bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of Nonenteric Protozoan Infections in Immunocompromised People
Authors: Barratt J. L. N. , Harkness J. , Marriott D. , Ellis J. T. , Stark D. 
Published: October 2010

SUMMARYThere are many neglected nonenteric protozoa able to cause serious morbidity and mortality in humans, particularly in the developing world. Diseases caused by certain protozoa are often more severe in the presence of HIV. While information regarding neglected tropical diseases caused by trypanosomatids andPlasmodiumis abundant, these protozoa are often not a first consideration in Western countries where they are not endemic. As such, diagnostics may not be available in these regions. Due to global travel and immigration, this has become an increasing problem. Inversely, in certain parts of the world (particularly sub-Saharan Africa), the HIV problem is so severe that diseases like microsporidiosis and toxoplasmosis are common. In Western countries, due to the availability of highly active antiretroviral therapy (HAART), these diseases are infrequently encountered. While free-living amoebae are rarely encountered in a clinical setting, when infections do occur, they are often fatal. Rapid diagnosis and treatment are essential to the survival of patients infected with these organisms. This paper reviews information on the diagnosis and treatment of nonenteric protozoal diseases in immunocompromised people, with a focus on patients infected with HIV. The nonenteric microsporidia, some trypanosomatids,Toxoplasmaspp.,Neosporaspp., some free-living amoebae,Plasmodiumspp., andBabesiaspp. are discussed.
Helicobacter pyloriand Gastric Cancer: Factors That Modulate Disease Risk
Authors: Wroblewski Lydia E. , Peek Richard M. , Wilson Keith T. 
Published: October 2010

SUMMARYHelicobacter pyloriis a gastric pathogen that colonizes approximately 50% of the world's population. Infection withH. pyloricauses chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection withH. pyloriis the strongest known risk factor for gastric cancer, which is the second leading cause of cancer-related deaths worldwide. OnceH. pyloricolonizes the gastric environment, it persists for the lifetime of the host, suggesting that the host immune response is ineffective in clearing this bacterium. In this review, we discuss the host immune response and examine other host factors that increase the pathogenic potential of this bacterium, including host polymorphisms, alterations to the apical-junctional complex, and the effects of environmental factors. In addition to host effects and responses,H. pyloristrains are genetically diverse. We discuss the main virulence determinants inH. pyloristrains and the correlation between these and the diverse clinical outcomes followingH. pyloriinfection. SinceH. pyloriinhibits the gastric epithelium of half of the world, it is crucial that we continue to gain understanding of host and microbial factors that increase the risk of developing more severe clinical outcomes.
Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy
Authors: Ram Sanjay , Lewis Lisa A. , Rice Peter A. 
Published: October 2010

SUMMARYThe complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, includingStreptococcus pneumoniae,Neisseria meningitidis, andHaemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, andEscherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.
Serum Intercellular Adhesion Molecule 1 Variations in Young Children with Acute Otitis Media
Authors: Liu Keyi , Casey Janet , Pichichero Michael 
Published: October 2010

ABSTRACTAcute otitis media (AOM) is an inflammatory reaction in the middle ear, most often occurring in young children.Streptococcus pneumoniae, nontypeableHaemophilusinfluenzae, andMoraxella catarrhalisare the most common bacteria isolated. Intercellular adhesion molecule 1 (ICAM-1) is involved in the innate immune response to infection by microorganisms, in effective antigen presentation, and in subsequent T-cell activation. Here we prospectively studied levels of serum soluble ICAM-1 (sICAM-1) before, at the time of, and after antimicrobial treatment of AOM in a group of 138 children ages 6 to 30 months. Middle ear fluids were collected by tympanocentesis to identify otopathogens. We found that (i) serum levels of sICAM-1 were significantly higher inS. pneumoniae-, nontypeableH. influenzae-, andM. catarrhalis-infected children than in well children (P< 0.001), confirming that a systemic inflammatory response occurs during AOM; (ii) sICAM-1 levels varied from no elevation (110 ng/ml) to elevation to high levels (maximum, 1,470 ng/ml) among children with AOM; (iii) in paired samples, sICAM-1 levels increased 4- to 20-fold when children developed AOM compared to their sICAM-1 levels before infection; and (iv) the level of sICAM-1 returned to the pre-AOM level at the convalescent stage of AOM after successful antimicrobial therapy. We conclude that AOM often causes a systemic inflammatory reaction, as measured by elevation of the serum sICAM-1 level, and that a high variability in sICAM-1 responses occurs with the presence of otopathogens during AOM.
Development and Characterization of ProtectiveHaemophilus parasuisSubunit Vaccines Based on Native Proteins with Affinity to Porcine Transferrin and Comparison with Other Subunit and Commercial Vaccines
Authors: Frandoloso Rafael , Martínez Sonia , Rodríguez-Ferri Elías F. , García-Iglesias María José , Pérez-Martínez Claudia , Martínez-Fernández Beatriz , Gutiérrez-Martín César B. 
Published: October 2010

ABSTRACTHaemophilus parasuisis the agent responsible for causing Glässer's disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis in pigs. In this study, we have characterized native outer membrane proteins with affinity to porcine transferrin (NPAPT) fromH. parasuisserovar 5, Nagasaki strain. This pool of proteins was used as antigen to developed two vaccine formulations: one was adjuvanted with a mineral oil (Montanide IMS 2215 VG PR), while the other was potentiated with a bacterial neuraminidase fromClostridium perfringens. The potential protective effect conferred by these two vaccines was compared to that afforded by two other vaccines, consisting of recombinant transferrin-binding protein (rTbp) A or B fragments fromH. parasuis, Nagasaki strain, and by a commercially available inactivated vaccine. Five groups of colostrum-deprived piglets immunized with the vaccines described above, one group per each vaccine, and a group of nonvaccinated control animals were challenged intratracheally with a lethal dose (3 × 108CFU) ofH. parasuis, Nagasaki strain. The two vaccines containing rTbps yielded similar results with minimal protection against death, clinical signs, gross and microscopic lesions, andH. parasuisinvasion. In contrast, the two vaccines composed of NPAPT antigen and commercial bacterin resulted in a strong protection against challenge (without deaths and clinical signs), mild histopathological changes, and no recovery ofH. parasuis, thus suggesting their effectiveness in preventing Glässer's disease outbreaks caused by serovar 5.
Detection of Humoral Response Using a Recombinant Heat Shock Protein 70, DnaK, ofMycoplasma haemofelisin Experimentally and Naturally Hemoplasma-Infected Cats
Authors: Barker Emily N. , Helps Chris R. , Heesom Kate J. , Arthur Christopher J. , Peters Iain R. , Hofmann-Lehmann Regina , Tasker Séverine 
Published: October 2010

ABSTRACTHemoplasmas is the trivial name given to a group of erythrocyte-parasitizing bacteria of the genusMycoplasma. Of the feline hemoplasmas,Mycoplasma haemofelisis the most pathogenic, while “CandidatusMycoplasma haemominutum” and “CandidatusMycoplasma turicensis” are less pathogenic. Shotgun libraries of fragmentedM. haemofelisgenomic DNA were constructed, and random colonies were selected for DNA sequencing.In silico-translated amino acid sequences of putative open reading frames were compared to mass spectrometry data fromM. haemofelisprotein spots identified as being immunogenic by two-dimensional gel electrophoresis and Western blotting. Three of the spots matched the predicted sequences of a heat shock protein 70 (DnaK) homolog, elongation factor Ts, and a fragment of phosphoglycerate kinase found during library screening. A full-length copy of theM. haemofelis dnaKgene was cloned intoEscherichia coliand recombinantly expressed. RecombinantM. haemofelisDnaK was purified and then used in Western blotting and an enzyme-linked immunosorbent assay (ELISA) to investigate the humoral immune response during acute infection in cats experimentally infected withM. haemofelis, “Ca.Mycoplasma haemominutum,” or “Ca.Mycoplasma turicensis”. The recombinantM. haemofelisDnaK ELISA also was used to screen clinical samples submitted for hemoplasma PCR testing to a commercial laboratory (n= 254). Experimentally infected cats became seropositive following infection, with a greater and earlier antibody response seen in cats inoculated withM. haemofelisthan those seen in cats inoculated with “Ca.Mycoplasma haemominutum” or “Ca.Mycoplasma turicensis,” by both Western blotting and ELISA. Of the clinical samples, 31.1% had antibodies detected by the ELISA but only 9.8% were positive by PCR for one or more hemoplasmas.
Sensitive Assay for Quantification of Hepatitis B Virus Mutants by Use of a Minor Groove Binder Probe and Peptide Nucleic Acids
Authors: Hige Shuhei , Yamamoto Yoichi , Yoshida Shigeru , Kobayashi Tomoe , Horimoto Hiromasa , Yamamoto Keiko , Sho Takuya , Natsuizaka Mitsuteru , Nakanishi Mitsuru , Chuma Makoto , Asaka Masahiro 
Published: October 2010

ABSTRACT

Lamivudine is the first nucleoside analogue that was shown to have a potent effect on hepatitis B virus (HBV). However, the emergence of mutants resistant or cross-resistant to nucleoside/nucleotide analogues remains a serious problem. Several assays for the detection and quantification of antiviral-resistant mutants have been reported, but it has been difficult to measure the amounts of mutants accurately, especially when the target strain is a minor component of the mixed population. It has been shown that accurate measurement of a minor strain is difficult as long as a matching reaction with a single probe is included in the assay. We developed a new method for the quantification of lamivudine-resistant strains in a mixed-virus population by real-time PCR using minor groove binder probes and peptide nucleic acids, and we achieved a wide and measurable range, from 3 to 10 log
10
copies/ml, and high sensitivity, with a discriminative limit of 0.01% of the predominant strain. The clinical significance of measuring substitutions not only of M204 but also of L180 residues of HBV polymerase was demonstrated by this method. This assay increases the versatility of a sensitive method for the quantification of a single-nucleotide mutation in a heterogeneous population.
Evaluation of Time to Detection of
Mycobacterium tuberculosis
in Broth Culture as a Determinant for End Points in Treatment Trials
Authors: Weiner Marc , Prihoda Thomas J. , Burman William , Johnson John L. , Goldberg Stefan , Padayatchi Nesri , Duran Paula , Engle Melissa , Muzanye Grace , Mugerwa Roy D. , Sturm A. Willem 
Published: October 2010

ABSTRACT

Time to detection of
Mycobacterium tuberculosis
in broth culture was examined for utility as a treatment efficacy end point. Of 146 patients in a phase IIB trial, a decreased mean time to detection was found in 5 with treatment failure. Time to detection in an analysis-of-covariance model was associated with lung cavities, less intensive treatment, and differences in the bactericidal effects of treatment regimens.
Feasibility Study of a Human Papillomavirus E6 Oncoprotein Test for Diagnosis of Cervical Precancer and Cancer
Authors: Schweizer Johannes , Lu Peter S. , Mahoney Charles W. , Berard-Bergery Marthe , Ho Minh , Ramasamy Valli , Silver Jon E. , Bisht Arnima , Labiad Yassine , Peck Roger B. , Lim Jeanette , Jeronimo Jose , Howard Roslyn , Gravitt Patti E. , Castle Philip E. 
Published: October 2010

ABSTRACT
In a feasibility study using a prototype, lateral-flow test for human papillomavirus type 16, 18, and/or 45 (HPV16/18/45) E6 oncoproteins, 51 of 75 (68%; 95% confidence interval [95% CI] of 56 to 78%) of HPV16/18/45 DNA-positive specimens from women with a diagnosis of CIN3+ (cervical intraepithelial neoplasia grade 3+ or cervical cancer) tested positive for HPV16/18/45 E6 oncoprotein. None of 16 (95% CI of 0 to 37%) HPV16/18/45 DNA-positive cervical specimens from women with a negative or CIN1 diagnosis tested positive for HPV16/18/45 E6 oncoprotein.
Isolation of a Novel
Orientia
Species (
O. chuto
sp. nov.) from a Patient Infected in Dubai
Authors: Izzard Leonard , Fuller Andrew , Blacksell Stuart D. , Paris Daniel H. , Richards Allen L. , Aukkanit Nuntipa , Nguyen Chelsea , Jiang Ju , Fenwick Stan , Day Nicholas P. J. , Graves Stephen , Stenos John 
Published: October 2010

ABSTRACT

In July 2006, an Australian tourist returning from Dubai, in the United Arab Emirates (UAE), developed acute scrub typhus. Her signs and symptoms included fever, myalgia, headache, rash, and eschar.
Orientia tsutsugamushi
serology demonstrated a 4-fold rise in antibody titers in paired serum collections (1:512 to 1:8,192), with the sera reacting strongest against the Gilliam strain antigen. An
Orientia
species was isolated by the
in vitro
culture of the patient's acute blood taken prior to antibiotic treatment. The gene sequencing of the 16S rRNA gene (
rrs
), partial 56-kDa gene, and the full open reading frame 47-kDa gene was performed, and comparisons of this new
Orientia
sp. isolate to previously characterized strains demonstrated significant sequence diversity. The closest homology to the
rrs
sequence of the new
Orientia
sp. isolate was with three strains of
O. tsutsugamushi
(Ikeda, Kato, and Karp), with a nucleotide sequence similarity of 98.5%. The closest homology to the 47-kDa gene sequence was with
O. tsutsugamushi
strain Gilliam, with a nucleotide similarity of 82.3%, while the closest homology to the 56-kDa gene sequence was with
O. tsutsugamushi
strain TA686, with a nucleotide similarity of 53.1%. The molecular divergence and geographically unique origin lead us to believe that this organism should be considered a novel species. Therefore, we have proposed the name “
Orientia chuto
,” and the prototype strain of this species is strain Dubai, named after the location in which the patient was infected.
Molecular Phylogeny and Proposal of Two New Species of the Emerging Pathogenic FungusSaksenaea
Authors: Alvarez E. , Garcia-Hermoso D. , Sutton D. A. , Cano J. F. , Stchigel A. M. , Hoinard D. , Fothergill A. W. , Rinaldi M. G. , Dromer F. , Guarro J. 
Published: October 2010

ABSTRACTSaksenaeais a monotypic genus belonging to the orderMucoralesand capable of producing severe human infections. Through a polyphasic study based on analysis of the sequences of the internal transcribed spacer (ITS) region, domains D1 and D2 of the 28S rRNA gene, and the elongation factor 1α (EF-1α) gene, as well as by evaluation of relevant morphological and physiological characteristics of a set of clinical and environmental strains, we have demonstrated thatSaksenaea vasiformisis a complex of species. We propose as new speciesSaksenaea oblongispora, characterized by oblong sporangiospores and unable to grow at 42°C, andSaksenaea erythrospora, characterized by large sporangiophores and sporangia and by ellipsoid sporangiospores, biconcave in the lateral view. Itraconazole, posaconazole, and terbinafine were active against all isolates included in the study, while amphotericin B, voriconazole, and the echinocandins showed low activity.
Genomic Profiling of Tumor Necrosis Factor Alpha (TNF-α) Receptor and Interleukin-1 Receptor Knockout Mice Reveals a Link between TNF-α Signaling and Increased Severity of 1918 Pandemic Influenza Virus Infection
Authors: Belisle Sarah E. , Tisoncik Jennifer R. , Korth Marcus J. , Carter Victoria S. , Proll Sean C. , Swayne David E. , Pantin-Jackwood Mary , Tumpey Terrence M. , Katze Michael G. 
Published: October 2010

ABSTRACTThe influenza pandemic of 1918 to 1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated proinflammatory cytokine response. In the present study, we compared the host transcriptional response to infection with the reconstructed 1918 virus in wild-type, tumor necrosis factor (TNF) receptor-1 knockout (TNFRKO), and interleukin-1 (IL-1) receptor-1 knockout (IL1RKO) mice as a means of further understanding the role of proinflammatory cytokine signaling during the acute response to infection. Despite reported redundancy in the functions of IL-1β and TNF-α, we observed that reducing the signaling capacity of each of these molecules by genetic disruption of their key receptor genes had very different effects on the host response to infection. In TNFRKO mice, we found delayed or decreased expression of genes associated with antiviral and innate immune signaling, complement, coagulation, and negative acute-phase response. In contrast, in IL1RKO mice numerous genes were differentially expressed at 1 day postinoculation, including an increase in the expression of genes that contribute to dendritic and natural killer cell processes and cellular movement, and gene expression profiles remained relatively constant at later time points. We also observed a compensatory increase in TNF-α expression in virus-infected IL1RKO mice. Our data suggest that signaling through the IL-1 receptor is protective, whereas signaling through the TNF-α receptor increases the severity of 1918 virus infection. These findings suggest that manipulation of these pathways may have therapeutic benefit.
Hepatitis C Virus Nonstructural Protein 5A: Biochemical Characterization of a Novel Structural Class of RNA-Binding Proteins
Authors: Hwang Jungwook , Huang Luyun , Cordek Daniel G. , Vaughan Robert , Reynolds Shelley L. , Kihara George , Raney Kevin D. , Kao C. Cheng , Cameron Craig E. 
Published: October 2010

ABSTRACT

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) exhibits a preference for G/U-rich RNA
in vitro
. Biological analysis of the NS5A RNA-binding activity and its target sites in the genome will be facilitated by a description of the NS5A-RNA complex. We demonstrate that the C-4 carbonyl of the uracil base and, by inference, the C-6 carbonyl of the guanine base interact with NS5A. U-rich RNA of 5 to 6 nucleotides (nt) is sufficient for high-affinity binding to NS5A. The minimal RNA-binding domain of NS5A consists of residues 2005 to 2221 (referred to as domain I-plus). This region of the protein includes the amino-terminal domain I as well as the subsequent linker that separates domains I and II. This linker region is the site of adaptive mutations. U-rich RNA-binding activity is not observed for an NS5A derivative containing only residues 2194 to 2419 (domains II and III). Mass spectrometric analysis of an NS5A-poly(rU) complex identified domains I and II as sites for interaction with RNA. Dimerization of NS5A was demonstrated by glutaraldehyde cross-linking. This dimerization is likely mediated by domain I-plus, as dimers of this protein are trapped by cross-linking. Dimers of the domain II-III protein are not observed. The monomer-dimer equilibrium of NS5A shifts in favor of dimer when U-rich RNA is present but not when A-rich RNA is present, consistent with an NS5A dimer being the RNA-binding-competent form of the protein. These data provide a molecular perspective of the NS5A-RNA complex and suggest possible mechanisms for regulation of HCV and cellular gene expression.
Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection
Authors: Parker Michael D. , Buckley Marilyn J. , Melanson Vanessa R. , Glass Pamela J. , Norwood David , Hart Mary Kate 
Published: October 2010

ABSTRACTSix monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells.