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1. A review of adjuvants for Leishmania vaccine candidates. J Biomed Res, 2010; 24(1):16-25 Joshua M. Mutisoa, John C. Machariaa, Michael M. Gicherub a Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museums of Kenya,P.O. Box 24481-00502, Karen,Nairobi, Kenya; b Department of Zoological Sciences, School of Pure and Applied Sciences, Kenyatta University,P.O. Box 43844-00100, Nairobi, Kenya. Abstract: Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. Although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to lack of an appropriate adjuvant. In view of this, this review paper outlines some of the adjuvants that have been used in Leishmania vaccine candidates and cites a few of the responses obtained from these studies. The aim of the present review is to consolidate these findings to facilitate the application of these adjuvants in general and experimental vaccinology. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100103&flag=1 2. Ultraviolet- attenuated cercariae of Schistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice. J Biomed Res, 2010; 24(4): 277-284 Meijuan Zhanga,b, Fang Tiana, Yanan Gaoa, Minjun Jia,c, Guanling Wua,c a Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China; b Department of Clinical Laboratory, the first Affliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; c Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 210029, China. Abstract: Objective: To better understand the reason that Schistosoma japonicum (S. japonicum) ultraviolet (UV)-radiated cercariae could not induce high level of protection in C57BL/6 mice. Methods: Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes (sdLNs) at 1 w after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC-infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure. Results: The gene expressions of Th1 cytokines, including interferon-γ (IFN-γ), interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3rd w after vaccination with UV-AC. Conclusion: UV-AC of S. japonicum could not effectively induce a Th1 response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR100404&flag=1 3. Antigen presenting cells may be able to distinguish between normal and radiated Schistosoma japonicum cercaria: an in vitro observation. J Biomed Res, 2010; 24(4):285-291 Guixia Tanga, Minjun Jia,b, Haiwei Wua,b, Guanling Wua,b a Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China; b Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 210029, China. Abstract: Objective: To observe the discrepancies of responses induced by Schistosoma japonicum (S. japonicum) normal cercaria antigen (NCA) and ultraviolet (UV) -radiation-attenuated cercaria antigen (UVACA) in an in vitro system. Methods: S. japonicum cercariae were collected and UVACA and NCA were prepared. Mouse macro-phage model cells (RAW 264.7) were treated with medium, NCA (40 μg/mL) or UVACA (40 μg/mL) in the presence or absence of recombinant mouse interferon gamma (rmIFN-γ; 4 ng/mL) for 48 h. Cell surface staining and flow cytometry were used to assess the major histocompatibility complex (MHC)Ⅱ expression, and data were expressed as mean fluorescence intensities (MFI). Interleukin (IL) -10, IL-6 and prostaglandin E2 (PGE2) in cell culture supernatant were evaluated by commercial enzyme-linked immunosorbent assays. Results: NCA significantly suppressed IFN-γ-induced MHCⅡ expression on RAW 264.7 cells. In the presence of IFN-γ, NCA significantly promoted IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells. In the presence of IFN-γ, UVACA significantly promoted IL-10 but not IL-6 and PGE2 secretion from RAW 264.7 cells and showed no effect on IFN-γ-induced MHC Ⅱ expression. Compared with UVACA, NCA significantly suppressed IFN-γ-induced MHC Ⅱ expression and significantly promoted IL-6, PGE2 and IL-10 secretion from RAW 264.7 cells. Conclusion: RAW 264.7 cells respond differently to NCA and UVACA. NCA can significantly suppress IFN-γ-induced MHC Ⅱ expression and significantly promote IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells compared with UVACA. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR100405&flag=1 4. Clostridium difficile infections in China. J Biomed Res, 2010; 24(6):411-416 Ke Jina,b,c, Shixia Wangc,d, Zuhu Huanga,b,c, Shan Lub,c,d a Department of Infectious Diseases, bJiangsu Province Key Laboratory in Infectious Diseases, cChina-US Vaccine Research Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; d Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Abstract: Clostridium difficile (C. difficile) infection has become one of the major hospital-associated infections in Western countries in the last two decades. However, there is limited information on the status of C. difficile infection in Chinese healthcare settings. Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China, it is critical to understand the epidemiology and potential risk factors that may contribute to C. difficile infection in China. A literature review of available published studies, including those in Chinese language-based journals, was conducted. A review of the currently available literature suggested the presence of C. difficile infections in China, but also suggested that these infections were not particularly endemic. This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C. difficile infection in China, including the identification of any associated risk factors. Such information is ultimately valuable to develop appropriate strategies to pre-vent C. difficile infection and the vast negative impact of such infections in China and other developing countries. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100601&flag=1 5. Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway. J Biomed Res, 2010; 24(6):444-451 Lingyun Lia,b, Jing Chia, Feng Zhoua, Dandan Guoa, Fang Wangc, Genyan Liuc, Chun Zhanga, Kun Yaoa a Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China; bDepartment c of Developmental Genetics, Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. Abstract: Apoptosis plays an important role in the pathogenesis of viral infections. In this study, we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms. Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known to be an important substrate for activated caspase-3. Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8 was not activated obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated, caspase-dependent apoptosis in HHV-6A-infected cells. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100605&flag=1 6. Cryptosporidiosis-an overview. J Biomed Res, 2011; 25(1):1-16 Gordon J Leitcha, Qing Heb a Department of Physiology, and bDepartment Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA. Abstract: Apicomplexan protozoan parasites of the genus Cryptosporidium infect the gastrointestinal tract and lungs of a wide variety of animals, including humans. The majority of human infections are due to either Cryptosporidium hominis (C. hominis) and/or Cryptosporidium parvum (C. parvum). The parasite has a complex life cycle that includes both asexual and sexual stages. While there are invasive free living stages, proliferation and differentiation take place within a unique parasitrophorous vacuole under the host cell brush border but outside the host cell cytoplasm. Infection is spread by environmentally resistant spores that primarily contaminate drinking water and occasionally food sources, which may cause significant outbreaks of diarrhea that generally lasts less than 2 w in immunocompetent individuals. In immunodeficient or immunosuppressed individuals, diarrhea may be copious and can result in significant morbidity and mortality, particularly in AIDS patients. Although diagnosis is relatively simple, effective drug treatment, particulary for infections in immunodeficient patients, has not been uniformly successful. This overview summarizes the species known to infect humans, aspects of the parasite life cycle, sources of infection, the pathophysiology of cryptosporidiosis, the immune response to infection, diagnosis, treatment and some aspects of cryptosporidiosis in China. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110101&flag=1 7. A survey of HIV infection and related high-risk factors among men who have sex with men in Suzhou, Jiangsu, China. J Biomed Res, 2011; 25(1):17-24 Hongling Baia, Xiping Huanb, Weiming Tanga, Xin Chena, Hongjing Yanb, Xiaoyan Liub, Haitao Yangb, Zhihang Penga, Xiuping Zhaoc, Rongbin Yua, Hao Yua, Feng Chena a Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China; b Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu 210009, China; c Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu 215004, China. Abstract: A cross-sectional study using the snowball sampling method was conducted in May 2008 to investigate human immunodeficiency virus (HIV) infection status and related high risk factors among men who have sex with men (MSM) in Suzhou city of Jiangsu province. The researchers carried out a face-to-face questionnaire interview among MSM, and collected their blood samples to test for HIV and other sexually transmitted diseases (STDs). Among the 280 respondents, 91.1% had homosexual acts in the past 6 months and 87.5% had multiple homosexual partners; 46.4% had heterosexual sex in the past 6 months and 33.1% had multiple heterosexual partners. The rate of continued condom use was 44.3% in homosexual sex in the past 6 months, while the rate in heterosexual sex was 33.9%. Laboratory test results showed that the prevalences of HIV and syphilis were 7.1% (20/280) and 15.0% (42/280), respectively, but no HCV-positive person was found. In the multivariate logistic regression mod-el, subjects with a monthly income of more than RMB ¥ 1,000 (OR=4.83,95% CI=1.44-16.22), subjects who often went to bars for sexual partners (OR=2.25, 95%CI=1.21-4.20), and subjects who had more than one sexual partner in the past 6 months (OR=0.49, 95%CI=0.25-0.97) and had sex with fixed sexual partners in the past 6 months (OR=0.42, 95%CI=0.25-0.75) were significantly associated with the rate of continued condom use in homosexual sex in the past 6 months. Unprotected sex and multiple sexual partners were more common among MSM in Suzhou city; furthermore, the prevalences of HIV infection and syphilis were relatively high. HIV preventive measures should be designed to address these risk factors and control the spread of HIV among MSM. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110102&flag=1 8. A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes. J Biomed Res, 2011; 25(2):111-119 Christopher D. Conradya, Heather Jonesa, Min Zhengb, Daniel J.J. Carra,b a Departments of Microbiology, Immunology, and bOphthalmology, The University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA. Abstract: Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-α. We also report mice deficient in the A1 chain of the type I IFN receptor (CD118-/-) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea compared to wild type (WT) controls. The enhanced susceptibility correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CD118-/- mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110204&flag=1 9. Identification of distant co-evolving residues in antigen 85C from Mycobacterium tuberculosis using statistical coupling analysis of the esterase family proteins. J Biomed Res, 2011; 25(3):165-169 Veeky Baths, Utpal Roy Department of Biological Sciences, BITS Pilani K. K Birla Goa Campus, GOA 403726, India. Abstract: A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis (SCA) is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family (pfam ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These residues were then mapped on the crystal structure of antigen 85C (PDB ID: 1DQZ). The mapping revealed correlation between 3 distant residues (Asp38, Leu123 and Met125) and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110302&flag=1 10. Role of remote sensing, geographic bioinformatics system and bioinformatics in kala-azar epidemiology. J Biomed Res, 2011; 25(6):373-384 Gouri Sankar Bhunia, Manas Ranjan Dikhit, Shreekant Kesari, Ganesh Chandra Sahoo, Pradeep Das Rajendra Memorial Research Institute of Medical Sciences (ICMR), Agamkuan, Patna, Bihar 800007, India. Abstract: Visceral leishmaniasis or kala-azar is a potent parasitic infection causing death of thousands of people each year. Medicinal compounds currently available for the treatment of kala-azar have serious side effects and de-creased efficacy owing to the emergence of resistant strains. The type of immune reaction is also to be considered in patients infected with Leishmania donovani (L. donovani). For complete eradication of this disease, a high level modern research is currently being applied both at the molecular level as well as at the field level. The computational approaches like remote sensing, geographic information system (GIS) and bioinformatics are the key re-sources for the detection and distribution of vectors, patterns, ecological and environmental factors and genomic and proteomic analysis. Novel approaches like GIS and bioinformatics have been more appropriately utilized in determining the cause of visearal leishmaniasis and in designing strategies for preventing the disease from spreading from one region to another. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110601&flag=1 11. Leishmania donovani whole cell antigen delivered with adjuvants protects against visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops) . J Biomed Res, 2012; 26(1):8-16 Joshua Muli Mutisoa,b, John Chege Machariaa, Evans Tarachaa, Michael Muita Gicherub a Department of Tropical and Infectious Diseases, Institute of Primate Research, Karen, Nairobi 24481-00502, Kenya; b Department of Zoological Sciences, Kenyatta University, Nairobi 43844-00100, Kenya. Abstract: In a previous immunogenicity and efficacy study in mice, montanide ISA 720 (MISA) was indicated to be a better adjuvant than bacillus calmette guerin vaccine (BCG) for a Leishmania vaccine. In the present study, we report the safety, immunogenicity and efficacy of Leishmania donovani (L. donovani) sonicated antigen delivered with alum-BCG (AlBCG), MISA or monophosphoryl lipid A (MPLA) in vervet monkeys following intradermal inoculums. Vaccinated and control animals were challenged with virulent L. donovani parasites and the parasitic burden was determined. Only animals vaccinated with alum-BCG adversely reacted to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric ANOVA followed by a post test showed significantly higher IgG antibodies, and revealed the presence of lymphoproliferative and interferon gamma responses in both AlBCG+Ag and MISA+Ag as compared to the MPLA+Ag or other groups (P < 0.001). We conclude that L. donovani sonicated antigen containing MISA is safe and is associated with protective immune response against Leishmania donovani infection in the vervet monkey model. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120102&flag=1 12. Prevalence of intestinal parasitic infections in certified food-handlers working in food establishments in the City of Nairobi, Kenya. J Biomed Res, 2012; 26(2):84-89 Paul Kamaua, c, Penina Aloo-Obudhoa, Ephantus Kabirub, Kepha Ombachoc, Bernard Langatd, Obadiah Mucherue, Laban Irerie a Department of Zoological Sciences, Kenyatta University, Nairobi, Kenya; b Department of Pathology, Kenyatta University, Nairobi, Kenya; c Ministry of Public Health and Sanitation, Nairobi, Kenya; d Institute of Tropical Medicine and Infectious Diseases, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya; e Division of Vector Borne and Neglected Tropical Diseases, Embu, Kenya. Abstract: Most intestinal parasites are cosmopolitan with the highest prevalence in the tropics and subtopics. Rural-to-urban migration rapidly increases the number of food eating places in towns and their environs. Some of these eating estabishments have poor sanitation and are overcrowded, facilitating disease transmission, especially through food-handling. Our investigations in Nairobi, therefore, were set to determine the presence of intestinal parasites in food-handlers with valid medical certificates. Direct and concentrated stool processing techniques were used. Chi-square test and ANOVA were used for data analysis. The parasites Ascaris lumbricoides, Entamoeba histolytica and Giardia lamblia were observed in certified food-handlers. Significant difference was found in parasite frequency by eating classes and gender (χ2 = 9.49, P = 0.73), (F = 1.495, P = 0.297), but not in parasite occurrence between age brackets (χ2 = 6.99, P = 0.039). The six-month medical certificate validity period may contribute significantly to the presence of intestinal parasites in certified food-handlers. http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120203&flag=1