Myeloid sarcoma with megakaryoblastic differentiation mimicking a sellar tumor

Myeloid sarcoma (MS) is a localized extra‐medullary tumor mass of immature myeloid cells, arising de novo or related to acute myeloid leukemia, of which it can be a forerunner, a coinciding or late event. Less commonly, MS represents an acute blastic transformation of myelodysplastic syndromes or myeloproliferative neoplasms. This rare condition commonly consists of a proliferation of more or less immature cells with a myeloid immunophenotype, very exceptional cases showing a megakaryoblastic or erythroid differentiation. The most common localization of MS is the skin, lymph node, soft tissues and bones, but CNS involvement is exceedingly rare, with no cases reported in the sellar region. We report a 54‐year‐old man, affected by myeloproliferative neoplasm, JAK2 V617F‐positive of 13 years duration, who acutely presented with a third cranial nerve palsy; neuroradiology documented a space‐occupying lesion at the level of the sellar, upper clival and right parasellar regions, that was sub‐totally removed with a trans‐sphenoidal approach. The histological examination documented a proliferation of large, blastic cells, frequently multinucleated; a diagnosis of MS with megakaryoblastic differentiation, arising in a background of chronic idiopathic myelofibrosis, was suggested by immunohistochemistry, owing to CD42b, CD45, CD61 and LAT (linker for activation of T cells) positivity. In addition, homozygous JAK2 V617F mutation was detected from the myeloid sarcoma specimen. A few weeks after surgery, an acute blastic leukemic transformation occurred and, despite chemotherapy, the patient died 2 months after surgery. To the best of our knowledge, this is the first MS case with megakaryoblastic differentiation arising within the CNS.     

Dermal Adipose Tissue Secretes HGF to Promote Human Hair Growth and Pigmentation

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周围型肺癌的18F-FDGPET/CT显像

目的 探讨周围型肺癌18F-FDG PET/CT显像特点及其最大标准摄取值(SUVmax)与肺癌的病理类型及病灶大小的相关性.方法 回顾性分析50例经病理证实的周围型肺癌的18F-FDG PET/CT及螺旋CT资料,分析肺癌病理类型、病灶大小与SUVmax的相关性.结果 以SUVmax≥2.5作为判断恶性的标准,本组18F-FDG PET/CT阳性率为92.00％(46/50).鳞癌的SUVmax明显高于腺癌(P＜0.05);病灶大小与SUVmax呈正相关(r=0.674,P＜0.001).结论 18F-FDG PET/CT显像对诊断周围型肺癌有很高价值,结合螺旋CT形态学特点,能初步判断肺癌的病理类型.     

卡马拉素对HaCaT细胞体外增殖及对白细胞介素17C、CCL20、NF-κB表达的影响

目的 探讨卡马拉素对HaCaT细胞体外增殖及对白细胞介素17C(IL-17C)、趋化因子CCL20、NF-κB表达的影响.方法 用不同浓度卡马拉素组(0.5、1.0、2.0、4.0 μmol/L)、含与4.0 μmol/L卡马拉素等体积二甲基亚砜的RPMI 1640培养液(溶媒组)、RPMI 1640培养液(对照组)分别作用于HaCaT细胞.采用CCK8法检测卡马拉素作用于HaCaT细胞24、48、72 h对细胞体外增殖的影响;RT-PCR法检测卡马拉素对HaCaT细胞IL-17C和CCL20 mRNA表达的影响;Western印迹法检测卡马拉素对HaCaT细胞IL-17C、CCL20和NF-κB蛋白表达的影响.统计学处理采用重复测量的方差分析、单因素方差分析和Pearson相关分析.结果 各浓度组卡马拉素对HaCaT细胞增殖的抑制作用有随时间变化的趋势(F=126.936,P＜ 0.05),药物作用时间越长,抑制作用越强;HaCaT细胞增殖的抑制率也随卡马拉素浓度的增加而升高(F=838.308,P＜ 0.05);不同浓度卡马拉素组对HaCaT细胞体外增殖的抑制作用随时间变化的趋势不同,药物浓度与时间存在交互作用(F=15.961,P＜ 0.05).不同浓度卡马拉素作用于HaCaT细胞48 h后,IL-17C mRNA及其蛋白、CCL20 mRNA及其蛋白、NF-κB蛋白表达量均随卡马拉素浓度的增加而不断降低,差异均有统计学意义(F值分别为206.041、233.887、143.883、162.431、577.915,均P＜0.05).结论 卡马拉素可抑制HaCaT细胞的体外增殖,并可在mRNA和蛋白水平下调IL-17C、CCL20的表达,而两者表达量的降低可能与NF-κB表达下调有关.     

Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes

BackgroundCC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes.ObjectiveTo identify the mechanism underlying CCL22 production by HaCaT cells.MethodsWe investigated the signal transduction pathways by which TNF-α and IFN-γ stimulate HaCaT cells to produce CCL22 by adding various inhibitors.ResultsTNF-α- and IFN-γ-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1.ConclusionOur results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.     

Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer’s disease

The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a natural extract from the vine-like herb Tripterygium wilfordii Hook F,has potent anti-inflammatory and immunosuppressive efficacy.Therefore,we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice(aged 4–4.5 months) for 45 days.Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells,and transformed microglial cells into the resting state.Further,triptolide(5 μg/kg/d) also reduced the total number of hippocampal astrocytes.Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.     

Characterization of Moyamoya and Middle Cerebral Artery Diseases by Carotid Canal Diameter and RNF213 p.R4810K Genotype

ObjectivesIt is sometimes difficult to differentiate middle cerebral artery disease from moyamoya disease because the two can present similarly yet have different treatment strategies. We investigated whether the presence of a narrow carotid canal and the RNF213 mutation can help differentiate between the two phenotypes.Population and MethodsWe analyzed 78 patients with moyamoya disease, 27 patients with middle cerebral artery disease, and 79 controls from 2 facilities. The carotid canal diameter was measured using computed tomography. The p.R4810K mutation was genotyped by TaqMan assay. A receiver operating characteristics analysis was performed to assess the significance of the carotid canal diameter for the accurate diagnosis of moyamoya disease.ResultsThe carotid canal diameter was significantly narrower in patients with moyamoya disease than in controls. The optimal cutoff values were 5.0 mm for adult males and 4.5 mm for adult females and children (sensitivity: 0.82; specificity: 0.92). Among the patients with middle cerebral artery disease, 18.5% and 25.0% of the affected hemispheres had the p.R4810K mutation and narrow canal (i.e., below the cutoff), respectively, whereas only 3.1% of those had both. Contrastingly, 68.8% of the affected hemispheres in patients with moyamoya disease had both these characteristics. Among the patients with moyamoya disease, those with the p.R4810K mutation tended to have narrower carotid canals.ConclusionsAlthough the presence of a narrow carotid canal or the p.R4810K mutation alone could not be used to distinguish those with moyamoya disease from those with middle cerebral artery disease, the combination of these factors could better characterize the two phenotypes.     

Clinical and genetic features of Charcot‐Marie‐Tooth disease 2F and hereditary motor neuropathy 2B in Japan

Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.