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Kutty G.,U.S. National Institutes of Health | Achaz G.,University Pierre and Marie Curie | Maldarelli F.,U.S. National Cancer Institute | Varma A.,Laboratory of Clinical Infectious Diseases | And 4 more authors.
Journal of Infectious Diseases | Year: 2010

The life cycle of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, remains poorly defined. In the present study, we have identified and characterized an orthologue of dmc1, a gene specific for meiotic recombination in yeast, in 3 species of Pneumocystis. dmc1 is a single-copy gene that is transcribed as ∼1.2-kb messenger RNA, which encodes a protein of 336-337 amino acids. Pneumocystis Dmc1 was 61%-70% identical to those from yeast. Confocal microscopy results indicated that the expression of Dmc1 is primarily confined to the cyst form of Pneumocystis. By sequence analysis of 2 single-copy regions of the human Pneumocystis jirovecii genome, we can infer multiple recombination events, which are consistent with meiotic recombination in this primarily haploid organism. Taken together, these studies support the occurrence of a sexual phase in the life cycle of Pneumocystis. © 2010 by the Infectious Diseases Society of America. All rights reserved. Source

Bagci U.,Center for Infectious Diseases Imaging | Caban J.,National Library of Medicine | Palmore T.N.,Laboratory of Clinical Infectious Diseases | Suffredini A.F.,U.S. National Institutes of Health | Mollura D.J.,Center for Infectious Diseases Imaging
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2011

Abnormal nodular branching opacities at the lung periphery in Chest Computed Tomography (CT) are termed by radiology literature as tree-in-bud (TIB) opacities. These subtle opacity differences represent pulmonary disease in the small airways such as infectious or inflammatory bronchiolitis. Precisely quantifying the detection and measurement of TIB abnormality using computer assisted detection (CAD) would assist clinical and research investigation of this pathology commonly seen in pulmonary infections. This paper presents a novel method for automatically detecting TIB patterns based on fast localization of candidates using local scale information of the images. The proposed method combines shape index, local gradient statistics, and steerable wavelet features to automatically identify TIB patterns. Experimental results using 39 viral bronchiolitis human para-influenza (HPIV) CTs and 21 normal lung CTs achieved an overall accuracy of 89.95%. © 2011 IEEE. Source

Bow E.J.,University of Manitoba | Evans G.,Queens University | Fuller J.,University of Alberta | Laverdiere M.,University of Montreal | And 8 more authors.
Canadian Journal of Infectious Diseases and Medical Microbiology | Year: 2010

Candidemia and invasive candidiasis (C/IC) are life-threatening opportunistic infections that add excess morbidity, mortality and cost to the management of patients with a range of potentially curable underlying conditions. The Association of Medical Microbiology and Infectious Disease Canada developed evidence-based guidelines for the approach to the diagnosis and management of these infections in the ever-increasing population of at-risk adult patients in the health care system. Over the past few years, a new and broader understanding of the epidemiology and pathogenesis of C/IC has emerged and has been coupled with the availability of new antifungal agents and defined strategies for targeting groups at risk including, but not limited to, acute leukemia patients, hematopoietic stem cell transplants and solid organ transplants, and critical care unit patients. Accordingly, these guidelines have focused on patients at risk for C/IC, and on approaches of prevention, early therapy for suspected but unproven infection, and targeted therapy for probable and proven infection. ©2010 Pulsus Group Inc. All rights reserved. Source

Greenberg D.E.,Laboratory of Clinical Infectious Diseases | Marshall-Batty K.R.,Laboratory of Clinical Infectious Diseases | Brinster L.R.,U.S. National Institutes of Health | Zarember K.A.,Laboratory of Host Defenses | And 5 more authors.
Journal of Infectious Diseases | Year: 2010

Background. Members of the Burkholderia cepacia complex (Bcc) cause considerable morbidity and mortality in patients with chronic granulomatous disease and cystic fibrosis. Many Bcc strains are antibiotic resistant, which requires the exploration of novel antimicrobial approaches, including antisense technologies such as phosphorodiamidate morpholino oligomers (PMOs). Methods. Peptide-conjugated PMOs (PPMOs) were developed to target acpP, which encodes an acyl carrier protein (AcpP) that is thought to be essential for growth. Their antimicrobial activities were tested against different strains of Bcc in vitro and in infection models. Results. PPMOs targeting acpP were bactericidal against clinical isolates of Bcc (>4 log reduction), whereas a PPMO with a scrambled base sequence (scrambled PPMO) had no effect on growth. Human neutrophils were infected with Burkholderia multivorans and treated with AcpP PPMO. AcpP PPMO augmented killing, compared with neutrophils alone and compared with neutrophils alone plus scrambled PPMO. Mice with chronic granulomatous disease that were infected with B. multivorans were treated with AcpP PPMO, scrambled PPMO, or water at 0, 3, and 6 h after infection. Compared with water-treated control mice, the AcpP PPMO-treated mice showed an ∼80% reduction in the risk of dying by day 30 of the experiment and relatively little pathology. Conclusion. AcpP PPMO is active against Bcc infections in vitro and in vivo. © 2010 by the Infectious Diseases Society ot America. All right reserved. Source

Bax H.I.,Laboratory of Clinical Infectious Diseases | Bax H.I.,Erasmus Medical Center | Freeman A.F.,Laboratory of Clinical Infectious Diseases | Ding L.,Laboratory of Clinical Infectious Diseases | And 15 more authors.
Journal of Clinical Immunology | Year: 2013

Patients with deficiency in the interferon gamma receptor (IFN-γR) are unable to respond properly to IFN-γ and develop severe infections with nontuberculous mycobacteria (NTM). IFN-γ and IFN-α are known to signal through STAT1 and activate many downstream effector genes in common. Therefore, we added IFN-α for treatment of patients with disseminated mycobacterial disease in an effort to complement their IFN-γ signaling defect. We treated four patients with IFN-γR deficiency with adjunctive IFN-α therapy in addition to best available antimicrobial therapy, with or without IFN-γ, depending on the defect. During IFN-α treatment, ex vivo induction of IFN target genes was detected. In addition, IFN-α driven gene expression in patients' cells and mycobacteria induced cytokine response were observed in vitro. Clinical responses varied in these patients. IFN-α therapy was associated with either improvement or stabilization of disease. In no case was disease exacerbated. In patients with profoundly impaired IFN-γ signaling who have refractory infections, IFN-α may have adjunctive anti-mycobacterial effects. © 2013 Springer Science+Business Media New York. Source

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