James Chodosh

MD, MPH
Massachusetts Eye and Ear Infirmary - Harvard Medical School · Ophthalmology

Research interests

  • Interests
    Molecular Virology

Other

  • Languages
    English

Publications

  • Oral Acetazolamide after Boston Keratoprosthesis in Stevens Johnson Syndrome.

    Radhika Kumar, Claes H Dohlman, James Chodosh

    BMC research notes. 04/2012; 5(1):205.

    ABSTRACT: BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare but severe and sometimes fatal condition associated with exposure to medications; sulfamethoxazole is among the most common causes. We sought to address the safety of acetazolamide, a chemically related com... [more] ABSTRACT: BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare but severe and sometimes fatal condition associated with exposure to medications; sulfamethoxazole is among the most common causes. We sought to address the safety of acetazolamide, a chemically related compound, in patients with prior SJS/TEN and glaucoma. A retrospective case series is described of patients at the Massachusetts Eye and Ear Infirmary who underwent keratoprosthesis surgery for corneal blindness from SJS/TEN, and later required oral acetazolamide for elevated intraocular pressure. FINDINGS: Over the last 10 years, 17 patients with SJS/TEN received a Boston keratoprosthesis. Of these, 11 developed elevated intraocular pressure that required administration of oral acetazolamide. One of 11 developed a mild allergic reaction, but no patient experienced a recurrence of SJS/TEN or any severe adverse reaction. CONCLUSION: Although an increase in the rate of recurrent SJS/TEN due to oral acetazolamide would not necessarily be apparent after treating only 11 patients, in our series, acetazolamide administration was well tolerated without serious sequela.
  • 3.43
    Impact points
    Analysis of Human Adenovirus Type 19 Associated with Epidemic Keratoconjunctivitis and its Reclassification as Adenovirus Type 64.

    Xiaohong Zhou, Christopher M Robinson, Jaya Rajaiya, Shoaleh Deghan, Donald Seto, Morris S Jones, David W Dyer, James Chodosh

    Investigative ophthalmology & visual science. 03/2012;

    PURPOSE. Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified... [more] PURPOSE. Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified later with the identical serologic determinant is a significant ocular pathogen. METHODS. High throughput genome sequencing and bioinformatics analysis was performed on HAdV-D19p and three HAdV-D19 EKC strains, and compared to the previously sequenced clinical isolate, HAdV-D19 (C) and HAdV-D37. Corneas of C57BL/6J mice were injected with HAdV-D19p, HAdV-D19 (C), or virus-free buffer, and inflammation assessed by clinical examination, flow cytometry, and cytokine ELISA. Confocal microscopy and real-time PCR of infected corneal cell cultures were used to test viral entry.RESULTS. HAdV-D19 (C) and the other clinical EKC isolates showed nearly 100% sequence identity. EKC strains diverged from HAdV-D19p in the penton base, E3, and fiber transcription units. Simplot analysis showed recombination between EKC-associated HAdV-D19 with HAdV-D37, HAdV-D22, and HAdV-D19p, the latter contributing only the hexon gene, the principal serum neutralization determinant. HAdV-D19p induced stromal keratitis in the C57BL/6J mouse, but failed to productively infect human corneal epithelial cells. These data led to retyping of the clinical EKC isolates with a HAdV-D19 hexon gene as HAdV-D64.CONCLUSION. HAdV-D19 associated with EKC (HAdV-D64) originated from a recombination between HAdV-D19p, HAdV-D37, and HAdV-D22, and was mischaracterized because of a shared hexon gene. HAdV-D19p is not infectious for corneal epithelial cells, thus explaining the lack of any association with keratitis.
  • 5.15
    Impact points
    Over-Reliance on the Hexon Gene Leading to Misclassification of Human Adenoviruses.

    Gurdeep Singh, Christopher M Robinson, Shoaleh Dehghan, Timothy Schmidt, Donald Seto, Morris S Jones, David W Dyer, James Chodosh

    Journal of virology. 02/2012;

    The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences, each with an identical hexon gene, the same as previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusiv... [more] The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences, each with an identical hexon gene, the same as previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss co-infections. Whole genome sequencing remains the gold standard for proper classification of HAdVs.
  • 4.41
    Impact points
    Computational and serologic analysis of novel and known viruses in species human adenovirus d in which serology and genomics do not correlate.

    Elizabeth B Liu, Debra A Wadford, Jason Seto, Maria Vu, Nolan Ryan Hudson, Lisa Thrasher, Sarah Torres, David W Dyer, James Chodosh, Donald Seto, Morris S Jones

    PloS one. 01/2012; 7(3):e33212.

    In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using ... [more] In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate.
  • 5.15
    Impact points
    Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.

    Shoaleh Dehghan, Elizabeth B Liu, Jason Seto, Sarah F Torres, Nolan R Hudson, Adriana E Kajon, David Metzgar, David W Dyer, James Chodosh, Morris S Jones, Donald Seto

    Journal of virology. 01/2012; 86(1):635-6.

    Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, ... [more] Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment.
  • 5.15
    Impact points
    Complete genome sequence of human adenovirus prototype 17.

    Shoaleh Dehghan, Jason Seto, Nolan R Hudson, Christopher M Robinson, Morris S Jones, David W Dyer, James Chodosh, Donald Seto

    Journal of virology. 11/2011; 85(21):11540-1.

    As one of the first five human adenoviruses (HAdVs) to be sequenced, type 17 was important as a reference tool for comparative genomics of recently isolated HAdV pathogens in species D. HAdV-D17 was the first species D adenovirus to be sequenced and was deposited in GenBank in 1999. These genome dat... [more] As one of the first five human adenoviruses (HAdVs) to be sequenced, type 17 was important as a reference tool for comparative genomics of recently isolated HAdV pathogens in species D. HAdV-D17 was the first species D adenovirus to be sequenced and was deposited in GenBank in 1999. These genome data were not of high quality, and a redetermination of the same stock virus provides corrected data; among the differences are a length of 35,139 bp versus 35,100 bp in the original, and 160 mismatches to the original genome were found. Annotation of the coding sequences reveals 39 as opposed to 8, a finding which is important for phylogenomic studies.
  • 2.11
    Impact points
    The Boston keratoprosthesis type II: the Massachusetts Eye and Ear Infirmary experience.

    Siddharth Pujari, Sana S Siddique, Claes H Dohlman, James Chodosh

    Cornea. 09/2011; 30(12):1298-303.

    To report the long-term outcomes of Boston keratoprosthesis type II implantation in the management of severe ocular surface disease and corneal blindness through a retrospective interventional case series. This retrospective review included medical records of patients who underwent Boston keratopros... [more] To report the long-term outcomes of Boston keratoprosthesis type II implantation in the management of severe ocular surface disease and corneal blindness through a retrospective interventional case series. This retrospective review included medical records of patients who underwent Boston keratoprosthesis type II implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000 through December 31, 2009. The main outcome measures analyzed were visual acuity, keratoprosthesis retention, and postoperative complications. A total of 29 eyes of 26 patients received a Boston keratoprosthesis type II during the study period. Patients undergoing operation had corneal blindness because of mucous membrane pemphigoid (51.7%), Stevens-Johnson syndrome/toxic epidermal necrolysis (41.4%), or other ocular surface disease (6.9%). Visual acuity after surgery improved to 20/200 or better in 23 eyes (79.3%) and to 20/30 or better in 10 eyes (34.5%). In patients with at least 1 year of follow-up (n = 21), visual acuity of 20/200 or better was maintained in 12 eyes (57.1%). Of 13 eyes followed-up for more than 5 years, 6 eyes (46.2%) had visual acuity of 20/200 or better at the last follow-up examination. Eyes that did not improve to 20/200 or lost vision during the follow-up had end-stage glaucoma, previous retinal detachment, or age-related macular degeneration. Of the total of 29 eyes, 17 devices (58.6%) were retained without extrusion or replacement during a total follow-up time of 107.9 person-years. The Boston keratoprosthesis type II is a viable option for corneal blindness from severe autoimmune ocular surface diseases.
  • 4.16
    Impact points
    Computational analysis of two species C human adenoviruses provides evidence of a novel virus.

    Michael P Walsh, Jason Seto, Elizabeth B Liu, Shoaleh Dehghan, Nolan R Hudson, Alexander N Lukashev, Olga Ivanova, James Chodosh, David W Dyer, Morris S Jones, Donald Seto

    Journal of clinical microbiology. 08/2011; 49(10):3482-90.

    Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene deliv... [more] Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene delivery vectors for human gene therapy and in other biotechnological applications. Here, the full-genome analysis of the prototype HAdV-C6 and a recently identified virus provisionally termed HAdV-C57 are reported. Although the genomes of all species HAdV-C members are very similar to each other, the E3 region, hexon and fiber (ten proteins total) present a wide range of identity values at the amino acid level. Studies of these viruses in comparison to the other three HAdV-C prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and conservation within HAdV-C species. HAdV-C6 contains a recombination event within the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its loop 2 motif.
  • 3.43
    Impact points
    Hydroxyapatite for keratoprosthesis biointegration.

    Liqiang Wang, Kyung Jae Jeong, Homer H Chiang, David Zurakowski, Irmgard Behlau, James Chodosh, Claes H Dohlman, Robert Langer, Daniel S Kohane

    Investigative ophthalmology & visual science. 08/2011; 52(10):7392-9.

    Integration of keratoprosthesis with the surrounding cornea is very important in preventing bacterial invasion, which may cause ocular injury. Here the authors investigated whether hydroxyapatite (HAp) coating can improve keratoprosthesis (KPro) biointegration, using polymethyl methacrylate (PMMA)--... [more] Integration of keratoprosthesis with the surrounding cornea is very important in preventing bacterial invasion, which may cause ocular injury. Here the authors investigated whether hydroxyapatite (HAp) coating can improve keratoprosthesis (KPro) biointegration, using polymethyl methacrylate (PMMA)--the principal component of the Boston KPro--as a model polymer. HAp coatings were induced on PMMA discs after treatment with concentrated NaOH and coating with poly-dopamine (PDA) or polydopamine and then with 11-mercaptoundecanoic acid (11-MUA). Coatings were characterized chemically (Fourier transform infrared spectroscopy [FTIR], energy dispersive X-ray spectroscopy [EDX]) and morphologically (SEM) and were used as substrates for keratocyte growth in vitro. Cylinders of coated PMMA were implanted in porcine corneas ex vivo for 2 weeks, and the force required to pull them out was measured. The inflammatory reaction to coated discs was assessed in the rabbit cornea in vivo. FTIR of the coatings showed absorption bands characteristic of phosphate groups, and EDX showed that the Ca/P ratios were close to those of HAp. By SEM, each method resulted in morphologically distinct HAp films; the 11-MUA group had the most uniform coating. The hydroxyapatite coatings caused comparable enhancement of keratocyte proliferation compared with unmodified PMMA surfaces. HAp coating significantly increased the force and work required to pull PMMA cylinders out of porcine corneas ex vivo. HAp coating of implants reduced the inflammatory response around the PMMA implants in vivo. Conclusions: These results are encouraging for the potential of HAp-coated surfaces for use in keratoprostheses.
  • Relapsing polychondritis: systemic and ocular manifestations, differential diagnosis, management, and prognosis.

    Janie H Yoo, James Chodosh, Reza Dana

    Seminars in ophthalmology. 07/2011; 26(4-5):261-9.

    Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by episodic inflammation of cartilaginous tissues throughout the body. It is distinguished by recurrent bouts of inflammation, which lead to the permanent destruction of the involved structures. It can be a life-threat... [more] Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by episodic inflammation of cartilaginous tissues throughout the body. It is distinguished by recurrent bouts of inflammation, which lead to the permanent destruction of the involved structures. It can be a life-threatening, debilitating, and frightening disease and is often difficult to diagnose in its early stages. Ocular manifestations have been reported to occur in up to 65% of cases and include proptosis, eyelid edema, extraocular muscles palsy, episcleritis, scleritis, conjunctivitis, corneal infiltrate, peripheral ulcerative keratitis, corneal thinning or perforation, iridocyclitis, cataract, retinopathy, exudative retinal detachment, and optic neuritis. Corticosteroids remain the mainstay of treatment for RP; however, other treatment modalities include nonsteroidal anti-inflammatory drugs, colchicine, dapsone, and immunomodulatory drugs. This article reviews the literature and summarizes the epidemiology, pathogenesis, clinical features, treatment, and prognosis of the systemic and ocular manifestations of RP.
  • Delayed type hypersensitivity in the pathogenesis of recurrent herpes stromal keratitis.

    Kristen M Hawthorne, Reza Dana, James Chodosh

    Seminars in ophthalmology. 07/2011; 26(4-5):246-50.

    Recurrent herpes stromal keratitis (HSK) is one of the leading causes of blindness in the developed world. Cyokines characteristic of Th1 cells (in particular IFN-γ and IL-2) have been shown to dominate in HSK in addition to mechanisms by nonspecific, antigen-independent effector cells such as neutr... [more] Recurrent herpes stromal keratitis (HSK) is one of the leading causes of blindness in the developed world. Cyokines characteristic of Th1 cells (in particular IFN-γ and IL-2) have been shown to dominate in HSK in addition to mechanisms by nonspecific, antigen-independent effector cells such as neutrophils, basophils, and monocytes. More recently, the migration and maturation of dendritic cells (DC) within the corneal stroma of patients with HSK have been recognized as contributors to recurrent disease, suggesting a role for delayed type hypersensitivity (DTH) in the immunopathogenesis of HSK. The role of DC and DTH in recurrent HSK has not been studied extensively and experimental models of recurrent HSK focusing on DTH as the pathogenesis and viral particles as the triggering antigen may contribute to better understanding of the disease.
  • 2.56
    Impact points
    The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis.

    Christopher M Robinson, Jaya Rajaiya, Xiaohong Zhou, Gurdeep Singh, David W Dyer, James Chodosh

    Virus research. 06/2011; 160(1-2):120-7.

    Human adenovirus species D type 37 (HAdV-D37) is an important etiologic agent of epidemic keratoconjunctivitis. Annotation of the whole genome revealed an open reading frame (ORF) in the E3 transcription unit predicted to encode a 31.6kDa protein. This ORF, also known as CR1-γ, is predicted to be an... [more] Human adenovirus species D type 37 (HAdV-D37) is an important etiologic agent of epidemic keratoconjunctivitis. Annotation of the whole genome revealed an open reading frame (ORF) in the E3 transcription unit predicted to encode a 31.6kDa protein. This ORF, also known as CR1-γ, is predicted to be an integral membrane protein containing N-terminal signal sequence, luminal, transmembrane, and cytoplasmic domains. HAdV-D19 (C), another viral pathogen causing epidemic keratoconjunctivitis, contains an ORF 100% identical to its HAdV-D37 homologue but only 66% identical to other HAdV-D homologues. Kinetics of RNA expression and confirmation of splicing to the adenovirus tripartite leader sequence suggest a role for the protein product of CR1-γ in the late stages of the viral replication cycle. Confocal microscopy is consistent with expression in the cytoplasm. Sequence analysis reveals a hypervariable luminal domain and a conserved cytoplasmic domain. The luminal domain is predicted to contain multiple N-glycosylation sites. The cytoplasmic domain contains a putative protein kinase C phosphorylation site and potential YXXϕ and dileucine (LL) motifs suggesting a potential role in modification of host proteins.
  • 3.22
    Impact points
    Molecular evolution of human species D adenoviruses.

    Christopher M Robinson, Donald Seto, Morris S Jones, David W Dyer, James Chodosh

    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 05/2011; 11(6):1208-17.

    Adenoviruses are medium-sized double stranded DNA viruses that infect vertebrates. Human adenoviruses cause an array of diseases. Currently there are 56 human adenovirus types recognized and characterized within seven species (A-G). Of those types, a majority belongs to species D. In this review, th... [more] Adenoviruses are medium-sized double stranded DNA viruses that infect vertebrates. Human adenoviruses cause an array of diseases. Currently there are 56 human adenovirus types recognized and characterized within seven species (A-G). Of those types, a majority belongs to species D. In this review, the genomic conservation and diversity are examined among human adenoviruses within species D, particularly in contrast to other human adenovirus species. Specifically, homologous recombination is presented as a driving force for the molecular evolution of human adenoviruses and the emergence of new adenovirus pathogens.
  • 2.10
    Impact points
    Titanium back plate for a PMMA keratoprosthesis: clinical outcomes.

    Amit Todani, Joseph B Ciolino, Jared D Ament, Kathryn A Colby, Roberto Pineda, Michael W Belin, James V Aquavella, James Chodosh, Claes H Dohlman

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie. 04/2011; 249(10):1515-8.

    To compare the rate of retroprosthetic membrane (RPM) formation in Boston Keratoprosthesis (BKPro) with polymethyl methacrylate (PMMA) versus titanium backplates. Retrospective comparative chart review. Multicenter study population: a total of 78 eyes with keratoprosthesis implants with either PMMA ... [more] To compare the rate of retroprosthetic membrane (RPM) formation in Boston Keratoprosthesis (BKPro) with polymethyl methacrylate (PMMA) versus titanium backplates. Retrospective comparative chart review. Multicenter study population: a total of 78 eyes with keratoprosthesis implants with either PMMA or titanium backplates were included in the study. To be included in the study, all subjects had to have completed a minimum of 6-month follow-up period. Incidence of RPM development at 6-month postoperative period was noted across the study population. PMMA and titanium backplates were then compared by their rate of association with subsequent RPM. Twenty-three out of 55 eyes (41.8%) with PMMA backplates and three out of 23 eyes (13.0%) with titanium backplates had developed an RPM at 6 months after implantation. The titanium backplates were associated with significantly less RPM formation than PMMA backplates (p = 0.014, Chi-square test). Titanium seems to be associated with less RPM formation than PMMA when used as a material for the BKPro back plate.
  • 3.43
    Impact points
    Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis.

    Andrea Cruzat, Deborah Witkin, Neda Baniasadi, Lixin Zheng, Joseph B Ciolino, Ula V Jurkunas, James Chodosh, Deborah Pavan-Langston, Reza Dana, Pedram Hamrah

    Investigative ophthalmology & visual science. 04/2011; 52(8):5136-43.

    To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n ... [more] To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm(2); P < 0.0001), fungal (608.9 ± 812.5 cells/mm(2); P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm(2); P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm(2)). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = -0.44; P < 0.0005). IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea.
  • 5.15
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    Using the whole-genome sequence to characterize and name human adenoviruses.

    Donald Seto, James Chodosh, J Rodney Brister, Morris S Jones

    Journal of virology. 03/2011; 85(11):5701-2.

    We propose that human adenoviruses (HAdVs) be identified, characterized and typed on the basis of complete genome sequence analyses rather than serological approaches....... [more] We propose that human adenoviruses (HAdVs) be identified, characterized and typed on the basis of complete genome sequence analyses rather than serological approaches....
  • 4.41
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    Genetic analysis of a novel human adenovirus with a serologically unique hexon and a recombinant fiber gene.

    Elizabeth B Liu, Leonardo Ferreyra, Stephen L Fischer, Jorge V Pavan, Silvia V Nates, Nolan Ryan Hudson, Damaris Tirado, David W Dyer, James Chodosh, Donald Seto, Morris S Jones

    PloS one. 01/2011; 6(9):e24491.

    In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487) was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was seque... [more] In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487) was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was sequenced to elucidate its origin. Bioinformatic and phylogenetic analyses of this genome demonstrate that this virus, heretofore referred to as HAdV-D58, contains a novel hexon gene as well as a recombinant fiber gene. In addition, serological analysis demonstrated that HAdV-D58 has a different neutralization profile than all previously characterized HAdVs. Bootscan analysis of the HAdV-D58 fiber gene strongly suggests one recombination event.
  • 3.86
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  • 3.04
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    Computational analysis and identification of an emergent human adenovirus pathogen implicated in a respiratory fatality.

    Christopher M Robinson, Gurdeep Singh, Cécile Henquell, Michael P Walsh, Hélène Peigue-Lafeuille, Donald Seto, Morris S Jones, David W Dyer, James Chodosh

    Virology. 11/2010; 409(2):141-7.

    Adenoviral infections are typically acute, self-limiting, and not associated with death. However, we present the genomic and bioinformatics analysis of a novel recombinant human adenovirus (HAdV-D56) isolated in France that caused a rare neonatal fatality, and keratoconjunctivitis in three health ca... [more] Adenoviral infections are typically acute, self-limiting, and not associated with death. However, we present the genomic and bioinformatics analysis of a novel recombinant human adenovirus (HAdV-D56) isolated in France that caused a rare neonatal fatality, and keratoconjunctivitis in three health care workers who cared for the neonate. Whole genome alignments revealed the expected diversity in the penton base, hexon, E3, and fiber coding regions, and provided evidence for extensive recombination. Bootscan analysis confirmed recombination between HAdV-D9, HAdV-D26, HAdV-D15, and HAdV-D29 in the penton base and hexon proteins, centered around hypervariable loops within the putative proteins. Protein structure analysis of the fiber coding region revealed similarity with HAdV-D8, HAdV-D9, and HAdV-D53, possibly accounting for the ocular tropism of the virus. Based on these data, this virus appears to be a new HAdV-D type (HAdV-D56), underscoring the importance of recombination events in human adenovirus evolution and the emergence of new adenovirus pathogens.
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