Search

Sex chromosomes in poikilothermal vertebrates are characterized by rapid and diverse evolution at the species or population level. Our previous study revealed that the Taiwanese frog Odorrana swinhoana (2n = 26) has a unique system of multiple sex chromosomes created by three sequential translocations among chromosomes 1, 3, and 7. To reveal the evolutionary history of sex chromosomes in the Odorrana species complex, we first identified the original, homomorphic sex chromosomes, prior to the occurrence of translocations, in the ancestral‐type population of O. swinhoana. Then, we extended the investigation to a closely related Japanese species, Odorrana utsunomiyaorum, which is distributed on two small islands. We used a high‐throughput nuclear genomic approach to analyze single‐nucleotide polymorphisms and identify the sex‐linked markers. Those isolated from the O. swinhoana ancestral‐type population were found to be aligned to chromosome 1 and showed male heterogamety. In contrast, almost all the sex‐linked markers isolated from O. utsunomiyaorum were heterozygous in females and homozygous in males and were aligned to chromosome 9. Morphologically, we confirmed chromosome 9 to be heteromorphic in females, showing a ZZ‐ZW sex determination system, in which the W chromosomes were heterochromatinized in a stripe pattern along the chromosome axis. These results indicated that after divergence of the two species, the ancestral homomorphic sex chromosome 1 underwent highly rapid and diverse evolution, i.e., sequential translocations with two autosomes in O. swinhoana, and turnover to chromosome 9 in O. utsunomiyaorum, with a transition from XY to ZW heterogamety and change to heteromorphy. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) is important for body health. A few reports suggested that PA also influenced skin structure and components. Little data are available on the influence of PA on skin mechanical properties (SMP). Here, we investigated the relationship between PA and SMP. Methods: Twenty‐five healthy Japanese female subjects (31.0 ± 3.3 years) were enrolled in the study. To monitor the 24‐hr pulse rate, a wrist watch‐type pulse monitor was used. PA intensity was divided into five PA intensity zones (max, anaerobic, aerobic, fat combustion, and warm‐up) by the pulse monitor. The average values of the time spent on each intensity for 70 days were calculated. To measure SMP, a Cutometer was used at the end of the monitoring. R0 indicated the height of the maximal skin deformation, and R6 was the ratio between viscoelastic and elastic deformation. Results: R0 was positively correlated with the time spent in four of the five PA intensity zones (max, anaerobic, aerobic, and fat combustion), whereas R6 was negatively correlated with the time spent in these four PA intensity zones. The time of warm‐up did not correlate with SMP. Conclusion: These results suggest that habitual moderate‐to‐vigorous PA influences SMP. [ABSTRACT FROM AUTHOR]

Background: Outbreaks of enterovirus D68 (EV‐D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV‐D68 outbreak in the autumn of 2015 (September–October). The aim of this study was to compare EV‐D68‐specific polymerase chain reaction (PCR)‐positive and EV‐D68‐specific PCR‐negative patients. Methods: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV‐D68‐specific reverse transcription‐PCR. EV‐D68‐specific PCR‐positive and ‐negative patients were compared regarding demographic data and clinical information. Results: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV‐D68 was detected in 40 samples (52.6%). Median age in the EV‐D68‐specific PCR‐positive and ‐negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV‐D68‐positive group (3.0 days vs 5.0 days, P = 0.001). EV‐D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered. Conclusions: More than half of the samples from the children admitted with respiratory symptoms were positive for EV‐D68‐specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection. [ABSTRACT FROM AUTHOR]

Background: While determining sebaceous gland morphology is useful in the treatment of skin disorders such as acne, a non‐invasive assessment method has not been developed. Since age and gender affect sebum level, differences in sebaceous gland morphology according to these factors were investigated. Methods: Facial skin was measured using a high‐frequency three‐dimensional ultrasound microscope. First, the ultrasound images were compared with skin sections. Next, we assessed sebaceous gland morphology. Images of sebaceous gland in the cheeks of young male, young female and elderly female subjects were obtained using ultrasound microscopy, and en face images were processed to measure the sebaceous gland area. Results: In the ultrasound images, sebaceous glands and also thin collagen fibers, which surrounded the glands, could be detected as low‐intensity regions. We called them sebaceous units. In young male subjects, the sebaceous unit areas 900‐μm beneath the skin surface were larger than those at 700 μm. In contrast, depth‐dependent differences in sebaceous unit area were not observed in young female subjects, indicating that males had cauliflower‐shaped sebaceous glands while young females had somewhat more cylindrical and smaller sebaceous glands than the young males. Regarding age, the areas of sebaceous units at 900 μm were diminished and the depth of maximum area was shallower in elderly female subjects compared to young female subjects. Hence, sebaceous glands are considered to shrink with age. Conclusion: Differences in facial sebaceous unit morphology between genders as well as by age groups could be observed using high‐frequency ultrasound microscopy. [ABSTRACT FROM AUTHOR]

Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequent, but viral reactivations after autologous HSCT (auto-HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre- to 42 days post-HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV). Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto-HSCT patients, which was similar to the incidence in allo-HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto-HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto-HSCT patients. J. Med. Virol. 89:358-362, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post-HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first-line screening test and real-time PCR for subsequent quantitative evaluation. Five hundred ninety-one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV-6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV-7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV-6 DNA levels demonstrated four of the six HHV-6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV-6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV-6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV-6 encephalitis can be improved by confirming high HHV-6 DNA load in blood. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus-positive T-cell lymphoproliferative diseases ( EBV-T- LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T- LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse-transcriptase polymerase-chain reaction ( RT- PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T- LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T- LPDs patients, by RT- PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and si RNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T- LPDs. [ABSTRACT FROM AUTHOR]

Viral reactivations following hematopoietic stem cell transplantation are thought to result from the breakdown of both cell-mediated and humoral immunity. As a result, many viruses could be reactivated individually or simultaneously. Using a multiplex polymerase chain reaction (PCR), we prospectively examined many kinds of viral DNAs at a time in 105 patients who underwent allogeneic hematopoietic stem cell transplantation. In total, 591 whole blood samples were collected weekly from pre- to 42 days post-transplantation and the following 13 viruses were tested; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6), HHV-7, HHV-8, adenovirus, BK virus (BKV), JC virus (JCV), parvovirus B19, and hepatitis B virus (HBV). Several viral DNAs were detected in 12 patients before hematopoietic stem cell transplantation. The detection rate gradually increased after transplantation and peaked at 21 days. The most frequently detected virus was HHV-6 (n = 63; 60.0%), followed by EBV (n = 11; 10.5%), CMV (n = 11; 10.5%), and HHV-7 (n = 9; 8.6%). Adenovirus and HBV were each detected in one patient (1.0%). Detection of HHV-6 DNA was significantly more common among patients undergoing cord blood transplantation or with steroid treatment. EBV DNA tended to be more common in patients treated with anti-thymocyte globulin. Multiplex PCR was useful for detecting many viral reactivations after hematopoietic stem cell transplantation, simultaneously. Cord blood transplantation, steroid treatment, or anti-thymocyte globulin use was confirmed to be risk factors after transplantation. J. Med. Virol. 87:1427-1435, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Epstein- Barr virus ( EBV) infection is usually asymptomatic and persists lifelong. Although EBV-infected B cells have the potential for unlimited proliferation, they are effectively removed by the virus-specific cytotoxic T cells, and EBV-associated lymphoproliferative disease develops only in immunocompromised hosts. Rarely, however, individuals without apparent immunodeficiency develop chronic EBV infection with persistent infectious mononucleosis-like symptoms. These patients have high EBV-DNA load in the peripheral blood and systemic clonal expansion of EBV-infected T cells or natural killer ( NK) cells. Their prognosis is poor with life-threatening complications including hemophagocytic lymphohistiocytosis, organ failure, and malignant lymphomas. The term 'chronic active EBV infection' ( CAEBV) is now generally used for this disease. The geographical distribution of CAEBV is markedly uneven and most cases have been reported from Japan and other East Asian countries. Here we summarize the current understanding of CAEBV and describe the recent progress of CAEBV research in Japan. [ABSTRACT FROM AUTHOR]

Deregulation of nuclear factor (NF)-κB signalling is common in cancers and is essential for tumourigenesis. Constitutive NF-κB activation in extranodal natural killer (NK)-cell lymphoma, nasal type (ENKL) is known to be associated with aberrant nuclear translocation of BCL10. Here we investigated the mechanisms leading to NF-κB activation and BCL10 nuclear localization in ENKLs. Given that ENKLs are dependent on T-cell-derived interleukin-2 (IL2) for cytotoxicity and proliferation, we investigated whether IL2 modulates NF-κB activation and BCL10 subcellular localization in ENKLs. In the present study, IL2-activated NK lymphoma cells were found to induce NF-κB activation via the PI3K/Akt pathway, leading to an increase in the entry of G2/M phase and concomitant transcription of NF-κB-responsive genes. We also found that BCL10, a key mediator of NF-κB signalling, participates in the cytokine receptor-induced activation of NF-κB. Knockdown of BCL10 expression resulted in deficient NF-κB signalling, whereas Akt activation was unaffected. Our results suggest that BCL10 plays a role downstream of Akt in the IL2-triggered NF-κB signalling pathway. Moreover, the addition of IL2 to NK cells led to aberrant nuclear translocation of BCL10, which is a pathological feature of ENKLs. We further show that BCL10 can bind to BCL3, a transcriptional co-activator and nuclear protein. Up-regulation of BCL3 expression was observed in response to IL2. Similar to BCL10, the expression and nuclear translocation of BCL3 were induced by IL2 in an Akt-dependent manner. The nuclear translocation of BCL10 was also dependent on BCL3 because silencing BCL3 by RNA interference abrogated this translocation. We identified a critical role for BCL10 in the cytokine receptor-induced NF-κB signalling pathway, which is essential for NK cell activation. We also revealed the underlying mechanism that controls BCL10 nuclear translocation in NK cells. Our findings provide insight into a molecular network within the NF-κB signalling pathway that promotes the pathogenesis of NK cell lymphomas. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The oncogenic human herpes virus, the Epstein–Barr virus (EBV), expresses EBNA1 in almost all forms of viral latency. EBNA1 plays a major role in the maintenance of the viral genome and in the transactivation of viral transforming genes, including EBNA2 and latent membrane protein (LMP-1). However, it is unknown whether inhibition of EBNA1 from the onset of EBV infection disrupts the establishment of EBV’s latency and transactivation of the viral oncogenes. To address this, we measured EBV infection kinetics in the B cell lines BALL-1 and BJAB, which stably express a dominant-negative EBNA1 (dnE1) fused to green fluorescent protein (GFP). The EBV genome was surprisingly unstable 1 week post-infection: the average loss rate of EBV DNA from GFP- and GFP-dnE1-expressing cells was 53.4% and 41.0% per cell generation, respectively, which was substantially higher than that of an ‘established’ oriP replicon (2–4%). GFP-dnE1 did not accelerate loss of the EBV genome, suggesting that EBNA1-dependent licensing of the EBV genome occurs infrequently during the acute phase of EBV infection. In the subacute phase, establishment of EBV latency was completely blocked in GFP-dnE1-expressing cells. In contrast, C/W promoter-driven transcription was strongly restricted in GFP-dnE1-expressing cells at 2 days post-infection. These data suggest that inhibition of EBNA1 from the onset of EBV infection is effective in blocking the positive feedback loop in the transactivation of viral transforming genes, and in eradicating the EBV genome during the subacute phase. Our results suggest that gene transduction of GFP-dnE1 could be a promising therapeutic and prophylactic approach toward EBV-associated malignancies. ( Cancer Sci 2010; 101: 876–881) [ABSTRACT FROM AUTHOR]

With an increase in the importance of umbilical cord blood (CB) as an alternative source of haematopoietic progenitors for allogenic transplantation, donor lymphocyte infusion (DLI) with donor CB-derived activated CD4+ T cells in the unrelated CB transplantation setting is expected to be of increased usefulness as a direct approach for improving post-transplant immune function. To clarify the characteristics of activated CD4+ T cells derived from CB, we investigated their mRNA expression profiles and compared them with those of peripheral blood (PB)-derived activated CD4+ T cells. Based on the results of a DNA microarray analysis and quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR), a relatively high level of forkhead box protein 3 (Foxp3) gene expression and a relatively low level of interleukin (IL)-17 gene expression were revealed to be significant features of the gene expression profile of CB-derived activated CD4+ T cells. Flow cytometric analysis further revealed protein expression of Foxp3 in a portion of CB-derived activated CD4+ T cells. The low level of retinoic acid receptor-related orphan receptor γ isoform t (RORγt) gene expression in CB-derived activated CD4+ T cells was speculated to be responsible for the low level of IL-17 gene expression. Our data indicate a difference in gene expression between CD4+ T cells from CB and those from PB. The findings of Foxp3 expression, a characteristic of regulatory T cells, and a low level of IL-17 gene expression suggest that CB-derived CD4+ T cells may be a more appropriate source for DLI. [ABSTRACT FROM AUTHOR]

Neoplasm of follicular dendritic cells (FDC), follicular dendritic cell sarcoma (FDCS), is a rare tumor of intermediate to high-grade malignancy in lymph nodes and visceral organs. Reported herein is a case of FDCS arising from cervical lymph nodes in a 16-year-old Japanese boy, who died of the disease 3 years after diagnosis. The tumor cells were pale eosinophilic and elongated with euchromatic nuclei and were positive for CD21, clusterin, and CNA-42 on immunohistochemistry, as well as desmosome-like junctions on electron microscopy. The presence of microtubuloreticular structures (MTRS) in the tumor cells and associated lymphocytes characterized this case, suggesting some viral infection, although qualitative polymerase chain reaction of genomic and complementary DNA obtained from the tumor failed to demonstrate any viral infection at the laboratory level. The stimulation of dispersed tumor cells and peripheral blood mononuclear cells with mAb to CD3 and interleukin-2 was attempted; and the cell line established by the authors (FDCS-Sa) was stimulated with iododeoxyuridine. Virus-like particles (VLP) were successfully induced from each cellular source. The VLP, 100 nm in diameter, showed an electron-dense thorny envelope and granular core. This is the first case of FDCS with MTRS accompanying VLP production in vitro. [ABSTRACT FROM AUTHOR]

Nasal NK/T-cell lymphoma (NL) is a rare but clinically important entity of lymphoma. Its preferential incidence in Orientals but not Caucasians suggests possible genetic predisposition. 11q deletion is common in NL, indicating certain tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1), and its partner DAL-1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were detected in 2 NL and 4 of 8 (50%) of non-Hodgkin lymphoma (NHL) cell lines, but not in normal NK cells and normal PBMC. Absence of CADM1 protein was also detected in NL cell lines. 5-aza-2′-deoxycytidine (Aza) demethylation or genetic knockout of both DNMT1 and 3B genes restored CADM1 and DAL-1 expression. CADM1 methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly, DAL-1 was epigenetically inactivated in NL cell lines and virtually all the tumors with methylated CADM1. A significant correlation between the methylation of both genes was found ( p < 0.0001). Homozygous deletion of CADM1 was detected in only 3 of 18 (17%) of tumors. The stress-response of CADM1 was abolished when its promoter becomes methylated. Our results demonstrate a frequent, predominant epigenetic silencing of CADM1 and DAL-1 in NL, which likely play a synergic role in NL pathogenesis. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Omenn syndrome is a variant form of severe combined immunodeficiency. It is fatal unless treated by allogeneic stem cell transplantation (SCT), which is the only curative approach. However, both treatment-related complications and graft rejection are major obstacles to treatment success. This report describes a case with Omenn syndrome who developed mixed chimerism after unrelated cord blood transplantation (UCBT). This case was successfully treated by altering the patient's immunosuppression and donor lymphocyte infusion (DLI) with donor cord blood-derived activated CD4+ T cells ex vivo expanded from the cord blood cell residues in an infused bag. This novel development to expand CD4+ T-lymphocytes from the donor cord blood unit for the use of DLI would serve as a useful method to overcome the risk of graft rejection in SCT for primary immunodeficiency disorders with residual cell-mediated immunity without compounding graft-vs.-host disease, especially in the UCBT setting. [ABSTRACT FROM AUTHOR]

Nagasawa M, Zhu Y, Isoda T, Tomizawa D, Itoh S, Kajiwara M, Morio T, Nonoyama S, Shimizu N, Mizutani S. Analysis of serum soluble CD40 ligand (sCD40L) in the patients undergoing allogeneic stem cell transplantation: platelet is a major source of serum sCD40L.Eur J Haematol 2005: 74: 54–60.© Blackwell Munksgaard 2005.CD40 ligand (CD40L) is expressed not only on activated T cells but also on activated platelets. A soluble CD40 ligand (sCD40L) is released from the activated T cells and platelets by ill-defined proteolytic processin vitro. It has been reported that sCD40L is elevated in the serum of patients with systemic lupus erythematosus, unstable angina, essential thrombocythemia, and autoimmune thrombocytopenic purupura. However, source of sCD40Lin vivoremains to be elucidated. We investigated the serial sCD40L in the serum in patients undergoing allogeneic stem cell transplantation and compared with the platelets number and soluble IL2R, which is a marker of activated T cells. The value of sCD40L was well correlated with platelet number or thrombopoiesis. In cases of severe graft vs. host disease with markedly increased sIL2R, sCD40L was not increasedin vivo. These results indicate that sCD40Lin vivois released mainly from the platelets or in the process of platelet production but not from the activated T cells. [ABSTRACT FROM AUTHOR]

Summary. In this study, we describe the cytological and cytogenetic features of six Epstein-Barr virus (EBV)-infected natural killer (NK) cell clones. Three cell clones, SNK-1, -3 and -6, were derived from patients with nasal T/NK-cell lymphomas; two cell clones, SNK-5 and -10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK-11, was from a patient with hydroa vacciniforme (HV)-like eruptions. An analysis of the number of EBV-terminal repeats showed that the SNK cell clones had monoclonal EBV genomes identical to the original EBV-infected cells of the respective patients, and SNK cells had the type II latency of EBV infection, suggesting that not only the cell clones isolated from nasal T/NK-cell lymphomas but also those isolated from CAEBV and HV-like eruptions had been transformed by EBV to a certain degree. Cytogenetic analysis detected deletions in chromosome 6q in five out of the six SNK cell clones, while 6q was not deleted in four control cell lines of T-cell lineage. This suggested that a 6q deletion is a characteristic feature of EBV-positive NK cells, which proliferated in the diseased individuals. The results showed that EBV-positive NK cells in malignant and non-malignant lymphoproliferative diseases shared common cytological and cytogenetic features. [ABSTRACT FROM AUTHOR]

Chronic active Epstein–Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T / natural killer (NK)-cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK-cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein–Barr virus (EBV)-positive cells in the patient was of NK-cell origin. By means of high-dose recombinant interleukin-2, we established an EBV-positive cell line of NK-cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK-cell clones in the patient’s lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK-cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV-positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing serum granulysin as a possible biomarker of natural killer cell neoplasms is presented.

Granulysin is a newly identified CTL/NK cell-related cytotoxic protein, which is secreted in both constitutive and Ca-dependent manner. To evaluate its significance in stem-cell transplantation (SCT), serum granulysin was measured by newly established ELISA method in 26 patients undergoing SCT (21 allogeneic and 5 autologous). In the allogeneic SCT, granulysin was transiently increased in 3 weeks, which was not observed in autologous SCT. In acute GVHD, serum granulysin was markedly increased and correlated with the severity of GVHD. Elevation of granulysin was not necessarily associated with increase of sIL2R or IFN-gamma. In vitro, allospecific T cells released granulysin in an allo-specific manner, and it was correlated with allo-specific cytotoxic activity. These results indicate that increased release of granulysin presents alloreactivity and serum granulysin is useful as a marker of GVHD in SCT., (2006 Wiley-Liss, Inc.)

Recently, the involvement of Epstein-Barr virus (EBV) in hydroa vacciniforme (HV)-like eruptions has been suggested. To elucidate the role of EBV in this disease, we isolated EBV-infected cell clones from peripheral blood mononuclear cells (PBMC) and the skin lesions of a patient with HV-like eruptions; cells isolated from PBMC were designated SNK-12, and those from the eruption SNK-11. Both cells expressed CD16, CD56, and HLA-DR and had germline configurations of the T-cell receptor and the immunoglobulin genes, indicating that the cell clones were of NK cell lineage. The analysis of EBV terminal repeats indicated that the cells were monoclonal, had identical clonality, and originated from EBV-positive cells in the PBMC and eruption. Both clones expressed EBNA-1, but not EBNA-2. Although LMP-1 was weakly detected in SNK-11, no LMP-1 was detected in SNK-12. Interestingly, EBV-infected cells required less IL-2 for in vitro growth in the later phase of this disease and this appeared to correlate with the expression of LMP-1, suggesting that the proliferative capacity of the EBV-positive NK cells increased during the time course of the disease, and LMP-1 expression might be responsible for that. This is the first report of the isolation of EBV-infected cells from the skin lesions of HV-like eruptions and strongly suggests that the HV-like eruption in the patient was caused by clonal NK cells with latent EBV infection.