The pathology of encephalic arteriovenous malformations treated by prior embolotherapy

Summary A pathologic study was undertaken of seven encephalic arteriovenous malformations, including five resected from one to seven days after balloon embolization, one resected 10 days after embolization with polyvinyl alcohol foam (PVA), and a large mesencephalic AVM in a patient who died eight weeks after a series of embolization procedures with PVA and silicone spheres. AVM's resected 6–7 days following balloon embolization showed focal mural and adventitial inflammatory infiltrates and parenchymal (i.e. non-vascular) necrosis of a large portion of one AVM. The AVM examined 7 days post-balloon embolization showed an intraluminal thrombus containing refractile particles surrounded by foreign body giant cells (FBGC's). The AVM removed 10 days after PVA embolotherapy showed mural and perivascular necrosis with infiltration by polymorphonuclear leukocytes. The single autopsy case showed FBGC's surrounding residual PVA, refractile particles deep within vascular walls, and marked mural thickening of AVM channel walls, changes that may represent a response to previous angionecrosis and inflammation at the time of embolization. These findings, the pathogenesis of which is discussed in detail, may help to explain some of the rare complications of iatrogenic embolotherapy with these materials, as well as providing evidence for the basis of their efficacy.Presented in part at the 63rd Annual meeting of the American Association of Neuropathologists, Seattle, Washington, June, 1987     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.     

人胚额叶皮层和海马干细胞的自主分化研究

目的 研究人胚胎额叶皮层和海马组织神经干细胞的自主分化特性。观察额叶皮层神经干细胞和海马神经干细胞特性的异同。方法 从人胚胎额叶皮层和海马组织分别分离提出神经干细胞，经无血清体外培养、扩增，形成神经球。神经球贴壁进行不加诱导剂的自主分化。采用细胞生长曲线检测神经干细胞的增殖能力。使用5-溴脱氧尿嘧啶核苷（BrdU）标记分裂增生的细胞，观察细胞的分裂增殖情况。免疫细胞化学法鉴定神经干细胞的自主分化能力，比较额叶皮层和海马神经干细胞的分化特点。结果 从人胚胎额叶皮层和海马分离的神经干细胞具有增殖能力，额叶皮层神经干细胞的细胞倍增时间为3．9d，海马神经干细胞的细胞倍增时间为3．2d。细胞贴壁分化后出现Nestin、GFAP、Tuj-1表达阳性的细胞。皮层和海马神经干细胞分化产生的Tuj-1阳性细胞分别是40．7％和19．3％；皮层和海马神经干细胞分化产生的GFAP阳性细胞分别是59．3％和80．7％。结论 分离培养的额叶皮层和海马神经干细胞具有自我更新和增殖能力，可以向神经元、胶质细胞分化。额叶皮层神经干细胞与海马神经干细胞的倍增时问、自主分化特点和分化为神经细胞和胶质细胞的比率各有不同。     

The hevein domain of the major latex-glove allergen Hev b 6.01 contains dominant T cell reactive sites

BACKGROUND: Sensitization to natural rubber latex (Hevea brasiliensis) is a major cause of occupational asthma and rhinitis affecting frequent latex-glove users. Hev b 6.01, a known major latex allergen, is cleaved naturally into hevein (4.7 kDa) and a C-terminal fragment (14 kDa). Hevein is an abundant protein in latex-glove extracts. As the immune response to allergens is initiated by activation of allergen-specific CD4(+) T cells, identification of dominant T cell epitopes is crucial for the development of specific immunotherapy. OBJECTIVE: To identify dominant T cell epitopes of Hev b 6.01 in latex-allergic glove users. METHODS: Ten latex-allergic frequent glove users and six non-latex-allergic atopic control subjects were selected, based on clinical symptoms and positive latex-specific serum IgE. Serum IgE reactivity to glove extract and recombinant Hev b 6.01 (rHev b 6.01) were analysed by ELISA. Latex-specific short-term oligoclonal T cell lines were generated from peripheral blood of latex-allergic subjects. These lines were tested for proliferative responses to overlapping 20-mer peptides of the Hev b 6.01 molecule. CD4(+) T cell intracellular cytokines, IL-4 and IFN-gamma were assessed following stimulation with immobilized anti-CD3 in the presence of IL-2. RESULTS: All ten of the latex-allergic patients showed serum IgE binding to glove extract while eight of these also showed IgE binding to rHev b 6.01 by ELISA. Western blotting confirmed reactivity with rHev b 6.01 at around 20 kDa. T cell proliferation assays showed that latex-specific T cell lines from all subjects responded to one or more peptides, with greatest frequency of reactivity to peptides Hev b 6.01 p(10-29) and Hev b 6.01 p(19-38) in the hevein domain. An allergic-type cytokine profile with considerable IL-4 in addition to IFN-gamma was evident from intracellular cytokine staining. CONCLUSION: Hevein is an important T cell as well as B cell immunogen and contains dominant T cell reactive sites.     

人绒毛膜促性腺激素在脑实质生殖细胞肿瘤诊治中的意义

目的研究脑实质生殖细胞肿瘤(GCT)患者脑脊液和血清中人绒毛膜促性腺激素(HCG)水平变化,评价其在肿瘤诊断、疗效监测中的意义。方法对5例脑实质内GCT患者的脑脊液和血清HCG水平在治疗前后进行系列测定。以10例性别年龄匹配的因其他疾病接受腰穿检查的患者作为对照组,测定其脑脊液HCG水平。观察脑脊液和血清HCG水平在治疗前后的变化情况。结果10例对照组患者的脑脊液中均测不到HCG。从5例GCT患者共采集17对脑脊液和血清配对样本。所有5例患者都出现脑脊液和血清HCG水平升高。治疗后脑脊液和血清HCG水平迅速下降。血清和脑脊液HCG水平呈显著相关。每一对样本中,脑脊液HCG水平均高于血清。血清、脑脊液HCG水平比为0.245±0.190。结论脑脊液HCG升高对诊断脑实质内GCT具有高度特异性和较高灵敏度。对分泌HCG的GCT,脑脊液和血清HCG是评价治疗效果和监测肿瘤复发的重要指标。     

Role of progenitor endothelial cells in cardiovascular disease and upcoming therapies.

The field of cell-based transplantation has expanded considerably and is poised to become an established cardiovascular therapy in the near future. In this review, we will focus on endothelial progenitor cells (EPCs), which are immature cells capable of differentiating into mature endothelial cells. EPCs share many surface marker antigens such as CD34, AC133, Flk-1, etc. with hematopoietic stem cells (HSCs) and the major source of EPCs as well as HSCs is the bone marrow (BM). BM-derived EPCs are mobilized into peripheral blood and recruited to the foci of pathophysiological neovascularization and reendothelialization, thereby contributing to vascular regeneration. Severe EPC dysfunction is an indicator of poor prognosis and severe endothelial dysfunction. Indeed, number of circulating EPCs and their migratory activity are reduced in patients with diabetes, coronary artery disease (CAD), or subjects with multiple coronary risk factors. Effective neovascularization induced by EPC transplantation for hindlimb, myocardial, and cerebral ischemia has been demonstrated in many preclinical studies, and early clinical trials of EPC transplantation in chronic and acute CAD indicate safety and feasibility of myocardial cell-based therapies. For therapeutic reendothelialization in patients undergoing percutaneous coronary intervention, CD34 antibody-coated stents have been used clinically to capture circulating EPCs at the injury sites and enhance reendothelialization and safety of stents. Further development in cell processing technology for efficient isolation, expansion, mobilization, recruitment, and transplantation of EPCs into target tissues are underway and expected to be tested in clinical trials in the near future.     

Diagnosis and management of severe atherosclerosis of the ascending aorta and aortic arch during cardiac surgery: focus on aortic replacement

Objective: Severe atherosclerosis of the ascending aorta and arch frequently causes difficulties during heart operations, hindering surgical manoeuvres and potentially leading to systemic embolism. The aim of our study was to assess the safety and effectiveness of replacing the atherosclerotic ascending aorta in this setting. Methods: Aortic atherosclerosis was characterized by epiaortic ultrasonographic scanning in 90.1% of 1927 consecutive adult patients undergoing cardiac operations, and by computed tomographic chest scanning in selected cases. Thirty-six of the 152 patients requiring major derangements from our standard practice due to aortic atherosclerosis underwent replacement of the ascending aorta and constitute the study group. Replacement of the aorta was extended to the arch in 13 cases (36.1%). It was associated with single or multiple valve surgery in 34 patients (94.4%) and with coronary revascularization in 30 (83.3%). Two patients (5.6%) underwent coronary bypass grafting without valve surgery. A cryoablation procedure was associated in three patients with permanent atrial fibrillation. Deep hypothermic circulatory arrest was employed in 34 patients (94.4%), while proximal aortic disease allowed conventional distal crossclamping in 2 cases. The risk of operative mortality was estimated by the logistic EuroSCORE both with and withholding the variable ‘surgery of the thoracic aorta’. All survivors were followed-up for 1–41 months (16 ± 12). Results: Two patients died in the hospital (5.6%) and two during follow-up, for a cumulative survival of 91.3% and 85.6% at 1 and 3 years, respectively (hospital deaths included). The hospital death rate compared favourably with the expected estimates of 25.5% (p < 0.05) and 10.3% (p = 0.67) obtained by the EuroSCORE full model and without ‘aortic surgery’, respectively. In-hospital adverse neurologic events occurred in six patients (16.7%), including stroke in one patient (2.8%) and neurocognitive disturbances in five (13.9%), although they were all transient and cleared before discharge. Excess bleeding required re-exploration in four patients (11.1%), and one more patient underwent emergency grafting for acute postoperative coronary occlusion. Ten patients (38.5%) were intubated for longer than 24 h. Conclusion: Despite significant perioperative morbidity, replacement of the severely atherosclerotic aorta is worth consideration to avert expectedly higher death and stroke rates.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

抗CD44单克隆抗体A3D8对人白血病细胞系HL-60细胞增殖及分化的影响

目的 探讨抗CD44单克隆抗体A3D8对HL-60细胞增殖及分化的影响，寻找急性髓系白血病(AML)治疗的新靶点。方法 以AML细胞株HL-60为模型，通过观察细胞生长、形态学、表面分化抗原、细胞周期和细胞因子表达，以及应用硝基四氮唑蓝(NBT)还原实验来研究抗CD44单克隆抗体A3D8对细胞增殖及分化的影响。结果 HL-60细胞高表达CD44；A3D8以浓度和时间依赖性方式抑制HL-60细胞生长。A3D8使HL-60细胞周期阻滞在G0／G1期，CD11b、CD14表面抗原阳性率明显增高，细胞体积增大，核／浆比例减小，核染色质聚集，NBT还原实验阴性，细胞表达粒细胞集落刺激因子mRNA，呈现向单核细胞系方向分化。结论 A3D8可抑制HL-60细胞增殖，并诱导其向单核系细胞分化，CD44有可能成为AML治疗的新途径。