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T Deuse

Publications and source records attributed to T Deuse.

6 recordsLinked to original sources
PubMed2006

Tracheal allograft transplantation in rats: the role of different immunosuppressants on preservation of respiratory epithelium.

BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting the survival of lung allograft recipients. Injury and loss of epithelium are associated with obliteration of the airway lumen. The aim of this study was to examine the effects of various immunosuppressants on airway epithelium. METHODS: Tracheae from Brown Norway donors were heterotopically transplanted into the greater omentum of Lewis (allografts) or Brown Norway (isografts) animals. Recipients were treated for 28 days with FK778 (20 mg/kg), tacrolimus (4 mg/kg), or sirolimus (2 mg/kg). Tracheal segments were evaluated for the degree of luminal occlusion as well as the type and percent of luminal epithelial cell coverage. RESULTS: All agents inhibited peritracheal infiltration and luminal obliteration. Tacrolimus- more than sirolimus-treated recipients showed partial preservation of the luminal epithelial coverage, whereas animals that received FK778 showed no respiratory epithelium. The epithelial loss was accompanied by the appearance of fibrous tissue, which replaced the mucosa. CONCLUSIONS: Tacrolimus as well as sirolimus effectively prevented the development of obliterative airway disease whereas tacrolimus and, to a lesser degree, sirolimus preserved epithelial cells as a source of protective cytokines. With FK778 significant airway obliteration was suppressed despite complete epithelial loss. Thus, FK778-treated animals displayed an epithelial-independent inhibitory effect on myofibroblast proliferation.

Animals↗
PubMed2006

FK778: new cellular and molecular mechanisms of action.

PURPOSE: The new malononitrilamide FK778 is currently being evaluated as an immunosuppressant for organ transplantation. Its main mechanism is inhibition of a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms of action on different cell types involved in acute and chronic allograft rejection. METHODS: Purified Brown-Norway rat aortic endothelial cell (EC) cultures were pretreated with several concentrations of FK778. Endothelial adhesion molecule expression (ICAM-1/VCAM-1) stimulated with TNF-alpha was quantified by immunofluorescence. Purified Lewis rat lymphocytes (LC) incubated with FK778 were stimulated via TCR/CD28 signals, and CD25 expression was quantified using FACS analysis. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. Lymphocyte-EC interaction was assessed by micromanipulator-assisted single-cell adhesion assays. Finally, smooth muscle cell (SMC) proliferation and migration was analyzed. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. RESULTS: TNF-alpha stimulation and TCR/CD28 co-stimulation significantly increased EC ICAM-1/VCAM-1-expression and LC CD25 surface expression, respectively. These effects were dose-dependently inhibited by FK778 and were not reversed by the addition of uridine. FK778 dose-dependently attenuated LC adhesion to allogeneic EC. The dose-dependent inhibition of SMC proliferation by FK778 was abolished by uridine addition, whereas the inhibitory effect on SMC migration was not affected by uridine supplementation. CONCLUSIONS: FK778 directly reduced endothelial adhesion molecule up-regulation, inhibited lymphocyte activation, and attenuated lymphocyte-endothelium interactions, critical early steps in graft rejection. These effects were separate from the blockade of pyrimidine synthesis. The antiproliferative potency of FK778 on SMC may be an important mechanism to inhibit the fibroproliferative lesions of chronic organ rejection.

Alkynes↗
PubMed2003

Robotically assisted coronary artery bypass surgery with the ZEUS telemanipulator system.

Our goal of minimally invasive coronary bypass surgery is a completely endoscopic operation and anastomosis. Minimally invasive procedures reduce the invasiveness of the operation and therefore the morbidity and length of hospitalization of the patients. A possible solution to the technical problems that accompany manually performed endoscopic anastomoses is telemanipulation, which provides surgeons with the necessary equipment to accomplish totally endoscopic coronary anastomoses. Robotic telemetric systems together with 3-D visualization provide the necessary platform. This article summarizes the current worldwide experience with the ZEUS(TM) system in cardiac surgery and describes the steps from preclinical to endoscopic operation, focusing on the potential limitations of the procedure and the system.

Anastomosis, Surgical↗
PubMed2002

Midterm results and quality of life after minimally invasive vs. conventional aortic valve replacement.

BACKGROUND: This study compares early and mid-term results as well as the quality of life (QOL) between the minimally invasive and conventional aortic valve replacement (AVR). METHODS: Between 7/97 and 4/01, 70 patients (mean age 64.3 +/- 1.3 years) underwent minimally invasive AVR (group M) through an L-shaped ministernotomy. The results were compared to those of 70 conventional AVR (group C) patients during the same period. Patients were equally matched according to age, sex, ejection fraction, valvular lesion, and valve prosthesis. In groups M and C, follow-up was 98.5 % and 95.4 % complete and averaged 34.0 +/- 10.3 and 33.1 +/- 12.9 months, respectively. RESULTS: There were no hospital deaths in group M but two deaths in group C (p = n. s.). Conversion to full sternotomy was necessary in two group M patients. Cross-clamping time (71 +/- 15 min vs. 58 +/- 18 min), cardiopulmonary bypass time (105 +/- 22 min vs. 84 +/- 24 min), and time of surgery (228 +/- 45 min vs. 184 +/- 48 min) were significantly longer in group M. No statistically significant differences between the two groups for postoperative ventilation time, transfusion rate, ICU stay or length of hospital stay were recorded. At the end of follow-up, 98.5 % vs. 96.9 % of the patients were free of thromboembolism (p = n. s.), 100.0 % vs. 96.9 % were free of endocarditis (p = n. s.), and 98.5 % vs. 100.0 % were free of reoperation (p = n. s.) in group M compared to group C. Survival was 97.0 % vs. 91.9 % (p = ns). No differences in any of the 8 QOL categories, in patient satisfaction with the operative result or in judgment of the cosmetic aspect were noted among groups. CONCLUSIONS: This study has failed to show any advantage of minimally invasive AVR in early or midterm follow-up.

Adult↗
PubMedDate not supplied

Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat.

Chronic cardiac transplant vasculopathy still remains the major cause of late graft failure after the 1st postoperative year, with iNOS playing a central role in the progression of this disease. Since VASP, a recently identified microfilament-associated protein in smooth muscle cells, endothelial cells, and platelets, is phosphorylated by cyclic nucleotide dependent protein kinases, changing amounts of NO-producing mononuclear infiltration cells during cardiac rejection are supposed to change platelet VASP phosphorylation patterns. We investigated whether platelet VASP Ser(157) phosphorylation (VASP shift) after coronary passage of rat cardiac allografts correlates with graft infiltration. The Lew-F344 heterotopic rat cardiac transplantation model was used. Native hearts and grafts were harvested 3-150 days after transplantation and were used for Langendorff perfusion. The platelet VASP shift after native heart and graft perfusion was identified. Additional iNOS stimulation and iNOS inhibition were achieved pharmacologically. Immunohistology revealed graft mononuclear infiltration. Platelet VASP Ser(157) and Ser(239) phosphorylation significantly increased after coronary passage of native hearts and grafts (p < 0.01). Though platelet VASP Ser(157) phosphorylation failed to directly express graft infiltration, we showed a significant correlation between changes of platelet VASP shift and extent of grafts' mononuclear infiltration after competitive iNOS inhibition (p < 0.01). The platelet VASP shift is modified during coronary perfusion, and this modification correlates with mononuclear infiltration in the graft. This emphasizes the influence of mononuclear infiltration cells on microfilamental structures of the cytoskeleton in adjacent cells.

Animals↗