The BCR gene recombines preferentially with Alu elements in complex BCR- ABL translocations of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR- ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.      

Silicone lymphadenopathy mimicking a lymphoma in a patient with a metatarsophalangeal joint prosthesis

With lymph node enlargement, the possibility of a malignant process such as metastatic carcinoma or lymphoma needs to be excluded. This report describes a 47 year old woman with inguinal lymph node enlargement initially suspicious for lymphoma. Fine needle aspiration findings favoured reactive hyperplasia, but a malignant process could not be excluded. The final histological diagnosis was a foreign body granulomatous inflammatory response as a result of regionally disseminated silicone particles from an over looked metatarsophalangeal joint prosthesis. Because of the large number of joint prostheses world wide, it should be kept in mind that migration of wear particles can create granulomatous inflammation and node enlargement.     

Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomized, controlled trial

In the search for a more potent alternative to a single i.m. injection of methotrexate for ectopic pregnancy, a randomized trial was organized. The efficacy of a combination of methotrexate and mifepristone was compared with methotrexate alone in the treatment of unruptured tubal pregnancies. The diagnosis of an unruptured tubal pregnancy was confirmed laparoscopically in 50 patients during a 2 year period. Women were randomized to receive a single i.m. injection of 50 mg/m2 methotrexate alone or a single dose of 600 mg oral mifepristone in combination with the same dose of methotrexate. Both treatment protocols were successful in achieving the resolution of unruptured ectopic pregnancy (18/25 in the methotrexate group and 22/25 in the combination group) following the initial intervention. A second injection was needed in four (16%) cases in the methotrexate group and in one (4%) case in the combination group. Overall, a complete resolution was achieved in 22/25 and 23/25 cases respectively. Unruptured ectopic pregnancy resolved faster in women given the combination of methotrexate and mifepristone compared to women given methotrexate only (P = 0.01). The effect of the methotrexate and mifepristone combination was more pronounced in women with higher human chorionic gonadotrophin concentrations.      

吸入性急性氯气中毒71例

1临床资料1994-08/2004-07两次氯气泄漏事故造成吸入性急性氯气中毒123例,其中资料完整的71(男34,女37)例,年龄15～84(平均35.4)岁.临床表现有:鼻咽不适、流涕、喉中灼热、声哑、呛咳、咯痰、胸闷、气急、呼吸喘促及窒息窘迫感;眼酸流泪、睁眼困难;吞咽不畅、恶心呕吐、食欲不振;头晕、心悸、全身无力及睡眠不安;结膜充血、咽部红肿、呼吸增速和心跳加快.肺部可闻及一过性干罗音和一侧或双侧肺底湿鸣等.以急性中毒性呼吸炎症为主要表现57例,急性中毒性肺炎14例.WBC升高16例.患者肺部X线普遍透光性降低,肺纹理增粗增多模糊15例,肺底湿鸣患者肺野中下部偏外侧有斑片密度增高的模糊阴影14例.     

Coarctation of the aorta in Kabuki syndrome

The incidence of congenital heart defects in patients with Kabuki syndrome is estimated to be about 30%. To date, no specific type of heart malformation is known to be associated with the syndrome. A further 20 unselected children with Kabuki syndrome are presented. The incidence of heart abnormalities in these children is almost twice that previously reported (55%) and juxta-ductal coarctation occurs with a frequency of 25%.     

Saliva and inhibition of HIV-1 infection: molecular mechanisms

Oral fluids are rarely a vehicle for HIV-1 infection in vivo , unlike other mucosal secretions. This unique property raises questions regarding (1) the molecular mechanisms responsible for the lack of salivary transmission, (2) the extent to which oral immunological responses mirror responses at other mucosal sites, (3) the use of promising salivary markers of HIV-1 disease progression, (4) the relationship between oral and blood viral loads, (5) cofactors that influence oro-genital transmission, and (6) the feasibility of oral-based antibody testing for HIV-1 diagnosis in the home. This paper discusses these questions and provides background summaries, findings from new studies, consensus opinions, practical relevance to developing countries, and suggestions for future research agenda on each of the key topics.     

Case control and family-based studies of tryptophan hydroxylase gene A218C polymorphism and suicidality in adolescents.

The association of suicidality with polymorphism A218C in intron 7 of tryptophan hydroxylase (TPH) gene remains controversial. The aim of this study was to use family-based methods to examine this association in adolescents in order to eliminate the difficulty of sampling a control group from the same ethnic population. Eighty-eight inpatient adolescents who recently attempted suicide were assessed by structured interview for detailed clinical history, diagnoses, suicide intent, suicide risk, impulsivity, aggression, and depression. DNA samples were collected from all subjects, from both biological parents of 40 subjects and from one parent of 9 subjects; TPH allele frequencies were calculated and tested for association to phenotype, stratified by severity, using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods (n = 49). The frequencies were also compared for all the Jewish subjects (n = 84) to the known frequencies of these alleles in healthy Jewish populations. There was no significant allelic association of A218C polymorphism with suicidal behavior or other phenotypic measures according to the HRR method (chi-square = 0.094; P = 0.76), the TDT (chi-square = 0.258; P = 0.61), or association analysis to known population frequencies (chi-square = 1.667, P = 0.19 for Ashkenazi, and chi-square = 0.810, P = 0.37 for non-Ashkenazi). Analysis of variance with the Scheffè test demonstrated a significant difference between CC and AA genotypes in suicide risk and depression among the patients (n = 88). The findings suggest that polymorphism A218C has no major relevance to the pathogenesis of adolescent suicidal behavior, but may have a subtle effect on some related phenotypes.     

建立胫骨癌痛模型的理论与实践

目的:骨癌痛动物模型已有报道,但还没有可接受的与人类骨癌痛相一致的模型。综述胫骨癌痛模型的研究进展及相关治疗前景。资料来源:应用计算机检索Medline1996-01/2006-03相关胫骨、癌痛和治疗的文献,检索词“tibial,cancerpain,therapy”,并限定文献语言种类为English。同时检索万方数据库1996-01/2006-05文献,检索词为“胫骨癌痛”,并限定语言种类为中文。资料选择:对资料进行初审,选取包括胫骨、癌痛和治疗的文献,开始查找全文。纳入标准:①胫骨和癌痛。②癌痛和治疗。排除标准:综述文献、重复研究、Meta分析类文章。资料提炼:共收集到51篇关于胫骨、癌痛和治疗的文献,纳入30篇关于胫骨和癌痛,癌痛和治疗的文献。资料综合:①目前认为,胫骨癌痛动物模型的疼痛表现与临床上所见的骨转移症状相似,可视为转移性骨癌痛模型。②恶性肿瘤骨损害的特征性变化是溶骨性骨吸收和恶性肿瘤疼痛本身,随骨质破坏的加剧,疼痛逐渐增强,移动或轻触可以引发急性痛,在到达极度痛之前,常因运动、负重或自发地间断发生突破痛,其发生的程度和频率与骨质破坏和溶骨活性成正相关。③目前从胫骨癌痛的实验研究中发现可供选择的药物主要有阿片类药、5-羟色胺受体阻断剂、抗惊厥药物加巴喷丁、环氧化酶2抑制剂表皮生长因子阻断剂。结论:利用动物胫骨癌痛模型来研究人类骨癌痛是可行的,但其研究有待进一步深入。从胫骨癌痛的实验研究中发现有许多药物可供选择,这展示了药物治疗骨癌痛的应用前景。