DNA错配修复基因甲基化在肝细胞癌发生发展中的作用

目的探讨DNA错配修复基因(MMR)hMLH1,hMSH2和hMSH3甲基化在肝细胞癌(HCC)发生发展中的作用。方法采用甲基化特异性聚合酶链反应(MSP)法对38例新鲜HCC组织,相应非肿瘤肝组织,2例正常的捐肝组织及6种肝癌细胞系的hMLH1,hMSH2和hMSH3基因启动子CpG岛甲基化进行检测;培养6种肝癌细胞系,MSP法检测加入5-aza-2‘-deoxycytidine前后hMSH2基因在HCC中的甲基化状态改变;逆转录．聚合酶链反应(RT-PCR)方法检测加入5-aza-2’-deoxycytidine前后hMSH2在肝癌细胞株中的mRNA表达改变。结果HCC标本中13．2％(5／38)发生了hMLH1启动子甲基化,68．4％(26／38)发生了hMSH2启动子甲基化;相应的非肿瘤肝组织中hMLH1,hMSH2启动子甲基化阳性率分别为2．6％(1／38),55．3％(21／38);2例正常肝组织中未发现甲基化;6株肝癌细胞系中有5株发生了hMSH2启动子甲基化,而未发现有MLH1启动子甲基化。所有标本中均未发现有hMSH3启动子甲基化。5-aza-2‘-deoxycytidine处理细胞株后,可部分或完全逆转hMSH2启动子甲基化,各细胞株的mRNA均有不同程度的表达增加。结论hMSH3基因启动子CpG岛甲基化与HCC的发生发展关系不大。hMSH2基因甲基化与mRNA表达密切相关,是基因表达调节的一种重要方式。hMLH1和hMSH2基因启动子CpG岛的高甲基化在HCC中是一个常见的基因改变,DNA错配修复基因尤其是hMSH2基因启动子甲基化在HCC的发生中起了重要作用,是早期事件,其可能为临床诊断HCC提供新的检测指标。     

Immunotactoid glomerulopathy with fingerprint immune deposits

Summary Immunotactoid glomerulopathy is a distinct clinico-pathological entity which has recently been defined. The term immunotactoid refers to highly organized immune depositions appearing as rod-like microtubular structures in ultrastructural examination. We describe a patient with mixed connective tissue disease who demonstrates characteristic features of immunotactoid glomerulopathy. The diagnosis was made after excluding amyloidosis, cryoglobulinaemia and lupus nephritis. In addition to immunotactoid microtubules, ultrastructural examination also demonstrated presence of fingerprint depositions which were intimately mixed with immunotactoid structures. Fingerprint deposits have been described in lupus nephritis and cryoglobulin-related nephropathy, but rarely in other glomerulonephritis. These unique findings in our patient may suggest a previously unsuspected relationship between the syndrome of immunotactoid glomerulopathy and systemic lupus erythematosus.     

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study

Objectives

Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.

A genipin-crosslinked gelatin membrane as wound-dressing material: in vitro and in vivo studies

A naturally occurring crosslinking agent (genipin) was used in this study to crosslink gelatin hydrogel to develop a wound-dressing membrane. The study was to investigate the in vitro characteristics of the genipin-crosslinked gelatin membrane. The glutaraldehyde-crosslinked counterpart, at a similar crosslinking degree, was used as control. Additionally, an in vivo experiment was undertaken to study the wound healings covered with the glutaraldehyde- and genipin-crosslinked dressings in a rat model. The in vitro results obtained suggested that crosslinking of gelatin membranes with glutaraldehyde or genipin may produce distinct crosslinking structures. The differences in crosslinking structure can significantly affect the mechanical property, water-vapor-transmission rate, swelling ratio, degradation against enzyme and cellular compatibility of the crosslinked membranes. In the in vivo study, it was found that the degree of inflammatory reaction for the wound treated with the genipin-crosslinked dressing was significantly less severe than that covered with the glutaraldehyde-crosslinked dressing throughout the entire course of the study. Additionally, the healing rate for the wound treated with the genipin-crosslinked dressing was notably faster than its glutaraldehyde-crosslinked counterpart.     

Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.     

Influence of interaction force levels on degree of motor adaptation in a stable dynamic force field

Studies have shown that the point-to-point reaching movements of subjects seated in a dark, rotating room demonstrate errors in movement trajectories and endpoints, consistent with the direction of the Coriolis force perturbations created by room rotation. Adaptation of successive reaches and the presence of postrotation aftereffects have indicated that subjects form internal models of the Coriolis field dynamics in order to make appropriate movement corrections. It has been argued that these findings are inconsistent with predictions of peripheral stabilization assumed in equilibrium-point models of motor control. A possibility that has been raised, however, is that the Coriolis field findings may in fact stem from changes in control commands elicited due to the magnitude and destabilizing nature of the Coriolis perturbations. That is, it has been suggested that a perturbation threshold exists, below which central reactions are not necessary in order to maintain movement stability. We tested the existence of a perturbation threshold in normal-speed reaching movements. Twelve normal human subjects performed non-visually guided reaching movements while grasping a robotic manipulandum. The endpoints and trajectory deviations of their movements were measured before, during, and after a position-dependent force field (similar to a Coriolis field in terms of the time history of applied forces) was applied to their movements. We examined the responses to a range of perturbation field strengths from small to considerable. Our experimental results demonstrated a substantial adaptation response over the entire range of perturbation field magnitudes examined. Neither the amount of adaptation after 5 trials nor after 25 trials was found to change as disturbance magnitudes decreased. These findings indicate that there is an adaptive response even for small perturbations; i.e., threshold behavior was not found. This result contradicts the assertion that peripheral stabilization mechanisms enable the central controller to ignore small details of peripheral or environmental dynamics. Our findings instead point to a central dynamic modeler that is both highly sensitive and continually active. The results of our study also showed that subjects were able to maintain baseline pointing accuracies despite exposure to perturbation forces of sizeable magnitude (more than 7 N).     

New HLA-A*11 allele,A*1112, identified by sequence-based typing

In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).     

Changes in HIV-1 incidence in heroin users in Guangxi Province, China

Guangxi Province, China recently experienced an outbreak of HIV-1 infection among heroin users. We studied HIV-1 incidence rates and associated risk factors for HIV-1 infection among heroin users residing in Pingxiang City. A total of 318 heroin users were followed from February 1998 through January 1999 (median follow-up: 8.1 months). Of these, 130 were prospectively followed from January through September 1999 (median follow-up: 8.3 months). HIV-1 and hepatitis C virus (HCV) incidence rates for each period were calculated. A generalized estimating equation approach was implemented to identify independent risk factors associated with HIV-1 infection across both periods. Among 318 study participants, 97.2% were men. The median age was 22 years. Approximately 60% reported sharing needles. HIV-1 prevalence at baseline was 15.4%. During the first follow-up period, HIV-1 incidence was 2.38 per 100 person years (py), and HCV incidence was 26.8 per 100 py. During the second follow-up period, HIV-1 incidence was 6.86 per 100 py, and HCV incidence was 28.9 per 100 py. After controlling for age and other factors, HCV seropositivity, history of sexually transmitted diseases, and sharing needles were independently associated with HIV-1 infection. These data suggest that HIV-1 incidence was rising over time in Pingxiang City, Guangxi Province. The high incidence of HCV heightens the importance of enhanced prevention programs to reduce injection and needle sharing among heroin users.     

Electrophysiological neurodifferentiation of subventricular zone-derived precursor cells following stroke

Stroke in rodents is associated with increased neurogenesis and the migration of newborn neurons to sites of brain ischemia, where they may participate in repair and recovery. To determine if neurogenesis following stroke yields functional new neurons, we labeled neuronal precursors in the mouse subventricular zone (SVZ) with a lentivirus-green fluorescent protein vector, produced stroke by occluding the middle cerebral artery, and detected newborn neurons 8 weeks later by fluorescence microscopy. Patch-clamp studies on fluorescent neurons in the cortical region surrounding infarction showed tetrodotoxin-sensitive Na⁺ action potentials and spontaneous excitatory post-synaptic currents, suggesting that ischemia led to functional neurogenesis with synaptic integration. These findings support the hypothesis that enhancing endogenous neurogenesis after stroke might have therapeutic benefit.     

肢端黏液样炎性纤维母细胞肉瘤2例及文献复习

目的探讨肢端黏液样炎性纤维母细胞肉瘤的临床病理学特征及鉴别诊断。方法对2例发生在下肢末端的黏液样炎性纤维母细胞肉瘤进行光镜观察和免疫组化标记，并复习文献。结果2例发生在下肢末端的病程较长的渐进性肿块，术后局部复发。镜检：病变呈多结节状，边界不清；黏液样基质中见数量不等的各类炎细胞浸润，散在或灶性分布梭形、奇异形和多空泡状脂肪母细胞样3种形态的瘤细胞。免疫表型：肿瘤细胞Vim弥漫阳性，CD68和CD34灶性阳性，CK、SMA、HHF-35、S-100蛋白、CD45、CD45R0、CD15、CD30均阴性。结论此病病程较长，术后易局部复发，是一种低度恶性的肿瘤。鉴于病变黏液样基质及各类炎细胞浸润的背景较为突出，而特征性的瘤细胞稀疏，应注意与炎症性病变或具有相似组织形态的良性或恶性肿瘤鉴别。