Showing papers by "Satoru Takahashi published in 1995"

The Yaa gene model of systemic lupus erythematosus.

Abstract: Discrimination between self and foreign structures operates through an active process that involves several different mechanisms including clonal deletion, clonal anergy and suppression. The failure of these regulatory mechanisms leads to the persistence and activation of potentially self-reactive cells and the development of autoimmune disorders. Such a situation occurs in the case of systemic lupus erythematosus (SLE). a severe chronic autoimmune disease in which antibodies are produced against self components and the resulting immune complexes are involved in the generation of various tissue lesions. Notably, glomerulonephritis, i.e. lupus nephritis, is the major cause of death in patients with SLE. Although the etiology and pathogenesis of SLE are still poorly understood, it is becoming clear that many genetic factors apparently play essential roles in SLE. The discovery of several murine strains that spontaneously develop an autoimmune syndrome resembling human SLE (Theofilopoulus & Dixon 1985) has allowed considerable progress in this field. In particular, these strains have been powerful tools to study the mechanisms by which genetic factors participate in the pathogenesis of SLE. Early genetic studies on New Zealand mice have demonstrated that many individual autoimmune traits segregate independently of each other (Shirai 1982, Izui et al. 1981, Raveche et al. 1981, Bocchieri et al. 1982). This suggests that there is no common genetic defect which causes a predisposition to overall autoimmune responses in the New Zealand strain. However, the clearest examples of the influence of single genes on the development and progression of murine SLE is the efTect of the lpr (lymphoproliferation) and gld (generalized lymphoproliferative disease) genes (Murphy & Roths 1978, Roths et al. 1984). Both mutations not only accelerate the progression of autoimmune

Transduction of LacZ gene into leukemia cells using viral vectors of retrovirus and adenovirus.

Abstract: Recent developments in gene therapy techniques enable us to introduce new genetic information into hematopoietic cells. Among the various techniques, we focused on two viral vector systems, one using a retrovirus and the other an adenovirus. By using an adenoviral vector we could transduce and highly express bacterial beta-galactosidase (LacZ) gene under the control of the CAG (cytomegalovirus enhancer with chicken beta-actin promoter) promoter in various hematopoietic cells, although the expression persisted for only two weeks. The retroviral vector (MFG) could transduce the LacZ gene into hematopoietic cells almost as well as the adenoviral vector using the repetitive infection protocol. The retroviral system could maintain the expression of transduced cells quite longer than the adenoviral system. Differential use of these two vector systems may be helpful for the gene transduction into various kinds of hematopoietic cells (Lin et al., manuscript in preparation).

Portal hypertension with intra- and extrasplenic arterial aneurysms and large venous varices.

Abstract: Imaging studies of two women with portal hypertension demonstrated multiple splenic artery aneurysms, splenomegaly, and large splenic vein varices with a spontaneous splenorenal shunt In each case, a large splenic hilar, as well as intrasplenic aneurysms were found along with portal vein pressures of about 15 mmHg Portal hypertension with splenomegaly might be an important factor in the pathogenesis of intra- and extraparenchymal splenic artery aneurysms

Multiple myeloma developing myelodysplastic syndrome with thrombocytosis

Abstract: A 64-year-old woman with multiple myeloma, IgG lambda type Durie-Salmon Stage II, was admitted because of gradually developing anemia and increased blasts with abnormal karyotype in her bone marrow after 10 years of treatment. The chromosomal analysis showed 44, XX, del(5q), del(7q), -9, add(12p), -21, typical of secondary MDS due to the cumulative alkylating agents. Thrombocytosis concomitantly occurred with emergence of chromosomal abnormality, but the serum interleukin 6 level was not elevated, which suggested that it was related to development of secondary MDS.