霍乱弧菌O139菌毛微球疫苗制备初探

为寻求Ｏ１３９型霍乱弧菌菌毛疫苗研制的新途径,用高分子聚乳酸－聚乙二醇共聚物（ＤＬ－ＰＬＧ）包裹毒素共调菌毛（ＴＣＰ）抗的,进行免疫学研究,结果表明微轩比游离疫苗诱导的抗体水平高,其中小鼠血清ＩｇＧ以皮下ＭＳ－ＴＣＰ组最高,唾液中的ｓＩｇＡ以口服ＭＳ－ＴＣＰ组最高,口服组主要诱导粘膜免疫,皮下组主要导全身性免疫,ＴＣＰ是霍乱弧菌的共同抗原之一,可作为霍乱疫苗的候选抗原。     

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.     

地高辛标记RT-PCR检测甲肝减毒活疫苗的研究

以编码甲肝病毒ＶＰ３ 羧基端的基因区为目标区,运用地高辛标记ＲＴＰＣＲ 法对甲肝疫苗进行检测,并与ＴＣＩＤ５０ 检测法进行比较。建立甲肝减毒活疫苗滴度的地高辛标记ＲＴＰＣＲ 检测法。结果显示：地高辛ＲＴＰＣＲ 法灵敏度略高于ＴＣＩＤ５０ 法,特异性与ＴＣＩＤ５０ 相似,且快速简便,易于推广应用。结果表明：地高辛标记ＲＴＰＣＲ 法是一种简便、快速、灵敏的甲肝病毒检测方法,可用作疫苗的常规检测。     

山东莒南HFRSⅡ型灭活疫苗效果观察

报告了ＨＦＲＳ地鼠肾细胞Ⅱ型灭活疫苗,自１９９４年以来,在莒南县高发疫区５个乡镇１７个村,对１６～６０岁的１１５１０人,全程免疫后４年的观察结果。疫苗初免３针后１４天、１年,血清中和抗体阳性率分别为６８９７％、１８５２％。加强１针后１４天达到１００％,加强后１年、２年、３年,中和抗体阳性率分别为６０００％、５３３３％、５０００％。几何平均滴度依次为８４、３２、１７０５、５７５、５３９、３６９。荧光抗体阳性率依次分别为９２００％、６２０７％、１００００％、５６００％、３２００％、２５００％。基础免疫后４年内,接种组发病１人,发病率为２１７／１０万;对照组发病６１人,发病率为１２８９１／１０万。疫苗保护率４年年均为９８３２％,安全性较好。疫苗接种者在流行高峰期后,荧光抗体滴度增高６人,均无临床表现。结论：ＨＦＲＳⅡ型灭活疫苗接种４年内,预防效果良好;接种人群未出现免疫增强反应病例。     

The effects of cyclosporin A,tamoxifen, and medroxyprogesterone acetate on the enhancement of Adriamycin cytotoxicity in primary cultures of human breast epithelial cells

Summary Adriamycin (Adr), the single most active agent used in the treatment of breast cancer, may become ineffective as treatment progresses due to the development of multidrug resistant (MDR) tumors. A major mechanism associated with MDR is increased P-glycoprotein (Pgp) expression. This study examined the abilities of the anti-estrogen tamoxifen (TAM) and the progestin medroxyprogesterone acetate (MPA) as well as cyclosporin A (CsA), a known resistance modifier, to enhance the cytotoxic effects of Adr on human breast epithelial cells (HBEC) in primary culture. Pgp and estrogen receptor (ER) expression were determined in each of the cultures by immunocytochemical assays using the monoclonal antibodies C219 and H222 Sp, respectively. The Adr-sensitive, Pgp-, ER+ MCF-7 cell line and the Adr-resistant, Pgp+, ER-MCF7-AdrR cell line were used as controls. Primary cultures were categorized as HBEC from tissues with or without previous chemotherapy. Pgp was detected in 1 of the 15 cell cultures from tissues without previous chemotherapy and in 5 of the 6 cell cultures from tissues previously exposed to chemotherapy. Incubation with either CsA or MPA plus Adr enhanced Adr toxicity in Pgp+ but not Pgp- cell cultures, whereas TAM had no effect on the sensitivity of any of the cultures. Of the 21 primary cultures of HBEC, 3 were ER+. There was no correlation between the enhancement of Adr cytotoxicity and ER status. The data suggest that MPA as well as CsA may be useful as modifying agents in overcoming Pgp-associated multidrug resistance.     

人肺癌相关抗原的基因克隆

目的克隆人肺癌相关抗原的基因。方法用λｇｔ１１Ｓｆｉ－Ｎｏｔ定向克隆载体构建人肺鳞癌细胞系Ｌ－７８的ｃＤＮＡ文库,并以抗人肺癌单抗ＡＬＴ－０４为探针进行了筛选。对名为ｈｌｃ－１４的ｃＤ－ＮＡ克隆作了测序分析与进一步研究。用重组的ｐＸＪ４１－ｈｌｃ１４质粒转染ＮＩＨ３Ｔ３细胞,通过免疫组化法对克隆基因进行了表达检测与鉴定,还观察了转染细胞的软琼脂集落形成能力。结果建成１．４×１０６ｐｆｕ／ｍｌ人肺癌ｃＤＮＡ文库,经过四轮免疫学筛选获得６个ｃＤＮＡ克隆,最大的ｃＤＮＡ克隆为ｈｌｃ－１４,长９５４ｂｐ。对该克隆的测序结果与基因库资料比较,未发现同源序列。ｈｌｃ－１４ｃＤＮＡ转染的ＮＩＨ３Ｔ３细胞有明显的肺癌相关抗原表达,并且在软琼脂中的集落形成能力增强。结论ｈｌｃ－１４是一个新的肺癌相关抗原的ｃＤＮＡ序列。这一序列的发现为阐明肺癌的发病机理、探索肺癌基因治疗的靶基因提供了新的线索     

Facial pain

Summary In a prospective material of 1052 patients the precipitating factors, associated symptoms, psychological and neurological deficits have been examined.Mastication and talking are the most frequently occurring precipitating factors, 76% as regards Neuralgia, with typical starting difficulties. As regards Non-neuralgiform Pain 24%, with precipitation late in the masticatory process. There were trigger zones in 50% of the cases of Typical Trigeminal Neuralgia and in 9% of the patients with Non-neuralgiform Pain. In a series of cases the jaw joint is perceived as a trigger zone. Cold precipitates pain in 48%–39%. Other precipitating factors are much more rare-psychological stress in 15% of the patients with Non-neuralgiform Pain, however.Vegetative associated symptoms were relatively frequent, lacrimation occurred in 31% of the cases of Typical Trigeminal Neuralgia and in 20% of the cases of Non-neuralgiform Pain. Rhinorrhea and salivation were less frequent. In terms of figures migrainoid associated symptoms had no connection with vegetative associated symptoms or with pain in the eye.In 11 % of the patients pain occurred most frequently during the night and in 20% the frequency of pain was the same day and night. About 1/3 of the patients with Neuralgia experienced seasonal variations.Tenderness of foramina is a symptom of no significance. Very few patients had primary sensory loss. No eye or ear symptoms have been found which may be referred to as the patho-anatomical basis of the pain.About 1/3 of the patients with Non-neuralgiform Pain had psychological symptoms whereas hardly any patients with Neuralgia had them. MMPI test performed on a small matched material showed no difference between Neuralgia and Non-neuralgiform Pain.In material B an examination has been made of the jaw joint arthrosis symptoms. A restriction of the diagnosis of arthrosis has had the effect that it must be recognized that patients with facial pain do not have the high frequency of jaw joint diseases previously assumed. As was also the case in a series of normal material previously published, between 1/5 and 1/3 of the patients with Neuralgia had jaw joint arthrosis which was due to old age.This study has not revealed any connection between previous diseases, the onset of pain, the character and course of the pain, the character of the attack, the localization of pain, precipitating factors, associated symptoms and symptoms of loss on the one hand and the patho-anatomical substratum on the other.The psychological examinations were performed by Mr. Peter Bruun, chief psychologist, for whose cooperation I am grateful.     

IL-2活化瘤苗对胃癌术后复发和转移的抑制作用

目的观察用细胞因子活化的特异性瘤苗辅助常规化疗,治疗外科手术后临床Ⅲ～Ⅳ期胃癌患者,抑制肿瘤术后复发、转移的临床疗效。方法于外科术后常规化疗结束后2周,用患者自体肿瘤细胞抗原致敏、IL-2活化的树突状细胞(DC)作为瘤苗给患者四肢皮下多点免疫注射1×106/(ml·次),每周1次,每疗程注射4次,0.5年后强化1次。定期胃镜、影象学和肿瘤标志物检查,随访至手术后第2年,观察生存期和生存率。结果经瘤苗治疗后,患者的免疫功能显著改善。术后24个月,瘤苗联合化疗组患者的生存率为50%,血清中CEA和CA724分别为(10±1.5)ng/ml和(5.5±1.5)U/ml,而单纯化疗组患者的生存率为10%,CEA和CA724的水平分别为(77.0±9.4)ng/ml和(55.0±7.6)U/ml;P<0.001。结论特异性瘤苗免疫治疗,能增强胃癌患者术后的特异性抗肿瘤免疫功能,提高手术后化疗疗效,抑制肿瘤复发和转移,能延长患者生存期,提高生存率。     

产前行妊娠相关血浆蛋白A筛查联合FISH诊断Down综合征

目的 :应用单项妊娠相关血浆蛋白A(PAPP A)筛查与羊水间期荧光原位杂交 (FISH)产前诊断相结合预防妊娠Down综合征胎儿。方法 :采用酶联免疫方法 (ELISA)对孕周分别为 6～ 2 7周的 1839例孕妇进行母血PAPP A单项筛查 ,以低于同一孕周的中位数时视为可能妊娠Down综合征胎儿的高风险孕妇。取高风险孕妇羊水细胞直接进行间期FISH产前诊断并同时用部分羊水细胞遗传学检查作对照。结果 :检出 1例孕 7周孕妇其PAPP A值为 0 0 5 1U/L ,低于同一孕周中位数 2 0多倍。羊水细胞间期FISH结果显示 ,含 5个杂交信号的核占所有杂交核的 38 5 % ,与细胞遗传学分析的 2 1三体核型完全一致。结论 :单项PAPP A筛查与羊水间期细胞FISH相结合是早期防治妊娠Down综合征有效可行的方法。     

Induction of carbohydrate‐specific antibodies in HLA‐DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human use

Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use.