1/49. Characterization of Epstein-Barr virus (EBV)-infected natural killer (NK) cell proliferation in patients with severe mosquito allergy; establishment of an IL-2-dependent NK-like cell line.The clinical evidence of a relationship between severe hypersensitivity to mosquito bite (HMB) and clonal expansion of EBV-infected NK cells has been accumulated. In order to clarify the mechanism of EBV-induced NK cell proliferation and its relationship with high incidence of leukaemias or lymphomas in HMB patients, we studied clonally expanded NK cells from three HMB patients and succeeded in establishing an EBV-infected NK-like cell line designated KAI3. immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that KAI3 cells as well as infected NK cells exhibited an EBV latent infection type II, where EBV gene expression was limited to EBNA 1 and LMP1. As KAI3 was established by culture with IL-2, IL-2 responsiveness of peripheral blood NK cells from patients was examined. The results represented markedly augmented IL-2-induced IL-2R alpha expression in NK cells. This characteristic property may contribute to the persistent expansion of infected NK cells. However, KAI3 cells as well as the NK cells from patients were not protected from apoptosis induced by either an anti-Fas antibody or NK-sensitive k562 cells. Preserved sensitivity to apoptosis might explain the relatively regulated NK cell numbers in the peripheral blood of the patients. To our knowledge, KAI3 is the first reported NK-like cell line established from patients of severe chronic active EBV infection (SCAEBV) before the onset of leukaemias or lymphomas. KAI3 cells will contribute to the study of EBV persistency in the NK cell environment and its relationship with high incidence of leukaemias or lymphomas in HMB patients.- - - - - - - - - - ranking = 1keywords = virus (Clic here for more details about this article) |
2/49. Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and reed-sternberg cells in Hodgkin's disease.In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) can be found in a background of otherwise typical B-CLL. To test these HRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micromanipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in HRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from HRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein-Barr virus (EBV) was detected in the HRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL. There is evidence that HRS-like cells in B-CLL, like HRS cells in HD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the HRS-like cells, and in 1 of the EBV-positive HRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional. We speculate that the HRS-like cells in B-CLL represent potential precursors for HRS cells causing HD.- - - - - - - - - - ranking = 0.25keywords = virus (Clic here for more details about this article) |
3/49. Virological and molecular characterisation of a new B lymphoid cell line, established from an AIDS patient with primary effusion lymphoma, harbouring both KSHV/HHV8 and EBV viruses.We report here a new case of primary effusion lymphoma (PEL), occurring in a French homosexual hiv-1 infected male with a pericardial, pleural and mesenteric tumour dissemination, and the establishment from his pleural effusion of a new cell line, Cra-BCBL, dually infected by EBV and KSHV/HHV8. Cra-BCBL cells are of B-cell origin as judged by their clonal immunoglobulin heavy chain (IgH) gene rearrangement, identical to that of the parental tumour. Both the cell line and the lymphoma cells expressed CD38 and CD45 antigens but no classical B-cell or T-cell lineage-restricted antigens. Cra-BCBL harbours a type I EBV virus, expressing a latency type II. Expression of KSHV/HHV8 ORF72 and ORF75 was detected by RT/PCR. In addition, KSHV lytic replication could be induced by treatment by n-butyrate. An equivalent and high copy number of KSHV genomes (20 to 200 copies by cell) was detected both in the primary tumour cells and in the cell line. Southern blot (SB) analysis of EBV terminal repeats (TR) displayed the same unique band in the cell line DNA and in the original tumour cells, consistent with a monoclonal infection of EBV. Furthermore, SB analysis of KSHV/HHV8 TR revealed the same hybridisation pattern between Cra-BCBL and the effusion cells, with a common band at around 30-40 kb corresponding to the fused termini of the viral episomes and a 5 Kb rearranged fragment. The new cell line characterised here could be a useful model to study interactions between two human herpes viruses and their contribution to lymphomagenesis.- - - - - - - - - - ranking = 1.5keywords = virus (Clic here for more details about this article) |
4/49. Epstein-Barr virus-associated high-grade B-cell lymphoma of mucosal-associated lymphoid tissue in a 9-year-old Boy.We report an unusual case of Epstein-Barr virus (EBV)-associated mucosal-associated lymphoid tissue (MALT) lymphoma involving the lungs, kidneys, and axillary lymph nodes in a child with congenital hypoadrenalism and panhypopituitarism. The patient presented with an aggressive clinical course and histologic evolution. Initial biopsies (1994) of the lung and kidney revealed histologic features of low-grade B-cell MALT lymphoma with lymphoepithelial lesions within the renal tubules and bronchial epithelium. Subsequent biopsies (1996, 1997, and 1999) revealed progressively greater cytologic atypia, polymorphism, and necrosis; an increased mitotic rate; and a preponderance of large cells, indicative of progression from a low-grade to a high-grade MALT lymphoma. immunophenotyping of the lung and lymph node lesions revealed identical surface marker profiles: cells were CD19( ), CD20( ), immunoglobulin (Ig) G( ), kappa( ), lambda(-), CD5(-), CD10(-), CD23(-), and IgM(-), and also negative for T-cell markers. Genotypic analysis demonstrated the presence of immunoglobulin heavy chain rearrangement and monoclonality of EBV in the lung lesion by Southern blot hybridization and polymerase chain re()action (PCR). The clinicopathologic features suggest that these lesions might represent an immunosupression-related continuum of low-grade to high-grade MALT lymphomas. infection with EBV may have contributed to this tumor's aggressive clinical and histologic evolution.- - - - - - - - - - ranking = 1.25keywords = virus (Clic here for more details about this article) |
5/49. Epstein-Barr virus (EBV)-induced B-cell proliferative disorder after chemotherapy in a patient with hemophagocytic lymphohistiocytosis with associated EBV-induced T-cell proliferation.We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ hybridization (ISH) and immunostaining. Southern blot analysis using EBV-TR and immunoglobulin JH probes revealed oligoclonal proliferation of B-cells in each organ involved by abnormal B-lymphoid cells at autopsy. Combined ISH and immunostaining disclosed the presence of EBV in proliferating B-cells. Cytokine analysis during the period of T-cell activation in HLH revealed marked elevation of interferon (IFN) gamma, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-alpha were observed, while IFN gamma, IL-10 and sIL-2R were elevated initially during the HLH phase, which then decreased as LPD developed and B-cell proliferation predominated. Immunosuppressive chemotherapy for HLH may then have allowed latent EBV in B lymphocytes to induce transformation and oligoclonal proliferation of B-cells, finally resulting in LPD. Mechanisms of EBV-induced cell proliferation remain unclear, but alteration of various cytokines may be responsible for it.- - - - - - - - - - ranking = 1.25keywords = virus (Clic here for more details about this article) |
6/49. CD20-positive adult T-cell leukemia.A 67-year-old woman was admitted to our hospital because of lymphadenopathy and lymphocytosis. Monoclonal integration of HTLV-I provirus DNA was detected, and a diagnosis of adult T-cell leukemia (ATL) was made. flow cytometry revealed that the ATL cells expressed CD20 as well as T-cell-associated antigens, and expression of CD20 mRNA was also demonstrated. A novel T-cell subpopulation expressing CD20 molecules has recently been identified. This is the first report of CD20-positive ATL, suggesting that HTLV-I can infect and transform CD20-positive T cells.- - - - - - - - - - ranking = 0.25keywords = virus (Clic here for more details about this article) |
7/49. Tissue-specific expression of SV40 in tumors associated with the li-fraumeni syndrome.Inactivation of wild-type p53 tumor suppressor function is the primary mechanism of tumor initiation in li-fraumeni syndrome (LFS) individuals with germline p53 mutations. Tumors derived from LFS patients frequently retain the normal p53 allele, suggesting that alternative mechanisms in addition to gene deletion must be involved in inactivating wild-type p53 protein. dna tumor viruses, such as SV40, target p53 for inactivation through the action of viral oncoproteins. We studied the probands from two unrelated LFS families, each of whom presented with multiple malignant neoplasms. Patient 1 developed an embryonal rhabdomyosarcoma (RMS) and a choroid plexus carcinoma (CPC), while patient 2 developed a CPC and subsequently presented with both an osteosarcoma (OS) and renal cell carcinoma (RCC). We utilized DNA sequence analysis and immunohistochemistry to determine p53 gene status in the germline and tumors, as well as evidence for SV40 T-antigen oncoprotein expression. Each patient harbored a heterozygous germline p53 mutation at codons 175 and 273, respectively. In patient 1, the normal p53 gene was lost while the mutant p53 allele was reduced to homozygosity in the RMS. Both normal and mutant genes were maintained in the CPC. In patient 2, normal and mutant p53 alleles were retained in both the CPC and RCC. Both specific PCR and immunostaining detected SV40 T-antigen in both CPCs and the RCC. In addition to chromosomal alterations, epigenetic mechanisms may disrupt p53 function during tumorigenesis. In two LFS patients, we found SV40 DNA sequences and viral T-antigen expression that could account for inactivation of the normal p53 protein. Inactivation of p53 or other tumor suppressors by viral proteins may contribute to tumor formation in specific tissues of genetically susceptible individuals.- - - - - - - - - - ranking = 0.25keywords = virus (Clic here for more details about this article) |
8/49. Successful allogeneic stem cell transplantation from an unrelated donor for aggressive Epstein-Barr virus-associated clonal T-cell proliferation with hemophagocytosis.We present here a case of aggressive Epstein-Barr virus (EBV)-associated clonal T-cell proliferation with hemophagocytosis that was successfully treated by allogeneic stem cell transplantation using an unrelated donor. A 17-year-old woman was admitted into the hospital with a high fever and liver dysfunction. Laboratory data including bone marrow aspiration revealed hemophagocytic syndrome with proliferation of immature T-lymphoid cells. The clonal proliferation of EBV-infected T cells was confirmed by Southern blot analysis using a terminal-repeat probe from the EBV genome and also by demonstrating T cell-receptor beta gene rearrangement. Intensive immunochemotherapy consisting of cyclosporin A, vincristine, etoposide, and high-dose methylprednisolone did not control the disease and relapse occurred repeatedly. Therefore, during remission after chemotherapy according to the CHOP-E regimen, the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched, unrelated donor. donor selection was performed with help from the Japanese association for Marrow Donor Program (JMDP). The patient has remained in good condition without recurrence of disease for 18 months after BMT. Allogeneic BMT is the treatment of choice for aggressive EBV-associated hemophagocytic lymphohistiocytosis even in the case where an HLA-matched sibling donor is not available, especially when the patient is refractory to intensive chemotherapy and/or there is a ready recurrence of disease after conventional therapy.- - - - - - - - - - ranking = 1.25keywords = virus (Clic here for more details about this article) |
9/49. Carrier detection in agammaglobulinemia by x chromosome inactivation analysis.Using a recently developed strategy to analyze patterns of x chromosome inactivation in cell populations, we found that two mothers and a sister were carriers in three atypical or sporadic cases of patients with agammaglobulinemia, two of whom were brothers. In this study, a phosphoglycerate kinase 1 (PGK1) gene probe was used to detect patterns of methylation of X-chromosome genes. A random pattern of X inactivation was observed in isolated peripheral blood granulocytes. In contrast, one of the two X chromosomes was preferentially active in the Epstein-Barr virus (EBV)-transformed peripheral B cells of the family members of these patients. The volume of the blood specimen could be significantly reduced using EBV-transformed B cell lines which contained multiple clones. The analysis described here can be used to distinguish between X-linked agammaglobulinemia (XLA) and other forms of a- or hypo-gammaglobulinemia as well as to detect the carrier state.- - - - - - - - - - ranking = 0.25keywords = virus (Clic here for more details about this article) |
10/49. acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation.The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (hiv-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta-chain [CT beta] rearrangement) and phenotypically (CD45RO , CD4 , CD5 , CD25 , CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4 , CD25 (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R rna is analogous to human T-lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated hiv-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphoma in which hiv-1 infection may have played a central role in the lymphocyte transformation process.- - - - - - - - - - ranking = 1.5keywords = virus (Clic here for more details about this article) |
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