Search PubMed⌕ Search

Biomedical subjects

J Schilling

Publications and source records attributed to J Schilling.

At least 37 records · Page 2Linked to original sources
PubMed1998

Beta-blockers and antithrombotic treatment for secondary prevention after acute myocardial infarction. Towards an understanding of factors influencing clinical practice. The European Secondary Prevention Study Group.

AIMS: Long-term beta-blockade reduced mortality after acute myocardial infarction by about a quarter in a series of published trials. Representative data on beta-blocker use for secondary prevention are scanty but indicate wide variations. We have analysed European practice, and sources of variation, by regional sampling of acute myocardial infarction patients admitted to hospital in 11 countries during the period January 1993-June 1994. METHODS AND RESULTS: Treatment data for 4035 representative patients were collected for the hospital phase and 6 months after discharge. A logistic regression model was developed to describe the predictors of beta-blocker use. In the 11 regional samples, 6-38% (20% overall) of patients had no recorded contraindications but were discharged without a beta-blocker. In the absence of perceived contraindications, there was a strong, independent negative association between age and odds of treatment (P < 0.001), and women were less likely to be treated than men (adjusted odds ratio 0.76, 95% CI 0.58-0.99). Discontinuation of beta-blocker treatment by 6 months was significantly less likely in regions where the proportion given such treatment at discharge was high. In contrast, use of antithrombotic agents in the samples was consistently high. CONCLUSIONS: There is persisting low use of beta-blocker secondary prophylaxis, particularly in the elderly and in women, not attributable to perceived contraindications or intolerance. Considerable regional variations persist despite shared trials evidence. Discharge treatment strongly influences long-term medication.

Adrenergic beta-Antagonists↗
PubMed1998

Use of coronary angiography and revascularization procedures following acute myocardial infarction. A European perspective.

AIMS: There is little evidence to inform routine practice in the use of coronary angiography and revascularization procedures after acute myocardial infarction. Large differences in the uptake of these procedures have been reported but representative data are scarce. Outcome studies have produced opposing conclusions concerning the impact of the high rate of these cardiac procedures. METHODS AND RESULTS: A population-based patient sampling approach was utilized to identify routine practice in representative samples from 11 European countries. Data were collected retrospectively on treatment in the 6 months following acute myocardial infarction (n=2807). There was wide variation in utilization of coronary angiography and revascularization procedures. Even after restricting the analysis to patients <65 years (n=1262), there remained a 6 13 fold variation in the use of these procedures. A decreased likelihood of undergoing these procedures was associated with older age. In addition, there was an independent and negative association between female sex and utilization of coronary angiography and coronary artery bypass grafting (CABG). CONCLUSION: The effect on patient outcome of the observed variation in use of these procedures is not known but has important cost and resource implications for the health services. Outcome research is needed to define patient selection criteria and to measure the cost-utility of different angiography and revascularization rates.

Adult↗
PubMed1997

Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by inducible proteolytic processing.

Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree of homology with cell adhesion molecules in their extracellular domains. We studied the functional significance of processing for the receptor-like PTPases LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled that of the related PTPase LAR and was expressed on the cell surface as a two-subunit complex. Both LAR and PTPsigma underwent further proteolytical processing upon treatment of cells with either calcium ionophore A23187 or phorbol ester TPA. Induction of LAR processing by TPA in 293 cells did require overexpression of PKCalpha. Induced proteolysis resulted in shedding of the extracellular domains of both PTPases. This was in agreement with the identification of a specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal microscopy studies identified adherens junctions and desmosomes as the preferential subcellular localization for both PTPases matching that of plakoglobin. Consistent with this observation, we found direct association of plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken together, these data suggested an involvement of LAR and PTPsigma in the regulation of cell contacts in concert with cell adhesion molecules of the cadherin/catenin family. After processing and shedding of the extracellular domain, the catalytically active intracellular portions of both PTPases were internalized and redistributed away from the sites of cell-cell contact, suggesting a mechanism that regulates the activity and target specificity of these PTPases. Calcium withdrawal, which led to cell contact disruption, also resulted in internalization but was not associated with prior proteolytic cleavage and shedding of the extracellular domain. We conclude that the subcellular localization of LAR and PTPsigma is regulated by at least two independent mechanisms, one of which requires the presence of their extracellular domains and one of which involves the presence of intact cell-cell contacts.

Amino Acid Sequence↗
PubMed1997

A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway.

Activation of the Ras/MAPK signaling cascade is essential for growth factor-induced cell proliferation and differentiation. In this report, we describe the purification, cloning, and characterization of a novel protein, designated FRS2, that is tyrosine phosphorylated and binds to Grb2/Sos in response to FGF or NGF stimulation. We find that FRS2 is myristylated and that this modification is essential for membrane localization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK activation. FRS2 functions as a lipid-anchored docking protein that targets signaling molecules to the plasma membrane in response to FGF stimulation to link receptor activation with the MAPK and other signaling pathways essential for cell growth and differentiation. Finally, we demonstrate that FRS2 is closely related and probably indentical to SNT, the long-sought target of FGF and NGF receptors.

3T3 Cells↗
PubMed1997

The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase.

Protein-tyrosine phosphatases (PTPs) are involved in the regulation of diverse cellular processes and may function as positive effectors as well as negative regulators of intracellular signaling. Recent data demonstrate that malignant transformation of cells is frequently associated with changes in PTP expression or activity. Our analysis of PTP expression in mammary carcinoma cell lines resulted in the molecular cloning of a receptor-like PTP, also known as DEP-1. DEP-1 was found to be expressed at varying levels in mammary carcinoma cell lines and A431 cells. In all tumor cell lines analyzed, DEP-1 was constitutively phosphorylated on tyrosine residues. Phosphorylation of DEP-1 increased significantly after treatment of cells with the PTP inhibitor pervanadate. In A431 cells, tyrosine phosphorylation of DEP-1 was also observed after stimulation with epidermal growth factor, however, only after prolonged exposure of the cells to the ligand, suggesting an indirect mechanism of phosphorylation. In addition, DEP-1 coprecipitated with several tyrosine-phosphorylated proteins from pervanadate-treated cells. In vitro binding experiments using a glutathione S-transferase fusion protein containing the catalytically inactive PTP domain of DEP-1 (Gst-DEP-1-C/S) identify these proteins as potential substrates of DEP-1. In addition, we found a 64-kDa serine/threonine kinase to be constitutively associated with DEP-1 in all tumor cell lines tested. The 64-kDa kinase forms a stable complex with DEP-1 and phosphorylates DEP-1 and DEP-1-interacting proteins in vitro. These data suggest a possible mechanism of DEP-1 regulation in tumor cell lines involving serine/threonine and/or tyrosine phosphorylation.

Adenosine Triphosphate↗
PubMed1997

A family of proteins that inhibit signalling through tyrosine kinase receptors.

Phosphotyrosine phosphatases are critical negative or positive regulators in the intracellular signalling pathways that result in growth-factor-specific cell responses such as mitosis, differentiation, migration, survival, transformation or death. The SH2-domain-containing phosphotyrosine phosphatase SHP-2 is a positive signal transducer for several receptor tyrosine kinases (RTKs) and cytokine receptors. To investigate its mechanism of action we purified a tyrosine-phosphorylated glycoprotein which in different cell types associates tightly with SHP-2 and appears to serve as its substrate. Peptide sequencing in conjunction with complementary DNA cloning revealed a new gene family of at least fifteen members designated signal-regulatory proteins (SIRPs). They consist of two subtypes distinguished by the presence or absence of a cytoplasmic SHP-2-binding domain. The transmembrane polypeptide SIRP alpha1 is a substrate of activated RTKs and in its tyrosine-phosphorylated form binds SHP-2 through SH2 interactions and acts as its substrate. It also binds SHP-1 and Grb2 in vitro and has negative regulatory effects on cellular responses induced by growth factors, oncogenes or insulin. Our findings indicate that proteins belonging to the SIRP family generally regulate signals defining different physiological and pathological processes.

Amino Acid Sequence↗
PubMed1997

Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions.

Receptor protein tyrosine phosphatase beta (RPTPbeta) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)-anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin-associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein-protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen beta/gamma, epidermal growth factor-like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline-rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral (cis) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPbeta to the contactin-Caspr complex could provide a mechanism for cell-cell communication between glial cells and neurons during development.

Amino Acid Sequence↗
PubMed1996

[Thrombolysis following myocardial infarct. European Secondary Prevention Study].

For evaluation of the management of patients with acute myocardial infarction, all cases of ten Zurich hospitals (278, 184 men and 94 women) in the period from 1 January to 31 March 1993 were analyzed retrospectively. 223 patients were released from hospital, 55 died. A follow-up was done 6 months after the patient's discharge by means of a questionnaires to the family doctor (return rate: 65.9%). 48.5% of patients were referred to hospital within the first 6 h. after onset of symptoms, 64% within the first 12 h. 28% (n = 76) of the patients received a thrombolytic therapy, of which 91% (n = 69) got streptokinase and 9% (n = 7) got tissue plasminogen activator. In 81% of the cases the thrombolytic therapy was done within the first hour in hospital, in accumulated 97% of the cases within two hours. In the age group under 65 years (39% of the patients, n = 109), 48 patients received thrombolysis (odds ratio [OR] = 1.0). In the age group between 65 and 74 years (24.5 % of the patients, n = 68), 19 patients received thrombolysis (OR: 0.49; 95% CI: 0.42-0.99; p < 0.05), and in the age group over 74 years (36.5% of the patients, n = 101), 9 patients were received thrombolysis (OR: 0.12; 95% CI: 0.05-0.28; p < 0.0001). 31% of the patients (n = 46) received a coronary angiography, 15% (n = 22) had coronary angioplasty, and 11% (n = 1) received coronary bypass surgery. There is evidence that there should be more importance attached to early hospitalization, if acute myocardial infarction is suspected. Thereby age alone should be considered as a contraindication for thrombolytic therapy. The issue of assumed underuse of thrombolytic therapy should be investigated all over Switzerland.

Acute Disease↗
PubMed1996

Daughter of sevenless is a substrate of the phosphotyrosine phosphatase Corkscrew and functions during sevenless signaling.

The SH2 domain-containing phosphotyrosine phosphatase Corkscrew (CSW) is an essential component of the signaling pathway initiated by the activation of the sevenless receptor tyrosine kinase (SEV) during Drosophila eye development. We have used genetic and biochemical approaches to identify a substrate for CSW. Expression of a catalytically inactive CSW was used to trap CSW in a complex with a 115 kDa tyrosine-phosphorylated substrate. This substrate was purified and identified as the product of the daughter of sevenless (dos) gene. Mutations of dos were identified in a screen for dominant mutations which enhance the phenotype caused by overexpression of inactive CSW during photoreceptor development. Analysis of dos mutations indicates that DOS is a positive component of the SEV signaling pathway and suggests that DOS dephosphorylation by CSW may be a key event during signaling by SEV.

Amino Acid Sequence↗
PubMed1996

[Quality management and quality assurance: terminology of a structural change in medicine].

The topic of quality assurance and management gains increasing interest by society, medical professionals, carriers of health expenses and government. In this review the most important terms borrowed from industry and management will be critically explained to persons employed in Health Systems in particular. Beside numerous novel quality terms, closer attention is paid to the Donabedian model, extended by indicational quality, audits, tracer systems, ISO models, technology assessment, total quality management, new control mechanisms in health care and costs. In the context of structural changes in society and medicine the new aspects of quality are featured as a real chance for a 'healthy' Public System and not as a threat.

Accreditation↗
PubMed1996

[Routine immunization of infants in the Canton of Zurich].

At present there is a shortage of data regarding the rate of routine immunization in Swiss children. To address this deficit, a representative cross sectional study was conducted in the Canton of Zurich with 210 children aged between 24 and 36 months. Data was taken from the individual official vaccination certificates. 178 vaccination certificates (55.1% female and 44.9% male) were evaluated, corresponding to a response rate of 84.8%. With children of foreign nationalities, the response rate was 66.7%, whereas the response rate of Swiss children was 90.6% (p < 0.001). The response rate of children of a European nationality outside the European Union was especially poor (33.3%). The immunization rate with three doses of diphtheria, tetanus and poliomyelitis vaccines was 99.4%, and that of the pertussis vaccine was 93.3%. With the vaccines for measles, mumps and rubella the rates were 80.3%, 78.1% and 77.5% respectively. Vaccination rate against Haemophilus influenzae type B was 74.7% with two doses, and 61.2% with three doses. The timing and the number of doses of the vaccines used for infants in the Canton of Zurich were satisfactory. However, the vaccination rate for measles, mumps and rubella is inadequate. Attention should be paid to this problem and also to possible insufficient care of foreign children.

Child, Preschool↗
PubMed1996

Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions.

In a prospective randomized trial in patients undergoing major abdominal surgery, the impact of a new enteral formula supplemented with arginine, omega-3 fatty acids, and nucleotides (A, n = 14) on immunological parameters was compared with a standard enteral formula (B, n = 14) and a low calorie/low fat intravenous solution (C, n = 13). Four days postoperatively, a statistically significant decrease in total leukocyte count (A, 9.0 +/- 2.9; B, 8.0 +/- 2.4; C, 11.1 +/- 3.5 x 10(6) cells/mL; A versus C, B versus C; p < 0.05), higher percentage of lymphocytes (A, 14.3 +/- 4.9; C, 8.2 +/- 6.1; p < 0.05), and decreased median CRP levels (A, 80.4 [69.9]; B, 70 [74]; C, 88.5 [142] in mg/L; A versus C, p < 0.05; B versus C; p < 0.05) were observed in the enteral nutrition groups. The expression of activated surface antigen HLA-DR was diminished on CD14+ cells over 4 d (A, 58.2 [39.2]; B, 52.2 [36.2]; C, 76.6 [25.2] in %; A versus C, p < 0.05; B versus C, p < 0.05) and 8-10 d (A, 37.9 [31.4]; C, 58.5 [37.6]; p < 0.05) postoperatively. Significantly enhanced median phagocytic activity of CD14+ monocytes and granulocytes was observed in group C 8-10 days postoperatively (A, 83.3 [11.8]; B, 71.6 [34.1]; C, 87.4 [10.8]; A versus B, B versus C, p < 0.05; and A, 75.7 [10.0]; B, 69.0 [37.8]; C, 80.0 [10.1] in %, B versus C, p < 0.05, respectively). Postoperative hospital and intensive care unit stay was similar among the three groups; however, infectious complications were less frequent in group A (A versus C, p = 0.15). Thus, a modified enteral nutritional support and supplementation may influence the immune competence toward a more efficient defense response.

Aged↗
PubMed1995

The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin.

Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracellular domain. Fusion proteins containing these domains were used to search for ligands of RPTP beta. The CAH domain bound specifically to a 140 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses were blocked by antibodies against contactin, demonstrating that contactin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The interaction between contactin and RPTP beta may generate unidirectional or bidirectional signals during neural development.

Amino Acid Sequence↗
PubMed1994

[Do antioxidants protect against myocardial infarct? Swiss contribution to the EURAMIC Study].

There is a growing interest in the function of antioxidants and free radicals and their roles in the development of arteriosclerosis. Oxidised LDL-cholesterol and polyunsaturated fatty acids may be involved in the development of arteriosclerotic lesions. The potential of antioxidant vitamins to prevent cardiovascular disease has been the subject of many studies. Up to now the results of different in vitro and in vivo studies remain controversial. For the first time, measurements of the concentrations of lipophilic antioxidants alpha-tocopherol (vitamin E) and beta-carotene (provitamin A) in fat-tissue have been used as an approach. This method is believed to provide an average of the antioxidant intake over a longer period of time and probably reflects steady-state levels rather than intake. A case-control study was conducted using first occurrence of myocardial infarction in men as disease endpoint. In the swiss part of EURAMIC, cases were recruited in collaboration with the hospitals of Zurich. Controls were chosen randomly from the population register of Zurich. Fifty-seven male cases and 74 male controls were enrolled in the protocol. The classical risk factors showed the expected pattern. Levels for beta-carotene were significantly lower in the patient group (0.36 microgram/g biopsy versus 0.52 microgram/g biopsy in controls, p < or = 0.02). In contrast, levels for alpha-tocopherol were similar in both groups (237.5 micrograms/g biopsy in patients and 233.4 micrograms/g biopsy in controls). The Swiss alpha-tocopherol levels were the highest of all participating centres. Analyses of the questionnaires showed significantly higher consumption of vitamin C supplements in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Treatment of acute pulmonary hypertension with inhaled nitric oxide.

We examined the effectiveness of inhaled nitric oxide (NO) as a selective pulmonary vasodilator in acute pulmonary hypertension in an in vivo canine model with fixed cardiac output. In 5 dogs, total right heart bypass was instituted, and pulmonary hypertension was induced by infusion of the thromboxane analogue U-46619. During U-46619 infusion, NO was administered at 10 and 40 ppm for 5 minutes followed by breathing of the oxygen mixture without NO. Pump flow was held constant during the experiment. Infusion of the thromboxane analogue resulted in an increase in pulmonary vascular resistance and systemic vascular resistance from 147 +/- 83 to 740 +/- 126 dyne.s.cm-5 and from 1,720 +/- 113 to 2,407 +/- 232 dyne.s.cm-5, respectively. During inhalation of 10 ppm NO, pulmonary vascular resistance significantly decreased to 613 +/- 55 dyne.s.cm-5 (p < 0.05) and further decreased to 527 +/- 163 dyne.s.cm-5 with 40 ppm NO inhalation (p < 0.05). Systemic vascular resistance did not change during NO treatment (2,300 +/- 70 dyne.s.cm-5 during 40 ppm NO). There was no increase in intrapulmonary shunting or methemoglobin levels during NO inhalation. In this setting, with a constant cardiac output throughout the experiment, NO acted as a selective pulmonary vasodilator without altering systemic vascular resistance. However, induced pulmonary vasoconstriction was only partially reversed by NO inhalation.

Acute Disease↗
PubMed1994

Reduced endogenous nitric oxide in the exhaled air of smokers and hypertensives.

We wanted to determine whether the production of endogenous nitric oxide (NO) is affected by cigarette smoking and various pathological conditions. Endogenously produced NO was measured by chemiluminescence in the exhaled air of 81 healthy volunteers (21 nonsmoking females (NSF), 12 smoking females (SF), 24 nonsmoking males (NSM) and 24 smoking males (SM)) and 38 patients (10 with hypertension, 10 intra- and 10 postoperative, 5 with renal failure and 3 with sepsis) entered the protocol. Subjects inspired from a NO-free air supply, which was also used to calibrate the NO-analyser. Endogenous NO production of volunteers was 18 +/- 8 per billion (ppb) depending on smoking habits. In exhaled air of NSF, NO concentration was 21 +/- 7 ppb, in SF 16 +/- 6 ppb, in NSM 19 +/- 8 ppb and in SM 15 +/- 6 ppb. Differences between smokers and nonsmokers were significant. Increased diastolic blood pressure was noted in SM compared to NSM (86 +/- 7 versus 78 +/- 7 mmHg). Patients with documented and treated hypertension (systolic and diastolic blood pressure: 141 +/- 18 and 82 +/- 9 mmHg) exhaled 13.7 +/- 5.3 ppb NO; hypertensive males 10 +/- 2 ppb NO and females 17 +/- 5 ppb NO. In patients with renal failure NO concentration in exhaled air was 20.2 +/- 6.8 ppb before and 19.8 +/- 6.4 ppb one hour after the onset of dialysis. In patients undergoing major surgery NO concentration was 5.6 +/- 2.5 ppb intra- and 10.3 +/- 3.5 ppb postoperatively. In three mechanically ventilated patients with documented septic syndrome, exhaled NO was 29.3 +/- 24 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗