重组2型腺相关病毒-转化生长因子β3对实验性肝纤维化大鼠肝脏组织病理学和Ⅰ型胶原表达的影响

Objective To investgate the effects of TGF β 3 on rat hepatic fibrosis. Methods The TGF β 3 cDNA was cloned into rAAV2 vector. Rats were randomly divided into four groups: normal control group, model group, negative control group and TGF β 3 group. Hepatic fibrosis was induced by hypodermic injection of 40% CCI4. Recombinant AAV2-TGF β 3 viral particles were injected via the vena caudalis one week before CCh treatment. Rats were executed 8 weeks after CCI4 treatment, global histological change was observed after HE staining, the distribution of the collagen fibers was observed after masson staining, his-tochemistry was done to observe the expression of collagen Ⅰ; The positive area rate of the collagen fibers and the average optical rate of collagen Ⅰ were quantified. Results HE staining indicated that collagen fibers were reduced in the TGF β 3 group. Masson staining shown that the collagen fibers were distributed around the blood vessel, in the portal area and disse space. Compared to the model group (13.2%±2.2%) and negative control group (12.3%±1.5%), the collagen fibers in liver tissues of TGF β3 group (7.7% ± 1.5%) were significantly decreased (q = 9.456, P < 0.01; q = 8.217, P < 0.01). Histochemistry indicated that the collagen fibers of liver tissues of TGF 15 3 group (0.185±0.033) were significantly higher than those in the model group (0.252±0.042) and the negative control group (0.230±0.029), (q = 6.228, P < 0.01; q = 4.346, P < 0.01). Conclusion TGF β 3 alleviates the damage to hepatic cell and the level offibrosis in CCI4 treated rats and inhibits the expression of collagen Ⅰ.     

Feline Immunodeficiency Virus Neuropathogenesis: From Cats to Calcium

Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that have greatly facilitated these efforts. This review summarizes contributions made from in vitro and in vivo studies on the infectious and pathological interactions of feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on FIV have provided insights into the natural progression of CNS disease as well as the contribution of various risk factors. In vitro studies have contributed to our understanding of immune cell trafficking, CNS infection and neuropathogenesis. Together, these studies have made unique contributions to our understanding of (1) lentiviral interactions at the blood–cerebrospinal fluid (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis in the brain, and (3) lentiviral effects on intracellular calcium deregulation and neuronal dysfunction. The ability to combine in vitro and in vivo studies on FIV offers enormous potential to explore neuropathogenic mechanisms and generate information necessary for the development of effective therapeutic interventions.     

乙型肝炎病毒免疫逃避株表面抗原决定簇编码区的序列分析

应用聚合酶链反应（ＰＣＲ）产物直接测序，在国内首次发现１例持续高滴度乙型肝炎表面抗原（ＨＢｓＡｇ）和抗一ＨＢｓ共存者携带的乙型肝炎病毒ＤＮＡ第５３２位碱基Ａ被Ｇ取代，推导其“ａ”决定簇中第１２６位苏氨酸被丙氨酸取代，提示该株“ａ”决定簇第一个结构环疏水性增加，由此可能导致其抗原性改变，而诱发免疫逃避株形成。     

Treatment of chronic hepatitis B

SUMMARY. Chronic infection with the hepatitis B virus (HBV) is a major cause of worldwide morbidity and mortality. A large number of therapeutic approaches has been tried, including interferon (IFN), nucleoside analogues and immunomodulators. To date controlled clinical trials have shown that only IFN is of long-term value but many patients fail to respond to treatment. New approaches to treating patients with IFN-resistant hepatitis B are currently undergoing clinical and experimental evaluation, and it seems likely that new therapeutic agents will be available in the near future.     

Detection of Epstein Barr virus in an hepatic leiomyomatous neoplasm in an adult human immunodeficiency virus 1-infected patient

We report the first case of a human immunodeficiency virus (HIV)-related primary hepatic leiomyoma in an adult patient. The diagnosis was made at autopsy and confirmed by immunohistochemistry. Epstein Barr virus (EBV) was identified in tumour cells by in situ hybridization. Review of the literature revealed 13 cases of visceral myogenic tumours occuring in acquired immunodeficiency syndrome children, and only 2 cases in adults. One was a spinal epidural leiomyoma, the other multiple smooth muscle tumours of the colon and adrenal gland. This is the first report of EBV in smooth muscle neoplastic cells in an HIV-infected adult patient.     

Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm     

聚合酶链反应检测尖锐湿疣皮损内人乳头瘤病毒

１３个皮损组织取自１３例尖锐湿疣（ＣＡ）患者，１３例基底细胞上皮瘤（ＢＣＣ）组织作为对照，用溴化钠液分离表真皮，从组织中提出的 ＤＮＡ和溴化钠液分别用聚合酶链反应检测 ＨＰＶ ＤＮＡ。１１例ＣＡ表皮中检出 ＨＰＶ ＤＮＡ，ＨＰＶ６有７例，ＨＰＶ１１有４例。３例ＣＡ真皮中发现有ＨＰＶ ＤＮＡ，ＨＰＶ６有２例，ＨＰＶ１１有１例。２例标本因溴化钠液被ＨＰＶ污染未作统计。在ＢＣＣ组织中未发现有ＨＰＶ ＤＮＡ。在某些ＣＡ真皮内含有 ＨＰＶ ＤＮＡ可以解释散发病例的复发性。     

An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

Infection dynamics and virus-induced apoptosis in cell culture-based influenza vaccine production—Flow cytometry and mathematical modeling

Cell culture-based influenza vaccine manufacturing is of growing importance. Depending on virus strains, differences in infection dynamics, virus-induced apoptosis, cell lysis and virus yields are observed. Comparatively little is known concerning details of virus–host cell interaction on a cellular level and virus spreading in a population of cells in bioreactors. In this study, the infection of MDCK cells with different influenza A virus strains in lab-scale microcarrier culture was investigated by flow cytometry. Together with the infection status of cells, virus-induced apoptosis was monitored. A mathematical model has been formulated to describe changes in the concentration of uninfected and infected adherent cells, dynamics of virus particle release (infectious virions, hemagglutinin content), and the time course of the percentage composition of the cell population.     

Impact of gastrointestinal endoscopy on HIV‐infected children

Objective: To evaluate the role of gastrointestinal (GI) endoscopy in human immunodeficiency virus (HIV)‐infected children with GI problems. Methods: From 1998 to 2002, we retrospectively reviewed all cases of HIV‐infected children presenting with GI problems in which an upper or lower GI endoscopy was indicated. The initial diagnostic endoscopic examination and any repeat endoscopic session leading to a new diagnosis were used in the data analysis. Tissue biopsies were obtained from all abnormal lesions and representative sites of normal‐appearancing GI mucosa. Results: Fourteen patients (median age: 22.5 months) underwent 23 sessions of GI endoscopy, including 10 esophagogastroduodenoscopy, nine colonoscopy and four flexible sigmoidoscopy. Chronic diarrhea was the most common indication, followed by lower GI bleeding, abdominal/retrosternal pain, dysphagia/odynophagia, and upper GI bleeding. Gross endoscopic abnormalities were observed in 78.3%; whereas histological inflammation and opportunistic pathogens were identified in 87% and 43.5%, respectively. Cytomegalovirus was the most common identified pathogen. Abnormal gross findings were significantly associated with histological inflammation and identification of pathogens (P = 0.006 and 0.046, respectively). Specific changes in medical management were made in 50% of cases as a result of endoscopic investigation. Conclusion: If non‐invasive investigations for HIV‐infected children with GI symptoms fail to establish a diagnosis, gastrointestinal endoscopy should be performed and often yields a positive result leading to changes in medical management.