Synthesis of a new carrier for immunization: polytuftsin

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCI)-Thr-Lys-(2-CI-Z)-Pro in the presence of HOBt . Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10–26 and 39–55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA . Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCI 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

Evaluating the impact of human papillomavirus vaccines

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.     

癌胚抗原DNA疫苗对大肠癌特异性细胞免疫的激活效果

目的检测以质粒pIRES为载体构建的带有全序列癌胚抗原(CEA)基因的核苷酸疫苗对机体特异性抗肿瘤免疫反应的激活效果。方法将CEA基因片段连接于真核表达质粒pIRES中,用肌肉注射方法接种核酸疫苗;检测CEA在小鼠肌肉组织中的表达情况及其对小鼠脾细胞CEA特异性细胞免疫反应的激活效果。结果小鼠经肌肉注射质粒后,免疫组化证实该核酸疫苗可在体内有效表达CEA;分子免疫检测显示注射后小鼠特异性淋巴细胞增值反应明显并且伴有自然杀伤细胞NK活性显著增高。结论实验所构建的核酸疫苗pIRESCEA可在体外及小鼠体内高效表达并表现出良好的细胞免疫原性。     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

胸腺肽增强狂犬病疫苗免疫效果的研究

目的　探索胸腺肽作为人用纯化Vero -细胞狂犬病疫苗佐剂的可能性。　方法　分为单针和多针狂犬疫苗免疫方案。单针免疫是用狂犬疫苗 1支加胸腺肽 1针免疫 ;多针免疫按常规五针免疫程序 (即 0、3、7、14、2 8d各注射1针 ) ,加胸腺肽组按三针免疫程序 (即 0、7、2 8d各注射 1针 ) ,实验小白鼠每只均以狂犬病疫苗 0 .2ml与胸腺肽混合后肌肉注射。　结果　单针免疫加入胸腺肽 ( 2mg/只 )后抗体效价高且抗体产生时间早 ,抗体水平显著高于疫苗组 (P <0 .0 1)。而且加入胸腺肽 ( 6mg/只 )后免疫三针可达到五针常规疫苗免疫效果。　结论　胸腺肽作为人用纯化Vero -细胞狂犬病疫苗的佐剂可减少免疫次数。     

Keratin 13基因在喉癌发生中的作用

探讨keratin 13基因在喉癌发生中的作用。方法在keratin 13基因内部及附近选择5个微卫星引物进行LOH分析，于DNA水平间接检测100例喉癌患者中该基因的缺失情况。结果5个STR位点均存在LOH，其中D17S1964E、D17S2092、D17S791、D17S1665及D17S808位点的LOH频率分别为30．48％、26．02％、21．62％、37．66%和21．51％，以D17S1665位点的LOH频率最高，杂合性丢失与临床分期无显著相关。结论Keratin13基因在喉癌的发生中具有重要作用，具体机制有待进一步研究。     

支气管哮喘患者白细胞介素4和白细胞介素13测定的临床意义

目的:探讨血清中白细胞介素4(IL-4)和白细胞介素13(IL-13)在支气管哮喘发病中的作用.方法:本研究对临床确诊的支气管哮喘46例,与正常对照组46例,分别抽取血清采用 ELISA 法测定其 IL-4、IL-13的含量.结果:支气管哮喘急性发作期病人和对照组正常人血清中的 IL-4水平分别为(460.84±27.11)和(132.97±24.66) ng/L,二组经 t 检验后 P＜0.001.两组 IL-13 的水平分别为(23.76±5.44)和(12.61±2.49) ng/L,二组经 t 检验后 P＜0.001.结论:哮喘病人 IL-4、IL-13 明显高于对照组,提示 IL-4、IL-13 对哮喘发病有一定的调控作用,对支气管哮喘气道非特异性炎症和局部免疫反应起重要作用.     

广东省儿童乙型肝炎疫苗纳入计划免疫管理10年后血清学效果分析

为研究广东省乙型肝炎 (乙肝 )疫苗纳入计划免疫管理 10年后儿童血清乙肝病毒感染标志物 (HBVM )的变化 ,采用分层多阶段随机抽样法 ,将全省分 4层 ,共抽取 12个县 2 4个村的 196 3名儿童为研究样本。采血用固相放射免疫法 (SPRIA)检测乙肝病毒表面抗原 (HBsAg)、乙肝病毒核心抗体 (抗 HBc)、乙肝病毒表面抗体 (抗 HBs)。2 0 0 2年调查 1～ 14岁儿童乙肝疫苗接种率为 78 81% ,全程接种率为 74 17%。其中 1～ 9岁儿童乙肝疫苗全程接种率为 81 73% ,10～ 14岁为 6 0 32 %。 1～ 14岁儿童HBsAg携带率、抗 HBc阳性率、HBV感染率分别从 1992年的 19 86 %、5 3 5 9%、71 4 1%降至 2 0 0 2年的 8 5 6 %、2 2 5 7%、31 33%。其中 1～ 9岁儿童的HBsAg携带率、抗 HBc阳性率、HBV感染率分别从 1992年的 17 88%、4 7 0 9%、6 7 4 4 %下降至 2 0 0 2年的 5 75 %、14 4 9%、2 1 81%。乙肝疫苗接种后 ,1～ 3岁儿童抗 HBs阳性率为 5 2 0 2 %～ 6 2 18%。由于实施了加强免疫 ,4～ 14岁儿童的抗 HBs维持在 5 9 32 %～ 6 5 80 %。广东省乙肝疫苗纳入计划免疫管理 10年后 ,全省 1～ 14岁儿童HBV感染率已大幅度下降 ,抗 HBs阳性率大幅度升高 ,取得了良好的经济和社会效益。     

Synthesis,Characterization, and in Vitro Stability of Chitosan-Methotrexate Conjugates

Pharmaceutical Research -     

Interference of oral poliovirus vaccine on RIT 4237 oral rotavirus vaccine

A vaccination trial, performed on 86 3-month-old infants, has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine. In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful. No interference by the RIT 4237 strain on live attenuated polioviruses was observed.