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Mesenchymal stem cells (MSC) are adult-derived multipotent stem cells that have been derived from almost every tissue. They are classically defined as spindle-shaped, plastic-adherent cells capable of adipogenic, chondrogenic, and osteogenic differentiation. This capacity for trilineage differentiation has been the foundation for research into the use of MSC to regenerate damaged tissues. Recent studies have shown that MSC interact with cells of the immune system and modulate their function. Although many of the details underlying the mechanisms by which MSC modulate the immune system have been defined for human and rodent (mouse and rat) MSC, much less is known about MSC from other veterinary species. This knowledge gap is particularly important because the clinical use of MSC in veterinary medicine is increasing and far exceeds the use of MSC in human medicine. It is crucial to determine how MSC modulate the immune system for each animal species as well as for MSC derived from any given tissue source. A comparative approach provides a unique translational opportunity to bring novel cell-based therapies to the veterinary market as well as enhance the utility of animal models for human disorders. The current review covers what is currently known about MSC and their immunomodulatory functions in veterinary species, excluding laboratory rodents.Abbreviations: AT, adipose tissue; BM, Bone marrow; CB, umbilical cord blood; CT, umbilical cord tissue; DC, dendritic cell; IDO, indoleamine 2;3-dioxygenase; MSC, mesenchymal stem cells; PGE2, prostaglandin E2; VEGF, vascular endothelial growth factorMesenchymal stem cells (MSC, alternatively known as mesenchymal stromal cells) were first reported in the literature in 1968.39 MSC are thought to be of pericyte origin (cells that line the vasculature)21,22 and typically are isolated from highly vascular tissues. In humans and mice, MSC have been isolated from fat, placental tissues (placenta, Wharton jelly, umbilical cord, umbilical cord blood), hair follicles, tendon, synovial membrane, periodontal ligament, and every major organ (brain, spleen, liver, kidney, lung, bone marrow, muscle, thymus, pancreas, skin).23,121 For most current clinical applications, MSC are isolated from adipose tissue (AT), bone marrow (BM), umbilical cord blood (CB), and umbilical cord tissue (CT; 11,87,99 Clinical trials in human medicine focus on the use of MSC both for their antiinflammatory properties (graft-versus-host disease, irritable bowel syndrome) and their ability to aid in tissue and bone regeneration in combination with growth factors and bone scaffolds (clinicaltrials.gov).131 For tissue regeneration, the abilities of MSC to differentiate and to secrete mediators and interact with cells of the immune system likely contribute to tissue healing (Figure 1). The current review will not address the specific use of MSC for orthopedic applications and tissue regeneration, although the topic is covered widely in current literature for both human and veterinary medicine.57,62,90
Open in a separate windowOpen in a separate windowFigure 1.The dual roles of MSC: differentiation and modulation of inflammation.Long-term studies in veterinary species have shown no adverse effects with the administration of MSC in a large number of animals.9,10,53 Smaller, controlled studies on veterinary species have shown few adverse effects, such as minor localized inflammation after MSC administration in vivo.7,15,17,45,86,92,98 Private companies, educational institutions, and private veterinary clinics (including Tufts University, Cummins School of Veterinary Medicine, University of California Davis School of Veterinary Medicine, VetStem, Celavet, Alamo Pintado Equine Medical Center, and Rood and Riddle Equine Hospital) offer MSC as a clinical treatment for veterinary species. Clinical uses include tendon and cartilage injuries, tendonitis, and osteoarthritis and, to a lesser extent, bone regeneration, spinal cord injuries, and liver disease in both large and small animals.38,41,113 Even with this broad clinical use, there have been no reports of severe adverse effects secondary to MSC administration in veterinary patients. 相似文献
Table 1.
Tissues from which MSC have been isolatedTissue source (reference no.) | |||||
Species | Fat | Bone marrow | Cord blood | Cord tissue | Other |
Cat | 134 | 83 | 56 | ||
Chicken | 63 | ||||
Cow | 138 | 12 | 108 | ||
Dog | 97 | 3, 59 | 78, 119 | 139 | Periodontal ligament65 |
Goat | 66 | 96 | 4 | ||
Horse | 26, 130 | 37, 40, 123 | 67 | 130 | Periodontal ligament and gingiva88 |
Nonhuman primate | 28, 54 | 5 | |||
Pig | 135 | 114 | 70 | 14, 20, 91 | |
Rabbit | 128 | 80 | 32 | Fetal liver93 | |
Sheep | 84 | 95 | 42, 55 |
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Crystal H Johnson Brianna L Skinner Sharon M Dietz David Blaney Robyn M Engel George W Lathrop Alex R Hoffmaster Jay E Gee Mindy G Elrod Nathaniel Powell Henry Walke 《Comparative medicine》2013,63(6):528-535
Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff.Abbreviations: CDC, Centers for Disease Control and Prevention; IHA, indirect hemagglutination assay; PEP, postexposure prophylacticBurkholderia pseudomallei, formerly known as Pseudomonas pseudomallei, is a gram-negative, aerobic, bipolar, motile, rod-shaped bacterium. B. pseudomallei infections (melioidosis) can be severe and even fatal in both humans and animals. This environmental saprophyte is endemic to Southeast Asia and northern Australia, but it has also been found in other tropical and subtropical areas of the world.7,22,32,42 The bacterium is usually found in soil and water in endemic areas and is transmitted to humans and animals primarily through percutaneous inoculation, ingestion, or inhalation of a contaminated source.8, 22,28,32,42 Human-to-human, animal-to-animal, and animal-to-human spread are rare.8,32 In December 2012, the National Select Agent Registry designated B. pseudomallei as a Tier 1 overlap select agent.39 Organisms classified as Tier 1 agents present the highest risk of deliberate misuse, with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. Select agents with this status have the potential to pose a severe threat to human and animal health or safety or the ability to be used as a biologic weapon.39Melioidosis in humans can be challenging to diagnose and treat because the organism can remain latent for years and is resistant to many antibiotics.12,37,41
B. pseudomallei can survive in phagocytic cells, a phenomenon that may be associated with latent infections.19,38 The incubation period in naturally infected animals ranges from 1 d to many years, but symptoms typically appear 2 to 4 wk after exposure.13,17,35,38 Disease generally presents in 1 of 2 forms: localized infection or septicemia.22 Multiple methods are used to diagnose melioidosis, including immunofluorescence, serology, and PCR analysis, but isolation of the bacteria from blood, urine, sputum, throat swabs, abscesses, skin, or tissue lesions remains the ‘gold standard.’9,22,40,42 The prognosis varies based on presentation, time to diagnosis, initiation of appropriate antimicrobial treatment, and underlying comorbidities.7,28,42 Currently, there is no licensed vaccine to prevent melioidosis.There are several published reports of naturally occurring melioidosis in a variety of nonhuman primates (NHP; 2,10,13,17,25,30,31,35 The first reported case of melioidosis in monkeys was recorded in 1932, and the first published case in a macaque species was in 1966.30 In the United States, there have only been 7 documented cases of NHP with B. pseudomallei infection.2,13,17 All of these cases occurred prior to the classification of B. pseudomallei as a select agent. Clinical signs in NHP range from subclinical or subacute illness to acute septicemia, localized infection, and chronic infection. NHP with melioidosis can be asymptomatic or exhibit clinical signs such as anorexia, wasting, purulent drainage, subcutaneous abscesses, and other soft tissue lesions. Lymphadenitis, lameness, osteomyelitis, paralysis and other CNS signs have also been reported.2,7,10,22,28,32 In comparison, human''s clinical signs range from abscesses, skin ulceration, fever, headache, joint pain, and muscle tenderness to abdominal pain, anorexia, respiratory distress, seizures, and septicemia.7,9,21,22
Open in a separate windowaCountry reflects the location where the animal was housed at the time of diagosis.Here we describe a case of melioidosis diagnosed in a pigtail macaque (Macaca nemestrina) imported into the United States from Indonesia and the implications of the detection of a select agent identified in a laboratory research colony. We also discuss the management and care of the exposed colony, zoonotic concerns regarding the animal care staff that worked with the shipment of macaques, effects on research studies, and the procedures involved in reporting a select agent incident. 相似文献
Table 1.
Summary of reported cases of naturally occurring Burkholderia pseudomalleiinfections in nonhuman primatesCountrya | Imported from | Date reported | Species | Reference |
Australia | Borneo | 1963 | Pongo sp. | 36 |
Brunei | Unknown | 1982 | Orangutan (Pongo pygmaeus) | 33 |
France | 1976 | Hamlyn monkey (Cercopithecus hamlyni) Patas monkey (Erythrocebus patas) | 11 | |
Great Britain | Philippines and Indonesia | 1992 | Cynomolgus monkey (Macaca fascicularis) | 10 |
38 | ||||
Malaysia | Unknown | 1966 | Macaca spp. | 30 |
Unknown | 1968 | Spider monkey (Brachytelis arachnoides) Lar gibbon (Hylobates lar) | 20 | |
Unknown | 1969 | Pig-tailed macaque (Macaca nemestrina) | 35 | |
Unknown | 1984 | Banded leaf monkey (Presbytis melalophos) | 25 | |
Singapore | Unknown | 1995 | Gorillas, gibbon, mandrill, chimpanzee | 43 |
Thailand | Unknown | 2012 | Monkey | 19 |
United States | Thailand | 1970 | Stump-tailed macaque (Macaca arctoides) | 17 |
India | Pig-tailed macaque (Macaca nemestrina) | |||
Africa | Rhesus macaque (Macaca mulatta) Chimpanzee (Pan troglodytes) | |||
Unknown | 1971 | Chimpanzee (Pan troglodytes) | 3 | |
Malaysia | 1981 | Pig-tailed macaque (Macaca nemestrina) | 2 | |
Wild-caught, unknown | 1986 | Rhesus macaque (Macaca mulatta) | 13 | |
Indonesia | 2013 | Pig-tailed macaque (Macaca nemestrina) | Current article |
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Yanbin Yin Huiling Chen Michael G. Hahn Debra Mohnen Ying Xu 《Plant physiology》2010,153(4):1729-1746
Carbohydrate-active enzyme glycosyltransferase family 8 (GT8) includes the plant galacturonosyltransferase1-related gene family of proven and putative α-galacturonosyltransferase (GAUT) and GAUT-like (GATL) genes. We computationally identified and investigated this family in 15 fully sequenced plant and green algal genomes and in the National Center for Biotechnology Information nonredundant protein database to determine the phylogenetic relatedness of the GAUTs and GATLs to other GT8 family members. The GT8 proteins fall into three well-delineated major classes. In addition to GAUTs and GATLs, known or predicted to be involved in plant cell wall biosynthesis, class I also includes a lower plant-specific GAUT and GATL-related (GATR) subfamily, two metazoan subfamilies, and proteins from other eukaryotes and cyanobacteria. Class II includes galactinol synthases and plant glycogenin-like starch initiation proteins that are not known to be directly involved in cell wall synthesis, as well as proteins from fungi, metazoans, viruses, and bacteria. Class III consists almost entirely of bacterial proteins that are lipooligo/polysaccharide α-galactosyltransferases and α-glucosyltransferases. Sequence motifs conserved across all GT8 subfamilies and those specific to plant cell wall-related GT8 subfamilies were identified and mapped onto a predicted GAUT1 protein structure. The tertiary structure prediction identified sequence motifs likely to represent key amino acids involved in catalysis, substrate binding, protein-protein interactions, and structural elements required for GAUT1 function. The results show that the GAUTs, GATLs, and GATRs have a different evolutionary origin than other plant GT8 genes, were likely acquired from an ancient cyanobacterium (Synechococcus) progenitor, and separate into unique subclades that may indicate functional specialization.Plant cell walls are composed of three principal types of polysaccharides: cellulose, hemicellulose, and pectin. Studying the biosynthesis and degradation of these biopolymers is important because cell walls have multiple roles in plants, including providing structural support to cells and defense against pathogens, serving as cell-specific developmental and differentiation markers, and mediating or facilitating cell-cell communication. In addition to their important roles within plants, cell walls also have many economic uses in human and animal nutrition and as sources of natural textile fibers, paper and wood products, and components of fine chemicals and medicinal products. The study of the biosynthesis and biodegradation of plant cell walls has become even more significant because cell walls are the major components of biomass (Mohnen et al., 2008), which is the most promising renewable source for the production of biofuels and biomaterials (Ragauskas et al., 2006; Pauly and Keegstra, 2008). Analyses of fully sequenced plant genomes have revealed that they encode hundreds or even thousands of carbohydrate-active enzymes (CAZy; Henrissat et al., 2001; Yokoyama and Nishitani, 2004; Geisler-Lee et al., 2006). Most of these CAZy enzymes (Cantarel et al., 2009) are glycosyltransferases (GTs) or glycoside hydrolases, which are key players in plant cell wall biosynthesis and modification (Cosgrove, 2005).The CAZy database is classified into 290 protein families (www.cazy.org; release of September 2008), of which 92 are GT families (Cantarel et al., 2009). A number of the GT families have been previously characterized to be involved in plant cell wall biosynthesis. For example, the GT2 family is known to include cellulose synthases and some hemicellulose backbone synthases (Lerouxel et al., 2006), such as mannan synthases (Dhugga et al., 2004; Liepman et al., 2005), putative xyloglucan synthases (Cocuron et al., 2007), and mixed linkage glucan synthases (Burton et al., 2006). With respect to the synthesis of xylan, a type of hemicellulose, four Arabidopsis (Arabidopsis thaliana) proteins from the GT43 family, irregular xylem 9 (IRX9), IRX14, IRX9-L, and IRX14-L, and two proteins from the GT47 family, IRX10 and IRX10-L, are candidates (York and O''Neill, 2008) for glucuronoxylan backbone synthases (Brown et al., 2007, 2009; Lee et al., 2007a; Peña et al., 2007; Wu et al., 2009). In addition, three proteins have been implicated in the synthesis of an oligosaccharide thought to act either as a primer or terminator in xylan synthesis (Peña et al., 2007): two from the GT8 family (IRX8/GAUT12 [Persson et al., 2007] and PARVUS/GATL1 [Brown et al., 2007; Lee et al., 2007b]) and one from the GT47 family (FRA8/IRX7 [Zhong et al., 2005]).The GT families involved in the biosynthesis of pectins have been relatively less studied until recently. In 2006, a gene in CAZy family GT8 was shown to encode a functional homogalacturonan α-galacturonosyltransferase, GAUT1 (Sterling et al., 2006). GAUT1 belongs to a 25-member gene family in Arabidopsis, the GAUT1-related gene family, that includes two distinct but closely related families, the galacturonosyltransferase (GAUT) genes and the galacturonosyltransferase-like (GATL) genes (Sterling et al., 2006). Another GAUT gene, GAUT8/QUA1, has been suggested to be involved in pectin and/or xylan synthesis, based on the phenotypes of plant lines carrying mutations in this gene (Bouton et al., 2002; Orfila et al., 2005). It has further been suggested that multiple members of the GT8 family are galacturonosyltransferases involved in pectin and/or xylan biosynthesis (Mohnen, 2008; Caffall and Mohnen, 2009; Caffall et al., 2009).Aside from the 25 GAUT and GATL genes, Arabidopsis has 16 other family GT8 genes, according to the CAZy database, which do not seem to have the conserved sequence motifs found in GAUTs and GATLs: HxxGxxKPW and GLG (Sterling et al., 2006). Eight of these 16 genes are annotated as galactinol synthase (GolS) by The Arabidopsis Information Resource (TAIR; www.arabidopsis.org), and three of these AtGolS enzymes have been implicated in the synthesis of raffinose family oligosaccharides that are associated with stress tolerance (Taji et al., 2002). The other eight Arabidopsis GT8 genes are annotated as plant glycogenin-like starch initiation proteins (PGSIPs) in TAIR. PGSIPs have been proposed to be involved in the synthesis of primers necessary for starch biosynthesis (Chatterjee et al., 2005). Hence, the GT8 family is a protein family consisting of enzymes with very distinct proven and proposed functions. Indeed, a suggestion has been made to split the GT8 family into two groups (Sterling et al., 2006), namely, the cell wall biosynthesis-related genes (GAUTs and GATLs) and the non-cell wall synthesis-related genes (GolSs and PGSIPs).We are interested in further defining the functions of the GAUT and GATL proteins in plants, in particular their role(s) in plant cell wall synthesis. The apparent disparate functions of the GT8 family (i.e. the GAUTs and GATLs as proven and putative plant cell wall polysaccharide biosynthetic α-galacturonosyltransferases, the eukaryotic GolSs as α-galactosyltransferases that synthesize the first step in the synthesis of the oligosaccharides stachyose and raffinose, the putative PGSIPs, and the large bacterial GT8 family of diverse α-glucosyltransferases and α-galactosyltransferases involved in lipopolysaccharide and lipooligosaccharide synthesis) indicate that the GT8 family members are involved in several unique types of glycoconjugate and glycan biosynthetic processes (Yin et al., 2010). This observation led us to ask whether any of the GT8 family members are sufficiently closely related to GAUT and GATL genes to be informative regarding GAUT or GATL biosynthetic function(s) and/or mechanism(s).To investigate the relatedness of the members of the GT8 gene family, we carried out a detailed phylogenetic analysis of the entire GT8 family in 15 completely sequenced plant and green algal genomes (Abbreviation Clade Species Genome Published Downloaded from mpc Green algae Micromonas pusilla CCMP1545 Worden et al. (2009) JGI version 2.0 mpr Green algae Micromonas strain RCC299 Worden et al. (2009) JGI version 2.0 ol Green algae Ostreococcus lucimarinus Palenik et al. (2007) JGI version 1.0 ot Green algae Ostreococcus tauri Derelle et al. (2006) JGI version 1.0 cr Green algae Chlamydomonas reinhardtii Merchant et al. (2007) JGI version 3.0 vc Green algae Volvox carteri f. nagariensis No JGI version 1.0 pp Moss Physcomitrella patens ssp. patens Rensing et al. (2008) JGI version 1.1 sm Spike moss Selaginella moellendorffii No JGI version 1.0 pt Dicot Populus trichocarpa Tuskan et al. (2006) JGI version 1.1 at Dicot Arabidopsis thaliana Arabidopsis Genome Initiative (2000) TAIR version 9.0 vv Dicot Vitis vinifera Jaillon et al. (2007) http://www.genoscope.cns.fr/ gm Dicot Glycine max Schmutz et al. (2010) JGI version 1.0 os Monocot Oryza sativa Goff et al. (2002); Yu et al. (2002) TIGR version 6.1 sb Monocot Sorghum bicolor Paterson et al. (2009) JGI version 1.0 bd Monocot Brachypodium distachyon Vogel et al. (2010) JGI version 1.0