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BDV naturally infects horses and sheep, and causes sporadic neurological disease. Serological evidence suggests an association of BDV, or a related virus, with specific psychiatric diseases in humans. Here, by using a nested RT-PCR technique, we demonstrate that human BDV RNA is present in the PBMC of psychiatric patients. In an examination of a total of 60 patients from 5 wards of a hospital in Japan, the detection rate differed within each ward, ranging from 8% to > 50% (37% on the average). Of particular note was the finding that the human derived BDV sequences, which included deleted forms in about 23% of the positive samples, were slightly different from those derived from horse BDV. These results suggest urgent consideration of the measures to be taken to cope with the effects of blood transfusion. In addition, the detection of a high level of BDV in the PBMC of patients will help our understanding of the pathogenesis in the disease.

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Overexpression of high mobility group AT-hook 2 (HMGA2) is found in a number of benign and malignant tumors, including the clonal PIGA ؊ cells in 2 cases of paroxysmal nocturnal hemoglobinuria (PNH) and some myeloproliferative neoplasms (MPNs), and recently in hematopoietic cell clones resulting from gene therapy procedures. In nearly all these cases overexpression is because of deletions or translocations that remove the 3 untranslated region (UTR) which contains binding sites for the regulatory micro RNA let-7. We were therefore interested in the effect of HMGA2 overexpression in hematopoietic tissues in transgenic mice (⌬Hmga2 mice) carrying a 3UTR-truncated Hmga2 cDNA. IntroductionParoxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by clonal expansion of a hematopoietic cell that lacks glycosyl phosphatidylinositol (GPI)-linked proteins because of a somatic mutation in the X-linked PIGA gene, which is essential for the synthesis of GPI-anchors (PNH cell). 1 The deficiency of GPI-linked proteins accounts for some features of the clinical phenotype such as intravascular hemolysis and hemoglobinuria but a major unanswered question concerns the mechanism underlying the clonal expansion of the mutated hematopoietic stem or early progenitor cell necessary for the development of disease. [2][3][4][5] A possible clue to the mechanism came from the observation that the HMGA2 gene was rearranged and the mRNA highly expressed, in the PNH cells of 2 patients, suggesting that in addition to the PIGA gene mutation an additional genetic event is required to confer a growth advantage to the PNH clone (two-hit-hypothesis). 6 We were thus interested in investigating the consequences of HMGA2 overexpression on hematopoiesis.The high mobility group AT-hook 2 (HMGA2) protein is a member of the HMGA family of nonhistone chromatin proteins, which also includes HMGA1a, HMGA1b, and HMGA1c. 7 Exons 1 to 3 of the HMGA2 gene encode DNA-binding AT-hook domains, which can modulate transcription by affecting the DNA conformation of specific AT-rich regulatory elements promoting transcriptional activity. Exon 4 acts as a linker, and exon 5 encodes the acidic C-terminal domain of the protein and the 3Ј untranslated region (UTR) of the mRNA. 8,9 The HMGA2 protein is important in a wide spectrum of biologic processes, including cell proliferation, cell-cycle progression, apoptosis, and senescence, 10,11 and is thought to play a crucial role in self-renewal and control of differentiation of embryonic stem (ES) cells, 12 cancer stem cells, 13 and neural stem cells. 14 The HMGA2 protein is expressed highly during embryogenesis but only at very low levels in normal adult tissues. 8 However, high levels of HMGA2 are found in various benign and malignant tumors, in particular those of mesenchymal origin, and are thought to contribute to transformation in these tumors. 7,10,11 In most cases these tumors harbor a rearrangement of chromosome 12q13-15, the location of the HMGA2 gene, causing a deletion of the HMGA2 3ЈUTR, ...