Biomedical subjects

M Weis

Publications and source records attributed to M Weis.

At least 19 recordsLinked to original sources

PubMed2007

[Development of a questionnaire for patient self-assessment of shoulder function based on the Rowe score].

BACKGROUND: A questionnaire for patient self-assessment of shoulder function was designed. It was based on the internationally accepted Rowe score. METHOD: Explanations and photographs were added to the various parameters to make them easier to understand for the patients. A total of 95 patients completed the assessment form. The validity was tested by a correlation analysis comparing the questionnaire with the original score. RESULTS: The questionnaire demonstrated a reproducible and significant (p<0.001), very high correlation (r>0.9) in the overall results and a moderate to very high correlation within single parameters (r>0.68). CONCLUSION: Based on these results, it can be concluded that a valid and reproducible assessment of the original score is possible with the new questionnaire. Self-evaluation allows reliable assessment which is not dependent on the examiners or location, resulting in a higher number of patients reachable for follow-up studies.

Adolescent↗

PubMed2006

Renal ischemia-reperfusion injury: new implications of dendritic cell-endothelial cell interactions.

In renal ischemia/reperfusion (I/R) injury endothelial cells are a main target. The disturbance of endothelial cell physiology leads to endothelial swelling and narrowing of the blood vessel lumen. We attribute this effect to impairment of endothelial cell nitric oxide synthase (NOS). NO is significantly reduced in the course of hypoxia causing dysfunction of the vascular smooth muscle tone. Subsequently to an I/R injury, the inflammatory response results in endothelial activation with enhanced dendritic cell (DC) adhesion and migration. Thus, alloreactive leukocytes are recruited to the inflammatory site. Finally, dendritic cell-endothelial cell interactions may play a crucial role in antigen-specific allograft rejection in I/R renal injury. DCs, which activate naïve alloreactive T cells, play a central role in the establishment of alloantigen-specific immunity. In the course of hypoxia rejection is initiated at the activated layer of foreign endothelial cells (EC), which forms an immunogenic barrier for migrating DCs and T cells. Host DCs that bind to postischemic activated ECs invade the allografted tissues, or remain stationary in the subendothelial layer, or transmigrate into lymphoid vessels and secondary lymphoid organs, where they present alloantigens to naïve host T cells. Organ rejection is mediated by host alloreactive T cells, which are activated by donor DCs (direct activation) or host DCs (indirect activation). We hypothesized that DC-EC binding and migration is the first step in the renal I/R injury that mediates allotransplant rejection. We sought to better understand the downstream events of a renal I/R injury by understanding DC binding and migration, thereby seeking new strategies for more specific immunomodulatory interventions. Herein we developed a new allotransplant-rejection model after renal I/R injury.

Antigen-Presenting Cells↗

PubMed2005

Conformation study of the membrane models by the Maxwell displacement current technique and oxidative stress.

The role of biological membranes as a target in biological radiation damage is still unclear. Recently much attention has been paid to the dynamic behaviour of the cell membrane. Maxwell displacement current technique (MDC) provides new possibility of conformation study of the membrane models. Oxidative stress can impair macromolecules in the cell on a molecular level. MDC technique enables to study the changes in molecular orientations and/or conformations of cell membranes. The combination of different methods in structural biology can clarify membrane chemical and physical properties.

Biophysical Phenomena↗

PubMed2005

Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation.

Dendritic cells (DCs) play a central role in the establishment of tolerance/immunity, because they activate naïve T cells (TCs). Therefore, the pharmacological modulation of DCs has become a major field of interest in immunology. A large body of literature has arisen from the studies of DC biology during immunosuppressive drug treatment. Immunosuppressive drugs have improved the therapeutic management of allograft organ transplantation and autoimmune diseases, significantly. There is now strong evidence that, DCs might be the key for antigen specific tolerance induction. Recently, the existence of a population of DCs that migrate to the regional lymph node in the steady state has been identified. Such steady state immature migrating DCs are loaded with tissue antigens and deliver self-antigens towards secondary lymphatic organs and might educate TCs towards self-tolerance. Latest experimental data from rodent solid organ allo-transplantation supports the idea, that DCs might even become regulatory DCs towards foreign antigen specific tolerance induction. Apparently, regulatory donor DCs invade host secondary lymphatic organs where they might eventually educate host TCs towards foreign antigen specific tolerance. Seemingly, it depends on the DC maturation state whether pharmacologically modulated DCs induce antigen specific long-term tolerance in allo-transplantation solid organ transplantation. Several authors reported a positive self-limiting feedback loop between tolerogenic DCs and allo-specific regulatory TCs. Thus, the DC-TC network appears as an exceptionally good target for pharmacological manipulations. Here we review how immunosuppressive agents interfere with DC maturation, migration and homeostasis. We are developing a rational to select different drugs for the generation of regulatory DCs, for allo-transplantation clinical settings.

Animals↗

PubMed2004

Measurement of the exclusive 3He(e,e'p) reaction below the quasielastic peak.

New, high-precision measurements of the 3He(e,e(')p) reaction using the A1 Collaboration spectrometers at the Mainz microtron MAMI are presented. These were performed in antiparallel kinematics at energy transfers below the quasielastic peak, and at a central momentum transfer of 685 MeV/c. Cross sections and distorted momentum distributions were extracted and compared to theoretical predictions and existing data. The longitudinal and transverse behavior of the cross section was also studied. Sizable differences in the cross-section behavior from theoretical predictions based on the plane wave impulse approximation were observed in both the two- and three-body breakup channels. Full Faddeev-type calculations account for some of the observed excess cross-section, but significant differences remain.

Journal Article↗

PubMed2004

Dendritic cell endothelium interaction in autoimmunity.

Monocyte derived dendritic cells play a central role in controlling immunity by activating naïve T lymphocytes. Monocytes can leave the blood stream by endothelial cell transmigration and differentiation into dendritic cells. A fundamental aspect of dendritic cell biology is their capacity to engulf tissue antigens and revers-migrate into lymph nodes. In lymph nodes dendritic cells can traffic to T-cell areas where they activate naïve T-cells. Throughout this review we are developing a model of in vivo activation of auto-reactive T-cells by activated dendritic cells.

Animals↗

PubMed2003

Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy.

Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the 'response to injury' paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importance.

Antibody Formation↗

PubMed2002

Measurement of the beam-helicity asymmetry in the p((-->)e,e'p)pi(0) reaction at the energy of the Delta(1232) resonance.

In a p((-->)e,e'p)pi(0) out-of-plane coincidence experiment at the three-spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has been precisely measured around the energy of the Delta(1232) resonance and Q(2) = 0.2(GeV/c)(2). The results are in disagreement with three up-to-date model calculations. This is interpreted as a lack of understanding of the nonresonant background, which in dynamical models is related to the pion cloud.

Journal Article↗

PubMed2001

Anti-CD20 antibody as consolidation therapy in a patient with primary plasma cell leukemia after high-dose therapy and autologous stem cell transplantation.

In multiple myeloma (MM), circulating malignant B cells are proposed as the proliferative compartment of the disease. In view of the close relationship between multiple myeloma and primary plasma cell leukemia (PCL), an anti-CD20 antibody treatment might also be considered as consolidation for patients with PCL. A 55-year-old patient diagnosed with PCL achieved complete remission after autologous transplantation. A total of four weekly courses of rituximab (375 mg/m(2)) were administered. Prior to antibody therapy, CD20+ cells comprised 22.6% of the mononuclear cells in peripheral blood (PB) assessed by flow cytometry and were enriched by magnetic activated cell sorting (MACS). In the enriched CD20+ fraction, 0.093% clonotypic cells were detected using a quantitative polymerase chain reaction (PCR) assay based on limiting dilutions. The proportion of clonotypic cells was 0.034% in PB and 0.032% in bone marrow (BM). Rituximab depleted CD20+ cells completely in PB and BM. Tumor load in PB and BM at day 40 and in PB at day 70 did not change in comparison to prior to therapy (0.037% in PB, 0.026% in BM). At day 90, the tumor load increased to 0.066% in PB. At day 120, the patient relapsed with 0.65% CD38++/CD138+/CD20- plasma cells and furthermore no CD20+ B cells in PB. The expansion of plasma cells was accompanied by an increase in the tumor load in both compartments (PB: 0.65%, BM: 1.8%). The accumulation of plasma cells during disease progression without the reappearance of CD20+ cells did not sustain the role of circulating clonotypic B cells as proliferative compartment in our patient. However, it cannot be excluded that rituximab was not able to eradicate malignant B cells, which subsequently contributed to relapse.

Antibodies, Monoclonal↗

PubMed2001

Neutral pion threshold production at Q(2) = 0.05 GeV(2)/c(2) and chiral perturbation theory.

New data are presented on the p(e,e'p)pi(0) reaction at threshold at a four-momentum transfer of Q(2) = 0.05 GeV(2)/c(2). The data were taken with the three-spectrometer setup of the A1 Collaboration at the Mainz Microtron MAMI. The complete center of mass solid angle was covered up to a center of mass energy of 4 MeV above threshold. Combined with measurements at three different values of the virtual photon polarization epsilon, the structure functions sigma(T), sigma(L), sigma(TT), and sigma(TL) are determined. The results are compared with calculations in heavy baryon chiral perturbation theory and with a phenomenological model. The measured cross section is significantly smaller than both predictions.

Journal Article↗

PubMed2001

Endothelin immunocytochemistry: indications of false-positive labeling patterns and non-detectable antigen concentrations.

Endothelin is an endothelium-derived peptide with potent vasoconstrictor and mitogenic properties. Since studies concerning the immunocytochemical localization of endothelin are often inconsistent we tried to clear up some of these discrepancies by comparing specificity and labeling patterns of different endothelin antibodies. Monoclonal and polyclonal endothelin antibodies ( n=7) were examined concerning their reactivity with endothelins and heart tissues by immunoblotting. Using immunofluorescence microscopy reactivities with human non-failing hearts, failing hearts, and cultured endothelial cells were examined. Specificity of labelings was assessed by absorption controls and functional controls using endothelial cells conditioned to produce different amounts of endothelin. As shown by immunoblotting five out of seven endothelin antibodies revealed both specific endothelin reactivity and negligible non-specific reactivities with heart proteins. Immunocytochemistry showed vascular reactivity of N-terminal endothelin antibodies to be associated with alpha-smooth muscle actin expression. One N-terminal antibody showed additional nuclear reactivity, and one C-terminal antibody vimentin-like labeling patterns. Although these reactivities were abolished in absorption controls these labelings had to be graded non-specific because functional specificity of endothelin antibodies could not be proven. The remaining antibodies revealed no endothelial reactivity even after tyramide signal amplification. Cellular endothelin concentrations ranged around 2,000-fold below the detection limit of immunocytochemical methods. Discrepancies in endothelin immunocytochemistry may originate from false-positive results and from expression levels of endothelin below the detection limit of immunocytochemical methods.

Antibodies, Monoclonal↗

PubMed2001

Expression of endomyocardial nitric oxide synthase and coronary endothelial function in human cardiac allografts.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts. METHODS AND RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.

Acetylcholine↗

PubMed2001

Measurement of the recoil polarization in the p(e-->, e'p-->)pi(0) reaction at the Delta(1232) resonance.

The recoil proton polarization has been measured in the p(e-->,e'p-->)pi(0) reaction in parallel kinematics around W = 1232 MeV, Q2 = 0.121 (GeV/c)2, and epsilon = 0.718 using the polarized cw electron beam of the Mainz Microtron. All three proton polarization components, Px/P(e) = (-11.4+/-1.3+/-1.4)%, P(y) = (-43.1+/-1.3+/-2.2)%, and P(z)/P(e) = (56.2+/-1.5+/-2.6)%, could be measured simultaneously. The Coulomb quadrupole to magnetic dipole ratio, CMR = (-6.4+/-0.7(stat)+/-0.8(syst))%, was determined from Px in the framework of the Mainz Unitary Isobar Model. The consistency among the reduced polarizations and the extraction of the ratio of longitudinal-to-transverse response is discussed.

Journal Article↗

PubMed2001

Continuous cardiac output measurements do not agree with conventional bolus thermodilution cardiac output determination.

PURPOSE: To evaluate the performance of two different continuous cardiac output monitoring systems based on the thermodilution principle in critically ill patients. METHODS: Nineteen cardiac surgical patients were randomly assigned to continuous cardiac output monitoring using one of the two systems under study (group I, IntelliCath(TM) catheter, n=9; group II, Opti-Q(TM) catheter, n=10). Each patient was studied over a period of three hours. Conventional bolus thermodilution cardiac output measurements were carried out every 15 min leading to 13 measurements in each patient. The continuous cardiac output values were compared with the bolus thermodilution measurements. Bias (mean difference between continuous and bolus thermodilution) and precision (SD of differences) were calculated as a measure of agreement between the respective continuous method and conventional bolus thermodilution. RESULTS: The range of measured cardiac outputs was 3.8-15.4 L*min(-1) (IntelliCath(TM)) and 3.5-8.3 L*min(-1) (OptiQ(TM)). Bias and precision was 0.06 +/- 0.76 L*min(-1) (IntelliCath(TM)) and -0.04 +/- 0.74 L*min(-1) (OptiQ(TM)), respectively. There was no difference in bias between the two systems (P=0.38). +/- 2 SD of the differences (i.e., 95% of the differences) did not fall within the predetermined limits of agreement of +/- 0.5 L*min(-1). CONCLUSIONS: There was no difference between the two systems regarding the agreement with conventional bolus thermodilution as the standard. A discrepancy between bolus and continuous thermodilution cardiac output measurement techniques above the clinically acceptable limits suggest that they are not interchangeable.

Adult↗

PubMed2001

Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation.

OBJECTIVES: This study was designed to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial function and cytokine activation in heart transplant recipients without angiographically detectable disease. BACKGROUND: Coronary endothelial dysfunction contributes to cardiac allograft vasculopathy. The vasoprotective effects of statins in heart transplant recipients may include restoration of endothelial function and suppression of allograft inflammatory activity. METHODS: Heart transplant recipients (one to three years after heart transplant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequately controlled with simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately treated with simvastatin; and group 3 (n = 40), patients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a prospective one-year follow-up study, changes in coronary endothelial function and cytokine levels were compared between 11 hypercholesterolemic patients treated with simvastatin and 9 controls. RESULTS: Epicardial and microvascular endothelial functions were better in groups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-alpha gradients were significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05; TNF-alpha: p < 0.01). Plaque areas were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients treated with simvastatin, coronary endothelial function and cardiac cytokine activity significantly improved during the one-year follow-up. CONCLUSIONS: Inhibition of allograft inflammatory activity and attenuation of the coronary endothelial dysfunction observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy.

Coronary Angiography↗

PubMed2001

Coronary flow reserve and nitric oxide synthases after cardiac transplantation in humans.

OBJECTIVE: Coronary endothelial dysfunction may precede morphological changes in both the epicardial conduit and microvascular resistance vessels in heart transplant recipients. Since the development of transplant atherosclerosis is the major limiting factor for long-term survival, the identification of early mediators of vasomotor dysfunction may be of therapeutic interest. We therefore investigated the potential relationship between the expression of nitric oxide synthases (NOS) and coronary endothelial function in human cardiac transplant recipients over time. METHODS: Forty-two human cardiac transplant recipients were studied at 1 and 12 months after heart transplantation (HTx). The microvascular coronary flow velocity reserve (CFVR) was tested for endothelium-dependent (acetylcholine) and -independent (adenosine) stimuli by intravascular Doppler flow-wire. Epicardial diameter changes were evaluated by quantitative coronary angiography. Endomyocardial inducible (iNOS) and endothelial constitutive nitric oxide synthase were determined by RT-PCR. Nitric oxide production (nitrite and nitrate (NOx)) and TNF-alpha were measured in plasma samples from the aorta and coronary sinus. RESULTS: CFVR was impaired in 26.1% (n=11) of patients at 1 month and in 31% (n=13) 12 months after HTx. iNOS-mRNA levels were significantly higher in patients with impaired endothelium-dependent CFVR. In addition, only in these patients were TNF-alpha levels higher and these correlated with plasma NOx levels at 1 and 12 months post-HTx (1 month: r=0.81, P=0.001; 12 months: r=0.62, P=0.04). CONCLUSIONS: Coronary microcirculatory dysfunction in response to acetylcholine is present in nearly 30% of patients during the first year following transplantation. These patients present with higher iNOS-mRNA expression and TNF-alpha plasma levels. Selective modulation of the TNF-alpha/iNOS-pathway may be of therapeutic value to improve coronary endothelial dysfunction in cardiac transplant recipients.

Adult↗

PubMed2001

Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis.

We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.

Animals↗

PubMed2000

Effects of Celsior and University of Wisconsin preservation solutions on hemodynamics and endothelial function after cardiac transplantation in humans: a single-center, prospective, randomized trial.

Optimal preservation of the myocardium remains a major concern in clinical and experimental heart transplantation. The present study compared the efficacy of University of Wisconsin (UW) and Celsior preservation solution with respect to myocardial performance, epicardial and microvascular endothelial vasomotor function and myocardial expression of endothelin and nitric oxide synthases in humans. Forty-one cardiac transplant recipients received either UW (n = 20) or Celsior (n = 21) preserved hearts. Catecholamine and vasodilator requirements were assessed within the first 5 postoperative days. Left ventricular performance and endothelial function was assessed 1 month after transplantation. Endothelin and nitric oxide synthase gene expression were detected in myocardial biopsy samples. Celsior preserved hearts required significantly more catecholamines and vasodilators within the first 5 postoperative days. Myocardial performance and endothelial function were comparable 1 month after transplantation. Total ischemic time correlated with impaired endothelial function in the Celsior but not in the UW group. Endothelin and inducible nitric oxide synthase gene expression were significantly higher in the Celsior group. The results of the study show that both solutions provide myocardial protection with regard to left ventricular performance and endothelial function 1 month after cardiac transplantation. The necessity for higher vasodilator and catecholamine therapy in Celsior preserved hearts suggests post-ischemic myocardial stunning within the first 5 postoperative days. The positive correlation between impaired endothelial function and total ischemic time in the Celsior group requires longitudinal investigation in particular with regard to the development of allograft vasculopathy.

Adenosine↗