活动性结核标志物'H-多肽的实验与临床研究

本题研究是经免疫学途径直接检测人体感染结核菌的情况，为现代结核病的实验诊断、临床监测、流行病调查提供了一个全新的检验指标。作者首先发现了一种仅存在于活动性结核病患者体液中的蛋白成份—活动性结核标志物（ＡｃｔｉｖｅＴｕｂｅｒｃｕｌｏｓｉｓＭａｒｋ—ＡＴＭ）１Ｈ—多肽；并为之创立了独特的检测方法，经四年多临床１９４６０例样本调查中确定了ＡＴＭ的临床价值。将ＡＴＭ检测与ＯＴ皮试、酶联免疫ＥＬＩＳＡ、ＤＮＡ探针、ＰＣＲ基因扩增技术及典型病例组患者行Ｘ线计算机断层摄影（ＣＴ）、磁共振像（ＭＲＩ）等多组对比试验中，实验与临床研究资料分析证明：ＡＴＭ检测的总敏感度为８６．０６％、特异度９６．２４％、准确度９３．４５％、诊断效率为８２．８２％、批内ＣＶ１．２％、批间ＣＶ２．０％、Ｐ＜０．０５。经ＮＭＲ光谱分析结构含有ＣＣＨ２官能团。     

ATM网络的差错检测和纠正

ATM（异步传送方式Asynchronous Transfer Mode)是一种网络数据传送技术,ATM的设计基于光纤网络,由于光纤传输的比特差错率非常低,因此ATM网的差错检测和纠正与CRC（循环冗余检验）不同,本文讨论ATM网的差错检测和纠正。     

手部肌腱吻合术后康复

目的作者自2000年初至2004年7月进行手部肌腱吻合120例,随访120例,手部肌腱吻合术后进行程序化的康复训练,方法肌腱吻合法均采用3-0或4-0聚丙烯单针缝线、改良的Bunnell、Kessler和肌腱编制缝合法,患者肌腱均为I期手术吻合,术后伤口I/乙愈合105例、II/乙15例,手部肌腱吻合术后均采用程序化的康复训练, 结果对手部肌腱吻合术后的患者进行程序化的康复训练,取得良好的效果. 结论本康复训练程序目前已逐渐形成我院的治疗常规,并逐步推广和普及.     

Absence of ATM truncations in patients with severe acute radiation reactions

Purpose: Severe acute toxicity limits the effective use of radiotherapy in patients who are radiosensitive, and it is not usually possible to identify these radiohypersensitive (R-H) individuals before treatment commences. Five such R-H patients were detected over a 3-year period. We undertook this study to determine whether the severe acute radiohypersensitivity of these five individuals showed any correlation with cellular and molecular parameters known to be abnormal in radiosensitivity-related syndromes such as ataxia–telangiectasia (A-T).

Methods and Materials: Lymphoblastoid cells were isolated from fresh blood from the 5 R-H individuals who had previously demonstrated clinical R-H at least 9 months prior to sampling. Lymphoblastoid cell lines (LCLs) were established to determine the extent of postradiation chromosomal aberrations, cell cycle delay, cell proliferation, and tumor suppressor p53 protein stabilization. The polymerase chain reaction (PCR) and protein truncation (PTT) assays were used to test for the possibility of mutations in the gene mutated in A-T, termed ATM.

Results: LCLs derived from R-H subjects retained a significantly higher degree of radiation-induced chromosomal aberrations when compared to normal control LCLs. p53 stabilization by ionizing radiation appeared normal in all but one R-H subject. There was no evidence of A-T gene truncation mutations in any of the R-H subjects tested.

Conclusions: All R-H subjects in this study had their cellular radiosensitivity confirmed by the chromosomal aberration assay. Delayed p53 stabilization at 4 hours postirradiation in one R-H subject suggested that different etiologies may apply in the radiohypersensitivity investigated in this study.     

The RETAIN project: dicom teleradiology over an ATM-based network

The RETAIN project (Radiological Examinations Transfer on an ATM Integrated Network) has aimed at testing videoconferencing and DICOM image transfers to get advice about difficult radiological cases over an asynchronous transfer mode (ATM)-based network, which affords a more comfortable interface than narrow-band networks and allows exchange of complete image series using the DICOM format of studies. For this purpose, an experimental ATM network was applied between six university hospitals in four different countries. An assessment of the functionalities of the system was performed by means of log-file analysis, video recording of the sessions and forms filled out by the participants at the end of each session. Questionnaires were answered by the users at the end of the project to bring out perspectives of utilisation and added value. We discussed 43 cases during 20 sessions. For technical or organisational problems, only 20 of the 36 planned sessions took place. The throughput over ATM (10.5 Mbit/s, 20 times faster than six ISDN B-channels) was adequate. Despite the experimental configuration of the network, the system was considered as satisfactory by all the physicians. In 72 % of the sessions, the expected result (answer to the question) was gained. By common consent, videoconferencing was unanimously regarded as a prominent tool in improving the interaction quality. Asynchronous transfer mode is an efficient method for fast transferring of radiologic examinations in DICOM format and for discussing them through high-quality videoconferencing. Received: 26 October 1998; Revised: 25 February 1999; Accepted: 2 April 1999     

Responding to DNA double strand breaks in the nervous system

Within the nervous system appropriate responses to DNA damage are required to maintain homeostasis and prevent disease. In this tissue, DNA double-strand breaks (DSBs) initiate a molecular response to repair DNA, or in many cases, activate apoptosis. The repair of DNA DSBs occurs via nonhomologous end-joining (NHEJ) or homologous recombination (HR). These mechanistically distinct pathways are critical for maintenance of genomic integrity. During nervous system development there are discrete requirements for each DNA DSB repair pathway at different stages of development. For example, in the nervous system HR is particularly important for proliferating cells, while NHEJ is critical for differentiating cells. Inactivation of either of these pathways can lead to embryonic lethality, neurodegeneration or brain tumors. Human syndromes that result from defective responses to DNA damage often feature overt neuropathology. A prime example is the neurodegenerative syndrome ataxia telangiectasia (A-T), which results from inactivation of the ATM kinase, a crucial nexus for the cellular response to DNA DSBs. This type of DNA damage activates ATM via the Mre11-Rad50-NBS1 (MRN) complex, which leads to selective phosphorylation of ATM substrates resulting in apoptosis or cell cycle arrest and DNA repair. Furthermore, DNA DSBs resulting from chronic genotoxic stress can also result in tumorigenesis, as inactivation of either HR or NHEJ can lead to certain types of brain tumors. Thus, there are distinct requirements for each DNA DSB repair pathway during neural development, which have important implications for understanding diseases of the nervous system.     

DNA damage responses in neural cells: Focus on the telomere

Postmitotic neurons must survive for the entire life of the organism and be able to respond adaptively to adverse conditions of oxidative and genotoxic stress. Unrepaired DNA damage can trigger apoptosis of neurons which is typically mediated by the ataxia telangiectasia mutated (ATM)-p53 pathway. As in all mammalian cells, telomeres in neurons consist of TTAGGG DNA repeats and several associated proteins that form a nucleoprotein complex that prevents chromosome ends from being recognized as double strand breaks. Proteins that stabilize telomeres include TRF1 and TRF2, and proteins known to play important roles in DNA damage responses and DNA repair including ATM, Werner and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). We have been performing studies of developing and adult neurons aimed at understanding the effects of global and telomere-directed DNA damage responses in neuronal plasticity and survival in the contexts of aging and neurodegenerative disorders. Deficits in specific DNA repair proteins, including DNA-PKcs and uracil DNA glycosylase (UDG), render neurons vulnerable to adverse conditions of relevance to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and stroke. Similarly, early postmitotic neurons with reduced telomerase activity exhibit accentuated responses to DNA damage and are prone to apoptosis demonstrating a pivotal role for telomere maintenance in both mitotic cells and postmitotic neurons. Our recent findings suggest key roles for TRF2 in regulating the differentiation and survival of neurons. TRF2 affects cell survival and differentiation by modulating DNA damage pathways, and gene expression. A better understanding of the molecular mechanisms by which neurons respond to global and telomere-specific DNA damage may reveal novel strategies for prevention and treatment of neurodegenerative disorders. Indeed, work in this and other laboratories has shown that dietary folic acid can protect neurons against Alzheimer's disease by keeping homocysteine levels low and thereby minimizing the misincorporation of uracil into DNA in neurons.