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Barr Virus (barr + virus)
Kinds of Barr Virus Terms modified by Barr Virus Selected AbstractsPrevention of cancer through immunization: Prospects and challenges for the 21st centuryEUROPEAN JOURNAL OF IMMUNOLOGY, Issue S1 2007Abstract Persistent infection by several microbial agents is responsible for at least 15% of cancer globally, including most cancers of the liver, stomach, and cervix. The recent development of vaccines that can prevent infection and premalignant disease caused by human papillomaviruses (HPV), which cause virtually all cases of cervical cancer as well as some other cancers, has focused renewed attention on infection control as a means of reducing the global cancer burden. For vaccines to prevent cancer-causing infection with hepatitis C virus, Helicobacter pylori, or Epstein Barr virus, new vaccine technologies to induce more effective protective responses are required. For the two available cancer control vaccines, designed to prevent infection with HPV and hepatitis B virus, the major challenge is to promote effective vaccine deployment through education programs and increased affordability/accessibility for underserved populations, particularly in the developing world, where the cancer burden attributable to infection by these two viruses is greatest. [source] Epstein,Barr virus reactivation and multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2008Ø. Torkildsen Infection with Epstein,Barr virus (EBV) is considered one of the possible key environmental factors in the aetiology of multiple sclerosis (MS). Whether EBV plays an underlying role as an activator of MS remains, however, controversial. Sixty-one patients with definite relapsing,remitting multiple sclerosis (RRMS) according to the Poser criteria were followed for 1 year. Blood samples were drawn at baseline, months 3, 6 and 12, and in case of any clinical exacerbation. Twenty-three baseline,paired exacerbation samples in the same set were quantitatively analysed to examine whether exacerbations in MS were associated with a change in anti-diffuse component of the EBV-early antigen (EA-D) IgG ratio. All the 61 patients (100%) were anti-viral capsid antigen (VCA) IgG positive, one (2%) was anti-VCA IgM positive and 60 (98%) were anti-EBV nuclear antigen IgG positive. Mean anti-EA-D IgG at baseline was 0.57 (range 0.12,2.70) and at the time of exacerbations 0.61 (range 0.11,2.70). Wilcoxon signed rank test revealed no differences between the 23 baseline and paired exacerbation samples (P = 0.58). Our findings suggest that reactivation of latent EBV infection does not play a significant role for exacerbations in RRMS. [source] Bilateral facial palsy: Epstein,Barr virus, not Lyme diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006J. Diedler Bilateral facial palsy is frequently linked with lyme disease. We report a patient with bilateral facial palsy due to Epstein-Barr virus infection but with Borrelia burgdorferi IgM in serum caused by polyclonal B-lymphocyte stimulation. [source] Application of combined immunofluorescence and fluorescence in situ hybridization on paraffin-embedded sections to characterize T-cell lymphoma with EBV-infected B-cell blastsGENES, CHROMOSOMES AND CANCER, Issue 4 2004Genevieve K. Temple Combined immunofluorescence (IF) and fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue sections were used to examine lymph node tissue from two patients diagnosed with T-cell lymphoma with Epstein,Barr virus (EBV),infected B-cell blasts. The majority of cells within the samples comprised T-cells staining positively for CD3. In addition, both patients had a population of large pleiomorphic cells that were positive for the B-cell marker CD20 and for EBV LMP-1. Standard PCR clonality testing of the nodes revealed both immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) clonal rearrangements in one patient, although in the other case monoclonality was demonstrated only for TCRG. Cytogenetics of cultured lymphocytes from nodal tissue revealed two apparently unrelated abnormal clones in both patients. Combined IF and FISH revealed that these phenomena reflected two abnormal populations of B- and T-cells rather than reactive B-cell hyperplasia or biphenotypic evolution from a common ancestral lymphoma. True B-cell malignancy probably emerged within a preexisting but unrelated T-cell lymphoma. This is the first study to relate the phenotype of the abnormal cells in such cases to specific clonal populations of cells, and it demonstrates a method that may easily be introduced into a diagnostic cytogenetics laboratory with access to standard pathology laboratory resources. © 2004 Wiley-Liss, Inc. [source] Sustained expression of Epstein,Barr virus episomal vector mediated factor VIII in vivo following muscle electroporationHAEMOPHILIA, Issue 3 2006W.-H. MEI Summary., Haemophilia A treatment is an attractive candidate for gene therapy. The aim of haemophilia gene therapy is to obtain long-term therapeutic level of factor VIII (FVIII). We investigated Epstein,Barr virus (EBV)-based episomal vector combined with in vivo electroporation of naked DNA as a safe, efficient and simple method for correcting FVIII deficiency. A combinant FVIII expression EBV-based episomal vector pcDNA3-FVIII-EBVR was constructed and expressed in COS-7 cells. Then the naked plasmid DNA was injected into the quadriceps of mice following the electric pulse stimulation. Our data showed that pcDNA3-FVIII-EBVR expression in transfected COS-7 can maintain stably for at least 60 days and the hFVIII:Ag in plasma in two pcDNA3-FVIII-EBVR groups mice was higher than that in pcDNA-FVIII groups no matter with or without electric pulse stimulation. With the stimulating of electric pulse, the FVIII expression in plasma of recipient mice was increased two- to fourfolds and can be lasted for at least 90 days. No severe muscle damage was detected. So this novel strategy that FVIII expression mediated by EBV episomal vector following muscle electroporation is efficient, safe, simple and economic and may be applicable to clinical usage. [source] HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2010Jessica H. Maxwell MD Abstract Background Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein,Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan patients with NPC. Methods From 2003 to 2007, 89 patients, 84 with oropharyngeal cancer (OPC) and 5 with NPC, were enrolled in an organ-sparing trial. Biopsy tissues from all 89 patients were evaluated for HPV and p16 expression. A separate HPV analysis of the 84 OPC patients is in progress. Among the patients with NPC, tumor tissue was also analyzed for EBV-encoded RNA (EBER). Results Five of 89 patients (5.6%) had NPC, all with nonkeratinizing histology. The 4 white patients with NPC were HPV(+) (subtype-16, subtype-18 [2 patients], and subtype-59)/p16(+)/EBER(-). One Asian patient with NPC had an HPV(-)/p16(-)/EBER(+) NPC tumor that developed distant metastases. Conclusion We postulate that HPV may be the etiologic factor in some EBV-negative, nonkeratinizing NPCs among whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Extranodal NK/T-cell lymphoma: diagnosis and treatment cuesHEMATOLOGICAL ONCOLOGY, Issue 2 2008Ritsuro Suzuki Abstract Extranodal NK/T-cell lymphoma, nasal type (ENKL) is mostly endemic to East Asia. It predominantly occurs in the nasal or paranasal areas and less frequently in the skin. Most of the tumours show NK-cell, but rarely T-cell, phenotypes. The Epstein,Barr virus (EBV) genome can be usually detected in lymphoma cells. Geographic localization of ENKL matches the endemic distribution of EBV, suggesting that EBV plays an important role in lymphomagenesis. Originally, NK-cell and T-cell types were believed to present the same clinicopathologic characteristics, but recent data suggest more aggressive characteristics for the NK-cell phenotype. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas due to expression of p-glycoprotein. Therefore, new therapeutic approaches must be considered. Several new clinical trials are now being conducted in East Asia. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pyothorax-associated lymphoma (PAL): a western case with marked angiocentricity and review of the literatureHISTOPATHOLOGY, Issue 1 2004A Androulaki Aims :,To report a case of pyothorax-associated lymphoma in a non-immunocompromised 78-year-old man with a 45-year history of tuberculous pleuritis and left pleural effusion. Pyothorax-associated lymphoma is a high-grade non-Hodgkin's lymphoma occurring in 2% of patients with long-standing tuberculous pleuritis and pyothorax. Pyothorax-associated lymphoma is frequently Epstein,Barr virus (EBV)-associated, mainly reported in Japan but exceedingly rare in western countries. Methods and results :,Histology revealed a high-grade, diffuse large B-cell lymphoma with immunoblastic and plasmacytoid features and marked angiocentricity with focal destruction of the vessel walls. Immunohistochemistry revealed a post germinal B-cell phenotype. RNA in-situ hybridization and molecular analysis showed a latent EBV infection and absence of human herpes virus-8 (HHV-8). Conclusions :,Pyothorax-associated lymphoma represents a rare but distinctive type of diffuse large B-cell lymphoma, with characteristic clinico-epidemiological, immunohistological, and biological features. [source] B-lymphocyte subpopulations are equally susceptible to Epstein,Barr virus infection, irrespective of immunoglobulin isotype expressionIMMUNOLOGY, Issue 4 2003Barbro Ehlin-Henriksson Summary While Epstein,Barr virus (EBV) is known to establish latency in the memory B-cell compartment, there is controversy as to whether the memory or the naïve B cell is the initial target for infection. Here we have explored the infectability of the B-cell subsets contained in peripheral blood and tonsils, as distinguished by their surface expression of the immunoglobulin isotypes that help to define naïve and memory pools. First we show that both CD21 and major histocompatibility complex (MHC) class II molecules , respectively, the major receptor and co-receptor for EBV on B cells , are expressed at similar levels on blood and tonsillar B cells, irrespective of surface immunoglobulin class, indicating that each of the subsets demonstrate an equal potential, at least for infection. Then, following in vitro infection of total tonsillar B cells, we found that the relative frequencies of immunoglobulin (Ig)M-, IgG- and IgA-positive cells containing EBV-encoded Epstein,Barr virus nuclear antigen 5 (EBNA5) protein at 48 hr were similar to those of the starting population. However, IgD expression was uniformly decreased, probably as a consequence of cellular activation. These data indicate that recirculating B cells have both the potential for, and susceptibility to, initial infection by EBV, irrespective of the immunoglobulin isotype expressed. [source] Epstein,Barr virus and parvovirus B19 coinfection in a Crohn's disease patient under azathioprineINFLAMMATORY BOWEL DISEASES, Issue 6 2010Teresa Moreira MD No abstract is available for this article. [source] Infliximab and the risk of latent viruses reactivation in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 7 2007Alessandro Lavagna MD Abstract Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein,Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007) [source] Urgent liver transplantation for acute liver failure due to parvovirus B19 infection complicated by primary Epstein,Barr virus and cytomegalovirus infections and aplastic anaemiaINTERNAL MEDICINE JOURNAL, Issue 3 2007K. So Abstract An 11-year-old boy presented with hepatic failure secondary to parvovirus B19 infection, requiring urgent liver transplantation. His recovery was complicated by primary Epstein,Barr virus and cytomegalovirus infections. He subsequently developed aplastic anaemia that has been refractory to antithymocyte globulin and cyclosporine therapy and may now require bone marrow transplantation. We present this case to emphasize parvovirus as a rare cause of hepatic failure and of aplastic anaemia as a complication of the virus. [source] Patients with Epstein Barr virus-positive lymphomas have decreased CD4+ T-cell responses to the viral nuclear antigen 1INTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Kevin N. Heller Abstract Epstein Barr virus (EBV) causes lymphomas in immune competent and, at increased frequencies, in immune compromised patients. In the presence of an intact immune system, EBV-associated lymphomas express in most cases only 3 or fewer EBV antigens at the protein level, always including the nuclear antigen 1 of EBV (EBNA1). EBNA1 is a prominent target for EBV-specific CD4+ T cell and humoral immune responses in healthy EBV carriers. Here we demonstrate that patients with EBV-associated lymphomas, primarily Hodgkin's lymphoma, lack detectable EBNA1-specific CD4+ T-cell responses and have slightly altered EBNA1-specific antibody titers at diagnosis. In contrast, the majority of EBV-negative lymphoma patients had detectable IFN, expression and proliferation by CD4+ T cells in response to EBNA1, and carry EBNA1-specific immunoglobulins at levels similar to healthy virus carriers. Other EBV antigens, which were not present in the tumors, were recognized in less EBV positive, than negative lymphoma patients, but detectable responses reached similar CD8+ T cell frequencies in both cohorts. Patients with EBV-positive and -negative lymphomas did not differ in T-cell responses in influenza-specific CD4+ T cell proliferation and in antibody titers against tetanus toxoid. These data suggest a selective loss of EBNA1-specific immune control in EBV-associated lymphoma patients, which should be targeted for immunotherapy of these malignancies. © 2008 Wiley-Liss, Inc. [source] Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remissionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Tomonobu Ito MD A 76-year-old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (67Ga single-photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T-cell lymphoma, nasal. Because imaging analysis indicated a small-sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low-dose steroid therapy. ,Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen (Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 106/µL), and platelet count (112 × 103/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224,454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10,30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3,29 U/L) levels were elevated. The soluble interleukin-2 (IL-2) receptor level was high (25,300 U/mL; normal, 167,497 U/mL). Epstein,Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen-diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes (Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3,, CD4,, CD8,, CD20,, CD56+, granzyme B+, and T-cell intracellular antigen (TIA-1) positive. Furthermore, EBV-encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T-cell receptor-, (TCR-,), TCR-,, and TCR-, gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T-cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m2, cyclophosphamide 500 mg/m2, vincristine 1 mg/m2, prednisolone 30 mg/m2, etoposide 80 mg/m2). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. Figure 1. Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen Figure 2. Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400) [source] Epstein,Barr virus (EBV)-associated aggressive peripheral T-cell lymphoma showing folliculotropismINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Hye-Jin Choi MD No abstract is available for this article. [source] Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2001Arnon D. Cohen MD A 91-year-old patient presented with a nonfebrile, pruritic, widespread eruption that appeared 10 days after starting therapy with cefuroxime tablets, 1000 mg/day, due to stasis dermatitis with secondary infection. The patient was also treated with paracetamol tablets, 500,1000 mg/day, 10 days before the onset of the eruption. Previous diseases included congestive heart disease, hyperglycemia, and ectropion. There was no personal or family history of psoriasis. Additional medications, taken for more than 2 years at the time of the eruption, included indomethacin, captopril, hydrochlorothiazide, isosorbide-5-mononitrate tablets, and a combination drug Laxative®. Examination revealed widespread erythema involving 95% of the total body surface area, with numerous 1,2 mm nonfollicular pustules (Fig. 1). There was no predilection to the body folds. Within 24 h of hospitalization, during intravenous therapy with cefuroxime, the patient's condition worsened and bullae containing clear fluid appeared. Nikolsky's sign was positive on erythematous skin, and eventually skin detachment involved 41% of the total body surface area (Fig. 2). There were no target or target-like lesions and there was no involvement of the mucous membranes. Figure 1. Numerous, 1,2 mm, nonfollicular pustules, with confluence (viewed in the lower left part of the photograph), on erythematous skin Figure 2. Widespread skin detachment An early biopsy from a pustule revealed subcorneal and intraepidermal spongiform pustules, papillary edema, perivascular mononuclear infiltrate with a few eosinophils in the dermis, and leukocytoclastic vasculitis. A later biopsy showed similar findings with no evidence of full-thickness epidermal necrosis or necrotic keratinocytes. Direct immune fluorescence (DIF) taken from erythematous skin was negative. Laboratory studies showed the following results: sedimentation rate, 80 mm/h; white blood cell count, 26,200/mm3 with 87% polymorphonuclears and 1.8% eosinophils; hemoglobin, 13.0 g/dL; albumin, 2.8 g/dL (normal, 3.5,5.5 g/dL); other blood chemistry tests were normal. Immunologic studies for rheumatoid factor, antinuclear antibodies, antismooth muscle antibodies, antiparietal cell antibodies, antimitochondrial antibodies, C3, and C4 were normal or negative. Serology for venereal disease research laboratory (VDRL) test, Epstein,Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and antistreptolysin titer was negative. Chest X-ray was normal. Blood cultures were negative. Swab cultures taken from the pustules revealed Staphylococcus aureus as well as coagulase-negative Staphylococcus. All systemic drugs, including intravenous cefuroxime, were withdrawn with close monitoring for signs of heart failure or infection. Topical therapy consisted of application of wet dressings. Within 10 days, the eruption resolved with re-epithelialization of the erosions and the appearance of widespread post-pustular desquamation (Fig. 3) Figure 3. Post-pustular desquamation on the trunk [source] A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence of past exposure to hepatitis EINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2000Freddye M. Lemons-Estes CDR, MC USN The patient was a 52-year-old white man who had worked in remote areas of the world during the past 2 years, including an extended period in rural areas of Central Africa and in Central and South America. He had no acute illnesses during the 2-year period except for rare, mild, upper respiratory tract infections. For approximately 1 year, however, he had developed recurrent, papular-vesicular, slightly painful lesions on the fingers and palms, that spontaneously healed over weeks to months ( Fig. 1). The patient had no other concurrent illnesses and no abnormal laboratory findings, except for positive enzyme-linked immunoabsorbent assay (ELISA) for immunoglobulin G (IgG) antibodies for hepatitis E virus (HEV) using a recombinant expressed HEV antigen (Genelabs Technologies, Inc., San Antonio). Prolonged treatment with minocycline did not appear to moderate the lesions. At approximately 2.5 years after the development of his first cutaneous lesion, however, the patient reported that he had had no new lesions for over 3 months. Figure 1. Vesicular ,lesion on the finger which regressed over a period of weeks A biopsy specimen showed an intraepidermal vesicle with prominent epidermal necrosis and reticular degeneration ( Fig. 2). Within the epidermis, there was a dense infiltrate of lymphoid cells. The majority of these cells were pleomorphic with prominent nucleoli and frequent mitotic figures ( Fig. 3). Sheets of atypical cells were found in the subjacent dermis. The infiltrate extended down into the reticular dermis. With extension into the dermis, the infiltrate became more polymorphous with more small lymphoid cells, large numbers of eosinophils, and some plasma cells located more deeply. Figure 2. Intraepidermal ,blister showing reticular degeneration and marked epidermotrophism of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (30×) Figure 3. Intraepidermal ,infiltrate of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (400×) Immunohistochemical stains for CD3 (DAKO), CD4 (Becton Dickinson), CD8 (Becton Dickinson), CD15 (LeuM1, Becton Dickinson), CD20 (L-26, DAKO), CD30 (Ber-H2, DAKO), CD45RO (UCHL1, DAKO), S-100 protein (DAKO), T-cell intracellular antigen (TIA) (Coulter), epithelial membrane antigen (EMA) (DAKO), KP-1 (CD68, DAKO), MAC-387 (DAKO), Epstein,Barr virus (EBV) latent membrane antigen-1 (LMP-1, DAKO), and EBV-encoded nuclear antigen 2 (EBNA2, DAKO) were performed on formalin-fixed tissue using the ABC method with DABA as the chromagen. CD3 showed diffuse membrane staining of the large atypical lymphoid cells, as well as the majority of the small lymphoid cells ( Fig. 4). CD4 showed positive membrane staining of the large atypical lymphoid cells and the majority of the small lymphoid cells. CD8 showed only scattered light membrane staining of small lymphoid cells. CD15 was negative, and CD20 showed foci of groups of small lymphoid cells mainly within the reticular dermis. CD30 showed positive membrane and paranuclear staining of the large atypical cells, most abundant within the epidermis and papillary dermis ( Fig. 5). CD45RO showed positive membrane staining of the large atypical cells and the majority of the small lymphoid cells. S-100 protein showed increased dendritic cells within the surrounding viable epidermis and the subjacent papillary dermis ( Fig. 6). TIA showed granular staining in the large atypical lymphoid cells and only rare staining in small lymphoid cells ( Fig. 7). EMA staining was essentially negative. KP-1 showed only scattered positive cells mainly in the lower papillary and the reticular dermis. MAC-387 showed membrane staining in the viable epidermis ( Fig. 8). LMP-1 and EBNA2 for EBV were negative within the lymphoid cells as well as within the overlying epidermis. Figure 4. Immunohistochemical ,staining for CD3 showing diffuse staining of lymphoid cells within the epidermis and dermis (150×) Figure 5. Immunohistochemical ,staining for CD30 showing membrane and paranuclear staining of large atypical lymphoid cells within the epidermis and papillary dermis (a, 150× b, 400×) Figure 6. Immunohistochemical ,staining for S-100 protein within the epidermis and in the papillary dermis (a, 150× b, 300×) Figure 7. Immunohistochemical ,granular staining of large atypical lymphoid cells for TIA (200×) Figure 8. Immunohistochemical ,staining for MAC-387 showing epidermal staining (100×) Gene rearrangement studies showed a ,-T-cell receptor gene rearrangement. The monoclonal band was detected with VJ1, VJ2, and D1J2 primer sets. The T-cell receptor , rearrangement assay has a sensitivity of 61% and a specificity of 94% for the detection of a monoclonal rearrangement in T-cell lymphomas for which amplifiable DNA can be recovered. Electron microscopy was performed on formalin-fixed material, positive-fixed with 2.5% phosphate-buffered glutaraldehyde and further with 1% osmium tetroxide by standard techniques. Intracellular, 50,60-nm, cytoplasmic, spherical, viral-like particles were identified ( Fig. 9). Figure 9. Electron ,microscopy showing 50,60-nm diameter, intracellular, viral-like particles (arrows) (70,000×) [source] Subacute immune response to primary EBV infection leading to post-transplant lymphoproliferative disease in a renal transplant patientINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2004S. Leaver Summary A 23-year-old man sero-negative for Epstein,Barr virus (EBV) developed recurrent sore throats 3 and 6 months after a renal transplant from an EBV sero-positive donor. Tonsillar biopsy at 9 months post-transplant showed post-transplant lymphoproliferative disease (PTLD) caused by EBV. Following reduction of immunosuppressive treatment, he developed further signs and symptoms, and serological evidence of infectious mononucleosis followed by resolution of lymphadenopathy. This case emphasizes the difficulty in interpreting EBV serology in immunosuppressed patients and the importance of pre-transplant EBV serology. [source] Herpes viruses in periodontal compromised sites: comparison between HIV-positive and -negative patientsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2008Sabrina Rosa Grande Abstract Aim: The objective of this study was to compare the frequency of herpes simplex virus type 1 (HSV-1), Epstein,Barr virus (EBV) and human cytomegalovirus (HCMV) in subgingival plaque, saliva and peripheral blood of HIV-positive and-negative patients with periodontal disease. Material and Methods: Fifty HIV-positive subjects (23 with gingivitis, 27 with periodontitis) and 50 healthy HIV-negative patients with chronic periodontitis were included in the study. Parameters of probing depth (PD), clinical attachment level (CAL), gingival index and plaque index were recorded. The samples were processed for viral identification by the nested polymerase chain reaction technique. Results: HCMV was the most prevalent virus in HIV-positive (82%) and-negative patients (84%), and the detection in the three samples was similar (p>0.05). HSV-1 was the least prevalent virus in both groups, being detected in similar frequencies in oral sites and in peripheral blood. EBV-1 was found more frequently in saliva and subgingival plaque of HIV-positive patients than in HIV-negative patients (p0.05). Conclusions: EBV-1 was more frequently recovered in oral sites of HIV-positive patients than in HIV-negative patients. [source] KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with Castleman's disease and Kaposi's sarcomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2006Wenhua Liu Three months following the diagnosis of KS affecting a left cervical lymph node and Castleman's disease with bone marrow involvement, he presented with a subcutaneous, tender lesion on his left arm. A skin biopsy demonstrated a superficial and deep, interstitial-nodular infiltrate of severely atypical lymphoid cells showing plasmacytoid features, numerous mitotic figures, and frequent individual apoptotic tumor cells. The morphologic features were those of plasmablastic lymphoma (PBL). Immunohistochemical study showed that the lymphoma cells strongly expressed CD45, CD30, and KSHV/HHV8 latency-associated nuclear antigen. KSHV/HHV8 was also detected in the biopsy sections of the patient's KS and Castleman's disease. Epstein,Barr virus in situ hybridization was diffusely positive. In situ hybridization demonstrated ,-light chain restriction. Although KSHV/HHV8 has been individually associated with KS, Castleman's disease, and PBL, this appears to be the first reported case in which all three entities were present simultaneously in one person, suggesting a critical role of KSHV/HHV8 as a common denominator in the pathogenesis of these diseases. [source] EBNA1 sequences in Argentinean pediatric acute and latent Epstein,Barr virus infection reflect circulation of novel South American variants,JOURNAL OF MEDICAL VIROLOGY, Issue 10 2010Mario Alejandro Lorenzetti Abstract Epstein,Barr virus (EBV) is related to the development of lymphomas and is also the etiological agent for infectious mononucleosis (IM). Sequence variation of the EBNA1 gene, consistently expressed in all EBV-positive cells, has been widely studied. Based on the amino acid at codon 487 five major EBNA1 variants have been described, two closely related prototypic variants (P-ala and P-thr) and three variant sequences (V-leu, V-val, and V-pro). Sub-variants were then further classified based on mutations other than the originally described. While several studies proposed associations with tumors and/or anatomical compartments, others argued in favor of a geographical distribution of these variants. In the present study, EBNA1 variants in 11 pediatric patients with IM and 19 pediatric EBV lymphomas from Argentina were compared as representatives of benign and malignant infection in children, respectively. A 3-month follow-up study of EBNA1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. A new V-ala variant which includes five V-ala sub-variants and three new V-leu sub-variants was described. These data favor the geographical association hypothesis since no evidence for a preferential compartment distribution of EBNA1 variants and sub-variants was found. This is the first study to characterize EBNA1 variants in pediatric patients with infection mononucleosis worldwide. J. Med. Virol. 82:1730,1738, 2010. © 2010 Wiley-Liss, Inc. [source] New variations of Epstein,Barr virus-encoded small RNA genes in nasopharyngeal carcinomas, gastric carcinomas, and healthy donors in northern ChinaJOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Yun Wang Abstract It has been generally believed that the Epstein,Barr virus (EBV)-encoded small RNA 1 and 2 (EBER1 and EBER2) genes are conserved as two families that correlated with type 1 (B95-8) and type 2 (AG876 or P3HR-1) EBV strains. EBER polymorphism and its association with EBV-associated disease have not received much attention. To explore the variations of EBER genes in different malignancies and healthy donors, the sequences of EBER genes were analyzed in 154 EBV-positive samples, including 47 nasopharyngeal carcinoma (NPC), 50 EBV-associated gastric carcinoma (EBVaGC) biopsies and 57 throat washing (TW) samples from healthy donors in northern China, where NPC is non-endemic. Three main distinct variants of EBER genes, designated as EB-6m, EB-8m, and EB-10m, were identified. EB-6m had a previously identified EBER sequence identical to P3HR-1 and was found in 33/47 (70.2%) NPC, 48/50 (96.0%) EBVaGC, and 54/57 (94.7%) TW isolates. EB-8m and EB-10m were new EBER variants with more mutations in EBER2 genes. They were found in 13/47 (27.7%) NPC cases, whereas in only 1/50 (2.0%) EBVaGC cases and not found in TW cases. The distributions were significantly different (P,<,0.05). Other five isolates (one NPC, one EBVaGC and three TW cases) showed different sequences and could not be assigned to any of the three groups. Type 1 EBV strains showed heterogeneous in terms of EBER variants. These results suggest that EBER locus can be useful to identify different EBV isolates, and it would be interesting to evaluate the association of EBER polymorphisms with EBV-associated tumors. J. Med. Virol. 82: 829,836, 2010. © 2010 Wiley-Liss, Inc. [source] Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West AfricaJOURNAL OF MEDICAL VIROLOGY, Issue 11 2009Lara Isobel Compston Abstract Only limited epidemiological data, pertaining to the prevalence of common persistent viruses has been reported in Ghana. This study was conducted to determine the prevalence of persistent viruses in individuals with untreated HIV-1 infection and uninfected blood donors. Paired plasma and cellular samples from HIV-negative blood donors, asymptomatic HIV and symptomatic/AIDS cohorts were screened by multiplex PCR then qPCR for parvovirus B19 (B19V), hepatitis B virus (HBV), GB virus-C (GBV-C), cytomegalovirus (CMV), Epstein,Barr virus (EBV), human herpesvirus-8 (HHV-8) and varicella-zoster virus (VZV). IgG antibodies specific to each target virus were tested to determine exposure rates. No evidence of viraemia was found for B19V and VZV in any group. Prevalence of GBV-C plasma viraemia was significantly higher in asymptomatic and symptomatic HIV infection (16.7%) and (16.2%) than in blood donors (4%) P,<,0.005. Occult HBV infection was significantly more frequent in symptomatic HIV infection (10.9%) compared to asymptomatic HIV (3.6%) and blood donors (1.6%) P,<,0.005. Although there was a high background of EBV viraemia in cellular fractions of blood donors (8.3%), it was significantly higher in asymptomatic (44.6%) and symptomatic HIV (14.6%) P,<,0.0001. For CMV, the significantly increased prevalence of viraemia was only observed in the plasma fraction of the symptomatic HIV-1/AIDS patients (7.6%) compared to asymptomatic individuals (1.8%) and blood donors (0.8%) P,,,0.001. The background seroprevalence in blood donors was high for B19V (,64%), HBV (,70%), CMV and EBV (,90%) and was significantly increased in HIV infections for HBV, CMV, VZV (symptomatic HIV), and HHV-8 (asymptomatic and symptomatic HIV). J. Med. Virol. 81:1860,1868, 2009. © 2009 Wiley-Liss, Inc. [source] Prevalence of human papilloma virus and human herpes virus types 1,7 in human nasal polyposisJOURNAL OF MEDICAL VIROLOGY, Issue 9 2009Apostolos Zaravinos Abstract This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein,Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions. J. Med. Virol. 81:1613,1619, 2009. © 2009 Wiley-Liss, Inc. [source] Regulatory T cell activity in primary and persistent Epstein,Barr virus infectionJOURNAL OF MEDICAL VIROLOGY, Issue 5 2009P.J. Wingate Abstract Regulatory T cells (Treg) provide a balance to immune T cell activation thereby protecting the body from pathogen-induced immunopathology. Several persistent viruses induce Treg that subvert protective immune mechanisms and promote viral persistence. Epstein,Barr virus (EBV) generally infects children subclinically and persists thereafter, but primary infection in early adulthood may cause immunopathological damage manifest as infectious mononucleosis. In this study the role of Treg was investigated in acute infectious mononucleosis and healthy EBV seropositive donors. The proportion of CD4+CD25high T cells in blood from infectious mononucleosis patients was significantly lower than in seropositive donors (P,=,0.05). Using the FOXP3 marker for Treg the same frequency and extra-follicular distribution of Treg was noted in infectious mononucleosis and control tonsils. Regulatory cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-,, were significantly raised in infectious mononucleosis compared to seropositive donor plasma (P,=,0.0001, P,=,0.0004 respectively) although levels of IL-10 peaked earlier in infectious mononucleosis than TGF-,. Previous studies identified EBV latent membrane protein (LMP)-1-induced Treg activity [Marshall et al. (2003): J Immunol 170:6183,6189; Marshall et al. (2007): Brit J Haematol 139:81,89], and in this study a significant reduction in interferon-, production was found from infectious mononucleosis but not seropositive donor lymphocytes after stimulation with a recall antigen when LMP-1 peptide PRG was added (P,=,0.03). It is possible that Treg are important in controlling primary EBV infection to a subclinical level in most cases and that infectious mononucleosis represents a failure of this protective mechanism. J. Med. Virol. 81:870,877, 2009. © 2009 Wiley-Liss, Inc. [source] Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein Barr virus infections in the setting of pre-emptive therapyJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Céline Bressollette-Bodin Abstract Two quantitative duplex real-time PCR assays were developed for co-amplification of human albumin and cytomegalovirus (CMV) or Epstein Barr virus (EBV) genes after automated extraction on whole blood, and compared two units for expressing viral DNA loads (copies per ml of blood or per 106 peripheral blood leukocytes (PBLs)) on 1,138 positive samples. Both PCRs were characterized by high sensitivity, reproducibility, and linear range. Automated extraction by a MagNA Pure LC Instrument was shown to be more efficient when peripheral blood cell count was inferior to 5,×,109 PBLs/L. Albumin co-amplification allows the detection of PCR inhibitors and normalization of viral load according to the number of cells calculated in the sample. The two ways of expressing viral load results were highly correlated, but quantitative differences varied in relation to variations of blood cell count. As these two viruses are highly cell associated, viral loads can be underestimated in patients with leucopenia. In the setting of pre-emptive strategies during CMV infection, the units in which results are expressed can influence clinical management, as illustrated in this article. J. Med. Virol. 81:90,98, 2009. © 2008 Wiley-Liss, Inc. [source] Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulinJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Christine Ma Abstract Viral loads and cytokine responses Epstein,Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-,, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery. J. Med. Virol. 81:99,105, 2009. © 2008 Wiley-Liss, Inc. [source] Structural variability of the carboxy-terminus of Epstein,Barr virus encoded latent membrane protein 1 gene in Hodgkin's lymphomasJOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Deisy M. Guiretti Abstract Epstein,Barr virus (EBV) is implicated in the pathogenesis of several lymphoid and epithelial neoplasms. Latent membrane protein 1 (LMP1) is the major viral oncogene and it is controversial whether tumor LMP1 variants reflect their geographical predominance or are associated with enhanced oncogenic properties. This study aimed to analyze LMP1 molecular variability of 62 EBV+ Hodgkin's lymphomas and 22 non-neoplastic controls from Brazil and Argentina. EBV association was characterized by EBER-ISH, LMP1 immunohistochemistry and PCR assays for EBNA2 and 3C (typing), LMP1 30 bp deletion (del30) and number of 33 bp tandem repeats. LMP1 C-terminal sequencing was performed in 42 cases. EBV1 was the predominant strain in both geographical Hodgkin's lymphoma groups (average 82%). A higher frequency of del30 variant was observed in lymphomas (41/63) than in non-neoplastic controls (6/22) (OR 4.97, CI 95% 1.53,16.79; P,=,0.005, ,2 test). A large number (5,7) of 33 bp repeat units was characteristic of del30 LMP1 variants (P,<,0.0001, Fisher's exact test). Sequence analysis showed a similar mutation spectrum to that described worldwide but none of the current classification schemes could be applied completely. A distinct structural pattern was observed in del30 variants, characterized by a large number of 33 bp repeat units and the presence of a 15 bp insertion encoding the JAK3 Box-1a motif (3/15 wt vs. 16/20 del30; P,=,0.001, ,2 test). The results suggest a pathogenic role for LMP1 del30 variants in Hodgkin's lymphoma from South America and point to particular virus-host molecular mechanisms, such as genomic instability in LMP1 carboxy-terminus, leading to enhanced production and selection of these deletion variants. J. Med. Virol. 79:1722,1730, 2007. © 2007 Wiley-Liss, Inc. [source] Latent membrane protein 1 encoded by Epstein,Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways,JOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Lin Ding Abstract Elevated telomerase activity is observed in about 90% of human cancers. This activity correlates strictly with human telomerase reverse transcriptase (hTERT). Previously, it was shown that the Epstein,Barr virus-encoded latent membrane protein 1 (LMP1) induced telomerase activity in nasopharyngeal carcinoma cells. In this study, it was indicated that LMP1 inhibited p16INK4A expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression as well as transactivation, and overexpression of E2F1 alone was sufficient to upregulate telomerase activity. The JNK kinase cascade could also promote telomerase activity modulated by LMP1, that inhibition of JNK by JIP and TAM 67 dominant negative mutant abrogated telomerase activity. The data show that p16INK4A/Rb/E2F1 and JNK signaling pathways are involved in the regulation of telomerase activity via LMP1. The present study provides new perspectives on carcinogenesis of nasopharyngeal carcinoma that may be exploited for novel therapeutic strategies. J. Med. Virol. 79: 1153,1163, 2007. © 2007 Wiley-Liss, Inc. [source] Cell specific internal translation efficiency of Epstein,Barr virus present in solid organ transplant patientsJOURNAL OF MEDICAL VIROLOGY, Issue 5 2007Åsa Isaksson Abstract The U leader exon in the 5, untranslated region of the Epstein,Barr virus nuclear antigen 1 (EBNA1) gene contains an internal ribosome entry site, the EBNA internal ribosome entry segment (IRES), which promotes cap-independent translation and increases the expression level of the EBNA1 protein. It was previously reported that immunosuppressed organ transplanted patients showed an alternatively spliced EBNA1 transcript, excluding the EBNA IRES element. To further investigate the function of the EBNA IRES, sequence analysis of the EBNA IRES mRNA was performed in samples from seven organ transplant patients. Two nucleotide changes, G,,,A at position 67531 and C,,,U at position 67585 were found in the EBNA IRES mRNA, relative to the corresponding genomic Epstein,Barr virus (EBV) sequence in all patients. Moreover, the patient derived EBNA IRES mRNA was shown to differ from the IRES mRNA derived from the cell line B95.8 at position 67531 and from the cell lines Rael and P3HR1 at positions 67531 and 67585. cDNA from the various EBNA IRES sequences were cloned into bicistronic vectors, respectively, and used in transient transfection experiments in six human cell lines. The patient specific sequence significantly decreased the IRES activity in T-cells, while the base changes had no significant impact on the activity in B- or in epithelial cells. The genetic mechanisms behind EBV-associated diseases are complex, involving gene regulation by alternative promoters, alternative splicing, and translational control. The nucleotide changes in the patient specific EBNA IRES transcript and its influence on the translational activity, might illustrate new strategies utilised by the EBV to adapt to the immune control in patients with EBV associated diseases. J. Med. Virol. 79:573,581, 2007. © 2007 Wiley-Liss, Inc. [source] |