Diagnosis of Kala-Azar by Nested PCR Based on Amplification of the Leishmania Mini-Exon Gene

To diagnose visceral leishmaniasis (kala-azar), we have developed a nested PCR method based on amplification of the mini-exon gene, which is unique and tandomly repeated in the Leishmania genome. Nested PCR was sufficiently sensitive for the detection of DNA in an amount equivalent to a single Leishmania parasite or less. We examined the usefulness of this PCR method using bone marrow aspirates and buffy coat cells collected from kala-azar patients who had or had not received chemotherapy in northwest China. We obtained PCR positivity for all of the parasitologically positive bone marrow samples from the patients. Some ambiguities with the primary PCR results were eliminated by the subsequent nested PCR. The buffy coat samples from 7 of 12 patients with splenomegaly were positive by the nested PCR, although only 2 of them were positive for parasites by culture. However, buffy coat samples from nine children, whose splenomegaly has been reduced and clinically cured by antimony treatment, were all negative. Thus, this nested PCR method represents a new tool for the diagnosis of kala-azar with patient blood samples instead of bone marrow or spleen aspirates obtained by more invasive procedures.     

Stress analysis between implant prostheses with different moduli and surrounding bones北大核心

背景:应力遮挡效应会导致植入假体修复骨缺损手术失败,其主要原因是由于植入假体的弹性模量大于骨组织弹性模量。目的:分析植入假体弹性模量对应力分布的影响,寻求消除应力遮挡现象的方法。方法:通过CT扫描的方式获取实验犬与人体骨组织的模型,分别对其优化后进行梯度赋值,建立较为可靠的骨骼力学模型,并与植入假体组合后进行有限元仿真。首先,通过对比格犬骨骼模型和人体骨骼模型及其对应的植入假体进行有限元仿真,模拟了不同弹性模量对植入假体修复术后的应力和位移分布情况;其次,分析了较小弹性模量差仍会形成应力遮挡现象的原因,建立了骨骼模型及植入假体模型,确立了材料属性赋予方法;最后,验证了该模型及材料属性赋予方法的可行性,并通过随机选取受力点的方式,定量分析植入假体弹性模量与骨骼弹性模量之间的关系对应力遮挡形成的影响。结果与结论:通过梯度赋值法建立与骨骼力学性质更加接近的实验犬骨骼模型和人体骨骼模型,该方法重建的力学模型与真实骨骼的力学性质更为接近;通过有限元仿真力学测试证明,不同弹性模量植入假体对假体本身与周围骨骼间相对位移的影响较小;另外量化弹性模量对假体植入骨骼后对应力分布的影响,可为后续的相关研究提供帮助。     

Fast Dipstick Dye Immunoassay for Detection of Immunoglobulin G (IgG) and IgM Antibodies of Human Toxoplasmosis

A dipstick dye immunoassay (DDIA) was developed to detect immunoglobulin G (IgG) or IgM antibodies of toxoplasmosis infection in humans. The assays employ a blue colloidal dye particles (D-1) conjugated to sheep anti-human IgG and rabbit anti-human IgM as the visualizing agents and a soluble antigen of tachyzoites of Toxoplasma gondii strain RH (TSA) as the detective antigen. The mixture of dye-labeled anti-human antibody-special human antibody was captured by TSA onto a nitrocellulose membrane dipstick by means of immunochromatography. The assays are rapid (the whole test can be completed within 15 min), simple, and cheap, and they don't require any equipment. They are sensitive and specific for the detection of anti-Toxoplasma IgG or IgM antibodies and generally agree closely with the results from the enzyme-linked immunosorbent assay. The assays are especially suitable for field applications.     

Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.     

Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b)

The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.     

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.     

Arthrobacter scleromae sp. nov. isolated from human clinical specimens

A gram-positive, coryneform bacterium was isolated from swollen scleromata of a dermatosis patient. An analysis of its phenotypic, chemotaxonomic, and genotypic characteristics showed that this bacterium is closely associated with Arthrobacter oxydans and Arthrobacter polychromogenes but that it belongs to a distinct species, for which the name Arthrobacter scleromae sp. nov. is proposed.     

Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma

AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.     

抑郁障碍患者与家属家庭亲密度适应性和情绪状况的研究

目的探讨抑郁障碍患者与家属的家庭亲密度适应性和情绪状况,为抑郁障碍患者的健康教育及家庭干预提供科学有效的理论依据。方法选择2006年6～9月在北京大学第六医院就诊的抑郁障碍患者95例及共同陪伴的直系家属95例为调查对象。采用家庭亲密度和适应性量表中文版(FACES-CV)、Zung氏焦虑自评量表和Zung氏抑郁自评量表。结果1患者的家庭亲密度得分与国内常模一致(P>0.05),但适应性得分低于国内常模(P<0.01);焦虑、抑郁得分高于国内常模(P<0.01)。家属的家庭亲密度得分高于国内常模(P<0.01),适应性得分低于国内常模(P<0.01)。家属的焦虑得分与国内常模一致(P>0.05),但抑郁得分高于国内常模(P<0.05)。2家庭模式分型构成比:中间型47.9%,平衡性26.3%,极端型25.8%。患者的家庭"拱极模式"以"僵硬—松散型"居多,家属则以"自由—缠结型"居多。3家庭亲密度与患者的家属的文程化度有关,相关系数范围(r=0.21～0.26,P<0.05)、与家庭人数呈负相关(r=-0.21,P<0.01);与患者及家属的焦虑、抑郁情绪呈显著负相关,相关系数范围(r=-0.30～0.37,P<0.01);家庭适应性与患者的年龄(r=0.28,P<0.01)、文化程度(r=0.34,P<0.01)有关。与家属的年龄(r=0.26,P<0.05)文化程度(r=0.22,P<0.05)有关。与患者和家属的焦虑、抑郁情绪呈显著负相关,相关系数范围(r=-0.30～-0.42,P<0.01)。结论家庭亲密度适应性与患者和家属的文化程度、焦虑、抑郁情绪有关,家庭亲密度与患者的家庭人数有关,家庭适应性与患者和家属的年龄有关。