Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (Treg). Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for Treg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ Treg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased Treg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ Treg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of Treg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

Multiplicative error accounts for much of the size‐scaling and leptokurtosis in fluctuating asymmetry. It arises when growth involves the addition of tissue to that which is already present. Such errors are lognormally distributed. The distribution of the difference between two lognormal variates is leptokurtic. If those two variates are correlated, then the asymmetry variance will scale with size. Inert tissues typically exhibit additive error and have a gamma distribution. Although their asymmetry variance does not exhibit size‐scaling, the distribution of the difference between two gamma variates is nevertheless leptokurtic. Measurement error is also additive, but has a normal distribution. Thus, the measurement of fluctuating asymmetry may involve the mixing of additive and multiplicative error. When errors are multiplicative, we recommend computing log E(l) − log E(r), the difference between the logarithms of the expected values of left and right sides, even when size‐scaling is not obvious. If l and r are lognormally distributed, and measurement error is nil, the resulting distribution will be normal, and multiplicative error will not confound size‐related changes in asymmetry. When errors are additive, such a transformation to remove size‐scaling is unnecessary. Nevertheless, the distribution of l − r may still be leptokurtic. © 2003 The Linnean Society of London, Biological Journal of the Linnean Society, 2003, 80, 57–65.

CD10 and MUM1 are representative B cell differentiation markers. Follicular lymphoma (FL) is usually positive for CD10 and negative for MUM1. In this study, however, we compared 22 FLs with peculiar phenotype CD10 ؊ MUM1 ؉ with 119 typical CD10 ؉ MUM1 ؊ FLs. All CD10 ؊ MUM1 ؉ FL patients exhibited follicular structure with follicular dendritic meshwork, and a high rate of somatic hypermutation and ongoing mutation, similar to typical FL. However, CD10 ؊ MUM1 ؉ FLs were encountered frequently in the elderly compared with CD10 ؉ MUM1 ؊ typical FLs (67.0 versus 58.7 years, P < .01), showed high grade (grade 3A or 3B) morphology (91% versus 17%, P < .001), diffuse proliferation (59% vs 19%, P < .001), and lacked BCL2/IGH translocation (5% versus 92.5%, P < .001), which is the most characteristic aberration in FL, and 88% showed BCL6 gene abnormalities (translocation or amplification IntroductionFollicular lymphoma (FL) is the most prevalent form of low-grade B-cell lymphoma in adults. 1 Typically, FL cells express CD10, BCL2, and BCL6. CD10 is a marker for germinal center (GC) B cells, and thus its expression suggests that GC B cells are a normal counterpart of FL. 2 However, some reports, including our previous study, described the existence of CD10 Ϫ FL, especially in high-grade (grade 3) FL. [3][4][5][6] However, it is not clear whether CD10 negativity is just aberrant loss or whether it is meaningful, reflecting a specific differentiation stage and affecting clinical features. MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a lymphoid-specific member of the interferon regulatory factor family of transcription factors, 7-9 and it is a reliable marker of "late-stage GC" or "post-GC" B cells. 8 In this study, we clinicopathologically compared CD10 Ϫ MUM ϩ and "classical" CD10 ϩ MUM1 Ϫ FLs. Materials and methods Biologic materialTissue specimens were obtained from human lymph nodes filed at the Department of Pathology at Fukuoka University and Kurume University. The 147 FL patients have already been reported in our previous publication. 5 Paraffin-embedded tissues were available in almost all patients, while frozen tissues and cell suspensions were available in some patients. Histopathological diagnoses and grading were based on the new WHO classification and carried out by 4 pathologists (Y.G., K.K., M.K., and K.O.). 1 Clinical information was obtained by reviewing the tumor registry records and/or patients' medical charts. This study was approved by the Kurume University institutional review board (Kurume, Japan), and patients provided informed consent in accordance with the Declaration of Helsinki. ImmunohistochemistryParaffin sections from each sample were immunostained with monoclonal antibodies against CD10 (Novocastra, Newcastle, United Kingdom), Bcl2 (DAKO, Glostrup, Denmark), MUM1 (DAKO), CD21 (DAKO), CD138 (Novocastra), and Bcl6 (Novocastra) following the method described previously. 5 The following 2 categories were defined: negative (Ͻ 30% positively-stained tumor cells) and ...

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