<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Walk, Seth T</style></author><author><style face="normal" font="default" size="100%">Xu, Guang</style></author><author><style face="normal" font="default" size="100%">Stull, Jason W</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Correlation between tick density and pathogen endemicity, New Hampshire.</style></title><secondary-title><style face="normal" font="default" size="100%">Emerg Infect Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Emerging Infect. Dis.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Anaplasma phagocytophilum</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Arachnid Vectors</style></keyword><keyword><style  face="normal" font="default" size="100%">Babesia microti</style></keyword><keyword><style  face="normal" font="default" size="100%">Babesiosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Biosurveillance</style></keyword><keyword><style  face="normal" font="default" size="100%">Borrelia burgdorferi</style></keyword><keyword><style  face="normal" font="default" size="100%">Communicable Diseases, Emerging</style></keyword><keyword><style  face="normal" font="default" size="100%">Ehrlichiosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Ixodes</style></keyword><keyword><style  face="normal" font="default" size="100%">Lyme Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">New Hampshire</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2009 Apr</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">585-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">To assess the endemicity of tick-borne pathogens in New Hampshire, we surveyed adult tick vectors. Pathogens were more prevalent in areas of high tick density, suggesting a correlation between tick establishment and pathogen endemicity. Infection rates in ticks correlated with disease frequency in humans.</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/19331738?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Leendertz, Fabian H</style></author><author><style face="normal" font="default" size="100%">Xu, Guang</style></author><author><style face="normal" font="default" size="100%">LeBreton, Matthew</style></author><author><style face="normal" font="default" size="100%">Djoko, Cyrille F</style></author><author><style face="normal" font="default" size="100%">Aminake, Makoah N</style></author><author><style face="normal" font="default" size="100%">Takang, Eric E</style></author><author><style face="normal" font="default" size="100%">Diffo, Joseph L D</style></author><author><style face="normal" font="default" size="100%">Pike, Brian L</style></author><author><style face="normal" font="default" size="100%">Rosenthal, Benjamin M</style></author><author><style face="normal" font="default" size="100%">Formenty, Pierre</style></author><author><style face="normal" font="default" size="100%">Boesch, Christophe</style></author><author><style face="normal" font="default" size="100%">Ayala, Francisco J</style></author><author><style face="normal" font="default" size="100%">Wolfe, Nathan D</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The origin of malignant malaria.</style></title><secondary-title><style face="normal" font="default" size="100%">Proc Natl Acad Sci U S A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Proc. Natl. Acad. Sci. U.S.A.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Glycoproteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">N-Acetylneuraminic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Pan troglodytes</style></keyword><keyword><style  face="normal" font="default" size="100%">Phylogeny</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium falciparum</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Infections, Animal</style></keyword><keyword><style  face="normal" font="default" size="100%">Protozoan Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Alignment</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2009 Sep 1</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">106</style></volume><pages><style face="normal" font="default" size="100%">14902-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Plasmodium falciparum, the causative agent of malignant malaria, is among the most severe human infectious diseases. The closest known relative of P. falciparum is a chimpanzee parasite, Plasmodium reichenowi, of which one single isolate was previously known. The co-speciation hypothesis suggests that both parasites evolved separately from a common ancestor over the last 5-7 million years, in parallel with the divergence of their hosts, the hominin and chimpanzee lineages. Genetic analysis of eight new isolates of P. reichenowi, from wild and wild-born captive chimpanzees in Cameroon and Côte d'Ivoire, shows that P. reichenowi is a geographically widespread and genetically diverse chimpanzee parasite. The genetic lineage comprising the totality of global P. falciparum is fully included within the much broader genetic diversity of P. reichenowi. This finding is inconsistent with the co-speciation hypothesis. Phylogenetic analysis indicates that all extant P. falciparum populations originated from P. reichenowi, likely by a single host transfer, which may have occurred as early as 2-3 million years ago, or as recently as 10,000 years ago. The evolutionary history of this relationship may be explained by two critical genetic mutations. First, inactivation of the CMAH gene in the human lineage rendered human ancestors unable to generate the sialic acid Neu5Gc from its precursor Neu5Ac, and likely made humans resistant to P. reichenowi. More recently, mutations in the dominant invasion receptor EBA 175 in the P. falciparum lineage provided the parasite with preference for the overabundant Neu5Ac precursor, accounting for its extreme human pathogenicity.</style></abstract><issue><style face="normal" font="default" size="100%">35</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/19666593?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Li, Xiaohong</style></author><author><style face="normal" font="default" size="100%">Foulkes, Andrea S</style></author><author><style face="normal" font="default" size="100%">Yucel, Recai M</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">An expectation maximization approach to estimate malaria haplotype frequencies in multiply infected children.</style></title><secondary-title><style face="normal" font="default" size="100%">Stat Appl Genet Mol Biol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Stat Appl Genet Mol Biol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Likelihood Functions</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria Vaccines</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2007</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">Article33</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Characterizing genetic variability in the human pathogenic Plasmodium species, the group of parasites that cause Malaria, may have broad global health implications. Specifically, discerning the combinations of mutations that lead to viable parasites and the population level frequencies of these clonal sequences will allow for targeted vaccine development and individualized treatment choices. This presents an analytical challenge, however, since haplotypic phase (i.e. the alignment of bases on a single DNA strand) is generally unobservable in multiply infected individuals. This manuscript describes an expectation maximization (EM) approach to maximum likelihood estimation of haplotype frequencies in this missing data setting. The approach is applied to a cohort of N=341 malaria infected children in Uganda, Cameroon and Sudan to characterize regional differences. A simulation study is also presented to characterize method performance and assess sensitivity to distributional assumptions.</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/18052916?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The unpredictable past of Plasmodium vivax revealed in its genome.</style></title><secondary-title><style face="normal" font="default" size="100%">Proc Natl Acad Sci U S A</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Proc. Natl. Acad. Sci. U.S.A.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Biological Evolution</style></keyword><keyword><style  face="normal" font="default" size="100%">Culicidae</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetics, Population</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Genomics</style></keyword><keyword><style  face="normal" font="default" size="100%">Haplorhini</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Malaria, Vivax</style></keyword><keyword><style  face="normal" font="default" size="100%">Plasmodium vivax</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2004</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2004 Nov 2</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">101</style></volume><pages><style face="normal" font="default" size="100%">15547-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">44</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/15505201?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tumwine, James K</style></author><author><style face="normal" font="default" size="100%">Kekitiinwa, Addy</style></author><author><style face="normal" font="default" size="100%">Nabukeera, Nicolette</style></author><author><style face="normal" font="default" size="100%">Akiyoshi, Donna E</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Widmer, Giovanni</style></author><author><style face="normal" font="default" size="100%">Feng, Xiaochuan</style></author><author><style face="normal" font="default" size="100%">Tzipori, Saul</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Cryptosporidium parvum in children with diarrhea in Mulago Hospital, Kampala, Uganda.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Trop Med Hyg</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Trop. Med. Hyg.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Cross-Sectional Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidiosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidium parvum</style></keyword><keyword><style  face="normal" font="default" size="100%">Diarrhea</style></keyword><keyword><style  face="normal" font="default" size="100%">Diarrhea, Infantile</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Protozoan</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Hospitalization</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant, Newborn</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Nutrition Disorders</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Restriction Fragment Length</style></keyword><keyword><style  face="normal" font="default" size="100%">Prevalence</style></keyword><keyword><style  face="normal" font="default" size="100%">Uganda</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2003</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2003 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">68</style></volume><pages><style face="normal" font="default" size="100%">710-5</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">A cross-sectional case-control study (ratio = 3:1) was conducted over a 15-month period to determine the prevalence and consequences of cryptosporidiosis in hospitalized diarrheic children (0-5 years old) at Mulago Hospital in Kampala, Uganda. Cryptosporidium parvum was detected and genotyped among 2,446 children of whom 1,779 (72.7%) had diarrhea, and 667 (27.3%) were age- and sex-matched controls. Of the 1,779 children with diarrhea, 532 (29.9%) had persistent (&gt; 14 days) diarrhea and 1,247 (70.1%) had acute diarrhea. Overall, 444 (25.0%) of the 1,779 children with diarrhea had C. parvum, compared with only 57 (8.5%) of the 667 children without diarrhea (chi2 = 80.2, P &lt; or = 0.0001). Within this group of infected children, 72.8% were infected with genotype 1, 18.4% with genotype 2, and 4.1% with a mixture of both genotypes, and 4.1% isolates were either unclassified or C. meleagridis. The prevalence was highest during the rainy months of April to June. Of the 532 children with persistent diarrhea, 166 (31.2%) had C. parvum compared with 278 (22.3%) of the 1,247 children with acute diarrhea (chi2 = 15.8, P &lt; or = 0.0001). There was a significant association between C. parvum and malnutrition including stunting, being underweight, and wasting. Unfavorable outcome (death or failure to resolve within 14 days) occurred in 139 (72.8%) of the 191 children with C. parvum, and in only 65.1% of the 545 without (odds ratio = 1.117, 95% confidence interval = 1.005-1.243, P = 0.05), Of the 191 children with C. parvum, 24 (12.6%) died, compared with 34 (6.2%) of the 545 without C. parvum (P = 0.005). Mortality rates were higher among children with severe dehydration and persistent diarrhea, and in stunted or underweight children infected with C. parvum. Among Ugandan children, cryptosporidiosis, which remains untreatable, is frequently associated with diarrhea and other serious and unfavorable consequences.</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/12887032?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Feng, Xiaochuan</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Tzipori, Saul</style></author><author><style face="normal" font="default" size="100%">Widmer, Giovanni</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Experimental evidence for genetic recombination in the opportunistic pathogen Cryptosporidium parvum.</style></title><secondary-title><style face="normal" font="default" size="100%">Mol Biochem Parasitol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol. Biochem. Parasitol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Conserved Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Crosses, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidiosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidium parvum</style></keyword><keyword><style  face="normal" font="default" size="100%">Deer</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">Microsatellite Repeats</style></keyword><keyword><style  face="normal" font="default" size="100%">Opportunistic Infections</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombination, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Survival Rate</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2002</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2002 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">119</style></volume><pages><style face="normal" font="default" size="100%">55-62</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Cryptosporidium parvum is an intracellular protozoan parasite causing intestinal malabsorption and diarrhea in humans. The infection is usually self-limiting, although persistent cryptosporidosis is observed in immunocompromised and malnourished individuals. As with other Apicomplexa, the life cycle of Cryptosporidium is thought to comprise a sexual phase, during which a motile microgamont fuses with a sessile macrogamont. The four sporozoites found within each oocyst (the infectious form excreted in the feces) are thought to be the product of a meiotic division taking place immediately following fertilization, but the existence of a meiotic cycle in this genus has not been tested experimentally. To substantiate the occurrence of meiotic recombination in this species, we performed a genetic cross between two distinct isolates of C. parvum co-infected in INF-gamma knockout mice. We found that mixed infections produced recombinant progeny characterized by multilocus genotypes comprising alleles inherited from each parental line. This observation represents the first demonstration of sexual recombination in this pathogen. Together with the occurrence of genetically heterogeneous infections, this finding suggests that outcrossing between genotypes may occur in nature. Experimental crosses among Cryptosporidium populations will facilitate mapping of clinically relevant genes, the delineation of Cryptosporidium species, and defining the taxonomical status of C. parvum subtypes and host-specific genotypes.</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/11755186?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mukherjee, Jean</style></author><author><style face="normal" font="default" size="100%">Chios, Kerry</style></author><author><style face="normal" font="default" size="100%">Fishwild, Dianne</style></author><author><style face="normal" font="default" size="100%">Hudson, Deborah</style></author><author><style face="normal" font="default" size="100%">O'Donnell, Susan</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Donohue-Rolfe, Arthur</style></author><author><style face="normal" font="default" size="100%">Tzipori, Saul</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Human Stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli O157:H7 infection.</style></title><secondary-title><style face="normal" font="default" size="100%">Infect Immun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Infect. Immun.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Bacterial</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Monoclonal</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibody Specificity</style></keyword><keyword><style  face="normal" font="default" size="100%">Disease Models, Animal</style></keyword><keyword><style  face="normal" font="default" size="100%">Escherichia coli O157</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Germ-Free Life</style></keyword><keyword><style  face="normal" font="default" size="100%">HeLa Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Hemolytic-Uremic Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunization, Passive</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin G</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin Isotypes</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin kappa-Chains</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Neutralization Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Shiga Toxin 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Swine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2002</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2002 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">70</style></volume><pages><style face="normal" font="default" size="100%">612-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Hemolytic-uremic syndrome (HUS) is a serious complication predominantly associated with infection by enterohemorrhagic Escherichia coli (EHEC), such as E. coli O157:H7. EHEC can produce Shiga toxin 1 (Stx1) and/or Shiga toxin 2 (Stx2), both of which are exotoxins comprised of active (A) and binding (B) subunits. In piglets and mice, Stx can induce fatal neurological symptoms. Polyclonal Stx2 antiserum can prevent these effects in piglets infected with the Stx2-producing E. coli O157:H7 strain 86-24. Human monoclonal antibodies (HuMAbs) against Stx2 were developed as potential passive immunotherapeutic reagents for the prevention and/or treatment of HUS. Transgenic mice bearing unrearranged human immunoglobulin (Ig) heavy and kappa light chain loci (HuMAb___Mouse) were immunized with formalin-inactivated Stx2. Thirty-seven stable hybridomas secreting Stx2-specific HuMAbs were isolated: 33 IgG1kappa A-subunit-specific and 3 IgG1kappa and 1 IgG3kappa B-subunit-specific antibodies. Six IgG1kappa A-subunit-specific (1G3, 2F10, 3E9, 4H9, 5A4, and 5C12) and two IgG1kappa B-subunit-specific (5H8 and 6G3) HuMAbs demonstrated neutralization of &gt; 95% activity of 1 ng of Stx2 in the presence of 0.04 microg of HuMAb in vitro and significant prolongation of survival of mice given 50 microg of HuMAb intraperitoneally (i.p.) and 25 ng of Stx2 intravenously. When administered i.p. to gnotobiotic piglets 6 or 12 h after infection with E. coli O157:H7 strain 86-24, HuMAbs 2F10, 3E9, 5H8, and 5C12 prolonged survival and prevented development of fatal neurological signs and cerebral lesions. The Stx2-neutralizing ability of these HuMAbs could potentially be used clinically to passively protect against HUS development in individuals infected with Stx-producing bacteria, including E. coli O157:H7.</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/11796590?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Okhuysen, Pablo C</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Chappell, Cynthia L</style></author><author><style face="normal" font="default" size="100%">Grimes, Kevin A</style></author><author><style face="normal" font="default" size="100%">Widmer, Giovanni</style></author><author><style face="normal" font="default" size="100%">Feng, Xiaochuan</style></author><author><style face="normal" font="default" size="100%">Tzipori, Saul</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Infectivity of a Cryptosporidium parvum isolate of cervine origin for healthy adults and interferon-gamma knockout mice.</style></title><secondary-title><style face="normal" font="default" size="100%">J Infect Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Infect. Dis.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Weight</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidiosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryptosporidium parvum</style></keyword><keyword><style  face="normal" font="default" size="100%">Deer</style></keyword><keyword><style  face="normal" font="default" size="100%">Diarrhea</style></keyword><keyword><style  face="normal" font="default" size="100%">Disease Susceptibility</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Interferon-gamma</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2002</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2002 May 1</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">185</style></volume><pages><style face="normal" font="default" size="100%">1320-5</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The infectivity of a Cryptosporidium parvum isolate of cervine origin (type 2, Moredun) propagated in calves was investigated simultaneously in healthy adult human volunteers and in interferon-gamma knockout (GKO) mice. After exposure to 100-3000 oocysts, 16 volunteers recorded, for a duration of 6 weeks, the number and form of stools that they passed and any symptoms that they experienced. Oocyst excretion was assessed by enzyme-linked immunosorbent assay and direct immunofluorescence assay. Eleven subjects (69%) became ill, and 8 subjects (50%) shed oocysts in stool. The median duration of illness was 169 h, and the median number of unformed stools passed was 24. The duration and intensity of symptoms were more severe than were those associated with previously studied isolates. The median infectious dose was estimated to be 300 oocysts for humans and 1 oocyst for the GKO mouse model. The Moredun isolate was more pathogenic than the reference GCH-1 isolate. The GKO mouse model of cryptosporidiosis is useful for discerning isolate-specific differences in pathogenicity.</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/12001050?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mukherjee, Jean</style></author><author><style face="normal" font="default" size="100%">Chios, Kerry</style></author><author><style face="normal" font="default" size="100%">Fishwild, Dianne</style></author><author><style face="normal" font="default" size="100%">Hudson, Deborah</style></author><author><style face="normal" font="default" size="100%">O'Donnell, Susan</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen M</style></author><author><style face="normal" font="default" size="100%">Donohue-Rolfe, Arthur</style></author><author><style face="normal" font="default" size="100%">Tzipori, Saul</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Production and characterization of protective human antibodies against Shiga toxin 1.</style></title><secondary-title><style face="normal" font="default" size="100%">Infect Immun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Infect. Immun.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Bacterial</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibodies, Monoclonal</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Escherichia coli</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">HeLa Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Hemolytic-Uremic Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hybridomas</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunization, Passive</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin G</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunoglobulin M</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Neutralization Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Shiga Toxin 1</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2002</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2002 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">70</style></volume><pages><style face="normal" font="default" size="100%">5896-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Hemolytic-uremic syndrome (HUS) is a serious complication which is predominantly associated in children with infection by Shiga toxin-producing Escherichia coli (STEC). By using HuMAb-Mouse (Medarex) animals, human monoclonal antibodies (Hu-MAbs) were developed against Shiga toxin 1 (Stx1) for passive immunotherapy of HUS. Ten stable hybridomas comprised of fully human heavy- and light-chain immunoglobulin elements and secreting Stx1-specific Hu-MAbs (seven immunoglobulin M(kappa)() [IgM(kappa)] elements [one specific for the A subunit and six specific for the B subunit] and three IgG1(kappa) elements specific for subunit B) were isolated. Two IgM(kappa) Hu-MAbs (2D9 and 15G9) and three IgG1(kappa) Hu-MAbs (5A4, 10F4, and 15G2), all specific for subunit B, demonstrated marked neutralization of Stx1 in vitro and significant prolongation of survival in a murine model of Stx1 toxicosis.</style></abstract><issue><style face="normal" font="default" size="100%">10</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/12228326?dopt=Abstract</style></custom1></record></records></xml>