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M Kusaka

Publications and source records attributed to M Kusaka.

123 records · Page 7Linked to original sources
PubMedDate not supplied

Gene expression profile in rat renal isografts from brain dead donors.

BACKGROUND: Brain death (BD) and the subsequent ischemia/reperfusion (I/R) injury have cardinal implications for the pathogenesis of kidney transplantation (Tx). However, the precise mechanistic pathway of BD and the subsequent I/R injury are unknown. In this study, we performed genome-wide analysis for differential gene expression in kidney isografts from BD donors. Their gene expressions were compared with those from living sources. METHODS: Kidneys from BD rats were engrafted and their gene expressions were compared with those from living controls. Donors were intubated, and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and 1 hour after engraftment. The expression profile of approximately 20,500 genes was analyzed. RESULTS: Gene expression of chemokines (Scya2 and Gro1), cytokines (IL-1 and -6) and adhesion molecules (E- and P-selectin and ICAM-1) were upregulated in the BD kidneys and 1 hour after engraftment. An antiapoptotic gene (Birc2), IkappaB-zeta, and protective gene (HO-1) were also upregulated. Other upregulated genes included oncogenes (lipocalin2, Bcl3, and CCAAT/enhancer binding protein delta), Calgranulin B, DEXRAS1, insulin-like growth factor binding protein-1, inhibin beta-B-subunit gene, IgG Fc receptor, and FK 506 binding protein 5. We also observed downregulation of the genes Amphiphsin, Jagged 1, Pace 4, Slc15a2, Kcnn2, and gap junction membrane channel protein alpha5 only in kidneys from BD donors. CONCLUSIONS: This is the first demonstration of global gene expression analysis using the rat brain-death isograft model. These results provide new insights for the detection of novel target genes for treatment and prognosis of grafts from brain-dead and extended marginal donors.

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PubMedDate not supplied

IP-10, apoptotic genes, and calcineurin subtype messenger RNA kinetics occurring in rat renal isografts from brain-dead donors.

BACKGROUND: Brain death (BD) and following ischemia/reperfusion(I/R) injury has cardinal implications in kidney transplantation (Tx). We hypothesize that inflammation, apoptosis, and drug nephrotoxicity are central mechanisms leading to initial organ damage in transplantation from BD donors. In this study, the gene kinetics of a chemokine (IP-10), an apotosis-related gene, and of calcineurin (Cn) subtype were compared using kidney isografts from BD versus living donors. METHODS: Donors were intubated and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and at 1, 6, and 24 hours and 5 days after engraftment. Messenger RNA (mRNA) expression was assessed using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Gene expression of IP-10 was up-regulated only among BD donor kidneys, particularly following I/R injury. These changes recovered to baseline levels thereafter. Bcl-2 was suppressed within 6 hours of BD and 1 hour after engraftment. In contrast, Bax in kidneys from BD donors was significantly up-regulated at 6 hours after engraftment. These changes were minimal in the controls. Cn Aalpha and Abeta were decreased in kidneys from BD donors before and within 1 hour after engraftment. However, these differences became insignificant thereafter. CONCLUSIONS: Marked up-regulation of IP-10 may predict the initial graft injury and the onset of delayed graft function. Apoptotic gene changes may lead kidney grafts to a preapoptotic condition and up-regulate renal toxicity caused by Cn inhibitors. This initial antigen-independent donor circumstance may be one risk factor for chronic rejection.

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A case of high-grade endometrial stromal sarcoma arising from endometriosis in the cul-de-sac.

This report describes a rare case of high-grade endometrial stromal sarcoma (ESS) arising from pathologically confirmed endometriosis in the cul-de-sac. A 37-year-old woman presented with irregular menstruation, pelvic pain, and diarrhea. Magnetic resonance imaging and colon biopsy suggested endometriotic nodule of the cul-de-sac. The tumor size was reduced with hormonal therapy, and the residual tumor was excised, resulting in the pathologic diagnosis of endometriosis. Two years later, a soft mass reappeared with rapid growth. Tumor extraction was performed, and the histopathologic diagnosis was high-grade ESS. Neither hormonal therapy nor chemotherapy was effective, and the patient died 6 months postoperatively. ESS should be included in the differential diagnosis of malignant transformation of endometriosis.

Adult↗
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Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients.

The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25- T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123). Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:1/4 to 1/2. In addition, Treg dominancy of FoxP3 and CTLA-4 expression and Tneg dominancy of CD132 expression found in HD were lost in SIL. These results indicated that the Treg fraction in SIL may be substituted with chronically activated T cells due to recurrent exposure to silica, resulting in a reduction in the frequency and function of Treg. Since the reduction of Treg may precede the clinical manifestation, as silicosis may be a pre-clinical status for autoimmune diseases, control of Treg function using cell and/or gene therapy may be a good way to manage autoimmune disease.

Aged↗
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Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases.

To explore the effects of asbestos and silica on the human immune system, an experimental model of low-dose and long-term exposure was established using a human HTLV-1-immortalized polyclonal T cell line, MT-2 (MT-2Org). MT-2 cells were continuously exposed to asbestos at a concentration (10 microg/ml) which does not induce complete cell death during short-term exposure. After acquiring resistance to CB-induced apoptosis (designated MT-2Rst), an immunological comparison was made between the MT-2Org and MT-2Rst lines in terms of T cell receptor-Vbeta (TcR-Vbeta) expression. MT-2Rst cells showed excess expression of various TcR-Vbeta, although TcR-Vbeta-overpresenting cells were characterized as undergoing apoptosis due to first contact with CB. Patients with asbestos-related diseases (ARD), such as asbestosis and malignant mesothelioma, were compared with silicosis (SIL) patients as a disease control and with healthy donors (HD). SIL and ARD not only differed in their causative materials, silica and asbestos as mineral silicates, but also in terms of complications; autoimmune disorders in SIL and tumors in ARD. ARD patients showed a restricted overpresentation of TcR-Vbeta without clonal expansion, whereas SIL patients revealed significant overpresentation of TcR-Vbeta 7.2. These experimental and clinical analyses indicate the superantigenic and dysregulation of autoimmunity-inducing effects of asbestos and silica, respectively.

Adult↗
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Local etoposide injection for treatment of tubal pregnancy with cardiac activity.

Etoposide was injected locally under sonographic management for the treatment of tubal pregnancy with cardiac activity in the distal region of the tube; the serum beta-hCG level was 14,000 mIU/mL. Two doses of 50 mg each, three days apart, were employed. No side effects appeared either during or after the treatment. Hysterosalpingography performed 1 month 3 weeks after treatment demonstrated the patency of the affected tube. Local etoposide instillation may be an option in the management of unruptured ectopic pregnancies, even in the presence of fetal cardiac activity and high trophoblastic activity.

Adult↗
PubMedDate not supplied

Effect of recombinant human granulocyte colony-stimulating factor on variations of morphologically identifiable bone marrow cells in myelosuppressed mice.

To examine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophilic recovery after cytotoxic agents, the variations of marrow colony-forming units of granulocytes and macrophages (CFU-GM) and morphologically identifiable bone marrow cells were investigated in cyclophosphamide (CPA)-treated mice. In mice treated with CPA at 200mg/kg intraperitoneally (day 0), marked decreases in peripheral neutrophils and nucleated cells in the femur were observed. In the femur of mice treated with CPA, the greatest depression in number occurred firstly with CFU-GM and the most immature granulocytes, such as myeloblasts and promyelocytes, followed in turn by myelocytes, metamyelocytes and mature neutrophils. Administration of rhG-CSF for four successive days (days 1-4) after CPA treatment completely prevented the neutropenia. In the femur, rhG-CSF enhanced the recovery of progenitors and immature granulocytes from their depression in the order of their differentiation, and recovery of marrow neutrophils was also promoted. From these studies, we confirmed that rhG-CSF effects an increase in peripheral neutrophils by enhancing the proliferation and differentiation of CFU-GM and immature marrow granulocytes.

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