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Biomedical subjects

M Walter

Publications and source records attributed to M Walter.

At least 73 records · Page 4Linked to original sources
PubMed1999

Highly efficient inhibition of human chymase by alpha(2)-macroglobulin.

The inhibition of human chymase by the protease inhibitor alpha(2)-macroglobulin (alpha2M) was investigated. Titration of chymase hydrolytic activity with purified alpha2M showed that approximately 1 mol of alpha2M tetramer inhibits 1 mol of chymase. Inhibition was associated with cleavage of the alpha2M bait region and formation of a 200-kDa covalent complex. NH(2)-terminal sequencing of chymase-treated alpha2M revealed cleavage at bonds Phe684-Tyr685 and Tyr685-Glu686 of the bait region. alpha2M pretreated with methylamine, an inactivator of alpha2M, did not inhibit chymase. The apparent second-order rate constant for inhibition (k(ass)) was 5 x 10(6) M(-1) s(-1), making alpha2M the most efficient natural protein protease inhibitor of chymase so far described. The k(ass) value for inhibition was decreased approximately 10-fold by addition of heparin, a glycosaminoglycan produced by mast cells that binds to chymase. Heparin did not change significantly the stoichiometry of inhibition or block covalent complex formation. These results indicate that alpha2M is an important inhibitor to consider in the regulation of human chymase.

Chymases↗
PubMed1999

Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: the German BABYDIAB study.

AIMS/HYPOTHESIS: Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus. The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity. METHODS: HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up: 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age. RESULTS: The HLA genotypes DRB1*03/04(DQB1*57non-Asp) and DRB1*04/04(DQB1*57non-Asp) were present in 7.1% and 5.0% of offspring of parents with Type I diabetes. The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3% vs 5.5%, odds ratio 6.3 [p = 0.002] and 22.7% vs 4.2%, odds ratio 6.6 [p = 0.003]) and half of all offspring who developed antibodies had these genotypes. Other genotypes were not associated with an increase in risk. By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20% (95% CI 9.4,30.6) for offspring carrying either the DRB1*03104(DQB1*57non-Asp) or the DRB1*04/04(DQB1*57non-Asp) genotype compared with 2.7% (95% CI 1.2,4.2) for offspring without these genotypes (p < 0.0001). CONCLUSION/INTERPRETATION: These data show that early appearance of islet autoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homozygous offspring and indicate that primary prevention could be considered once available in an offspring cohort selected for these genotypes.

Adult↗
PubMed1999

Closure of atrial septal defects via limited right anterolateral thoracotomy as a minimal invasive approach in female patients.

OBJECTIVE: The closure of atrial septal defects via sternotomy is a low-risk and high-benefit procedure. Limited right anterolateral thoracotomy is an alternative approach with regard to cosmetic aspects. However, it is discussed that a lateral approach is not appropriate for more complex lesions and is associated with an increased incidence of phrenic nerve damage. METHODS AND RESULTS: The perioperative and long-term outcomes (mean follow-up time: 73.2 months) of 87 female patients, mean age 20.4 years (range: 3-56 years), operated on for all types of atrial septal defects via limited right anterolateral thoracotomy between 1982 and 1993, were analysed retrospectively. Special features of the operation technique were a limited skin incision, protection of mammary gland tissue, prevention of phrenic nerve damage, and aortic cannulation in all patients. There were no intraoperative complications. Postoperative complications occurred in 12/87 patients including one rethoracotomy for postoperative bleeding and one late pericardial tamponade due to coumadine overdose. Follow-up was assessed by a survey obtained by the patients or their parents, and their family doctors in 79 patients (90.8%) Cardiac symptoms, mostly supraventricular arrhythmias, were observed in 13.9%. Echocardiography revealed mild tricuspid valve regurgitation (one patient) and mild mitral valve incompetence (one patient with ostium primum defect); there were no residual shunts. Cosmetic results were considered good and excellent in 87.3% and satisfactory in 8.9%. Three patients (3.8%) complained of a broad scar. Anaesthetic areas and optional scar pain were quite frequent (16.5%), whereas restriction of shoulder movement, breast asymmetry and scoliosis were rare. In summary, only one patient, suffering from intercostal neuralgia, would prefer sternotomy. CONCLUSION: Limited right anterolateral thoracotomy has a high cosmetic acceptance and was proven to be safe and effective for closure of any kind of atrial septal defects. Therefore, it is recommended as standard approach for atrial septal defects especially in female patients. reserved.

Adolescent↗
PubMed1999

Six-year follow-up of titanium and high-gold porcelain-fused-to-metal fixed partial dentures.

In a randomized clinical study 47 titanium and gold-alloy fixed partial dentures (FPDs) were placed during a 1-year period. In the titanium group (n = 22) all metal substructures were made of unalloyed titanium. The titanium substructures were fabricated by copy milling, spark erosion and laser welding (Procera, Nobelpharma). Ceramic veneering was carried out with Duceratin titanium ceramics (Ducera, Germany). In the control group (n = 25) the high-gold alloy Degudent U (Degussa, Germany) and Vita VMK 68 ceramics (Vita, Germany) were used. The longest observation time was 6 years. Only one FPD had to be removed due to metal-ceramic failure (titanium group). The clinical performance of all 125 porcelain-fused-to-metal (PFM) veneers with respect to the longevity of the metal-ceramic compound was described by Kaplan-Meyer survivor analyses. Relating survival to a completely intact ceramic veneer, the 5-year survivor rate was 84% for titanium and 98% for the high-gold alloy. PFM titanium restorations exhibited a significantly increased risk of metal-ceramic failure. However, concerning defects requiring removal, no significant differences in titanium versus high-gold alloy occurred. There were no significant differences in the survival distributions between crowns and pontics within the two groups.

Adult↗
PubMed1999

Linear theory of multistage forward-wave amplifiers.

A small-signal theory describing multistage gyro-traveling-wave tubes (gyro-TWTs) is developed. Multistage configurations of gyro-TWTs as well as conventional TWTs seem to be attractive because of their principal ability to operate stably with a high gain, since the stability can be provided by a shortening of each stage while the gain increases with the number of stages. Two regimes of operation, far from cutoff and near cutoff, are considered. In the former case, the equations can be reduced to those describing conventional TWTs and free electron laser amplifiers. Thus a part of the results obtained is also valid for these devices. For two-stage configurations (two waveguides separated by a drift region) the effect of the difference in waveguide cutoff frequencies on the gain and bandwidth is studied. This effect has a common nature with stagger-tuning of cavities, which is widely used in conventional klystrons and gyroklystrons for bandwidth enlargement. The trade-off in gain and bandwidth of such "stagger-tuned," two-stage gyro-TWTs and TWTs is analyzed. Also, the theory of two-stage gyro-TWTs with tapered waveguides and external magnetic field is discussed.

Journal Article↗
PubMed1999

Polyethylene terephthalate and polyurethane coatings for endovascular stents: preliminary results in canine experimental arteriovenous fistulas.

PURPOSE: To evaluate polyethylene terephthalate and polyurethane as coatings of vascular endoprostheses in the treatment of experimental arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Nineteen bilateral carotid artery-to-external jugular vein AVFs were created in 10 adult dogs. Fourteen polyethylene terephthalate-coated and five polyurethane-coated self-expandable nitinol stents were placed with a transfemoral approach. Angiography was performed immediately after placement, after 1 and 3 weeks, and at months 3, 6, 9, and 12. All grafts were examined histopathologically. RESULTS: The AVF was successfully occluded with all but one of the polyethylene terephthalate-coated stents. Graft patency was seen with 12 polyethylene terephthalate-coated stents, while acute vessel occlusion was evident with two polyethylene terephthalate-coated stents following percutaneous transluminal angioplasty immediately after implantation. In the group with polyurethane-coated stents, three graft dislocations and two delayed vessel occlusions were observed. In both groups, histologic examination disclosed a mild foreign body reaction with a few macro-phages. No inflammatory reactions were seen. An unorganized fibrin layer was found adjacent to the polyurethane coating. CONCLUSION: Polyethylene terephthalate-coated nitinol stents showed good biocompatibility and a high rate of occlusion of experimental AVFs. The mechanical properties of the polyethylene terephthalate coating were similar to those of the nitinol stents, which facilitated handling. Polyurethane-coated stents showed frequent dislocation.

Alloys↗
PubMed1999

[Institutional handling of sexual abuse: experiences, evaluations, and desires of nonabusing parents of sexually abused children].

This article describes experiences of parents of sexual abused children and their evaluations of institutional interventions on sexual child abuse. Results are presented of a study investigating 'individual and institutional reactions on sexual child abuse'. The number of contacted institutions, personnel experiences with these institutions and resulting requirements are described. The results are based on a sample of 47 (82.5%) girls and 10 (17.5%) boys (range 6-18 years) and interviews with their 'non-abusing' parents. 28 (49.1%) of these children were abused by a member of the family, 29 (50.9%) children by non-familiar persons. It could be shown that 70.2% of the children had contacted four or more different institutions soon after the sexual abuse had been revealed. In cases of sexual abuse by a family member the first contacted institution was the Youth-and-Health-Care-System whereas in cases of sexual abuse by non-familiar persons mostly the police was contacted. Nevertheless in most cases both judicial and supporting approach were chosen. Additionally to concrete advices and professional competences the interviewed parents reported that emotional warmth was a very helpful aspect of the professional intervention. Generally the perspective of the parents seems to give some interesting informations about 'consumer satisfaction'.

Adolescent↗
PubMed1999

[Utilization of dental services--results of an oral hygiene study in Saxony].

The utilisation of dental services is a precondition for professional preventive measures. The representative oral survey "Bevölkerungsrepräsentative Studie zum zahnärztlich-prothetischen Versorgungsgrad und Behandlungsbedarf" aimed at gaining data on the frequency and motives for dental visits and the existence of barriers. The sample consisted of 714 subjects aged fifteen years and older. It was representative for the German Federal State Saxony. Socio-economic and behavioural data were collected via self-completed questionnaire. The caries history was evaluated by assessing the DMFT Index. Data collection in 1996 was carried out by three calibrated dentists. Utilisation of dental services was found to be high. Subjective barriers played no crucial role in the decision to utilise dental services. Costs as an objective barrier to dental visits had a growing importance with age. Lower rates of tooth loss and enhanced levels of restoration were found in subjects aged over 24 years who regularly utilised dental services compared to subjects with non-regular utilisation. These differences were significant for subjects over 54 years (tooth loss) and subjects aged 25-44 years and over 54 years (level of restoration). Compared to previous studies the utilisation was similar or higher in our sample. The enhanced oral health belief paves the way for professional preventive measures. In the over 64-year-olds the need for regular dental visits was obvious and this age group must definitely be given more relevant information on the subject.

Adolescent↗
PubMed1998

Gasless videoendoscopic implantation of aortobifemoral vascular prostheses via transperitoneal versus extraperitoneal approach in an animal model.

BACKGROUND: The goal of this acute experimental study was to demonstrate the practicability and reproducibility of aortobifemoral bifurcational prosthesis implantations via either a transperitoneal or extraperitoneal approach using gasless videoendoscopic instrumentation. The endoscopically sutured end-to-side aortic anastomoses were also examined for fluid tightness. METHODS: Eighteen of the 20 domestic pigs in this experimental study received aortobifemoral vascular prostheses in a gasless videoendoscopic procedure. Bursting pressures and leakage (ml/min) were compared for the endoscopically sutured aortic end-to-side anastomoses versus those sutured in conventional techniques using 6-h-old porcine aortas and 6-mm prostheses. RESULTS: The surgical procedures averaged 4 h for the transperitoneal approach (n = 9) and 4.5 h for the extraperitoneal approach (n = 9). However, these times were significantly reduced with increasing routine. Average aortic occlusion times were 1 h for the transperitoneal approach and 1 h 15 min for the extraperitoneal approach; the average iliacofemoral occlusion time ranged from 1 h 45 min with the transperitoneal approach to 1 h 15 min with the extra-peritoneal approach, depending on which side was involved: There were no significant differences in in vitro bursting pressure or leakage amounts between endoscopic and conventionally sutured aortic end-to-side anastomoses. CONCLUSIONS: Gasless videoendoscopic implantation of aortobifemoral vascular prostheses in animal subjects is both practicable and reproducible using either a transperitoneal or extraperitoneal approach. The extraperitoneal approach has proven advantages over the transperitoneal approach. The in vitro fluid tightness achieved with endoscopically sutured aortic end-to-side anastomoses is comparable to conventionally sutured anastomoses.

Anastomosis, Surgical↗
PubMed1998

Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy.

A low level of high density lipoprotein (HDL) cholesterol is a strong predictor of ischaemic heart disease (IHD) and myocardial infarction. One cause of low HDL-cholesterol is Tangier disease (TD), an autosomal codominant inherited condition first described in 1961 in two siblings on Tangier Island in the United States of America. Apart from low HDL-cholesterol levels and an increased incidence of atherosclerosis, TD is characterized by reduced total cholesterol, raised triglycerides, peripheral neuropathy and accumulation of cholesteryl esters in macrophages, which causes enlargement of the liver, spleen and tonsils. In contrast to two other monogenic HDL deficiencies in which defects in the plasma proteins apoA-I and LCAT interfere primarily with the formation of HDL (refs 7-10), TD shows a defect in cell signalling and the mobilization of cellular lipids. The genetic defect in TD is unknown, and identification of the Tangier gene will contribute to the understanding of this intracellular pathway and of HDL metabolism and its link with IHD. We report here the localization of the genetic defect in TD to chromosome 9q31, using a genome-wide graphical linkage exclusion strategy in one pedigree, complemented by classical lod score calculations at this region in a total of three pedigrees (combined lod 10.05 at D9S1784). We also provide evidence that TD may be due to a loss-of-function defect.

Chromosome Mapping↗
PubMed1998

The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.

UNLABELLED: In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. IMPLICATIONS: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.

Aged↗
PubMed1998

Are superabsorbers useful for endovascular embolization of saccular aneurysms? An in vitro study.

RATIONALE AND OBJECTIVES: The authors conducted in vitro evaluation of superabsorber for endovascular embolization of saccular aneurysms. METHODS: The swelling properties of the superabsorber Sanwet IM-7000 were investigated in various solvents. The material used was granulate (group A: particle size approximately 459 microm; group B: particle size approximately 20 microm) as well as cubes with an edge length of 1 mm prepared from a block. With ascending concentrations of Sanwet IM-7000 held in suspensions made of Lipiodol and 96% ethanol, the injectability was determined using microcatheters (2.1 F/3 F). The behavior of Sanwet IM-7000 as occlusion material for aneurysms was examined in a sacciform glass-model aneurysm. RESULTS: The granule showed no significant increase in size in Lipiodol and in 96% ethanol, so that they were chosen for catheter measurement. In Lipiodol suspension the maximum fraction of the granulate suitable for injection through a 3 F catheter was 3.2%. In 96% ethanol suspension the maximum fraction of granulate suitable for injection through a 3 F catheter was 0.8%. Suspended in Lipiodol Sanwet IM-7000 showed a moderate swelling in the aneurysm model, whereas the use of 96% ethanol resulted in a pronounced swelling of the granulate (100 vol%) after the 96% ethanol was washed off. Irrespective of the granulate size used, a rinse-off process of the granulate occurred in the model aneurysm at a flow rate above 200 mL x min(-1). Cubes prepared from a block of the base polymerisate of Sanwet IM-7000 showed a delayed increase in size. The final size in 0.9% NaCl solution was reached in the cubes after 220 min, in the granulate already after 20 mins. The cubes displayed a high form stability. CONCLUSIONS: Due to the substance-related absence of intercorporeal cross-linking and the unpredictable increase in size, embolization of aneurysms using Sanwet IM-7000 granulate is inadvisable at present. In spite of a longer swelling time and because of its form consistency, the use of prepared cubes could provide a reasonable alternative.

Aneurysm↗
PubMed1998

HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen binding occurs via decreased production of phosphoinositide-derived second messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate.

We demonstrate that physiological concentrations of HDL3 inhibit the thrombin-induced platelet fibrinogen binding and aggregation in a time- and concentration-dependent fashion. The underlying mechanism includes HDL3-mediated inhibition of phosphatidylinositol 4,5-bis-phosphate turnover, 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate formation, and intracellular calcium mobilization. The inhibitory effects of HDL3 on inositol 1,4,5-tris-phosphate formation and intracellular calcium mobilization were abolished after covalent modification of HDL3 with dimethylsuberimidate. Furthermore, they could be blocked by calphostin C and bis-indolylmaleimide, 2 highly selective and structurally unrelated protein kinase C inhibitors. However, the inhibitory effects of HDL3 were not blocked by H89, a protein kinase A inhibitor. In addition, HDL3 failed to induce cAMP formation but stimulated the phosphorylation of the protein kinase C 40- to 47-kD major protein substrate. We observed a close temporal relationship between the HDL3-mediated inhibition of thrombin-induced inositol 1,4,5-tris-phosphate formation, intracellular calcium mobilization, and fibrinogen binding and the phosphorylation of the protein kinase C 40- to 47-kD major protein substrate. Taken together, these findings indicate that the HDL3-mediated inhibition of thrombin-induced fibrinogen binding and aggregation occurs via inhibition of phosphatidylinositol 4,5-bis-phosphate turnover and formation of 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate. Protein kinase C may be involved in this process.

Adult↗
PubMed1998

Recombinant expression of human mast cell proteases chymase and tryptase.

Expression of recombinant human chymase and tryptase was achieved in a baculovirus-insect cell system using a fusion protein construct. Recombinant baculovirus was produced with DNA coding for a NH2-ubiquitin-chymase-COOH or NH2-ubiquitin-tryptase-COOH fusion protein inserted immediately downstream of the signal sequence for the secreted envelope protein, glycoprotein 67. In each construct, the natural prepropeptide sequence of the protease was replaced by the amino acid sequence for the enterokinase cleavage site of trypsinogen. High Five insect cells infected with either of the modified baculovirus produced mg quantities of each fusion protein per liter of culture. Treatment of the chymase-fusion protein with enterokinase or the tryptase-fusion protein with enterokinase in the presence of a highly charged polysaccharide (dextran sulfate or heparin) produced enzymatically active proteases with properties of the native enzymes. A procedure for the purification of mg quantities of recombinant chymase from infected-cell medium is presented.

Animals↗