Biomedical subjects
Publications and source records attributed to H Kanamori.
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The digital imaging and communications in medicine (DICOM) standard proposed the grey-scale standard display function (GSDF) as a calibration tool for making the gradation characteristic of a radiographic output image consistent. This is designed in such a manner that the contrast visually recognised by observers (called psychophysical contrast) becomes a constant for all digital driving levels. The DICOM standard calls such an ideal characteristic perceptual linearisation. The psychophysical gradient that can express the psychophysical contrast was introduced for the evaluation of the GSDF using a liquid crystal display monitor. Investigations regarding its ability to yield a constant psychophysical contrast, independent of the digital driving level change and under an actual observation environment, such as for clinical radiographic diagnosis in hospital, were carried out. The psychophysical gradients of the GSDF were obtained for two kinds of observation environment: one was a restricted environment such as in a dark room, under steady-state adaptation, using the sinusoidal grading pattern corresponding to the peak frequency of the human eye response. The other was an actual environment reflecting that encountered during clinical diagnosis in a hospital. As a result, the psychophysical gradient under the restricted environment became almost constant and independent of the change in digital driving level, i.e. perceptual linearisation could be satisfied. Furthermore, under the actual observation environment, the psychophysical gradient decreased gradually with the increase in digital driving level, i.e. the perceptual linearisation could not be satisfied. The percentage decrease in the value of the psychophysical gradient at the maximum luminance area was approximately 60% compared with that at the minimum luminance area. Accordingly, the GSDF is unsuitable as a calibration tool for the liquid crystal display monitor, which will be used in actual clinical diagnosis, as it cannot achieve 'perceptual linearisation' under the actual environment. For the purpose of clinical diagnosis, it is necessary to enlarge the physical gradient of GSDF further in the high digital driving level range (which relates to a high luminance area) to give an approximation that is as close to the idealised form as possible.
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Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.
We analyzed 24 T-cell receptor (TCR)beta chain subfamilies (Vbeta) and the chimerism of a patient with chronic myelogeneous leukemia who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed liver dysfunction at day 19 leading to worsening of his condition. He died on day 91 of hepatic failure. Complete donor chimerism was observed after day 19. The average complexity score of TCR-Vbeta, which was low on day 19 (5.50), because much lower on day 82 (3.77). The average value of normal volunteers is 7.69. Neither immunosuppressive therapy nor antiviral therapy was effective to treat his hepatic dysfunction. A liver specimen at autopsy showed necrotic tissue with invasion of lymphocytes under the endothelial cells of the bile ducts. These findings suggest that the liver dysfunction was due to graft-versus-host disease (GVHD). Careful monitoring of chimerism and TCR-Vbeta complexity may help to predict the prognosis of GVHD after allogeneic BMT.
In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.
A 37-year-old Japanese man with systemic hemochromatosis due to multiple transfusions was referred to us for the treatment of severe aplastic anemia (SAA), from which he had been suffering for 24 years. The patient had diabetes arising from the hemochromatosis, chronic anal fissures, and a kidney abscess due to neutropenia. He was treated with a nonmyeloablative preconditioning regimen followed by non-T-cell-depleted (non-TCD) allogeneic peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical 2-loci-mismatched sibling. Prompt engraftment of granulocytes and platelets was observed, and graft-versus-host disease was easy to control. Noninherited maternal antigens in the donor were confirmed prior to PBSCT, and they were also detected in small quantities in the recipient. This report describes the first successful nonmyeloablative hematopoietic stem cell transplant in a heavily transfused SAA patient from an HLA-haploidentical 2-loci-mismatched sibling donor. The result suggests that a long-term fetomaternal microchimerism-positive sibling can be a second-line donor if an alternative HLA-identical donor is not available.
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We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.
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Focal adhesions (FAs) are essential structures for cell adhesion, migration, and morphogenesis. Integrin-linked kinase (ILK), which is capable of interacting with the cytoplasmic domain of beta1 integrin, seems to be a key component of FAs, but its exact role in cell-substrate interaction remains to be clarified. Here, we identified a novel ILK-binding protein, affixin, that consists of two tandem calponin homology domains. In CHOcells, affixin and ILK colocalize at FAs and at the tip of the leading edge, whereas in skeletal muscle cells they colocalize at the sarcolemma where cells attach to the basal lamina, showing a striped pattern corresponding to cytoplasmic Z-band striation. When CHO cells are replated on fibronectin, affixin and ILK but not FA kinase and vinculin concentrate at the cell surface in blebs during the early stages of cell spreading, which will grow into membrane ruffles on lamellipodia. Overexpression of the COOH-terminal region of affixin, which is phosphorylated by ILK in vitro, blocks cell spreading at the initial stage, presumably by interfering with the formation of FAs and stress fibers. The coexpression of ILK enhances this effect. These results provide evidence suggesting that affixin is involved in integrin-ILK signaling required for the establishment of cell-substrate adhesion.
Nonstructural (NS) proteins of hepatitis C virus (HCV) play major roles in viral replication and the pathogenesis of liver diseases. Current studies on antiviral strategies targeting these proteins have been hampered by the lack of efficient cell culture systems. Combining tetracycline-regulated gene expressing system and enhanced green fluorescent protein (EGFP), we generated a human hepatoma cell line inducibly expressing the HCV NS proteins. This cell line exhibited high induction of a full NS transcript ( approximately 7 kb). In the absence of tetracycline, NS proteins 3, 4A, and 5A of mature sizes were detected by immunoblot analysis and the induction of NS proteins 3 to 5B are confirmed by immunofluorescent staining. Using DNA microarray analysis, we characterized the changes in mRNA expression profile of 6416 genes and identified several genes, whose mRNAs are specifically upregulated by the induction of NS proteins. This cell line provides a unique in vitro hepatoma cell system for the investigation of structural and functional properties of HCV NS proteins.
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We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case.