Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

Why study transport of peptides and proteins at the neurovascular interface

The blood–brain barrier (BBB) is an immense neurovascular interface. In neurodegenerative, ischemic, and traumatic disorders of the central nervous system (CNS), the BBB may hinder the delivery of many therapeutic peptides and proteins to the brain and spinal cord. Fortunately, the mistaken dogma that peptides and proteins do not cross the BBB has been corrected during the past two decades by the accumulating evidence that peptides and proteins in the periphery exert potent effects in the CNS. Not only can peptides and proteins serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream. Their passage may be mediated by simple diffusion or specific transport, both of which can be affected by interactions in the blood compartment (outside the BBB) and within the endothelial cells (at the BBB level). Although the majority of current delivery strategies focuses on modification of the molecule to be delivered, understanding the mechanisms of transport will eventually facilitate regulation of the BBB directly. We review the different aspects of interactions and discuss recent advances in the cell biology of peptide/protein transport across the BBB. Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS.     

原发性肝癌患者肝切除术前、后免疫细胞表型分析

目的研究原发性肝癌(PrimaryLiverCarcinoma,PLC)患者肝切除术前、后免疫细胞表型的变化。方法采用直接免疫荧光标记,流量血细胞计数法(FlowCytometry,FCM)检测方法,动态观察120例PLC患者肝切除术前后外周血T淋巴细胞亚群、NK细胞和HLA鄄DR含量变化。结果肝切除术前肝功能Child鄄PughB级、OGTTL型和术前施行肝动脉栓塞化疗患者外周血CD8+T细胞含量明显低于正常人组,CD4+/CD8+比值则较高(P<0郾05)。全部肝癌患者肝切除术前、后CD3+CD4+T细胞和NK细胞(CD3-CD16+CD56+)含量无明显差异。术后第1天、第3天、第7天和第2周外周血淋巴细胞CD3+CD8+含量明显低于肝切除术前和术后第3周(P<0.01);而CD4+/CD8+比值则显著高于肝切除术前和术后第3周(P<0郾01)。结论PLC合并肝硬变肝储备功能不足、术前肝动脉栓塞化疗和肝切除术可导致机体细胞免疫功能低下,PLC患者肝切除术前行肝动脉栓塞化疗的价值有待深入研究。     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.     

Treatment of osteoporosis in men

Osteoporosis in men is recognised worldwide as an important and increasing public health problem. The causes are more heterogeneous than those in women. About 50% are diagnosed as secondary cases. In some secondary forms of osteoporosis the specific diagnosis results in additional therapeutic options (e.g. androgen therapy in proven hypogonadism). The basic therapy for osteoporosis in men is no different to that in postmenopausal women, namely recommendations for counteracting modifiable risk factors, especially with regard to diet, physical exercise, and calcium and vitamin D supplementation. Concerning specific drug medications, however, even today there is still a therapeutic dilemma in male osteoporosis. While older substances (e.g. calcitonin, fluoride, alfacalcidol) are approved for both sexes, all newer medications have primarily been approved for the treatment of postmenopausal osteoporosis. Health authorities request studies in purely male populations. For new drugs, fracture data are necessary while for new substances within a class (e.g. bisphosphonates), at the very least consistent effects on bone mineral density (BMD) and bone turnover markers are requested. Due to these regulatory rules, ibandronate, teriparatide and strontium ranelate are not approved in the European Union. Some years ago, alendronate was the first bisphosphonate that was approved for the treatment of men with osteoporosis, based on consistent results from two independent male studies using a daily 10 mg dosage. Very recently risedronate was approved by the FDA and EMEA. A randomised, placebo-controlled multicentre trial of 285 male patients showed, after 2 years, a 5.8% increase in lumbar spine BMD in the risedronate 35 mg once weekly group vs 1.2% in the placebo group. In a prospective controlled study on 316 men with primary or secondary osteoporosis we found, after 12 months, a lumbar spine BMD of +4.7% vs +1.0% in controls. The number of patients with one or more new vertebral fractures was 8 in the risedronate group and 20 in the placebo group (a fracture reduction of 60%). Furthermore, we found a significantly smaller decrease in height and a steeper decrease in back pain in the risedronate group. Risedronate is the first oral bisphosphonate available for men with the more comfortable once weekly dosage.     

经皮椎体成形术中骨水泥对老年骨质疏松症患者凝血功能的影响

目的 观察经皮椎体成形术(PVP)中骨水泥对老年骨质疏松症患者凝血功能的影响.方法 于椎弓根穿刺前10 min、注入骨水泥后1、20 min、2 h分别抽血检测11例患者的凝血功能相关指标,包括血浆凝血酶原时间(PT)、活化的部分凝血酶原时间(APTT)、血浆纤维蛋白原(FIB)和鱼精蛋白副凝固实验(3P实验),并汇总数据进行统计学分析.结果 PVP中骨水泥注入后20 min,PT缩短、FIB增高、3P实验阳性率升高(P<0.05),骨水泥注入2 h后基本恢复至注入前水平.除1例患者PTA术后2 h稍高于正常值(126%),其余患者各个时间点的各项指标均在正常参考值范围内.结论 PVP术中注入骨水泥对于凝血功能正常的患者基本安全,但在注入后会产生一过性轻微的高凝倾向.     

The effect of Echinacea purpurea (L.) Moench extract on experimental prostate hyperplasia

The aim of this study was to examine the effect of purple coneflower (Echinacea purpurea L. Moench) on the prostate gland of rats using an experimental model of benign prostate hyperplasia (BPH). The animals were administered 50 mg/kg of extract preparation for 4 and 8 weeks and the prostate mass and structural degenerative changes were evaluated in the course of the experiment. The administration of E. purpurea extract to rats with hyperplasia for 4 and 8 weeks gradually and significantly reduced the prostate mass and reversed the degenerative changes in the structure of the prostate gland. The present investigation suggests extract of purple coneflower prevents the development of BPH. Copyright © 2009 John Wiley & Sons, Ltd.     

手法治疗肘关节错缝86例

2000年1月-2005年10月共治疗肘关节错缝86例,临床效果满意,现报告如下。1临床资料86例中男61例,女25例;年龄13~46岁。受伤机制:均为跌倒时手掌着地,肘关节过伸导致。摄X线片未见骨折及关节异常。肘关节伸屈活动障碍,伸20°~40°,屈90°~110°,屈伸平均(70·57°±3·01°)的活动范围。肘关节轻度肿胀,以内后方为甚,压痛点为尺骨半月切迹的内侧,强作旋后活动时会引起剧烈疼痛,肘三角正常。受伤至就诊时间1~3 d,平均1·5 d。2治疗方法2·1复位左肘错缝者坐于靠背椅上,助手立于患者侧背后方,紧握患者上臂,术者于患者前侧,左手握患者腕部,右手…