Identification of differentially expressed molecules in adult T-cell leukemia cells proliferating in vivo

HTLV-I is the causative agent of adult T-cell leukemia (ATL). However, the precise mechanism underlying the neoplastic cell growth of ATL remains unclear. In this study, we established a leukemic cell line, termed SYK-11L(+), from tumor cells (S-YU) in an in vivo cell proliferation model of ATL using severe combined immunodeficiency (SCID) mice. Unexpectedly, SYK-11L(+) was found to have no tumorigenicity in SCID mice. Flow cytometric analysis showed that S-YU expressed cell adhesion molecules including CD44, ICAM-1 and OX40, whereas SYK-11L(+) had lost the expression of these molecules. The administration of anti-OX40 monoclonal antibody inhibited the engraftment of S-YU cells into SCID mice, suggesting that OX40 is a potential target for immunotherapy. Significant differences in responsiveness to IL-2 and IL-15 were observed between the two cell types. To better understand the molecular basis of tumorigenicity, cDNA microarray analysis was performed using tumorigenic S-YU and non-tumorigenic SYK-11L(+) cells. We obtained several candidate genes differentially overexpressed in S-YU compared with SYK-11L(+). Interestingly, one such gene, regulator of G protein signaling 1 (RGS1), was shown to be overexpressed in most ATL patients. Further characterization of the differentially expressed molecules, such as OX40 and RGS1, would provide useful information not only to elucidate the mechanism of ATL cell growth in vivo, but also to develop novel molecularly targeted therapies.     

Successful treatment of supraventricular tachycardia exhibiting hydrops fetalis with flecainide acetate. A case report

BACKGROUND: The efficacy of flecainide acetate for the treatment of fetal supraventricular tachycardia with hydrops fetalis and changes in venous blood flow patterns in the fetus during treatment are reported. CASE: Oral flecainide administration was started at 30 weeks of gestation. Cardioversion was achieved 6 days after treatment. Sustained abnormal venous Doppler indices were shown and complete normalization of venous returns was observed 6 days after cardioversion. A vigorous male baby was born, and he is now 1 year of age and in good condition with no medication. CONCLUSION: Reversible cardiac dysfunction was observed even after cardioversion in the fetus with supraventricular tachycardia, which could be assessed precisely by venous Doppler analysis.     

Advances in the development of a reliable assay for the measurement of stool decay-accelerating factor in the detection of colorectal cancer

We have previously shown that stool concentrations of decay-accelerating factor (DAF; CD55), a membrane-bound complement-regulatory protein, are significantly elevated in patients with colorectal cancer and that the measurement of stool DAF may be a valuable test for the detection of colorectal cancer. Accordingly, we are working to develop a clinically useful immunoassay for fecal DAF. A requirement for such assay is a plentiful and reliable supply of anti-DAF antibodies. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for DAF in stool specimens, using two monoclonal anti-DAF antibodies recognizing different epitopes on the DAF molecule. When we first used a biotin-labeled antibody and enzyme-linked streptavidin method, we often observed stool interference, probably due to the presence of a substance(s) with biotin activity which non-specifically bound to the Fc portion of IgG of the first anti-DAF antibody on the ELISA wells. By the use of inorganic salts in the sample-dilution buffer and HRP-labeled anti-DAF as second antibody, we circumvented the stool interference and established that the new ELISA system could reliably measure DAF at low concentrations in stool specimens. Because the new assay system uses only monoclonal antibodies, we can now consistently supply ample amounts of antibodies for routine measurement of stool DAF.     

Thrombocytopenia due to deficient platelet production

Impaired platelet production may result from four mechanisms: 1) marrow hypoplasia, 2) ineffective thrombopoiesis, 3) aberration of thrombopoietic regulation and 4) hereditary thrombocytopenia. Megakaryocytic hypoplasia(reduced numbers of megakaryocytes) is seen in a wide variety of disorders including aplastic anemia, radiation, drugs such as chemotherapeutic agents, infiltrative neoplasms of the marrow, acquired amegakaryocytic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria(PNH), and Fanconi's anemia. Ineffective thrombopoiesis(normal to increased numbers of megakaryocytes) is recognized in megaloblastic anemia and myelodysplastic syndrome. Disorders of thrombopoietic control are uncommon and seen in cyclic thrombocytopenia and thrombocytopenia with absent radii. Hereditary thrombocytopenia is overall a very rare disorder, and may be inherited as an X-linked recessive trait, an autosomal dominant trait, or autosomal recessive trait. It is important to recognize hereditary thrombocytopenia because clinically they resemble ITP, but the patients do not respond to steroid treatment or splenectomy.     

Autopsy case of microcephalic osteodysplastic primordial "dwarfism" type II

Microcephalic osteodysplastic primordial "dwarfism" (MOPD) is a group of disorders similar to Seckel syndrome. Three subtypes (types I-III) have been reported. We report here the first autopsy case of MOPD type II. The patient was a Japanese girl with typical clinical and radiological manifestations of MOPD type II. The manifestations included severe intrauterine and postnatal growth failure, microcephaly, a distinctive facial appearance, micromelia, brachytelephalangy, coxa vara, and V-shaped metaphyses of the distal femora. Other than small cerebral hemispheres, no neuropathological abnormalities were found. Chondro-osseous histology showed thinning of the growth plate, ballooned chondrocytes, reduced cellularity, lack of zonal and columnar formations, and poor formation of primary trabeculae. These findings suggest that impairment of chondrocytic formation and differentiation is the major pathogenesis of MOPD type II.     

Analysis of T-cell repertoire and mixed chimaerism in a patient with aplastic anaemia after allogeneic bone marrow transplantation

We analysed 26 T-cell receptor (TCR) beta chain subfamilies (VB) of a patient with aplastic anaemia (AA) who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed pancytopenia at d 80. The patient's T cells were skewed in 10 of 26 TCR-VB on d 83. These TCR-VB, especially VB15, which were almost entirely CD8-positive cells, were skewed throughout her clinical course. Chimaerism analysis of the CD8-positive cells indicated that they were of recipient origin. Therefore, some immune responses induced by the recipient CD8-positive T cells had an important role in pancytopenia in AA patients after allo-BMT.