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Biomedical subjects

F Jung

Publications and source records attributed to F Jung.

At least 73 records · Page 4Linked to original sources
PubMed1997

Antibodies against a peptide sequence located in the linker region of the HMG-1/2 box domains in sera from patients with juvenile rheumatoid arthritis.

OBJECTIVE: To extend our work on the mapping of B cell epitopes on nucleosomal high mobility group (HMG) proteins in the sera of patients with juvenile rheumatoid arthritis (JRA). METHODS: Seventy-seven pauciarticular-onset JRA serum samples from antinuclear antibody (ANA)-positive patients and 42 polyarticular-onset JRA patient sera found to react with HMG-2 by immunoblotting were used in this study. To identify B cell epitopes on HMG-2, recombinant HMG-2 protein fragments were used in enzyme-linked immunosorbent assay (ELISA) and in competition ELISA experiments with a set of overlapping synthetic peptides. Fine epitope mapping was achieved by oligopeptide synthesis, followed by immunoblotting. RESULTS: Pauciarticular, but not polyarticular, JRA patient sera were found to recognize a lysine-rich major epitope (KKGKKKDP), which is located in the linker region of the HMG box domains of the HMG-2 nonhistone chromosomal protein. No significant immunoreactions were observed in sera from ANA-negative JRA patients and in sera from children with nonrheumatic diseases, indicating that this epitope seems to be specific for pauciarticular-onset JRA. CONCLUSION: In addition to our previous finding that JRA sera will react with a defined epitope on HMG-17, pauciarticular JRA patient sera were also found to recognize a defined epitope on the HMG-2 protein, thus suggesting the importance of this epitope in the etiology of JRA.

Amino Acid Sequence↗
PubMed1997

[Hemocompatibility of various synthetic granulates].

The adherence of platelets to different polymer granulates was examined in a perfusion chamber filled with platelet-rich plasma. The surface area of each of the granulates was of a standardised size. The results were compared with those found for a non-thrombogenic and a highly thrombogenic foreign-body surface. The three polymers examined-Cryolite, Styrolux and Zylar-must be considered non-thrombogenic. Platelet adherence to these substances is significantly less (3%) than that to a highly thrombogenic surface such as glass (95%). The three materials did not differ in terms of platelet adherence, and would appear to be suitable potential materials for use in cell separators.

Biocompatible Materials↗
PubMed1997

[Cap image--a new kind of computer-assisted video image analysis system for dynamic capillary microscopy].

We describe a newly developed multi-function video image analysis system for the computer-aided evaluation of capillaroscopic findings in microcirculation research. The Cap image analysis system comprises an IBM-compatible PC with a Matrox image processing card and real-time video tape digitalization. The video recorder is driven by a personal computer to which it is connected via an RS-232 interface. In contrast to currently available systems, the program presented here makes it possible to select any of several integrated image analysis functions, depending on the quality of the video image. Some examples of the analysis functions available are measurements of erythrocyte flow velocity using the line shift diagram method, the spatial correlation method, and the auto flying spot method. The standard features of the new program include a number of special functions and automatic movement correction. The system thus makes it possible not only to measure numerous morphological parameters such as capillary diameter, length, torquation index and capillary density, but also to perform video densitometric analysis, for example using fluorescent dyes.

Blood Flow Velocity↗
PubMed1997

Postangioplasty restenosis: a practical model in the porcine carotid artery.

Transluminal coronary angioplasty is a routine therapeutic intervention in coronary heart disease. Despite the high rate of primary success, restenosis continues to be its major limitation. Porcine models have been considered to be the most adequate experimental models for studying restenosis. One limitation of porcine models is the need for radiological guidance and the expenses involved. The objective of the present study was to adapt an experimental model of angioplasty in the porcine carotid artery that does not require radiological equipment. Eight animals were used to develop the technique of balloon injury to the common carotid artery by dissection without radiological guidance. This technique was then employed in six other animals. Under anesthesia, the left common carotid artery was dissected and incised at the carotid sinus for insertion of an over-the-wire angioplasty balloon towards the aorta. Overstretch injury of the carotid artery was performed under direct visualization. After 30 days, the arteries were excised and pressure-fixated. Uninjured carotid arteries from 3 additional animals were used as controls. A decreased luminal area associated with intimal hyperplasia and medial reaction was observed in all injured arteries. Immunohistochemistry identified the intimal hyperplastic cells as smooth muscle cells. Computerized morphometry of the ballooned segments revealed the following mean areas: lumen 2.12 mm2 (+/- 1.09), intima 0.22 mm2 (+/- 0.08), media 3.47 mm2 (+/- 0.67), and adventitia 1.11 mm2 (+/- 0.34). Our experimental model of porcine carotid angioplasty without radiological guidance induced a vascular wall reaction and permitted the quantification of this response. This porcine model may facilitate the study of vascular injury and its response to pharmacological interventions.

Angioplasty↗
PubMed1997

Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases.

The present study provides a detailed kinetic analysis of diazepam metabolism by all four known members of the human P4502C subfamily expressed from their cDNAs in Escherichia coli. Both P4502C18 and P4502C19 were found to be low K(M) diazepam N-demethylases with apparent K(M) values of 24 +/- 4 microM and 21 +/- 3 microM, respectively. These values closely resemble the low K(M) component of diazepam N-demethylase activity exhibited by human liver microsomes. In addition, P4502C19 also catalyzed diazepam 3-hydroxylation with a K(M) value of 21 +/- 9 microM. Although P4502C8 was essentially inactive in catalyzing diazepam metabolism, P4502C9 catalyzed the N-demethylation with a relatively high K(M) of 80 +/- 15 microM and an overall 3- to 6-fold lower catalytic efficiency, compared with P4502C18 and P4502C19, respectively. At a substrate concentration of 10 microM, diazepam N-demethylation in a panel of human liver microsomes was inhibited 42 +/- 12% (mean +/- SD, N = 6) by a polyclonal anti-CYP2C antibody. In the same experiment, 3-hydroxylation remained unaffected (<10% inhibition). 1 microM of the CYP3A inhibitor ketoconazole inhibited 37 +/- 19% of the N-demethylation and 86 +/- 5% of 3-hydroxylation. Estimates of relative contributions to diazepam N-demethylation of P4502C9 (8 +/- 4%), P4502C18 (<2%), and P4502C19 (33 +/- 14%) and to diazepam 3-hydroxylation of P4502C19 (9 +/- 3%) based on the kinetic parameters of the recombinant enzymes and on specific contents of the individual 2C P450s determined in immunoblots are consistent with the inhibition data. In conclusion, these data confirm that both P4502C19 and P4503A are major contributors to human liver microsomal diazepam N-demethylation at low substrate concentrations, whereas P4503A is the major enzyme responsible for 3-hydroxylation.

Aged↗
PubMed1997

Increased haemorrhagic risk after repeated infusion of highly substituted medium molecular weight hydroxyethyl starch.

Infusion of the large volumes of high molecular weight hydroxyethyl starch (HES) has been know to lead to coagulation disorders. Medium molecular starch is considered a safe alternative, even after repeated administration. In 10 patients with cerebrovascular diseases, a 10-day hemodilution was carried out using 10% HES 200/0.62. Initially, a loading dose of 500 ml was administered once over 45-60 min, followed by 500 ml maintenance dose per day for 10 days. Its high intravascular molecular weight (120,000 D) showed that cleavage of the starch is slowed due to the higher degree of substitution. The continuous increase of HES-serum concentration to 27.7 mg/ml gave evidence of a cumulation of poorly degradable molecules. Although this caused a prolonged volume effect, plasma viscosity and erythrocyte aggregation were influenced in an unfavourable way. The negative effects were not evident in their influence on the coagulation system. Under therapy, a significant 42.8% increase (p < 0.01) in activated partial thromboplastin time occurred. Factor VIII:C, von Willebrand ristocetin co-factor and von Willebrand factor antigen dropped during the therapy below the hemostasiological limit of 30% (p < 0.01), and in some patients below 10%. A high degree of substitution, particularly after repeated infusion, leads to a cumulation of large molecules that are difficult to break down and which unfavourably affect rheological and hemostasiological parameters.

Blood Coagulation↗
PubMed1997

[Standardization of nailfold capillary microscopy in routine diagnosis].

BACKGROUND: Nailfold capillary microscopy is scientifically established and recognized as a diagnostic tool in clinical routine. It is, however, practiced in only a few centres. METHODS: But since a more widespread use of the method is to be expected for the near future, a consensus-meeting was held, where all German-speaking clinicians and scientists, involved in capillary microscopy, were invited. Here, the technical procedure and the most important morphological parameters were evaluated and defined according to practical clinical aspects. RESULTS AND CONCLUSION: The main task of the consensus-meeting was to develop a standard evaluation sheet, accompanied by an explanation sheet. This standard evaluation sheet focuses on semiquantitative registration of morphological parameters like density, dilation, avascular fields, perivascular edema, microbleeding, torsion, atypical capillaries and giant capillaries. This standard evaluation sheet is to be validated by determining the inter-observer-variance. Later-on an illustrated practical guideline will be published.

Capillaries↗
PubMed1997

Heterologous expression of human drug-metabolizing enzymes.

This article is a report on a symposium held at the March 1997 meeting of the American Society for Pharmacology and Experimental Therapeutics in San Diego. Current developments in the heterologous expression of cytochrome P450, NADPH-cytochrome P450 reductase, glutathione transferase, and UDP-glucuronosyltransferase enzymes are described. Systems include bacteria, insect cells, and transient and stable mammalian cells. Uses of the products are described for discernment of which enzymes are involved in metabolism of drugs, genotoxicity assays, mutagenesis (for structure-activity relationships), large scale production of enzyme products, antibody production, and production of proteins for biophysical studies.

Enzymes↗
PubMed1996

Haemorheology in patients with branch retinal vein occlusion with and without risk factors.

PURPOSE: The study was carried out to ascertain the role of blood viscosity in patients with branch retinal vein occlusion (BRVO) with and without risk factors. METHODS: In 292 patients with acute BRVO (mean age 65 +/- 10 years) and 292 controls matched for gender, age, and cardiovascular risk factors, haematocrit, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity were measured. A subgroup analysis in patients with and without risk factors was performed. RESULTS: Haematocrit and plasma viscosity values were significantly higher in BRVO patients than in controls, but erythrocyte rigidity and erythrocyte aggregation did not differ. Subgroup analysis revealed no differences in haematocrit and plasma viscosity values between patients with and those without cardiovascular risk factors. CONCLUSIONS: This study shows increased plasma viscosity and haematocrit values in patients with BRVO which are not associated with the presence of other cardiovascular risk factors. Thus, changes in blood fluidity appear to be important factors in the pathogenesis of BRVO.

Adult↗
PubMed1996

Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVES: The efficacy of a buckwheat herb tea was determined in patients with chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind, placebo-controlled clinical trial. METHODS: Sixty-seven male and female patients (22-74 years) with CVI were randomly divided into two groups after a 2-week run-in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a placebo tea for a period of 3 months. The main outcome measure was the lower leg volume determined by ultrasound. Subjective symptoms were assessed by a clinical symptom score system. The femoral vein diameters were measured by B-scan sonography. In a subgroup of patients capillary permeability was determined by cutaneous fluorescence angiography. RESULTS: Although the mean partial leg volume did not change in the treatment group (from 2041 to 2073 ml), it increased in the placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The difference between the groups was significant. The subjective clinical symptoms were significantly reduced in both groups. The mean diameters of the femoral veins were reduced and capillary permeability was improved, but neither change was statistically significant. No drug-related adverse effects were observed. CONCLUSION: CVI is a very placebo-sensitive condition. The treatment with buckwheat herb tea is safe and could have a favourable influence on patients with CVI such that further oedema development is prevented.

Adult↗
PubMed1996

Role of rheologic factors in patients with acute central retinal vein occlusion.

PURPOSE: To assess the rheologic findings in acute central retinal vein occlusion (CRVO) with respect to associated risk factors, the clinical appearance of ischemic or nonischemic CRVO, and to elucidate the etiology of possible changes. METHODS: The authors enrolled 173 patients with acute CRVO (ischemic, 33%; nonischemic, 67%) in this prospective study. One hundred seventy-three patients who were matched for age, sex, and cardiovascular risk factors served as control subjects. All patients underwent testing to determine hematocrit values, plasma viscosity (PV), erythrocyte aggregation (SEA), and erythrocyte rigidity (SER). RESULTS: Hemocrit values and PV were increased significantly (P<0.01) in patients with ischemic and nonischemic CRVO compared with control subjects but did not differ significantly between the two groups. No significant differences were found in SEA and SER values between the clinical subsets of patients with CRVO and when the patients were compared with matched control subjects. Analysis revealed that hemocrit and PV values were (P<0.001) increased significantly independent of associated cardiovascular risk factors. CONCLUSION: These results suggest that increased hemocrit and PV values may be contributing factors in the pathogenesis of CRVO.

Acute Disease↗
PubMed1996

Antiarrhythmic drug therapy in the treatment of atrial fibrillation.

Treatment of atrial fibrillation is often unsatisfactory because no available drug has been shown to be clearly superior for maintaining patients in sinus rhythm, and all agents have significant potential for toxicity. Selection of an antiarrhythmic drug is more likely to be based on the drug's potential for toxicity, rather than its demonstrated superior efficacy in the treatment of atrial fibrillation. Careful assessment of each patient for contraindications to individual agents and the likelihood of treatment success needs to be done before initiating antiarrhythmic therapy.

Amiodarone↗
PubMed1996

Influence of a non-ionic radiography contrast medium on the microcirculation.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: Microcirculatory disturbances may be responsible for some of the adverse effects induced by contrast media. The influence of iopromide 370 (Ultravist) on cutaneous microcirculation was therefore investigated in 15 patients in a prospective study. Twenty ml of iopromide and 20 ml 0.9% NaCl were injected as reference in the subclavian artery at the beginning of a diagnostic coronary angiography. Erythrocyte velocity was measured in ipsilateral nailfold capillaries at the beginning of, during, and after the injection continuously up to 6 min after injection. RESULTS: On average, 30 s after injection of contrast medium, erythrocyte velocity decreased significantly by 51.3% (p<0.0001) and remained reduced up to 120 s. This reaction was observed in 14 out of 15 patients. Three patients showed a temporary cessation of capillary blood flow. CONCLUSION: The adverse effects sometimes seen during coronary angiography can be explained if similar contrast medium induced microcirculatory disturbances in the myocardial vasculature.

Adult↗
PubMed1996

[Flow rates of roentgen contrast media of different viscosity in 4.1 Charrière coronary catheters].

The studies presented here investigated the obtainable flows of different contrast media (Iopromide 370 mg iodine/ml, ZK 119 095 370 mg iodine/ml, ZK 139 129 370 mg iodine/ml, Iopamidol 370 mg iodine/ml, Iopromide 300 mg iodine/ml, ZK 119 095 300 mg iodine/ml, ZK 139 129 300 mg iodine/ml, Iopamidol 300 mg iodine/ml, aqua dest.) in 4.1 Charrière coronary catheters. The measurements of the flow achieved by a standardised power of 100 N show that the highest values are reached with the substance ZK 119 095 (both for 300 mg iodine/ml and 370 mg iodine/ml). On comparison of the catheter types there are no differences in the delivery rate. The x-ray contrast-media, however, are significantly different: the lowest iodine delivery rate is found for iopromide 370 with 384.5 mg iodine/s; the highest rate for the test substance ZK 119 095 with 648.9 mg iodine/s. Although contrast media with low viscosity contain considerably less iodine/ml it is possible to achieve an iodine density in coronary vessels by about 86% higher than that achieved by contrast media with 370 mg iodine/ml. Therefore, the possibility to choose a viscosity-adapted x-ray contrast-medium allows the use of very thin cardiac catheter systems without leading to a worsening of picture quality.

Cardiac Catheterization↗
PubMed1995

A universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in Escherichia coli.

Human cytochrome P450s 2C8, 2C9, 2C18, and 2C19 and rabbit cytochrome P450s 2C1, 2C2, 2C4, 2C5, and 2C16 were expressed from their respective cDNAs in Escherichia coli as chimeric enzymes in which a portion of the N-terminal membrane anchor sequence was replaced with a modified sequence derived from P450 17A. For 2C1 and 2C2 removal of the extraneous 3'-untranslated sequence allowed the successful expression of constructs that were unproductive in its presence. The levels of expression varied from 180 to 1500 nmol/liter of culture and the addition of delta-aminolevulinic acid to the culture media increased the amount of spectrally detectable P450 for several of these enzymes 2- to 10-fold. The catalytic properties of the modified human 2C P450s expressed in E. coli were concordant with previously published data for several marker substrates including (S)-mephenytoin for P450 2C19, tolbutamide and tetrahydrocannabinol (THC) for P450 2C9, and taxol for P450 2C8. Interestingly, P450 2C19 catalyzed the 21-hydroxylation of progesterone and, to a lesser extent, catalyzed the formation of 16 alpha-hydroxyprogesterone. The rabbit enzyme P450 2C16 catalyzed the formation of 17 alpha- and 16 alpha-hydroxyprogesterone in addition to 21-hydroxylation. P450 2C19 also catalyzed the methylhydroxylation of tolbutamide and the 7-hydroxylation of THC at rates that were similar to or greater than that of P450 2C9. This work has identified important factors required for the high-level expression of 2C subfamily P450s in E. coli. The availability of these enzymes will facilitate detailed kinetic measurements for known and yet to be identified substrates.

Alleles↗
PubMed1995

In vivo spin trapping of glyceryl trinitrate-derived nitric oxide in rabbit blood vessels and organs.

BACKGROUND: The objectives of this study were (1) to assess glyceryl trinitrate (GTN)-derived nitric oxide (NO) formation in vascular tissues and organs of anesthetized rabbits in vivo, (2) to establish a correlation between tissue NO levels and a biological response, and (3) to verify biotransformation of GTN to NO by cytochrome P-450. METHODS AND RESULTS: NO was trapped in tissues in vivo as a stable paramagnetic mononitrosyl-iron-diethyldithiocarbamate complex [NOFe(DETC)2]. After removal of the tissues, NO was determined by cryogenic electron spin resonance spectroscopy. NO formation in vitro was assessed by spin trapping and by activation of soluble guanylyl cyclase. The GTN-elicited decrease in coronary perfusion pressure was monitored in isolated, constant-flow perfused rabbit hearts. NO was not detected in control tissues. In GTN-treated rabbits, NO formation was higher in organs than in vascular tissues and higher in venous than in arterial vessels. In isolated hearts, ventricular NO levels and decreases in coronary perfusion pressure achieved by GTN were closely correlated. Purified cytochrome P-450 catalyzed NO formation from GTN in a P-450-NADPH reductase- and NADPH-dependent fashion. CONCLUSIONS: Since GTN-derived NO formation in myocardial tissue correlates to the GTN-elicited vasodilator response, we conclude that GTN-derived NO detected in vivo correlates with the systemic effects of GTN. Therefore, the higher rate of NO formation detected in veins compared with arteries explains the preferential venodilator activity of GTN. High NO formation in cytochrome P-450-rich organs in vivo and efficient NO formation from GTN by cytochrome P-450 in vitro highlights the importance of this pathway for NO formation from GTN in the intact organism.

Animals↗
PubMed1995

Temperature-sensitive SV40 immortalized rat proximal tubule cell line has functional renin-angiotensin system.

Immortalized rat proximal tubule cell (IRPTC) lines should be useful for investigation of proximal tubule (PT) regulation and function but previously have been unavailable. We now report the establishment and characterization of an immortalized transformed, temperature-sensitive IRPTC cell line containing renin-angiotensin system (RAS) components. Primary PT cells prepared from male Wistar rats (4-5 wk old) after collagenase digestion, sieving, and Percoll gradient were cultured on collagen-coated T-75 flasks in Dulbecco's modified Eagle's medium containing 5% fetal calf serum. Subconfluent PT cells were transfected with the temperature-sensitive SV40 mutant viruses (tsA SV40) by direct exposure. After 7-8 wk, several clones were obtained, from which one has been characterized and designated as line 3-2. This cell line appears stable up to 45 passages. Clonal cells transformed with this virus exhibit a transformed phenotype at a permissive temperature of 34 degrees C and grow in multiple layers. When the cells are subsequently placed at a nonpermissive temperature of 41 degrees C, they return to morphology similar to that of untransformed cells of the same lineage. At either 34 degrees C or 41 degrees C, this cell line expresses a variety of PT markers including alkaline phosphatase, cytokeratin, carbonic anhydrase, and glucose transporter isoform 2 (GLUT2), while not expressing factor VIII. Uniquely, these cells also appear to express PT proteins gp330 and CHIP28, markers which are usually lost in cultured cells. Furthermore, the cell line expresses protein and mRNA components of RAS, including angiotensinogen, angiotensin converting enzyme, and renin. The IRPTC cell line expresses few angiotensin II (ANG II) receptors at 34 degrees C, the permissive temperature. However, at the nonpermissive temperature, 41 degrees C, IRPTC expresses ANG II receptor (dissociation constant of 0.7 nM; maximum binding capacity of 265 fmol/mg protein). ANG II (10(-8) M) induced a transient rise in cytoplasmic Ca2+ concentration, which was nearly abolished with losartan but not PD-123319, suggesting this finding is AT1 receptor mediated. This cell line should provide an excellent model of PT and should make it possible to study the cell and molecular biology of the RAS, as well as other regulatory systems of the PT.

Animals↗