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U Kaufmann

Publications and source records attributed to U Kaufmann.

At least 19 recordsLinked to original sources
PubMed2004

Activation of caspase-like activity and poly (ADP-ribose) polymerase degradation during sporulation in Aspergillus nidulans.

Mycelium vacuolization, protein degradation, and as the final stage autolysis, often accompanies developmental changes in fungi and similarities between autolysis and apoptosis have previously been suggested. Caspases are the key executors of apoptosis and in this study caspase-like activities were detected in protein extracts from Aspergillus nidulans during sporulation. This was shown by hydrolysis of the fluorescent DEVD- and IETD-AFC peptide substrates specific for caspase 3- and 8-like activities, respectively. These activities were repressed by the caspase 3 and 8 specific irreversible peptide inhibitors DEVD-fmk and IETD-fmk, but were not affected by the unspecific inhibitor E-64. Isoelectric focusing of protein extracts followed by activity staining revealed the presence of two bands with caspase-like activity. One of the proteins degraded both caspase 3 and caspase 8 specific substrates whereas the other only degraded the caspase 8 substrate. Searches in an A. nidulans genome database revealed two genes encoding metacaspase proteins with predicted sizes of 45 kDa that could be responsible for the measured caspase-like activities. The searches also found a single gene encoding a poly (ADP-ribose) polymerase (PARP) protein with a predicted size of 81 kDa. PARP is one of the known target proteins inactivated by caspase degradation in animal cells. Western blotting of fungal extracts using a bovine PARP antibody confirmed the presence of a fungal PARP-like protein of about 81 kDa. By Western blotting it was shown that this PARP-like protein band was present only at early time points until the start of conidia formation and the accompanying increase in caspase-like activity. Thereafter, a degradation product of about 60 kDa appeared indicating that the degradation of the fungal PARP-like protein was specific. The PARP antibody also recognized an 85 kDa protein band that was not degraded, and which conceivably represents a modified form of the 81 kDa PARP. Fungal extracts high in caspase-like activity could degrade both the fungal 81 kDa PARP and bovine PARP. In the presence of the caspase 3 inhibitor DEVD-fmk this degradation was delayed. Thus, as in animal apoptotic cells, caspase activities are involved in fungal mycelium self-activated proteolysis.

Animals↗
PubMed2003

Seasonal and diel activity of Ixodes ricinus (Acari: Ixodidae) subpopulations in Denmark. Aspects of size, physiological age, and malate dehydrogenase genotype in a forest site without any undergrowth.

UNLABELLED: The underlying population dynamics and the behavioural patterns of the vectors are key issues in understanding the transmission of vector borne pathogens. For the tick Ixodes ricinus both seasonal and diel activity have been described as bimodal patterns, which in seasonal aspect has been interpreted as representing two cohorts. However, recent studies have shown that this interpretation may be incorrect. The aim of this study was to obtain more detailed information on nymph host seeking by studying subpopulations of ticks during the day and season. The study was designed to allow for comparisons of the diel variation and seasonal variation in their dependency in a number of tick characteristics. The study took place in a forest with planted beech trees without any undergrowth. Ticks were collected by flagging the dead leaves on the forest floor. For each nymph, a number of visual observations were made. The size and physiological age was observed and the nymphs were genotyped in the malate dehydrogenase locus (MDH, E.C. 1.1.1.37). Briefly the main results can be given as: (i) There were significant differences in the composition of size classes during the season, but only limited trends in time. (ii) The proportion of the small nymphs was highly variable, with a variation from 3% to 24% in October and September, respectively. (iii) The diel variation in MDH genotypes was significant in May and August. (iv) Nymph size classes and physiological age appeared to interact. The non-random interaction was caused by a relatively even distribution of small nymphs in all four age classes, while large nymphs tended to fall into age class 2 and 3. The length by age interaction for the individual months was noted to be significant in May, July, August and September, but not in June. Similarly the interaction was significant in the morning and afternoon, but not at midday. The overall results describe the seasonal and diel activity patterns as changing systematically for several characteristics under the influence of weather condition and population dynamics. IN CONCLUSION: The observations are best interpreted as being produced of a single cohort of ticks, but the revealed complexity of the host seeking activity suggest that measures of activity x abundance should be interpreted very cautiously in relation to population dynamics.

Aging↗
PubMed2001

[Scoring multiple organ failure after severe trauma. Comparison of the Goris, Marshall and Moore scores].

INTRODUCTION: MOF scores are used to predict, describe and define organ failure. The aim of this study was to compare MOF scoring systems regarding their precision. METHODS: Data on the ICU course of 301 severely injured patients (PTS > 20, age > 16 years) were documented daily for calculation of three MOF Scores (Goris, Moore, Marshall) for 14 days. Every day the patients were graded by clinical criteria into a group with and a group without MOF by an experienced intensive care physician. The cut-off point for MOF was determined by ROC analysis for each score; the sensitivity and specificity were calculated. RESULTS: The patients were 36.3 +/- 1.0 years old, the mean injury severity was 36.2 +/- 0.7 points according to the PTS. Forty-seven (15.6%) of all patients died 17.7 +/- 5.6 days after trauma. The MOF incidence was 26.1%, the MOF mortality 58.4%. The calculated cut-off point for MOF was more than 4 points for the Goris and Marshall scores and more than 3 points for the Moore score. The Moore score is, with sensitivity of 81% and specificity of 88%, superior to the other scores. The Moore score identified 93 patients (30.9%) for MOF; this corresponds with a right answer in 85%. The lower specificity of the Goris and Marshall scores was due to the judgement of liver (GOT) and cardiovascular (PAH) dysfunction respectively. CONCLUSION: For evaluation of MOF after severe trauma the Moore score is superior to other scoring systems (sensitivity 81%; specificity 87%). A score of more than 3 points is associated with MOF. The Moore score did not consider distinct parameters (S-GOT, PAH) which are included in the other systems and were of little importance in our calculations.

Adult↗
PubMed2000

The armadillo repeat region targets ARVCF to cadherin-based cellular junctions.

The cytoplasmic domain of the transmembrane protein M-cadherin is involved in anchoring cytoskeletal elements to the plasma membrane at cell-cell contact sites. Several members of the armadillo repeat protein family mediate this linkage. We show here that ARVCF, a member of the p120 (ctn) subfamily, is a ligand for the cytoplasmic domain of M-cadherin, and characterize the regions involved in this interaction in detail. Complex formation in an in vivo environment was demonstrated in (1) yeast two-hybrid screens, using a cDNA library from differentiating skeletal muscle and part of the cytoplasmic M-cadherin tail as a bait, and (2) mammalian cells, using a novel experimental system, the MOM recruitment assay. Immunoprecipitation and in vitro binding assays confirmed this interaction. Ectopically expressed EGFP-ARVCF-C11, an N-terminal truncated fragment, targets to junctional structures in epithelial MCF7 cells and cardiomyocytes, where it colocalizes with the respective cadherins, beta-catenin and p120 (ctn). Hence, the N terminus of ARVCF is not required for junctional localization. In contrast, deletion of the four N-terminal armadillo repeats abolishes this ability in cardiomyocytes. Detailed mutational analysis revealed the armadillo repeat region of ARVCF as sufficient and necessary for interaction with the 55 membrane-proximal amino acids of the M-cadherin tail.

Amino Acid Sequence↗
PubMed2000

A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.

OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.

Adult↗
PubMed1999

Importance of dural ectasia in phenotypic assessment of Marfan's syndrome.

BACKGROUND: Early identification of Marfan's syndrome is fundamental in the prevention of aortic dilatation, but the wide phenotypic expression of the disorder makes the clinical diagnosis very difficult. Dural ectasia has been classified as a major diagnostic criterion; however, its prevalence is not known. We aimed to identify the true prevalence of dural ectasia in Marfan's syndrome, and to investigate its relation to aortic pathology. METHODS: A magnetic-resonance-imaging (MRI) study of the thoracic aorta and of the lumbosacral spine was done in an inclusive series of 83 patients with Marfan's syndrome to assess the presence and degree of dural ectasia and aortic involvement; 12 patients were younger than 18 years. 100 individuals who underwent MRI of the lumbar spine for routine clinical indications represented the control group; none of them had any potential causes for dural ectasia. FINDINGS: Dural ectasia was identified in 76 (92%) patients and none of the control group. The severity of dural ectasia was related to age; the mean (SD) age of patients with mild dural ectasia was 26 years (14) whereas that of those with severe disease (meningocele) was 36 years (9) (p=0.038). 11 of 12 patients younger than 18 years had dural ectasia. No association was found between aortic dilatation and dural ectasia. INTERPRETATION: Dural ectasia is a highly characteristic sign of Marfan's syndrome, even at an early age.

Adolescent↗
PubMed1999

[Invasive diagnosis of coronary heart disease in patients over 75 years old].

Between January 1, 1993, and August 31, 1995, 268 patients over 75 years underwent coronary angiography at the University Hospital of Bern. Their clinical reports were analyzed in order to determine whether invasive diagnosis of coronary artery disease (CAD) is justifiable also in the elderly considering risks and complications. The main indication for coronary angiography were symptoms of ischemic heart disease. Twenty-nine underwent the procedure for planned cardiac surgery, mostly valve replacement. In 79% of patients, coronary angiography revealed CAD. In the remaining 21% there were no significant coronary stenoses, but 82% of them had valvular heart disease. Only 4% had neither coronary nor valvular heart disease. Following coronary angiography 63% of patients had a therapeutical intervention: 24% coronary angioplasty (PTCA), 13% bypass-grafting, 17% valve replacement, 8% combined surgery (revascularization and valve-replacement), and 1% another intervention. Four percent had no cardiac disease, 1% died before a planned surgery. The remaining 32% were continued on medical therapy. As indicators of appropriateness and success of the invasive procedure the rates of complications and the duration of hospitalization were analyzed. The incidence of deaths, myocardial infarctions, cerebral complications, and arrhythmias was five to ten times higher for cardiac surgery than for PTCA or conservative treatment. Invasive diagnosis and therapy of CAD in patients over 75 years can nevertheless be reasonable and successful if the decision is taken carefully considering risk factors and concomitant disease.

Aged↗
PubMed1999

[Bj"ork-Shiley heart vales at the Bern University Hospital. Long-term follow-up of 12 to 23 years after mitral and aortic valve replacement in 503 patients].

Long-term follow-up, cardial complications and factors influencing the survival time have been investigated retrospectively in 503 patients, who underwent 344 aortic and 191 mitral valve replacements with Björk-Shiley heart valve prosthesis between 1973 and 1984 at the University Hospital of Berne, Switzerland. Informations were assessed from the patient's files and a questionnaire to the family physician. The cumulative follow-up contains a total of 4,810 patient years or a median of 14 years per patient. The median survival time was 19 years, hardly less than the normal life expectancy. Of the 135 patients found alive in 1996 66% had no cardiac problems at all. Two cases of outlet strut fracture of the Björk-Shiley valve were reported during the follow-up time. Both patients had a mitral valve replacement in 1982 with a 31 mm Björk-Shiley valve because of mitral stenosis. The most common complication was a thromboembolic incident (1.6 in 100 patient years). Furthermore eight cases of valve thrombosis, 16 of endocarditis and 24 of myocardial infarction occurred in this population. The study showed that survival time after heart valve replacement with Björk-Shiley valve is long. The mortality was elevated significantly with the following preoperative findings: severe dyspnea (x 2.0), pulmonary congestion (x 1.7) and increased cardiac size (x 1.5). The survival time was shorter when a valve prosthesis with a diameter larger than 27 was used or when in addition coronary heart disease, hypertension, diabetes mellitus or obesity were present.

Adolescent↗
PubMed1999

M-cadherin and its sisters in development of striated muscle.

Cadherins are calcium-dependent, transmembrane intercellular adhesion proteins with morphoregulatory functions in the development and maintenance of tissues. In the development of striated muscle, the expression and function of mainly M-, N-, and R-cadherin has been studied so far. While these three cadherins are expressed in skeletal muscle cells, of these only N-cadherin is expressed in cardiac muscle. In this review, M-, N-, and R-cadherin are discussed as important players in the terminal differentiation and possibly also in the commitment of skeletal muscle cells. Furthermore, reports are described which evaluate the essential role of N-cadherin in the formation of heart tissue.

Animals↗
PubMed1999

A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) Multicenter Trial of Angioplasty for Shock-(S)MASH.

AIM: To test whether emergency revascularization improves survival in patients with acute myocardial infarction and shock. METHODS AND RESULTS: Patients with acute myocardial infarction and early shock were randomized either to undergo emergency angiography, followed immediately by revascularization when indicated, or to receive initial medical management. In five of the nine participating centres, patients with shock but not randomized were entered in a registry. Only 55 patients could be randomized. Of the 32 patients in the invasive group, 30 (94%) underwent early angiography, 27 (84%) PTCA, and one (4%) CABG. Twenty-two (69%) died within 30 days in the invasive group vs 18/23 (78%) in the medically managed group (ns, RR=0.88, 95% confidence interval 0.6-1.2). Among the registry patients, 24/51 were excluded from randomization solely because of patient or physician preference for the invasive approach: 23 (96%) of them underwent emergency angiography, 21 (88%) PTCA, and 12 (50%) died within 30 days. Among the remaining registry patients (n=27) only nine (33%) underwent early angiography, nine (33%) PTCA and 20 (74%) died. CONCLUSION: We failed to demonstrate that emergency PTCA significantly improves survival in patients with acute myocardial infarction and early cardiogenic shock. Because the study was stopped prematurely, due to an insufficient patient inclusion rate, a clinically meaningful benefit of early reperfusion may have been missed.

Aged↗
PubMed1999

Diurnal activity of Ixodes ricinus in Denmark: aspects of physiological age and genotypic variation.

Four different alleles in the nymphal Ixodes ricinus were found for the Malate Dehydrogenase enzyme (MDH). The allele frequency of the MDH genotypes in nymphal I. ricinus was observed to change during the day. Some genotypes were present in the morning, but not in the afternoon and evening. The physiological age of the nymphs was also determined. No significant correlation could be found between physiological age and genotypes. Based on the results it must be anticipated that the comparability of tick samples not only differs in quantity but also in quality for various hours, but not necessarily for various months. Therefore isoenzyme analysis of nymphs at least as regards the MDH alleles appears to be a convenient biological tool to analyse differences in host seeking behaviour.

Aging↗
PubMed1999

The M-cadherin catenin complex interacts with microtubules in skeletal muscle cells: implications for the fusion of myoblasts.

M-cadherin, a calcium-dependent intercellular adhesion molecule, is expressed in skeletal muscle cells. Its pattern of expression, both in vivo and in cell culture as well as functional studies, have implied that M-cadherin is important for skeletal muscle development, in particular the fusion of myoblasts into myotubes. M-cadherin formed complexes with the catenins in skeletal muscle cells similar to E-cadherin in epithelial cells. This suggested that the muscle-specific function of the M-cadherin catenin complex might be mediated by additional interactions with yet unidentified cellular components, especially cytoskeletal elements. These include the microtubules which also have been implicated in the fusion process of myoblasts. Here we present evidence that the M-cadherin catenin complex interacts with microtubules in myogenic cells by using three independent experimental approaches. (1) Analysis by laser scan microscopy revealed that the destruction of microtubules by nocodazole leads to an altered cell surface distribution of M-cadherin in differentiating myogenic cells. In contrast, disruption of actin filaments had little effect on the surface distribution of M-cadherin. (2) M-cadherin antibodies coimmunoprecipitated tubulin from extracts of nocodazole-treated myogenic cells but not of nocodazole-treated epithelial cells ectopically expressing M-cadherin. Vice versa, tubulin antibodies coimmunoprecipitated M-cadherin from extracts of nocodazole-treated myogenic cells but not of nocodazole-treated M-cadherin-expressing epithelial cells. (3) M-cadherin and the catenins, but not a panel of control proteins, were copolymerized with tubulin from myogenic cell extracts even after repeated cycles of assembly and disassemly of tubulin. Moreover, neither M-cadherin nor E-cadherin could be found in a complex with microtubules in epithelial cells ectopically expressing M-cadherin. Our data are consistent with the idea that the interaction of M-cadherin with microtubules might be essential to keep the myoblasts aligned during fusion, a process in which both M-cadherin and microtubules have been implicated.

Animals↗
PubMed1998

Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease.

BACKGROUND: Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. METHODS AND RESULTS: In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. CONCLUSIONS: Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.

Antihypertensive Agents↗
PubMed1998

Prolonged heparin after uncomplicated coronary interventions: a prospective, randomized trial.

BACKGROUND: Continuous heparin infusion after percutaneous transluminal coronary angioplasty (PTCA) procedures prolongs the hospital stay and could increase the occurrence of bleeding complications. The aim of this randomized trial was to evaluate whether omission of heparin infusion after uncomplicated coronary interventions in patients with stable and unstable angina with or without stent implantation increased the incidence of acute cardiac complications. METHODS AND RESULTS: A total of 191 consecutive patients who underwent successful PTCA were randomly assigned to receive either prolonged heparin (heparin group) or no postprocedure heparin (control group). The 2 treatment groups were comparable with respect to clinical and angiographic characteristics. Stents were used in 36% of the control group and in 33% of the heparin group. Cardiac complications occurred in 8 (4%) patients. Four (4%) patients in the control group and 3 (3%) patients in the heparin group had a myocardial infarction. One patient in the control group died 3 days after the intervention. No patient in either group needed a repeat revascularization during the target hospitalization. Peripheral vascular complications in the control and heparin groups occurred in 1% and 3% of the patients, respectively. CONCLUSIONS: Omission of heparin after successful PTCA with or without stent implantation in patients with stable and unstable angina did not significantly increase the incidence of acute cardiac complications. It allows for early sheath removal and patient discharge and saves costs. This study, combined with other small studies in the field, provides strong evidence that heparin should not be used routinely.

Adult↗
PubMed1998

[The Magnum wire for the angioplasty of coronary occlusions and stenoses].

The "Magnum wire" is a stiff shaft, blunt tip wire constructed for recanalization of total coronary occlusions. Smaller series have demonstrated superior qualities if compared to conventional wires. The purpose of this study was to analyze its efficacy in total and nontotal lesions in a large number of consecutive procedures. A database analysis identified the use of the Magnum wire in 569 procedures from October 1992 to February 1995, which accounted for 26% of all angioplasties during the time period at our Institution. There were 347 total occlusions and 222 nontotal occlusions. Technical success was achieved in 69% of total occlusions and 90% of subtotal occlusions. Procedural success was recorded in 58 and 75%, respectively. Stents were implanted in 29 patients with total occlusion (8%) and 19 patients with nontotal lesions (9%). Acute occlusion of the treated lesion occurred in 4.5% of patients with nontotal lesion and 1.5% of the patients with total occlusion. In conclusion, the Magnum wire is an efficient tool for angioplasty of total occlusions and severe nonocclusive stenoses. In light of the complexity of the attempted lesions, achieved success rates were remarkable.

Adult↗
PubMed1997

[Measurements of intracoronary pressure and blood flow velocity].

Quantitative coronary angiography and new intracoronary imaging devices are not able to provide functional data for the assessment of the severity of coronary artery stenotic lesions. The functional characterization of coronary artery stenosis gives insight into whether it compromises myocardial perfusion under conditions of pharmacologic or physical stress, i.e., whether the stenosis has hemodynamic relevance. The measurement of trans-stenotic pressure gradients and/or post-stenotic blood flow velocities using very recently developed, miniaturized pressure- and Doppler-angioplasty guidewires (1/3 mm in diameter) provides a valuable alternative to traditional, non-invasive means for the functional assessment of coronary artery disease. The most widely employed parameters for the functional characterization of coronary artery stenoses are the ratio between flow velocities during pharmacologically induced hyperemia and at resting conditions (coronary flow velocity reserve), and the pressure-derived fractional flow reserve, i.e., the ratio of mean poststenotic to mean aortic pressure during hyperemia. Furthermore, poststenotic pressure and flow velocity measurements during and after occlusion of stenosis can be used for the quantitative assessment of collateral circulation among different vascular regions.

Angioplasty, Balloon, Coronary↗