Biomedical subjects

Shinichiro Machida

Publications and source records attributed to Shinichiro Machida.

4 recordsLinked to original sources

PubMed2005

Factor XI deficiency with a novel homozygous mutation Trp599Arg near the C-terminal region.

We identified a novel mutation in an asymptomatic 72-year old Japanese woman with severe factor XI (FXI) deficiency. Sequence analysis showed a homozygous missense mutation Trp599Arg (g.234T-->C according to Genbank accession number M20218). This residue belongs to a region conserved in human FXI and the FXI of several animals. Molecular modeling showed that the Trp599 residue is positioned in an alpha helix in the C-terminal region of the FXI molecule.

Aged↗

PubMed2004

A non-immunological phospholipid-dependent coagulation inhibitor associated with IgGlambda-type multiple myeloma.

We investigated the rare case of a patient with IgGlambda multiple myeloma for whom both prothrombin time and APTT were significantly prolonged. The IgG inhibited coagulation reactions upstream from prothrombin when coagulation was initiated by mRVVT, but not by FXa, as indicated by a chromogenic substrate for FXa. The mPT and the mAPTT showed inhibition of FXa generation in both the intrinsic and extrinsic pathways. The IgG inhibited both protein C (indicated by APTT) and FX (indicated by RVV) but not amidolysis for either activated protein C or FXa. The addition of excess phospholipid significantly shortened the prolonged RVVT of the patient. It inhibited the coagulation reactions of normal plasma and was dependent on decreasing the PS concentration in the APTT reagent. It was suggested that the IgG showed lupus anticoagulant (LA)-like activity that inhibited phospholipid-dependent coagulation reactions in the intrinsic, extrinsic, and common pathways. However, the IgG did not bind cardiolipin-beta2GPI complex, beta2GPI, or prothrombin in ELISA assays. The IgG did not bind to either PS or phospholipid complexes in the presence or absence of prothrombin, FX, or FXa. Interestingly, the IgG lost its LA like-activity when it was degraded to F(ab')2 and Fc fragments by pepsin. We suspected that the IgG might inhibit the interaction between coagulation factors and acid phospholipid non-immunologically and that this process requires an intact IgG conformation, although the reaction mode is still not clear.

Blood Coagulation↗

PubMed2004

Imatinib mesylate-sensitive blast crisis immediately after discontinuation of imatinib mesylate therapy in chronic myelogenous leukemia: report of two cases.

Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate-resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re-introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression.

Aged↗

PubMed2004

[Remission induction of refractory diffuse large B-cell lymphoma with allogeneic peripheral blood stem cell transplantation followed by interferon-alpha and donor lymphocyte infusion].

Graft-versus-lymphoma (GVL) effect has been described in patients with malignant lymphoma after allogeneic stem cell transplantation (alloSCT). The effect of interferon-alpha (IFN-alpha) on the GVL effect still remains unclear. Here we report on a 29-year-old woman with refractory diffuse large B-cell lymphoma (DLBL). Her clinical findings included multiple masses in the liver, stomach, bilateral kidneys, thyroid, vertebral bones and a bulky mediastinal mass. Since the patient did not respond to various combination chemotherapies and further developed superior vena cava syndrome, allogeneic peripheral blood stem cell transplantation (PBSCT) from a HLA-identical brother was carried out after a myeloablative TBI/CY-based conditioning regimen. DLIs have been also performed every 4 weeks since day +14. As a result, the lymphoma masses showed a partial response. In order to enhance the GVL effect, IFN-alpha was further given at a maximum of 3 MU four times per week. Although the patient only experienced graft-versus-host disease of the skin (grade II) even after both DLIs and IFN, complete clinical remission was observed. 200 days after transplantation, the patient is still disease-free and in good condition. This report suggests the curative potential of IFN-alpha combined with DLI after allogeneic SCT in refractory DLBL.

Adult↗