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Biomedical subjects

F Jung

Publications and source records attributed to F Jung.

At least 109 records · Page 6Linked to original sources

Effect of garlic on platelet aggregation in patients with increased risk of juvenile ischaemic attack.

A platelet-inhibiting effect is described for garlic. In this double-blind, placebo-controlled study on 60 voluntary subjects with cerebrovascular risk factors and constantly increased platelet aggregation it was demonstrated that the daily ingestion of 800 mg of powdered garlic (in the form of coated tablets) over 4 weeks led to a significant inhibition of the pathologically increased ratio of circulating platelet aggregates and of spontaneous platelet aggregation. The ratio of circulating platelet aggregates decreased by 10.3%, from 1.17 +/- 0.08 to 1.05 +/- 0.11 (P < 0.01), and spontaneous platelet aggregation by 56.3%, from 40.7 +/- 23.3 to 17.8 +/- 23.2 degrees (P < 0.01) during the garlic phase. There were no significant changes in the placebo group. The parallel group comparison (garlic versus placebo) revealed a significantly different ratio of circulating platelet aggregates after 4 weeks of treatment (P < 0.05). After the 4-week wash-out phase the values increased again to 1.19 +/- 0.32 and 34.9 +/- 28.7 degrees, reaching the initial values (run-in phase prior to the ingestion of garlic). Since garlic is well tolerated it would be worth testing it in a controlled clinical trial for usefulness in preventing disease manifestations associated with platelet aggregation.

Brain Ischemia↗

Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and beta-lactamase stability.

Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability. Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series.

Animals↗

[The effect of molecular structure of hydroxyethyl starch on the elimination kinetics and fluidity of blood in human volunteers].

Influence of the Molecular Structure of Hydroxyethyl Starch on Elimination Kinetics and Blood Fluidity in Voluntary Subjects In a cross-over study 6 volunteers received an infusion of 500 ml hydroxyethyl starch of a batch with a high C2/C6-substitution ratio (10.8), or after a washout period of 3 months they received a batch with a low C2/C6-substitution ratio (5.8). The infusion solution was administered at random. The batches were identical as regards their physicochemical characteristics (HES 200/0.5 10%). The concentration and molecular weight distribution of the intravascular hydroxyethyl starch molecules were determined after infusion up to 24 h, the blood fluidity before and after infusion. The substitution ratio of the C2- or C6-atoms in the glucose ring has an effect on the degradation of the hydroxyethyl starch molecule: the molecules with a high C2/C6-substitution ratio appear to be degraded within the same period of time, the resulting degradation products, however, have a higher molecular weight. This influences the blood fluidity. While the haematocrit decrease occurring 1 h after end of infusion is comparable, it keeps up for a longer time in case of a higher C2/C6-substitution ratio. The increase of plasma viscosity is more pronounced in case of a high C2/C6-substitution ratio. Clinical consequences are discussed.

Adult↗

[Quality assurance in autologous blood collection from critically ill patients].

Quality controls of autologous blood collections in critically ill patients comprise the control of blood products, blood collection, and of the patients themselves. The control of products is defined in European guidelines, the AMG (law governing the manufacture and prescription of medicine) and GMP regulations. The products are described in the monograph of the Federal Health Office. The quality control of blood collection in patients with a critical vascular disease is important since vagotonic or hypertensive crises may occur frequently (in 10-15% of cardiosurgical patients). The quality control of the critically ill patients themselves is important in order to be able to balance benefits against risks. A phlebotomy of 500 ml may lead to a considerable deterioration of the clinical condition. The clinical condition can be controlled by simple exercise tests prior to and after the blood collection (bicycle ergometer, treadmill or climbing stairs). In our own investigations only about 25% of cardiosurgical patients (40% of patients with aortocoronary venous bypass) received autohemotherapy, and 20% of them showed a clinical deterioration during the phase of blood collection. Other problematic patients are those suffering from a tumor. A clear clinical benefit of autohemotherapy in these patients has not been demonstrated up to now; nevertheless, when a curative therapy is possible, they should be treated with autohemotherapy.

Blood Transfusion, Autologous↗

N-hydroxylation of benzamidine to benzamidoxime by a reconstituted cytochrome P-450 oxidase system from rabbit liver: involvement of cytochrome P-450 IIC3.

Previous investigations have provided evidence for the participation of the cytochrome P-450 (P-450) enzyme system in the established N-hydroxylation of benzamidine to benzamidoxime by microsomal fractions from rabbit liver homogenates. In the present investigation, a representative mixture of P-450 isoenzymes was first isolated from the livers of untreated rabbits and then, together with purified NADPH-P-450 reductase, successfully used in a reconstituted enzyme system for the N-hydroxylation of benzamidine. In order to identify the participating isoenzyme, the P-450 mixture was separated by preparative high performance liquid chromatography on an anion exchange column. A P-450 fraction was obtained that was able to transform benzamidine with a specific activity > 3-fold higher than that of the P-450 mixture. The electrophoretic and spectral properties, as well as the inhibition by monoclonal antibodies against P-450 IIC3, show that the isolated P-450 fraction must consist of one or more variants of the isoenzyme P-450 IIC3. By means of reconstitution experiments with highly purified variants of P-450 IIC3 from rabbit liver and with purified variants of P-450 IIC expressed by recombinant Escherichia coli, the participation of the two variants P-450 IIC3 (6 beta H) and P-450 IIC3 (6 beta L) in the N-hydroxylation of benzamidine was unequivocally confirmed.

Animals↗

Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues.

Cephalosporins with new catechol substituents at C-3' have been synthesized, including novel compounds with C-3' carbon-carbon bonds. Many of these compounds have high potency against Gram-negative bacteria, in particular against resistant strains like Pseudomonas aeruginosa. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-3' catechol and also in terms of steric and conformational factors of the C-3' substituent. The best overall properties were found in compounds with a bulky and/or conformationally restricted acidic C-3' catechol.

Animals↗

[Cardiac function and the skin microcirculation in acromegaly].

The microcirculation was measured by nail-fold capillary video microscopy in 21 patients (12 men, 9 women; mean age 54.7 [29-74] years) with acromegaly. Levels of growth hormone (12.0-71.7 microU/ml) and of somatomedin C (2.4-10.5 IU/ml) were elevated in 10 patients, despite preceding treatment. Eleven patients had an increase in myocardial thickness and nine had impairment of left ventricular function, although only slight in most. Left ventricular hypertrophy was demonstrable even in the absence of hypertension. No patient had evidence of coronary heart disease. Nail-fold capillary video microscopy (capillary density, torque index, reactive hyperaemia, epidermal blood flow) failed to distinguish between successfully treated patients and those with persistently elevated growth hormone concentrations or disease duration of over 5 years. There was no evidence of inadequate capillary blood flow as a cause of abnormal function in hypertrophied organs.

Acromegaly↗

An affinity-amplified immunoassay for juvenile hormone esterase.

A method is described for increasing the specificity of an immunoassay for catalytically active enzymes and is specifically illustrated with a sensitive assay for an important regulatory enzyme from insects. Trifluoromethyl ketone haptens, potent inhibitors of insect juvenile hormone esterase, were bound to proteins such as hemocyanin (keyhole limpet) and conalbumin (chicken embryo). Haptens containing a thiol group were conjugated using heterobifunctional coupling reagents, and haptens with a carboxylic acid moiety were conjugated by the mixed anhydride method. The trifluoromethyl ketone-protein conjugates, shown to retain their inhibitory activity against juvenile hormone esterase, were used as coating antigens in several solid-phase enzyme-linked immunosorbent assay formats along with specific antibodies raised in rabbits against purified juvenile hormone esterase. The previously unreported format, termed affinity-amplified immunoassay (AAIA), was successfully used for quantitative monitoring of low levels of the esterase in dilute hemolymph and egg homogenates from various lepidopteran insect species, as well as for detection of the native and mutant forms of the enzyme obtained in a recombinant baculovirus expression system. The AAIA format was more sensitive for the target esterase and detected only the catalytically active form of the enzyme.

Animals↗

[Noninvasive function tests in the evaluation of vascular reactivity in pregnancy and pregnancy-induced hypertension].

At present, there is an increasing discussion regarding the change of the prostacyclin/thromboxane ratio as an aetiological factor of pregnancy-induced hypertension (PIH). By means of videophotometric capillaroscopy in the capillaries of the nailfold, it is possible to visualise the resulting changes in the microcirculation. This method employs a special illumination microscope (magnification of the optical system x 560). Red blood cell velocity is measured under test conditions and microcirculatorical reaction capacity on ischaemic stress. Studies were conducted on healthy non-pregnant women and on healthy pregnant women as well as on patients suffering from pregnancy-induced hypertension. A markedly reduced velocity of red blood cells in patients with pregnancy-induced hypertension was seen as a sign of vasoconstriction, namely, 0.53 mm/sec. versus 0.74 mm/sec. Furthermore, these patients have a higher reactivity to ischaemic stress, probably also as a result of the already existing vasoconstriction; however, the duration of the hyperaemic phases is reduced in pregnancy-induced hypertension. By this method, an insight can be gained into microcirculation in pregnancy and in pregnancy-induced hypertension. In addition, as preliminary studies have already shown, the influence exercised by different medications on microcirculation can be assessed.

Blood Flow Velocity↗

Identification and characterization of a cardiac-specific transcriptional regulatory element in the slow/cardiac troponin C gene.

The slow/cardiac troponin C (cTnC) gene has been used as a model system for defining the molecular mechanisms that regulate cardiac and skeletal muscle-specific gene expression during mammalian development. cTnC is expressed continuously in both embryonic and adult cardiac myocytes but is expressed only transiently in embryonic fast skeletal myotubes. We have reported previously that cTnC gene expression in skeletal myotubes is controlled by a developmentally regulated, skeletal muscle-specific transcriptional enhancer located within the first intron of the gene (bp 997 to 1141). In this report, we show that cTnC gene expression in cardiac myocytes both in vitro and in vivo is regulated by a distinct and independent transcriptional promoter and enhancer located within the immediate 5' flanking region of the gene (bp -124 to +32). DNase I footprint and electrophoretic mobility shift assay analyses demonstrated that this cardiac-specific promoter/enhancer contains five nuclear protein binding sites (designated CEF1, CEF-2, and CPF1-3), four of which bind novel cardiac-specific nuclear protein complexes. Functional analysis of the cardiac-specific cTnC enhancer revealed that mutation of either the CEF-1 or CEF-2 nuclear protein binding site abolished the activity of the cTnC enhancer in cardiac myocytes. Taken together, these results define a novel mechanism for developmentally regulating a single gene in multiple muscle cell lineages. In addition, they identify previously undefined cardiac-specific transcriptional regulatory motifs and trans-acting factors. Finally, they demonstrate distinct transcriptional regulatory pathways in cardiac and skeletal muscle.

3T3 Cells↗

Blockers of platelet-derived growth factor-activated nonselective cation channel inhibit cell proliferation.

In serum-deprived G(o)-arrested cells, the addition of serum or growth factors initiates a cascade of events that culminates in DNA synthesis and mitosis. Recently, we showed that in mouse L-M(TK-) fibroblasts a 28-pS nonselective cation channel (NS channel) becomes quiescent at G(o) arrest and rapidly active within seconds of platelet-derived growth factor (PDGF) or serum addition, placing this response very early in the postreceptor signaling cascade. However, lack of specific channel blockers hindered determination of whether channel activation was necessary for mitogenesis. Derivatives of N-phenylanthranilic acid (DCA) have been reported to block a pancreatic nonselective channel. Therefore, using single-channel analysis, we examined the effect of these agents on the L-M(TK-) NS channel. Flufenamic acid and mefenamic acid rapidly produced reversible channel block with an inhibitory constant (Ki) approximately 10 microM. Furthermore, the component of the macroscopic K+ efflux shown to be mediated by the NS channel was blocked with a similar Ki value. DCA effects on cell proliferation were tested by measuring cloning efficiency and growth rate. Both were inhibited over the range of concentration that affected channel activity, and a 50% inhibitory dose of 50-100 microM was determined. This observation further substantiates the hypothesis that NS channel activation forms a necessary component in the transduction of the mitogenic signal from the PDGF receptor.

Animals↗

[Movement correction of digital sequence angiographies of the retina].

Retinal hemodynamics can be quantified from videoangiographic image sequences by digital image processing. Intensity changes of dye dilution curves provide dynamics parameters of the local retinal blood flow. The measuring points of dye dilution curves have to be fixed on identical image contents in each image of a complete image sequence. To obtain measurements for every pixel on the retinal surface a motion-compensated image sequence is required. A new method adapted to the compensation of eye motion and movement artifacts in Scanning Laser Ophthalmoscopy in long image sequences (300-500 images) is presented in this paper. To inhibit error propagation of time sequential motion estimation, the eye movement is divided into two dynamic movements components. The method presented permits compensation for eye motion in retinal fluorescein angiographic sequences. Owing to the short calculation times, this algorithm can be used in clinical routine.

Artifacts↗

Molecular biology techniques and their applicability to the study of diabetes and hypertension: the renin-angiotensin system as an example.

Recently developed molecular biology techniques lend themselves to the study of both normal physiology and pathophysiology. This review discusses a number of such techniques and their applicability to the study of diabetes and hypertension with the renin-angiotensin system as an example. The demonstration of specific mRNA in tissue provides strong evidence that the protein for which it encodes is expressed there. The contribution of several methods to demonstrate mRNA expression including Northern analysis, slot blot analysis, solution hybridization, in situ hybridization, run-on assays, and polymerase chain reaction are discussed in the light of how these are used to study renin-angiotensin system mechanisms. Additionally, recent developments in the study of gene transfer and identification of genes are reviewed.

Animals↗

Capillary occlusion and secondary angiogenesis: case report.

The first follow-up control 5 days later (14.1.1990) showed a fresh capillary occlusion with massive red blood cell diapedesis. The arteriolar limb of the capillary is filled with erythrocytes up to the occlusion. Since capillary occlusion probably allowed some plasma flow at first, blood cells distal to the occlusion were washed away. After 53 days (8.3.1990) extravasal cells could no longer be made out. At the upper margin of the image a newly formed capillary loop can be seen. The channel of the old capillary seemed to have disappeared. Seventy-three days after occlusion, on 28th of March, the tip of the capillary, already demonstrated on 8th of March, had further grown distally. The capillary had crossed the neighbouring diagonal capillary. Twelve days later (9.4.1990) a remarkable growth connected with formation of a collateral was observed. The new capillary grew in direction of the former capillary channel. On 22nd of April the new capillary had almost got back to its old form. The collateral vessel formed on 9th of April had also grown and could be well distinguished. The different branches were immediately well perfused (mean erythrocyte velocity is v = 0.74 mm/s). The capillary were growing at different speeds. The new capillary had visibly grown by 220 microns over a period of 47 days which corresponds to an average growth of 4.7 microns a day. The capillary was growing fastest between the 9th and 22nd of April. A minimum of growth of 2 microns was observed within the first 11 days of the observation period.

Adult↗

Hemorrheological and circulatory effects of Gincosan.

Gincosan is a combined preparation containing 60 mg ginkgo biloba and 100 mg ginseng, standardized of 24% ginkgo flavone glycosides and 4% ginsenosides. Hemorrheological and circulatory effect as well as blood pressure behavior after the administration of gincosan were studied in an acute trial on 10 voluntary subjects with a mean age of 26 years. Systolic blood pressure decreased significantly both for the large-dose (120 mg ginkgo biloba +200 mg ginseng) and low-dose administration (60 mg ginkgo biloba +100 mg ginseng). Diastolic blood pressure and heart rate decreased only in the high dosage group. The pathologically increased spontaneous platelet aggregation is reduced by both dosages. Erythrocyte velocity in nail fold capillaries increased significantly only in the high dosage group. The parallel group comparison of the high dosage and placebo group showed that they differ only significantly concerning the erythrocyte rigidity, erythrocyte velocity in nail fold capillaries and spontaneous platelet aggregation. A trend towards a decrease in the systolic blood pressure is revealed (p less than 0.1).

Adult↗

[The microvasculature and microcirculation of the peri-macular capillary network. New diagnostic possibilities with the scanning laser ophthalmoscope].

The scanning laser technique makes it possible for the first time to perform objective measurements of blood flow velocities in retinal capillaries. This new technique allows for continuous recording of retinal pictures at high resolution. Only the quality of the optical media of the eye limits the resolution of the retinal image. Sequences with a sample frequency of up to 50 images/s can be stored using a digital recorder. In these digital sequences the moving blood stream in retinal capillaries is visible. Segments of high and low fluorescence can be observed moving through the capillary network of the perifoveal capillaries. The flow velocities of these segments can be measured objectively using image analysis. In addition, morphologic information about the perifoveal capillary bed can be obtained by this new technique. Determination of flow velocities and morphological parameters give an objective means of assessing oxygen supply to the macular tissue. Furthermore, the degree of changes in the perifoveal microcirculation may provide objective data for estimating the prognosis of diabetic or senile maculopathy. Further investigation is needed to examine the relationship between changes in perifoveal microcirculation and the development of macular edema in various diseases.

Adult↗

Retinal blood flow in diabetic children and adolescents.

A total of 209 diabetic children and adolescents aged 6-17 years (mean, 12.6 +/- 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) test. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6-10 years, 27% in those aged 11-13 years and 36% in those aged 14-17 years. Only five diabetics aged 11-17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7 +/- 2.5 s and that for AVP was 1.43 +/- 0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbA1c, less than 7%; AVP, 1.35 +/- 0.44 s) than in those with bad glycemic control (HbA1c, greater than or equal to 9%; AVP, 1.65 +/- 0.51 s).

Adolescent↗

Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results.

The scanning laser technique in combination with digital image analysis allows direct objective measurement of flow velocities in perimacular capillaries. In addition, the complete macular network of capillaries can be observed. By means of digital frame-to-frame picture analysis of digital recordings, blood flow velocities and morphologic data have been measured. The mean flow velocity in perimacular capillaries observed with the scanning laser ophthalmoscope in healthy subjects (n = 21) amounted to 3.28 +/- 0.45 mm/second. In patients (n = 13) with diabetes mellitus (no or background retinopathy), the mean flow velocity was significantly reduced (2.89 +/- 0.57 mm/seconds) compared with healthy subjects. Morphologic data of the perifoveal capillary bed showed a significant reduction of capillaries in patients with diabetes mellitus when compared with healthy subjects.

Adult↗