^1H磁共振波谱在大鼠C6脑胶质瘤致痫性评估中的应用

目的:1H磁共振波谱是研究活体脑组织及肿瘤组织代谢与生化指标测定的非侵袭技术,实验通过对种植C6脑胶质瘤大鼠的1H磁共振波谱在体观察,为非侵袭性评价肿瘤的致痫性提供帮助。方法:实验于2007-03/07在中国医科大学附属盛京医院中心实验室完成。①分组处理:选用雌性近交系Wistar大鼠共40只,随机分为实验组和对照组两组各20只。实验组制作C6脑胶质瘤移植动物模型,根据皮质脑电图记录结果确定癫痫发作,并将其分为致痫组与非致痫组;对照组在相同部位注射等量Ham'sF-12培养液。②观察指标:所有大鼠取出内置皮质电极后行1H磁共振波谱检查。分别选择肿瘤周围区及肿瘤实质区作为感兴趣区对每一体积元进行化学位移成像。所测定的主要代谢产物包括N-乙酰基天门冬氨酸、肌酸、胆碱、乳酸/脂质、谷氨酸及γ-氨基丁酸。以肌酸为参照波峰,分别计算各代谢产物与肌酸波的积分面积进行比较。结果:32只大鼠纳入结果分析。①实验组大鼠C6脑胶质瘤肿瘤实质区及肿瘤周围区胆碱及脂质波峰高于对照组(P<0.01,0.05);而肿瘤实质区N-乙酰基天门冬氨酸及谷氨酸波峰高于对照组(P<0.05)。②C6脑胶质瘤致痫组肿瘤周围区谷氨酸波峰高于非致痫组(P<0.01);而γ-氨基丁酸波峰低于非致痫组(P<0.01)。同时,肿瘤周围区乳酸/肌酸两组间比较差异也具有统计学意义(P<0.05)。结论:①1H磁共振波谱检查可为脑胶质瘤的恶性程度及其侵袭性的活体判定提供依据。②通过活体监测肿瘤周围皮质谷氨酸与γ-氨基丁酸二者含量的变化,也可为非侵袭性评价肿瘤的致痫性提供帮助。     

Cytokines in Sjögren's syndrome

Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the current knowledge of the expression and the function of pro- and anti-inflammatory cytokines both locally and systemically in Sjögren's syndrome patients. In the salivary glands, saliva and serum of these patients, many pro-inflammatory cytokines are upregulated. Concomitantly, most anti-inflammatory cytokines are not detectable or are expressed at low levels. Besides a role in inflammation, cytokines are also thought to be involved in salivary gland dysfunction by directly interfering with the epithelial cells in the glands. Future research on the role of novel cytokines in Sjögren's syndrome in combination with a better understanding of the effect of cytokines on exocrine dysfunction will aide the identification of the best therapeutic targets for Sjögren's syndrome.     

Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow

We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2- 23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.     

Immunoglobulin D myeloma and amyloidosis: immunochemical and structural studies of Bence Jones and amyloid fibrillar proteins

Urinary Bence Jones protein and amyloid fibril protein isolated from the subcutaneous tissue of a patient with IgD myeloma and associated amyloidosis were subjected to physicochemical and immunochemical identification. Peptide maps and amino-terminal tetrapeptide composition obtained from the two proteins were comparable. Immunochemical cross-reactivity between the two proteins, with other lambda-type amyloid and Bence Jones proteins, and with a serum component was demonstrated. The results suggest that the source of the amyloid fibril protein is an intact circulating light polypeptide chain as well as smaller amino-terminal fragments.     

An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection

The gene for the most common and severe form of autosomal dominant polycystic kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to result in an integral membrane protein of 4302 amino acids. The major challenge faced by researchers attempting to complete mutation analysis of the PKD1 gene has been the presence of several homologous loci also located on chromosome 16. Because the sequence of PKD1 and its homologs is nearly identical in the 5' region of the gene, most traditional approaches to mutation analysis cannot distinguish sequence variants occurring uniquely in PKD1. Therefore, only a small number of mutations have been identified to date and these have all been found in the 3', unique portion of the gene. In order to begin analysis of the duplicated region of PKD1, we have devised a novel strategy that depends on long-range PCR and a single gene-specific primer from the unique region of the gene to amplify a PKD1-specific template that spans exons 23-34. This 10 kb template, amplified from genomic DNA, can be employed for mutation analysis using a wide variety of sequence- based approaches. We have used our long-range PCR strategy to begin screening for sequence variants with heteroduplex analysis, and several affected individuals were discovered to have clusters of base pair substitutions in exons 23 and 25. In two patients, these changes, identified in exon 23, would be predicted to result in multiple amino acid substitutions in a short stretch of the protein. This clustering of base pair substitutions is unusual and suggests that mutation may result from unique structural features of the PKD1 gene.      

近红外光谱技术在元胡止痛散定量分析中的初步应用研究

目的为元胡止痛散建立一种快速有效的定量分析方法,并为将近红外光谱分析技术应用于中药的定量分析提供指导。方法按处方配制25个模拟样本,随机挑选18个组成训练集,另外7个组成预示集,采集各样本的近红外光谱数据,用BP神经网络和PIS法对数据进行处理,并实际分析了三批样品。结果模拟样本中,对于元胡,采用BP网络和PLS法,平均相对预示误差分别为1．5％,2．5％,对于白芷,平均相对预示误差分另为2．9％,4．4％,对于实际样本,各组分标示量的百分含量都在95％～105％之间。结论近红外光谱结合BP神经网络或PLS应用于元胡止痛散的定量分析是可行和有效的。     

Spontaneous growth in idiopathic short stature. European Study Group

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.