elicits leukocyte/endothelium interaction in vivo, and whether (b) leukotrienes play a mediator role in this event. Leukocyte/endothelium interaction was assessed in the time course after intravenous injection of native human LDL (4 mg/kg body wt) and of oxLDL (7.5 microM Cu++, 6 h, 37 degrees C) into control hamsters and into hamsters, pretreated with the selective leukotriene biosynthesis inhibitor MK-886 (20 mumol/kg, i.v.). While no effect was seen after injection of native LDL, oxLDL elicited an immediate induction of leukocyte adhesion to the endothelium of arterioles and postcapillary venules. Total and differential leukocyte counts suggest that all leukocyte subsets were likewise affected by oxLDL with no specific preference for monocytes. Stimulation of leukocyte adhesion was entirely prevented in inhibitor-treated animals, suggesting the important mediator role of leukotrienes in oxLDL-induced leukocyte/endothelium interaction.

Adult↗
PubMed1990

Effects of membrane lipid and fluidity modifications on HIV-1 infectibility of primate lymphocytes in vitro.

Although most non-human primates, except the chimpanzee and the gibbon in vivo are not infectible by HIV-1, lymphocytes of several of these species can be infected by HIV-1 in vitro. In order to investigate whether the in vitro infectibility of primate lymphocytes might be attributed to plasma membrane adaptation processes or to serum factors, we compared HIV-1 infectibility of cultivated peripheral blood lymphocytes of macaques and of baboons on day one and on day ten of cultivation. These data were correlated to plasma membrane lipid composition and membrane fluidity. We found a correlation between increased HIV-1 in vitro infectibility and changes in plasma membrane lipid composition resulting in decreased membrane fluidity of cultured primate lymphocytes.

Animals↗
PubMed1990

Decreased binding of HIV-1 and vasoactive intestinal peptide following plasma membrane fluidization of CD4+ cells by phenytoin.

Plasma membrane fluidity of intact peripheral blood lymphocytes (PBL) of phenytoin-treated nonepileptic patients and phenytoin-treated CD4+ lymphoid cells H9 and K37 was determined by fluorescence anisotropy measurements. Anisotropy values of the membrane probe 6-(9-anthroyloxy) stearic acid were decreased in all cell types as compared with controls, indicating increased plasma membrane fluidity of phenytoin-treated cells. Specific binding of 125I-labeled vasoactive intestinal peptide (VIP) to its cellular receptor CD4 on PBL was decreased in PBL of phenytoin-treated patients as compared with untreated, healthy subjects. Adsorption of a different ligand to the CD4 receptor on PBL, the human immunodeficiency virus type 1 (HIV-1), was likewise abolished to PBL of phenytoin-treated patients and phenytoin-treated CD4+ H9 and K37 cells, as assessed by indirect immunofluorescence. Subsequent HIV-1 infection of phenytoin-treated H9 and K37 cells was reduced as measured by indirect immunofluorescence and p24 antigen production. These data indicate that CD4 receptor availability for VIP and HIV-1 was reduced in phenytoin-treated cells. Using the DNA-specific dye Hoechst 33258, we examined cell cycle phase distributions of HIV-1 adsorbing and nonadsorbing H9 cells, as separated by flow cytometry. The majority of HIV-1 adsorbing cells were found to be in the G2/M phase, while nonadsorbing cells were mainly in the G0/G1 phase, during which plasma membrane fluidity is supposed to be increased. This study indicates that plasma membrane fluidization by phenytoin may serve to disrupt CD4 receptor function and emphasizes the impact of plasma membrane properties on HIV-1 adsorption and infection.

Adsorption↗
PubMed1989

Decreased plasma membrane fluidity of peripheral blood lymphocytes after diethyldithiocarbamate (DTC) therapy in HIV-infected patients.

In seeking the putative mechanism of action of diethyldithiocarbamate (DTC) on the immune status of HIV infected patients, the plasma membrane fluidity of peripheral blood lymphocytes (PBL) from DTC-treated and untreated patients (CDC III-IVc1) was determined. Anisotropy values of the fluorescent probe 6-(9-anthroyloxy) stearic acid were increased in DTC-treated patients (0.175 vs 0.161), indicating decreased PBL plasma membrane fluidity. The membrane rigidifying effect was significantly greater 4 h after i.v. drug administration (0.185 in treated patients). As the membrane fluidity and the function of membrane embedded antigen are interdependent, it is possible that alterations in biophysical and/or biochemical properties of membranes may account for the beneficial effect of DTC on the immune function and clinical status of HIV infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Increased plasma membrane fluidity and decreased receptor availability of nonmuscle cells in myotonic dystrophy.

Plasma membrane fluidity of intact nonmuscle cells from patients with myotonic dystrophy (MyD) was determined by fluorescence anisotropy measurements. Anisotropy values of the probe diphenylhexatriene were decreased in patient mononuclear cells (0.163 +/- 0.017, n = 13) versus controls (0.181 +/- 0.013, n = 13, P less than 0.01) and in patient platelets (0.087 +/- 0.017, n = 9) versus controls (0.137 +/- 0.015, n = 9, P less than 0.001) indicating increased plasma membrane fluidity in patient nonmuscle cells. Vasopressin plasma concentrations were increased in patients (7.4 +/- 2.1 pg/ml, n = 12) versus controls (4.5 +/- 1.4 pg/ml, n = 22, P less than 0.0005), whereas serum osmolality was normal. These data are compatible with a decreased vasopressin sensitivity in MyD patients. Specific binding of 125I-labelled vasoactive intestinal peptide (VIP) was decreased in patient mononuclear cells (2.9 +/- 0.9%/10(6) cells, n = 8) versus controls (5.2 +/- 1.6%/10(6) cells, n = 9, P less than 0.005) and receptor affinity for VIP was decreased in patient mononuclear cells (Kd = 0.26 +/- 0.05 nM, n = 8) versus controls (Kd = 0.19 +/- 0.02 nM, n = 9, P less than 0.005). In nonmuscle cells of MyD patients, increased membrane fluidity correlated with decreased receptor availability. This might explain the various endocrine defects described in MyD patients.

Adolescent↗