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991.
Wolfgang Stremmel Thomas Longerich Ren Liere Vladimir Vacata Josef van Helden Ralf Weiskirchen 《World Journal of Clinical Cases》2021,9(6):1386-1393
BACKGROUNDIn Wilson disease lack of biliary copper excretion causes hepatocellular injury by accumulation of free toxic copper. Its overspill to serum accounts for neuronal damage as second common manifestation. Therapy with copper chelators or zinc targets the removal of this free copper. However, in some patients liver disease persists for unknown reason despite normalized free copper. The discovery of a hyperimmunity as a contributing pathogenetic factor was discovered in this case report with implication also for other liver diseases.CASE SUMMARYA 9-year-old girl was diagnosed in August 2009 by family screening of having asymptomatic Wilson disease with elevated transaminases. Already at time of diagnosis antinuclear antibodies (ANA) were elevated without hyperimmunoglobulinemia (immunoglobulin G, IgG). After one year of therapy with D-penicillamine transaminases normalized together with free serum copper. Under continuous therapy with copper chelators free copper remained normal until today, whereas transaminases raised to alanine aminotransferase values of 571 U/L in December 2019. For hyperimmunity a tentative steroid course on top of D-penicillamine improved transaminases. Thus, hyperimmunity may have impact on liver inflammation after control of the metabolic disturbance. A retrospective cohort study confirmed the common association of elevated transaminases with ANA, but no IgG elevation.CONCLUSIONThis hyperimmune-triggered condition may represent a new entity which per se or on top of other liver diseases induces liver inflammation responsive to steroids. 相似文献
992.
Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2 总被引:18,自引:0,他引:18
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Vajkoczy P Farhadi M Gaumann A Heidenreich R Erber R Wunder A Tonn JC Menger MD Breier G 《The Journal of clinical investigation》2002,109(6):777-785
Tumors have been thought to initiate as avascular aggregates of malignant cells that only later induce vascularization. Recently, this classic concept of tumor angiogenesis has been challenged by the suggestion that tumor cells grow by co-opting preexisting host vessels and thus initiate as well-vascularized tumors without triggering angiogenesis. To discriminate between these two mechanisms, we have used intravital epifluorescence microscopy and multi-photon laser scanning confocal microscopy to visualize C6 microglioma vascularization and tumor cell behavior. To address the mechanisms underlying tumor initiation, we assessed the expression of VEGF, VEGF receptor-2 (VEGFR-2), and angiopoietin-2 (Ang-2), as well as endothelial cell proliferation. We show that multicellular aggregates (< 1 mm(3)) initiate vascular growth by angiogenic sprouting via the simultaneous expression of VEGFR-2 and Ang-2 by host and tumor endothelium. Host blood vessels are not co-opted by tumor cells but rather are used as trails for tumor cell invasion of the host tissue. Our data further suggest that the established microvasculature of growing tumors is characterized by a continuous vascular remodeling, putatively mediated by the expression of VEGF and Ang-2. The results of this study suggest a new concept of vascular tumor initiation that may have important implications for the clinical application of antiangiogenic strategies. 相似文献
993.
994.
van der Loo B Bachschmid M Labugger R Schildknecht S Kilo J Hahn R Palacios-Callender M Lüscher TF 《Biogerontology》2005,6(5):325-334
We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide
(•NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and
old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for
30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min
normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R.
However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels
could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective
of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where
a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable
either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute
pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially
involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging
process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process. 相似文献
995.
Previous reports on the follicle-stimulating hormone receptor and choriogonadotropic/LH receptor, which belong to the glycoprotein hormone receptor family, suggest that the extracellular loop (ECL) 3 could be a key domain for ligand binding and intramolecular receptor signaling. In contrast to ECLs 1 and 2 of glycoprotein hormone receptors, the ECL3 displays high sequence homology, particularly in the central portion of the loop. Therefore, we opted to identify amino acids with functional importance within ECL3 of the TSH receptor (TSHR). Single alanine substitutions of all residues in ECL3 were generated. Functional characterization revealed the importance of five amino acids in the central portion of ECL3 and K660 at the ECL3/transmembrane helix (TMH) 7 junction for TSHR signaling. Decrease of G(s) activation and loss of G(q) activation by substitutions of K660 demonstrates a role for this position for TSHR conformation and signal transduction. By molecular modeling, we predicted potential interaction partners of K660:E409 and D410 in the N terminus of TMH1 and D573 in the ECL2. Complementary double mutants did not reconstitute G(s)/G(q)-mediated signaling, suggesting that K660 is not directly involved in a structural unit between ECL3 and the N terminus of TMH1. These results support a TSHR model in which the side chain of K660 is orientated toward the backbone of ECL2. Moreover, our findings provide evidence that a hydrophobic cluster, comprising residues 652-656 of ECL3, strongly influences intramolecular signal transduction and G protein activation of the TSHR. 相似文献
996.
Polymerase chain reaction detection of aspergillus DNA in experimental models of invasive aspergillosis 总被引:8,自引:0,他引:8
Loeffler J Kloepfer K Hebart H Najvar L Graybill JR Kirkpatrick WR Patterson TF Dietz K Bialek R Einsele H 《The Journal of infectious diseases》2002,185(8):1203-1206
To determine the sensitivity of polymerase chain reaction (PCR) assays for the diagnosis of invasive aspergillosis, results of quantitative culture, PCR-ELISA, and a quantitative LightCycler assay (Roche Diagnostics) of blood and organ specimens of experimentally infected mice and rabbits were compared. By PCR-ELISA, 297 of 379 murine lung specimens were positive, but only 235 of 379 were culture positive. Whereas 64 culture-negative lungs were positive by PCR, Aspergillus was grown from only 2 PCR-negative samples. The PCR assay was 19.4 times more sensitive than culture. None of the 68 blood cultures from mice and rabbits were positive for Aspergillus fumigatus, whereas PCR detected Aspergillus DNA in 17 of 68 blood samples. Quantitative PCR analysis of blood samples showed a fungus load of 10(1)-10(2) cfu/mL of blood. The data confirm the superior sensitivity of PCR for the diagnosis of experimental Aspergillus infections. 相似文献
997.
Ruperto N Nikishina I Pachanov ED Shachbazian Y Prieur AM Mouy R Joos R Zulian F Schwarz R Artamonova V Emminger W Bandeira M Buoncompagni A Foeldvari I Falcini F Baildam E Kone-Paut I Alessio M Gerloni V Lenhardt A Martini A Hanft G Sigmund R Simianer S;Pediatric Rheumatology International Trials Organization 《Arthritis and rheumatism》2005,52(2):563-572
OBJECTIVE: In an international, multicenter, double-blind, randomized clinical trial we evaluated the short-term (3 months) and long-term (12 months) efficacy and safety of 2 different doses of meloxicam oral suspension compared with the efficacy and safety of naproxen oral suspension in children with oligoarticular-course (oligo-course) or polyarticular-course (poly-course) juvenile idiopathic arthritis (JIA). METHODS: Children ages 2-16 years who had active oligo-course or poly-course JIA and who required therapy with a nonsteroidal antiinflammatory drug were eligible for this trial. Patients were randomly allocated to receive therapy with meloxicam oral suspension, 0.125 mg/kg body weight in a single daily dose; meloxicam oral suspension, 0.25 mg/kg body weight in a single daily dose; or naproxen, 10 mg/kg body weight in 2 daily doses. The trial drugs were administered in a double-blind, double-dummy design for up to 12 months. Response rates were determined according to the American College of Rheumatology pediatric 30% improvement criteria (ACR pediatric 30). Safety parameters were assessed by evaluating the frequency of adverse events in the 3 groups. RESULTS: Of 232 patients enrolled, 225 received treatment, 6 were not eligible for randomization, and 1 randomized patient was not treated. One hundred eighty-two patients (81%) completed the 12-month treatment period. Response rates according to the ACR pediatric 30 criteria improved from month 3 to month 12, as follows: from 63% to 77% in the meloxicam 0.125 mg/kg group, from 58% to 76% in the meloxicam 0.25 mg/kg group, and from 64% to 74% in the naproxen group. No statistically significant differences in response rates were observed between the groups. There were no differences in the frequency of adverse events or abnormal laboratory values between the 3 groups. CONCLUSION: The short- and long-term safety and efficacy of meloxicam oral suspension appear to be comparable with the safety and efficacy of naproxen oral suspension in the treatment of oligo-course and poly-course JIA. The once-daily administration of meloxicam oral suspension might represent an improvement in the treatment of JIA. 相似文献
998.
Jan Kaehler Ralf Koester Wibke Billmann Christian Schroeder Hans-Jürgen Rupprecht Thomas Ischinger Roland Jahns Albrecht Vogt Martin Lampen Rainer Hoffmann Reimer Riessen Joachim Berger Thomas Meinertz Christian W Hamm 《European heart journal》2005,26(20):2148-2153
AIMS: The German Angioplasty Bypass Surgery Investigation was designed to compare symptomatic efficacy and safety of percutaneous coronary balloon angioplasty (PTCA) with coronary artery bypass surgery (CABG) in patients with symptomatic multi-vessel disease. This follow-up study was performed to determine the long-term outcome of patients following these interventions. METHODS AND RESULTS: From 1986 to 1991, 359 patients with angina CCS class II-IV, age below 75 years, and coronary multi-vessel disease requiring revascularization of at least two major coronary vessels were recruited at eight German centres and randomized to PTCA or CABG. From 337 patients undergoing the planned procedure, 324 patients could be followed-up (96%). Baseline parameters were identical in both groups, 2.2+/-0.6 vessels were treated in CABG patients, whereas 1.9+/-0.5 vessels were treated in PTCA patients. Thirty-seven per cent of surgical patients received internal mammary artery grafts, while no stents were used in patients undergoing PTCA. At the end of the 13-year follow-up period, the degree of angina, the degree of dyspnea, and the utilization of nitrates were comparable in both groups. With a total number of 76 deaths, Kaplan-Meier analysis revealed a comparable distribution in both groups. Although time to first re-intervention was significantly shorter in the PTCA group, P<0.001, frequencies of re-intervention (CABG, n=94; PTCA, n=136) and crossover rates (CABG to PTCA, n=49; PTCA to CABG, n=51) were comparable in both groups. CONCLUSION: The results of our 13-year follow-up suggest that in patients with symptomatic multi-vessel disease, both PTCA and CABG are associated with a comparable long-term survival and symptomatic efficacy. How far these results may be altered by developments such as drug-eluting stents or off-pump surgery remains to be determined. 相似文献
999.
1000.
The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment
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Wernig G Janzen V Schäfer R Zweyer M Knauf U Hoegemeier O Mundegar RR Garbe S Stier S Franz T Wernig M Wernig A 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(33):11852-11857
Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels. 相似文献