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Biomedical subjects

H Meisner

Publications and source records attributed to H Meisner.

At least 19 recordsLinked to original sources
PubMed1995

Coupling of the proto-oncogene product c-Cbl to the epidermal growth factor receptor.

The proto-oncogene product, Cbl, is a 120-kDa protein present in lymphocytes that contains numerous PXXP motifs in its COOH-terminal region and constitutively binds the SH3-containing adaptor protein Grb2. Cross-linking of CD3 and CD4 receptors in Jurkat T cells causes tyrosine phosphorylation of Cbl and its association with phosphatidylinositol 3'-kinase (Meisner, H., Conway, B., Hartley, D., and Czech, M. P. (1995) Mol. Cell. Biol. 15, 3571-3578). Here we demonstrate that Cbl is also present in nonlymphoid cells, and that epidermal growth factor (EGF) elicits its rapid tyrosine phosphorylation in human embryonic 293 cells. Immunoprecipitates of Cbl from lysates of these cells contain Grb2 in the basal state, while EGF stimulation causes co-precipitation of tyrosine-phosphorylated EGF receptors. Similarly, EGF receptor immunoprecipitates from EGF-treated 293 cells contain Cbl and Grb2. Both Grb2 and EGF receptors are released from Cbl in the presence of a proline-rich peptide that binds the NH2-terminal SH3 domain of Grb2. These results indicate that autophosphorylated EGF receptors associate with the SH2 domain of Grb2, which is complexed through its SH3 domain with proline-rich regions of Cbl. Such recruitment of Cbl to EGF receptors may reflect an important mechanism for its tyrosine phosphorylation and for assembling signaling components that mediate or modulate EGF actions.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl.

Phosphatidylinositol-3 kinase (PI-3 kinase) has been implicated in cellular events such as mitogenic signaling, actin organization, and receptor sorting. The p85 subunit of PI-3 kinase contains multiple domains capable of protein-protein interactions that may contribute to mediate the multiple physiological functions of this enzyme. Here, we demonstrate that antibodies raised against the p85 subunit of PI-3 kinase immunoprecipitate a single tyrosine-phosphorylated protein of 120 kDa (pp120) from lysates of activated Jurkat T cells and A20 B cells. This protein is the only significant phosphotyrosine-containing protein in p85 immunoprecipitates from these cells, and it cannot be detected in immunoprecipitates of other signaling proteins such as PLC gamma. Furthermore, antibodies specific for the beta isoform of p85 but not antibodies specific for the alpha isoform immunoprecipitate this tyrosine-phosphorylated protein. pp120 completely comigrates with the proto-oncogene c-cbl, which is a 120 kDa protein product abundant in lymphoid cells. Furthermore, immunoblots of p85 immunoprecipitates using antibodies raised against c-cbl detect a band at exactly the position of pp120. In addition, p85 can be detected in immunoblots of c-cbl immunoprecipitates. Thus, pp120 appears to correspond to c-cbl. A direct association between c-cbl and p85 can be observed in vitro using a fusion protein comprising the Src homology 2 (SH2) domains of p85, and this binding is abolished by phenyl phosphate, suggesting that the interaction is mediated through phosphotyrosine-SH2 domain interactions. Thus, these results show important functional differences between the alpha and beta isoforms of p85 in vivo and point to c-cbl as a potentially important mediator of some of the functions of PI-3 kinase in intact cells.

Animals↗
PubMed1995

Pulmonary sling: morphological findings. Pre- and postoperative course.

Pulmonary sling (PS) is a congenital condition in which the left pulmonary artery (LPA) arises from the right pulmonary artery (RPA), forming a sling around the trachea causing tracheal compression. The incidence is not so rare as initially thought. Symptoms of severe airway obstruction often begin in the newborn or young infant. Echo-colour-Doppler may reveal the PS but emphysema can mask the typical findings. Deviation of fluid-filled lungs may be detected prenatally. Chest radiographs show unusual air distribution, deviation of heart and mediastinum and altered tracheobronchial angles. Bronchography and bronchoscopy demonstrate the high incidence of associated tracheal anomalies such as cartilagenous rings and long tracheal stenosis. Anterior oesophageal indentation is not always seen in the oesophogram. Magnetic resonance imaging (MRI) and computed tomography (CT) reveal the PS, but cautious interpretation is necessary because of different levels of the anomalous LPA. PS and associated cardiovascular malformations can be clearly detected by angiography. Associated extrathoracic anomalies are common. Early diagnosis and therapy of PS is mandatory and consists of reimplantation of the LPA into the pulmonary trunk and division of the ligamentum arteriosum. The postoperative course may be cumbersome necessitating bronchological interventions. Tracheal resection may be necessary but restenosis is frequent. A one-stage repair has been proposed in such cases and was successfully done in a few reported cases. Relief of respiratory obstruction is often complete when there are no associated tracheobronchial anomalies. Late postoperative course is favourable but respiratory obstructive attacks may occur with decreasing incidence over time and tracheal growth.

Abnormalities, Multiple↗
PubMed1995

Bioprosthetic and mechanical valves in the elderly: benefits and risks.

There is controversy over whether elderly patients benefit from the durability of mechanical valves when balanced against the risk of anticoagulation. From 1976 to 1993, 576 patients 65 years old or older underwent isolated valve replacement with mechanical (n = 250) or bioprosthetic valves (n = 326). Total follow-up was 2,222 patient-years. Probability of survival and freedom from thromboembolism and prosthetic valve endocarditis were not different between the two groups. There was a significant difference (p = 0.015) in freedom from anticoagulant-related hemorrhage. Two patients with mechanical prostheses and 7 patients with bioprostheses were reoperated. However, actuarial freedom from reoperation was not different (p = 0.73) in both groups, with no hospital mortality, whereas mortality from thromboembolic events and anticoagulant-related hemorrhage was three times higher in patients with mechanical prostheses as compared with patients with bioprostheses (1.08% versus 0.36% per patient-year). The benefit from the durability of mechanical valves, compared with bioprostheses, is smaller than expected because of the limited number of patients exposed to the onset of bioprosthetic structural deterioration. Elderly patients without absolute indication for anticoagulation should preferentially receive bioprostheses for valvular replacement.

Actuarial Analysis↗
PubMed1995

Allograft implantation in pediatric cardiac surgery: surgical experience from 1982 to 1994.

Between July 1982 and April 1994, a total of 290 patients (median age 6.5 years, range 1 month to 32.1 years, 69 patients younger than 1 year) underwent repair of their cardiac malformation by insertion of an allograft. The diagnoses were truncus arteriosus communis (n = 78, 27.0%), tetralogy of Fallot (n = 59, 20.0%), pulmonary atresia (n = 72, 25.0%), double outlet right ventricle (n = 15, 5.0%), complex transposition of the great arteries plus pulmonary stenosis (n = 37, 13.0%), and others (n = 29, 10.0%). Either pulmonary (n = 69) or aortic (n = 221) cadaver allografts were implanted. Two hundred twenty-nine of the allografts were antibiotic preserved. Since January 1991 (n = 61), a new cryopreservation procedure was employed for standardized uniform cooling using heat sinks and defined package geometry. Follow-up was complete for 95.2% (n = 276, 1,320 patient-years). Thirty-day mortality was 9.0% (n = 26) and late mortality was 12.1% (n = 35). Kaplan-Meier analysis revealed that patient survival was determined mainly by their underlying cardiac disease. All allografts with valve sizes less than 15.0 mm had to be exchanged within 7 years as these patients had outgrown their conduits. When the allograft was larger than 15.0 mm, exchange was necessary in 20% at 10 years. ABO compatibility and aortic or pulmonary origin of the allograft were not significant influences on allograft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Combined membranous obstruction and saccular aneurysm of the inferior vena cava.

The authors report the history of a 35-year-old man who was operated on because of an asymptomatic combined membranous obstruction and saccular aneurysm of the inferior vena cava (IVC) at diaphragmatic level. Using extracorporeal circulation as well as hypothermia, aneurysm and IVC obstruction were resected and the IVC reconstructed using pericardium. This case and the experience reported in the literature is discussed.

Adult↗
PubMed1995

Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells.

T-cell receptor (TCR) cross-linking increases tyrosine phosphorylation of multiple proteins, only a few of which have been identified. One of the most rapidly tyrosine-phosphorylated polypeptides is the 120-kDa product of the proto-oncogene c-cbl, a cytosolic and cytoskeletal protein containing multiple proline-rich motifs that are potential binding sites for proteins containing Src homology 3 (SH3) domains. We report here that in cultured Jurkat T cells, Cbl is coprecipitated with antibody against the adapter protein Grb2. Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross-linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain. Grb2 antisera also precipitated p85 from serum-starved cells, while TCR activation increased p85 and tyrosine-phosphorylated Cbl but not Cbl protein in Grb2 immunocomplexes. Phosphatidylinositol (PI) 3-kinase activity was immunoprecipitated from serum-starved cells with Cbl and to a lesser extent with Grb2 antisera, and TCR cross-linking increased this activity severalfold. The PI 3-kinase activity associated with Cbl amounted to 5 to 10% of the total cellular activity that could be precipitated by p85 antisera. The Ras exchange factor Son-of-sevenless 1 (Sos-1) was not found in anti-Cbl immunoprecipitates from activated cells, and Cbl was not detectable in anti-Sos-1 precipitates, supporting the likelihood that Sos-Grb2 and Cbl-Grb2 are present as distinct complexes. Taken together, these data suggest that Cbl function in Jurkat T cells involves its constitutive association with Grb2 and its recruitment of PI 3-kinase in response to TCR activation.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Bi-ventricular function assessed intraoperatively before and after anatomical correction of transposition of the great arteries.

After anatomical correction of transposition of the great arteries (TGA), the left ventricle (LV) is forced to develop systemic pressures without having had time for adaptation. Thus, one might expect dilatation of the LV at least in the very early intraoperative period following the operation. In nine patients with TGA aged 8-24 days (median 9.5 days) which were selected for arterial switch operation (ASO), Dacron-patch mounted thin piezoceramic transducers were attached intraoperatively by fibrin glue to opposite epicardial surfaces of the right (RV) and/or LV for continuous assessment of external minor diameters (RVD, LVD; sonomicrometry) before and after correction. Right and left ventricular pressures (RVP, LVP) were measured simultaneously and pressure-diameter loops were generated. Right and left ventricular power indices (RVPi, LVPi: = HRxVPxVsD) was calculated from heart rate, ventricular pressures, and systolic shortening of the respective ventricular diameter (RVsD, LVsD). Data obtained during circulatory steady-state immediately before extra-corporeal circulation (ECC) and up to 45 min after ECC were compared. By avoiding volume overload (CVP < or = 10 mmHg) at weaning off ECC and by lowering the systemic vascular resistance and, thus, LV afterload (approximately 8 micrograms.kg-1 min-1 dobutamine), the LV developed systemic pressure (70 +/- 7 vs. 41 +/- 4 mmHg) at unchanged diastolic LV end-diastolic pressure (LVedP) (10 +/- 3 mmHg). Left ventricular power index increased by 45 +/- 25%, although the extent of systolic shortening of LVD was reduced by 20 +/- 10%. Simultaneously, the RV was effectively unloaded (RVedP: 8 +/- 3 vs 11 +/- 6 mmHg; RVP: 39 +/- 7 vs 53 +/- 9 mmHg; RVPi: -42 +/- 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Circulation↗
PubMed1994

Sternal closure with resorbable synthetic suture material in children.

The use of resorbable sutures for sternal closure after median sternotomy in children has developed to a clinically routine procedure. Since there is no follow-up study so far about the influence of these synthetic sutures on sternal stability, wound healing, and compatibility in children, we evaluated the use of polydioxanon (PDS) cord in children particularly regarding those properties. In 59 children (weighing up to 30 kg) we could show that the use of synthetic resorbable materials (Vicryl 4/0, PDS) allows a complication-free stability of the sternum, good wound healing, and very good compatibility. It is concluded that the use of PDS cord is a suitable and reliable method for sternal closure with good clinical results.

Biocompatible Materials↗
PubMed1993

Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations.

The effect of high-dose aprotinin treatment on hemostatic activation during cardiopulmonary bypass in pediatric patients having cardiac operations was investigated. Sixty patients weighing less than 10 kg undergoing cardiac operations for different types of congenital heart diseases were studied: 20 patients were treated with aprotinin 2 x 15,000 KIU/kg, 20 patients with 2 x 30,000 KIU/kg, and 20 patients without aprotinin treatment served as the control group. Different split products of fibrinogen and/or fibrin and the fibrinolytic activity on fibrin plates were measured to assess fibrinolytic activation. F1/F2 prothrombin fragments, thrombin-antithrombin III-complex, and fibrin monomers were measured to estimate thrombin activation. There was a significant dose-dependent reduction in fibrin-fibrinogen split product formation during cardiopulmonary bypass: In the high-dose aprotinin group the concentration of the split products at the end of bypass was 1.5 +/- 0.6 micrograms/ml, compared with 3.4 +/- 3.0 micrograms/ml in the low-dose aprotinin group and 6.7 +/- 3.5 micrograms/ml in the control group (p < 00.5). Fibrinolytic activation on fibrin plates was also significantly reduced by aprotinin. Fibrin monomer formation was significantly diminished at the end of cardiopulmonary bypass in the high-dose group: 9.2 +/- 5.2 micrograms/ml compared with 21.6 +/- 14 micrograms/ml in the control group (p < 00.5). Elastase in complex with alpha 1-protease inhibitor at the end of bypass was increased to the same amount in the three groups: 784 +/- 278 ng/mL (control group), 693 +/- 189 ng/ml (low-dose aprotinin), and 719 +/- 270 ng/mL (high dose aprotinin) (no significant difference). Blood loss 6 hours postoperatively was significantly (p < 00.5) less in the high-dose group (99 +/- 32 ml/m2) than in the control group (164 +/- 87 ml/m2; low-dose group: 160 +/- 106 ml/m2). These observations suggest an attenuation of hemostatic activation during cardiopulmonary bypass with less plasmin formation and, because of inhibition of contact activation, less thrombin generation with aprotinin treatment. Thus the thrombotic-thrombolytic equilibrium is kept more balanced after cardiopulmonary bypass. High-dose aprotinin treatment is recommended for pediatric patients undergoing cardiac operations.

Antithrombin III↗
PubMed1992

Surgical evaluation of the modified Fontan procedure.

From 1980 to 1990 152 patients underwent Fontan operation at our institution. The following patient groups were identified: 1. patients with tricuspid atresia (n = 82, 54.0%); 2. patients with single ventricle (n = 31, 20.3%); 3. patients with a wide variety of non correctable, complex cardiac malformations (n = 39, 25.7%). In 27.0% of the patients a primary Fontan operation was performed. 45.0% of the patients received a previous shunt to increase pulmonary blood flow and in 29.4% of the patients a pulmonary artery band was placed to reduce pulmonary flow. Overall mortality was not significantly different in patients with previous palliative procedures (19.4%, n = 18) as compared to 17.4% (n = 6) in patients with primary Fontan operation. Risk of death was high in the group with complex cardiac malformations (28.2%, n = 11) and in patients with single ventricle (19.4%, n = 6). Early mortality was considerably less in patients tricuspid atresia (8.5%, n = 7). Postoperatively patients with incorporation of the residual right ventricular chamber and pulmonary valve (Fontan-Bjoerk) showed a significant (p less than 0.05) lower incidence of pleural effusion as compared to patients with other modifications of the Fontan procedure. Actuarial survival rate of all patients is 83.8 +/- 3.1% (mean +/- SEM) at ten years. The modified Fontan procedures are providing an accepted surgical method for patients with otherwise non correctable cardiac malformations.

Adolescent↗
PubMed1992

[Reconstruction of atrioventricular valves in partial and total atrioventricular canal].

Among the anomalies of endocardial cushion defects, the partial (PCAVC) and common (CCAVC) AV canal present a special challenge to the cardiac surgeon. In particular, reconstruction of the AV valve can be difficult in CCAVC because of morphologic variations. Within 17 years, 383 patients with this disease were operated on. Early mortality of PCAVC is below 1%, and of CCAVC below 5%. A total of 90% of the survivors are in NYHA class I. In general, plastic reconstruction of the mitral valve is performed. The risk of reoperation for recurrent mitral incompetence in both groups is between 7% and 10%. Mitral valve replacement is a rare event (1.5%).

Adolescent↗
PubMed1992

Risk factors for perioperative mortality in children with anomalous origin of the left coronary artery from the pulmonary artery.

The present study was conducted on 33 children (median age at initial cardiac catheterization 0.4 years [0.1 to 11.8]) with anomalous origin of the left coronary artery from the pulmonary artery, without associated hemodynamically significant cardiovascular anomalies, who were treated throughout a period of 18 years in our hospital. A two coronary artery circulation was reestablished in 31 of 33 children. One child died before the intended operation, and in one child the left coronary artery was ligated. There were six operative deaths, five intraoperative and one 12 hours after operation. The purpose of the study was to assess which preoperative clinical and angiographic features were associated with a higher perioperative mortality. The following preoperative factors were associated with a statistically significant higher perioperative mortality: young age at operation (p less than 0.03), left and balanced type of coronary circulation (p less than 0.01), and electrocardiographic signs of extensive acute myocardial infarction, namely, marked ST elevation (greater than or equal to 0.2 mV in at least two leads) (p less than 0.03). Left axis deviation on the electrocardiogram was associated with an extreme right dominant type of coronary circulation (p less than 0.005). The latter was also linked with adequate perfusion of the posterolateral left ventricular wall (p less than 0.005). At autopsy, severe increase of heart weight to two or three times the normal heart weight was established in six of seven children. Thus the perioperative mortality was determined primarily by the extent of myocardial ischemia. This in turn is decisively influenced by the dominant type of coronary circulation and the extent of inter-arterial collateralization. Young age, in addition, proved to be a risk factor for mortality at corrective surgery.

Aortography↗
PubMed1992

[Long-term results of Mustard operation in transposition of the great arteries. Angiographic and nuclear medicine study of ventricular function].

The fate of the right ventricle as systemic ventricle after atrial repair of complete transposition of the great arteries has not been clearly elucidated. In order to assess the long-term results of the Mustard operation in patients with complete transposition of the great arteries we present the clinical data of 23 patients who had been operated in the years 1974 and 1975. Twenty of these patients had simple complete transposition of the great arteries with intact ventricular septum, two had an additional small ventricular septal defect and one an additional left ventricular outflow tract obstruction with a 40 mm Hg systolic pressure gradient. The Mustard operation had been performed at a mean age of 2.2 (1 to 3.7) years. Seventeen of the 23 patients underwent a postoperative hemodynamic study with angiocardiography 1.1 (1 to 1.8) years following surgery. At that time the right ventricular ejection fraction, which had been calculated from biplane angiographic right ventricular volume measurements in twelve patients was 62 (52 to 68) %. However the right ventricle was dilated and the mean enddiastolic volume was 132 (108 to 192) % of normal. In twelve of the 23 patients right ventricular function was reassessed 12.6 (11 to 15.3) years after surgery by Technetium-99m-scintigraphy at rest and in ten of those after exercise with a workload of 2 watt/kg. The mean ejection fraction was 51 (38 to 66) % at rest and 52 (40 to 80) % during exercise. Only three patients had a normal response to exercise, which was defined as an increase of ejection fraction with exercise of more than 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiocardiography↗
PubMed1991

Experience with anatomical correction of transposition of the great arteries (TGA).

During the past seven years, 102 patients with TGA have been operated on using the switch operation. Overall early mortality was 5.9%, late mortality 2.%. Sixty-three newborns had an intact septum and were corrected between the 3th and 35th day after birth, 39 had a ventricular septal defect and/or associated anomalies. All operations were carried out under ECC and deep hypothermia. Myocardial function was recorded intraoperatively by using sonomicrometry. The data demonstrate that adaptation of the left ventricle to the new load conditions should be supported by drugs providing inotropic stimulation and afterload reduction. Mean follow-up time is 32.5 months, no rhythm problems have been recorded during that period, a few children revealed trivial pulmonary or aortic valve stenosis and/or incompetence. The switch operation permits good early results for newborns with TGA and intact septum and TGA with VSD. A decade has to pass in order to judge the long-term results.

Follow-Up Studies↗
PubMed1991

Long-term results after right ventricular outflow tract reconstruction with porcine and allograft conduits.

From 1975 to 1989, a total of 353 patients were operated for complex cardiac malformations with impaired pulmonary artery perfusion using 53 non-valved and 300 valved right heart to pulmonary artery conduits. In 108 patients a porcine conduit (Hancock or Carpentier-Edwards) 12-30 mm was used; the age range was 14 days to 37 years (mean 4.3 years) and body weight 2.9-68 kg (mean 15.3 kg). One hundred and ninety-two patients had an allograft of 9-29 mm implanted at the age of 17 days to 26 years (mean 3.8 years), body weight 2.7-73 kg (mean 14.2 kg). So far, 32 of the porcine valved conduits have had to be exchanged 2.5-10.5 years (mean 6.1 +/- 2.1 years) after the first implantation. In 3 patients, reoperated before 1982, another porcine valved conduit was used. After 1982, 29 exchanges were all performed using allografts. The main reason for xenograft conduit malfunction was degeneration and/or calcification of the valves. Some conduits, however, with rather small sizes of 12 and 14 mm had to be exchanged in spite of still sufficient function because the children had "outgrown" the conduit and needed a bigger one. Out of 192 patients with allografts implanted since 1982, so far 5 patients have had to be reoperated 2 months to 6 years (mean 4.6 +/- 2.8 years) after the first operation. The causes of allograft failure were degeneration and, in one case, infection of the conduit. Even though allografts seem to be the conduit of choice for right ventricular outflow tract reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗