Non-invasive imaging of adaptive immunity using positron emission tomography

Summary: Non-invasive monitoring of adaptive immunity in infection, cancer, and autoimmunity remains a major challenge. Current techniques to monitor lymphocytes involve numeric and functional determinations of immune cells isolated from the peripheral blood (most often) and tissue (rarely). Invasive measurements are prone to sampling errors and are poorly reflective of the dynamic changes in the location, number, and movement of lymphoid cells. These limitations indicate the need for non-invasive whole-body imaging methodologies that allow longitudinal, quantitative, and functional analyses of the immune system in vivo . Positron emission tomography (PET), a clinically based whole-body imaging modality, has the potential to revolutionize diagnostics and therapeutic monitoring in both clinical and pre-clinical settings. This review discusses studies using PET to image adaptive immune responses in small animal models. We address the challenges inherent in assessing whole-body immunity with PET and recent developments that can improve its performance. Finally, we discuss work to translate PET immune imaging into clinical practice.     

距骨颈骨折疗效分析

目的探讨距骨颈骨折治疗方案的选择以及疗效相关因素分析。方法距骨颈骨折15例，男13例，女2例。年龄16～63岁，平均40．5岁，合并腰椎、髋臼、跟骨、外踝骨折各1例。开放骨折2例。陈旧性骨折2例（〉1个月）。按Hawkins骨折分类：Ⅰ型3例、Ⅱ型9例、Ⅲ型3例。Ⅰ型骨折采用膝下管型石膏固定，其中1例复诊中因移位行切开复位松质骨螺钉固定。Ⅱ型骨折均行切开复位，克氏针或松质骨螺钉固定。Ⅲ型骨折1例开放性骨折，急诊行清创缝合，手法＋撬拔复位，脱位整复。一周后在C臂机引导下，采用二枚直径4．0mm中空螺钉由后向前固定距骨颈，1例急诊手术切开复位，克氏针内固定。结果本组13例获得随访，时间4～24个月，平均12.3个月。13例中发生距骨体缺血性坏死5例，其中Ⅱ型骨折4例，Ⅲ型骨折1例。另2例未统计在内。1例外院病例术后并发伤口感染长期不愈，行小腿截肢术。1例患者拒绝手术治疗。按Hawkims疗效标准，优4例，良4例，可3例，差2例，优良率69％。结论对无移位的距骨颈骨折，行膝下管型石膏固定6～12周，并定期拍片复查，距骨颈骨折脱位应急诊复位和可靠的内固定。以2枚拉力螺钉内固定为宜，尽量减少并发症。对距骨体缺血性坏死，或创伤性关节炎，则根据患者的实际情况采取相应治疗措施。     

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population

Summary Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40–59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/–, 54%; –/–, 35% (+ and – indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p<0.05).     

饮食性缺铜、缺锌对小鼠细胞因子产生的影响

３周龄小鼠饲用６周缺铜饮食后，出现胸腺萎缩、肝脏肿大以及明显的缺铜指征，包括血清Ｃｐ活性、肝Ｃｕ含量、ＣＣＯ和Ｃｕ，Ｚｎ－ＳＯＤ活性明显下降。缺钢小鼠产生的ＴＮＦ－α、ＩＬ－１和ＩＬ－６水平明显低于正常组小鼠。小鼠饲予７周缺锌饮食后，出现明显脱毛，虽然肝Ｚｎ含量降低不明显，但ＴＮＦ－α、ＩＬ－１和ＩＬ－６活性明显降低，说明上述细胞因子是小鼠缺锌的敏感指征之一。本文结果显示正常Ｃｕ、Ｚｎ水平对ＴＮＦ－α、ＩＬ－１和ＩＬ－６产生的重要性，并提示这些细胞因子的改变可能是缺铜、缺锌引起的免疫功能损害的细胞、分子学机理之一。     

豚鼠肠粘膜下神经丛淋巴管旁神经元的烯醇化酶免疫组织化学观察

作者曾报道豚鼠肠粘膜下神经丛内,可能有一种特殊类型的淋巴管旁神经元。为了对上述的研究提供进一步的证据,本文应用显示神经元特异性烯醇化酶(NSE)的免疫组织化学方法,对这种类型的神经元进行了观察。胃肠神经丛内所有的神经元都呈NSE阳性反应,小肠和结肠粘膜下丛内的淋巴管旁神经元,也显同样的阳性反应。平滑肌和结缔组织细胞均为阴性。大多数淋巴管旁神经元具有典型的神经元形态特征;有些细胞虽不具有明显的神经元形态特点,但它们都显相同的NSE阳性反应。本文为我们前文报道的淋巴管旁神经元提供了更可信的证据。     

2001至2005年上海部分地区腹泻住院患儿诺若病毒分子临床流行病学研究

目的通过对上海地区腹泻住院患儿进行诺若病毒检测,对其流行株进行基因序列的测定,以了解诺若病毒在上海地区的流行特征,为该病原体所致腹泻的防治提供基础数据和理论依据。方法收集2001至2005年复旦大学附属儿科医院5岁以下腹泻住院患儿的粪便标本。首先进行轮状病毒的检测,在轮状病毒抗原阴性标本中,每隔8个标本按编号顺序行机械随机抽样,建立RT-PCR方法进行诺若病毒的检测。对PCR产物进行双向测序,测序结果通过Clustal W和Mega 4.1软件进行分析。结果研究期间共收集腹泻患儿粪便标本5534份,轮状病毒抗原阴性4084份,机械随机抽得484份用于诺若病毒检测,45/484份(9.3%)检测到诺若病毒。对诺若病毒感染季节分布和患儿年龄特点的分析表明,除4月和7月份未检测到诺若病毒外,其余各月份均检测到诺若病毒,其高发的月份是8至11月。5~6月也呈一个小高峰。77.8%(35/45)的患儿<2岁,其中6~11个月的患儿所占比例最高,达35.6%(16/45),<6个月的婴儿占20%(9/45)。GⅡ-4型是这5年间尤其是2003年之后的主要流行型别,2001至2002年尚存在其他的流行型别GⅡ-3和GⅡ-7...     

碱性成纤维细胞生长因子与卵巢癌的关系

目的　探讨碱性成纤维细胞生长因子 (basic fibroblast growth factor,b FGF)对卵巢癌细胞增殖、浸润和肿瘤血管生成的影响 ,及 b FGF单克隆抗体 (b FGF monoclonal antibody,b FGF- MAb)的治疗作用。　方法　将人卵巢癌细胞株 SKOV3接种于 2 4孔板 ,加入不同浓度的 b FGF,每日行结晶紫染色后测定光密度 (D4 90 )值 ,绘制细胞生长曲线 ;将 SKOV3细胞团接种于铺设有细胞外基质凝胶的 4孔板 ,每日测定癌细胞在凝胶中的浸润距离 ;建立 SKOV3细胞裸鼠皮下移植瘤模型 ,每周两次分别将 b FGF、b FGF-MAb和生理盐水注射于移植瘤周围 ,8周后测量肿瘤体积 ;对移植瘤组织切片行 因子的免疫组化染色、测定肿瘤内微血管密度 (microvessel density,MVD)。　结果　 b FGF能促进 SKOV3细胞增殖并呈浓度依赖 ,实验第 5天 ,5 ng/ml、10 ng/ml组细胞 D4 90 值是对照组的 1.0 9倍和 1.2 1倍 ;b FGF能促进 SKOV3细胞浸润并呈浓度依赖 (P<0 .0 5 ) ,第 7天 ,5 ng/ml、10 ng/ml组细胞浸润距离分别是对照组的 1.5 3倍和2 .4 5倍 ;b FGF组移植瘤体积和 MVD分别是对照组的 1.80倍和 1.4 6倍 (P<0 .0 5 ) ,b FGF- MAb组移植瘤体积和 MVD分别是对照组的 6 3.7%和 6 2 .8% (P<0 .0 5 )。　结论　b FGF能明显促进卵巢癌细胞的增殖、     

Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia

Calcium is an important mediator of programmed cell death induced by transient cerebral ischemia, and calcium-binding proteins have been implicated in calcium-regulated signal transduction. Apoptosis-linked gene 2 is a calcium-binding protein required for cell death induced by different apoptotic stimuli. By Western blot analysis, we found that apoptosis-linked gene 2 protein was expressed in normal brains, and that expression increased in ischemic brains after 20 or 90 min of transient focal cerebral ischemia. Immunocytochemistry showed increased apoptosis-linked gene 2 protein expression in frontal cortex, a region where neurons underwent ischemic stress but still survived, after 20 or 90 min of focal cerebral ischemia. Apoptosis-linked gene 2 protein was also up-regulated in the ischemic border-zone of parietal cortex 24h after 20 min of focal ischemia, and was remarkably over-expressed in the caudate-putamen and parietal cortex, (where cells are destined to die) 24h after 90 min of ischemia. The expression pattern of apoptosis-linked gene 2 protein was similar to that of deoxyribonucleic acid damage detected by Klenow labeling assay.Our results suggest that apoptosis-linked gene 2 may be involved in the regulation of cell death after transient focal cerebral ischemia.     

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone. More importantly, the levels of neutralizing antibodies in the former groups were significantly higher than others and could last for at least four months in cattle trials. This study suggests that the prime-boost strategy significantly improves the effective immunity and may provide a longer protection against FMDV infection.