Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera

Essential thrombocythemia (ET) and polycythemia vera (PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks (MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive platelet-rich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin (β-TG), platelet factor 4 (PF4) and thrombomoduline (TM), increased urinary thromboxane B2 (TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase (COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complications, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression (not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2^V617F mutated compared to JAK2 wild type ET.     

Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

Klebsiella pneumoniae is among the most common Gram‐negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll‐like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre‐recombinase under control of the LysM promoter to generate LysMcre‐Hsp90b1‐flox mice. LysMcre‐Hsp90b1‐flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96‐deficient macrophages did not release pro‐inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre‐Hsp90b1‐flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1‐flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro‐inflammatory cytokines, while the inflammatory response during late‐stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre‐Hsp90b1‐flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram‐negative pneumonia by regulating TLR expression. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

人脂肪干细胞复合脱细胞软骨基质支架在生物反应器中构建组织工程软骨

目的:观察人脂肪干细胞复合脱细胞软骨基质支架在生物反应器中初步构建组织工程软骨的可行性。方法:实验于2005-04/2006-05在解放军总医院骨科研究所完成。脂肪组织和关节软骨均来自膝关节置换术中切除的组织,并经患者知情同意。关节软骨冻干后经粉碎机粉碎,过筛,选取25～38μm大小的软骨微粒。在样品中先加入2.5g/L胰蛋白酶,37℃消化24h,再加入1%Triton X-100震荡72h。将软骨微粒和蒸馏水按1∶3的比例混合后滴加在模板中,置入冷冻干燥机冻干后行紫外线交联。紫外线照射8h完成。最后经25kGy 60Co辐照灭菌完成支架制备。取膝关节置换术中切除的髌下脂肪垫,酶消法获得脂肪干细胞,扩增后复合于脱细胞软骨基质制成圆柱状三维支架上(细胞密度5×1010L-1),置于生物反应器中进行诱导培养,同时设静态培养组作为对照,3周后观测大体形态和组织学形态变化,同时进行组织化学(包括番红花O,阿利新蓝染色)和Ⅱ型胶原免疫组织化学分析。结果:生物反应器组诱导培养3周苏木精-伊红染色显示支架结构消失,只有中心区域残存少量支架结构;静态培养组支架结构尚存在,有少量基质分泌。番红花O染色显示生物反应器组细胞外有大量蛋白聚糖沉积,阿利新蓝染色表明有软骨特异性蛋白多糖的聚集;而静态培养组只有部分区域染色且淡于生物反应器组。Ⅰ型胶原免疫组化的结果显示,在生物反应器组细胞能够合成大量软骨细胞特异性胶原成分,而静态培养组呈弱阳性。结论:生物反应器培养明显促进了脂肪干细胞的增殖与软骨分化,是体外构建组织工程软骨的良好方法。     

麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

白花败酱醇甙结构的修正

白花败酱醇甙结构的修正吕扬吴楠康文俊郑启泰谢平陈淑凤梁晓天（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）徐成俊等［１］报道从败酱科植物白花败酱（ＰａｔｒｉｎｉａｖｉｌｏｓａＪｕｓ）的稀醇提取物中分离得到Ａ，Ｂ，Ｃ，Ｄ４个成分，其中Ｃ...     

Percutaneous angioplasty in clinical management of renovascular hypertension: initial and long-term results

Between January 1980 and July 1983, percutaneous transluminal angioplasty was attempted on 137 stenotic renal arteries in 100 patients. At termination of follow-up studies (3-39 months, mean of 16 months), 70% of those treated for hypertension had benefited from the procedure. Stenosis secondary to fibromuscular dysplasia responded better than stenosis from arteriosclerosis (85% and 65% of the patients, respectively). Benefit was minimal for those with stenosis of the renal artery ostium or renal insufficiency. Determining levels of renal vein renin before angioplasty is helpful in selecting patients; following angioplasty, this has considerable significance in predicting the success of the procedure.