Bone mineral density and bone turnover markers of patients with Behçet's disease

Background Behçet's disease (BD) is a systemic inflammatory disease of unknown aetiology. The pathogenesis of rheumatological findings and the status of bone metabolism in this disease are unknown. Inflammatory diseases may predispose to a decrease in bone mineral density (BMD) and there are many studies concerning osteoporosis in chronic inflammatory diseases. Objective The aim of this study was to investigate BMD and bone turnover markers in patients with BD. Methods Thirty BD patients (17 male and 13 female patients, mean age 36.9 ± 12.6 years) and a total of 30 age‐ and sex‐matched healthy controls (17 male and 13 female controls, mean age 34.9 ± 8.95 years) recruited from the general population were enrolled in the study. Bone mineral density was measured at the lumbar spine (L1‐4) and the left hip (total hip) using dual energy X‐ray absorptiometry. Serum samples were collected between 8 and 10 am after overnight fasting. Serum calcium (Ca), phosphate (P), parathormone (PTH), total alkaline phosphatase (ALP), osteocalcin (OC), erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP) were measured. Free deoxypyridinoline cross‐links (DPD) in second‐void urine and total daily urinary calcium excretion were analysed. Results No statistically significant difference in lumbar spine or femoral BMD and bone turnover markers were found between BD patients and control groups (P > 0.05). Conclusion Although it is difficult to draw definite conclusions because of the limited number of patients involved, our study indicates that bone mineral density and bone turnover markers in Behçet's disease were no different than in healthy subjects.     

Molecular analysis of cutaneous B- and T-cell lymphomas

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor- suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.     

Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro

Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocytes is regulated by interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), cytokines that also have inhibitory effects on hematopoiesis. We investigated Fas antigen expression on human marrow cells and the effects of Fas activation on hematopoiesis in vitro. Freshly isolated immature hematopoietic cells, as defined by the CD34 marker, did not express Fas antigen at levels detectable by fluorescent staining. CD34+ cells, which include progenitors and stem cells, showed low levels of Fas expression in culture, even in the presence of growth factors. Stimulation by TNF alpha and IFN gamma markedly increased Fas antigen expression on CD34+ cells. Anti-Fas antibody, which mimics the action of the putative ligand, enhanced IFN gamma- and TNF alpha-mediated suppression of colony formation by bone marrow (BM) in a dose-dependent manner. This effect did not require the presence of accessory cells. Colony formation from mature (CD34+ CD38+) and immature (CD34+ CD38-) progenitor cells and long-term culture initiating cells were susceptible to the inhibitory action of anti-Fas antibody in the presence of IFN gamma and TNF alpha. Apoptosis assays performed on total BM cells and CD34+ cells showed that anti-Fas antibody induced programmed cell death of CD34+ BM cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Overview on SARS in Asia and the World

Severe Acute Respiratory Syndrome (SARS) is the first major novel infectious disease to hit the international community in the 21st century. It originated in southern China in November 2002, reached Hong Kong in February 2003 and spread rapidly thereafter to 29 countries/regions on five continents. At the end of the epidemic, the global cumulative total was 8098 with 774 deaths. Seven Asian countries/regions were among the top ten on the list. Mainland China and Hong Kong, SAR, accounted for 87% of all cases and 84% of all deaths. Severe acute respiratory syndrome is caused by a novel coronavirus. It has alarmed the world with its infectivity and significant morbidity and mortality, its lack of a rapid, reliable diagnostic test and lack of effective specific treatment and vaccination. The adverse impact on travel and business around the world, particularly in Asia, has been enormous.
Some lessons learnt from this epidemic included: (1) any outbreak of infectious disease can rapidly spread around the world by air travel; (2) early reporting of the outbreak to neighbouring countries/regions and the World Health Organization is essential to prevent international spread; and (3) infection control, tracing and quarantine of contacts are essential to control the epidemic. Many questions remain unanswered, including the origin and pathogenesis of the novel coronavirus, the natural history and the best specific treatment of the disease. The SARS-CoV has probably jumped from an animal host to humans. There is an urgent need to evaluate the human–animal habitat in southern China and to remove animal reservoirs if found.     

Reversal of slow flow phenomenon during primary stenting by bail-out administration of abciximab

BACKGROUND: Slow flow or no reflow phenomenon is increasingly being recognized as a serious problem during coronary angioplasty and stenting. This phenomenon is seen more often during angioplasty in highly thrombogenic milieux, especially in a setting of acute myocardial infarction. The treatment of this complication is often not satisfactory. efficacy of abciximab, a potent antiplatelet drug, in treating slow flow or no reflow phenomenon during primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI). METHODS: Twenty-one instances of persistent slow flow phenomenon were encountered in 131 consecutive patients subjected to primary PTCA for AMI (16%). It was more common in patients presenting with AMI complicated by cardiogenic shock (nine of 21, 43%). Of these 21 cases of slow flow, 10 patients were given injection abciximab during the procedure of primary PTCA as a bail-out measure after encountering the complication of slow flow or no reflow. A predischarge coronary angiography was carried out in all patients who survived. RESULTS: In seven of 10 patients in the abciximab group flow had improved to TIMI-3. In contrast, in the non-abciximab group TIMI flow improved in only four of 11 patients. Patients with persistent slow In this study the authors assessed the flow had significantly higher mortality at the first 30-day follow-up than patients with TIMI-3 flow (33% versus 1.8%, p<0.001). CONCLUSION: In this small nonrandomized study significant improvement in coronary flow was achieved by using intravenous abciximab after observing slow flow or no reflow phenomenon during primary PTCA. More frequent use of this drug in this milieu might help in preventing the development of this complication. Larger studies are warranted to confirm this life-saving beneficial effect of bail-out administration of abciximab during primary angioplasty. (Int J Cardiovasc Intervent 2000; 3:35–39)     

人近端肾小管上皮细胞上表达黏附分子CD146与细胞的增殖生长状态

目的:观察正常人近端肾小管上皮细胞(HK2)是否表达黏附分子CD146,初步探讨CD146与肾小管上皮细胞的关系及其生理意义。方法:实验于2005-05/2006-02在上海交通大学医学院临床检验系实验室完成。①实验材料:人近端肾小管上皮细胞株(HK2,由中国科学院上海生物化学与细胞生物学研究所惠赠)。②实验干预:体外培养的HK2连续观察72h。③实验评估:采用倒置显微镜、光学显微镜下观察肾小管上皮细胞的形态;用反转录-聚合酶链反应方法检测CD146 mRNA的表达;流式细胞仪和免疫荧光法测定CD146蛋白质的表达及其定位;进一步在培养细胞的上清液中检测CD146的可溶性形式(sCD146)。结果:①肾小管上皮细胞的形态学观察和鉴定:传代培养的HK2三四天融合后呈铺路石样铺于培养瓶底,相关抗原检测抗人keratin阳性,抗Ⅷ因子相关抗原阴性。②CD146 mRNA水平的表达:HK2在培养早期(24h)即表达CD146 mRNA(0.092±0.012),但延长细胞的培养时间似乎并没有进一步改变CD146 mRNA的表达水平(0.097±0.005,0.113±0.015,P>0.05)。③CD146蛋白质水平的表达和定位:CD146不仅位于肾小管上皮细胞膜上,而且在细胞核和胞浆中也有表达。体外培养的HK2相互融合时,位于细胞膜上的CD146表达增强,呈线性、持续性地表达于细胞-细胞间的连接部位,同时胞内的CD146标记也相应增强。④细胞上清液中sCD146的检测:HK2上清液中存在CD146的可溶性形式(sCD146)。培养细胞观察24～72h,sCD146水平在48h升高[(18.00±0.80)μg/L],到72h达到高峰[(29.33±1.22)μg/L],与24h[(13.87±0.46)μg/L]比较,差异均有显著性意义(P<0.05)。结论:人近端肾小管上皮细胞组成性地表达CD146,是肾小管上皮细胞新的生物学标志;CD146在细胞内外的表达强度有赖于细胞间联系的建立和细胞增殖的程度,CD146在促进细胞生长和维持组织完整性等方面发挥重要作用。肾小管上皮细胞上清液中存在CD146的可溶性形式,sCD146在一定程度上也反映了细胞的生长和增殖状况。