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991.
Strach K Sommer T Grohé C Meyer C Fischer D Walter MC Vorgerd M Reilich P Bär H Reimann J Reuner U Germing A Goebel HH Lochmüller H Wintersperger B Schröder R 《Neuromuscular disorders : NMD》2008,18(6):475-482
We report the clinical, genetic and cardiac magnetic resonance imaging (MRI) findings in 11 German patients with heterozygous E245D, D339Y, R350P and L377P desmin mutations and without cardiac symptoms. Clinical evaluation revealed a marked variability of skeletal muscle, respiratory and cardiac involvement even between patients with identical mutations, ranging from asymptomatic to severely affected. While echocardiography did not show any pathological findings in all 11 patients, cine MRI revealed focal left ventricular hypertrophy in 2 patients and MR delayed enhancement imaging displayed intramyocardial fibrosis in the left ventricle in 4 patients indicating early myocardial involvement. Our data argue against distinct genotype-phenotype correlations and suggest that comprehensive cardiac MRI is superior to conventional echocardiography for the detection of early and clinically asymptomatic stages of cardiomyopathy in desminopathy patients. Therefore, cardiac MRI may serve as a screening tool to identify patients at risk, which might benefit from early pharmacological and/or interventional (e.g. implantable cardioverter-defibrillator devices) therapy. 相似文献
992.
Moonen AF Pilot P Meijers WG Waelen RA Leers MP Grimm B Heyligers IC 《Acta orthopaedica Belgica》2008,74(2):210-215
A pilot study was undertaken to evaluate whether filters integrated in postoperative retransfusion systems affect the amount of blood cells retransfused after total knee arthroplasty. Twenty-two consecutive patients received either the Donor retransfusion system (n=12 patients) or the Bellovac ABT retransfusion system (n=10). Both systems differ with respect to the type of filter, a Pall Lipiguard filter and a Sangopur filter, respectively. At the beginning of the retransfusion, blood samples were taken before and after the filter. The filter of the Donor system significantly decreased the amount of leukocytes and erythrocytes, whereas the filter of the Bellovac system did not. As a result the haemoglobin level of retransfused blood with the Donor system was significantly lower than with the Bellovac system. It can be concluded that the type of filter integrated in two postoperative autologous blood retransfusion systems significantly affected the amount of blood cells retransfused in patients undergoing total knee arthroplasty. 相似文献
993.
Fink B Egl M Singer J Fuerst M Bubenheim M Neuen-Jacob E 《Arthritis and rheumatism》2007,56(11):3626-3633
OBJECTIVE: To investigate the frequency of structural changes in the vastus medialis muscle in patients with osteoarthritis (OA) of the knee. METHODS: Specimens of vastus medialis muscle from 78 patients with end-stage OA of the knee undergoing total joint arthroplasty were examined histopathologically. Morphologic changes were assessed in relation to clinical features that might have contributed to muscle injury. RESULTS: All muscle specimens exhibited atrophy of type 2 fibers. In 32% of the patients, atrophy of type 1 fibers was also noted. Fiber type grouping of type 1 fiber in 15% of the patients and type 2 fiber in 37%, indicating reinnervation, led to the diagnosis of neurogenic muscular atrophy in 32% of the patients; selective atrophy of type 2 fiber in 68% of the specimens was interpreted as possibly resulting from pain-associated disuse. Signs of muscle degeneration and regeneration were found in 65% and 96% of the samples, respectively. Soft tissue changes indicating long-term disease, such as calcification, fibrosis, and lipomatosis, were frequently observed (in 69%, 71%, and 94% of the patients, respectively). Statistical analysis of clinical and morphologic parameters revealed a significant association between degenerative muscle changes and the presence of a varus deviation of the leg axis. CONCLUSION: Patients with OA of the knee frequently exhibit muscle changes, with probable multifactorial etiology. Selective atrophy of type 2 fibers might reflect pain-related immobilization of a limb. Changes such as neurogenic muscular atrophy, muscle fiber degeneration, and regeneration might contribute as cofactors in the development or progression of OA. 相似文献
994.
The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo 总被引:3,自引:0,他引:3 下载免费PDF全文
Reimann M Loddenkemper C Rudolph C Schildhauer I Teichmann B Stein H Schlegelberger B Dörken B Schmitt CA 《Blood》2007,110(8):2996-3004
In addition to the ARF/p53 pathway, the DNA damage response (DDR) has been recognized as another oncogene-provoked anticancer barrier in early human tumorigenesis leading to apoptosis or cellular senescence. DDR mutations may promote tumor formation, but their impact on treatment outcome remains unclear. In this study, we generated ataxia telangiectasia mutated (Atm)-proficient and -deficient B-cell lymphomas in Emu-myc transgenic mice to examine the role of DDR defects in lymphomagenesis and treatment sensitivity. Atm inactivation accelerated development of lymphomas, and their DNA damage checkpoint defects were virtually indistinguishable from those observed in Atm+/+-derived lymphomas that spontaneously inactivated the proapoptotic Atm/p53 cascade in response to Myc-evoked reactive oxygen species (ROS). Importantly, acquisition of DDR defects, but not selection against the ARF pathway, could be prevented by lifelong exposure to the ROS scavenger N-acetylcysteine (NAC) in vivo. Following anticancer therapy, DDR-compromised lymphomas displayed apoptotic but, surprisingly, no senescence defects and achieved a much poorer long-term outcome when compared with DDR-competent lymphomas treated in vivo. Hence, Atm eliminates preneoplastic lesions by converting oncogenic signaling into apoptosis, and selection against an Atm-dependent response promotes formation of lymphomas with predetermined treatment insensitivity. 相似文献
995.
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998.
Eike Staub Joern Groene Maya Heinze Detlev Mennerich Stefan Roepcke Irina Klaman Bernd Hinzmann Esmeralda Castanos-Velez Christian Pilarsky Benno Mann Thomas Brümmendorf Birgit Weber Heinz-Johannes Buhr André Rosenthal 《Molecular cancer》2007,6(1):1-7
Background
The normal human prostate glandular epithelium has the unique function of accumulating high levels of zinc. In prostate cancer this capability is lost as an early event in the development of the malignant cells. The mechanism and factors responsible for the ability of the normal epithelial cells to accumulate zinc and the loss of this capability in the malignant cells need to be identified. We previously reported that Zip1 is an important zinc uptake transporter in prostate cells and is down regulated in the malignant cells in situ along with the depletion of zinc levels. In this report we investigated the expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein levels were determined by immunohistochemistry analysis of human prostate tissue sections.Results
Normal and BPH glandular epithelium consistently exhibited the strong presence of both Zip 2 and Zip3; whereas both transporters consistently were essentially non-detectable in the malignant glands. This represents the first report of the expression of Zip3 in human prostate tissue; and more importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins were localized predominantly at the apical cell membrane, which is in contrast to the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are associated with the re-uptake of zinc from prostatic fluid.Conclusion
These results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as important zinc uptake transporters involved in the unique ability of prostate cells to accumulate high cellular zinc levels. Zip1 is important for the extraction of zinc from circulation as the primary source of cellular zinc. Zip 2 and Zip3 appear to be important for retention of the zinc in the cellular compartment. The down regulation of all three transporters in the malignant cells is consistent with the loss of zinc accumulation in these cells. Since zinc imposes tumor suppressor effects, the silencing of the gene expression for these transporters is a required event for the manifestation of the malignant activities of the neoplastic cells. This now provides new insights into the genetic/molecular events associated with the development of prostate cancer; and supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes and zinc as a tumor suppressor agent. 相似文献999.
BACKGROUND: Post-transplant non-Hodgkin lymphoma is a feared complication of immunosuppressive treatment and is associated with high mortality. Most post-transplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr-virus (EBV)-infected B lymphocytes. No reliable methods for the prevention of EBV infection and lymphoma are available. We aimed to elucidate the effect of prophylactic treatment for cytomegalovirus (CMV) infection on the incidence of post-transplant lymphomas. METHODS: In a multicentre retrospective study, we analysed the incidence of post-transplant non-Hodgkin lymphoma in 44 828 recipients of deceased-donor kidney transplants who were reported to the scientific registry of the Collaborative Transplant Study. Patients had received antiviral drugs (aciclovir or ganciclovir) or anti-CMV immunoglobulin to prevent CMV infection according to the transplant centres' protocols, or no CMV prophylaxis. Standardised incidence ratios (SIR) of lymphoma were calculated and compared by chi(2) analyses FINDINGS: During the first post-transplantation year, 30 255 patients who did not receive CMV prophylaxis developed lymphomas at SIR 26.4. Lymphoma incidence in 12 470 patients who received antiviral treatment was nearly identical (SIR 24.2, p=0.62) to that in patients who did not receive CMV prophylaxis. However, 2103 patients who received anti-CMV immunoglobulin showed a complete absence of lymphomas in the first after-transplantation year (SIR 0; p=0.012 vs no treatment, p=0.016 vs antivirals). In the subsequent 5 years of follow-up, new cases of lymphoma developed at similar rates in all three groups (p=0.97). INTERPRETATION: These findings suggest that prophylactic anti-CMV immunoglobulin prevents the development of early post-transplant non-Hodgkin lymphoma in kidney-graft recipients. Prophylactic treatment with antiviral drugs does not reduce the risk of post-transplant lymphoma. 相似文献
1000.
Primary sarcomas of the sellar region are uncommon, although a wide variety have been reported. To date, no cases of primary synovial sarcoma have been described as occurring at this site. We report an immunohistochemically and molecular genetically confirmed primary synovial sarcoma involving the sellar/parasellar region and cavernous sinus in an adult male. Subtotal resection and radiosurgery proved to be efficacious. The spectrum of primary sellar region sarcomas is summarized. 相似文献