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Biomedical subjects

K Shimazaki

Publications and source records attributed to K Shimazaki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Possible immortalization of Hodgkin and Reed-Sternberg cells: telomerase expression, lengthening of telomere, and inhibition of apoptosis by NF-kappaB expression.

Telomerase, an enzyme associated with cellular immortality, is expressed on malignant tumor cells. Deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells with unlimited proliferation capacity. Hodgkin and Reed-Sternberg (H&RS) cells are generally considered as neoplastic cells in Hodgkin's disease (HD), however, such cells are only found in a minority of HD lesions. In addition, H&RS cells with mitotic features are rare and mummified forms are occasionally encountered. There are no available data on the relationship between telomerase activity and apoptosis in HD. We studied 14 cases with Hodgkin's disease (mixed cellularity type, nine cases; nodular sclerosis type, five cases) to clarify the relationship between telomerase activity and apoptosis using in situ hybridization of human telomerase reverse transcriptase (hTERT), reverse transcriptase-polymerase chain reaction (RT-PCR) of hTERT, using extracted RNA and immunohistochemistry of nuclear factor-?B (NF-?B), and TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for apoptosis. We also analyzed the telomere length, using sorted H&RS cells. TUNEL showed a few apoptotic H&RS cells, but the cells frequently expressed hTERT, as confirmed by ISH and RT-PCR. Lengthening of the telomere of H&RS cells was noted in ten cases. In addition, H&RS cells frequently expressed NF-?B, which is known as an inducible transcription factor and inhibitor of apoptosis. Our findings of telomerase activity in H&RS cells indicate that these cells are neoplastic and are potentially immortal. In addition, NF-?B expression on H&RS cells suggests its possibility in inhibition of apoptosis of these cells.

Adult↗
PubMed2001

Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seals from the coast of Hokkaido, Japan.

Chlorinated hydrocarbon (CHC) levels in the blubber of larga seals (Phoca largha) and ribbon seals (Phoca fasciata) collected from the coastal waters of Hokkaido, Japan, were determined in order to assess the hormonal effects of CHC exposure in free-ranging pinnipeds. Plasma thyroid hormone levels, including total thyroxine (T4), free thyroxine (free T4), total triiodothyronine (T3), and free triiodothyronine (free T3), were also measured. Higher concentrations of polychlorinated biphenyl congeners (PCBs), dichlorodiphenyltrichloroethane and its metabolites, and chlordane compounds were found in the range of 380 to 2,600 ng/g, 350 to 2,600 ng/g, and 120 to 760 ng/g on a wet-weight basis, respectively. Spearman rank correlation analyses showed that in larga seals, plasma total T3 and free T3 levels negatively correlated with levels of all the CHCs analyzed, although there was no such correlation between total or free T4 levels and CHC concentrations. In ribbon seals, total T3 levels significantly decreased with an increase of di-ortho PCB (PCB170 and 180) residues. These findings indicated that the plasma T3 deficiency could be associated with some CHC exposure in larga and ribbon seals and that the responses of plasma thyroid hormones may be useful biomarkers for CHC exposure in ribbon seals.

Animals↗
PubMed2001

[Analysis of factors related to the high incidence of tuberculosis in the city of Wakayama--analysis according to age groups, and sputum test results].

Over the last 20 years, the decrease in the incidence of Tuberculosis (TB) in Japan has slowed down. As of 1999, the incidence rate was 34.6 per 100,000 population in Japan, which was higher than that of the other developed countries, and the incidence rate in the city of Wakayama, one of the prefectural capital cities in Japan, during the same period was 42.9 per 100,000 population. We investigated the causes of this high incidence rate of TB in Wakayama City according to the analysis by age groups and sputum test results when patients are newly registered. Comparing our data during the period from 1.1.1998 to 12.31.1999 with data during the same period in the whole country and the rest of Wakayama Pref., the following results were obtained. Observing by age-groups, the incidence of TB in Wakayama City as well as in the rest of Wakayama Pref. and in the whole country was highest in the age-group above 70 years of age, though the rate of Wakayama City was significantly higher (146.2 per 100,000 population) than that in the rest of Wakayama Pref. (98.5 per 100,000 population) and that in the whole country (90.3 per 100,000 population). Furthermore, the incidence rate of cases diagnosed as TB without bacteriological proof in Wakayama City (57.1 per 100,000 population) was significantly higher than that of the whole country (33.7 per 100,000 population). Therefore, we concluded that one of the causes of high incidence of TB in Wakayama City was due to inappropriate method of diagnosing TB. More extensive use of sputum examination and strict evaluation of cases without bacteriological proof are desirable to increase the accuracy of TB diagnosis in Wakayama City.

Adolescent↗
PubMed2000

Quantitative analysis of microfilarial periodicity of Dirofilaria immitis in cats.

Microfilarial periodicity of Dirofilaria immitis in the venous blood of infected cats was analyzed by a trigonometric model. Cats were infected by subcutaneous transplantation with 120-day-old juvenile D. immitis. Microfilariae in the blood were first observed 98 days after transplantation. Blood was collected at 4h intervals for a 24h period, and examinations were repeated five times in two cats. The calculated periodicity index was 75.1 and 50.3 in these two cats. The estimated hour of peak microfilarial density ranged from 1.00 to 2.84h. Thus, the periodicity of microfilariae of D. immitis in the blood of cats was characterized as nocturnally sub-periodic.

Animals↗
PubMed2000

Self-amplification system for recombinant adeno-associated virus production.

A recently reported system for recombinant adeno-associated virus (rAAV) production does not require infection of a helper virus and depends on the transfection with a huge amount of three plasmids: AAV-vector, AAV-helper, and adenovirus-helper plasmids. Toward simplifying rAAV production, as a first step, we tested the use of the rAAV itself instead of the AAV-vector plasmid as a source of rAAV DNA and determined the optimal timing of infection and dose of the input rAAV. When 293 cells were infected just after transfection with 100 particles/cell of rAAV, irrespective of the purity, CsCl-purified or crude, up to 2000 particles/cell of rAAV were produced (9- to 20-fold self-amplification), a yield comparable to that obtained by an adenovirus-free transfection. These results indicate that infection of rAAV can greatly reduce the amount of plasmid DNA for a large-scale transfection. This strategy will also be useful when applied to packaging cell lines inducibly expressing Rep and Cap proteins.

Cells, Cultured↗
PubMed2000

Bovine lactoperoxidase and its recombinant: comparison of structure and some biochemical properties.

Biochemical properties of bovine lactoperoxidase isolated from milk and recombinant bovine lactoperoxidase expressed by Chinese hamster ovary cells were compared. The natural and recombinant lactoperoxidases showed the same conformational features as determined by circular dichroism (CD) measurements. The alpha-helix, beta-structure, and unordered structure contents were found to be 17. 8, 54.2, and 28.0% for the natural lactoperoxidase and 18.6, 50.1, and 31.3% for the recombinant lactoperoxidase, respectively. The microenvironments of aromatic amino acid residues in both lactoperoxidases seemed to be the same, although the CD spectral band due to the Soret band differed slightly. A difference in the pH-dependent spectral changes of absorbance at 413 nm was observed. From a pepsin hydrolysate of lactoperoxidase, a heme-binding peptide was isolated by reverse-phase HPLC and its amino acid sequence was examined.

Animals↗
PubMed2000

Improved generation of catalytic antibodies by MRL/MPJ-lpr/lpr autoimmune mice.

To compare the abilities of different strains of mice to elicit catalytic antibodies (Abs), we determined the occurrence of esterolytic Abs in BALB/c (normal strain) and MRL/MPJ-lpr/lpr (MRL/lpr, autoimmune) mice after immunization with the transition state analog (TSA) 1. Hybridoma supernatants elicited against TSA 1 were screened by ELISA for binding to the BSA-conjugated TSA 1 (=3b), and then screened for binding to the BSA-linked short TSA 2 (=4). We obtained eight times more positives from MRL/lpr mice than from BALB/c mice by these screening steps. The monoclonal antibodies (mAbs) obtained here were examined for binding and catalytic activity. Fifteen of 25 mAbs from MRL/lpr had esterolytic activity, compared with only two of 21 mAbs from BALB/c. These results demonstrated that the occurrence of catalytic Abs was much higher in MRL/lpr mice than in BALB/c mice, which is in good agreement with the previous report by Tawfik et al. [Tawfik, D.S., Chap, R., Green, B.S., Sela, M., Eshhar, Z., 1995. Proc. Natl. Acad. Sci. U.S.A. 92, 2145-2149] using a different kind of TSA. Thus, these studies strongly suggest that using the appropriate strain can be a key factor in the efficient production of catalytic Abs. Furthermore, these mAbs were characterized to elucidate the mechanism of strain difference, and determine whether MRL/lpr mice can be used with other TSAs for the efficient production of catalytic Abs.

Animals↗
PubMed2000

Adeno-associated virus vector-mediated bcl-2 gene transfer into post-ischemic gerbil brain in vivo: prospects for gene therapy of ischemia-induced neuronal death.

The proto-oncogene bcl-2 is known as an anti-apoptotic gene that confers the ability to block neuronal cell death after transient ischemia. In order to examine whether the bcl-2 gene can be used for protection of ischemic brain injury, we generated adeno-associated virus (AAV) vectors capable of expressing human bcl-2. Replication-defective AAV vectors were found effectively to transfer and express bcl-2 gene in the gerbil hippocampal neurons. Transduction with AAV bcl-2 5 days before forebrain ischemia prevented the DNA fragmentation in the CA1 neurons that is commonly associated with ischemia-induced cell death. Furthermore, the application of AAV bcl-2 as late as 1 h following an ischemic insult also prevented DNA fragmentation in CA1 neurons. These results suggest that the bcl-2 protein has neuroprotective functions that inhibit ischemic cell death and demonstrate the potential of AAV bcl-2 for use in post-ischemic gene therapy in the brain. Gene Therapy (2000) 7, 1244-1249.

Adenoviridae↗
PubMed2000

Evaluation of apoptosis as a prognostic factor in myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hypercellular bone marrow. This is thought to be as a result of the apoptosis of haematopoietic bone marrow cells resulting in ineffective haematopoiesis. To clarify the relationship between prognosis and apoptosis and/or cell proliferation in the bone marrow, we studied 51 cases with MDS. Bone marrow biopsies were stained immunohistochemically for MIB-1 (marker for proliferating cells) and CD34 (marker for stem cells). Apoptosis was visualized by detection of DNA fragmentation using TdT incorporation of nucleotides on 3' ends of DNA (TUNEL technique) and expressed as the apoptotic rate. MDS patients included 32 with refractory anaemia (RA), one RA with ringed sideroblasts (RARS) patient, seven RA with excess of blasts (RAEB) patients, eight patients with RAEB in transformation (RAEB-t) and three patients with chronic myelomonocytic leukaemia (CMMoL). In addition, we also studied six cases with acute myeloid leukaemia (AML) arising from MDS (AML-MDS) and ten control subjects. Fatal pancytopenia was the cause of death in 19 out of 51 patients. The apoptotic rate was higher in MDS patients (5.5%) than in control subjects (0.6%) and AML-MDS patients (0.4%). The percentage of MIB-1 positive cells was higher in MDS and AML-MDS than in control. The percentage of CD34-positive cells was higher in AML-MDS, RAEB, RAEB-t and CMMoL patients than control subjects and RA patients. Our findings indicate the activation of both the proliferative and apoptotic rates in MDS. Poor prognosis correlated significantly with higher apoptotic rates, but not with percentages of MIB-1 and CD34-positive cells. Our results suggest that apoptosis might be a useful prognostic factor and inhibition of apoptotic mechanisms may induce leukaemic transformation in MDS.

Adult↗
PubMed2000

Gastrointestinal T cell lymphoma: predominant cytotoxic phenotypes, including alpha/beta, gamma/delta T cell and natural killer cells.

Gastrointestinal T cell lymphoma (TCL) is a rare subset of peripheral TCL, presenting with or without cytotoxic phenotype, a history of coeliac disease (CD) and enteropathy. However, CD is rare in Japan. Here, we describe the clinicopathological features of 18 Japanese cases. Lesions were found in the small intestine (n=13), stomach (n=3) and colon (n=2). Seven patients presented with enteropathy but none had a history of CD. Lymphomas appeared as ulceration (n=11), tumour formation (n=6), or polypoid growth (n=1). Histologically (REAL classification), neoplastic lesions were composed of intestinal type T cell lymphoma (ITCL, n=13, including one case with NK type), anaplastic large cell (ALCL, n=2), adult T cell leukaemia/lymphoma (ATLL, n=2), and lymphoblastic type (n=1). Epstein Barr virus infection was detected by EBER-1 in situ hybridization in 6 of 11 cases with ITCL but not in the other types. ALCL expressed CD30. CD56 was expressed in 3 of 11 cases of ITCL but not in other types. Among the 10 examined cases, 8 were alphabeta T cell type [CD2+, CD3+, T cell receptor (TCR)delta-1-, betaF1+], one was gammadelta T cell type [CD2+, CD3+, TCRdelta-1+, betaF1-], and the remaining case expressed natural killer (NK) cell type [CD2+, CD3-, CD56+, TCRdelta-1-, betaF1-]. Among the 8 examined cases, 3 expressed CD103 molecule, which was associated with extrathymic T cells of intraepithelial lymphocytes. All cases except ATLL expressed the cytotoxicity-associated molecule of TIA-1, and 11 of 14 TIA-1 positive cases expressed activated cytotoxic molecules of perforin, granzyme B, and/or Fas ligand. Despite the morphological, genetic and phenotypic heterogeneity, prognosis was poor, and 11 of 13 patients with small intestinal lesions died albeit appropriate treatment, but 3 of 4 patients with gastric or colonic lesions were still alive. The main cause of death was intestinal perforation. The latter might be due to the site specificity of small intestine and tumour cytotoxicity.

Adult↗
PubMed1999

The ABC-exporter genes involved in the lipase secretion are clustered with the genes for lipase, alkaline protease, and serine protease homologues in Pseudomonas fluorescens no. 33.

In Pseudomonas fluorescens no. 33, the lipase gene is clustered with the genes for alkaline protease, AprDEF exporter, and two homologue proteins of Serratia serine proteases (pspA and pspB). Secretion of the lipase and alkaline protease through AprDEF was shown in the Escherichia coli cells. Interestingly, the E. coli cells carrying the pspA gene secreted PspA to the media AprDEF-independently.

ATP-Binding Cassette Transporters↗
PubMed1999

Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells.

Cytotoxic lectins (KML-C) were isolated from an extract of Korean mistletoe [Viscum album C. (coloratum)] by affinity chromatography on a hydrolysed Sepharose 4B column, and the chemical and biological properties of KML-C were examined, partly by comparing them with a lectin (EML-1) from European mistletoe[Viscum album L. (loranthaceae)]. The hemagglutinating activity of KML-C was inhibited by N-acetyl-D-galactosamine and D-galactose at the minimum concentrations of 6.3 and 12.5 microM/ml, respectively. Further biochemical analyses indicated that KML-C consists of four chains (Mr = 27.5, 30, 31 and 32.5 kDa) which, in some of the molecules, are disulfide-linked, and that the chains of KML-C are distributed over a broad range of isoelectric points (pI), 8.0 to 9.0, whereas the range for EML-1 is 6.6-7.0. A difference was also observed between the N-terminal sequences of KML-C and EML-1. The isolated lectins showed strong cytotoxicity against various human and murine tumor cells, and the cytotoxic activity of KML-C was higher than that of EML-1. Tumor cells treated with KML-C exhibited typical patterns of apoptotic cell death, such as apparent morphological changes and DNA fragmentation, and its apoptosis-inducing activity was blocked by addition of Zn2+, an inhibitor of Ca2+/Mg2+ -dependent endonucleases, in a dose-dependent manner. These results suggest that KML-C is a novel lectin related to the cytotoxicity of Korean mistletoe, and that its cytotoxic activity against tumor cells is due to apoptosis mediated by Ca2+/Mg2+ -dependent endonucleases.

Animals↗
PubMed1999

Clinical, immunohistochemical and phenotypic features of aggressive nodal cytotoxic lymphomas, including alpha/beta, gamma/delta T-cell and natural killer cell types.

Cytotoxic cells include natural killer (NK) cells and cytotoxic alpha beta and gamma delta T lymphocytes (CTLs). These cells express cytotoxic molecules of T-cell restricted intracellular antigen (TIA-1), and activated cytotoxic molecules of perforin, granzyme B, and FasL. Recent studies suggest that most extranodal T-cell lymphomas are derived from CTLs, and that NK cell lymphomas are extranodal. However, only a few nodal NK and cytotoxic lymphomas have been described so far. We present here the clinicopathological features of seven cases of nodal cytotoxic T and NK cell lymphomas. The study excluded anaplastic large-cell lymphomas expressing cytotoxic molecules. The neoplastic cells of all cases contained activated cytotoxic molecules of TIA-1, granzyme B, Fas ligand, and/or perforin. Phenotypically and genotypically, four cases showed alpha beta T cell type [CD2+, CD3+, T-cell receptor (TCR)-delta-1-, beta F1+, and TCR gene rearrangement], two cases showed gamma delta cell type [CD2+, CD3+, T-cell receptor (TCR) delta-1+, beta F1-, and TCR gene rearrangement], and one case showed NK cell type [CD2+, CD3-, CD56+, T-cell receptor (TCR) delta-1-, beta F1-, and TCR gene germline]. Using Southern blot analysis, Epstein-Barr virus (EBV) sequences were detected in six cases, and monoclonal terminal repeat proliferation was confirmed. In addition, in situ hybridization (ISH) studies for EBV showed EBV infection in almost all neoplastic cells. Clinically, all patients presented with peripheral lymphadenopathy in high clinical stages and showed an aggressive course. Hepatosplenomegaly was detected in six cases. During the course of the disease, bone marrow and extranodal invasion were noted in five cases. The nodal type showed an aggressive clinical course in all cases but one, as did the extranodal type. The nodal type varied in phenotype, but was closely associated with EBV infection.

Adolescent↗
PubMed1999

Absence of cytotoxic molecules in CD8- and/or CD56-positive adult T-cell leukaemia/lymphoma.

Adult T-cell leukaemia/lymphoma (ATLL) cells usually exhibit a CD4+ (helper/inducer) phenotype (CD4+/8-/56-), and only a minority of tumours express the CD8 (cytotoxic/suppressor) or CD56 (natural killer [NK]-associated) antigens. TIA-1 is a cytotoxic granule-associated protein expressed in NK cells and cytotoxic T lymphocytes (CTLs). Granzyme B, perforin and Fas ligand (FasL) are also expressed in activated CTLs and NK cells. To clarify the cytotoxic potential of ATLL cells, immunohistochemistry was performed in CD8+ and/or CD56+ ATLL cells, using anti-TIA-1, anti-granzyme B, anti-perforin and anti-FasL antibodies. We studied nine cases of CD8+ and/or CD56+ ATLL, all of which exhibited monoclonal integration of human T-cell leukaemia virus type 1 (HTLV-1) proviral DNA. Four cases exhibited a CD8+/CD56- phenotype, four others had a CD8-/CD56+ phenotype, and one was CD8+/CD56+. All but one case also expressed the surface antigens CD3, TCR alpha beta, and CD4. Expression of granzyme B and TIA-1 were demonstrated in three and two cases, respectively, but none expressed perforin or FasL. In the control study, 10 cases with typical CD3+/4+/8-/56- ATLL demonstrated no expression of those cytotoxic-associated proteins. Our findings suggest that CD8 and/or CD56 positivity probably confer(s) no cytotoxic function on ATLL cells, and it is possible that CD8 and CD56 may be simply aberrant surface markers in ATLL.

Adult↗
PubMed1999

Characterization of Korean native goat lactoferrin.

We purified lactoferrin from the colostrum of the Korean native goat (Capra hircus) by ion-exchange chromatography using CM-Toyopearl 650M followed by affinity chromatography on AF-Heparin Toyopearl 650M. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis suggested the molecular mass of Korean native goat lactoferrin is 82 kDa with an iron saturation of 30% as estimated by spectroscopic analysis. Circular dichroism analysis shows goat lactoferrin molecule contains 24.5%, alpha-helix; 36.0%, beta-structure; 13.5%, beta-turn and 26.0%, unordered structure. Heparin binding affinity is the same as that of bovine lactoferrin, but lower than that of human lactoferrin. An analysis using synthetic peptides shows that the peptide from residue 22 to 31--WQRRMRKLGA--exerts a positive heparin-binding ability.

Animals↗
PubMed1999

Basic fibroblast growth factor and fibrosis in Hodgkin's disease.

Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg (H-RS) cells against a hyperplastic background of reactive cells such as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils and stromal cells. In addition, the HD nodular sclerosis (NS) subtype shows characteristic fibrous bundles, while the other subtypes do not. The fibrosis is considered to correlate with multiple cytokines and cytokine networks. Basic fibroblast growth factor (bFGF), one of the potent stimulators of fibroblasts, has also been linked to the fibroproliferative process. To investigate the relationship of fibrosis and bFGF, we thus performed both immunostaining, in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) on 25 cases of HD, which included 12 cases with NS subtype, 10 cases with mixed cellularity (MC), and 3 cases with lymphocyte predominance (LP). In NS, the expression of bFGF was stronger than that in LP and MC. In addition, the H-RS cells in NS frequently expressed bFGF. The stromal cells and histiocytes in the background expressed bFGF in NS. However, in MC and LP the number of bFGF-expressed H-RS cells was small, and the bFGF expression of background cells was rarely detected. However, the amount of bFGF varied in each case with HD NS. The above results support the possibilities that H-RS cells and background cells are a cellular source of bFGF and that the bFGF expression of those cells is also one of the influencing factors in the development of fibrosis in the HD NS subtype.

Adolescent↗
PubMed1999

Genotypic and phenotypic alterations in Epstein-Barr virus-associated lymphoma.

AIMS: Epstein-Barr virus (EBV) is associated with numerous reactive and neoplastic lymphoproliferative disorders. In vitro, EBV infection can transform B-lymphocytes and induce phenotypic alterations. This study presents the clinicopathological features of four cases with malignant lymphoma, which showed phenotypic and/or genotypic alterations during the course of the disease. METHODS AND RESULTS: To determine the type of EBV genotype, we performed polymerase chain reaction (PCR) for lymphocyte-defined membrane antigen (LYDMA) of EBV, subtype A/B and latent membrane protein (LMP)-1 deletion. In addition, we analysed the terminal repeat (TR) band of EBV and receptor genes (T-cell receptor gene, TCR; immunoglobulin gene heavy chain, IgH) for EBV-infected cell clonality. Double staining of cell markers (B, T-lymphocytes; histiocytes), and in-situ hybridization (ISH) for EBV were performed using tissues obtained during the course of the disease. The first case showed genotypic and phenotypic alterations of T-cell type to B-cell type. The first TCR rearrangement and T-cell markers (CD3+, CD4+, CD8-) were lost and IgH rearrangement and B-cell markers (CD19+, CD20+) were identified. During the course of the disease, EBV-TR bands changed in size; however, the EBV genotype type B, LMP1 deletion type, and single LYDMA band remained the same. The initial T-cell lymphoma clone was considered to be different from the latter B-cell lymphoma clone. The second case showed phenotypic alterations. The first B-cell marker (CD19+, CD20+, CD68-) changed to histiocytic markers (CD19-, CD20-, CD68+). However, IgH rearrangement and EBV-TR bands remained the same throughout the course of the disease and EBV genotype type A, LMP1 deletion type, and single LYDMA band remained unchanged. The third case showed phenotypic alterations. The B-cell marker (CD20+) was lost; however, IgH rearrangement of PCR and EBV genotype remained the same. In the second and third cases, the initial lymphoma clones were considered to be same as the latter clones. The last case showed lineage alterations from Hodgkin's disease to natural killer (NK) cell leukaemia. However, EBV genotype did not change. The second case and Hodgkin's disease showed LMP expression, but the first and third cases showed no LMP, and EBNA2 was not detected in all cases. CONCLUSIONS: We report the genotypic and/or phenotypic alterations in four patients with EBV-associated lymphoma/leukaemia. However, EBV genotype did not change in all four. These findings suggest that EBV might induce the cell marker and lineage alteration in vivo, as in vitro.

Adult↗