环介导等温基因扩增技术及其在病毒检测中的应用

环介导等温扩增是一门新兴的分子生物学检测技术,因其具有特异性高、敏感性高、简单、快捷及不需要昂贵的仪器设备等特点,受到了生物医学研究者的高度关注。目前,该方法已经被广泛应用于各种病原微生物检测。简要综述了环介导等温扩增技术的原理、特点,及其在病毒检测中的应用。     

Giardia and Cryptosporidium join the 'Neglected Diseases Initiative'

Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens that infect humans, domestic animals and wildlife worldwide. Both pathogens are significant causes of diarrhea and nutritional disorders in institutional and community settings. They are also significant waterborne pathogens. In developing regions of the world, Giardia and Cryptosporidium constitute part of the complex group of parasitic, bacterial and viral diseases that impair the ability to achieve full potential and impair development and socio-economic improvements. All diseases included in the WHO Neglected Diseases Initiative have a common link with poverty and, as the current view is to take a comprehensive approach to all these diseases, both Giardia and Cryptosporidium were included in 2004. Our current state of knowledge of Giardia and Cryptosporidium is summarized here, and some important questions are raised that need to be addressed if control strategies are to be effective.     

Pathogenic bacteria as vaccine vectors: teaching old bugs new tricks

As our scientific knowledge of bacteria grows, so does our ability to manipulate these bacteria to protect rather than infect mammalian hosts from a diverse group of diseases. The old axiom that the best way to protect from a disease is to get infected in the first place is not feasible in the face of the diverse group of pathogens that infect humans. Therefore, reprogramming bacteria to protect against diverse bacterial, viral, and parasitic diseases as well as cancer is a new reality in the field of vaccines.     

DNA疫苗免疫佐剂的研究进展

DNA疫苗是最近几年从基因治疗研究领域发展起来的一种新型疫苗,它能诱导机体产生持久的体液免疫和细胞免疫应答,能够抗病毒,细菌和寄生虫的感染,对自身免疫性疾病和过敏性疾病有一定的疗效作用。但与传统的灭活疫苗相比,其免疫效价还比较低,最近的研究表明：联合使用DNA疫苗和疫苗佐剂如细胞因子,协同刺激分子等有助于提高DNA疫苗的免疫效价,这一发现有利于研制更有效的DNA疫苗,本文就通过使用免疫佐剂提高DNA免疫效价的最新进展做一综述。     

Niclosamide: Beyond an antihelminthic drug

Niclosamide is an oral antihelminthic drug used to treat parasitic infections in millions of people worldwide. However recent studies have indicated that niclosamide may have broad clinical applications for the treatment of diseases other than those caused by parasites. These diseases and symptoms may include cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, and systemic sclerosis. Among the underlying mechanisms associated with the drug actions of niclosamide are uncoupling of oxidative phosphorylation, and modulation of Wnt/β-catenin, mTORC1, STAT3, NF-κB and Notch signaling pathways. Here we provide a brief overview of the biological activities of niclosamide, its potential clinical applications, and its challenges for use as a new therapy for systemic diseases.     

The role of tetraspanins in the pathogenesis of infectious diseases

Tetraspanin proteins on host cells are involved in the pathogenesis of infectious diseases at different stages. In this review, we will focus on tetraspanins expressed in the immune system and the role they play in the defense to viral, bacterial, parasitic and fungal infections.     

Identification of a common gene expression response in different lung inflammatory diseases in rodents and macaques

To identify gene expression responses common to multiple pulmonary diseases we collected microarray data for acute lung inflammation models from 12 studies and used these in a meta-analysis. The data used include exposures to air pollutants; bacterial, viral, and parasitic infections; and allergic asthma models. Hierarchical clustering revealed a cluster of 383 up-regulated genes with a common response. This cluster contained five subsets, each characterized by more specific functions such as inflammatory response, interferon-induced genes, immune signaling, or cell proliferation. Of these subsets, the inflammatory response was common to all models, interferon-induced responses were more pronounced in bacterial and viral models, and a cell division response was more prominent in parasitic and allergic models. A common cluster containing 157 moderately down-regulated genes was associated with the effects of tissue damage. Responses to influenza in macaques were weaker than in mice, reflecting differences in the degree of lung inflammation and/or virus replication. The existence of a common cluster shows that in vivo lung inflammation in response to various pathogens or exposures proceeds through shared molecular mechanisms.     

Descriptive epidemiology of roe deer mortality in Sweden

A retrospective epidemiologic study was conducted to examine causes of mortality of 985 wild roe deer (Capreolus capreolus) submitted to the National Veterinary Institute (SVA; Uppsala, Sweden) from January 1986 to December 1995. Age, sex, body condition, and geographic distribution as related to disease conditions are reported herein. The most common causes of mortality in roe deer were trauma (19%), winter starvation (18%), gastritis/enteritis (15%), bacterial infections (11%), parasitic infection (11%), systemic diseases (11%), neoplasia (2%), congenital disorders (1%), and miscellaneous causes (6%). Cause of death was not determined in 6% of the cases. The distribution of causes of death reported in this study differ from previous works in Sweden in that infectious and parasitic diseases were more common than winter starvation. The pathologic findings in studies like this do not necessarily represent what is occurring in the natural environment, but they do provide a good indication of distribution of diseases over time as well as age and sex structure in relation to disease conditions. Further research and more detailed studies are in progress to better understand specific mortality factors as well as etiologies of certain described diseases in roe deer in Sweden.     

二氢乳清酸脱氢酶的结构特征和催化循环研究进展

二氢乳清酸脱氢酶是黄素依赖的线粒体酶,它催化嘧啶从头合成的第4步反应,将二氢乳清酸氧化为乳清酸。通过选择性抑制二氢乳清酸脱氢酶,从而抑制嘧啶的合成,已被开发用于治疗癌症、自身免疫性疾病、细菌或病毒感染以及寄生虫疾病等。抑制剂的开发需详细了解二氢乳清酸脱氢酶的结构特征和催化循环机制。因此,文中主要从这两个方面进行了综述,并展望了该酶的抑制剂在临床应用中的前景。     

An immunologic method of producing antigens for the treatment and prevention of leishmaniasis

Antigens isolated from lysates of L. infantum promastigotes by electroelution from polyacrylamide gels and by gel filtration, have already been proven to induce anti-Leishmania protective immunity in BALB/c mice when injected subcutaneously. At the present time, five preparations including either Leishmania antigens or anti-idiotypic reagents as vaccines can be considered as candidates for immunoprophylaxis in natural hosts of Leishmania parasites. We present a new method for producing Leishmania antigenic preparations which is of considerable interest, since it can be proposed for immunotherapy and prevention of other parasitic, bacterial, viral and perhaps, retroviral diseases.     

Breach of IL-12 monopoly in the initiation of type 1 immunity to intracellular infections: IL-12 is not required.

IL-12 is believed to play an important role in type 1 T-cell differentiation and type 1 cytokine IFN-gamma release by T- and NK-cells and macrophages in host defense against intracellular infections by bacteria, parasites, fungi and viruses. However, recent studies by us and others have provided unequivocal evidence that while IL- 12 is critically required for the development of type 1 immunity to the majority of intracellular bacterial, parasitic and fungal infections, it is not required for anti-viral type 1 immune responses. These findings have provoked our re-thinking about the role of IL-12 in type 1 immunity and the search for additional cytokines capable of initiating anti-viral type 1 immunity. We hypothesize that there exist multiple cytokines including IL-12 which play a redundant role in the initiation of type 1 immunity against viral infection. These cytokines are likely released from not only antigen-presenting macrophages/dendritic cells but many other cell types, which suits the mode of viral infection. The existence of multiple factors capable of driving type 1 immunity endows the host with additional safeguards to cope with prevalent viral foes.     

Substance P is associated with heart enlargement and apoptosis in murine dilated cardiomyopathy induced by Taenia crassiceps infection

Dilated cardiomyopathy (degeneration of heart muscle and heart enlargement) is an important cause of heart failure among young adults. Dilated cardiomyopathy may be a complication during or after various viral, bacterial, or parasitic diseases. Substance P (SP) is a neurotransmitter that is involved in the pathogenesis of various diseases. To determine whether SP is associated with cardiac changes in murine cysticercosis, we compared heart-weight to body-weight ratio, cardiac pathology, cardiomyocyte size, and cardiac-apoptosis (TUNEL assay) in hearts from Taenia crassiceps-infected (wild-type vs. SP-knockout) mice. We noted that, as compared with control uninfected wild-type mice, elevated protein levels of SP and its receptor as studied by ELISA or immunohistochemistry, respectively, were elevated in the hearts of parasite-infected wild-type mice. The heart-weight to body-weight ratios were significantly higher in the parasite-infected wild-type mice versus those of the infected SP-knockout mice. Furthermore, wild-type infected mice developed dilated cardiomyopathy with increased chamber size of both ventricles, decreased ventricular wall thickness, compensatory cardiomyocyte hypertrophy, and increased cardiac apoptosis. This cardiac pathology did not develop in mice lacking SP activity (i.e., in infected SP knockout mice) or in uninfected mice. These data indicate that SP is associated with cardiac changes in an animal model of parasitic dilated cardiomyopathy.     

Chemotherapy of fish diseases: a review

Fish suffer from environmental, nutritional, viral, bacterial, parasitic, and neoplastic diseases, many of which are similar to those of higher animals. The prevention and treatment of these diseases follow the same principles as diseases of other animals. Fish culture is similar to poultry husbandry in that large numbers of animals are crowded into relatively small areas, feeding is free choice, and medication for systemic infections is usually oral. External treatment of fishes is more common than of poultry, due to a higher frequency of external diseases. Many of the drugs and chemicals used in chemotherapy of fishes are the same as for higher animals. The following is a brief review of the more important drugs and their methods of administration.     

Diseases of the Callitrichidae: a review.

The Callitrichidae contains four genera that embrace up to 50 species and subspecies found in neotropical habitats. Certain members have either naturally occurring or induced conditions that serve as important models of human disease. They include viral, bacterial, and parasitic infections, nutritional deficiencies, neoplasia, and various other conditions. The spontaneous diseases of captive callitrichids and those to which these species are experimentally susceptible were reviewed.     

Infectious disease mortality in the USSR

In recent decades infectious and parasitic diseases (class 1 according to the International Classification of Diseases-9) constitute 2-3% of causes in the total morbidity structures in the USSR. The main causes of death among diseases of class 1 are tuberculosis (37%), acute enteric infections (30%), septicemia (11%), viral hepatitides (11%), meningococcal infection (4%), measles (2%). The main groups are children aged up to 2 years (48% of fatal cases of diseases belonging to class 1). The territorial irregularity of mortality indices has been revealed.     

Signalling C‐Type lectin receptors,microbial recognition and immunity

Signalling C‐type lectin receptors (CLRs) are crucial in shaping the immune response to fungal pathogens, but comparably little is known about the role of these receptors in bacterial, viral and parasitic infections. CLRs have many diverse functions depending on the signalling motifs in their cytoplasmic domains, and can induce endocytic, phagocytic, antimicrobial, pro‐inflammatory or anti‐inflammatory responses which are either protective or not during an infection. Understanding the role of CLRs in shaping anti‐microbial immunity offers great potential for the future development of therapeutics for disease intervention. In this review we will focus on the recognition of bacterial, viral and parasitic pathogens by CLRs, and how these receptors influence the outcome of infection. We will also provide a brief update on the role of CLRs in antifungal immunity.     

Histology in diagnosis of parasitic diseases

Many pathogenic organisms cause inflammatory lesions and microscopic findings are a useful diagnostic tool for the aetiological diagnosis. However, the histological lesions are limited in respect to many biological agents that can damage the tissues. The histologic hallmark of parasitic diseases is mostly granulomatous inflammation. It is characterized by a focal infiltration of macrophages and epithelioid cells. Many giant cells, lymphocytes, plasma cells, fibroblasts and granulocytes can be found. Agents inducing granulomas include helminths and parasites that replicate intracellularly. Some special stains are utilized in histopathology, for example Giemsa's stain is useful to identify Leishmania. Using specific antibodies, immunohistochemical methods provide an aetiological diagnosis. Sometimes, tissue damage can be immuno-mediated depending on deposit of circulating immunocomplexes or T-lymphocytes involvement rather than by direct parasitic injury. Generally, the lesions which can be observed are respectively vasculitis and inflammatory reactions predominantly composed of mononuclear cells, as observed in many viral or bacterial diseases. In these cases, aetiological diagnosis is improved by in situ-PCR. For microscopic identification of parasites in tissues it is also important to be familiar with the kind of parasites most likely to be found in the examined tissue and in that particular host. Localization of parasites can induce hyperplastic-neoplastic lesions. Many parasites have been associated with the occurrence of specific types of neoplasms, but the mechanisms involved are still not well defined. Chronic inflammation and/or immune suppression seem to induce neoplastic proliferation.     

Parasites and immune responses: memory illusion?

Immunological memory responses to intracellular protozoa and extracellular helminths govern host resistance and susceptibility to reinfection. Humans and livestock living in parasitic disease endemic regions face continuous exposure from a very early age that often leads to asymptomatic chronic infection over their entire lifespan. Fundamental immunological studies suggest that the generation of T-cell memory is driven by tightly coordinated innate and adaptive cellular immune responses rapidly triggered following initial host infection. A key distinguishing feature of immune memory maintenance between the majority of parasitic diseases and most bacterial or viral diseases is long-term antigen persistence. Consequently, functional parasite immune memory is in a continuous, dynamic flux between activation and deactivation producing functional parasite killing or functional memory cell death. In this sense, T-cell immune memory can be regarded as "memory illusion." Furthermore, due to the finite capacity of memory lymphocytes to proliferate, continuous parasite antigen stimulation may exceed a threshold level at some point in the chronically infected host. This may result in suboptimal effector immune memory leading to host susceptibility to reinfection, or immune dysregulation yielding disease reactivation or immune pathology. The goal of this review is to highlight, through numerous examples, what is currently known about T-cell immune memory to parasites and to provide compelling hypotheses on the survival and maintenance of parasite "memory illusion." These novel concepts are discussed in the context of rationale parasite vaccine design strategies.