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991.
Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia 下载免费PDF全文
Shakkottai VG Chou CH Oddo S Sailer CA Knaus HG Gutman GA Barish ME LaFerla FM Chandy KG 《The Journal of clinical investigation》2004,113(4):582-590
Cerebellar ataxia, a devastating neurological disease, may be initiated by hyperexcitability of deep cerebellar nuclei (DCN) secondary to loss of inhibitory input from Purkinje neurons that frequently degenerate in this disease. This mechanism predicts that intrinsic DCN hyperexcitability would cause ataxia in the absence of upstream Purkinje degeneration. We report the generation of a transgenic (Tg) model that supports this mechanism of disease initiation. Small-conductance calcium-activated potassium (SK) channels, regulators of firing frequency, were silenced in the CNS of Tg mice with the dominant-inhibitory construct SK3-1B-GFP. Transgene expression was restricted to the DCN within the cerebellum and was detectable beginning on postnatal day 10, concomitant with the onset of cerebellar ataxia. Neurodegeneration was not evident up to the sixth month of age. Recordings from Tg DCN neurons revealed loss of the apamin-sensitive after-hyperpolarization current (IAHP) and increased spontaneous firing through SK channel suppression, indicative of DCN hyperexcitability. Spike duration and other electrogenic conductance were unaffected. Thus, a purely electrical alteration is sufficient to cause cerebellar ataxia, and SK openers such as the neuroprotective agent riluzole may reduce neuronal hyperexcitability and have therapeutic value. This dominant-inhibitory strategy may help define the in vivo role of SK channels in other neuronal pathways. 相似文献
992.
Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets 下载免费PDF全文
Kunio Okudaira Hidenori Nakai Tetsuo Hayakawa Takamichi Kashiwado Kiyoaki Tanimoto Yoshihiko Horiuchi Takeo Juji 《The Journal of clinical investigation》1979,64(5):1213-1220
The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M.The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tgamma) and lacking (Tgamma[-]) cells, 64% of ALA showed preferential reactivity with Tgamma cells and 14% with Tgamma(-) cells. The remainder had no selective reactivity against Tgamma or Tgamma(-) cells. Tgamma cells were shown to have suppressor activity, whereas Tgamma(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tgamma cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tgamma(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis.These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets. 相似文献
993.
Liu JC Chiou HJ Chen WM Chou YH Chen TH Chen W Yen CC Chiu SY Chang CY 《Journal of clinical ultrasound : JCU》2004,32(6):294-298
PURPOSE: This study was conducted to evaluate the usefulness of sonography (US)-guided needle biopsy in the diagnosis of soft tissue masses. PATIENTS AND METHODS: Thirty-seven patients with a mean age of 49 years were enrolled in the study. The size of the biopsy needle was selected according to the kind of tumor suspected (ie, primary or metastatic). In patients with suspected metastases, smaller biopsy needles were used; in patients with suspected primary tumors, larger needles were used so that larger specimens could be obtained. Prebiopsy color Doppler sonography (CDUS) was routinely used to guide the cutting needle to areas of the lesion showing sufficient vascularity. From 3 to 6 cores were obtained, depending on their quality. We compared the diagnoses yielded by the core biopsy and the final histopathologic analysis of the resected tumor by classifying the results as "concordant" or "discordant." RESULTS: A total of 37 tumors were examined. Final diagnoses were 24 malignant tumors (6 metastases and 18 primary tumors) and 13 benign tumors. The lesions were diagnosed correctly as either benign or malignant in 35 of the 36 cases for which needle biopsy specimens were adequate, with only 1 misdiagnosis. The diagnoses were concordant in 33 cases (17 primary malignant tumors, 6 metastatic tumors, and 10 benign tumors) and were discordant diagnosis in the other 4 cases (1 primary malignant tumor and 3 benign tumors). No complications were attributable to the needle biopsy. CONCLUSIONS: US-guided percutaneous core needle biopsy of soft tissue neoplasms is an easy, safe, and useful procedure. It can be considered a first-line procedure for the acquisition of tissue specimens adequate for histopathologic diagnosis. 相似文献
994.
Phenotyping of cytomegalovirus drug resistance mutations by using recombinant viruses incorporating a reporter gene 总被引:7,自引:0,他引:7 下载免费PDF全文
Chou S Van Wechel LC Lichy HM Marousek GI 《Antimicrobial agents and chemotherapy》2005,49(7):2710-2715
A new recombinant phenotyping method was developed for the analysis of drug resistance mutations in human cytomegalovirus (CMV). CMV strain T2211 was derived from strain AD169 by inserting unique restriction sites and a secreted alkaline phosphatase (SEAP) reporter gene for rapid viral quantitation. Specific viral UL97 and pol gene mutations were transferred by recombination into T2211, and their drug resistance phenotypes (for ganciclovir, foscarnet, or cidofovir) were determined by the drug concentrations required to reduce supernatant SEAP activity by 50% (IC50). Changes in the IC50 conferred by the mutations tested (UL97 M460V, C592G, A594V, and L595S and pol del981-2) were similar to those previously reported in marker transfer and conventional plaque reduction assays. The combination of UL97 C592G and pol del981-2 conferred much higher ganciclovir resistance than either mutation alone. The UL97 polymorphism D605E had no measurable effect on ganciclovir susceptibility, alone or in combination with common UL97 resistance mutations. Transfer into strain T2211 facilitates the phenotyping of newly observed mutations, combinations of mutations, and clinical CMV sequences without an accompanying viral isolate. 相似文献
995.
Evaluating the service quality of undergraduate nursing education in Taiwan--using quality function deployment 总被引:2,自引:0,他引:2
Chou SM 《Nurse education today》2004,24(4):310-318
This study applies quality function deployment (QFD) techniques to evaluate the quality of service of undergraduate nursing education in Taiwan from the perspective of nursing students. Survey data from 560 undergraduate nursing students at four Taiwanese universities were subjected to QFD analysis in order to identify the quality characteristics most highly valued by students, the elements of educational service they consider most important and least important, and relationships/discrepancies between student quality requirements and institutional service elements. Results show that students value traditional elements of nursing education - clinical practice and lectures - more highly than recent additions such as computer-aided instruction and multimedia teaching. Results also show that students are looking for quality primarily in the area of faculty characteristics. The implication is that institutions which provide nursing education should not neglect the importance of investing in faculty when they are seeking to upgrade the quality of their programs. Further QFD studies are recommended to evaluate the quality of nursing education from the perspective of preceptors and nurses who help to train students in clinical settings. 相似文献
996.
997.
Yu-Wen Chen Jun-Yen Guo Shih-Yu Tzeng Ting-Chun Chou Ming-Jen Lin Lynn Ling-Huei Huang Chao-Chun Yang Chao-Kai Hsu Sheng-Hao Tseng 《Biomedical optics express》2016,7(2):542-558
Spatially resolved diffuse reflectance spectroscopy (SRDRS) has been employed to quantify tissue optical properties and its interrogation volume is majorly controlled by the source-to-detector separations (SDSs). To noninvasively quantify properties of dermis, a SRDRS setup that includes SDS shorter than 1 mm is required. It will be demonstrated in this study that Monte Carlo simulations employing the Henyey-Greenstein phase function cannot always precisely predict experimentally measured diffuse reflectance at such short SDSs, and we speculated this could be caused by the non-negligible backward light scattering at short SDSs that cannot be properly modeled by the Henyey-Greenstein phase function. To accurately recover the optical properties and functional information of dermis using SRDRS, we proposed the use of the modified two-layer (MTL) geometry. Monte Carlo simulations and phantom experiment results revealed that the MTL probing geometry was capable of faithfully recovering the optical properties of upper dermis. The capability of the MTL geometry in probing the upper dermis properties was further verified through a swine study, and it was found that the measurement results were reasonably linked to histological findings. Finally, the MTL probe was utilized to study psoriatic lesions. Our results showed that the MTL probe was sensitive to the physiological condition of tissue volumes within the papillary dermis and could be used in studying the physiology of psoriasis.OCIS codes: (170.5280) Photon migration, (170.3660) Light propagation in tissues, (170.7050) Turbid media 相似文献
998.
Wen-Chien?Chou Wei-Han?Huang Ming-Chung?Wang Chao-Sung?Chang Shih-Peng?Yeh Tzeon-Jye?Chiou Yeu-Chin?Chen Tseng-Hsi?Lin Ming-Ching?Shen 《Thrombosis journal》2016,14(1):39
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and acquired hematopoietic stem cell disease, with florid clinical presentations. Although this disease has been characterized in the western countries, its clinical and laboratory features in Taiwan have not yet been reported.Results
As a part of an international prospective, non-interventional, observational registration trial of PNH, we have analyzed 63 patients recruited between 2009 and 2015 in Taiwan, with comparison to the 3857 patients in the rest of the world (ROW). The median age of diagnosis of our patients is 46 (range 9–84), without sex preponderance. While most of the clinical and laboratory presentations of our patients are similar to the ROW, ours have higher lactate dehydrogenase levels, lower hemoglobin, and higher frequencies of symptoms including shortness of breath and erectile dysfunction at the time of diagnosis. The incidence of thromboembolism was not statistically different between ours and the ROW (6.7 % vs 13.5 %, P = 0.178). The patients in Taiwan were treated more frequently with corticosteroid (53.2 % vs 32 %, P < 0.001), but less frequently with cyclosporine/anti-thymocyte globulin and heparin/warfarin, both P < 0.001).Conclusions
This is the first systematic review on the Taiwanese PNH patients. Our analysis would provide key information about our PNH patients and would help understanding the basic characteristics of this rare disease in Taiwan.Trial registration
This trial has been registered to ClinicalTrails.gov NCT01374360.999.
1000.