Publications by authors named "Daniel D Sedmak"

Based on cell culture data, MHC class I downregulation by HCMV on infected cells has been suggested as a means of immune evasion by this virus. In order to address this issue , an immunohistochemical analysis of tissue sections from biopsy and autopsy materials of HCMV infected organs was performed. HCMV antigens from the immediate early, early, and late phase of viral replication, and cellular MHC class I molecules were detected simultaneously or in serial sections by immuno-peroxidase and immuno-alkaline phosphatase techniques.

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In terms of managing thrombotic disorders, genotype-based individualized patient care emerged as early as 1994 when the association of factor V Leiden (G1691A), and later, prothrombin (G20210A), with thrombotic phenotypes were discovered. Since then, genetic tests for specific thrombophilic SNPs have been routinely incorporated into daily practices in both thrombotic risk assessment and clinical decision-making with respect to prophylactic anti-thrombotic therapy. Recently, the area of pharmacogenomics in major anti-thrombotic drugs, such as warfarin and clopidogrel, has been the principal driver for personalized therapy based on one's own individual characteristics.

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Personalized healthcare has regained momentum through the unprecedented surge of research in the genomics field and related areas of biology. These new insights compel the optimization of healthcare and therapy for individual subjects. While the potential benefits are large, substantial obstacles need to be overcome for attaining clinical utility in general medial practice.

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Background: In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function.

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We have previously shown that cytomegalovirus (CMV) can reactivate in lungs of nonimmunosuppressed patients during critical illness. Our recent work has shown that polymicrobial bacterial sepsis can trigger reactivation of latent murine CMV (MCMV). We hypothesize that MCMV reactivation following bacterial sepsis may be caused by inflammatory mediators.

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Objective: Cytomegalovirus (CMV) is a ubiquitous herpes virus that persists in the host in a latent state following primary infection. We have recently observed that CMV reactivates in lungs of critically ill surgical patients and that this reactivation can be triggered by bacterial sepsis. Although CMV is a known pathogen in immunosuppressed transplant patients, it is unknown whether reactivated CMV is a pathogen in immunocompetent hosts.

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The human cytomegalovirus tegument protein pp71 is the product of the UL82 gene. Roles for pp71 in stimulating gene transcription, increasing infectivity of viral DNA, and the degradation of retinoblastoma family proteins have been described. Here we report a novel function for pp71 in limiting accumulation of cell surface major histocompatibility complex (MHC) class I complexes.

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Purpose: To determine if prior exposure to pathogens associated with vascular disease, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori correlates with neovascular age-related macular degeneration (AMD).

Design: An experimental study.

Setting: Institutional.

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Background: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated.

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The scientific usefulness of the data obtained from tissue analysis is related to specimen quality, which may be affected by conditions that may contribute to the degradation of the specimen before processing and analysis. We determined the usability of nucleic acids extracted from banked human tissues for further molecular analyses. We assayed 151 tissue specimens, storedfor various times at 4 divisions of the Cooperative Human Tissue Network, National Cancer Institute, Bethesda, MD, for DNA and RNA degradation.

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We hypothesized that US28, a cytomegalovirus (CMV) CC chemokine receptor homolog, plays a role in modulating the host antiviral defense. Monocyte chemotaxis was induced by supernatants from fibroblasts infected with a US28 deletion mutant of CMV (CMV Delta US28) due to endogenously produced CC chemokines MCP-1 and RANTES. However, these chemokines were sequestered from the supernatants of CMV-infected cells that did express US28.

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CD8(+) and CD4(+) T lymphocytes are important in controlling human CMV (HCMV) infection, but the virus has evolved protean mechanisms to inhibit MHC-based Ag presentation and escape T lymphocyte immunosurveillance. Herein, the interaction of HCMV with the MHC class II Ag presentation pathway was investigated in cells stably transfected with class II transactivator. Flow cytometry experiments demonstrate that HCMV infection decreases cell-surface MHC class II expression.

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Critically ill surgery patients are susceptible to pulmonary reactivation of latent cytomegalovirus (CMV), but what triggers this reactivation is unknown. Immunosuppression and bacterial sepsis are thought to stimulate reactivation of CMV, and in this study it was hypothesized that immunosuppressive effects of surgery with or without concomitant bacterial infection may reactivate latent CMV. Mice infected with CMV were allowed to develop latent infections.

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