蛋白激酶C对人胰腺癌细胞放射敏感性的影响及其机制

目的 研究蛋白激酶C对人胰腺癌细胞Panc-1体外放射敏感性的影响并探讨其机制。方法 应用蛋白激酶C激活剂PMA和抑制剂CH分别观察其对Panc-1细胞存活分数的影响。采用多靶单击数学模型拟合细胞剂量存活曲线,明确CH对人胰腺癌细胞Panc-1的放射增敏效应。采用Annexin Ⅴ/PI法流式细胞仪检测CH对细胞凋亡的影响。采用免疫细胞化学方法检测Bcl-2、Bax蛋白表达的变化。结果 单纯照射组、PMA处理组和CH处理组细胞SF₂值分别为0.78±0.02、0.92±0.11和0.19±0.20。浓度为0.5、2和8μmol/L 的CH作用4h后,放射增敏比分别为1.05、1.24和1.77,呈药物浓度依赖性。流式细胞仪检测显示PMA可使照射后肿瘤细胞凋亡指数降低,而CH则使凋亡指数增加。CH作用后,肿瘤细胞Bax蛋白表达水平增加,Bcl-2蛋白表达水平无明显变化,但Bax/Bcl-2值增大。结论 蛋白激酶C通过改变肿瘤细胞的凋亡水平实现对人胰腺癌细胞Panc-1放射敏感性的调控。     

一种简单的骨龄评估方法:头状骨-钩骨平面测量

目的为确定头状骨-钩骨(CH)平面测量是否可以作为评估骨龄的可靠指标,并将其与Greulich-Pyle(GP)图谱法进行比较。方法回顾性分析391例儿童(1～180个月)影像资料,2名研究人员手动测量平片上头状骨和钩骨的面积,CH平面几何测量定义为测量头状骨和钩骨总面积。2位研究人员独立将CH平面测量和GP图谱法应用于109例身高在增长图的第50百分位的儿童。结果实际年龄与CH平面测量之间存在较强的正相关(右手,r=0.970 2;左手,r=0.970 9),CH平面测量方法与GP图谱法准确度分别为(84.39%～84.46%)、(85.15%～87.66%),差异无统计学意义(P≥0.086 7)。CH平面几何测量的观察者间的可重复性[准确度,4.42%;95%协议限制(LOA),-10.5~13.4个月]高于GP方法(准确度,8.45%;95%LOA,-29.5~21.1个月)。结论 CH平面测量可能是骨龄评估的可靠方法。     

不同HBV感染者病毒前C区信号酶裂解位点变异的检测

运用错配聚合酶链反应 (PCR)和限制性片段长度多态性 (RFLP)分析方法 ,检测乙型肝炎病毒(HBV)基因前C区信号酶裂解位点 (T186 2 )变异在重型乙型肝炎、乙型肝炎无症状携带者 (AsC)、乙型肝炎病毒感染后肝硬化 (LC)及慢性肝炎 (CH)病人中的发生率 ,以探讨T186 2变异在各组肝病中的临床意义。T186 2变异在 4组病人中的发生率分别为 :重型乙型肝炎 17.3% (9/ 5 2 ) ,AsC无一例变异 ,LC 2 .7% (1/ 37) ,CH 2 .3% (1/44 )。重型乙型肝炎病人T186 2变异率与AsC、LC和CH比较 ,差异有显著性意义 (P <0 .0 1) ,而AsC与LC、CH比较 ,T186 2变异差异无显著意义 (P >0 .0 5 )。提示T186 2变异与乙型肝炎病毒引起的急性重症肝炎或慢性肝炎急性加重有关。     

体重变化对老年2型糖尿病患者代谢的影响

 目的 观察住院老年2型糖尿病超重患者体重变化对营养代谢的影响.方法 收集本院2004～2005年进入营养治疗的体质指数≥24 kg/m2的老年2型糖尿病86例,根据营养治疗结束时体重动态分为A组(体重下降)、B组(体重无变化)、C组(体重上升).了解3组体重、体质指数与空腹血糖(FPG)、餐后2 h血糖(2 hPPG)、三酰甘油(TG)、总胆固醇(CH)、总蛋白、白蛋白代谢关联性.结果 组内比较:A组FPG、2 hPPG、TG、CH和B组FPG、2 hPPG下降差异有统计学意义(P＜0.01).组间比较:治疗后A组2 hPPG、TG、CH低于B组,差异有统计学意义(P＜0.05);A、B组CH低于C组,差异有统计学意义(P＜0.05或P＜0.01).结论 体重超标的老年糖尿病患者血糖、血脂的变化与体重变化相一致,体重降低,血糖、血脂恢复理想.     

MRI及CT对软组织海绵状、蔓状血管瘤的诊断价值

目的 :探讨软组织海绵状血管瘤 (CH)、蔓状血管瘤 (RH)的MRI、CT表现及诊断价值。方法 :回顾性总结经手术及病理证实 2 1例CH及 14例RH的MRI和CT表现。结果 :CH在MRI上呈团块或不规则状 ,边界清楚 ,血窦呈不均匀等T1长T2 信号 ,瘤内纤维、脂肪组织呈花边、条状分隔或串珠样短T2 信号 ;CT示肿瘤密度不均 ,有分隔 ,呈中等度强化。RH形态不规则、边界欠清 ,MRT1WI及T2 WI可见其内管状流空血管影 ;CT示瘤内见结节状、蚓状等、高密度影 ,部分有钙化、静脉石 ,增强扫描呈结节状、条状明显强化。结论 :CH和RH影像表现具有相对特征性 ;CT有利于显示瘤内钙化、静脉石 ,MRI则可反映瘤内脉管及非血管组织成分 ,对定性诊断有重要的价值。     

单管法自动化合成 11C-碘代甲烷

目的　研究液相单管法自动化合成1 1 C 碘代甲烷 (CH3I)的设备和工艺。方法　由压缩空气对反应管制冷至 - 5℃左右 ,反应管内装氢化锂铝溶液。1 1 CO2 经减压后传到反应管内。待1 1 CO2传输完毕 ,加热反应管至 10 0～ 190℃ ,并通入气体 ,除有机溶剂。冷却反应管 ,通过气动方式加入质量分数 5 7%的氢碘酸 ,再次加热至 10 0～ 190℃ ,冷却反应上部 ,产生的1 1 C CH3I由氩气载出。对 3种1 1 C化合物前体甲基化反应 ,均获得了较高的产率。结果　1 1 C CH3I合成效率为 (85 3± 1 7) % ,合成时间 7min。结论　该技术及自动化设备高效合成了1 1 C CH3I,可满足PET中心的使用要求。     

β淀粉样蛋白显像剂2-(4'-N-11C-甲胺苯基)-6-羟基苯并噻唑的研究

目的 用改良法合成β淀粉样蛋白(AB)显像剂2-(4'-N-11C-甲胺苯基)-6-羟基苯并噻唑(N-11CH3-6-OH-BTA-1),并评价其生物学性质.方法 采用改良法合成N-11CH3-6-OH-BTA-1,即"C-CH3-Triflate与1～2 mg的6-OH-BTA4)(前体)丙酮溶液在-20℃下捕获,80℃反应,再经高效液相色谱仪(HPLC)纯化,固相萃取分离.同时用常规法合成N-11CH3-6-OH-BTA-1,比较2种方法的合成效率.研究NH正常小鼠体内N-11CH3-6-OH-BTA-1的生物学分布.选阿尔茨海默病(AD)患者1例,健康志愿者1名,研究N-11CH-6-OH-BTA-1在其体内的摄取及清除.结果 改良法的不校正合成效率为29.8%(合成次数n=22),与常规法(30.2%,合成次数n=3)接近,但前体量<1 mg,效率下降至14%.改良法产品放化纯>95%,比活度为18.0 TBq/mmol.NH小鼠脑摄取N-11CH3-6-OH-BTA-1较多,2 min每克组织百分注射剂量率(%ID/g)达(5.46±1.06)%ID/g;清除快,30 min时为(0.22±0.02)%ID/g.AD患者在注射N-11CH3-6-OH-BTA-1后45 min时,颞叶及枕叶有明显的放射性滞留,而健康志愿者45 min时脑内放射性基本清除.结论 改良法合成N-11CH3-6-OH-BTA-1可降低前体用量.N-11CH3-6-OH-BTA-1有可能成为临床AD诊断及治疗中评价Aβ分布的显像剂.     

腰池持续引流联合高压氧对重型颅脑损伤术后并发慢性脑积水的影响

目的 探讨重型颅脑损伤(severe craniocerebral injury,SCI)术后早期行腰池持续引流(continuous lumbar drainage,CLD)联合高压氧(hyperbaric oxygen,HBO)治疗对患者慢性脑积水(chronic hydrocephalus,CH)的影响.方法 将我院390例SCI术后患者分为3组:A组130例早期HBO联合CLD治疗,B组130例CLD治疗,C组130例常规药物治疗.比较1年内患者发生CH的差异.结果 3组病例1年内发生CH的比例(例数)分别为:A组5.38%(7例),B组12.31%(16例),C组21.54%(28例),采用x2检验比较3组发病率差异性,A、B组比较x2=3.864,P<0.05;B、C组比较x2=3.939,P<0.05;A、C组比较x2=14.560,P<0.01.结论 CLD可以有效降低SCI术后CH的发生率,若联合HBO治疗效果更明显.     

庚型肝炎病毒感染对慢性丙型肝炎的临床与病理学影响

目的　探讨庚型肝炎病毒 (HGV)感染对慢性丙型肝炎 (CH C)的临床与病理学影响。方法　应用逆转录 聚合酶链反应 (RT PCR)法对 5 3例经肝穿活检确诊的CH C患者血清标本进行了HGV RNA检测 ,并将合并与未合并HGV感染者进行了临床与病理学对比。结果　HGV RNA阳性 1 5例 (2 8 3 0 % )。合并与未合并HGV感染者在临床表现 ,肝功能等生化指标水平 ,HCV RNA阳性率及肝脏病理损害等方面差异均无显著性 (P >0 .0 5 )。结论　HGV感染对CH C的肝脏损害及HCV复制无影响。     

E-钙黏蛋白和N-钙黏蛋白启动子的构建及活性测定

目的：构建含有E-钙黏蛋白（cadherin）基因和N-钙黏蛋白基因启动子的荧光素酶报告基因载体,并检测E-钙黏蛋白启动子和N-钙黏蛋白启动子的活性。方法利用PCR技术从乳腺癌细胞ZR75-1基因组中扩增出E-钙黏蛋白和N-钙黏蛋白启动子片段,插入到荧光素酶报告基因载体pGL4-basic中,确定所扩增的DNA序列后,将其转染至乳腺癌细胞ZR75-1和肝癌细胞HepG2中,检测启动子的活性。结果测序结果表明,扩增的E-钙黏蛋白启动子序列正确;荧光素酶活性实验表明,E-钙黏蛋白启动子和N-钙黏蛋白启动子在乳腺癌细胞ZR75-1和肝癌细胞HepG2中表达都具有活性。结论成功构建了E-钙黏蛋白启动子和N-钙黏蛋白启动子报告基因表达载体,为进一步筛选调节E-钙黏蛋白和N-钙黏蛋白表达的转录因子提供了重要基础。     

部分脱抗原同种异体牙本质盖髓剂的临床应用研究

目的 :评价部分脱抗原同种异体牙本质 (HPDD)盖髓剂的疗效 ,为临床盖髓剂的选择提供依据。方法 :以HPDD、氢氧化钙 (CH)两种材料盖髓剂 ,进行临床远期疗效观察。结果 :HPDD间接盖髓成功率 10 0 % ,直接盖髓成功率 87 88% ;CH组间接盖髓成功率 94 87% ,直接盖髓成功率 80 6 5 % ,两组盖髓剂临床成功率统计学分析无显著差异性 ,P >0 0 5。结论 :两组盖髓剂临床效果良好 ,HPDD抗原性弱 ,不产生免疫反应 ,对牙本质修复有促进作用 ,是可选择的盖髓剂。     

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).     

1,4萘醌和1,2萘醌化合物对肌质网钙通道Ryanodine受体的调节作用

目的 研究萘醌－钙通道蛋白（ＮＱ－ＲｙＲ）的作用机制。方法 地ＮＱ旋的１,４ＮＱ、１,４ＮＱ－２－ｓｕｌｆｏｎａｔｅ（１,４ＮＱ２Ｓ）、１,２ＮＱ、１,２ＮＱ－４ｓｕｌｆｏｎａｔｅ（１,２ＮＯ４Ｓ）、２－ＣＨ３－１,４ＮＱ和２－ＯＨ－１,４ＮＱ等６种ＮＱ与骨骼肌肌质网（ＳＲ）ＲｙＲ）的相互作用进行了观察和比较。结果 所有ＮＱ都不同程度地激活钙通道引起钼流释放;１,４ＮＱ、１、,２ＮＱ、１,２ＮＱ、     

18F]fluoromethyl triflate, a novel and reactive [18F]fluoromethylating agent: preparation and application to the on-column preparation of [18F]fluorocholine.

The production and use of [18F]fluoromethyl triflate ([18F]CH2FOTf), a more reactive [18F]fluoromethylating agent than [18F]fluoromethyl bromide ([18F]CH2BrF), is described. [18F]CH2FOTf was prepared from [18F]CH2BrF. The latter was synthesized by nucleophilic substitution of CH2Br2 with no-carrier-added [18F]fluoride and purified by four Sep-Pak Plus silica cartridges connected in series. It was then quantitatively converted on-line to [18F]CH2FOTf by passing through a heated AgOTf column. Decay-corrected radiochemical yields of [18F]CH2FOTf based on [18F]fluoride were 47 +/- 8% (n = 20). Both [18F]CH2BrF and [18F]CH2FOTf were applied to solid-supported [18F]fluoromethylation of N,N-dimethylaminoethanol on a Sep-Pak Plus C18 cartridge to produce the 18F-labeled choline analogue, (beta-hydroxyethyl)dimethyl-[18F]fluoromethylammonium ([18F]fluorocholine). Depending on flow rate and amount of precursor used, decay corrected radiochemical yields of [18F]fluorocholine from [18F]CH2BrF ranged from 6% to 63%, while [18F]CH2FOTf afforded yields of more than 80%. Thus, by using the latter reagent and a subsequent purification on a Sep-Pak Accell CM cartridge, [18F]fluorocholine was produced from [18F]fluoride in overall radiochemical yields of 40% (decay corrected) in less than 30 min.     

Patient motion correction for multiplanar, multi-breath-hold cardiac cine MR imaging

PURPOSE: To correct for spatial misregistration of multi-breath-hold short-axis (SA), two-chamber (2CH), and four-chamber (4CH) cine cardiac MR (CMR) images caused by respiratory and patient motion. MATERIALS AND METHODS: Twenty CMR studies from consecutive patients with separate breath-hold 2CH, 4CH, and SA 20-phase cine images were considered. We automatically registered the 2CH, 4CH, and SA images in three dimensions by minimizing the cost function derived from plane intersections for all cine phases. The automatic alignment was compared with manual alignment by two observers. RESULTS: The processing time for the proposed method was <20 seconds, compared to 14-24 minutes for the manual correction. The initial plane displacement identified by the observers was 2.8 +/- 1.8 mm (maximum = 14 mm). A displacement of >/=5 mm was identified in 15 of 20 studies. The registration accuracy (defined as the difference between the automatic parameters and those obtained by visual registration) was 1.0 +/- 0.9 mm, 1.1 +/- 1.0 mm, 1.1 +/- 1.2 mm, and 2.0 +/- 1.8 mm for 2CH-4CH alignment and SA alignment in the mid, basal, and apical regions, respectively. The algorithm variability was higher in the apex (2.0 +/- 1.9 mm) than in the mid (1.4 +/- 1.4 mm) or basal (1.2 +/- 1.2 mm) regions (ANOVA, P < 0.05). CONCLUSION: An automated preprocessing algorithm can reduce spatial misregistration between multiple CMR images acquired at different breath-holds and plane orientations.     

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.     

High-yield synthesis of the terminal 188Re triple bond N multiple bond from generator-produced [188ReO4](-)

A novel procedure for the high-yield preparation of Re-188 radiopharmaceuticals containing a terminal Re identical with N multiple bond is described. This method involves the reaction of [(188)Re][ReO(4)](-) with N-methyl S-methyl dithiocarbazate (DTCZ), as donor of nitrido nitrogen atoms, sodium oxalate and SnCl(2) to afford a mixture of two intermediate compounds. When this mixture is reacted with the sodium salt of a dithiocarbamate ligand (L) of the type Na[R(2)N-C(=S)S] (R = CH(3), CH(3)CH(2), CH(3)CH(2)CH(2)), the formation of the bis-substituted, neutral complexes [(188)Re][Re(N)(L)(2)] is easily obtained in high yield (> 95%). The complexes [(188)Re][Re(N)(L)(2)] were characterized by chromatographic methods, and by comparison with the corresponding complexes prepared at macroscopic level starting from a non-radioactive rhenium precursor. Biodistribution studies were carried out in rats. Results showed that the complexes [(188)Re][Re(N)(L)(2)] exhibited the same biological behavior of the analogous Tc-99m complexes reported previously. The easy application of the new synthetic procedure indicates that it could be conveniently employed for preparing a large class of new Re-188 complexes having potential utilization in nuclear medicine as therapeutic agents.     

Intracranial contrast-enhancing masses in infants with capillary haemangioma of the head and neck: intracranial capillary haemangioma?

Contrast-enhancing intracranial masses are rarely found in infants with extracranial capillary haemangiomas (CH). We aimed to assess their nature and progression in three patients undergoing CT and/or MRI. The changes in size of both extra- and intracranial lesions were recorded. In a fourth case, a single examination was obtained. All patients harboured one or two enhancing intracranial nodular, meningeal-based lesions. Diffuse leptomeningeal enhancement of the cerebellar surface was also seen in one, which disappeared at follow-up. In all but one of the cases, the intracranial lesions were on the same side as the extracranial CH. These lesions and the extracranial CH demonstrated parallel changes in size (suggesting that both represent CH) during follow-up of 1–2 years: the size of intracranial lesions and the extracranial CH decreased in two cases, whereas it was unchanged in the third. One patient had a persistent trigeminal artery, while another had cerebellar atrophy with high signal in the cortex on T2-weighted images. In some cases, extracranial CH are part of PHACE syndrome; the association with intracranial CH might represent a peculiar phenotype of this rare vascular phakomatosis. As extracranial CH are known to regress spontaneously in the majority of cases, a conservative approach is recommended also for presumed intracranial CH; surgery should be avoided unless follow-up studies demonstrate growth. Received: 7 July 1998 Accepted: 13 October 1998     

Temperature dependence of relaxation times in proton components of fatty acids

We examined the temperature dependence of relaxation times in proton components of fatty acids in various samples in vitro at 11 tesla as a standard calibration data for quantitative temperature imaging of fat. The spin-lattice relaxation time, T(1), of both the methylene (CH(2)) chain and terminal methyl (CH(3)) was linearly related to temperature (r>0.98, P<0.001) in samples of animal fat. The temperature coefficients for the 2 primary proton components differed significantly; in 5 bovine fat samples, the coefficient at 30 °C was 1.79±0.07 (%/°C) for methylene and 2.98±0.38 (%/°C) for methyl. Numerical simulations based on such a difference demonstrated the possibility of considerable error from inconsistent ratios in fatty acid components when calibrating and estimating temperature. The error reached 3.3 °C per 15 °C in temperature elevation when we used a pure CH(2) signal for calibration and observed the signal with 18% of CH(3) to estimate temperature. These findings suggested that separating the fatty acid components would significantly improve accuracy in quantitative thermometry for fat. Use of the T(1) of CH(2) seems promising in terms of reliability and reproducibility in measuring temperature of fat.