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Martin Haas

Publications and source records attributed to Martin Haas.

17 recordsLinked to original sources
PubMed2004

c-Myb protein interacts with Rcd-1, a component of the CCR4 transcription mediator complex.

Transcriptional initiation of eukaryotic genes depends on the cooperative interaction of various transcription factors. Using the yeast two-hybrid assay, we have identified the murine Rcd-1 protein as a cofactor of the c-myb proto-oncogene product. Rcd-1 is evolutionarily conserved among many species, and moreover the yeast homologue CAF40 is part of the carbon catabolite repressor protein transcriptional mediator thought to be involved in the negative regulation of genes transcribed by RNA polymerase II. Rcd-1 is located mainly in the nucleus, and it interacts with c-Myb both in vitro and in vivo. The activation of the myeloid c-myb-specific mim-1 promoter is repressed by Rcd-1. Interestingly, rcd-1 is an erythropoietin regulated gene, which also represses the action of the AP-1 transcription factor on its target genes.

Amino Acid Sequence↗
PubMed2004

Renal osteodystrophy.

Patients with chronic renal failure suffer from four different kinds of typical bone lesions which are summarized as renal osteodystrophy (ROD). These changes can occur early during renal disease and are dependent on several factors, such as the calcium-phosphorus homeostasis, the type of renal disease or the frequency and dose of potentially harmful drugs administered. ROD usually gets worse as renal failure progresses, and during hemodialysis, and culminates, in the case of kidney transplantation, in the early post-transplant phase. Although the decrease of parathyroid hormone (PTH) and the dose of immunosuppression administered subsequently permit a certain restitution of bone stability, ROD persists lifelong in the majority of cases and is associated with a high rate of bone fractures. However, the abnormalities of mineral metabolism that lead to ROD are not only confined to bone morphology but also predispose to vascular or soft tissue calcification. This might lead to severe tissue or coronary artery calcification. It is therefore not surprising that life expectancy on hemodialysis is correlated to the expression and form of ROD. The awareness and early diagnosis of renal osteodystrophy are therefore of great importance, in particular since a number of new treatment options have recently evolved. Previously-used phosphate binders, which contain either aluminium or calcium, might be replaced by non-absorbable drugs which bind phosphate through ion exchange. In addition, PTH production can be reduced efficiently by administration of recently developed calcimimetic agents that increase the sensitivity of calcium-sensing receptors in the parathyroid gland. In patients with high-turnover bone disease or after transplantation, bisphosphonates might prevent or restore bone loss.

Biopsy↗
PubMed2004

The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function.

BACKGROUND: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function. METHODS: We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels. The effect of different variables on the occurrence of delayed graft function (DGF) was analyzed by means of stepwise logistic regression. Improvement in kidney function during the first week after transplantation was compared between groups by means of Kaplan-Meier survival analysis. RESULTS: Intake of an ACE inhibitor or ATII blocker did not influence immediate posttransplantation graft function or the occurrence of DGF. Conversely, serum creatinine levels decreased significantly faster in patients administered an ACE inhibitor/ATII blocker than in those without therapy (P < 0.01). The only variables delaying graft function were number of previous transplantations, cold ischemia time, and male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy had significantly faster graft recovery (P < 0.001). CONCLUSION: Our results suggest that intake of an ACE inhibitor or ATII blocker during the immediate posttransplantation course is safe and does not impair graft function. Additionally, patients with DGF might profit from blockade of the renin-angiotensin-aldosterone system, which possibly shortens the time to graft recovery.

Angiotensin II↗
PubMed2004

Maintenance and self-renewal of long-term reconstituting hematopoietic stem cells supported by amniotic fluid.

The maintenance and self-renewal of hematopoietic stem cells (HSC) in culture is a central focus of hematopoietic stem cell research. In vivo, the balance between HSC differentiation, apoptosis, and self-renewal is regulated at the endosteal surface niche in the bone marrow (BM). In feeder-free cultures, the fate of HSC is affected by growth factors/interleukins and serum, which affect the balance between self-renewal, differentiation, and apoptosis and lead to the rapid loss of multipotent HSC. We report that substituting human amniotic fluid (AF) for serum in HSC cultures provides a growth milieu in which HSC differentiation and apoptosis are down-regulated and multipotent HSC are maintained. Murine BM cells were cultured in serum-free medium containing 25% amniotic fluid and stem cell factor (SCF) only, "AF/SCF" cultures. Compared with serum and multiple growth factor-containing medium, cells cultured for 4 weeks in AF/SCF medium displayed downregulation of differentiation markers while maintaining a high fraction of cells expressing Sca1 (51.8%) and c-kit (10.2%). Reconstitution of lethally irradiated C57BL/6 (Ly5.2) mice with cultured Ly5.1 BM cells resulted in high levels of (cultured) donor cells in primary (78 +/- 19.4% and 94.32 +/- 2.5%, 10(5) and 10(6) cells injected, respectively) and secondary (96.5%) recipients at 8 and 11 months post-transplantation. Hence, long-term repopulation with AF/SCF cultured BM cells was maintained. Addition to the cultures of 10% serum, interleukin (IL)-3, IL-6, granulocyte colony stimulating factor (G-CSF), or granulocyte-macrophage colony stimulating factor (GM-CSF), singly or in combination, resulted in rapid differentiation and apoptosis, leading to the total loss of HSC.

Amniotic Fluid↗
PubMed2004

Nonsustained effect of short-term bisphosphonate therapy on bone turnover three years after renal transplantation.

BACKGROUND: We recently showed that two doses of 4 mg of zoledronic acid (ZOL) ameliorated the bone loss and improved bone histology within the first six months after kidney transplantation. The aim of the present study was to evaluate whether this early short-term intervention exhibited a sustained bone-sparing effect. METHODS: A homogenous group of 20 de novo renal transplant recipients were equally randomized to two infusions of 4 mg of ZOL or placebo at two weeks and three months after engraftment. Patients were followed up for three years by sequential determination of bone densitometry and specific biochemical markers. RESULTS: From month six to three years after transplantation, both treatment groups exhibited an improvement of bone mineralization. Femoral neck bone mineral density z-scores increased statistically significantly from -1.3 (2.6) to -0.2 (3.6) in the placebo group and from -1.6 (2.9) to -1.2 (1.9) in the ZOL group (median, range). Biochemical parameters of osteoblast activity such as osteocalcin and bone-specific alkaline phosphatase did not increase significantly in both groups. Osteoprotegerin, a marker of osteoclast inhibition, was significantly elevated over the first six months in the ZOL group, but decreased to similar levels, as in the placebo group, over the next two and a half years. Other markers of osteoclast activity such as c-telopeptide of type 1 collagen, calcitonin, and intact parathyroid hormone were not different between six months and three years in either group. CONCLUSION: The early bone-sparing effect of short-term ZOL therapy confers no sustained benefit versus placebo at three year post-transplantation.

Acute Disease↗
PubMed2003

Lamb shift of laser-dressed atomic states.

We discuss radiative corrections to an atomic two-level system subject to an intense driving laser field. It is shown that the Lamb shift of the laser-dressed states, which are the natural state basis of the combined atom-laser system, cannot be explained in terms of the Lamb shift received by the atomic bare states which is usually observed in spectroscopic experiments. In the final part, we propose an experimental scheme to measure these corrections based on the incoherent resonance fluorescence spectrum of the driven atom.

Journal Article↗
PubMed2003

Zoledronic acid to prevent bone loss in the first 6 months after renal transplantation.

BACKGROUND: Bisphosphonates can prevent bone mineral density loss after renal transplantation, but their effect on trabecular mineralization and bone morphology, two key factors of bone stability, remains unknown. METHODS: In a 6-month, randomized, placebo-controlled study, 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment. At transplantation and after 6 months, mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies. Bone mineral density (BMD) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry, and serum biochemical markers of bone metabolism were determined monthly. RESULTS: Trabecular calcium content increased significantly in the zoledronic acid group, but remained unchanged in the placebo group. BMD at femoral neck showed no change in the zoledronic acid group, but decreased in the placebo group. BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group. High-turnover bone disease resolved similarly in both groups, as evidenced by a significant decrease of eroded bone surface, osteoclast and osteoblast surface. Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study. Kidney transplant function was stable after zoledronic acid therapy. CONCLUSIONS: Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation. The beneficial effect of bisphosphonate therapy is further evidenced by an increase of lumbar spine BMD, and stabilization of femur BMD.

Biomarkers↗
PubMed2002

Influence of plasma immunoglobulin level on antibody synthesis.

In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were obtained simultaneously. The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter. Total immunoglobulin G (IgG) and specific antibody concentrations increased to pretreatment values in 88% and 43% of the patients, respectively, and remained below the original values in the others. In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis. The restoration of serum IgG levels after IA, therefore, does not result from increased antibody synthesis but is probably related to changes of catabolism and immunoglobulin backflow.

Adult↗
PubMed2002

Antioxidant treatment of therapy-resistant idiopathic membranous nephropathy with probucol: a pilot study.

BACKGROUND: Proteinuria in Heymann's nephritis, an experimental rat model disease corresponding to membranous nephropathy, has been shown to be due to lipid peroxidation. Since the pathophysiology might be similar to idiopathic membranous nephropathy in humans, we performed a prospective multicenter trial to investigate the efficacy of the lipid peroxidation scavenger, probucol. METHODS: Fifteen patients with biopsy-proven idiopathic membranous nephropathy resistant to conventional immunosuppressive therapy (n = 7) and/or ACEI treatment (n = 12) were recruited. Probucol (1 g/d orally) was administered for three months, followed by a washout period of four weeks, whereon lovastatin (10-20 mg/d orally) was administered for additional three months. RESULTS: A significant reduction in proteinuria was seen during the probucol treatment (median (range): 6.4 (3.8-9.1) g/d vs. 4.7 (1.3-16) g/d; P < 0.05), with partial remission achieved in four patients. Three of these patients had previously been resistant to immunosuppressive therapy. Median protein excretion increased to pretreatment values during the washout period (6.2 (1.9-15) g/d; P < 0.05) and was not significantly different after the intake of lovastatin (4.9 (1.8-19) g/d; P = NS). None of the patients achieved partial remission during lovastatin therapy (P < 0.05 vs. probucol). CONCLUSION: The present study led us to conclude that proteinuria can be reduced by probucol in some patients with idiopathic membranous nephropathy. A randomized multicenter study to further elucidate the influence of lipid peroxidation scavengers on membranous nephropathy is warranted.

Adult↗
PubMed2002

Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis.

BACKGROUND: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99mTc-Exametazime (99mTc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. METHODS: The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99mTc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99mTc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROIs were drawn over the nasal region, the right lung, kidneys, and liver. RESULTS: Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 +/- 0.07 vs. 0.37 +/- 0.11, p < 0.05). Distinct to moderate lung uptake was observed in 2 patients with WG and in one with ING. No correlation was found between scintigraphic results, medication, ANCA status or cretinine levels. CONCLUSION: Nasal leukocyte accumulation is increased in systemic vasculitis, independent of the immunosuppressive treatment and later clinical course. However, this finding is not specific for vasculitis. 99mTc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis.

Adult↗
PubMed2002

Long-term treatment of myasthenia gravis with immunoadsorption.

Acute treatment of myasthenic crisis with immunoadsorption (IA) or plasma exchange is well established. The efficiency of chronic apheresis therapy in myasthenia gravis (MG), however, and its efficacy in reducing concomitant potentially harmful immunosuppressive therapy, is unknown. We treated 13 patients with therapy-resistant MG or severe steroid or azathioprine therapy-related side effects, or both, with long-term IA [median, 38 (range: 16-59) months]. IA was performed every second day until partial remission was achieved (modified Osserman score <2). Subsequently, oral immunosuppressive therapy was reduced and the frequency of IA adapted to the clinical symptoms. After initiation of IA the mean (SEM) Osserman score decreased from 3.23 +/- 0.12 to 1.23 +/- 0.08 within 1 month (P < 0.01). Mean azathioprine dose was reduced concomitantly from 89 +/- 9.4 mg/day to 56 +/- 11 mg/day (P < 0.05), and mean prednisolone dose from 41 +/- 7.6 mg/day to 22 +/- 8.5 mg/day (P < 0.05). After 36 months the number of IA-sessions/month had been reduced from 4.81 +/- 0.24 to 2.64 +/- 0.4 (P < 0.05), the mean azathioprine dose to 25 +/- 17 mg/day and the mean prednisolone dose to 9 +/- 3.6 mg/day. Six out of thirteen patients were weaned from IA after a median of 33 (range, 16-50) months and a decrease of the Osserman score to 0.33 +/- 0.33. In these patients MG remained stable during a follow-up period of 28 (range, 16-38) months. We conclude that long-term IA enables the reduction of oral immunosuppressants in patients with contraindications or resistance to steroid and azathioprine therapy. Furthermore, almost 50% of the patients can be weaned from IA with then substantial lower need of further immunosuppressive therapy.

Adult↗
PubMed2002

Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients.

Osteoprotegerin (OPG) has a profound inhibitory effect on osteoclast differentiation and bone resorption. Because high-turnover renal osteodystrophy (ROD) is characterized by increased osteoclast activity, serum OPG concentrations might be used to distinguish between forms of ROD. Twenty-six patients on maintenance hemodialysis therapy underwent a transiliac crest biopsy for evaluation of histopathologic characteristics and histomorphometric studies. ROD was diagnosed as type II (normal or low turnover) or type III (high turnover plus osteoidosis) disease. Bone mineralization density distribution (BMDD) was characterized by measuring the mean trabecular calcium concentration in the biopsy specimen with quantitative backscattered electron imaging. Patients underwent additional dual-energy x-ray absorptiometry (DEXA) of the spine and hip and measurement of such biochemical markers of bone turnover as OPG, intact parathyroid hormone (iPTH), osteocalcin, calcitonin, bone alkaline phosphatase, and cross-laps. OPG levels were significantly reduced in patients with ROD III compared with ROD II (118 +/- 38 versus 204 +/- 130 pg/mL; P < 0.05) and correlated with BMDD (r = 0.43; P < 0.05). Patients with ROD III showed significantly lower BMDD compared with healthy controls (21.42% +/- 0.12% versus 22.17% +/- 0.81% weight; P < 0.01). Besides iPTH, which showed significantly greater levels in patients with ROD III than ROD II (382 +/- 322 versus 136 +/- 156 pg/mL; P < 0.05), none of the serological markers or DEXA was useful in separation of the groups. Discriminant function analysis showed that a combination of OPG and iPTH correctly classifies ROD II in 72% and ROD III in 88% of patients. We conclude that OPG in combination with iPTH can be used as a marker for noninvasive diagnosis of ROD in hemodialysis patients. Furthermore, OPG serum levels might be used to estimate trabecular bone mineralization in these subjects.

Biomarkers↗
PubMed2002

Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors effectively reduce proteinuria; however, the optimal antiproteinuric dose is still unknown. We conducted this study to determine whether an increase in ACE-inhibitor dose above the maximal antihypertensive effect has additional antiproteinuric potential. METHODS: Twenty-three proteinuric patients were administered the ACE inhibitor spirapril at a starting dose of 3 to 6 mg/d. The dose was increased every 6 weeks until the maximal antihypertensive effect, assessed by 24-hour ambulatory blood pressure (ABP) monitoring, was achieved (spir(max)), then increased to a supramaximal dose (spir(supramax)). Renal parameters, urinary protein excretion, and systemic activity of the renin-angiotensin system were compared between baseline, spir(max), and spir(supramax). Glomerular filtration rate and renal plasma flow were determined before the administration of spirapril and after administration of the supramaximal dose. RESULTS: Median ABP and proteinuria decreased significantly between baseline and spir(max) (median, 102 mm Hg; range, 82 to 122 mm Hg versus 97 mm Hg; range, 82 to 113 mm Hg; median protein, 2.56 g/d; range, 1.05 to 22.1 g/d versus 1.73 g/d; range, 0.42 to 4.7 g/d). Both creatinine level and creatinine clearance remained unchanged. Suppression of angiotensin II formation led to a significant increase in renin and angiotensin I concentrations and a nonsignificant decrease in aldosterone levels. The increase in spirapril to a supramaximal dose had no further effect on serum renin or angiotensin I levels or proteinuria. There was an additional slight decrease in aldosterone levels and, subsequently, a significantly lower level than at baseline. CONCLUSION: Our results show that the antiproteinuric effect of spirapril is associated with its antihypertensive effect. Although high-dose ACE-inhibitor therapy has no additional influence on proteinuria, a possible beneficial long-term effect cannot be ruled out.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Peri-operative immunoadsorption in sensitized renal transplant recipients.

BACKGROUND: Re-transplanted kidney allograft recipients with high levels of panel reactive antibodies (PRA) are at increased risk of early immunologic graft loss. In these patients, prophylactic peri-operative antibody depletion by immunoadsorption (IA) could prevent humoral graft injury and thus, in combination with anti-cellular rejection therapy, improve graft survival. METHODS: Twenty re-transplanted and broadly immunized cadaver kidney recipients (median PRA reactivity 87%, range 55-100%) were treated with IA (protein A) immediately before transplantation and during the early post-transplantation period (median number of IA sessions 11, range 1-24). Patients received additional prophylactic anti-lymphocyte antibody therapy. Nineteen patients had a negative pre-transplant cross-match. In one patient, a positive cross-match was rendered negative by the pre-transplant IA session. RESULTS: One-year graft survival was 80% and patient survival 95%. Median (range) serum creatinine in functioning grafts was 1.6 (0.8-2.7) mg/dl at discharge and 1.5 (1.0-5.8) mg/dl at 1 year. Two grafts were lost due to acute vascular rejection, whereby one rejection occurred after withdrawal of immunosuppression due to septicaemia. One patient had acute cellular rejection, which was reversed by a second course of anti-lymphocyte antibody therapy. Thrombotic microangiopathy and surgical complications were the causes for one graft loss each. Retrospective immunohistochemistry revealed peritubular C4d staining, a presumed marker for humoral alloreactivity, in 12 out of 15 biopsies. CONCLUSIONS: These results suggest that prophylactic peri-operative IA and anti-lymphocyte antibody therapy might be an effective therapeutic strategy for the prevention of early graft failure in sensitized re-transplant recipients.

Adult↗
PubMedDate not supplied

Effects of tumor suppressor gene (p53) on brain tumor angiogenesis and expression of angiogenic modulators.

BACKGROUND: p53 retarded tumor growth by several known mechanisms, including suppression of cell proliferation and inhibition of tumor angiogenesis. Vascular endothelial growth factors (VEGF) and angiopoietins (Ang-1, Ang-2) are major angiogeneic modulators. The current study examined the effect of p53 on the expression of these factors in conjunction with tumor growth and vascular formation. MATERIALS AND METHODS: Growth characteristics of rat glioma cells (RT-2) infected with retrovirus (MSCV) encoding a full-length human wild-type p53 gene were examined by clonogenic assay. Expression of the transgene in vitro was verified by RT-PCR and immunoprecipitation. Tumor morphology, vascular architecture and the expression of VEGF, Ang-1, Ang-2 and Tie-2 were examined by immunohistochemistry and semi-quantitative RT-PCR. RESULTS: p53-infected cells showed retardation in growth and colony formation. In vivo, expression of the transgene resulted in prolonged survival and reduction of tumor volume (62%) and reduced the expression of VEGF (57.8%) and Tie-2 (15.4%) but not Ang-1 and Ang-2. The tumor exhibited increased necrosis (38%), hemorrhage and abnormal vascular architecture. CONCLUSION: p53 causes tumor regression by suppressing tumor proliferation and indirectly induces involution of tumor vessels by fostering unopposed activity of Ang-2 in an environment of diminishing VEGF.

Angiogenic Proteins↗