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991.
Yang SH Lee KS Yang HJ Jeon BH Lee YS Nam SW Chung DS Lee SW Hong YK 《Journal of neuro-oncology》2012,106(2):243-250
We have determined O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status by methylation-specific polymerase chain reaction
(MSP) in 22 paraffin-embedded specimens of glioblastoma multiforme. A MGMT methylation-specific high resolution melting (HRM)
assay was performed to compare the methylation levels of the tumorous and non-tumorous portions of each sample, which were
selectively collected using a microdissection technique. MGMT methylation was detected in 10 patients using MSP, while 8 patients
had both methylated and unmethylated MGMT promoters. HRM assays showed that there was no difference in the level of methylation
between tumorous and non-tumorous portions of each sample. In patients with MSP-positive tumors, the overall survival (median,
22 months) was longer as compared to those with MSP-negative tumors (median, 14 months). A correlation between the methylation
status of the MGMT promoter and MGMT protein expression was observed in 12 samples. This study demonstrates that MGMT methylation
is not restricted to glioblastoma cells. Additionally, methylation-specific HRM is a feasible approach that can be readily
applied to the methylation analysis of MGMT. A further study will be needed to determine the dynamic change of MGMT methylation
in the tumor environment. 相似文献
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Dinesh Khanna Philip J. Clements Daniel E. Furst Joseph H. Korn Michael Ellman Naomi Rothfield Fredrick M. Wigley Larry W. Moreland Richard Silver Youn H. Kim Virginia D. Steen Gary S. Firestein Arthur F. Kavanaugh Michael Weisman Maureen D. Mayes David Collier Mary E. Csuka Robert Simms Peter A. Merkel Thomas A. Medsger Martin E. Sanders Paul Maranian James R. Seibold 《Arthritis \u0026amp; Rheumatology》2009,60(4):1102-1111
Objective
A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 μg/kg/day was safe and clinically effective in improving skin disease and reducing functional disability in scleroderma (systemic sclerosis; SSc). We undertook a large randomized, double‐blind, placebo‐controlled clinical trial to compare placebo with 10 μg/kg/day and 25 μg/kg/day recombinant human relaxin, given for 24 weeks in patients with stable, diffuse, moderate‐to‐severe SSc.Methods
Men and women ages 18–70 years with diffuse cutaneous SSc (dcSSc) were administered recombinant human relaxin (10 μg/kg/day or 25 μg/kg/day) or placebo for 24 weeks as a continuous subcutaneous infusion. There was a followup safety visit at week 28.Results
The primary outcome measure, the modified Rodnan skin thickness score, was similar among the 3 groups at baseline and at weeks 4, 12, and 24. Secondary outcomes such as functional disability were similar in all 3 groups, while the forced vital capacity decreased significantly in the relaxin groups. The discontinuation of both doses of relaxin at week 24 led to statistically significant declines in creatinine clearance and serious renal adverse events (defined as doubling of serum creatinine, renal crisis, or grade 3 or 4 essential hypertension) in 7 patients who had received relaxin therapy but in none who had received placebo.Conclusion
Recombinant relaxin was not significantly better than placebo in improving the total skin score or pulmonary function or in reducing functional disability in patients with dcSSc. In addition, relaxin was associated with serious renal adverse events, the majority of which occurred after stopping the infusion. If relaxin is used therapeutically for any conditions other than scleroderma, close monitoring of blood pressure and renal function must be performed.994.
Leonidas G. Alexopoulos Inchan Youn Paolo Bonaldo Farshid Guilak 《Arthritis \u0026amp; Rheumatology》2009,60(3):771-779
Objective
Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the “pericellular matrix” (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading.Methods
Col6a1−/− mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1‐month‐old Col6a1−/−, Col6a1+/−, and Col6a1+/+ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique.Results
In Col6a1−/− and Col6a1+/− mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wild‐type controls. With age, Col6a1−/− mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD.Conclusion
These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1−/−‐derived joint laxity, can lead to progression of OA.995.
The implicit and explicit memory in patients with obsessive-compulsive disorder (OCD) was investigated using the event-related potential (ERP). For the assessment of implicit memory, a lexical decision task was administered. Among a total of 320 words and 140 non-words, 200 words were repeated, while the remaining 120 words and the 140 non-words were not repeated. For explicit memory, a continuous recognition task was administered, in which 280 words were repeated and 100 were not repeated. On the recognition task, both the controls and OCD patients showed more positivity to the old words than to the new words during the 200-600 ms period post-stimulus. Both groups showed faster response time to the old words than to the new words. On the lexical decision task, the controls showed the old/new effect during the 200-500 ms period post-stimulus, while the OCD patients did not. However, OCD patient showed faster response time to the old words than to the new words, although OCD patients showed prolonged response times to the old words compared to the controls. These results indicate that OCD patients have preserved explicit and implicit memory. The absence of old/new effect on ERP in OCD patients was discussed in terms of dysfunction of frontostriatal system, which plays an important role in both OCD and implicit memory. 相似文献
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Young Gyu Eun Sung Wan Kim Youn Wha Kim Kee Hwan Kwon 《Otolaryngology--head and neck surgery》2010,143(4):544-548
Objective
Raf-1 kinase inhibitor protein has potential as a molecular determinant of tumor metastasis and may serve as a prognostic marker. The aim of this study is to analyze the correlation between Raf-1 kinase inhibitor protein expression and the clinicopathologic characteristics of papillary thyroid cancer.Study Design
Immunohistochemical analysis.Setting
Tertiary care teaching hospital.Subjects and Methods
Fifty-nine patients with papillary thyroid cancer underwent total thyroidectomy and central neck dissection. Using specimens from total thyroidectomy and central neck dissection, we performed immunohistochemistry for Raf-1 kinase inhibitor protein and evaluated associations between Raf-1 kinase inhibitor protein expression and lymph node metastasis, tumor size, number of tumors, extrathyroidal invasion, angiolymphatic invasion, and status of the tumor border.Results
We found significantly low Raf-1 kinase inhibitor protein expression in papillary thyroid cancer with lymph node metastasis. However, Raf-1 kinase inhibitor protein expression was not associated with tumor size, multifocality, extrathyroidal invasion, or status of the tumor border.Conclusion
The loss of Raf-1 kinase inhibitor protein expression is associated with lymph node metastasis of papillary thyroid cancer but not with the progression of primary tumors. 相似文献1000.
Ung-Kyu Chang Sang Min Youn Sukh Que Park Chang Hun Rhee 《Journal of Korean Neurosurgical Society》2009,46(6):538-544