抗大肠癌噬菌体人单链抗体的初步鉴定及序列分析

目的 :对抗大肠癌细胞的单克隆噬菌体单链抗体进行初步鉴定和测序分析。方法 :采用细胞ELISA ,免疫组化 ,DNA序列测定和计算机分析方法 ,对 5个单克隆噬菌体抗体 (CH2 73,CH2 0 5 ,CH2 0 9,CHA12 ,CH72 3)进行初步鉴定和序列分析。结果 :5个抗体均对人大肠癌细胞、人胚肾上皮细胞和其它某些人肿瘤细胞反应 ,也与人正常肝细胞有弱阳性反应 ,但不与鼠源性的癌细胞和正常细胞反应。细胞免疫组化进一步证实了ELISA结果的正确性。大肠癌免疫组化对大肠癌组织有特异性的结合反应 ,而不与正常大肠组织反应。测序结果为CH2 73ScFv全长 732bp ;V ,D ,J分别属于VH3 30 D1 2 6 JH3 linker V1 13 JL2 ,GenBank序号为AY0 2 8777和AY0 2 8996 ;CH2 0 5全长 36 6bp ,V ,D ,J分别VH1 4 6 D6 13 JH3,GenBank序号为AF35 936 5 ;CH2 0 9,CHA12和CH72 3的ScFv基因完全相同 ,全长 72 3bp ,其VH DH JH与CH2 73ScFv基因中的VH DH JH 完全一致 ,V ,D ,J分别属于VH3 30 D1 2 6 JH3 linker L2 Jκ2 ,GenBank序号为AF36 3774。结论 :噬菌体抗体具有结合人大肠癌组织和细胞的活性 ,为进一步开发临床应用人源抗肿瘤抗体和小分子抗体片段奠定基础     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Differentiation of Helicobacter pylori isolates by polymerase chain reaction—restriction fragment length polymorphism

Objective: To investigate the association between the diversity of urease gene and urease activity of clinical isolates of Helicobacter pylori (H. pylori). Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of urease gene and rapid urease activity test were used to study the urease activity of different clinical isolates of H. pylori. Results: H. pylori clinical isolates were divided into 4 types according to their PCR-RFLP results of urease gene and urease activity. Type Ⅰ , possessing strong urease activity (0. 11) and presented 1 fragment of 1. 7 kb by PCR-RFLP, had close relations with gastric ulcer; type Ⅱ , with the weakest urease activity (0. 07) and 2 fragments (1. 3 and 0. 4 kb respectively) , was associated with duodenal bulb ulcer; type Ⅲ , with the strongest urease activity (0. 12) and 2 fragments (0. 4 and 0. 17 kb) with or without 1 fragment (0. 23 or 0. 37 kb) , was responsible for gastritis; type Ⅳ , with weak urease activity (0. 09) and 2 fragments     

Prediction of steady-state bioequivalence relationships using single dose data I-linear kinetics

Simulated data using a linear one- and two-compartment body model with different absorption characteristics were used to evaluate the ability of single dose bioavailability data to predict the relationships that exist at steady state. This was done by comparing the confidence intervals obtained from single and multiple dose data sets for the parameters of Tmax, Cmax, and area under the curve from time zero to infinity (AUC0-infinity). As a consequence of Tmax and Cmax decreasing and increasing from single to multiple dosing regimens, the confidence intervals for these parameters reflected these changes. The 90 per cent confidence interval expressed as a percentage of the reference mean increased or decreased for Tmax dependent upon the ratio of Ka test/Ka reference, and decreased for Cmax while the interval for AUC0-infinity exhibited no predictable pattern and appeared to be influenced by the amount of error in the data set. Alteration of either the dosing interval or the fraction absorbed did not affect the pattern of change in the confidence intervals for Tmax and Cmax, but the latter did result in a decrease in the interval for AUC0-infinity. Analysis of the confidence intervals for Tmax, Cmax and AUC0-infinity in bioequivalency studies for quinidine gluconate and procainamide hydrochloride following administration of single and multiple doses to different subjects appeared to be consistent with the patterns observed for the simulated data sets.     

单能量X线测定骨密度的初步分析

目的：了解温州地区人群不同年龄组骨质疏松患病率及同年龄组男女骨质疏松患病的差异，强调早期预防治疗老年人及绝经期妇女骨质疏松的重要性，方法：应用单能量X线（SXA）骨密度仪测量246例正常人的右跟骨骨密度，结果：男性大于60岁组较小于60岁组骨密度（BMD）降低明显（P＜0．05）；女性50岁以上组与小于50岁组相比，BMD下降差异有极显性（P＜0．01）；各年龄组男女相比，男性BMD明显高于女性（P＜0．05）。结论：女性骨质疏松症的发病大多以绝经后为主，雌激素在维持骨量方面具有重要的作用。SXA检测的跟骨含95％小梁骨，能较好地确定骨质疏松的风险水平，且其具有价廉、简便，快捷，较准确等特点，故不失为一种较好的临床筛查手段。     

维生素D受体基因多态性与汉族人群慢性牙周炎易感性的关系

目的 探讨维生素D受体(VDR)基因多态性与汉族人群慢性牙周炎(CP)易感性的关系。方法 收集汉族轻、中、重度CP患者共166例及80名无牙周炎对照者的颊黏膜拭子，以Chelex-100法提取DNA，采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定VDR BsmI、VDR ApaI和VDR TaqI的基因型，分析组间基因型分布和等位基因频率的差异。结果 轻、中、重度CP患者中VDR ApaI等位基因A携带者明显多于对照组，重度CP与中度CP、重度CP与轻度CP患者间VDR ApaI基因型的分布差异均有统计学意义，中度CP与轻度CP患者间VDR ApaI基因型分布差异无统计学意义，而VDR BsmI、TaqI位点的基因型分布在患者组和对照组间差异无统计学意义。结论 VDR ApaI等位基因A可能与汉族人群CP的易感性有关。     

Discriminative conditioning-related slow potential and single-unit responses in the frontal cortex of urethane-anesthetized rats

A model is described for obtaining long-term and stable discriminative conditioning-related slow-potential and single-unit responses from the frontal cortex of urethane-anesthetized rats. Responses were recorded and analyzed to reinforced (rewarding medial forebrain bundle stimulation) and non-reinforced tone cues. In the present study, cortical event-related slow potentials provided an adequate index of the level of discriminative conditioning. Single-unit response patterns are described for 57 neurons which demonstrated a discriminative response to either the reinforced or non-reinforced tone cue.     

Association of the Platelet Glycoprotein Ⅰa C807T Gene Polymorphism With Risk of Myocardial Infarction in Chinese

Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction (MI) in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same race. An allele-specific polymerase chain reaction (PCR) was used for genotyping of C807T polymorphism. Results An apparent association was found between the T807 allele and MI among individuals younger than the mean age of 60 years (odds ratio,2.49; 95% confidence interval, 1.08 ～ 6.22 ). The T807 allele remained an independent risk factor for MI when age, sex, smoking, hypertension, diabetes, bodymass index, LDL-cholesterol and HDL-cholesterol were adjusted by logistic regression. Conclusions GPⅠa T807 appears to be an independent risk factor for MI.     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.