Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell--mediated cytotoxicity that does not require direct cellular contact.
The emergence of computers resulted in the application revolution to instruction; till the emergence of the Internet, the strong communication ability became the major role and fully developed the integration of technology and network. The emergence of artificial intelligence teaching systems really fulfilled leaner-centered learning. Based on learner needs, the design changed the learning interaction in automatic teaching from the interaction with machines to the interaction with knowledge.
Change is a constant truth in a modern society; an organization no longer faces environments as stable as they used to be. In the face of the stronger market competition, an organization should deliberately consider and make proper responses in the operation in order to cope with the changeable environment and sustain the organizational life. When facing the changes in markets, an organization not only needs to constantly consider the changes in external environments, but also has to face the boycott or resistance of internal members to the organizational change. The effects of Human Resource Management System on Organizational Commitment therefore become critical.We have taken the Hsinchu Science Park as the research sample, in which the employees and supervisors of manufacturers have been randomly sampled. A total of 600 copies of questionnaires were e-mailed and 276 valid copies were retrieved, with the retrieval rate of 46%. The research results conclude significant correlations between 1. Human Resource Management System and Organizational Commitment, 2. Organizational Commitment and Business Performance, and 3. Human Resource Management System and Business Performance.
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