Search PubMed⌕ Search

Biomedical subjects

F Jung

Publications and source records attributed to F Jung.

At least 55 records · Page 3Linked to original sources
PubMed2000

Capillary microscopic and rheological dimensions for the diagnosis of von Willebrand disease in comparison to other haemorrhagic diatheses.

It is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis. Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14: 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101). severe haemophilia A (n = 50) and severe haemophilia B (n = 20). congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 microm; median: 15.1 microm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 microm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%. In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%. As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

Adult↗
PubMed1999

Effect of X-ray contrast media on blood flow properties after coronary angiography.

In vitro studies suggest that ionic and nonionic X-ray contrast media have different effects on rheological parameters. The risk of thrombotic complications in coronary interventions was reported to be lower using ionic contrast media. The aim of the present study was to compare the effects of different types of contrast media on rheological parameters after coronary angiography. Sixty patients were randomized to four groups: ioxaglate 320 (dimeric, ionic, n = 18), iomeprol 400 (monomeric, nonionic, n = 12), iobitridol 350 (monomeric, nonionic, n = 12), and iodixanol 320 (dimeric, nonionic, n = 18). Blood samples were collected via the side port of the arterial sheath immediately before and at the end of coronary angiography. In our study, all types of contrast media caused a significant decrease in haematocrit (Hct), plasma viscosity (PV), erythrocyte aggregation (EA), and in the platelet reactivity index (PRI). The most pronounced decrease in Hct was found using the ionic dimer ioxaglate. There were no significant differences between the contrast media with respect to their effects on PV, EA, and PRI.

Aged↗
PubMed1999

A novel series of non-nucleoside inhibitors of inosine 5'-monophosphate dehydrogenase with immunosuppressive activity.

Inhibitors of inosine 5'-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205) are effective immunosuppressive drugs that may also have additional potential applications as antitumour and antimicrobial agents. The clinical value of the most potent and specific inhibitor of IMPDH, mycophenolic acid, is limited by its rapid metabolism in vivo to an inactive glucuronide derivative. There is, therefore, a considerable incentive to develop structurally novel, preferably non-nucleoside, inhibitors with greater metabolic stability than mycophenolic acid. Here, we describe a high throughput screen for inhibitors of IMPDH, which facilitated the discovery of a single novel non-nucleoside inhibitor from a collection of approximately 80,000 compounds. The inhibitor is a pyridazine, which, like mycophenolic acid, exerts uncompetitive inhibition of IMPDH. Analysis of the enzyme kinetics suggests that the inhibitory action of the pyridazine is similar to that of mycophenolic acid, which involves trapping of a covalent intermediate formed during the conversion of IMP to xanthosine monophosphate. Chemical modification of the lead compound resulted in pyridazine derivatives with enhanced potency against IMPDH and guanine nucleotide synthesis in cultured cells in vitro and also against guanine nucleotide synthesis in the mouse spleen in vivo. One of the compounds was available in sufficient quantity to demonstrate highly effective immunosuppressive activity in a model of delayed type hypersensitivity in mice. To our knowledge, the novel pyridazines described in this report represent the first non-nucleoside uncompetitive inhibitors of IMPDH with immunosuppressive activity since the discovery of the inhibitory activity of mycophenolic acid and its derivatives thirty years ago.

Animals↗
PubMed1999

Rat proximal tubule cell line transformed with origin-defective SV40 DNA: autocrine ANG II feedback.

The renal proximal tubule (PT) is a major site for a complete tissue renin-angiotensin system (RAS) and produces endogenous angiotensin II (ANG II). The present studies demonstrate autocrine RAS feedback in a line of origin-defective SV40 plasmid transformed immortalized rat PT cells (IRPTC) designated as line 93-p-2-1, which are highly differentiated and express all RAS components. Receptor competition assays and Southern blot following RT-PCR demonstrated that these IRPTC express AT1 and AT2 angiotensin receptor subtypes. Autocrine RAS feedback was examined following exposure to ANG II (10(-8) M), and it was noted that angiotensinogen mRNA increases significantly by 1 h and remains elevated through 24 h. The AT1 blocker losartan prevents this increase. Moreover, ANG II upregulates expression of ANG II receptor mRNA (both AT1 and AT2). Thus the present studies demonstrate positive ANG II feedback with angiotensinogen and ANG II receptors in PTC, suggesting that the main site of such intrarenal feedback in vivo is within PT. ANG II secreted by line 93-p-2-1 is increased by isoproterenol, suggesting beta-adrenergic regulation in IRPTC.

Angiotensin II↗
PubMed1999

Characterization of an E-box-dependent cis element in the smooth muscle alpha-actin promoter.

Identification of the regulators of smooth muscle specific gene expression is critical for understanding smooth muscle cell (SMC) differentiation and the alterations in SMC phenotype seen in vascular diseases. Previous studies have identified that a 2-bp mutation in a conserved cis-acting element (TGTTTATC) in the promoter of the chicken smooth muscle (SM) alpha-actin gene abolished nuclear factor binding and decreased transcriptional activity of a 271-bp SM alpha-actin promoter fragment when transfected into rat aortic SMC. However, the promoter region containing this conserved sequence has negative cis regulatory activity when studied in homologous systems. The goal of the present studies was to further characterize the transcriptional activity of the rat SM alpha-actin promoter region between -224 and -236 that is conserved across mammals. DNAse I analysis and electrophoretic mobility shift assays demonstrated that SMC nuclear proteins bound an extended sequence (TGTTTATCCCCATAA). Transient transfection experiments of wild-type and mutant rat SM alpha-actin promoter-luciferase constructs into rat aortic SMC revealed that promoter activity was enhanced by mutations of specific nucleotides in the TGTTTATCCCCA region. Interestingly, the TGTTTATCCCCA element in the rat SM alpha-actin promoter is centered between 2 canonical E-boxes. Mutations of the flanking E-boxes abolished the enhancement in promoter activity seen with mutation of the TGTTTATCCCCA element alone. Thus studies provide evidence for a regulatory cassette in the rat SM alpha-actin promoter that regulates gene expression via combinatorial interactions between 2 E-boxes and a newly described TGTTTATCCCCA element.

Actins↗
PubMed1999

Intramuscular oxygen partial pressure in the healthy during exercise.

The oxygen partial pressure (pO2) in the anterior tibial muscle was measured in n=12 (6 physically active and 6 sedentary) apparently healthy subjects. This was the first time a flexible micro catheter with an outer diameter of 0.45 mm was used during skeletal muscular activity in men. A two level tread mill test which is used in the diagnosis of peripheral arterial occlusive disease was chosen to induce physical stress. In the healthy volunteers a pO2 increase was noted at the beginning of exercise. This was followed by a pO2 decrease because of an increased O2 demand in the working muscle. The initial pO2 increase was thought to be due to the recruitment of capillaries and not the subsequently increased heart rate. At rest and during activity pO2 values were higher in physically active subjects than in the sedentary and the exercise induced decrease of pO2 values was slower and in addition to this the compensation to baseline values quicker.

Adult↗
PubMed1999

Influence of radiographic contrast media (Iomeprol 350 versus Iopentol 350) on cutaneous microcirculation: single-center prospective randomized double-blind phase iv study in parallel-group design.

OBJECTIVE: This single-center, prospective, randomized, double-blind phase IV study in parallel-group design was carried out to investigate whether either of two different x-ray contrast media (iomeprol 350 or iopentol 350) injected into the axillary artery has any influence on cutaneous microcirculation. METHODS AND RESULTS: The investigation was carried out on two groups of patients (n = 10 in each group) who had to undergo a diagnostic heart catheter angiography. The confirmatory response variable for the study was the mean capillary erythrocyte velocity (mm/sec). Blood flow through the ipsilateral nail-fold capillaries was recorded continuously for 3 minutes before and 6 minutes after the injection of the randomly assigned x-ray contrast medium, and was evaluated off-line. A contrast medium-induced, rheologically determined disturbance of the microcirculation was found, which was due to two different effects. First, the high intrinsic viscosity (iopentol = 12.3 mPa.sec) led to an immediate reduction in capillary blood flow. This did not occur in the case of iomeprol (intrinsic viscosity = 7.5 mPa.sec). Second, the contrast medium molecules cause a morphological change in the erythrocyte membrane; echinocytes are formed and are further desiccated depending on osmolality of the contrast medium. CONCLUSION: The time course of the conversion of erythrocytes into echinocytes leads to a maximum reduction in capillary erythrocyte velocity of 30 seconds after the bolus of contrast medium. For the more viscous contrast medium of higher osmolarity (iopentol), this led to a significant overall reduction of up to 48.6% in capillary blood flow (p < 0.0001) that lasted for up to 150 seconds, while iomeprol did not significantly affect capillary blood flow (p = 0.2759).

Arteriosclerosis↗
PubMed1999

Influence of Iodixanol-270 and Iopentol-150 on the microcirculation in man: influence of viscosity on capillary perfusion.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: The aim of this study was to investigate the influence of direct intraarterial application of the contrast agents Iodixanol-270 and Iopentol-150 on the capillary perfusion. This was accomplished through continuous recording of the capillary perfusion in the nailfold capillaries of the right hand before and after a bolus injection of 20 ml of contrast agent into the right axillary artery. RESULTS: After injecting 20 ml of Iodixanol-270, which has a high viscosity compared to the plasma viscosity, a statistically significant decrease in the erythrocyte velocity of 60.8% from 0.439+/-0.273 mm/s to 0.172+/-0.090 mm/s was observed already 10 s after the injection (p = 0.0001). The decreased velocity was maintained until the end of the observation period of 6 min. In contrast to this finding, no change in the erythrocyte velocity was observed after injection of 20 ml of the low-viscous Iopentol-150 (p = 0.1508). CONCLUSIONS: The erythrocyte velocity in cutaneous capillaries therefore strongly depends on the viscosity of the contrast agent.

Aged↗
PubMed1998

Identification of amino acid substitutions that confer a high affinity for sulfaphenazole binding and a high catalytic efficiency for warfarin metabolism to P450 2C19.

Human cytochrome P450s 2C9 and 2C19 metabolize many important drugs including tolbutamide, phenytoin, and (S)-warfarin. Although they differ at only 43 of 490 amino acids, sulfaphenazole (SFZ) is a potent and selective inhibitor of P450 2C9 with an IC50 and a spectrally determined binding constant, KS, of <1 microM. P450 2C19 is not affected by SFZ at concentrations up to 100 microM. A panel of CYP2C9/2C19 chimeric proteins was constructed in order to identify the sequence differences that underlie this difference in SFZ binding. Replacement of amino acids 227-338 in 2C19 with the corresponding region of 2C9 resulted in high-affinity SFZ binding (KS approximately 4 microM) that was not seen when a shorter fragment of 2C9 was substituted (227-282). However, replacement of amino acids 283-338 resulted in extremely low holoenzyme expression levels in Escherichia coli, indicating protein instability. A single mutation, E241K, which homology modeling indicated would restore a favorable charge pair interaction between K241 in helix G and E288 in helix I, led to successful expression of this chimera that exhibited a KS < 10 microM for SFZ. Systematic replacement of the remaining differing amino acids revealed that two amino acid substitutions in 2C19 (N286S, I289N) confer high-affinity SFZ binding (KS < 5 microM). When combined with a third substitution, E241K, the resulting 2C19 triple mutant exhibited a high cataltyic efficiency for warfarin metabolism with the relaxed stereo- and regiospecificity of 2C19 and a lower KM for (S)-warfarin metabolism (<10 microM) typical of 2C9.

Amino Acid Sequence↗
PubMed1998

[Optimal x-ray contrast media for ambulatory coronary angiography from the microcirculatory point of view].

PROBLEM: Side effects must be expected in 7 to 8% of cases, even when non-ionic radiocontrast agents are used. Contrast agent-induced microcirculatory disturbances constitute one potential cause under discussion. These disturbances may be caused by either the hyperviscosity or the hyperosmolality of the contrast agents. Within the framework of 3 comparative studies, the influence of viscosity and/or osmolality in intraarterial bolus injections on downstream microcirculation was tested in patients with coronary heart disease. Blood flow in the nailfold capillaries was recorded by intravital videomicroscopy and evaluated off-line, before and after randomized injection of 20 ml of each different radiocontrast agent into the Arteria auxillaries ipsilateral. Injection of 20 ml of a radiographic contrast agent into the Arteria auxillaries with a viscosity of 9.9 mPas and an osmolality of 770 mOsmol/kg H2O (Iopromid with 370 mg iodine/ml) results in a significant reduction in mean erythrocyte velocity in the ipsilateral nailfold capillaries from 0.76 +/- 0.27 to 0.39 +/- 0.31 mm/s after 30 s (p = 0.0001), corresponding to a reduction of 51.3%, whereas electrolyte solution shows no influence. With one exception, all patients reacted with a pronounced reduction in perfusion following injection of the radiocontrast agent, 3 patients showed an extreme reaction with flow cessation in the capillaries, in 1 case lasting up to 2 minutes. Following injection of 20 ml of Iodixanol with 270 mg iodine/ml (5.8 mPas, 290 mOsmol/kg H2O) a significant reduction of mean erythrocyte velocity of 60.8% was recorded from 0.44 +/- 0.27 mm/s to 0.17 +/- 0.09 mm/s only 10 s after the injection (p = 0.0001) lasting to the end of the observation period (6 minutes). Following injection of 20 ml of low-viscosity Iopentol with 150 mg iodine/ml and comparable osmolality (1.7 mPas, 340 mOsmol/kg H2O) no change in erythrocyte velocity was recorded (p = 0.151). Following injection of 2 high-viscosity radiocontrast agents of varying osmolality, mean erythrocyte velocity is reduced significantly in the first 30 s, after which period the erythrocyte velocity gradually increases (ANOVA repeated measures, category "time": p < 0.0001). The time curve for the 2 radiocontrast agents do not, however, differ (ANOVA, category "agents x time": p = 0.9890). Perfusion of the nailfold capillaries depends significantly on the viscosity, but not the osmolality, of the radiocontrast agent injected in coronary heart disease patients. From a microcirculatory point of view, it would therefore make sense to use low-viscosity radiocontrast agents in outpatients to exclude the existing risk of an induced myocardial microcirculatory disturbance.

Ambulatory Care↗
PubMed1998

Treatment strategies for atrial fibrillation.

Atrial fibrillation is the most common arrhythmia observed in clinical practice, occurring in 0.4% of the general population and in up to 4% of people greater than 60 years old. It is often associated with other cardiovascular disorders, such as hypertension, coronary artery disease, or cardiomyopathy. Critical evaluation and management of patients with atrial fibrillation requires knowledge of etiology, prognosis, and treatment options of this arrhythmia. On initial presentation, emergency electrical cardioversion should be performed if the patient is hemodynamically unstable. If the patient is stable, initial rate control is recommended, using atrioventricular nodal blocking agents. Further treatment mainly depends upon the duration of the episode. Patients who are in atrial fibrillation <48 hours can be safely cardioverted. Patients who are in atrial fibrillation for >48 hours are commonly anticoagulated for 3 to 4 weeks before and after cardioversion because of the risk of thromboembolism formation in the left atrial appendage. An alternate strategy, which is especially attractive when immediate cardioversion is desired, is transesophageal echocardiography to exclude left atrial thrombus followed by prompt cardioversion. After cardioversion, sinus rhythm can be maintained with class I and III drugs, such as flecainide and propafenone or amiodarone and sotalol. New treatment options, such as atrial defibrillation, atrioventricular junctional ablation, or modification of atrial pacing to prevent atrial fibrillation, are currently under investigation. Although atrial fibrillation is so common in clinical practice, it still remains difficult to treat. Conversion and maintenance to sinus rhythm with antiarrhythmic drug therapy has not shown any improvement in mortality, and some patients may benefit more from ventricular rate control. This review article discusses different treatment strategies for patients with atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed1998

Electron-microscopic examination of silicon-carbide-coated endovascular stents.

The problem of restenosis in blood vessels after balloon angioplasty could not be overcome by the use of metallic stents as had been anticipated. With respect to restenosis, clinical and experimental results now focus the attention on the risk that stents could initiate or potentiate vascular lesions, especially by inhomogenous stent expansion. Here the stent design seems to dominante depending on the use of well rounded structural stent-elements with appropriate surfaces and a material deposition which is compatible with a homogeneous stent expansion. With respect to hemocompatibility the surface quality of the stents is of great importance, too. Coating of surfaces of metallic stents for the enhancement of hemocompatibility might create new risks of blood vessel damages and requires a careful consideration of the co-expansional behaviour of the metallic substrate and the coating material. With these problems in mind the surface coated stent Tensum 3 of the Biotronik company was investigated.

Angioplasty, Balloon, Coronary↗
PubMed1998

Early rheological and microcirculatory changes in children with type I diabetes mellitus.

In order to determine early changes in microcirculation and hemorheological parameters in diabetics, a cross-sectional study was carried out with 273 children with diabetes mellitus type I during their vacation in a state country convalescent home for diabetic children and teenagers in Kaiserslautern. Compared to healthy children, typical changes of hemorheological variables as well as in the microcirculation of the skin and retina are observed in poorly controlled diabetic children. Morphological changes are obvious in capillary areas in form of marked capillary contortions and dilatations of venous branches, rigid erythrocytes, and hyperaggregable thrombocytes. An effort should be undertaken to normalize the pathologically changed parameters of blood fluidity and the microcirculation by an adequate control of blood glucose, and possibly by changes in dietary habits.

Adolescent↗
PubMed1997

Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51.

The epitope recognized by the inhibitory monoclonal antibody designated 2F5, which was raised against P450 2C5, was mapped to amino acids 237-260 by immunoblotting using a combination of recombinant antigens and chimeric and partial fusion proteins constructed from rabbit P450s 2C2, 2C4, 2C5, and 2C16, which are recognized by 2F5, and from 2C1 and 2C3, which are not. When the sequence of the epitope for 2F5 (amino acids 237-260) was compared with those of other rabbit 2C P450s, a single lysine residue at position 253 appeared to be a likely determinant of 2F5 immunoreactivity. Substitution of lysine for glutamic acid 253 in P450 2C3 (2C3E253K) conferred immunoreactivity and the ability of 2F5 to inhibit progesterone metabolism catalyzed by P450 2C3E253K. Sequence alignment revealed that this epitope lies in close proximity to the epitope identified for LKM-1 autoantibodies to P450 2D6. Based on these results, an antipeptide antibody was raised to the corresponding region (amino acids 252-263) of human P450 2C18. The resulting antipeptide antiserum recognizes P450 2C18 but not P450 2C8, 2C9, or 2C19. However, the antipeptide 2C18 antiserum did not inhibit 2C18-catalyzed diazepam N-demethylation. Human 2C P450s were also quantitated by immunoblot analysis in a panel of six human liver microsomes using Escherichia coli expressed P450s as standards. Analysis of immunoblots indicated that, if present, P450 2C18 was expressed at very low levels (<2.5 pmol/mg), whereas P450s 2C8, 2C9, and 2C19 were easily detected.

Amino Acid Sequence↗