Synthesis of [uniformly ring‐14C]‐labelled 4‐hydroxybenzaldehyde,vanillin, and protocatechualdehyde

[Uniformly ring‐¹⁴C]‐labelled 4‐hydroxybenzaldehyde, vanillin, and protocatechualdehyde were synthesized from [¹⁴C]‐labelled phenol, guaiacol, and catechol with methyl dichloromethyl sulfide (CH₃SCHCl₂) under Friedel–Crafts alkylation conditions in dichloromethane at ?78°C for 5 min (in the case of phenol and guaiacol) or at ?20°C for 1 min (in the case of catechol), by rapid addition of SnCl₄ to mixtures of the phenolic compound and CH₃SCHCl₂, followed by hydrolysis with HCl. Regioselective formylation (para to the –OH group) was achieved. The conversion rates were 96, 81, and 88% for 4‐hydroxybenzaldehyde, vanillin, and protocatechualdehyde, respectively, and the yields of the recovered products after work‐up amounted to 88, 75, and 83%, respectively. In the case of guaiacol, 17% of isovanillin was obtained as by‐product. It was found that the presence of water or ethyl acetate in the reaction mixture, at a molar ratio of 60:1 (water:guaiacol) or 120:1 (ethyl acetate:guaiacol), had little influence on the yields under the reaction conditions. Factors influencing the yields are discussed in the study. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis of deuterium,tritium, and carbon‐14 labeled BIRB 796, a p38 MAP kinase inhibitor

1‐(5‐tert‐Butyl‐2‐p‐tolyl‐2H‐pyrazol‐3‐yl)‐3‐[4‐(2‐morpholin‐4‐yl‐ethoxy)naphthalen‐1‐yl]urea (BIRB 796), currently in clinical trials for the treatment of inflammatory diseases, is a potent inhibitor of p38 MAP kinase. Labeled BIRB 796 with stable and radioactive isotopes was required for metabolism, distribution, and absorption studies. We first report the synthesis of carbon‐14 labeled BIRB 796 with a specific activity of 2 GBq/mmol (54.2 mCi/mmol), using [¹⁴C]‐phosgene under modified Schotten–Baumann conditions; second the preparation of tritium‐labeled BIRB 796 with a specific activity of 659 GBq/mmol (17.81 Ci/mmol) by reductive dehalogenation of iodo‐BIRB 796 with tritium gas; and finally, the synthesis of ²H₈‐BIRB 796 using morpholine‐2,2,3,3,5,5,6,6‐²H₈ with isotopic enrichment of 98.9 at% ²H. Copyright © 2004 John Wiley & Sons, Ltd.     

Effects of new polymer-coated extracorporeal circuits on biocompatibility during cardiopulmonary bypass

An inflammatory response due to bioincompatibility of extracorporeal circuits is a major clinical issue during cardiopulmonary bypass (CPB). By using a swine model, we determined whether new polymer-coated circuits, the blood-contacting surfaces of which are coated with poly(2-methoxyethylacrylate) (PMEA), would reduce the inflammatory response during CPB. Plasma bradykinin levels and the percentages of CD35-positive monocytes in PMEA-coated circuits were significantly lower than those in uncoated circuits during CPB. The amount of proteins adsorbed on the PMEA-coated circuits was significantly lower than that on the uncoated circuits (0.30 microg/cm2 versus 3.42 microg/ cm2). Almost no IgG, IgM, or C3c/d was detected in proteins adsorbed on the PMEA-coated circuits although these proteins were clearly detected in proteins adsorbed on the uncoated circuits. We concluded that PMEA coating could reduce complement activation during CPB by suppressing the adsorption of IgG and IgM, which activate C3 via the classical pathway, on the surface of the circuits.     

多参数流式细胞术观察251例白血病细胞CD14表达的意义

目的　探讨 CD14在白血病细胞的表达及其在白血病诊断和鉴别诊断中的意义。方法　采用 CD45 /SSC参数设门多色流式细胞术分析 2 5 1例白血病细胞 CD14及其它白血病相关抗原的表达情况。结果　 2 5 1例中有 19例 ( 7.5 % )白血病细胞表达 CD14,95例急性髓系白血病 ( AML )中 16例 ( 16 .8% )白血病细胞表达 CD14,130例淋系白血病未见 CD14阳性的病例。 M4和 M5b CD14的阳性率 ( 9/ 14;6 / 6 )明显高于 M2 ( 1/ 30 ) ( P=0 .0 0 1;P=3.6× 10 - 6 )及 M5a( 0 / 5 ) ( P=0 .0 3;P=2 .2× 10 - 3 )。标准 CD14单抗均不与 5例 M5a细胞反应 ,而自制 CD14新克隆 2 F9单抗则全部阳性。5例 M5a中 1例 CD15和 2 9例 M2 中 13例 CD11b的阳性率明显低于 M5b( 6 / 6 ,P=0 .0 2 ;6 / 6 ,P=0 .0 2 )。在 AML 组中 ,CD14的表达与 CD117呈负相关 ( r=- 0 .2 ,n=81,P=0 .0 3) ,与 CD11b、CD15及HL A- DR呈正相关 ( r=0 .5 ,n=93,P=0 .0 0 1;r=0 .4,n=95 ,P=0 .0 0 1;r=0 .2 ,n=95 ,P=0 .0 2 )。结论　 CD14有助于淋巴系白血病、髓系白血病及其单核细胞相关性白血病的诊断与鉴别 ,其对单核细胞相关性白血病免疫分型诊断中的特异性为 96 .7% ,敏感性为 6 0 .0 %。     

甲硫腺苷磷酸化酶在非小细胞肺癌中转录表达

目的 探讨甲硫腺苷磷酸化酶(MTAP)及其连锁基因p14，p15和p16在非小细胞肺癌中的转录表达变化情况。方法 采用RT-PCR方法检测15例新鲜肺癌标本及相应癌旁组织中MTAP及其边锁基因p14、p15和p16mRNA的表达情况。结果 MTAP在73．3％的肿瘤标本中不表达或转录水平降低5倍以上，而MTAP在癌旁对照组织中的表达率却高达93．3％；此外，MTAP在肺腺癌和鳞癌中的低表达现象无显著性差异，但在中／低分化肺癌中低表在显著高于高于分化癌。对7例标本分析表明，1例P15基因在正常组织及癌瘤中都高水平表达，1例均不表达。5例在癌标本中基本不表达．而在正常组织中表达；而p14和p16正常组织中转录表达水平很低，而在配对的7例肺癌组织中却分别有3项高表达。结论 MTPA基因低表达或丢失可能与肺癌的恶性程度密切相关，MTAP的缺失可能独立于p16之外，提示MTAP的低表达或缺失在肿瘤生物学中有其功基础的基础。     

青蒿琥酯对中暑内毒素血症小鼠腹腔巨噬细胞内CD14和Toll样受体4的影响

目的探讨青蒿琥酯对中暑内毒素血症小鼠腹腔巨噬细胞内CD14和Toll样受体4 (TLR4)表达的影响。方法昆明种小鼠随机分为常温组、高温组、生理盐水组和青蒿琥酯组(均按60 mg/kg连续5 d腹腔注射),常温组在干球温度25℃±0．5℃、相对湿度43%±5%的条件下暴露2 h,其他组在干球温度35℃±0．5℃、相对湿度65%±5%的条件下热暴露,观察不同时间点(1、2 h)小鼠腹腔巨噬细胞内CD14和TLR 4 mRNA的表达及血浆中肿瘤坏死因子α(TNF-α)的含量。结果常温组CD14和TLR 4 mRNA表达分别为0．34%±0．047%和0．31%±0．062%；高温1 h组分别为0．53%±0．085%和0．45%±0．049%,与常温组的差异均有统计学意义(P＜0．01),并在2 h时呈现继续升高的趋势；生理盐水1 h组CD14和TLR4表达升高,但在2h时有轻度下降；青蒿琥酯1 h组CD14和TLR4的表达则分别为0．26%±0．051%和0．25%±0．084%,并在2 h有轻微的下降。各组TNF-α含量的变化呈现出与CD14、TLR 4变化基本一致的趋势。结论青蒿琥酯能明显降低内毒素信号转导通路上CD14和TLR 4的表达,减少TNF-α的产生,这可能是其抗中暑内毒素血症的机制之一。     

2004年天津市农村14岁及以下居民健康体检结果分析

目的2004年对天津市14岁及以下年龄组农村居民进行身体健康检查，及时了解农村少年儿童的健康状况及影响因素，为改善农村居民健康提供科学依据。方法对天津市559103名14岁及以下农村人口进行身体健康检查，内容包括身高、体重等基本体征，内、外、五官科各项体征及3岁以下儿童的佝偻病、男童外生殖器、女童月经初潮年龄、7岁以下儿童的血红蛋白和血浆维生素A水平等项目进行健康检查。结果14岁及以下人群中，皮肤、耳、听力、心脏、肝脏、脾脏、肺、躯干四肢、精神发育正常、无内分泌及代谢性疾病、无染色体疾病的儿童在99．0％以上，0-6岁儿童的肥胖率为12．76％，7-14岁儿童的肥胖率为9．30％，5岁以下儿童生长迟缓率为12．79％，低体重率为5．17％，消瘦率为3．16％，3岁以下儿童佝偻病检出率为5．74％，7岁及以下儿童的贫血率为12．42％，维生素A缺乏率为2．23％。结论14岁及以下少年儿童的身体健康状况基本良好，存在的营养缺乏和超重肥胖问题应引起关注。     

P14ARF基因联合氟尿嘧啶对人结肠癌LOVO细胞的作用

目的观察p14ARF基因转染联合氟尿嘧啶对人结肠癌LOVO细胞的作用.方法采用RT-PCR和Western blot方法检测转染前后LOVO细胞中p14ARF基因的表达.四唑蓝比色法（MTT法）检测细胞增殖,流式细胞术分析细胞周期,对比在不同浓度的氟尿嘧啶作用下转染前后LOVO细胞的增殖情况.结果LOVO细胞呈现p14ARF基因缺失变异.RT-PCR和Western blot法证实转染后LOVO细胞中有p14ARF基因的表达.p14ARF基因转染后细胞增殖受抑,流式细胞仪显示p14ARF基因诱发凋亡.在氟尿嘧啶0.1 g/mL的作用下,未转染的LOVO细胞的增殖速度未受影响,而转染后LOVO细胞较未用药时的抑制率增加;氟尿嘧啶1、10、100 μg/mL时,对转染前后LOVO细胞均有增殖抑制作用,且呈剂量相关性.氟尿嘧啶对转染后LOVO细胞的抑制率明显高于未转染的LOVO细胞.结论p14ARF基因转染可抑制LOVO细胞增殖.p14ARF基因和氟尿嘧啶联合用于LOVO细胞能够加强氟尿嘧啶的增殖抑制作用,明显提高LOVO细胞对氟尿嘧啶的敏感性.     

Relationship between p53-associated proteins and estrogen receptor status in ovarian serous neoplasms

We studied the immunoexpression of p14ARF, MDM2, and p53, in addition to relationships between those protein expressions and estrogen receptor (ER)alpha in ovarian serous tumors including benign (n= 23), borderline (n= 41), and malignant (n= 94). The aberrant expressions of p14ARF, MDM2, and p53 were observed in 19.6% (31/158), 47.5% (75/158), and 39.9% (63/158) of cases, respectively. The expression of MDM2 was significantly higher in borderline tumors compared to benign (P= 0.04) and malignant (P < 0.01) tumors. p53 expression in borderline tumors was uncommon, and p14ARF expression loss was mainly observed in carcinomas. Altered expression of p14ARF, MDM2, and p53 shows significant relationship with stage. Overexpression of MDM2 (P= 0.01) and loss of p14ARF expression (P= 0.04) were significantly associated with ER expression. Our results suggest that alteration of p14ARF-MDM2-p53 pathway proteins may contribute significantly to the tumorigenesis of ovarian serous neoplasms, and ER is involved in cellular regulation of p14ARF-MDM2-p53 pathway in ovarian serous neoplasms.