237 results on '"Gilden DH"'
Search Results
2. VZV vasculopathy and postherpetic neuralgia: progress and perspective on antiviral therapy.
- Author
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Gilden DH, Cohrs RJ, and Mahalingam R
- Published
- 2005
- Full Text
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3. Clinical practice. Bell's palsy.
- Author
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Gilden DH
- Published
- 2004
4. Improved resolution of human cerebrospinal fluid proteins on two-dimensional gels.
- Author
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Hammack, BN, Owens, GP, Burgoon, MP, and Gilden, DH
- Subjects
CEREBROSPINAL fluid ,PROTEINS ,MULTIPLE sclerosis ,ULTRAFILTRATION ,ACETONE - Abstract
Proteomics combines two-dimensional gel electrophoresis and peptide mass fingerprinting and can potentially identify a protein(s) unique to disease. Such proteins can be used either for diagnosis or may be relevant to the pathogenesis of disease. Because patients with multiple sclerosis (MS) have increased amounts of immunoglobulin (Ig) G in their cerebrospinal fluid (CSF) that is directed against an as yet unidentified protein, we are applying proteomics to MS CSF, studies that require optimal separation of proteins in human CSF. We found that recovery of proteins from CSF of MS patients was improved using ultrafiltration, rather than dialysis, for desalting. Resolution of these proteins was enhanced by acetone precipitation of desalted CSF before electrophoresis and by fractionation of CSF using Cibacron Blue sepharose affinity chromatography. Improved protein recovery and resolution will facilitate excision from gels for analysis by peptide mass fingerprinting. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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5. Two patients with unusual forms of varicella-zoster virus vasculopathy.
- Author
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Gilden DH, Lipton HL, Wolf JS, Akenbrandt W, Smith JE, Mahalingam R, and Forghani B
- Published
- 2002
6. Medical progress. Neurologic complications of the reactivation of varicella- zoster virus.
- Author
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Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, and Cohrs RJ
- Published
- 2000
7. Strategies to identify sequences or antigens unique to multiple sclerosis.
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Owens, GP, Burgoon, MP, Devlin, ME, and Gilden, DH
- Published
- 1996
- Full Text
- View/download PDF
8. The search for virus in multiple sclerosis brain.
- Author
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Gilden, DH, Devlin, ME, Burgoon, MP, and Owens, GP
- Published
- 1996
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9. Bell's palsy -- is glucocorticoid treatment enough?
- Author
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Gilden DH and Tyler KL
- Published
- 2007
10. Varicella-zoster virus vaccine -- grown-ups need it, too.
- Author
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Gilden DH
- Published
- 2005
11. Brown-Séquard syndrome after herpes zoster.
- Author
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Young-Barbee C, Hall DA, LoPresti JJ, Schmid DS, Gilden DH, Young-Barbee, C, Hall, D A, LoPresti, J J, Schmid, D S, and Gilden, D H
- Published
- 2009
- Full Text
- View/download PDF
12. Cerebral vasculopathy with aneurysm formation in HIV-infected young adults.
- Author
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Gilden DH and Nagel MA
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- 2006
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13. Relapsing demyelinating disease after chicken pox in a child.
- Author
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Mariotti P, Colosimo C, Frisullo G, Caggiula M, Marca GDD, Valentini P, Baranello G, Tonali PA, Batocchi AP, and Gilden DH
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- 2006
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14. MRI abnormalities in chronic active varicella zoster infection.
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Blumenthal DT, Salzman KL, Baringer JR, Forghani B, Gilden DH, Blumenthal, D T, Salzman, K L, Baringer, J R, Forghani, B, and Gilden, D H
- Published
- 2004
- Full Text
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15. Bell's palsy.
- Author
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Stuart ME, Strite SA, Magaldi JA, Djalilian HR, and Gilden DH
- Published
- 2005
16. A vaccine to prevent herpes zoster.
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Kessler KM, Carroll I, Gaeta R, Mackey S, Oxman MN, Levin MJ, Johnson GR, Tsai AG, and Gilden DH
- Published
- 2005
17. Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia.
- Author
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Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, and Cullen BR
- Subjects
- Aged, Alphaherpesvirinae classification, Alphaherpesvirinae genetics, Alphaherpesvirinae metabolism, Alphaherpesvirinae physiology, Animals, Chlorocebus aethiops, Gene Expression Regulation, Viral, HeLa Cells, Herpesvirus 1, Human genetics, Herpesvirus 1, Human physiology, Herpesvirus 3, Human genetics, Herpesvirus 3, Human physiology, Humans, Male, MicroRNAs chemistry, MicroRNAs genetics, Middle Aged, RNA, Viral chemistry, RNA, Viral genetics, Vero Cells, Herpesvirus 1, Human metabolism, Herpesvirus 3, Human metabolism, MicroRNAs metabolism, RNA, Viral metabolism, Trigeminal Ganglion virology, Virus Latency
- Abstract
Analysis of cells infected by a wide range of herpesviruses has identified numerous virally encoded microRNAs (miRNAs), and several reports suggest that these viral miRNAs are likely to play key roles in several aspects of the herpesvirus life cycle. Here we report the first analysis of human ganglia for the presence of virally encoded miRNAs. Deep sequencing of human trigeminal ganglia latently infected with two pathogenic alphaherpesviruses, herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV), confirmed the expression of five HSV-1 miRNAs, miR-H2 through miR-H6, which had previously been observed in mice latently infected with HSV-1. In addition, two novel HSV-1 miRNAs, termed miR-H7 and miR-H8, were also identified. Like four of the previously reported HSV-1 miRNAs, miR-H7 and miR-H8 are encoded within the second exon of the HSV-1 latency-associated transcript. Although VZV genomic DNA was readily detectable in the three human trigeminal ganglia analyzed, we failed to detect any VZV miRNAs, suggesting that VZV, unlike other herpesviruses examined so far, may not express viral miRNAs in latently infected cells.
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- 2009
- Full Text
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18. Simian varicella virus induces apoptosis in monkey kidney cells by the intrinsic pathway and involves downregulation of bcl-2 expression.
- Author
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Pugazhenthi S, Gilden DH, Nair S, McAdoo A, Wellish M, Brazeau E, and Mahalingam R
- Subjects
- Animals, Caspases metabolism, Chickenpox pathology, Chlorocebus aethiops, Down-Regulation genetics, Haplorhini, Kidney pathology, RNA, Messenger analysis, Time Factors, Vero Cells, Apoptosis, Kidney virology, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Varicellovirus pathogenicity
- Abstract
Simian varicella virus (SVV) causes varicella in primates, becomes latent in ganglionic neurons, and reactivates to produce zoster. SVV produces a cytopathic effect in monkey kidney cells in tissue culture. To study the mechanism by which SVV-infected cells die, we examined markers of apoptosis 24 to 64 h postinfection (hpi). Western blot analysis of virus-infected cell lysates revealed a significant increase in the levels of the cleaved active form of caspase-3, accompanied by a parallel increase in caspase-3 activity at 40 to 64 hpi. Caspase-9, a marker for the intrinsic pathway, was activated significantly in SVV-infected cells at all time points, whereas trace levels of the active form of caspase-8, an extrinsic pathway marker, was detected only at 64 hpi. Bcl-2 expression at the mRNA and protein levels was decreased by 50 to 70% throughout the course of virus infection. Release of cytochrome c, an activator of caspase-9, from mitochondria into the cytoplasm was increased by 200% at 64 hpi. Analysis of Vero cells infected with SVV expressing green fluorescent protein (SVV-GFP) at 64 hpi revealed colocalization of the active forms of caspase-3 and caspase-9 and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining with GFP. A significant decrease in the bcl-2 mRNA levels along with an abundance of mRNA specific for SVV genes 63, 40, and 21 was seen in the fraction of Vero cells that were infected with SVV-GFP. Together, these findings indicate that SVV induces apoptosis in cultured Vero cells through the intrinsic pathway in which Bcl-2 is downregulated.
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- 2009
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19. CSF IgG heavy-chain bias in patients at the time of a clinically isolated syndrome.
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Bennett JL, Haubold K, Ritchie AM, Edwards SJ, Burgoon M, Shearer AJ, Gilden DH, and Owens GP
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- Adult, B-Lymphocytes immunology, Female, Flow Cytometry, Humans, Immunoglobulin Variable Region cerebrospinal fluid, Male, Middle Aged, Multiple Sclerosis immunology, Plasma Cells immunology, Reverse Transcriptase Polymerase Chain Reaction, Demyelinating Diseases cerebrospinal fluid, Demyelinating Diseases immunology, Immunoglobulin G cerebrospinal fluid, Immunoglobulin Heavy Chains cerebrospinal fluid
- Abstract
Using FACS and single cell reverse transcriptase polymerase chain reaction, we examined the cerebrospinal fluid (CSF) IgG VH repertoires from 10 subjects with a clinically isolated demyelinating syndrome (CIS). B and plasma cell repertoires from individual subjects showed similar VH family germline usage, nearly identical levels of post-germinal center somatic hypermutation, and significant overlap in their clonal populations. Repertoires from 7 of 10 CIS subjects demonstrated a biased usage of VH4 and/or VH2 family gene segments in their plasma or B cell repertoires. V-regionbias, however, was not observed in the corresponding peripheral blood CD19+ B cell repertoires from 2 CIS subjects or in normal healthy adults. Clinically, subjects with VH4 or VH2 CSF IgG repertoire bias rapidly progressed to definite MS, whereas individuals without repertoire bias did not develop MS after a minimum of 2 years of follow-up (p=0.01).
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- 2008
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20. Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency.
- Author
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Mueller NH, Gilden DH, Cohrs RJ, Mahalingam R, and Nagel MA
- Subjects
- Analgesics, Opioid therapeutic use, Antidepressive Agents therapeutic use, Antiviral Agents therapeutic use, Chickenpox physiopathology, Chickenpox transmission, Chickenpox virology, Ganglia virology, Herpes Zoster physiopathology, Herpes Zoster transmission, Herpes Zoster virology, Herpes Zoster Vaccine administration & dosage, Humans, Neuralgia, Postherpetic drug therapy, Neuralgia, Postherpetic virology, Retinal Necrosis Syndrome, Acute cerebrospinal fluid, Retinal Necrosis Syndrome, Acute prevention & control, Retinal Necrosis Syndrome, Acute virology, Time Factors, Virus Diseases prevention & control, Herpesvirus 3, Human isolation & purification, Virus Diseases physiopathology, Virus Diseases virology
- Abstract
Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia along the entire neuraxis. Years later, in association with a decline in cell-mediated immunity in elderly and immunocompromised individuals, VZV reactivates and causes a wide range of neurologic disease. This article discusses the clinical manifestations, treatment, and prevention of VZV infection and reactivation; pathogenesis of VZV infection; and current research focusing on VZV latency, reactivation, and animal models.
- Published
- 2008
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21. Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts.
- Author
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Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, and Pierson DL
- Subjects
- Adult, Aged, Antibodies, Viral analysis, Antibodies, Viral blood, Cell Line, Chickenpox virology, DNA, Viral analysis, DNA, Viral blood, Female, Genotype, Herpesvirus 1, Human genetics, Herpesvirus 1, Human isolation & purification, Herpesvirus 3, Human genetics, Herpesvirus 3, Human isolation & purification, Humans, Male, Middle Aged, Saliva virology, Astronauts, Herpesvirus 3, Human physiology, Virus Activation, Virus Shedding
- Abstract
Varicella zoster virus (VZV) causes varicella (chickenpox), after which virus becomes latent in ganglia along the entire neuraxis. Virus reactivation produces zoster (shingles). Infectious VZV is found in vesicles of patients with zoster and varicella, but virus shed in the absence of disease has not been documented. VZV DNA was previously detected in saliva of astronauts during and after spaceflight, a uniquely stressful environment in which cell mediated immunity (CMI) is temporally dampened. The decline in CMI to VZV associated with zoster led to the hypothesis that infectious VZV would also be present in the saliva of astronauts subjected to stress of spaceflight. Herein, not only was the detection of salivary VZV DNA associated with spaceflight validated, but also infectious virus was detected in saliva from 2 of 3 astronauts. This is the first demonstration of shed of infectious VZV in the absence of disease.
- Published
- 2008
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22. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.
- Author
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Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, Greenberg B, Russman AN, Katzan I, Gardner CJ, Häusler M, Nau R, Saraya T, Wada H, Goto H, de Martino M, Ueno M, Brown WD, Terborg C, and Gilden DH
- Subjects
- Cerebrovascular Disorders diagnosis, Cerebrovascular Disorders etiology, Chickenpox cerebrospinal fluid, Chickenpox complications, Chickenpox virology, Exanthema cerebrospinal fluid, Exanthema diagnosis, Exanthema virology, Herpes Zoster cerebrospinal fluid, Herpes Zoster complications, Herpes Zoster virology, Humans, Magnetic Resonance Imaging methods, Cerebrovascular Disorders cerebrospinal fluid, Cerebrovascular Disorders virology, Herpesvirus 3, Human
- Abstract
Background: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities., Methods: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both., Results: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis., Conclusions: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.
- Published
- 2008
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23. Is varicella zoster virus really involved in the pathogenesis of multiple sclerosis?
- Author
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Gilden DH
- Subjects
- Herpesvirus 3, Human ultrastructure, Humans, Multiple Sclerosis etiology, Herpesvirus 3, Human isolation & purification, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis virology
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- 2008
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- View/download PDF
24. Varicella-zoster virus in the saliva of patients with herpes zoster.
- Author
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Mehta SK, Tyring SK, Gilden DH, Cohrs RJ, Leal MJ, Castro VA, Feiveson AH, Ott CM, and Pierson DL
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- Acyclovir analogs & derivatives, Acyclovir therapeutic use, Adult, Aged, Aged, 80 and over, Antiviral Agents therapeutic use, Biomarkers, Case-Control Studies, Cohort Studies, DNA, Viral analysis, DNA, Viral isolation & purification, Female, Humans, Male, Middle Aged, Valacyclovir, Valine analogs & derivatives, Valine therapeutic use, Zoster Sine Herpete drug therapy, Herpesvirus 3, Human isolation & purification, Neuralgia virology, Saliva virology, Zoster Sine Herpete diagnosis
- Abstract
Fifty-four patients with herpes zoster were treated with valacyclovir. On treatment days 1, 8, and 15, pain was scored and saliva examined for varicella-zoster virus (VZV) DNA. VZV DNA was found in every patient the day treatment was started and later disappeared in 82%. There was a positive correlation between the presence of VZV DNA and pain and between VZV DNA copy number and pain (P <.0005). VZV DNA was present in 1 patient before rash and in 4 after pain resolved and was not present in any of 6 subjects with chronic pain or in 14 healthy subjects. Analysis of human saliva has potential usefulness in the diagnosis of neurological disease produced by VZV without rash.
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- 2008
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25. Construction of recombinant mouse IgG1 antibody directed against varicella zoster virus immediate early protein 63.
- Author
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Mueller NH, Graf LL, Shearer AJ, Owens GP, Gilden DH, and Cohrs RJ
- Subjects
- Animals, Cell Line, Chickenpox immunology, Chickenpox virology, Humans, Immunoglobulin G isolation & purification, Mice, Peptide Library, Recombinant Proteins immunology, Recombinant Proteins isolation & purification, Antigens, Viral immunology, Genes, Viral immunology, Herpesvirus 3, Human immunology, Immunoglobulin G immunology
- Abstract
Five varicella zoster virus (VZV) genes are known to be transcribed in latently infected human ganglia. Transcripts from VZV gene 63, which encodes an immediate early (IE) protein, are the most prevalent and abundant. To obtain a reagent that might facilitate studies of the role of the IE63 protein in latency and reactivation, we selected an IE63-specific Fab fragment from a phage library and used it to prepare a recombinant mouse IgG1 antibody that detects IE63 and functions in Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assays.
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- 2008
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26. Brain imaging abnormalities in CNS virus infections.
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Gilden DH
- Subjects
- Brain abnormalities, Brain virology, Humans, Magnetic Resonance Imaging, Brain pathology, Central Nervous System Viral Diseases pathology
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- 2008
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27. Analysis of multiple sclerosis cerebrospinal fluid reveals a continuum of clonally related antibody-secreting cells that are predominantly plasma blasts.
- Author
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Winges KM, Gilden DH, Bennett JL, Yu X, Ritchie AM, and Owens GP
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- Adult, Analysis of Variance, Antigens, CD19 analysis, Female, Flow Cytometry methods, Humans, Immunoglobulin G genetics, Immunoglobulin G metabolism, Immunoglobulin Variable Region chemistry, Immunoglobulin Variable Region genetics, Male, Middle Aged, Plasma Cells immunology, Syndecan-1 analysis, Antibody-Producing Cells immunology, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis immunology
- Abstract
Fluorescence-activated cell sorting (FACS) analysis of B cell subtypes in 17 CSF samples from 15 patients with clinically-definite MS revealed that CD19+ B cells accounted for 2 to 11% (mean 5%) and CD138+ cells constituted 0 to 5% (mean 2%) of total CSF lymphocytes. Further stratification of CD138+ cells based on expression levels of CD19 showed that CD138+19+ plasma blasts constituted 89+/-2% (mean+/-SE) of the CD138+ cell population (P<0.00001), with more mature plasma cells (CD138+19-) constituting the remaining 11+/-2%. Sequence analysis of immunoglobulin variable regions in single CD138+19+ and CD138+19- cells sorted from MS CSF identified many of the same clonal populations in both populations, indicating a continuum of clonally related plasma cell subtypes of which CD138+19+ plasma blasts are most abundant.
- Published
- 2007
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28. Simian varicella virus reactivation in cynomolgus monkeys.
- Author
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Mahalingam R, Traina-Dorge V, Wellish M, Lorino R, Sanford R, Ribka EP, Alleman SJ, Brazeau E, and Gilden DH
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- Animals, Chickenpox pathology, DNA, Viral analysis, Ganglia pathology, Ganglia virology, Immunosuppression Therapy, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents pharmacology, Lung pathology, Lung virology, Macaca fascicularis, Prednisone administration & dosage, Prednisone pharmacology, RNA, Viral analysis, Skin pathology, Skin virology, Stress, Psychological, Tacrolimus administration & dosage, Tacrolimus pharmacology, X-Rays, Chickenpox immunology, Chickenpox virology, Varicellovirus immunology, Varicellovirus physiology, Virus Activation
- Abstract
SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical reactivation. Virus reactivation was confirmed not only by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.
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- 2007
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29. VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis.
- Author
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Owens GP, Winges KM, Ritchie AM, Edwards S, Burgoon MP, Lehnhoff L, Nielsen K, Corboy J, Gilden DH, and Bennett JL
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- Adult, Antigens, CD19 immunology, B-Lymphocytes immunology, Child, Female, Health, Humans, Immunologic Memory immunology, Male, Middle Aged, Multiple Sclerosis cerebrospinal fluid, Syndecan-1 immunology, Antibody Formation immunology, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains immunology, Multiple Sclerosis genetics, Multiple Sclerosis immunology
- Abstract
A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138(+) plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138(+) cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138(+) cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138(+) cells with functionally rearranged V(H)4 gene segments as an overriding feature of MS CeSF repertoires. V(H)4 dominance was attributed to the preferential selection of specific V(H)4 genes, particularly gene segment V(H)4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in V(H)4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.
- Published
- 2007
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30. Arenaviruses: a neurological problem at any age.
- Author
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Gilden DH
- Subjects
- Arenaviridae Infections microbiology, Humans, Arenaviridae Infections diagnosis, Arenaviridae Infections therapy, Arenavirus, Lymphocytic Choriomeningitis diagnosis, Lymphocytic Choriomeningitis therapy
- Published
- 2007
- Full Text
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31. Characterization of phage peptide interaction with antibody using phage mediated immuno-PCR.
- Author
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Yu X, Burgoon MP, Shearer AJ, and Gilden DH
- Subjects
- Autoantibodies genetics, Bacteriophage M13 immunology, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G analysis, Immunoglobulin G cerebrospinal fluid, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis immunology, Peptides immunology, Recombinant Proteins genetics, Viral Proteins immunology, Autoantibodies metabolism, Bacteriophage M13 metabolism, Peptides metabolism, Polymerase Chain Reaction, Protein Interaction Mapping, Recombinant Proteins metabolism, Viral Proteins metabolism
- Abstract
Real-time immuno-PCR (RT-IPCR) is a powerful technique that combines ELISA with the specificity and sensitivity of PCR. RT-IPCR of phage-displayed peptides exploits the unique physical associations between phenotype (the displayed peptide) and genotype (the encoding DNA) within the same phage particle. Previously, we identified phage peptides specific for recombinant antibodies (rAbs) prepared from clonally expanded plasma cells in multiple sclerosis (MS) cerebrospinal fluid (CSF) and subacute sclerosing panencephalitis (SSPE) brain. Herein, we applied phage-mediated RT-IPCR to study reactivity of these specific phage peptides for the rAbs. Compared to standard ELISA, which required greater than 10(4) or 10(5) phage particles to detect binding to rAbs, RT-IPCR detected binding with as few as 100 phage particles. RT-IPCR was also superior to ELISA in determining relative affinities of rAbs for phage peptides and was effective in screening MS CSF for IgG reactivity to phage peptides. Phage-mediated RT-IPCR is a rapid, high-throughput technology that avoids the requirement for synthetic peptides and will facilitate the identification of candidate peptides that react with the IgG in MS CSF.
- Published
- 2007
- Full Text
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32. Prevention of shingles: safety and efficacy of live zoster vaccine.
- Author
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Quan D, Cohrs RJ, Mahalingam R, and Gilden DH
- Abstract
Primary infection with varicella zoster virus (VZV) causes chickenpox (varicella) after which virus becomes latent in cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. Virus may later reactivate, causing shingles (zoster), characterized by pain and rash restricted to 1-3 dermatomes. More than 40% of zoster patients over age 60 develop postherpetic neuralgia (PHN), pain that persists for months to years. The socioeconomic impact of primary varicella infection has been lessened by introduction of VZV vaccine for children. However, the effect of childhood vaccination on the incidence of zoster is unknown. Virus reactivation correlates with waning cell-mediated immunity (CMI) to VZV with normal aging. Adults exposed to children with varicella may have a boost in CMI to VZV. For at least several more decades, the incidence of zoster may increase as the elderly population grows. The anticipated increase in zoster burden of illness in future decades was a major impetus for the Shingles Prevention Study, a prospective, double-blind, placebo-controlled trial of attenuated VZV vaccine to prevent zoster in older adults. This review discusses clinical and virological aspects of zoster and its complications, current treatment options, and VZV vaccine development along with its future role in disease prevention.
- Published
- 2007
33. VZV spinal cord infarction identified by diffusion-weighted MRI (DWI).
- Author
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Orme HT, Smith AG, Nagel MA, Bert RJ, Mickelson TS, and Gilden DH
- Subjects
- Aged, 80 and over, Antiviral Agents therapeutic use, Arteries pathology, Arteries physiopathology, Arteries virology, Diffusion Magnetic Resonance Imaging, Female, Humans, Paralysis etiology, Paralysis pathology, Paralysis physiopathology, Spinal Cord blood supply, Spinal Cord pathology, Spinal Cord physiopathology, Spinal Cord Ischemia physiopathology, Treatment Failure, Urinary Bladder, Neurogenic etiology, Urinary Bladder, Neurogenic pathology, Urinary Bladder, Neurogenic physiopathology, Vasculitis, Central Nervous System physiopathology, Herpes Zoster complications, Spinal Cord Ischemia etiology, Spinal Cord Ischemia pathology, Vasculitis, Central Nervous System complications, Vasculitis, Central Nervous System virology
- Published
- 2007
- Full Text
- View/download PDF
34. The protean neurologic manifestations of varicella-zoster virus infection.
- Author
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Nagel MA and Gilden DH
- Subjects
- Age Factors, Analgesics therapeutic use, Antiviral Agents therapeutic use, Chickenpox Vaccine immunology, Herpes Zoster diagnosis, Humans, Nervous System Diseases virology, Neuralgia, Postherpetic diagnosis, Neuralgia, Postherpetic virology, Retinal Necrosis Syndrome, Acute diagnosis, Retinal Necrosis Syndrome, Acute virology, Risk Factors, Vascular Diseases diagnosis, Vascular Diseases virology, Herpesvirus 3, Human immunology, Nervous System Diseases diagnosis
- Abstract
Multiple neurologic complications may follow the reactivation of varicella-zoster virus (VZV), including herpes zoster (also known as zoster or shingles), postherpetic neuralgia, vasculopathy, myelitis, necrotizing retinitis, and zoster sine herpete (pain without rash). These conditions can be difficult to recognize, especially as several can occur without rash.
- Published
- 2007
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35. Stroke caused by human immunodeficiency virus-associated vasculopathy?
- Author
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Gilden DH and Nagel M
- Subjects
- HIV Infections pathology, Humans, Intracranial Aneurysm etiology, Intracranial Aneurysm pathology, Intracranial Aneurysm virology, HIV Infections complications, Stroke complications, Stroke etiology, Stroke virology
- Published
- 2007
- Full Text
- View/download PDF
36. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy.
- Author
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Nagel MA, Forghani B, Mahalingam R, Wellish MC, Cohrs RJ, Russman AN, Katzan I, Lin R, Gardner CJ, and Gilden DH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Arteries immunology, Cerebral Arteries pathology, Cerebral Arteries physiopathology, DNA, Viral analysis, DNA, Viral genetics, Female, Herpesvirus 3, Human genetics, Humans, Male, Middle Aged, Predictive Value of Tests, Vasculitis, Central Nervous System diagnosis, Antibodies, Viral cerebrospinal fluid, Chickenpox complications, Herpesvirus 3, Human immunology, Immunoglobulin G cerebrospinal fluid, Vasculitis, Central Nervous System cerebrospinal fluid, Vasculitis, Central Nervous System immunology
- Abstract
Background: Factors that may obscure the diagnosis of varicella zoster virus (VZV) vasculopathy include the absence of rash before TIAs or stroke as well as similar clinical features and imaging, angiographic, and CSF abnormalities to those of other vasculopathies. Diagnosis relies on virologic confirmation that detects VZV DNA, anti-VZV IgG antibody, or both in the CSF., Methods: We reviewed our current 14 cases of patients diagnosed with VZV vasculopathy based on combined clinical, imaging, angiographic, or CSF abnormalities. All CSFs must have been tested for VZV DNA by PCR and for anti-VZV IgG antibody by enzyme immunoassay and found to be positive for either or both. Of the 14 subjects, 8 had a history of recent zoster, whereas 6 had no history of zoster rash before developing vasculopathy., Results: All 14 subjects (100%) had anti-VZV IgG antibody in their CSF, whereas only 4 (28%) had VZV DNA. The detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001)., Conclusions: In varicella zoster virus (VZV) vasculopathy, the diagnostic value of detecting anti-VZV IgG antibody in CSF is greater than that of detecting VZV DNA. Although a positive PCR for VZV DNA in CSF is helpful, a negative PCR does not exclude the diagnosis of VZV vasculopathy. Only when the CSF is negative for both VZV DNA and anti-VZV IgG antibody can the diagnosis of VZV vasculopathy be excluded.
- Published
- 2007
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37. Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia.
- Author
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Cohrs RJ and Gilden DH
- Subjects
- Adult, Aged, Aged, 80 and over, DNA, Complementary, DNA, Viral analysis, DNA, Viral isolation & purification, Female, Herpesvirus 3, Human genetics, Humans, Male, Middle Aged, Polymerase Chain Reaction, RNA, Messenger genetics, RNA, Messenger metabolism, Sequence Analysis, DNA, Genes, Viral, Herpesvirus 3, Human physiology, Transcription, Genetic, Trigeminal Ganglion virology, Virus Latency
- Abstract
In human ganglia latently infected with varicella-zoster virus (VZV), sequence analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66) are transcribed. However, their comparative prevalence and abundance are unknown. Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for RNA corresponding to the five virus genes known to be transcribed in latently infected human ganglia. The most prevalent transcript found was VZV gene 63 (78%), followed by gene 66 (43%), gene 62 (36%), and gene 29 (21%). No gene 21 transcripts were detected in any of the 28 ganglia. VZV gene 63 RNA was also the most abundant (3,710 +/- 6,895 copies per 1 microg of mRNA) transcript detected in latently infected human ganglia, followed by VZV gene 29 (491 +/- 594), VZV gene 66 (117 +/- 85), and VZV gene 62 (64 +/- 38). Thus, the repeated detection and high abundance of VZV gene 63 transcripts in latently infected ganglia suggests that VZV gene 63 may be more important for the maintenance of virus latency than the less abundantly transcribed and randomly detected VZV genes 21, 29, 62, and 66.
- Published
- 2007
- Full Text
- View/download PDF
38. Herpesvirus infections of the nervous system.
- Author
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Gilden DH, Mahalingam R, Cohrs RJ, and Tyler KL
- Subjects
- Herpesviridae physiology, Humans, Virus Latency, Herpesviridae Infections, Nervous System virology, Nervous System Diseases virology
- Abstract
There are eight human herpesviruses (HHVs). Primary infection by any of the eight viruses, usually occurring in childhood, is either asymptomatic or produces fever and rash of skin or mucous membranes; other organs might be involved on rare occasions. After primary infection, the virus becomes latent in ganglia or lymphoid tissue. With the exception of HHV-8, which causes Kaposi's sarcoma in patients with AIDS, reactivation of HHVs can produce one or more of the following complications: meningitis, encephalitis, myelitis, vasculopathy, ganglioneuritis, retinal necrosis and optic neuritis. Disease can be monophasic, recurrent or chronic. Infection with each herpesvirus produces distinctive clinical features and imaging abnormalities. This Review highlights the patterns of neurological symptoms and signs, along with the typical imaging abnormalities, produced by each of the HHVs. Optimal virological studies of blood, cerebrospinal fluid and affected tissue for confirmation of diagnosis are discussed; this is particularly important because some HHV infections of the nervous system can be treated successfully with antiviral agents.
- Published
- 2007
- Full Text
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39. Disseminated simian varicella virus infection in an irradiated rhesus macaque (Macaca mulatta).
- Author
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Kolappaswamy K, Mahalingam R, Traina-Dorge V, Shipley ST, Gilden DH, Kleinschmidt-Demasters BK, McLeod CG Jr, Hungerford LL, and DeTolla LJ
- Subjects
- Animals, Herpesviridae Infections pathology, Herpesviridae Infections virology, Gamma Rays, Herpesviridae Infections veterinary, Macaca mulatta virology, Monkey Diseases pathology, Monkey Diseases virology, Varicellovirus radiation effects
- Abstract
We describe correlative clinicopathological/virological findings from a simian varicella virus (SVV)-seronegative monkey that developed disseminated varicella 105 days after gamma-irradiation. Twelve other monkeys in the colony were also irradiated, none of which developed varicella. Before irradiation, sera from the monkey that developed disseminated infection and one asymptomatic monkey were available. Analysis indicated that subclinical reactivation of latent SVV from an asymptomatic irradiated monkey likely led to disseminated varicella in the seronegative irradiated monkey. These findings parallel those from humans with disseminated varicella infection and support the usefulness of SVV infection as a model for human varicella-zoster virus infection, particularly virus reactivation after gamma-irradiation.
- Published
- 2007
- Full Text
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40. Screening random peptide libraries with subacute sclerosing panencephalitis brain-derived recombinant antibodies identifies multiple epitopes in the C-terminal region of the measles virus nucleocapsid protein.
- Author
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Owens GP, Shearer AJ, Yu X, Ritchie AM, Keays KM, Bennett JL, Gilden DH, and Burgoon MP
- Subjects
- Amino Acid Sequence, Computational Biology, Enzyme-Linked Immunosorbent Assay, Humans, Molecular Sequence Data, Peptide Library, Sequence Alignment, Sequence Analysis, DNA, Antibodies, Viral genetics, Epitopes genetics, Measles virus genetics, Nucleocapsid Proteins genetics, Peptides genetics, Subacute Sclerosing Panencephalitis immunology
- Abstract
Infectious and inflammatory diseases of the CNS are often characterized by a robust B-cell response that manifests as increased intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands. We previously used laser capture microdissection and single-cell PCR to analyze the IgG variable regions of plasma cells from the brain of a patient with subacute sclerosing panencephalitis (SSPE). Five of eight human IgG1 recombinant antibodies (rAbs) derived from SSPE brain plasma cell clones recognized the measles virus (MV) nucleocapsid protein, confirming that the antibody response in SSPE targets primarily the agent causing disease. In this study, as part of our work on antigen identification, we used four rAbs to probe a random phage-displayed peptide library to determine if epitopes within the MV nucleocapsid protein could be identified with SSPE brain rAbs. All four of the SSPE rAbs enriched phage-displayed peptide sequences that reacted specifically to their panning rAb by enzyme-linked immunosorbent assay. BLASTP searches of the NCBI protein database revealed clear homologies in three peptides and different amino acid stretches within the 65 C-terminal amino acids of the MV nucleocapsid protein. The specificities of SSPE rAbs to these regions of the MV nucleocapsid protein were confirmed by binding to synthetic peptides or to short cDNA expression products. These results indicate the feasibility of using peptide screening for antigen discovery in central nervous system inflammatory diseases of unknown etiology, such as multiple sclerosis, neurosarcoidosis, or Behcet's syndrome.
- Published
- 2006
- Full Text
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41. Acute cerebellar ataxia in a 41 year old woman.
- Author
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Moses H, Nagel MA, and Gilden DH
- Subjects
- Acute Disease, Adult, Diagnosis, Differential, Female, Humans, Risk Factors, Acyclovir therapeutic use, Antiviral Agents therapeutic use, Cerebellar Ataxia diagnosis, Cerebellar Ataxia drug therapy, Cerebellar Ataxia etiology, Herpesvirus 3, Human pathogenicity
- Published
- 2006
- Full Text
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42. Rapid and efficient identification of epitopes/mimotopes from random peptide libraries.
- Author
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Yu X, Owens GP, and Gilden DH
- Subjects
- Amino Acid Sequence, Bacteriophage M13, DNA chemistry, DNA genetics, Dose-Response Relationship, Immunologic, Enzyme-Linked Immunosorbent Assay, Epitopes genetics, Epitopes immunology, Humans, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis immunology, Recombinant Proteins immunology, Sequence Alignment, Sequence Analysis, DNA, Epitope Mapping methods, Epitopes analysis, Peptide Library
- Abstract
Phage-displayed random peptide libraries are important tools in identifying novel epitopes/mimotopes that may lead to the determination of antigen specificity. In this approach, high-affinity phage peptides are enriched by affinity selection (panning) on a monoclonal antibody. To facilitate identification of all potential phage peptides specific for recombinant monoclonal antibodies (rAbs) previously generated from clonally expanded plasma cells from the cerebrospinal fluid of patients with multiple sclerosis (MS), we developed a high-throughput method to determine phage specificity. In contrast to the 8-9 days needed in the standard large-scale method of amplifying phage clones for ELISA, the high-throughput method takes only 1 day. ELISA using phage clones amplified directly in 96-well plates avoids large-scale phage purification and enables rapid identification of specific epitopes/mimotopes. This technique will expedite identification of MS-specific peptides that can be used to discover the corresponding protein antigens.
- Published
- 2006
- Full Text
- View/download PDF
43. Recombinant antibodies generated from both clonal and less abundant plasma cell immunoglobulin G sequences in subacute sclerosing panencephalitis brain are directed against measles virus.
- Author
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Burgoon MP, Caldas YA, Keays KM, Yu X, Gilden DH, and Owens GP
- Subjects
- ADP-ribosyl Cyclase 1 blood, ADP-ribosyl Cyclase 1 immunology, Amino Acid Sequence, Antigens, CD blood, Antigens, CD immunology, Humans, Molecular Sequence Data, Plasma Cells immunology, Recombinant Proteins blood, Recombinant Proteins immunology, Subacute Sclerosing Panencephalitis blood, Subacute Sclerosing Panencephalitis pathology, Immunoglobulin G blood, Immunoglobulin G genetics, Measles immunology, Subacute Sclerosing Panencephalitis genetics, Subacute Sclerosing Panencephalitis immunology
- Abstract
Increased immunoglobulin G (IgG) and intrathecally produced oligoclonal bands (OGBs) are characteristic of a limited number of inflammatory central nervous system (CNS) diseases and are often directed against the cause of disease. In subacute sclerosing panencephalitis (SSPE), the cause of disease and the target of the oligoclonal response is measles virus (MV). The authors previously showed that clonally expanded populations of CD38+ plasma cells in SSPE brain, the likely source of OGBs, are directed against MV. In characterizing the breadth of the plasma cell reactivities, the authors found that a large proportion of the less abundant plasma cells are also directed against MV. The intrathecal response may be useful in determining the causes of other inflammatory CNS diseases, such as multiple sclerosis, Behcet's disease, and neurosarcoidosis.
- Published
- 2006
- Full Text
- View/download PDF
44. Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir.
- Author
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Quan D, Hammack BN, Kittelson J, and Gilden DH
- Subjects
- Acyclovir adverse effects, Administration, Oral, Aged, Aged, 80 and over, Antiviral Agents adverse effects, Drug Therapy, Combination, Female, Humans, Injections, Intravenous, Male, Middle Aged, Prospective Studies, Treatment Outcome, Valacyclovir, Valine administration & dosage, Valine adverse effects, Acyclovir administration & dosage, Acyclovir analogs & derivatives, Antiviral Agents administration & dosage, Neuralgia, Postherpetic drug therapy, Valine analogs & derivatives
- Abstract
Background: Postherpetic neuralgia (PHN) is a complication of shingles (herpes zoster), a painful rash due to varicella-zoster virus reactivation. Studies of patients with PHN and zoster sine herpete (radicular pain without rash) support the notion that low-grade viral ganglionitis contributes to pain. If chronic pain reflects active infection, then antiviral therapy may help patients with PHN., Objective: To determine whether antiviral treatment helps reduce PHN-associated pain., Design: Prospective, open-label phase I/II clinical trial., Setting: Tertiary care university hospital., Patients: Fifteen patients with moderate to severe PHN., Interventions: Intravenous acyclovir at a dosage of 10 mg/kg every 8 hours for 14 days followed by oral valacyclovir at a dosage of 1000 mg 3 times per day for 1 month., Main Outcome Measure: Numeric Rating Scale for Pain score., Results: As defined by a decrease of 2 or more points on the Numeric Rating Scale for Pain, 8 (53%) of 15 patients reported improvement., Conclusion: Clinical improvement reported by most of our patients warrants further investigation in a larger, randomized, double-blind, placebo-controlled trial.
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- 2006
- Full Text
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45. Epigenetic regulation of varicella-zoster virus open reading frames 62 and 63 in latently infected human trigeminal ganglia.
- Author
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Gary L, Gilden DH, and Cohrs RJ
- Subjects
- Acetylation, Adult, Aged, Aged, 80 and over, Cell Line, Chromatin genetics, Female, Histones metabolism, Humans, Male, Promoter Regions, Genetic, Trigeminal Ganglion metabolism, Epigenesis, Genetic physiology, Gene Expression Regulation, Viral genetics, Herpesvirus 3, Human genetics, Open Reading Frames genetics, Trigeminal Ganglion virology, Virus Latency genetics
- Abstract
Open reading frames (ORFs) 21, 29, 62, 63, and 66 of varicella-zoster virus (VZV) are transcribed during latency in human ganglia. ORF 63 is the most frequently expressed gene, and ORF 62 encodes a transcriptional activator. The mechanisms regulating the expression of these genes are not well understood, although analyses of other alphaherpesviruses indicate a role for chromatin in virus gene regulation during latent infection. Using chromatin immunoprecipitation (ChIP) assays to analyze the euchromatic state of ORFs 62 and 63 compared to the centromere from human chromosome 4 (heterochromatic) and the human glyceraldehyde-3-phosphate dehydrogenase promoter (euchromatic), we show that the promoters of ORFs 62 and 63 are associated with the histone protein H3K9(Ac) and thus maintained in a euchromatic state during latency. Conversely, the promoters of ORF 36 (thymidine kinase) and ORF 14 (glycoprotein C), genes expressed during lytic but not latent infection, were not enriched in the fraction of latently infected ganglia that bound to anti-H3K9(Ac) antibody. A ChIP assay using productively infected MeWo cells revealed that VZV ORFs 62, 63, 36, and 14 are all euchromatic. Together, these data indicate that the expression of the two latency-related VZV genes, ORFs 62 and 63, is regulated epigenetically through chromatin structure.
- Published
- 2006
- Full Text
- View/download PDF
46. Downregulation of varicella-zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency.
- Author
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Hoover SE, Cohrs RJ, Rangel ZG, Gilden DH, Munson P, and Cohen JI
- Subjects
- Adenoviridae genetics, Cell Line, Fibroblasts virology, Ganglia, Spinal virology, Gene Expression Regulation, Viral, Herpesvirus 3, Human genetics, Herpesvirus 3, Human growth & development, Humans, Melanoma ultrastructure, Melanoma virology, Precipitin Tests, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Virion metabolism, Virion ultrastructure, Down-Regulation, Herpesvirus 3, Human physiology, Immediate-Early Proteins genetics, Open Reading Frames genetics, Virus Latency genetics, Virus Replication genetics
- Abstract
Varicella-zoster virus (VZV) open reading frame 63 (ORF63) protein is expressed during latency in human sensory ganglia. Deletion of ORF63 impairs virus replication in cell culture and establishment of latency in cotton rats. We found that cells infected with a VZV ORF63 deletion mutant yielded low titers of cell-free virus and produced very few enveloped virions detectable by electron microscopy compared with those infected with parental virus. Microarray analysis of cells infected with a recombinant adenovirus expressing ORF63 showed that transcription of few human genes was affected by ORF63; a heat shock 70-kDa protein gene was downregulated, and several histone genes were upregulated. In experiments using VZV transcription arrays, deletion of ORF63 from VZV resulted in a fourfold increase in expression of ORF62, the major viral transcriptional activator. A threefold increase in ORF62 protein was observed in cells infected with the ORF63 deletion mutant compared with those infected with parental virus. Cells infected with ORF63 mutants impaired for replication and latency (J. I. Cohen, T. Krogmann, S. Bontems, C. Sadzot-Delvaux, and L. Pesnicak, J. Virol. 79:5069-5077, 2005) showed an increase in ORF62 transcription compared with those infected with parental virus. In contrast, cells infected with an ORF63 mutant that is not impaired for replication or latency showed ORF62 RNA levels equivalent to those in cells infected with parental virus. The ability of ORF63 to downregulate ORF62 transcription may play an important role in virus replication and latency.
- Published
- 2006
- Full Text
- View/download PDF
47. The B cell response in multiple sclerosis.
- Author
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Owens GP, Bennett JL, Gilden DH, and Burgoon MP
- Subjects
- Animals, Antibody Specificity, Blood-Brain Barrier physiopathology, Humans, Inflammation cerebrospinal fluid, Inflammation complications, Inflammation pathology, Multiple Sclerosis cerebrospinal fluid, B-Lymphocytes physiology, Multiple Sclerosis immunology, Multiple Sclerosis pathology
- Abstract
Multiple sclerosis (MS) plaques and CSF contain increased amounts of intrathecally synthesized IgG, manifest as oligoclonal bands (OCBs) after protein electrophoresis. OCBs are not unique to MS and are also produced in infectious diseases of the CNS, in which the oligoclonal IgG has been shown to be antibody directed against the disease-causing agent. Thus, analysis of antibody specificity may identify the causative agent/antigen in MS. This review discusses recent studies that have analyzed the phenotypes of B cells in MS which infiltrate the CNS and the molecular features of their antigen-binding regions. Together with histologic studies showing the presence of ectopic lymphoid follicles in the meninges of some MS patients, this data supports the notion of a targeted and compartmentalized humoral response in MS.
- Published
- 2006
- Full Text
- View/download PDF
48. Comparison of virus transcription during lytic infection of the Oka parental and vaccine strains of Varicella-Zoster virus.
- Author
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Cohrs RJ, Gilden DH, Gomi Y, Yamanishi K, and Cohen JI
- Subjects
- Blotting, Western, Cell Line, Genes, Viral, Herpesvirus 3, Human pathogenicity, Humans, Immediate-Early Proteins genetics, Nucleic Acid Hybridization, Open Reading Frames, RNA, Messenger, RNA, Viral analysis, Trans-Activators genetics, Transcription, Genetic, Viral Envelope Proteins genetics, Viral Proteins analysis, Chickenpox Vaccine genetics, Fibroblasts virology, Gene Expression Regulation, Viral, Herpesvirus 3, Human genetics, Immediate-Early Proteins physiology, Oligonucleotide Array Sequence Analysis, Trans-Activators physiology, Viral Envelope Proteins physiology, Virus Replication genetics
- Abstract
The attenuated Oka vaccine (V-Oka) strain of varicella-zoster virus (VZV) effectively reduces disease produced by primary infection and virus reactivation. V-Oka was developed by propagation of the Oka parental (P-Oka) strain of VZV in guinea pig and human embryo fibroblasts. Complete DNA sequencing of both viruses has revealed 63 sites that differ between P-Oka and V-Oka, 37 of which are located within 21 unique open reading frames (ORFs). Of the ORFs that differ, ORF 62 contains the greatest number (10) of mutated sites. ORF 62 encodes IE 62, the major immediate-early transactivator of virus genes, and is essential for lytic virus replication. To determine whether a disproportionate number of mutations in ORF 62 might account for virus attenuation, we compared the global pattern of V-Oka gene expression to that of P-Oka. Transcription of ORFs 62, 65, 66, and 67 was suppressed, whereas ORF 41 was elevated in V-Oka-infected cells compared to P-Oka-infected cells (P < 0.01; z test). Suppression of ORF 62, 65, and 66 transcription was confirmed by quantitative dot blot and Western blot analyses. Transient-transfection assays to determine whether mutations within V-Oka-derived IE 62 affected its ability to transactivate VZV gene promoters revealed similar IE 62 transactivation of VZV gene 20, 21, 28, 29, 65, and 66 promoters in both P-Oka and V-Oka. Together, our results indicate that mutations in V-Oka IE 62 alone are unlikely to account for vaccine virus attenuation.
- Published
- 2006
- Full Text
- View/download PDF
49. Specificity of recombinant antibodies generated from multiple sclerosis cerebrospinal fluid probed with a random peptide library.
- Author
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Yu X, Gilden DH, Ritchie AM, Burgoon MP, Keays KM, and Owens GP
- Subjects
- Adult, Blotting, Western methods, Enzyme-Linked Immunosorbent Assay methods, Epitopes, Female, Flow Cytometry methods, Humans, Middle Aged, Multiple Sclerosis blood, Multiple Sclerosis immunology, RNA, Messenger biosynthesis, Recombinant Proteins biosynthesis, Reverse Transcriptase Polymerase Chain Reaction methods, Sensitivity and Specificity, Antibodies cerebrospinal fluid, Antibody Specificity, Multiple Sclerosis cerebrospinal fluid, Peptide Library
- Abstract
We generated recombinant antibodies (rAbs) from over-represented IgG sequences expressed by single plasma cells from multiple sclerosis (MS) cerebrospinal fluid (CSF). Panning of a phage-displayed random peptide library with the rAbs revealed several specific peptide sequences. Inhibition assays confirmed specific binding of the peptides to the antigen-binding site of the antibody. The native IgG of MS CSF from which the recombinant antibody was cloned also recognized these peptides. Our data demonstrate that MS rAb reflects the specificity of IgG in the CSF. Thus, the epitopes/mimotopes identified by MS rAb may provide clues to disease-relevant antigens.
- Published
- 2006
- Full Text
- View/download PDF
50. Transactivation of the simian varicella virus (SVV) open reading frame (ORF) 21 promoter by SVV ORF 62 is upregulated in neuronal cells but downregulated in non-neuronal cells by SVV ORF 63 protein.
- Author
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Mahalingam R, Gilden DH, Wellish M, and Pugazhenthi S
- Subjects
- Amino Acid Sequence, Animals, Artificial Gene Fusion, Cell Line, Chlorocebus aethiops, Down-Regulation, Humans, Immediate-Early Proteins genetics, Luciferases analysis, Luciferases genetics, Molecular Sequence Data, Open Reading Frames, Protein Biosynthesis, Sequence Homology, Amino Acid, Up-Regulation, Varicellovirus physiology, Vero Cells, Viral Envelope Proteins genetics, Gene Expression Regulation, Viral, Genes, Viral, Neurons virology, Promoter Regions, Genetic, Transcriptional Activation, Varicellovirus genetics
- Abstract
Simian varicella virus (SVV) infection in primates closely resembles varicella-zoster virus (VZV) infection in humans. SVV ORF 63 has 51.6% homology at the amino acid level to VZV ORF 63. We cloned SVV ORFs 63 and 62, transcribed and translated in vitro, and immunoprecipitated the expected proteins with rabbit polyclonal antibodies. Immunoprecipitation analysis revealed that SVV ORF 63 is expressed as a 43-kDa phosphorylated protein in virus-infected cells. In both neuronal and non-neuronal cells, SVV ORF 62 protein alone upregulated the SVV 21 promoter, while SVV ORF 63 protein alone did not have any effect. SVV ORF 62-mediated transactivation of the SVV ORF 21 promoter was upregulated in neuronal cells, but downregulated in non-neuronal cells, by SVV ORF 63 protein. This is the first study in which a varicella protein (ORF 63) expressed during latency has been shown to have a differential effect on a promoter that is also active during latency, in neuronal as compared to non-neuronal cells.
- Published
- 2006
- Full Text
- View/download PDF
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