泛昔洛韦体内抗鸭乙型肝炎病毒核酸的疗效研究

我们用重庆麻鸭乙型肝炎动物模型，观察核苷酸类似物泛昔洛韦体内抗鸭乙型肝炎病毒（ｄｕｃｋｈｅｐａｔｉｔｉｓＢｖｉｒｕｓ，ＤＨＢＶ）的作用，为临床用药提供实验依据。一、材料与方法１．动物模型：采用健康成年的重庆麻鸭产的蛋孵化的１日龄雏鸭，经腹腔接种０．１ｍｌＤＨＢＶＤＮＡ阳性病毒血清。接种１周后，分别颈外静脉抽血，用地高辛标记的ＤＨＢＶＤＮＡ探针（标记药盒购于德国ＢｏｅｈｒｉｎｇｅｒＭａｎｎｈｅｉｍ公司）经斑点杂交检测筛选出感染阳性鸭，饲养至３周龄作为实验动物。２．实验分组及用药：将ＤＨＢＶ　ＤＮＡ…     

下丘脑内血管升压素在紧张应激引起大鼠血压升高反应中的作用

目的观察下丘脑血管升压素（ｖａｓｏｐｒｅｓｓｉｎ，ＡＶＰ）在慢性紧张应激引起大鼠血压升高过程中的作用。方法实验在给予慢性应激刺激后，引起动物血压出现显著升高的雄性Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠中进行。在通过侧脑室（ｉｃｖ．）及外周静脉（ｉｖ．）给予大鼠注射血管升压素Ｖ１受体拮抗剂ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后，观察其对动物平均动脉压（ＭＢＰ）的影响。结果在正常大鼠中ｉｃｖ．或ｉｖ．注射ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后，动物ＭＢＰ无显著改变，但在慢性应激引起血压出现显著升高的大鼠中，ｉｃｖ．ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后，动物血压出现显著降低，降压反应持续约２ｈ，最大效应出现在给药后约４５ｍｉｎ，大鼠ＭＢＰ从给药前的１３４±１１．９ｍｍＨｇ的基础上，平均下降３５．６±１２．６ｍｍＨｇ，而通过ｉｖ．ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后，却未观察到ＭＢＰ有显著改变。结论由下丘脑合成并释放的ＡＶＰ参与慢性应激引起的大鼠血压升高反应，其作用可能主要通过中枢Ｖ１受体实现     

基因疫苗诱导小鼠抗HBV皮下移植瘤免疫研究

目的　观察 ＨＢＶ ＤＮＡ 疫苗（ｐＣＲ３－１Ｓ） 诱导Ｂａｌｂ／ ｃ 小鼠（ Ｈ２ｄ） 的特异性细胞免疫应答及其对稳定表达ＨＢｓＡｇ 的小鼠肥大细胞瘤Ｐ８１５ 细胞（Ｐ８１５ＨＢＶＳ） （ Ｈ２ｄ） 成瘤性的影响．方法　肌肉注射ＤＮＡ 疫苗,背部皮下接种Ｐ８１５ＨＢＶＳ 细胞,观察成瘤情况,４ ｈ ５１Ｃｒ 释放法检测小鼠脾细胞ＣＴＬ 活性．结果　接种 ＤＮＡ 疫苗后小鼠成瘤率为１２－５ ％ , 对照组为１００ ％ ． 小鼠平均存活期大于３８－２ ｄ ,对照组为２８－４ ｄ ,４０ ｄ 后小鼠存活率为８７－５ ％ ,对照组为０ ％ ． ＣＴＬ 细胞杀伤活性明显增加,ｐＣＲ３－１Ｓ 组５１ ％ ,对照组为２１ ％ （ Ｐ＜ ０－００１） ．结论　ＤＮＡ 疫苗可以诱导细胞免疫应答,对体内ＨＢＶ 感染具有预防及治疗作用．     

丙型肝炎病毒E1，E2/NS1，NS5蛋白基因在大肠杆菌内的表达及其产物的初步应用

目的在体外表达及纯化ＨＣＶ不同功能区的病毒蛋白，用于研究ＨＣＶ各功能区抗体的临床意义。方法将ＨＣＶＥ１，Ｅ２／ＮＳ１，ＮＳ５区的部分基因片段克隆到表达质粒ＰＭＡＬ－ＣＲＩ中ＭＢＰ编码基因的下游，在大肠杆菌中进行表达。结果表达的融合蛋白ＭＢＰ－Ｅ１，ＭＢＰ－Ｅ２／ＮＳ１，ＭＢＰ－ＮＳ５的分子量分别为５７０００、６５０００、６２０００，ＷｅｓｔｅｒｎＢｌｏｔ分析表明这些融合蛋白具有ＨＣＶ的抗原活性。将这三种融合蛋白纯化后作为抗原检测了丙型肝炎患者血清９５份，其中抗－ＨＣＶＥ１阳性率为１０．５％，抗－ＨＣＶＥ２／ＮＳ１为６３．２％，抗－ＨＣＶＮＳ５为５３．７％。结论本实验表达的ＨＣＶ融合蛋白在ＨＣＶ感染的血清学诊断中具有一定的价值。     

PTF—V1值变化对判定经皮穿刺二尖瓣球囊扩张术疗效的价值

观察２３例二尖瓣狭窄者ＰＢＭＶ前，后ＰＴＦ－Ｖ１的变化，并与二尖瓣口面积、左房内径、心功能的变化特点进行比较。结果显示；ＰＢＭＶ前、后ＰＴＦ－Ｖ１二尖瓣口面积、左房内径分别是：－０．０９ｍｍ．Ｓ、１．０６ｃｍ＾２、４２．８ｍｍ和－０．０４ｍｍ．Ｓ、１．９３ｃｍ＾３、３７．７ｍｍ－ＰＴＦ－Ｖ１与二尖瓣口面积呈正相关与左房内径呈负相关。     

慢性HBV感染者外周血单个核细胞中白细胞介素-12 mRNA的表达

１．资料与方法：（１）病例为我科２０００年２－８月收治的５１例门诊及住院慢性ＨＢＶ感染者,男４２例,女９例,平均（３５±８）岁。诊断按１９９５年全国病毒性肝炎诊断标准,排除ＨＣＶ、ＨＤＶ、ＨＩＶ感染。（２）外周血单个核细胞（ＰＢＭＣ）总ＲＮＡ提取及ＩＬ—１２ Ｐ４０ ｍＲＮＡ基因扩增：常规分离ＰＢＭＣ按ＲＮＡ提取试剂盒（Ｐｒｏｍｅｇａ公司）操作说明提取ＰＢＭＣ中总ＲＮＡ;一步法ＲＴ－ＰＣＲ（试剂盒购于Ｑｕｉａｇｅｎ公司）进行ＩＬ－１２ Ｐ４０和β肌动蛋白（β－ａｃｔｉｎ）基因扩增,引物序列为ＩＬ－…     

检测慢性丙型肝炎患者抗－HCVIgM的临床意义

对８２例输血后慢性丙型肝炎病人丙型肝炎病毒抗体（抗－ＨＣＶ）ＩｇＭ动态变化进行观察，８２例患者均检测到抗－ＨＣＶ抗体，其中５１例抗－ＨＣＶＩｇＭ阳性。抗－ＨＣＶＩｇＭ出现规律表现为４种类型：（１）持续检出型２４例（２９．２７％）；（２）间断检出型８例（９．７６％）；（３）短暂检出型１９例（２３．１７％）；（４）阴性型３１例（３７．８０％）。将８２例输血后慢性丙型肝炎抗－ＨＣＶＩｇＭ出现类型与丙氨酸转氨酶（ＡＬＴ）、ＨＣＶＲＮＡ消长情况比较，发现阴性型具有较低的ＡＬＴ峰值，而其它３型ＡＬＴ峰值较高（Ｐ＜０．０１）。８例经干扰素治疗的慢性活动性丙型肝炎患者，治疗前均有ＡＬＴ明显异常及ＨＣＶＲＮＡ、抗－ＨＣＶＩｇＭ阳性，治疗后１～３个月ＡＬＴ均转为正常，ＨＣＶＲＮＡ转为阴性，但其中只有３例伴抗－ＨＣＶＩｇＭ的阴转，随访１年发现，只有抗，ＨＣＶＩｇＭ阴转的３例病人得以痊愈，其余５例均在治疗后半年内病情复发。提示治疗中伴有抗－ＨＣＶＩｇＭ阴转的患者预后良好。     

PTF－V_1值变化对判定经皮穿刺二尖瓣球囊扩张术疗效的价值

观察２３例二尖瓣狭窄者ＰＢＭＶ前、后ＰＴＦ－Ｖ１的变化，并与二尖瓣口面积、左房内径、心功能的变化特点进行比较，结果显示：ＰＢＭＶ前、后ＰＴＦ－Ｖ１、二尖瓣口面积、左房内径分别是：一０．０９ｍｍ·Ｓ、１．０６ｃｍ２、４２．８ｍｍ和－０．０４ｍｍ·Ｓ、１．９３ｃｍ２、３７．７ｍｍ（Ｐ＜０．００１），ＰＴＦ－Ｖ１与二尖瓣口面积呈正相关，与左房内径呈负相关。提示ＰＴＦ－Ｖ１变化可作为判定ＰＢＭＶ疗效的一项简便、有效的指标。     

免疫吸印法检测实验感染戊型肝炎病毒的猕猴血清抗—HEV,ORF2和 …

目的与方法 应用戊型肝炎病毒（ＨＥＶ）中国株基因结构区的３种重组融合蛋白ＧＳＴ－ＯＲＦ２．１，ＧＳＴ－ＯＲＦ２．３，ＧＳＴ－ＯＲＦ３建立的免疫吸印法（ｗｅｓｔｅｍｂｌｏｔ，ＷＢ）对实验感染中ＨＥＶ的２只猕猴的３４份系列血清抗－ＨＥＶＯＲＦ２．１，ＯＲＦ２．３和ＯＲＦ３抗体进行了检测。结果 抗－ＨＥＶＯＲＦ２．１出现较早，于感染后１３天即阳转，且持续时间较长，在康复后１５个月仍呈现强阳性；抗－ＨＥＶ     

膦甲酸钠治疗巨细胞病毒感染的临床观察

目的：研究国产膦甲酸钠（ＰＦＡ）治疗肾移植术后巨细胞病毒（ＣＭＶ）感染患者的疗效与不良反应。方法：肾移植术后５５例ＣＭＶ活动必发６例有明显临床症状）患者使用ＰＦＡ,随机另选１０例静止期感染患者不予处理作对照。ＰＦＡ用量为４０ｍｇ／ｋｇ,２／日,２～３周为１疗程。结果：无症状者ＰＦ和３．４天后血清学抗ＣＭＶ－ＩｇＭ。转阴,有症状者１４天后全部显效,临床症状消失,血清学抗ＣＭＶ－ＩｇＭ转阴,另２例治疗     

Rofecoxib: a possible cause of acute colitis

Nonsteroidal antiinflammatory agents may cause relevant small bowel and colonic side effects, apart from gastroduodenal lesions. The synthesis of selective cyclooxygenase-2 (COX-2) inhibitors has been an important breakthrough in antiinflammatory therapy by decreasing the incidence of upper gastrointestinal lesions. However, there is little information available concerning their effects on gut mucosa distally to the duodenum. A case history is described of a 52-year-old woman with a temporary colostomy after resection of a sigmoid tumor and who presented with bloody diarrhea 5 days after beginning therapy with rofecoxib. The hemorrhage had its origin in the transverse colon, and the endoscopic appearance was that of actively bleeding acute hemorrhagic colitis. No other colonic lesions were detected, nor was there any evidence of related infection, bleeding diathesis, or other systemic diseases. On discontinuing rofecoxib and instituting parenteral rehydration, the bleeding and diarrhea stopped. Endoscopic follow-up revealed regenerating mucosa in the transverse colon. The time relation, the absence of other causes of hemorrhage, and the clinical evolution all strongly support the probability of a causal relation between rofecoxib and hemorrhagic colitis. This case may raise awareness concerning the possibility of colonic lesions related to the new COX-2 inhibitors, similar to what is known about nonselective antiinflammatory agents.     

Infection of rhesus and cynomolgus macaques with a rapidly fatal SIV (SIVSMM/PBj) isolate from sooty mangabeys.

A variant of simian immunodeficiency virus (SIVSMM/PBj), isolated from a chronically infected pig-tailed macaque has been shown in previous studies to produce acutely fatal disease uniformly in pig-tailed macaques and in some rhesus macaques. The present study extends investigation of SIVSMM/PBj pathogenesis in rhesus and cynomolgus monkeys. Cynomolgus and rhesus macaques were found to be uniformly susceptible to infection, but as previously reported, the rhesus were found to not be uniform in their response during the acute disease. Homogenized tissues from a rhesus that died acutely from SIVSMM/PBj were passaged to 6 rhesus monkeys in an attempt to increase lethality. Five of 6 rhesus monkeys receiving intravenous inoculation of either spleen (10(3) TCID50) or lymph node (10(5) TCID50) homogenate developed acute disease; 4 died (days 8-10), 1 recovered, and one rhesus remained asymptomatic. Three of 3 cynomolgus macaques and 4 of 4 pig-tailed macaques receiving the same inoculum died acutely within 9 days. Clinical disease in macaques that died was characterized by diffuse lymphadenopathy within 5 days of inoculation and severe diarrhea beginning 1 to 3 days before death. Anorexia, lymphopenia (< 1000 cells/mm3), and mild hypoalbuminemia preceded onset of diarrhea by 24 h. Viral p27 was detected in circulation by day 6 postinfection, with all animals dying acutely having detectable serum p27 and no detectable humoral response. Acute lethality was attributed to severe metabolic acidosis (pH < 7.20) which was observed 24-48 h prior to death in the pig-tailed and cynomolgus macaques. Immunohistochemistry revealed numerous SIV antigen-positive lymphocytes and macrophages in the lymph nodes, spleen, gut-associated lymphoid tissues and gastrointestinal lamina propria. Histopathologic lesions included marked to severe hyperplasia of the T-cell-dependent areas in lymphoid tissues and diffuse nonulcerative lymphohistiocytic gastroenteritis. Surviving rhesus developed strong humoral immune responses to the major SIV proteins.     

Induction of congenital hydrocephalus with mumps virus in rhesus monkeys.

Rhesus monkey fetuses were inoculated intracerebrally with wild-type mumps virus near the beginning of the last third of the gestation period. Within three days after inoculation, mumps virus was isolated from many fetal tissues. Thirteen animals receiving virus were delivered at term. Five of these showed slight to severe hydrocephalus. Hydrocephalus was most prominent in the posterior horns of the lateral ventricles, but other lesions occurred at various levels of the ventricular system. Virus was isolated from three animals at one day of age (two months after inoculation). However, mumps virus was not recovered from one-month-old monkeys. The recovery of mumps virus from newborn rhesus monkeys two months after inoculation suggests that attempts should be made to document similar persistence of the virus in humans. Furthermore, this model indicates that mumps virus infection in humans may result in hydrocephalus.     

Pathology of dual Mycobacterium leprae and simian immunodeficiency virus infection in rhesus monkeys

Three rhesus monkeys were experimentally inoculated with sooty-mangabey-derived Mycobacterium leprae and were inadvertently infected with the simian immunodeficiency virus (SIV) as well. They died of an immunodeficiency syndrome, and at autopsy all had lesions caused by M. leprae. One monkey was inoculated twice with M. leprae, initially with an inoculum from a sooty mangabey that was not infected with SIV and, subsequently, with an inoculum from a mangabey that was SIV infected. The monkey did not develop clinical lesions and became strongly lepromin skin test (LST) positive after the first inoculation, but became infected with both agents and LST negative following the second inoculation. These observations suggest that SIV-infected rhesus monkeys have an increased susceptibility to M. leprae infection and, by analogy, imply that HIV-infected human beings may have an increased susceptibility as well.     

Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses.

The purpose of this study was to determine whether rhesus monkeys of Chinese origin are suitable for studies of mucosal lentivirus transmission by comparing the relative ability of these animals and rhesus macaques of Indian origin to become infected by vaginal (IVAG) inoculation with SIVmac251. In addition, we sought to test the hypothesis that differences in viral load during the first few weeks after inoculation were due to the relative strength of the anti-SIV immune responses in the two populations of rhesus macaques. Significant difference was not observed between the number of Indian and Chinese origin monkeys that were infected after IVAG SIV inoculation in this study. For 8-9 weeks after infection there was considerable overlap in the range of viral loads among the Indian and Chinese animals and the variation among the Indian origin animals was greater than the variation among the Chinese origin monkeys. By 6 weeks postinfection, viral loads in SIV-infected Chinese origin monkeys tended to be at the lower end of the range of viral loads observed in SIV-infected Indian origin monkeys. The strength of the anti-SIV antibody response was also more variable in the Indian origin rhesus macaques, but at 6-8 weeks postinfection, Chinese and Indian origin rhesus macaques had similar titers of anti-SIV antibodies. Microsatellite allele frequencies differed between Chinese and Indian rhesus macaques; however, the majority of alleles present in Indian-origin animals were also found in Chinese macaques. Together these results show that host factors, other than geographic origin, determine the ability of a rhesus macaque to be infected after IVAG SIV exposure and that geographic origin does not predict the viral load of SIV-infected animals during the first 8-9 weeks after IVAG inoculation.     

Acute right-sided hemorrhagic colitis associated with oral administration of ampicillin

Among 56 cases who presented to Kanto-Teishin Hospital complaining of bloody diarrhea or considerable hematochezia of acute onset, 8 cases (14.3%) were considered due to colitis associated with oral ampicillin therapy. The bloody diarrhea, often with abdominal cramps, began 2–7 days after starting the treatment. The dosage of ampicillin taken ranged from 2.0 to 4.5 g. Early total colonoscopy and biopsy revealed marked mucosal hemorrhage with minimal or no inflammatory changes mainly in the right colon. Rectum and sigmoid colon are completely normal except in one case. Symptoms rapidly resolved after the endoscopy. At follow-up colonoscopy, performed 4–12 days later, the mucosal changes had cleared completely. There was no evidence to support a hypersensitivity reaction of the colonic mucosa to ampicillin. We believe that right-sided hemorrhagic colitis is one of the common forms of colitis associated with ampicillin. Its differentiation from other kinds of acute colitis and the importance of early total colonoscopy are discussed.     

Protective Effect of Lactulose on Dextran Sulfate Sodium-Induced Colonic Inflammation in Rats

Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS), and histology were examined. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. These results demonstrated the protective effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora.     

Post-antibiotic diarrheas: role of Klebsiella oxytoca]

From May 1989 to January 1991, 20 patients were investigated for antibiotic-associated acute diarrhea. Colonoscopy or rectosigmoidoscopy was performed in each patient. Cultures of colonic mucosal biopsies were carried out using conventional culture grounds (cystine-lactose-electrolyte-deficient). The aim of this study was to investigate the role of a gram negative bacillus: Klebsiella oxytoca. Among the 20 patients with antibiotic-associated acute diarrhea, 11 had bloody and mucus diarrhea and colitis ranging from a right-sided hemorrhagic to diffuse acute ulcerative or erosive colitis, 7 had a grossly normal colonic appearance, while 2 had mucus diarrhea and pseudomembranous colitis. Of colonic biopsies cultures obtained from 36 control patients, 15 had a normal colonic appearance, 15 had ulcerative or crohn's colitis, 6 had well-tolerated amoxicillin therapy. Klebsiella oxytoca was never found in the 36 control patients; Klebsiella oxytoca was noted among 8/11 patients with mucus-discharging and bloody diarrhea. These results suggest that antibiotic-associated, non pseudomembranous colitis is frequently associated with Klebsiella oxytoca infection, which may be the cause of this type of colitis.     

A rhesus monkey model for the study of Bolivian hemorrhagic fever.

Two groups of rhesus monkeys were inoculated with either 10(5) (group 1) or 10(3) (group 2) plaque-forming units of Machupo virus, the etiologic virus of Bolivian hemorrhagic fever. The monkeys were observed for clinical signs; body temperatures, viremias, hematologic changes, and virus-neutralizing antibody were measured. The onset of clinical signs for groups 1 and 2 occurred on days 4-6 and 7-10, respectively, with fever, anorexia, and depression. These and other signs became more severe, and all of the monkeys died; the respective mean times to death for groups 1 and 2 were 14.3 and 19.5 days. Hematocrit, neutrophil, and lymphocyte values decreased in both groups until a few days before death and then increased slightly. Viremias in the two groups peaked on days 13 and 16, respectively, and persisted until death; the sole exception was one monkey in group 2 that developed neutralizing antibody by day 21. The response of the rhesus monkey to Machupo virus thus provides a useful model for the study of Bolivian hemorrhagic fever.