Redox stress is a hallmark of the rewired metabolic phenotype of cancer. The underlying dysregula... more Redox stress is a hallmark of the rewired metabolic phenotype of cancer. The underlying dysregulation of reactive oxygen species (ROS) is interconnected with abnormal mitochondrial biogenesis and function. In chronic lymphocytic leukemia (CLL), elevated ROS are implicated in clonal outgrowth and drug resistance. The pro-survival oncogene T-cell leukemia 1 (TCL1) is causally linked to the high threshold towards classical apoptosis in CLL. We investigated how aberrant redox characteristics and bioenergetics of CLL are impacted by TCL1 and if this is therapeutically exploitable. Bio-organometallic chemistry provided compounds containing a cytosine nucleobase, a metal core (ferrocene, ruthenocene, Fe(CO)3), and a 5'-CH2O-TDS substituent. Four of these metal-containing nucleoside analogues (MCNA) were tested for their efficacy and mode of action in CLL patient samples, gene-targeted cell lines, and murine TCL1-transgenic splenocytes. The MCNA showed a marked and selective cytotoxicit...
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 24, 2016
The aims of this study were to assess the influence of left bundle branch block (LBBB)-like condu... more The aims of this study were to assess the influence of left bundle branch block (LBBB)-like conduction abnormalities on left ventricular (LV) blood flow patterns and to characterize their potential impact on LV efficiency by measuring the changes in vortex formation and energy dissipation in the left ventricle using echocardiographic particle image velocimetry. Thirty-six subjects were prospectively studied, including 20 patients with pacemakers, six patients with LBBB, and 10 healthy control subjects, all of whom had normal ejection fractions (>50%). In patients with pacemakers, data were acquired in both DDD and AAI modes. Standard grayscale, tissue Doppler myocardial imaging, and contrast-enhanced echocardiographic particle image velocimetric data were acquired, and LV flow patterns were analyzed using dedicated software. Dyssynchrony was quantified by measuring apical transverse motion. Apical transverse motion was significantly higher in patients with LBBB compared with norm...
� Abstract Enterochromaffin-like (ECL) cells are neuroendocrine,cells in the gas- tric mucosa,tha... more � Abstract Enterochromaffin-like (ECL) cells are neuroendocrine,cells in the gas- tric mucosa,that control acid secretion by releasing histamine as a paracrine stimulant. The antral hormone,gastrin and,the neural messenger,pituitary adenylyl,cyclase‐ activating peptide (PACAP) potently stimulate histamine synthesis, storage, and secretion by ECL cells. Histamine is stored in secretory vesicles via V-type ATPases and vesicular monoamine,transporters of the subtype 2 (VMAT-2). Plasmalemmal,cal-
Infection with H pylori leads to a persistent chronic infl ammation of the gastric mucosa, thereb... more Infection with H pylori leads to a persistent chronic infl ammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of
Journal of the American Society of Echocardiography, 2011
The aim of this study was to investigate the imaging capabilities of recent hand-held ultrasound ... more The aim of this study was to investigate the imaging capabilities of recent hand-held ultrasound scanners. Three hundred forty-nine patients were scanned with hand-held ultrasound (HAND) and high-end echocardiography (HIGH). Segmental endocardial border delineation was scored (2 = good, 1 = poor, 0 = invisible) to describe image quality. Assessments of left ventricular (LV) dimensions, regional and global LV function, and grades of valve disease were compared. The mean endocardial visibility grades were 1.6 ± 0.5 with HAND and 1.7 ± 0.4 with HIGH (P < .01). Regional wall motion was scored very similarly (κ = 0.73, P < .01). Ejection fraction assessment (bias = 1.8%, 1.96 × SD = 8.3%) and LV measurements (r = 0.99, P < .01; interventricular septum: bias = 0.91 mm, 1.96 × SD = 2.1 mm; LV end-diastolic diameter: bias = 0.5 mm, 1.96 × SD = 4.1 mm; LV posterior wall: bias = 0.61 mm, 1.96 × SD = 2.4 mm) showed negligible deviations. No pericardial effusion or valve stenosis was missed. Regurgitations missed by HAND were all graded "minimal" on HIGH. Regurgitations were mildly overestimated by HAND. Overall concordance for detection of regurgitations was very good (κ = 0.9, P < .01). Handheld echocardiography was feasible and missed no relevant findings. Given the future implementation of spectral Doppler capabilities, this handheld scanner can safely be used in clinical routine.
Enterochromaffin (EC) cells are distributed throughout the diges-tive epithelium. This cell type ... more Enterochromaffin (EC) cells are distributed throughout the diges-tive epithelium. This cell type releases serotonin besides a variety of peptides and hormones, thereby being a key messenger for intestinal motility as well as secretion. Studies using highly enriched, isolated EC cells from rat ileum now reveal a large spectrum of receptors spe-cifically expressed on this cell type, for example b-adrenergic, mus-carinic as well as GABA-ergic receptors. Interestingly, also EC cells seem to express several bitter taste and olfactory receptors, which might shed a light on a physiological function as a 'sentinel cell' in the gut. Current studies determine the response of these enriched cells towards receptor antagonists as well as antagonists, offering a large perspective to treat patients with motility disorders, diarrhoea or cons-tipation. Gastric EC-like cells, in contrast, have been characterised since already ten years. This cell type releases histamine as a paracrine stimula...
Left ventricular rotation is physiologically affected by acute changes in preload. We investigate... more Left ventricular rotation is physiologically affected by acute changes in preload. We investigated the acute effect of preload changes in chronically underloaded and overloaded left ventricles in children with shunt lesions. A total of 15 patients with atrial septal defects (Group A: 7.4 ± 4.7 years, 11 females) and 14 patients with patent arterial ducts (Group B: 2.7 ± 3.1 years, 10 females) were investigated using 2D speckle-tracking echocardiography before and after interventional catheterisation. The rotational parameters of the patient group were compared with those of 29 matched healthy children (Group C). Maximal torsion (A: 2.45 ± 0.9°/cm versus C: 1.8 ± 0.8°/cm, p < 0.05), apical peak systolic rotation (A: 12.6 ± 5.7° versus C: 8.7 ± 3.5°, p < 0.05), and the peak diastolic torsion rate (A: -147 ± 48°/second versus C: -110 ± 31°/second, p < 0.05) were elevated in Group A and dropped immediately to normal values after intervention (maximal torsion 1.5 ± 1.1°/cm, p < 0.05, apical peak systolic rotation 7.2 ± 4.1°, p < 0.05, and peak diastolic torsion rate -106 ± 35°/second, p < 0.05). Patients in Group B had decreased maximal torsion (B: 1.8 ± 1.1°/cm versus C: 3.8 ± 1.4°/cm, p < 0.05) and apical peak systolic rotation (B: 8.3 ± 6.1° versus C: 13.9 ± 4.3°, p < 0.05). Defect closure was followed by an increase in maximal torsion (B: 2.7 ± 1.4°/cm, p < 0.05) and the peak diastolic torsion rate (B: -133 ± 66°/second versus -176 ± 84°/second, p < 0.05). Patients with chronically underloaded left ventricles compensate with an enhanced apical peak systolic rotation, maximal torsion, and quicker diastolic untwisting to facilitate diastolic filling. In patients with left ventricular dilatation by volume overload, the peak systolic apical rotation and the maximal torsion are decreased. After normalisation of the preload, they immediately return to normal and diastolic untwisting rebounds. These mechanisms are important for understanding the remodelling processes.
Meimarakis and colleagues 1 reported that infection with Helicobacter pylori is a beneficial prog... more Meimarakis and colleagues 1 reported that infection with Helicobacter pylori is a beneficial prognostic factor in patients with early-stage gastric cancer. The researchers analysed prospectively 166 patients who received curative resection for gastric cancer, and showed ...
Bile duct lesions, including leaks and strictures, are immanent complications of open or laparosc... more Bile duct lesions, including leaks and strictures, are immanent complications of open or laparoscopic cholecystectomy. Endoscopic procedures have gained increasing potential as the treatment of choice in the management of postoperative bile duct injuries. Between January 1996 and December 2006, 44 patients with biliary leakages and 12 patients with biliary strictures after cholecystectomy were identified by analyzing the endoscopic retrograde cholangiopancreatography database, clinical records, and cholangiograms. The long-term follow up of endoscopic treatment in biliary lesions after cholecystectomy was evaluated by this retrospective study. In 34 of 35 patients (97%) with peripheral bile duct leakages, endoscopic therapy was successful. Transpapillary endoprothesis and/or nasobiliary drainage were removed after 31 (5-399) days. After stent removal, the median follow-up period was 81 (11-137) months. In patients with central bile duct leakages, the success rate after median 90 (4-145) days of endoscopic therapy was 66.7% (6/9 patients). The median follow up after stent removal in six successfully treated patients was 70 (48-92) months. Eleven of 12 patients (91.6%) with bile duct strictures had successfully completed stent therapy. The follow-up period of this patient group was 99 (53-140) months. Endoscopic treatment of bile duct lesions after cholecystectomy is effective, particularly in patients with peripheral bile duct leakages and bile duct strictures. Therefore, it should be the first-line therapy used in these patients. Although endoscopic management is less successful in patients with central bile duct leakages, an attempt is warranted.
Redox stress is a hallmark of the rewired metabolic phenotype of cancer. The underlying dysregula... more Redox stress is a hallmark of the rewired metabolic phenotype of cancer. The underlying dysregulation of reactive oxygen species (ROS) is interconnected with abnormal mitochondrial biogenesis and function. In chronic lymphocytic leukemia (CLL), elevated ROS are implicated in clonal outgrowth and drug resistance. The pro-survival oncogene T-cell leukemia 1 (TCL1) is causally linked to the high threshold towards classical apoptosis in CLL. We investigated how aberrant redox characteristics and bioenergetics of CLL are impacted by TCL1 and if this is therapeutically exploitable. Bio-organometallic chemistry provided compounds containing a cytosine nucleobase, a metal core (ferrocene, ruthenocene, Fe(CO)3), and a 5'-CH2O-TDS substituent. Four of these metal-containing nucleoside analogues (MCNA) were tested for their efficacy and mode of action in CLL patient samples, gene-targeted cell lines, and murine TCL1-transgenic splenocytes. The MCNA showed a marked and selective cytotoxicit...
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 24, 2016
The aims of this study were to assess the influence of left bundle branch block (LBBB)-like condu... more The aims of this study were to assess the influence of left bundle branch block (LBBB)-like conduction abnormalities on left ventricular (LV) blood flow patterns and to characterize their potential impact on LV efficiency by measuring the changes in vortex formation and energy dissipation in the left ventricle using echocardiographic particle image velocimetry. Thirty-six subjects were prospectively studied, including 20 patients with pacemakers, six patients with LBBB, and 10 healthy control subjects, all of whom had normal ejection fractions (>50%). In patients with pacemakers, data were acquired in both DDD and AAI modes. Standard grayscale, tissue Doppler myocardial imaging, and contrast-enhanced echocardiographic particle image velocimetric data were acquired, and LV flow patterns were analyzed using dedicated software. Dyssynchrony was quantified by measuring apical transverse motion. Apical transverse motion was significantly higher in patients with LBBB compared with norm...
� Abstract Enterochromaffin-like (ECL) cells are neuroendocrine,cells in the gas- tric mucosa,tha... more � Abstract Enterochromaffin-like (ECL) cells are neuroendocrine,cells in the gas- tric mucosa,that control acid secretion by releasing histamine as a paracrine stimulant. The antral hormone,gastrin and,the neural messenger,pituitary adenylyl,cyclase‐ activating peptide (PACAP) potently stimulate histamine synthesis, storage, and secretion by ECL cells. Histamine is stored in secretory vesicles via V-type ATPases and vesicular monoamine,transporters of the subtype 2 (VMAT-2). Plasmalemmal,cal-
Infection with H pylori leads to a persistent chronic infl ammation of the gastric mucosa, thereb... more Infection with H pylori leads to a persistent chronic infl ammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of
Journal of the American Society of Echocardiography, 2011
The aim of this study was to investigate the imaging capabilities of recent hand-held ultrasound ... more The aim of this study was to investigate the imaging capabilities of recent hand-held ultrasound scanners. Three hundred forty-nine patients were scanned with hand-held ultrasound (HAND) and high-end echocardiography (HIGH). Segmental endocardial border delineation was scored (2 = good, 1 = poor, 0 = invisible) to describe image quality. Assessments of left ventricular (LV) dimensions, regional and global LV function, and grades of valve disease were compared. The mean endocardial visibility grades were 1.6 ± 0.5 with HAND and 1.7 ± 0.4 with HIGH (P < .01). Regional wall motion was scored very similarly (κ = 0.73, P < .01). Ejection fraction assessment (bias = 1.8%, 1.96 × SD = 8.3%) and LV measurements (r = 0.99, P < .01; interventricular septum: bias = 0.91 mm, 1.96 × SD = 2.1 mm; LV end-diastolic diameter: bias = 0.5 mm, 1.96 × SD = 4.1 mm; LV posterior wall: bias = 0.61 mm, 1.96 × SD = 2.4 mm) showed negligible deviations. No pericardial effusion or valve stenosis was missed. Regurgitations missed by HAND were all graded "minimal" on HIGH. Regurgitations were mildly overestimated by HAND. Overall concordance for detection of regurgitations was very good (κ = 0.9, P < .01). Handheld echocardiography was feasible and missed no relevant findings. Given the future implementation of spectral Doppler capabilities, this handheld scanner can safely be used in clinical routine.
Enterochromaffin (EC) cells are distributed throughout the diges-tive epithelium. This cell type ... more Enterochromaffin (EC) cells are distributed throughout the diges-tive epithelium. This cell type releases serotonin besides a variety of peptides and hormones, thereby being a key messenger for intestinal motility as well as secretion. Studies using highly enriched, isolated EC cells from rat ileum now reveal a large spectrum of receptors spe-cifically expressed on this cell type, for example b-adrenergic, mus-carinic as well as GABA-ergic receptors. Interestingly, also EC cells seem to express several bitter taste and olfactory receptors, which might shed a light on a physiological function as a 'sentinel cell' in the gut. Current studies determine the response of these enriched cells towards receptor antagonists as well as antagonists, offering a large perspective to treat patients with motility disorders, diarrhoea or cons-tipation. Gastric EC-like cells, in contrast, have been characterised since already ten years. This cell type releases histamine as a paracrine stimula...
Left ventricular rotation is physiologically affected by acute changes in preload. We investigate... more Left ventricular rotation is physiologically affected by acute changes in preload. We investigated the acute effect of preload changes in chronically underloaded and overloaded left ventricles in children with shunt lesions. A total of 15 patients with atrial septal defects (Group A: 7.4 ± 4.7 years, 11 females) and 14 patients with patent arterial ducts (Group B: 2.7 ± 3.1 years, 10 females) were investigated using 2D speckle-tracking echocardiography before and after interventional catheterisation. The rotational parameters of the patient group were compared with those of 29 matched healthy children (Group C). Maximal torsion (A: 2.45 ± 0.9°/cm versus C: 1.8 ± 0.8°/cm, p < 0.05), apical peak systolic rotation (A: 12.6 ± 5.7° versus C: 8.7 ± 3.5°, p < 0.05), and the peak diastolic torsion rate (A: -147 ± 48°/second versus C: -110 ± 31°/second, p < 0.05) were elevated in Group A and dropped immediately to normal values after intervention (maximal torsion 1.5 ± 1.1°/cm, p < 0.05, apical peak systolic rotation 7.2 ± 4.1°, p < 0.05, and peak diastolic torsion rate -106 ± 35°/second, p < 0.05). Patients in Group B had decreased maximal torsion (B: 1.8 ± 1.1°/cm versus C: 3.8 ± 1.4°/cm, p < 0.05) and apical peak systolic rotation (B: 8.3 ± 6.1° versus C: 13.9 ± 4.3°, p < 0.05). Defect closure was followed by an increase in maximal torsion (B: 2.7 ± 1.4°/cm, p < 0.05) and the peak diastolic torsion rate (B: -133 ± 66°/second versus -176 ± 84°/second, p < 0.05). Patients with chronically underloaded left ventricles compensate with an enhanced apical peak systolic rotation, maximal torsion, and quicker diastolic untwisting to facilitate diastolic filling. In patients with left ventricular dilatation by volume overload, the peak systolic apical rotation and the maximal torsion are decreased. After normalisation of the preload, they immediately return to normal and diastolic untwisting rebounds. These mechanisms are important for understanding the remodelling processes.
Meimarakis and colleagues 1 reported that infection with Helicobacter pylori is a beneficial prog... more Meimarakis and colleagues 1 reported that infection with Helicobacter pylori is a beneficial prognostic factor in patients with early-stage gastric cancer. The researchers analysed prospectively 166 patients who received curative resection for gastric cancer, and showed ...
Bile duct lesions, including leaks and strictures, are immanent complications of open or laparosc... more Bile duct lesions, including leaks and strictures, are immanent complications of open or laparoscopic cholecystectomy. Endoscopic procedures have gained increasing potential as the treatment of choice in the management of postoperative bile duct injuries. Between January 1996 and December 2006, 44 patients with biliary leakages and 12 patients with biliary strictures after cholecystectomy were identified by analyzing the endoscopic retrograde cholangiopancreatography database, clinical records, and cholangiograms. The long-term follow up of endoscopic treatment in biliary lesions after cholecystectomy was evaluated by this retrospective study. In 34 of 35 patients (97%) with peripheral bile duct leakages, endoscopic therapy was successful. Transpapillary endoprothesis and/or nasobiliary drainage were removed after 31 (5-399) days. After stent removal, the median follow-up period was 81 (11-137) months. In patients with central bile duct leakages, the success rate after median 90 (4-145) days of endoscopic therapy was 66.7% (6/9 patients). The median follow up after stent removal in six successfully treated patients was 70 (48-92) months. Eleven of 12 patients (91.6%) with bile duct strictures had successfully completed stent therapy. The follow-up period of this patient group was 99 (53-140) months. Endoscopic treatment of bile duct lesions after cholecystectomy is effective, particularly in patients with peripheral bile duct leakages and bile duct strictures. Therefore, it should be the first-line therapy used in these patients. Although endoscopic management is less successful in patients with central bile duct leakages, an attempt is warranted.
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Papers by Christian Prinz