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91.
92.
Value of comparative genomic hybridization and fluorescence in situ hybridization for molecular diagnostics in multiple myeloma 总被引:4,自引:0,他引:4
Liebisch P Viardot A Bassermann N Wendl C Roth K Goldschmidt H Einsele H Straka C Stilgenbauer S Döhner H Bentz M 《British journal of haematology》2003,122(2):193-201
Chromosomal abnormalities, such as 13q deletions, are emerging as important prognostic factors in multiple myeloma. Fluorescence in situ hybridization (FISH) using specific DNA probes is the technique most widely used for the determination of genomic aberrations in this disease. The utility of comparative genomic hybridization (CGH) for molecular diagnostics in plasma cell malignancies has not been systematically analysed. We investigated tumour samples of patients with multiple myeloma (n = 43) or plasma cell leukaemia (n = 3) using CGH and FISH with five DNA probes localized to chromosome bands 1p22, 6q21, 11q22-q23, 13q14 and 17p13. By CGH, the most frequent genomic changes were gains on chromosomes 1q, 9q and 11q, as well as losses on chromosomes 13q, 6q, Xp and Xq. By FISH, trisomy 11q was identified at a similar frequency to the 13q deletion (42%). Compared with FISH data, the sensitivity of CGH was 80.7% and the specificity was 97.5%. Thirty-two aberrations found by FISH were not identified by CGH, mostly as a result of the proportion of cells carrying the respective aberrations, or because of the limited spatial resolution of CGH. Our data indicate that, for clinical molecular diagnostics in multiple myeloma, FISH with a disease-specific DNA probe set is superior to CGH analysis. 相似文献
93.
Susanne Brakemeier Ines Eichler Hartmut Hopp Ralf K?hler Joachim Hoyer 《Cardiovascular research》2002,53(1):209-218
OBJECTIVE: Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca(2+) influx through SAC could induce an intracellular Ca(2+) signal stimulating Ca(2+)-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested whether laminar shear stress (LSS) regulates SAC function. METHODS: Electrophysiological properties of SAC were investigated in human umbilical vein endothelial cells (HUVEC) subjected to defined levels of LSS in a flow-cone apparatus. RESULTS: In HUVEC, we identified a Ca(2+) permeable SAC that was activated by membrane stretch. Single-channel current densities of SAC in cell-attached patches were significantly increased in HUVEC exposed to an LSS of 5 dyn/cm(2) for 4 h (1.15+/-0.17 SAC/patch) compared to HUVEC kept in stationary culture (0.46+/-0.07 SAC/patch). Exposure of HUVEC to a higher LSS of 15 dyn/cm(2) for 4 h induced similar up-regulation of SAC (1.27+/-0.21 SAC/patch). After 24 h exposure to LSS of 15 dyn/cm(2), single-channel current densities of SAC remained up-regulated (1.07+/-0.18 SAC/patch) compared to controls. In addition, stretch-sensitivity of SAC (channel activity NP(o) at -30 mmHg) significantly increased after 2 h of exposure to LSS of 5 and 15 dyn/cm(2) and remained up-regulated after 24 h. Inhibition of protein kinases and tyrosine kinases by H7 and genistein, respectively, prevented LSS-induced alteration of SAC function. CONCLUSION: Single-channel current density and mechanosensitivity of SAC in HUVEC is up-regulated by LSS. Up-regulation of SAC function leads to enhanced mechanosensitive Ca(2+) influx, and represents a novel adaptive mechanism of the endothelium in the presence of altered hemodynamic forces. 相似文献
94.
Schulteis RD Chu H Dai X Chen Y Edwards B Haribhai D Williams CB Malarkannan S Hessner MJ Glisic-Milosavljevic S Jana S Kerschen EJ Ghosh S Wang D Kwitek AE Lernmark A Gorski J Weiler H 《Blood》2008,112(13):4905-4914
The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5(-/-) bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5(-/-) bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms. 相似文献
95.
Percutaneous transluminal laser angioplasty was carried out for the dilatation of 30 completely occluded peripheral arterial segments and three subtotal stenoses. A neodymium-YAG laser and an optical fibre delivery system with a sapphire tip were used. All three arterial stenoses and 26 of the 30 occluded arterial segments were successfully dilated. In 20 patients additional dilatation was carried out with a balloon catheter. Laser angioplasty failed to recanalise four occlusions, and vessel leakage without clinical consequences occurred in one patient. Reocclusion occurred within 48 h in two patients and after five months in one patient during a follow up period of at least six months. It is concluded that percutaneous transluminal laser angioplasty using direct contact with a sapphire tip is highly effective (89% success rate) in reopening peripheral vascular occlusions. The procedure is safe, and reocclusion of vessels is rare during the six month follow up period. 相似文献
96.
Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial
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Burkhard Möller Judith Everts‐Graber Stefan Florentinus Yihan Li Hartmut Kupper Axel Finckh 《Arthritis care & research》2018,70(6):861-868
Objective
To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA).Methods
Post hoc analyses were performed in patients from the PREMIER trial with early RA undergoing 2 years of adalimumab (ADA), methotrexate (MTX), or ADA + MTX combination therapy. Low disease activity was defined as a score <3.2 on the 28‐joint Disease Activity Score using the C‐reactive protein level (DAS28‐CRP), and clinical response by the American College of Rheumatology criteria for 20% improvement at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex‐specific World Health Organization criteria, were analyzed in mixed‐effects models for longitudinal data in men and women as predictors of progressive joint damage, as measured by the modified total Sharp/van der Heijde score (ΔSHS). Data were adjusted for treatment and other patient characteristics, including the DAS28‐CRP.Results
Baseline hemoglobin was inversely associated with ΔSHS in adjusted analyses (P < 0.05 for both sexes). Baseline anemia predicted greater ΔSHS in MTX‐treated patients over 104 weeks, and in ADA‐ and combination‐treated patients over 26 weeks. Lower hemoglobin concentrations over time, as well as time with anemia, were associated with greater damage progression (P < 0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity.Conclusion
Low hemoglobin is a DAS28‐CRP‐independent predictor of radiographic joint damage progression in MTX‐treated patients with early RA. This effect decreases over time in ADA‐ and combination‐treated patients, and in clinical responders irrespective of treatment modality.97.
Kucinskas L Jeroch J Vitkauskiene A Sakalauskas R Petrenkiene V Kucinskas V Naginiene R Schmidt H Kupcinskas L 《World journal of gastroenterology : WJG》2008,14(38):5876-5879
AIM: To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson's disease (WD) in Lithuania. METHODS: Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction (PCR) technique was used to detect the c.3207C〉A (p.H1069Q) mutation. Patients not homozygous for the c.3207C〉A (p.H1069Q) mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler (Biometra T3 Thermocycler, G0ttingen, Germany). Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer (Applied Biosystems, Darmstadt, Germany). RESULTS: Total of 13 WD patients (mean age 26.4 years; range 17-40; male/female 3/10) presented with hepatic disorders and 16 their first degree relatives (including 12 siblings) were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders (hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2). Liver biopsy specimens were available in all of 13 WD patients (8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis). Twelve of 13 (92.3%) WD patients had the c.3207C〉A (p.HI069Q) mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T (p.RI041W) or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder (Leipzig score 6), no mutations were found. Out of 16 first degree WD relatives, 11 (68.7%) were heterozygous for the c.3207C〉A (p.H1069Q) mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilam 相似文献
98.
Frank Tacke Kai Fiedler Mario von Depka Tom Luedde Hartmut Hecker Michael P Manns Arnold Ganser Christian Trautwein 《Liver international》2006,26(2):173-181
BACKGROUND/AIMS: Alterations of plasma coagulation factor XIII may contribute to bleeding disorders in patients with liver cirrhosis. As standard clotting tests such as prothrombin time or activated thromboplastin time (aPTT) cannot detect factor XIII deficiency, this may often be overlooked in clinical practice. We aimed to define factor XIII's clinical and prognostic role in chronic liver disease. PATIENTS AND METHODS: Factor XIII activities were assessed among various other parameters in 111 patients with chronic liver diseases during evaluation for liver transplantation in a prospective study. RESULTS: Unlike coagulation factors II, V or VII, factor XIII activity was maintained in the majority of patients with liver cirrhosis. However, although rarely, factor XIII deficiencies (<50%) occurred, especially in Child C cirrhosis. Factor XIII levels correlated with liver's biosynthetic capacity (cholinesterase activity, albumin, total protein) as well as with platelet count, global coagulation tests and other single coagulation factors. Patients reporting a current systemic bleeding tendency at study entry had significantly reduced factor XIII. In a 6-year follow-up, patients with factor XIII<50% had a significantly increased risk of severe upper gastrointestinal bleed, and reduced factor XIII (<50%, 50-75% vs. normal) was associated with increased mortality. CONCLUSIONS: Factor XIII deficiency is rare in patients with liver cirrhosis, but is associated with a clinical bleeding tendency and an unfavorable prognosis for future hemorrhages and survival. 相似文献
99.
Elizabeth A. Gilpin James A. Koziol Erling B. Madsen Hartmut Henning John Ross 《The American journal of cardiology》1983,52(3):240-244
The mortality rate after acute myocardial infarction (AMI) has generally been modeled by a single exponential function. The present study was undertaken to determine, in 3 different populations, whether or not periods exist during the first year after AMI which have mortality distributions that differ from this pattern. The 3 patient populations included San Diego (346 patients, 71 deaths), Vancouver (704 patients, 146 deaths), and Copenhagen (1,140 patients, 262 deaths). Hospital admission was within 24 hours of the onset of symptoms, and patients dying within the first 24 hours after hospital admission or of noncardiac or unknown causes were not analyzed. The mortality between 2 and 21 days in the combined data base was 11.4% (range 10.9 to 11.7) and from 3 weeks to 1 year 10.5% (range 9.0 to 11.3). A high degree of similarity was noted among the shapes of the 3 survival curves. The hypothesis of an exponential mortality rate during the entire first year was rejected. Using a special statistic, changepoints at days 17,23, and 24 in the 3 populations (21 days for the combined data base) were identified and used thereafter to divide the year into 2 separate periods of mortality within which exponentiality for the mortality rate was not rejected. The point by which exactly 50% of deaths had occurred was day 19, with 75% of deaths occurring by day 100. These data further define the natural history after AMI and indicate optimal follow-up periods for short- and longer-term management strategies based on risk assessment or trials of risk reduction after AMI. 相似文献
100.
INTRODUCTION: Vascular injury and accumulation of red blood cells in the space of Disse (hemorrhage) is a characteristic feature of acetaminophen hepatotoxicity. However, the mechanism of nonparenchymal cell injury is unclear. Therefore, the objective was to investigate if either Kupffer cells or intracellular events in endothelial cells are responsible for the cell damage. RESULTS: Acetaminophen treatment (300 mg/kg) caused vascular nitrotyrosine staining within 1 h. Vascular injury (hemorrhage) occurred between 2 and 4 h. This paralleled the time course of parenchymal cell injury as shown by the increase in plasma alanine aminotransferase activities. Inactivation of Kupffer cells by gadolinium chloride (10 mg/kg) had no significant effect on vascular nitrotyrosine staining, hemorrhage or parenchymal cell injury. In contrast, treatment with allopurinol (100 mg/kg), which prevented mitochondrial injury in hepatocytes, strongly attenuated vascular nitrotyrosine staining and injury. CONCLUSIONS: Our data do not support the hypothesis that acetaminophen-induced superoxide release leading to vascular peroxynitrite formation and endothelial cell injury is caused by activated Kupffer cells. In contrast, the protective effect of allopurinol treatment suggests that, similar to the mechanism in parenchymal cells, mitochondrial oxidant stress and peroxynitrite formation in sinusoidal endothelial cells may be critical for vascular injury after acetaminophen overdose. 相似文献