Epstein-Barr virus and gastric carcinoma

Immunohistopathological staining for p53, PCNA and Ki67 was performed in 120 specimens from previously untreated laryngeal carcinomas using the avidin-biotin method with peroxidase as a marker enzyme and diaminobenzidine as a chromogen. A 5-grade staining score system was used. Statistically significant correlations (Chi-square) were seen between T- and N-stage and histopathological grading. p53 and Ki67 scoring correlated with T- and N-stage whereas PCNA with T-stage. All staining correlated with histopathological grading. The score of staining for p53, PCNA and Ki67 correlated with each other. The patients with recurrences within 3 years had mainly carcinomas with higher staining scores. Using Chi-square analysis the p53, PCNA and Ki67 staining scores were also independent prognostic indicators.     

Manifestations of relapsing Epstein-Barr virus illness

The Epstein-Barr Virus is well known for its pattern of communicability and features of clinical disease. It is a member of the herpes virus family and may establish a latency state in infected individuals. Characteristics of latency and reactivation have been well defined for both herpes and varicella. The Epstein-Barr Virus has been shown to establish a latency state within B lymphocytes, salivary gland epithelium, and oropharyngeal epithelial cells. Reactivation of the virus from these sites could produce relapse of EBV illness. Characteristics of relapse are described in this report.     

Epstein-Barr virus in pyothorax-associated pleural lymphoma

Pleural B-cell lymphoma was found in five patients with a history of pyothorax that was the sequelae of tuberculosis 35 to 47 years previously. Epstein-Barr virus (EBV) DNA was detected in all five pleural tumors by polymerase chain reaction and Southern blot hybridization. The lymphoma cells were shown to express the latent membrane protein-1 and the EBV-encoded nuclear antigen-2 by immunocytochemistry and EBV-encoded small RNA by in situ hybridization. Three cases were shown to be EBV subtype A, whereas the remaining two were subtype B, as determined by differences in the EBV-encoded nuclear antigen-2 nucleotide sequence. The patients also had high titers of antibodies against EBV. These findings suggest that EBV is causally associated with the pleural lymphomas that originate at the site of chronic inflammation and fibrosis with a latent period of more than 40 years.     

Detection of Epstein-Barr virus in oral papilloma

Infantile hemangioendothelioma of the thymus is a rare disease. We describe a patient who developed a large anterior mediastinal mass, severe thrombocytopenia and massive pleural effusion at 1 month of age. Glucocorticosteroid and irradiation therapy had no effect on either the tumor size or clinical symptoms and the tumor was resected subtotally. Three months after the subtotal resection, the remaining tumor had almost disappeared and the symptoms had resolved. The patient has now been well for 1 year after surgery without evidence of recurrence. The tumor tissue was characterized by prominent vascular endothelial proliferation intermixed with a normal thymic structure, producing a picture consistent with that of an infantile hemangioendothelioma in the thymus. Immunohistochemically, the tumor cells showed positive staining for vimentin, factor VIII and CD34. The DNA stemline and proliferative activity were examined by flow cytometry, which revealed a diploid stemline with a low growth fraction. DNA content and cell cycle analyses of the tumor tissue may be useful for predicting the biological behavior of the tumor.     

Method of diagnosis of Epstein-Barr virus infection

The CO2 laser can be used for the treatment of various lesions of the eyelids and peri-orbital region with the advantage over other modalities of precise, controllable, hemostatic, non contact atraumatic ablation with the reduction of post-operative pain and improved cosmetic results. Its application in palpabral and peri-orbital surgery is recommended.     

Epstein-Barr virus recombinants from overlapping cosmid fragments

Five overlapping type 1 Epstein-Barr virus (EBV) DNA fragments constituting a complete replication- and transformation-competent genome were cloned into cosmids and transfected together into P3HR-1 cells, along with a plasmid encoding the Z immediate-early activator of EBV replication. P3HR-1 cells harbor a type 2 EBV which is unable to transform primary B lymphocytes because of a deletion of DNA encoding EBNA LP and EBNA 2, but the P3HR-1 EBV can provide replication functions in trans and can recombine with the transfected cosmids. EBV recombinants which have the type 1 EBNA LP and 2 genes from the transfected EcoRI-A cosmid DNA were selectively and clonally recovered by exploiting the unique ability of the recombinants to transform primary B lymphocytes into lymphoblastoid cell lines. PCR and immunoblot analyses for seven distinguishing markers of the type 1 transfected DNAs identified cell lines infected with EBV recombinants which had incorporated EBV DNA fragments beyond the transformation marker-rescuing EcoRI-A fragment. Approximately 10% of the transforming virus recombinants had markers mapping at 7, 46 to 52, 93 to 100, 108 to 110, 122, and 152 kbp from the 172-kbp transfected genome. These recombinants probably result from recombination among the transfected cosmid-cloned EBV DNA fragments. The one recombinant virus examined in detail by Southern blot analysis has all the polymorphisms characteristic of the transfected type 1 cosmid DNA and none characteristic of the type 2 P3HR-1 EBV DNA. This recombinant was wild type in primary B-lymphocyte infection, growth transformation, and lytic replication. Overall, the type 1 EBNA 3A gene was incorporated into 26% of the transformation marker-rescued recombinants, a frequency which was considerably higher than that observed in previous experiments with two-cosmid EBV DNA cotransfections into P3HR-1 cells (B. Tomkinson and E. Kieff, J. Virol. 66:780-789, 1992). Of the recombinants which had incorporated the marker-rescuing cosmid DNA fragment and the fragment encoding the type 1 EBNA 3A gene, most had incorporated markers from at least two other transfected cosmid DNA fragments, indicating a propensity for multiple homologous recombinations. The frequency of incorporation of the nonselected transfected type 1 EBNA 3C gene, which is near the end of two of the transfected cosmids, was 26% overall, versus 3% in previous experiments using transfections with two EBV DNA cosmids. In contrast, the frequency of incorporation of a 12-kb EBV DNA deletion which was near the end of two of the transfected cosmids was only 13%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Epstein-Barr virus serology and Epstein-Barr virus-associated lymphoproliferative disorders in pediatric liver transplant recipients

Epstein-Barr virus serology was performed before and after transplantation in 116 patients of a total series of 261 pediatric OLT recipients. Thirty-nine percent had no immunity before OLT, but this percentage decreased to 11.2% at 6 months and 10.5% at 2 years after transplantation. In this series, 10 children developed a B cell lymphoproliferative disease. Four had adenotonsillar involvement, 2 of them with associated digestive tract invasion. Three of these are alive, 2 after retransplantation for chronic rejection subsequent to arrest of immunosuppression. The fourth died from bone marrow aplasia. Three patients with multiorgan involvement died from multisystemic failure. The remaining 3 patients had a pseudotumoral mass. Two of these are alive, 1 after retransplantation for hepatic localization and secondary vascular and biliary complication. The last died from cachexia. Four patients developed the syndrome after viral reactivation, and 6 after primo infection. Four patients were under FK506 rescue therapy. We conclude that a high rate of EBV primo infection is observed in the first months after transplantation. A significant percentage will develop EBV-associated lymphoproliferative disease, which causes death in half of the patients, including all these with multiorgan involvement. Half of the patients may survive, but because immunosuppression must be stopped, retransplantation for chronic rejection is often necessary in survivors.     

Systemic candidiasis with acute Epstein-Barr virus infection

The binding of a classical cannabinoid agonist, [3H]R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2 ,3-de]-1,4-benzoxazin-6-yl)(1-napthalenyl)methanone monomethanesulfonate ([3H] WIN55212-2), and a selective cannabinoid receptor (CB1) antagonist, N-(piperidin-1-yl)-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4-meth yl-1H-pyrazole-3-carboxamide hydrochloride ([3H]SR141716A), to rat cannabinoid receptors was evaluated using rat cerebellar membranes. Guanine nucleotides inhibited [3H]WIN55212-2 binding by approximately 50% at 10 microM and enhanced [3H]SR141716A binding very slightly. In the same tissue, the binding of guanosine 5'-O-[gamma-[35S]thio]triphosphate ([35S]GTP-gamma-S) was characterized and the influence of cannabinomimetics evaluated on this binding. Cannabinoid receptor agonists enhanced [35S]GTP-gamma-S binding, whereas SR141716A was devoid of action by itself but antagonized the action of cannabinoid receptor agonists. The good correlation obtained between the half maximum efficient concentration (EC50) values in [35S]GTP-gamma-S binding and the IC50 values [3H]WIN55212-2 binding shows that [35S]GTP-gamma-S binding could be a good functional assay for brain cannabinoid receptors.     

Meningo-encephalitis and hydrocephalus caused by Epstein-Barr virus

In a 35-year-old woman who presented with acute somnolence, confusion and slow irregular breathing, Epstein-Barr virus (EBV) meningoencephalitis was diagnosed after serological testing and a polymerase chain reaction of the cerebrospinal fluid. She developed papilloedema and bilateral nervus abducens paresis. A CT scan showed generalized oedema of the brain and triventricular hydrocephalus. Treatment with a ventriculoperitoneal shunt and ganciclovir led to complete recovery. Meningoencephalitis is a not uncommon, yet rarely reported complication of infectious mononucleosis. It usually runs a mild course with spontaneous and full recovery. Hydrocephalus secondary to aqueduct stenosis is a complication of Epstein-Barr virus (EBV) meningoencephalitis which has not been reported in adults before. The disease should be considered whenever the clinical condition deteriorates or neurological symptoms increase.     

Epstein-Barr virus infection in Desert Storm reservists

Approximately 150 U.S. Army reservists from Indiana reported symptoms consistent with chronic fatigue syndrome after returning stateside from the tour of duty in Saudi Arabia. A psychiatric team confirmed the diagnosis, evaluated possible etiology, and treated the service members when appropriate. Those available service members who met the study's diagnostic criteria for chronic fatigue syndrome (n = 37) received an Epstein-Barr virus panel. Seventy-three percent of these selected service members were positive either for an acute or reactivated Epstein-Barr viral infection. These data suggest that service members who suffer from chronic fatigue syndrome may have their symptoms increased and prolonged by secondary viral infections.     

Association of Epstein-Barr virus with pediatric Hodgkin's disease

A bimodal age incidence curve has been shown for Hodgkin's disease (HD). In developing countries, the first age incidence peak occurs in childhood; however, this peak is delayed until young adulthood in developed countries. This difference may reflect differences in the age of exposure to infectious agents involved in the development of HD or may suggest different etiological agents. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a proportion of HD cases. In this study, EBV association was investigated in a series of 55 pediatric HD cases from three geographical locations (United Kingdom, Brazil, and Saudi Arabia) and the relationship between country, age, sex, histological subtype, and EBV positivity was evaluated. EBV was detected in 38 cases using RNA in situ hybridization, Southern blot, or immunohistochemical analysis. No significant difference in EBV positivity by country, age, or sex was observed; however, children under 10 years of age were particularly likely to be EBV-associated. The difference in EBV association in the pediatric group compared with that observed previously for young adult HD was highly statistically significant (P < 0.0001). These results are consistent with the hypothesis that pediatric and young adult HD have different etiologies and suggest that EBV is likely to be involved in the pathogenesis of pediatric HD.     

The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders and several epithelial neoplasms, including undifferentiated nasopharyngeal carcinoma (UNPC; lymphoepithelioma). Lymphoepithelioma-like carcinomas (LEC) are tumors with morphologic features identical to UNPC that occur outside the nasopharynx. To determine whether EBV is associated with LEC, the authors conducted a comprehensive literature review of all pathologically documented LEC reported to date in the English literature. In summary, EBV is associated consistently with LEC from only four anatomic sites: stomach, salivary gland, lung, and thymus. Racial and/or geographic factors influence the association of EBV with LEC in some of these organs. Specifically, the association of EBV with LEC of the salivary gland and lung is restricted to Asian patients, whereas the association of EBV with gastric and thymic LEC is independent of race. The presence or absence of EBV in LEC does not appear to be prognotically important in those cases studies to date.     

Spontaneous retropharyngeal haematoma attributable to Epstein-Barr virus infection

Life-threatening sequelae of Epstein-Barr virus infection are uncommon but may present as: local pharyngeal manifestations, splenic rupture, neurological and haematological disorders and altered hepatic function. We present a case of retropharyngeal haematoma with posterior hypopharyngeal wall necrosis, thrombocytopenia and altered clotting function as a result of Epstein-Barr virus infection. A review of the literature on retropharyngeal haematoma reveals this to be the only recorded case which can be directly attributed to Epstein-Barr virus infection.