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Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer 总被引:3,自引:3,他引:3
Onishi M; Mui AL; Morikawa Y; Cho L; Kinoshita S; Nolan GP; Gorman DM; Miyajima A; Kitamura T 《Blood》1996,88(4):1399-1406
Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5. 相似文献
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Small GW McDonnell DD Brooks RL Papadopoulos G 《Journal of the American Geriatrics Society》2002,50(2):321-327
OBJECTIVES: ITo examine the economic impact of Alzheimer's disease (AD) as the disease progresses on patients' medical costs and caregivers' productivity. DESIGN: A 12-page, self-administered mail survey, fielded in November 1999. SETTING: Households with AD caregivers, selected from a nationwide (U.S.) consumer database. PARTICIPANTS: One thousand seven hundred fifteen caregivers of noninstitutionalized AD patients. MEASUREMENTS: Disease progression was measured using a scale of symptom frequency and measures of instrumental and physical functioning. Cost components included hospital days, physician visits, and emergency room visits. Lost productivity was assessed using hours per week that caregivers provided care and the number of days that they missed from work because of caregiving. RESULTS: The direct costs of caring for AD patients for 6 months totaled $3,129, whereas the indirect costs were $26,080. Patients with more-frequent symptoms used all healthcare resources, including the hospital, emergency room, and physicians, more often than those with less-frequent symptoms. Those with lower levels of physical and instrumental functioning also used the hospital and physicians more often than those with higher levels of physical and instrumental functioning. Caregivers of these more severely impaired patients spent more hours providing care and reported missing more work than those caring for higher-functioning patients. These relationships remained after controlling for potentially confounding factors. CONCLUSIONS: This large study of patients at all stages of AD shows that the direct and indirect costs of AD are considerably lower for patients with fewer symptoms. Longitudinal studies will determine the impact on the overall cost of care of interventions that reduce symptoms and maintain patients at earlier stages of the disease. 相似文献
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The enterohepatic circulation of bile salts 总被引:10,自引:0,他引:10
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DM Clarkson 《Journal of medical engineering & technology》2013,37(3):125-131
An overview is provided of the scope and application of IEC TR 60825-9 in determination of hazards of non coherent optical radiation sources. Specific areas reviewed in detail include those relating to hazards of ultraviolet radiation, retinal thermal hazard and blue light photochemical hazard. The effect of spectral temperature on relative risk relating to retinal thermal hazard and blue light photochemical hazard are outlined. Assessment of risk factors of these hazards was determined using a range of measurement devices including spectral radiometer, broad band power meter and a locally developed device for determination of pulse profile of pulsed light sources. 相似文献
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The circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA). In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells. Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny. 相似文献
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Recurrent Spontaneous Paresthesia in the Upper Limb Could Be Due to Migraine: A Case Series 下载免费PDF全文
Sanjay Prakash DM Chaturbhuj Rathore DM Prayag Makwana MD Mitali Rathod MD 《Headache》2015,55(8):1143-1147
Transient neurologic dysfunction is a characteristic feature of migraine. About 20% of migraineurs may experience various symptoms in the absence of any headache at one time or another. Visual auras are the most common auras of migraine, and migraine is considered as the most common cause of transient vision loss in young patients. Sensory auras are the second most common migrainous auras. However, the literature is silent for isolated sensory aura as a migraine equivalent. Herein we report 14 patients with recurrent episodic paresthesia in the limbs and other body parts. All patients fulfilled the diagnostic criteria of “typical aura without headache” of ICHD‐3β. All patients were subjected to various investigations to rule out secondary causes. Ten patients received antimigraine drugs and all showed a positive response to therapy. Recurrent spontaneous paresthesia is quite common in the general population and many patients remain undiagnosed. We speculate that a subset of patients might be related to migrainous sensory auras. 相似文献
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