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41.
Matthew D. Cykowski Richard A. Allen Angela C. Kanaly Kar-Ming Fung Roxanne Marshall Arie Perry Ethan D. Stolzenberg S. Terence Dunn 《Journal of neuro-oncology》2013,115(3):477-486
Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF–KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF–KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF–KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion. 相似文献
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Dani?lle Horst Ruben J. Geerdink Anna M. Gram Arie J. Stoppelenburg Maaike E. Ressing 《Viruses》2012,4(10):2379-2399
The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway. 相似文献
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BACKGROUND: Normal spirometry is required for medical clearance of professional divers in many countries. Divers frequently have unusually large lung volumes associated with a low ratio of FEV(1) to FVC (FEV(1)%), suggestive of obstructive airways disease. We retrospectively analyzed the records of divers in the Israeli Navy with a low FEV(1)% who fulfilled the criteria for large lungs, to determine whether this might be the effect of training or natural selection. We also investigated changes in pulmonary function in relation to diving experience. METHODS: A total of 171 divers with FEV(1)% < 80% on simple spirometry were evaluated. We conducted a retrospective analysis of lung function data for those subjects who met the criteria for large lungs. RESULTS: One hundred nine of 171 divers with low FEV(1)% met the criteria for large lungs and were included in the study. Their average age was 25 years (range, 18 to 44 years), and their mean diving experience was 7 years (range, 0 to 26 years). No difference was found in FVC values between experienced and inexperienced divers. The mean forced expiratory flow at 50% of vital capacity was significantly reduced in the most experienced group compared with the novice or less experienced divers. No difference was found in the diffusing capacity of the lung for carbon monoxide between experienced and inexperienced divers. CONCLUSIONS: We suggest that large lungs may represent part of the natural selection for diving, rather than a training effect. Prolonged diving experience may result in the development of small airways disease. 相似文献
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Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease 总被引:5,自引:0,他引:5
Neff GW O'Brien CB Reddy KR Bergasa NV Regev A Molina E Amaro R Rodriguez MJ Chase V Jeffers L Schiff E 《The American journal of gastroenterology》2002,97(8):2117-2119
Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus. 相似文献
48.
Eder L Zisman D Barzilai M Laor A Rahat M Rozenbaum M Bitterman H Feld J Rimar D Rosner I 《The Journal of rheumatology》2008,35(5):877-882
OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted. 相似文献
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