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G Meinhardt

Publications and source records attributed to G Meinhardt.

At least 19 recordsLinked to original sources
PubMed2006

Transient left ventricular dysfunction with apical ballooning (tako-tsubo cardiomyopathy) in Germany.

AIMS: A peculiar type of an acute coronary syndrome is characterised by acute onset of chest pain, STsegment changes, elevated troponin I levels and a transient balloon-like apical left ventricular dysfunction, but without significant coronary artery disease. We sought to assess this syndrome in German patients. METHODS AND RESULTS: A total of 22 females and 1 male with acute transient left ventricular dysfunction were identified during an interval of 2 years and were investigated clinically and angiographically. All patients presented without obstructive coronary artery disease. In 16 patients (70%) ST-segment elevations were observed mimicking acute myocardial infarction, whereas the remaining patients (30%) revealed only negative T waves. Deep negative Twaves were characteristically seen during the course of recovery in all patients. Elevated troponin I levels>2.0 microg/l (upper level of normal) were measured in all patients (mean 18+/-26.5 microg/l, range from 2.2-135.7 microg/l). Creatine kinase rose up to a mean of 282+/-236 IU/l (upper level of normal 180 U/l). Emotional or physical stress situations associated with the onset of the symptoms were observed in 16 patients (70%). Other suspected trigger factors were gastrointestinal infection and in one case a surgical intervention. In four patients a trigger factor could not be identified. Left ventriculography showed an ejection fraction of 53+/-15%. After an interval of 7+/-2 days after the first angiogram, ejection fraction had increased from 48+/-11% to 64+/-11% in eight controlled patients by repeated ventriculography. Coronary spasm with a lumen reduction>75% could be provoked using acetylcholine in 10 of 17 tested patients (59%) with reproduction of the symptoms. Within 14 days the LV dysfunction returned to normal in all patients. The ECG abnormalities disappeared completely as early as 3 months (74%) and were not seen in any patient after 6 months. CONCLUSION: Tako-tsubo cardiomyopathy is not exclusively a Japanese or Northern American phenomenon. Despite increased patient reports the exact underlying cause and pathophysiology of this syndrome remain unclear. However, despite the initial dramatic presentation of this disease the prognosis is good.

Aged↗
PubMed2006

Vascular ectasia of the whole intestine as a cause of recurrent gastrointestinal bleeding after high-dose chemotherapy.

We present the first case in the literature of vascular ectasia of the whole intestine as a cause of recurrent and profuse gastrointestinal bleeding in a patient with relapsing Hodgkin's disease. The 17-year-old patient experienced early relapse of his Hodgkin's disease after first-line chemotherapy. Salvage chemotherapy was followed by high-dose chemotherapy and autologous stem cell transplantation. Complete remission was achieved after another relapse by means of a second transplant. The patient presented with profuse gastrointestinal bleeding 5 months later, however. Gastric antral vascular ectasia following hematopoietic stem cell transplantation was diagnosed by endoscopy, with histological confirmation. Similar lesions were found in the duodenum, the ileum, and throughout the entire colon. In conclusion, vascular ectasia of the whole intestine should be considered as cause of acute gastrointestinal bleeding after stem cell transplantation. Physicians should be aware of this complication because its onset is typically delayed. Importantly, this disease is not limited to patients who have undergone allogeneic transplantation, but can also occur after autologous transplantation.

Adolescent↗
PubMed2006

Cell-cell contact mediated signalling - no fear of contact.

Cancer research with sole focus on the cancer cell and possibly growth factors cannot faithfully reproduce the environmental interaction, such as adhesion of tumor cells to e.g. stromal cells, which may determine the response of these tumors to therapy. Methodologically cell adhesion studies are often difficult since complete but careful detachment is the prerequisite for most signal transduction assays. We describe for the first time an alternative method for the co-incubation of multiple myeloma cells on long term primary bone marrow stromal cultures using the bone marrow stromal cell line HS-5. The methods are precisely described, advantages and disadvantages are discussed, and troubleshooting advises are given.

Bone Marrow Cells↗
PubMed2005

[Enlarged lymph nodes--rapid diagnosis of infectious and neoplastic causes].

Although lymphadenopathy is usually an expression of a harmless, self-limiting immune reaction, it may nevertheless also signify the presence of a malignant tumor or relevant infectious disease--in particular when the swelling is sizeable, rapidly progressive, and associated symptoms are present. If, however, unfavorable criteria are definitely absent (Table 1), a wait-and-see policy with re-evaluation in three to four weeks may initially be adopted.

Adult↗
PubMed2005

Tissue-specific and ubiquitous basic helix-loop-helix transcription factors in human placental trophoblasts.

Tissue-specific class B basic helix-loop-helix (bHLH) transcription factors, dimerising with ubiquitously produced class A bHLH proteins, play a major role in murine trophoblast development. Here, we investigated expression patterns of class A and B bHLH factors in the human placenta and different trophoblast culture systems. Semi-quantitative RT-PCR and RNase protection assay revealed expression of the tissue-restricted factors Hash-2, I-mfa and Stra13 in placentae of early and late pregnancy, in purified villous trophoblasts as well as in invasive trophoblasts isolated from first trimester villous explant cultures. Accordingly, RNA in situ hybridisation localised Hash-2, I-mfa and Stra13 to the trophoblast epithelium, cell columns and extravillous trophoblasts invading maternal decidua. Villous stromal cells in situ and cultivated placental fibroblasts also produced I-mfa and Stra13 but failed to express Hash-2. The widely expressed class A proteins, E12/E47 were absent from all placental cell types while ITF-2 was restricted to placental stromal cells of early and late gestation. In contrast, HEB was identified in all trophoblast cell types using RT-PCR, Western blotting and immunohistochemistry. The negative HLH-regulators Id-1 and Id-2 lacking the DNA-binding domain, were detected in villous stromal cells and different cytotrophoblast subtypes but were absent from the syncytium. The data suggest that a complex interplay of activators (Hash-2, HEB) and repressors (Stra13, I-mfa) could be involved in extravillous trophoblast differentiation whereas downregulation of Id proteins could play a role in syncytialisation.

Adult↗
PubMed2004

Evaluation of aortic stenosis by cardiovascular magnetic resonance imaging: comparison with established routine clinical techniques.

OBJECTIVE: To evaluate whether direct planimetry of aortic valve area (AVA) by cardiac magnetic resonance (CMR) imaging is a reliable tool for determining the severity of aortic stenosis compared with transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE), and cardiac catheterisation. METHODS: 44 symptomatic patients with severe aortic stenosis were studied. By cardiac catheterisation AVA was calculated by the Gorlin equation. AVA was measured with CMR from steady state free precession (true fast imaging with steady state precession) by planimetry. AVA was also determined from TOE images by planimetry and from TTE images by the continuity equation. RESULTS: Bland-Altman analysis evaluating intraobserver and interobserver variability showed a very small bias for both (-0.016 and 0.019, respectively; n = 20). Bias and limits of agreement between CMR and TTE were 0.05 (-0.35, 0.44) cm2 (n = 37), between CMR and TOE 0.02 (-0.39, 0.42) cm2 (n = 32), and between CMR and cardiac catheterisation 0.09 (-0.30, 0.47) cm2 (n = 36). The sensitivity and specificity of CMR to detect AVA < or = 0.80 cm2 measured by cardiac catheterisation was 78% and 89%, of TOE 70% and 70%, and of TTE 74% and 67%, respectively. CONCLUSION: CMR planimetry is highly reliable and reproducible. Further, CMR planimetry had the best sensitivity and specificity of all non-invasive methods for detecting severe aortic stenosis in comparison with cardiac catheterisation. Therefore, CMR planimetry of AVA with steady state free precession is a new powerful diagnostic tool, particularly for patients with uncertain or discrepant findings by other modalities.

Aged↗
PubMed2002

Learning to discriminate simple sinusoidal gratings is task specific.

Learning transfer effects of a modified spatial frequency discrimination task with simple sinusoidal gratings on various untrained test tasks, testing performance in relative position, local width and global size discrimination, have been investigated. Six subjects were exposed to grating stimuli of varying spatial frequency and size but constant relative position while they had to respond only to spatial frequency. In the course of 7 consecutive days all subjects showed significant reduction of spatial frequency discrimination thresholds. Comparison of discrimination thresholds for the untrained test tasks, taken before and after the learning epoch, reveals complete learning transfer to spatial frequency discrimination with gratings of constant size and variable relative position, but complete lack of transfer when grating spatial frequency is shifted about one octave lower. Further, there is improvement of relative position discrimination and width discrimination of single luminance bars, which is not very specific for the learnt spatial frequency. Although size variation was part of the learning procedure, discrimination of global stimulus size did not improve. Generally, the observed scheme of learning transfer reveals that there is learning only for stimulus attributes that are behaviorally relevant in the learning task. The differential scheme of improvement and code usage in the test tasks strongly indicates involvement of higher stages capable of independent access to different coding domains, as well as attentionally guided attribute selection and suppression. Supported by other recent findings, it is suggested that discrimination learning can be understood as a higher level process of gradual refinement of code selection out of a rich code base provided by lower level stages.

Adult↗
PubMed2002

Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN.

Inhibition of bcl-2 expression by antisense oligodeoxynucleotides (ODN) might render bcl-2 overexpressing malignant B cells more susceptible to chemotherapy. ODN containing unmethylated CG dinucleotides (CpG) are known to activate B cells. We studied the effects of two bcl-2 antisense ODN, with (G3139) or without CG dinucleotides (NOV 2009) within the sequence, and the effects of a nonantisense, CpG-containing ODN (ODN 2006) on activation and apoptosis of malignant B cell lines and primary B-CLL cells. Without cationic lipids, no antisense-mediated inhibition of bcl-2 synthesis was achieved with G3139 and NOV 2009. Instead, G3139, but not NOV 2009, induced similar changes as ODN 2006 in proliferation, expression of costimulatory and antigen-presenting molecules, as well as in bcl-2 and bcl-xL levels of primary B-CLL cells. G3139 and ODN 2006 inhibited in vitro, spontaneous apoptosis in B-CLL cells of patients with high serum thymidine kinase activity (s-TK, marker for proliferative activity of malignant B cells), whereas in patients with low s-TK activity, apoptosis was induced. In conclusion, our results suggest that modulation of malignant B cell apoptosis by G3139 depends on its immunostimulatory properties rather than on antisense-mediated reduction of bcl-2 expression. Immunostimulatory CpG ODN may have a therapeutic potential in patients with B-CLL, especially those with low s-TK activity.

Adjuvants, Immunologic↗
PubMed2001

[Aortic stenosis with low transvalvular pressure gradients and impaired left ventricular function. Dobutamine stress echocardiography helps in therapy planning].

BACKGROUND: Aortic valve replacement is recommended in case of symptomatic severe aortic stenosis. This decision is difficult for patients with low-gradient aortic stenosis and severely impaired left ventricular function because of high perioperative mortality in this group. Although aortic valve replacement is usually justified if severe aortic stenosis is proved, patients with primary myocardial dysfunction and subsequent reduced aortic valve opening do not benefit from aortic valve replacement. Distinguishing these two groups of patients is necessary but not possible with echocardiography at rest. Positive inotropic stimulation with dobutamine stress echocardiography enables a more reliable graduation of aortic stenosis under these circumstances. CASE REPORT: We report on a symptomatic 58-year-old man with aortic stenosis and severely impaired left ventricular function. Using echocardiography at rest, there was a severely reduced aortic valve area of 0.6 cm2 and a mean pressure gradient of 24 mm Hg. Determined by cardiac catheterization, the peak-to-peak gradient was 20 mm Hg and the aortic valve area calculated by the Gorlin formula was 0.6 cm2. After positive inotropic stimulation using dobutamine stress echocardiography, the aortic valve area increased to 1.5 cm2 indicating an only moderate aortic stenosis. Thus aortic valve replacement was not performed and myocardial failure was medically treated. After 1.5 years of follow-up, the patient is in good condition and without complaints.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Learning a grating discrimination task broadens human spatial frequency tuning.

The effect of spatial frequency discrimination learning on spatial frequency detection tuning curves, obtained by a summation to threshold paradigm, has been investigated. Three human observers were exposed to a grating discrimination task for longer than two weeks, and their detection thresholds for compound Gabor gratings were measured before and after this time interval. Discrimination thresholds decreased continuously and substantially during the course of learning, while the spatial frequency detection tuning curves show significant broadening in the posttest. Calculating the discrimination resolution of an ensemble of sensory coding units shows that larger bandwidths lead to better spatial frequency discrimination performance if pattern discrimination rests on multidimensional comparison or one-dimensional scaling of the spatial frequency parameter. Further, it is shown that a multiple-mechanism nonlinear pooling model is capable of explaining the results if plasticity of coding unit bandwidth or adaptive weights of the coding unit responses at the stage of response integration is assumed. The alternative sources of plasticity and the consequences of the findings for psychophysical modeling are discussed.

Computer Simulation↗
PubMed2001

Detection of sinusoidal gratings by pattern-specific detectors: further evidence for the correlation principle in human vision.

The detection of compound sinusoidal gratings of various spatial frequency separations and four different grating sizes has been studied using the summation-to-threshold paradigm. Contrast interrelation functions have been measured and spatial frequency tuning estimates, based on the slope of the contrast interrelation function at two definite points, were derived using the "negative gradient technique" proposed by Logvinenko [Logvinenko (1995) Biol Cybern 73: 547-552]. It is shown that compound grating detection can be modelled by assuming pattern-specific sensory mechanisms for each of the spatial frequency components, which adapt to the periodicity and the size of the stimulus but not to its envelope function. Further, it is shown that relative sensitivity for a given spatial frequency separation can be predicted with good accuracy by the correlation of the grating components used for superposition. It is suggested that the most plausible implementation of the pattern correlation principle in human grating detection is the "grating cell" model.

Computer Simulation↗
PubMed2001

Detection of simple radially symmetric targets: further evidence for the matched filter processing scheme in human pattern detection.

The detection of small radially symmetric targets was studied using a subthreshold summation paradigm. Small disc and disc-like patterns with diameters up to 0.60 were used for superposition on Bessel functions of zero order, subthreshold contrast and various spatial frequencies. Contrast interrelation functions prove linear over the whole range of contrasts used for the Bessel functions while their slopes show systematic variation with spatial frequency. An extrapolation of sensitivity from the slopes reveals that sensitivity can be predicted by a simple model assuming detection to be mediated by a transfer function made up as a cascade of an even bandpass function and the disc pattern spectrum, as has been found previously using one dimensional luminance distributions. Problems concerning the formation of pattern-specific radial symmetric filters are discussed.

Contrast Sensitivity↗
PubMed2001

STAT3 is constitutively active in some patients with Polycythemia rubra vera.

OBJECTIVE: Polycythemia vera is a clonal stem cell disorder characterized by hyperproliferation of the erythroid, myeloid, and megakaryocytic lineages. While it has been shown that progenitor cells of P. vera patients are hypersensitive to several growth factors including erythropoietin, insulin-like growth factor-1, thrombopoietin, interleukin-3, and granulocyte/monocyte colony-stimulating factor, the molecular pathogenesis of this disease remains unknown. Growth factor hypersensitivity could be mediated by changes in signal transduction pathways. We therefore investigated a common downstream effector of cytokines, the signal transducers and activators of transcription (STATs). A constitutive activation of STAT factors could explain the increased proliferation of P. vera cells even in the absence of growth factor stimulation. METHODS: Peripheral granulocytes from patients with P. vera and from healthy volunteers were assayed for STAT1, 3, and 5 DNA binding by electrophoretic mobility shift assay. RESULTS: Four of 14 P. vera patients analyzed showed constitutive STAT3 DNA binding in unstimulated peripheral granulocytes, while none of the 17 healthy volunteers tested did. None of the subjects showed constitutive STAT1 or STAT5 activity. Western blotting demonstrated that, in the three patients, STAT3 is constitutively phosphorylated on Tyr 705, whereas it is unphosphorylated in the other patients and in controls. Interestingly, constitutive STAT3 activity did not correlate with the duration of disease or the treatment regimen. It was observed in a recently diagnosed patient and in two patients treated only with phlebotomy. CONCLUSION: Our data suggest that constitutive phosphorylation and activation of STAT3 is not a secondary event induced by mutagenizing agents or by prolonged hyperproliferation of hematopoietic cells, but rather represents a primary molecular aberration. Constitutively active STAT3 may contribute to the growth factor hypersensitivity of P. vera cells.

Adult↗
PubMed2001

Phosphodiesterase type 4 inhibitor suppresses expression of anti-apoptotic members of the Bcl-2 family in B-CLL cells and induces caspase-dependent apoptosis.

B cell chronic lymphocytic leukemia (B-CLL) is an incurable clonal disease which shows initial responsiveness to a number of chemotherapeutic drugs. However, in most patients the disease becomes resistant to treatment. Rolipram, a specific inhibitor of phosphodiesterase (PDE) type 4, the PDE predominantly expressed in B-CLL cells, has been shown to induce cAMP-dependent apoptosis in these cells. In the present study, we demonstrate that the extent of rolipram-induced apoptosis is similar to fludarabine-induced apoptosis in vitro. The combination of rolipram and fludarabine results in an enhancement in the number of apoptotic cells compared to apoptosis induced by either agent alone. Second, rolipram suppresses the expression of anti-apoptotic members of the Bcl-2 family and induces the pro-apoptotic protein Bax, thereby shifting the balance between pro- and anti-apoptotic members of the Bcl-2 family towards a pro-apoptotic direction. Finally rolipram-induced apoptosis is caspase-dependent. PDE 4 inhibitors are currently under investigation for chronic obstructive pulmonary disease and asthma in phase III clinical trials showing promising results with tolerable side-effects. In conclusion, by inducing apoptosis, by enhancing apoptosis induced by fludarabine, by suppressing Bcl-2, Bcl-X and by inducing Bax expression, PDE 4 inhibitors may add a new therapeutic option for patients with B-CLL.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens.

Multiple factors, including expression of costimulatory molecules, antigen-presenting molecules, and target antigens, likely impact the efficacy of antibody therapy and other approaches to the immunotherapy of B cell malignancy. Unmethylated CpG-dinucleotides in select base contexts ("CpG motifs") that resemble sequences found in bacterial DNA are potent immunostimulatory agents capable of inducing a complex immune response, including a strong B cell stimulus. We examined the effect of a potent human CpG oligonucleotide (CpG ODN 2006) on different types of primary human malignant B cells and reactive follicular hyperplasia. CpG oligodeoxynucleotide (CpG ODN), but not control (non-CpG ODN), increased the expression of costimulatory molecules (CD40, CD80, CD86, CD54) on malignant B cells without altering the phenotype of B cells obtained from reactive follicular hyperplasia. CpG ODN also enhanced expression of class I and class II MHC in most samples. CD20 expression was increased in response to CpG ODN, most notably in B-CLL and marginal zone lymphoma. An inverse correlation was found between baseline expression of CD20 and CD40 and their expression after exposure to CpG ODN, thus the most significant increase in expression of these molecules was found in those samples that had the lowest baseline levels. In conclusion, CpG ODN can lead to increasing expression of molecules involved in costimulation, antigen presentation, and as targets for antibody-based therapy and deserve further evaluation as potential immunotherapeutic agents for B cell malignancy.

Antigen Presentation↗
PubMed2000

Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by hyperproliferation of the erythroid, myeloid, and megakaryocytic lineages. Although it has been shown that progenitor cells of patients with PV are hypersensitive to several growth factors, the molecular pathogenesis of this disease remains unknown. To investigate the molecular defects underlying PV, we used subtractive hybridization to isolate complementary DNAs (cDNAs) differentially expressed in patients with PV versus normal controls. We isolated a novel gene, subsequently named PRV-1, which is highly expressed in granulocytes from patients with PV (n = 19), but not detectable in normal control granulocytes (n = 21). Moreover, PRV-1 is not expressed in mononuclear cells from patients with chronic myelogenous leukemia (n = 4) or acute myelogenous leukemia (n = 5) or in granulocytes from patients with essential thrombocythemia (n = 4) or secondary erythrocytosis (n = 4). Northern blot analysis showed that PRV-1 is highly expressed in normal human bone marrow and to a much lesser degree in fetal liver. It is not expressed in a variety of other tissues tested. Although PRV-1 is not expressed in resting granulocytes from normal controls, stimulation of these cells with granulocyte colony-stimulating factor induces PRV-1 expression. The PRV-1 cDNA encodes an open reading frame of 437 amino acids, which contains a signal peptide at the N-terminus and a hydrophobic segment at the C-terminus. In addition, PRV-1 contains 2 cysteine-rich domains homologous to those found in the uPAR/Ly6/CD59/snake toxin-receptor superfamily. We therefore propose that PRV-1 represents a novel hematopoietic receptor. (Blood. 2000;95:2569-2576)

Adult↗
PubMed2000

Detection of compound spatial patterns: further evidence for different channel interactions.

It is shown that contrast interrelation functions for small compound gratings and for small compound edge-type patterns have different shapes: the former are lozenges, the latter ellipses in the normalised contrast space. These findings can be described by a simple p-norm model, comprising one channel which is most sensitive to the first pattern, another channel which is most sensitive to the second pattern and a non-linear summation of the channel outputs. Since the value of the summation exponent p is constant within but varies between pattern classes, an interpretation of the model parameters is limited to pattern class. Channel models based on the p-norm are discussed, taking into account the interpretation of the first derivative of the contrast interrelation function and the summation exponent, p.

Computer Simulation↗