Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 142
Filter
1.
Int J Cardiol ; 280: 117-123, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30654912

ABSTRACT

BACKGROUND: Data regarding the effects of vitamin D on cardiac function are inconclusive. METHODS: In a post-hoc analysis of the EVITA (Effect of vitamin D on mortality in heart failure) trial, we investigated whether a daily vitamin D3 supplement of 4000 IU for three years affects echocardiography parameters like left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), and LV ejection fraction (LVEF) in patients with advanced heart failure (HF) and 25­hydroxyvitamin D levels <75 nmol/L. Of 400 patients enrolled, 199 were assigned to vitamin D and 201 to placebo. We assessed time × treatment interaction effects using linear mixed models and analyzed in subgroups vitamin D effects at 12 and 36 months post-randomization using analysis of covariance with adjustments for baseline values. RESULTS: At baseline, values of LVEDD, LVESD, and LVEF were 67.5 ±â€¯10.5 mm, 58.9 ±â€¯12.0 mm, and 30.47 ±â€¯10.2%, respectively. There were no time × treatment interaction effects on LV echocardiographic parameters in the entire study cohort, neither at 12 months nor at 36 months post-randomization (P-values > 0.05). However, in the subgroup of patients aged ≥50 years, vitamin D treatment was associated with an increase in LVEF of 2.73% (95%CI: 0.14 to 5.31%) at 12 months post-randomization (n = 311). The increase was slightly attenuated to 2.60% (95%CI: -2.47 to 7.67%) at 36 months post-randomization (n = 242). CONCLUSION: Our data indicate that vitamin D supplementation does not significantly improve cardiac function in all patients with advanced HF. However, vitamin D probably improves LV function in HF patients aged ≥50 years.


Subject(s)
Dietary Supplements , Heart Failure/diagnostic imaging , Heart Failure/drug therapy , Ventricular Function, Left/drug effects , Vitamin D/administration & dosage , Adult , Aged , Drug Administration Schedule , Female , Follow-Up Studies , Heart Failure/physiopathology , Humans , Male , Middle Aged , Ventricular Function, Left/physiology
2.
Osteoporos Int ; 29(3): 579-586, 2018 03.
Article in English | MEDLINE | ID: mdl-29260292

ABSTRACT

Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status. INTRODUCTION: Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D3 dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L. METHODS: In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values. RESULTS: Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)2D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05). CONCLUSIONS: A daily vitamin D3 dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure.


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Cholecalciferol/pharmacology , Dietary Supplements , Heart Failure/complications , Vitamin D Deficiency/drug therapy , Biomarkers/blood , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/therapeutic use , Bone Resorption/blood , Bone Resorption/prevention & control , Cholecalciferol/administration & dosage , Cholecalciferol/therapeutic use , Drug Administration Schedule , Heart Failure/blood , Heart Failure/physiopathology , Humans , Male , Middle Aged , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/etiology , Vitamin D Deficiency/physiopathology
3.
Nutr J ; 16(1): 49, 2017 Aug 23.
Article in English | MEDLINE | ID: mdl-28835271

ABSTRACT

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels (< 75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF. METHODS: EVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels < 75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n = 85; placebo group: n = 87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences. RESULTS: In the vitamin D and placebo group, baseline proportions of patients with anemia (Hb < 12.0 g/dL in females and < 13.0 g/dL in males) were 17.2% and 10.6%, respectively (P = 0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P > 0.99). There was no between-group difference in change in the Hb concentrations (- 0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P = 0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n = 26; placebo group: n = 23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels. CONCLUSIONS: A daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels. TRIAL REGISTRATION: The study was registered at EudraCT (No. 2010-020793-42) and clinicaltrials.gov ( NCT01326650 ).


Subject(s)
Anemia/epidemiology , Cholecalciferol/administration & dosage , Heart Failure/complications , Anemia/drug therapy , Anemia/etiology , Dietary Supplements , Female , Heart Failure/blood , Heart Failure/mortality , Hemoglobins/analysis , Humans , Male , Middle Aged , Placebos , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy
4.
Transplant Proc ; 47(8): 2400-3, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26518940

ABSTRACT

BACKGROUND: In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost. PATIENTS AND METHODS: Patients from 2 ongoing studies in kidney (KTx) and heart (HTx) transplantation were monitored blinded on a scheduled basis, by means of a published universal droplet digital polymerase chain reaction to quantify the GcfDNA. RESULTS: Immediately after engraftment, GcfDNA reaches high values (>5% of total cfDNA), with a rapid decrease to values of <0.5% within 1 week. Living-related KTx recipients show lower initial values, reflecting the absence of preservation injury. Episodes of rejection in KTx and HTx are accompanied by a significant increase of GcfDNA (>5-fold) above values in patients without complications, occurring earlier than clinical or biochemical hints to rejection. One case of rejection, which became clinically suspect after 1 year and was proven with biopsy, showed a significant 10-fold increase 3 months earlier. CONCLUSIONS: The quantification of GcfDNA has the potential to detect rejection episodes at early stages, when other means of diagnosis are not effective. The method's noninvasiveness enables the monitoring recipients at intervals that are desired to catch rejections at early actionable stages to prevent full-blown rejection. This biomarker will be particularly valuable in regimens to minimize immunosuppression.


Subject(s)
DNA/blood , Graft Rejection/blood , Heart Transplantation , Kidney Transplantation , Allografts , Biomarkers/blood , Cross-Sectional Studies , Graft Rejection/diagnosis , Humans , Kidney , Polymerase Chain Reaction , Tissue Donors
5.
Herz ; 39(1): 66-73, 2014 Feb.
Article in German | MEDLINE | ID: mdl-24452762

ABSTRACT

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.


Subject(s)
Graft Rejection/mortality , Heart Failure/mortality , Heart Failure/surgery , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/surgery , Postoperative Complications/mortality , Comorbidity , Germany , Heart-Lung Transplantation/mortality , Humans , Incidence , Patient Selection , Risk Factors , Survival Rate , Treatment Outcome
6.
Transplant Proc ; 45(5): 2000-4, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769094

ABSTRACT

Tacrolimus (TAC) retard is a new oral formulation of TAC that is given once instead of twice daily. We investigated the efficacy and safety of TAC retard in heart transplant recipients during a 36-month follow-up period. We included 11 patients receiving TAC retard (once-daily [OD] group) and 11 age- and sex-matched patients receiving TAC (twice-daily [TD] group). The primary endpoint was a composite of death, graft loss, and drug discontinuation (treatment failure). Secondary endpoints were biopsy-proven rejection, malignancy, infection, and safety parameters determined on the basis of laboratory evaluations. In the OD and TD groups, the primary endpoint was reached by 18.2% and 45.54% of patients, respectively (P = .277). In detail, 3-year survivals were 90.0% and 70.0% (P = .291) and freedom from drug discontinuation 90.9% and 77.9% (P = .533), respectively. Freedom from biopsy-proven rejection, malignancy, and infection were similar between the groups. Moreover, biochemical parameters of kidney and liver function, hematologic parameters, and C-reactive protein levels were similar. Despite a remarkably higher prescribed dose, blood trough levels of TAC were below the lower target value in several patients of the OD group at the end of the follow-up period, but in none of the patients in the TD group. In conclusion, this small 3-year follow-up study suggests efficacy and safety in patients receiving TAC retard similar to those in patients receiving TAC. Nevertheless, the required dose of TAC retard for achieving acceptable blood trough levels should be investigated in more detail.


Subject(s)
Heart Transplantation , Immunosuppressive Agents/administration & dosage , Tacrolimus/administration & dosage , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Treatment Outcome
7.
Thorac Cardiovasc Surg ; 60(1): 26-34, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21432755

ABSTRACT

BACKGROUND: In heart failure (HF) patients, pulmonary hypertension (PH) is associated with a poor prognosis. We assessed whether low dose treatment with the dual endothelin-1 receptor antagonist bosentan is associated with improved hemodynamics and clinical outcome in these patients. METHODS: We performed a retrospective data analysis in 82 end-stage heart failure patients on the waiting list for cardiac transplantation since January 2006. All patients had pulmonary arterial pressure >35 mmHg, pulmonary vascular resistance >240 dyn × s × cm-5, and/or a transpulmonary gradient (TPG) >15 mmHg. Fifty-four patients received a median dose of 125 mg bid bosentan (BOS group), and 28 patients received standard medical treatment (CON group). Data were assessed until June 2009. RESULTS: Hemodynamic parameters improved significantly in the BOS group but remained unchanged in the CON group. The percentage of patients who fell below the thresholds of PAP, PVR, and TPG for cardiac transplantation increased significantly by 20.3%, 34.5%, and 20.8%, respectively (p = 0.007-0.013) in the BOS group, but did not change significantly in the CON group. One-year survival on the waiting list was approximately 20% higher in the BOS group than in the CON group (p = 0.020). Bosentan treatment remained an independent predictor of reduced mortality risk on the waiting list after propensity score adjustment (relative risk = 0.107; 95% CI: 0.013-0.869; p = 0.036). CONCLUSION: Treatment with the endothelin-1 antagonist bosentan is associated with improvements in hemodynamics and clinical outcome in end-stage heart failure patients with PH. If these results can be confirmed by randomized controlled trials, bosentan may represent a treatment option in these patients.


Subject(s)
Antihypertensive Agents/therapeutic use , Heart Failure/drug therapy , Heart Transplantation , Hemodynamics/drug effects , Hypertension, Pulmonary/drug therapy , Pulmonary Artery/drug effects , Sulfonamides/therapeutic use , Waiting Lists , Adult , Aged , Analysis of Variance , Bosentan , Endothelin Receptor Antagonists , Female , Germany , Heart Failure/etiology , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/physiopathology , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Odds Ratio , Propensity Score , Proportional Hazards Models , Pulmonary Artery/physiopathology , Retrospective Studies , Time Factors , Treatment Outcome , Waiting Lists/mortality
8.
Transplant Proc ; 43(5): 1839-46, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21693287

ABSTRACT

The calcineurin inhibitor cyclosporine (CSA) displays nephrotoxic side effects. We switched 95 maintenance heart transplant recipients with chronic kidney disease (CKD) stages 3-4 from CSA to everolimus (EVL). The CSA dosage was reduced by 50%. Kidney function, lipid metabolism, and cardiac function investigated during a 2-year follow-up were compared with heart transplant recipients with CKD stages 2-3 who continued to receive CSA (CSA group; n = 84). Whereas 64/95 patients received reduced CSA plus EVL during the entire follow-up period (EVL continued subgroup, ECN), 31 discontinued EVL (EVL discontinued subgroup, EDS) after 4.3 months (median) because of various clinically relevant adverse events. Glomerular filtration rates (estimated using the modification of diet in renal disease formula) increased by 4.0 mL/min/1.73 m(2) in the ECN subgroup but decreased by 2.4 mL/min/1.73 m(2) and 9.0 mL/min/1.73 m(2) in the EDS subgroup and the CSA group, respectively (P < .001). Triglyceride and total cholesterol concentrations increased significantly among the ECN group, but remained constant in the EDS subgroup and the CSA group. Statin use was increased by 15% in the ECN group (P < .01). Mortality and cardiac rejection rates did not differ significantly among the 3 groups. In summary, EVL combined with low-dose CSA had modest beneficial effects on kidney function in heart transplant recipients with CKD stages 3-4. A significant percentage of patients had to stop EVL because of various adverse events.


Subject(s)
Cyclosporine/therapeutic use , Heart Transplantation , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Sirolimus/analogs & derivatives , Aged , Cyclosporine/administration & dosage , Everolimus , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Sirolimus/administration & dosage , Sirolimus/therapeutic use
9.
Biotech Histochem ; 86(4): 226-31, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20297946

ABSTRACT

Magnetic force combined with magnetic nanoparticles recently has shown potential for enhancing nucleic acid delivery. Achieving effective siRNA delivery into primary cultured cells is challenging. We compared the utility of magnetofection with lipofection procedures for siRNA delivery to primary and immortalized mammalian fibroblasts. Transfection efficiency and cell viability were analyzed by flow cytometry and effects of gene knockdown were quantified by real-time PCR. Lipofectamine 2000 and magnetofection achieved high transfection efficiencies comparable to similar gene silencing effects of about 80%; the cytotoxic effect of magnetofection, however, was significantly less. Magnetofection is a reliable and gentle alternative method with low cytotoxicity for siRNA delivery into difficult to transfect cells such as mammalian fibroblasts. These features are especially advantageous for functional end point analyses of gene silencing, e.g., on the metabolite level.


Subject(s)
Magnetite Nanoparticles/administration & dosage , RNA, Messenger/metabolism , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Transfection/methods , Animals , Cell Culture Techniques , Cell Line, Tumor , Cell Survival , Fibroblasts , Gene Silencing , Lipids/administration & dosage , Lipids/chemistry , Mice , RNA Interference/physiology
10.
Leukemia ; 21(8): 1739-51, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17541401

ABSTRACT

The chromosomal translocation t(8;14) is the hallmark of Burkitt's-lymphoma (BL) and fuses the proto-oncogene c-MYC to the IGH locus. We analyzed the genomic structure of MYC/IGH fusions derived from a large series of 78 patients with t(8;14) and asked (i) whether distinct breakpoint clusters exist within the MYC gene and (ii) whether any pairwise association between particular IGH and MYC breakpoints exist. Identification of such associations will help elucidate the etiology of the breaks on the MYC locus. Scan statistic analyses revealed two distinct, but large clusters within c-MYC containing 60/78 (77%) of the breakpoints. Clusters 1 and 2 were 560 and 779 bp in length within a 4555 bp breakpoint cluster region. Breaks within IGH switch mu and joining region did not differ with respect to their corresponding MYC breakpoints. However, there was a highly significant correlation between breakpoints 5' of MYC cluster 1 and fusions to IGH switch gamma region and breakpoints downstream of MYC cluster 2 and fusions to IGH switch alpha region (chi(2)-test: P<0.005). Chromatin changes governing choice of IGH-Fc region recombination may parallel changes in the MYC gene 5' region chromatin leading to some degree of coordinated ontological specificity in breakpoint location.


Subject(s)
Burkitt Lymphoma/genetics , Chromosome Breakage , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 8/genetics , Genes, myc , Immunoglobulin Heavy Chains/genetics , Translocation, Genetic/genetics , Adolescent , Child , Child, Preschool , DNA, Neoplasm/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Male , Molecular Sequence Data , Proto-Oncogene Mas , Repetitive Sequences, Nucleic Acid , Tumor Cells, Cultured
12.
Minerva Cardioangiol ; 54(4): 499-501, 2006 Aug.
Article in English | MEDLINE | ID: mdl-17016420

ABSTRACT

We report the case of a 56-year-old male heart transplant recipient, who underwent postoperative pacemaker implantation through a left sided superior vena cava (LSVC) via anonymous vein. We describe our successful management of this case. We suggest that the specific anatomic conditions should be considered in all heart transplant recipients with LSVC if pacemaker implantation is necessary postoperatively.


Subject(s)
Heart Transplantation , Pacemaker, Artificial , Vena Cava, Superior/abnormalities , Cardiac Surgical Procedures/methods , Humans , Male , Middle Aged
13.
Transplant Proc ; 38(5): 1511-3, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16797345

ABSTRACT

An 18-year-old female Japanese patient who suffered from heart failure and severe pulmonary hypertension was referred to our clinic. The etiology of her cardiomyopathy was unclear. Inhaled prostacyclin therapy resulted in an improvement of pulmonary arterial pressure and allowed us to avoid lung transplantation. Heart transplantation resulted in a complete remission of her respiratory function. Autopsies of the explanted heart revealed massive endomyocardial fibroelastosis. We concluded that endomyocardial fibroelastosis has to be considered a cause of heart failure in young adults with unclear cardiomyopathy.


Subject(s)
Endocardial Fibroelastosis/surgery , Heart Transplantation , Adolescent , Blood Pressure , Cardiomyopathies/surgery , Endocardial Fibroelastosis/pathology , Female , Humans , Lung Transplantation , Myocardium/pathology , Vascular Resistance
14.
Br J Cancer ; 94(2): 323-32, 2006 Jan 30.
Article in English | MEDLINE | ID: mdl-16404424

ABSTRACT

We report the isolation of the 5' flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive.


Subject(s)
GTPase-Activating Proteins/genetics , Leukemia, Myeloid/genetics , Myelodysplastic Syndromes/genetics , Promoter Regions, Genetic , Acute Disease , Base Sequence , Child , Humans , K562 Cells , Methylation , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction
15.
Protoplasma ; 226(1-2): 75-80, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16231103

ABSTRACT

Filamentous fungi are an important group of tip-growing organisms, which include numerous plant pathogens such as Magnaporthe grisea and Ustilago maydis. Despite their ecological and economical relevance, we are just beginning to unravel the importance of endocytosis in filamentous fungi. Most evidence for endocytosis in filamentous fungi is based on the use of endocytic tracer dyes that are taken up into the cell and delivered to the vacuole. Moreover, genomewide screening for candidate genes in Neurospora crassa and U. maydis confirmed the presence of most components of the endocytic machinery, indicating that endocytosis participates in filamentous growth. Indeed, it was shown that in U. maydis early endosomes cluster at sites of growth, where they support morphogenesis and polar growth, most likely via endosome-based membrane recycling. In humans, such recycling processes to the plasma membrane involve small GTPases such as Rab4. A homologue of this protein is encoded in the genome of U. maydis but is absent from the yeast Saccharomyces cerevisiae, suggesting that Rab4-mediated recycling is important for filamentous growth. Furthermore, human Rab4 regulates traffic of early endosomes along microtubules, and a similar microtubule-based transport is described for U. maydis. These observations suggest that Rab4-like GTPases might regulate endosome- and microtubule-based recycling during tip growth of filamentous fungi.


Subject(s)
Endocytosis , Plants/parasitology , Ustilago/physiology , Amino Acid Sequence , Animals , Conserved Sequence , Humans , Molecular Sequence Data , Sequence Alignment , Signal Transduction , Ustilago/genetics , rab GTP-Binding Proteins/genetics
17.
Transplant Proc ; 37(10): 4522-4, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16387159

ABSTRACT

It is unclear whether heart donors positive for hepatitis B core antibodies (anti-HBc) can transfer hepatitis B virus (HBV) infection to immunosuppressed heart recipients, or whether passive transfer of anti-HBc simulates a hepatitis B infection. Therefore, we performed a case-controlled study in 46 heart recipients who all tested negative for hepatitis B antigen (HbsAg), antiHBc, and hepatitis B surface antibodies before heart transplantation. Twenty-three patients (group 1) received hearts from anti-HBc-positive donors, while 23 other patients (group 2) received hearts from anti-HBc-negative donors. After heart transplantation, anti-HBc were present in 65.0% of blood samples among group 1 and 47.8% of the blood samples among group 2 (P > .05). HbsAg was undetectable in blood samples of all patients of both study groups. The immunoglobulin preparation that we regularly use for immune suppression immediately after heart transplantation contained a relatively high concentration of anti-Hbc antibodies. The nearly identical presence of anti-HBc in both study groups indicated that passive transfer via immunoglobulin preparations rather than HBV infection is the cause for the anti-HBc detected in heart recipients. Since only a small volume of blood is transferred with the donor heart, it seems to be rather unlikely that the donor heart might be the source of anti-HBc. In summary, we observed no evidence for HBV infection in those heart recipients who received organs from anti-HBc-positive donors. Moreover, our data demonstrated that the presence of anti-HBc in heart recipients frequently occurs but does not necessarily indicate a preceding HBV infection.


Subject(s)
Antibodies, Viral/blood , Heart Transplantation/immunology , Hepatitis B Core Antigens/immunology , Hepatitis B/diagnosis , Adult , Cardiomyopathy, Dilated/surgery , Case-Control Studies , Coronary Disease/surgery , Creatinine/blood , Female , Heart Transplantation/physiology , Hepatitis B/blood , Hepatitis B/transmission , Humans , Male , Middle Aged
18.
Curr Mol Med ; 4(5): 507-17, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15267222

ABSTRACT

In recent years a new mechanism of posttranscriptional gene silencing has been discovered and named RNA interference. The interference is based on mRNA degradation mediated by small double-stranded RNA molecules approximately 21 nucleotides in length, the so-called short interfering or siRNAs. These molecules are produced from long dsRNAs by Dicer, a dsRNA-specific endonuclease, and cause specific degradation of their mRNA-targets by Watson-Crick base-pairing within a 300 kD multi-enzyme complex named RISC. RNAi is highly conserved between plants and animals of various phyla including mammals. The high sequence-specificity of RNAi makes it a new, promising tool in gene-function analysis as well as in potential therapeutics. In this review the discovery and molecular background of RNAi are summarized and possible fields of application pointed out.


Subject(s)
Endoribonucleases/metabolism , Gene Expression Regulation/physiology , RNA Helicases/metabolism , RNA Interference/physiology , RNA Stability/physiology , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Animals , Communicable Diseases/genetics , Communicable Diseases/therapy , DEAD-box RNA Helicases , Endoribonucleases/genetics , Gene Expression Regulation/genetics , Genetic Therapy , Humans , Neoplasms/genetics , Neoplasms/therapy , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/therapy , RNA Helicases/genetics , RNA Stability/genetics , RNA, Messenger/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/therapeutic use , Ribonuclease III
19.
J Microsc ; 214(Pt 2): 114-23, 2004 May.
Article in English | MEDLINE | ID: mdl-15102060

ABSTRACT

Microtubules are an important part of the eukaryotic cytoskeleton, which participates in numerous essential cellular processes. In fungi interphase microtubules mediate cell polarity and participate in polar growth. However, our understanding of their detailed role in fungal growth is just at the beginning. In growing cells of the plant pathogenic fungus Ustilago maydis microtubules are organized by polar microtubule organizing centres that focus the microtubule minus ends at the small bud. Two opposing motor complexes utilize this microtubule polarity. Cytoplasmic dynein and a kinesin of the Unc104/Kif1A family of kinesins mediate rapid bi-directional transport of early endosomes. A balance of their activity is required for cell cycle-dependent accumulation of early endosomes at the growth site, the rear cell pole and the region of cell cleavage. Mutant phenotypes suggest that these endosomes participate in polar growth, bud site selection and cell separation. Therefore, our data suggest that endocytotic membrane recycling participates in local exocytosis, and that the microtubule cytoskeleton has a crucial role in this process.


Subject(s)
Microtubules/physiology , Ustilago/physiology , Ustilago/pathogenicity , Cytoskeleton/physiology , Dyneins/metabolism , Endocytosis , Endosomes/physiology , Fungal Proteins/metabolism , Kinesins/metabolism , Movement , Plant Diseases/microbiology , Ustilago/growth & development , Ustilago/ultrastructure
20.
FEBS Lett ; 554(1-2): 10-6, 2003 Nov 06.
Article in English | MEDLINE | ID: mdl-14596906

ABSTRACT

In acute myelogenous and lymphoid leukemias, rearrangements involving the MLL (mixed lineage leukemia) gene at chromosome 11q23 are frequent. The truncated MLL protein is fused in-frame to a series of partner proteins. We previously identified the formin-binding protein 17 (FBP17) as such an MLL fusion partner. In this study, we explored in vivo physiological interaction partners of FBP17 using a two-hybrid assay and found tankyrase (TNKS), an ADP-ribose polymerase protein involved in telomere maintenance and mitogen-activated protein kinase signaling. We demonstrate that FBP17 binds via a special TNKS-binding motif to tankyrase. The physiological relevance is indicated by co-immunoprecipitation of endogenous proteins in 293T cells.


Subject(s)
Tankyrases/metabolism , Amino Acid Motifs , Binding Sites , Cell Line , Cytoplasm/chemistry , Humans , Mutagenesis, Site-Directed , Precipitin Tests , Protein Binding , Sequence Deletion , Tankyrases/physiology , Telomere/metabolism , Two-Hybrid System Techniques
SELECTION OF CITATIONS
SEARCH DETAIL
...