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Biomedical subjects

T Miyazaki

Publications and source records attributed to T Miyazaki.

At least 127 records · Page 7Linked to original sources
PubMed2000

Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis.

OBJECTIVE: To clarify the mechanism by which osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear factor kappaB ligand (RANKL)/osteoclast differentiation factor (ODF). METHODS: Osteoclast formation was evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood mononuclear cells (PBMC) in the presence of macrophage colony stimulating factor and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) utilizing separating membrane filters. RANKL/ODF expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with giant cell tumor (GCT), osteosarcoma (OS), and osteoarthritis (OA). RANKL/ODF expression and the ability of synovial fibroblasts to support osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1,25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) were measured by enzyme-linked immunosorbent assay. The effects of OPG/OCIF on the osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. RESULTS: Synovial fibroblasts did not induce osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced osteoclastogenesis in the presence of 1,25(OH)2D3, which was accompanied by up-regulated expression of RANKL/ODF and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG/OCIF. CONCLUSION: RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing osteoclastogenesis and would therefore be a good therapeutic target.

Arthritis, Rheumatoid↗
PubMed2000

Treatment with a metallic endovascular stent in a patient with iliac venous stenosis due to endometrial cancer.

There are few cases, to our knowledge, that report the successful treatment of iliac venous stenosis due to gynecologic malignancies with the use of self-expanding metallic endovascular stents. Our patient, who had right lower limb edema, had iliac lymph node metastases which caused iliac vein stenosis by direct invasion from endometrial cancer. The patient was not considered to be a good surgical candidate. A 10-mm diameter self-expanding metallic endovascular stent was placed in the external iliac vein. The patient's symptoms of right lower limb edema improved dramatically, and she was discharged at 3 weeks after stent placement. The patient had no further symptoms, with continued resolution of the right leg edema during the 10 months following stent placement, at which time she died from the primary disease. The treatment to this patient with a self-expanding metallic endovascular stent proved to be very efficacious and less stressful than direct venous reconstruction or femorofemoral venous bypass grafting. In addition, this procedure dramatically improved the patient's quality of life.

Aged↗
PubMed2000

Aspergilloma: comparison of treatment methods and prognoses.

We report five cases of aspergilloma. Three patients had a previous history of tuberculosis, including one who fully recovered after resection of the right lower lobe. Four patients were treated mainly with oral itraconazole. Two of these four patients, died, one of massive hemosputa, and one of heart valve disease, while two had a good outcome, although one of them has since developed respiratory insufficiency and has received oxygen therapy. In itraconazole therapy, the daily dose may be 200 mg or more, and the duration of treatment may be 1 year or more. Percutaneous intracavitary instillation of amphotericin B, performed in one patient, showed no efficacy. The efficacy of this treatment may depend on the width and number of drainage bronchi, and on the mechanism of acceleration of degradation of the fungus ball. It is important to carefully choose the therapy for aspergilloma, with due consideration being given to the patient's pulmonary function and general status.

Administration, Oral↗
PubMed2000

B2 exon splicing of nonmuscle myosin heavy chain IIB is differently regulated in developing and adult rat brain.

Two isoforms of nonmuscle myosin heavy chain IIB (MHC-IIB) are generated by alternative splicing; MHC-IIB(B2) differs from MHC-IIB(DeltaB2) by the insertion of B2 exon cassette near the actin binding region. Here we examined expressions of the two splice variants in developing and adult rat brains by in situ hybridization with isoform-specific oligonucleotide probes. In adult, MHC-IIB(DeltaB2) mRNA was highly expressed in neurons of the cerebral cortex, hippocampus, and cerebellum, whereas MHC-IIB(B2) mRNA was mainly distributed in the brainstem and cerebellum, with the highest level in Purkinje cells. During development, MHC-IIB(DeltaB2) mRNA was predominantly expressed in various regions of embryonic and neonatal brains, whereas MHC-IIB(B2) mRNA was low during embryonic stages. Up-regulation of MHC-IIB(B2) started in the cerebellum during early postnatal stages when dendritogenesis and synaptogenesis occur actively in Purkinje cells. We further employed immunofluorescence using two antibodies (one recognizing both splicing variants and another specific to MHC-IIB(B2)), and found similar and dense localization in cell bodies and dendrites of Purkinje cells. Therefore, splicing of the B2 exon cassette undergoes distinct temporal and spatial regulations in the brain in vivo, and the different exon usage seems unlikely to affect the somato-dendritic localization of MHC-IIB.

Alternative Splicing↗
PubMed2000

Relationship between indoor and outdoor carbonaceous particulates in roadside households.

Concentrations of particulate matter (PM) and carbonaceous particulates in indoor and outdoor air at roadside private households were measured in Osaka, Japan. The particulate samples were collected on filters using a portable AND sampler capable of separating particles into three different size ranges: over 10 microm, 2-10 microm (coarse) and below 2 microm (fine) in aerodynamic diameter. The filters were weighed and then analyzed for elemental carbon (EC) and organic carbon (OC) by thermal oxidation using a CHN CORDER. The results showed that indoor fine PM concentration is considerably affected by fine EC and the fine EC in indoor air is significantly correlated to that in outdoor air, r=0.86 (n=30, p<0.001). A simple estimation from EC content ratio in diesel exhaust particles indicated that about 30% of indoor particulates of less than 10 microm (PM10) were contributed from diesel exhaust. Additionally, the size characteristics of outdoor PM at roadside and background sites were examined using Andersen Cascade Impactors.

Journal Article↗
PubMed2000

Sibling incest and formulation of paternity probability: case report.

Paternity determination of a fetus whose mother was admitted to an institution for the welfare and health of handicapped persons was requested of us by a doctor and lawyer of the institution. The fetus was recovered by a legal artificial abortion based on the Act on Maternity Health and Welfare (Japan) with the permission of the custodian. Commercially available MCT118, HLADQA, PM, and 9 STRs were tested for DNA samples from the fetus, the mother, her younger brother, her father, her grandfather, and 4 staff members of the institution. Only the brother was not excluded and the paternity probability was estimated at 99.857% on the basis of newly formulated expressions for multiallelic loci on the assumption of sibling incest. We concluded then that the fetus was fathered by the brother. DNA fingerprinting with multilocus and single locus minisatellite probes which were performed to confirm the paternity also support the conclusion. Bandsharing frequencies between the family members, however, did not necessarily reflect their actual kinship, which findings suggest that multilocus DNA fingerprinting requires further accumulation of data for consanguineous cases such as incest. Universal formulation for calculating paternity probability for a sibling incest case on the basis of multiallelic monolocus polymorphisms is also presented.

Journal Article↗
PubMed2000

Stromal cells in lymph nodes attract B-lymphoma cells via production of stromal cell-derived factor-1.

Stromal cell-derived factor-1 (SDF-1) is a chemokine produced by bone marrow stromal cells which plays an important role in B-lymphopoiesis and the homing of hematopoietic stem cells to the bone marrow. In the present study, we investigated the role of SDF-1 and its receptor, CXCR4, in the chemotactic interaction between non-Hodgkin B-lymphoma cells and lymph node stromal cells. SDF-1 mRNA was abundantly expressed in stromal cells isolated from the lymph nodes of patients with malignant lymphoma. All B-lymphoma cells freshly isolated from these patients and most laboratory B-lymphoma cell lines, including follicular, diffuse large, and Burkitt's lymphoma cells, expressed surface CXCR4 and migrated in the presence of recombinant human SDF-1alpha. Chemotaxis assays revealed that CXCR4-positive (but not CXCR4-negative) B-lymphoma cells migrated towards lymph node stromal cells, and this migration was almost completely inhibited by the addition of anti-CXCR4 monoclonal antibody to the lymphoma cells or of anti-SDF-1 neutralizing antibody to the culture supernatant of the stromal cells. Down-regulation of surface CXCR4 was detected in B-lymphoma cells which migrated towards the stromal cells but not in those which showed no migratory response. In addition, contact between the lymphoma cells and the stromal cells resulted in down-regulation of surface CXCR4 on the lymphoma cells. These data strongly suggest that SDF-1/CXCR4 is the main chemokine system involved in the chemotactic interaction between B-lymphoma cells and lymph node stromal cells.

Antibodies, Monoclonal↗
PubMed2000

HLA-mismatched CD34-selected stem cell transplant complicated by HHV-6 reactivation in the central nervous system.

We report here a patient who suffered from PCR- confirmed human herpesvirus type 6 (HHV-6) meningoencephalitis after allogeneic purified CD34+ cell transplantation from his HLA-mismatched sibling donor, even though he had been on intense prophylaxis with i.v. ganciclovir (GCV), acyclovir (ACV) and gamma-globulin containing a specific antibody against HHV-6. Serological evaluation disclosed that both the donor and recipient had IgG antibody against HHV-6 before transplantation. His blood WBC count started to transiently increase on day 10, and all blood components had decreased by day 20. He then developed a severe headache and high blood pressure, and sporadic abnormal neurological findings including nystagmus and delirium. An analysis of cerebrospinal fluid (CSF) revealed 8 cells/microl, a glucose level of 130 mg/dl and a protein level of 201 mg/dl (normal, 50 mg/dl) on day 26. At the time, HHV-6 was detected only in CSF by a PCR-based method and he was diagnosed as having meningoencephalitis due to the local reactivation of HHV-6. Although he failed to respond to high-dose therapy with ACV (60 mg/kg/day) and gamma-globulin, the DNA of this virus disappeared from the CNS upon treatment with GCV (30 mg/kg/day) combined with the intraventricular infusion of alpha-interferon. His clinical course was further complicated with meningoencephalitis due to staphylococcus epidermidis, and he died of tentorial herniation on day 79 without the recovery of blood components. This experience may indicate that intense prophylaxis to prevent reactivation of HHV-6 in the CNS is essential for the management of such profoundly immunosuppressed patients.

Acyclovir↗
PubMed2000

Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan.

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Intraplacental choriocarcinoma with fetomaternal transfusion.

Intraplacental choriocarcinoma is very rare, and is usually found only after maternal and fetal metastatic disease is identified. The purpose of this case report is to review the incidence and findings of intraplacental choriocarcinoma. A term placenta was investigated because the newborn was born with severe anemia (Hb 3.0 g/dL). A 2 cm nodule was noted on the surface of the amniotic membrane and grossly resembled an infarction. The tumor was examined microscopically with immunohistochemical staining for the alpha- and beta-human chorionic gonadotropin (alpha-hCG, beta-hCG) subunits, human placental lactogen (hPL) and Ki-67. Microscopically, the tumor consisted of necrotic areas with proliferation of atypical trophoblastic cells and destruction of the villi and capillaries. The cells were positive for the alpha-hCG, beta-hCG subunits, hPL and Ki-67, consistent with intraplacental choriocarcinoma. The mother and newborn were investigated for the presence of metastatic disease. Computed tomography scans and magnetic resonance imaging of the mother and infant were negative for metastatic disease. Choriocarcinoma, limited only to the placenta with no evidence of metastatic disease is very rare. Primary intraplacental choriocarcinoma may frequently be overlooked or missed, and choriocarcinoma may possibly arise in the placenta more often than in retained or persistent trophoblast following pregnancy.

Adult↗
PubMed2000

Electrophysiologic findings of a patient with inappropriate sinus tachycardia cured by selective radiofrequency catheter ablation.

Radiofrequency catheter ablation (RFCA) for inappropriate sinus tachycardia (IST) is associated with a high recurrence rate and sometimes requires pacemaker implantation, especially after extensive ablation. We report a patient with drug-refractory IST who was successfully treated by selective RFCA to the 2 earliest activation sites. During tachycardia, the earliest atrial activation preceded the surface P wave by 50 ms or more, whereas it was only 27 ms for the rest of the right atrium after ablation. Our patient had the longest activation period during tachycardia among the reported patients. In IST patients, a longer activation time at the site of the earliest atrial activation may imply that the abnormality is confined to a small area within the sinus node and may predict the efficacy of selective RFCA.

Adult↗
PubMed2000

Effect of uric acid on liver injury during hemorrhagic shock.

BACKGROUND: It remains unproven whether nitric oxide (NO) exerts a toxic effect on hepatocytes directly or through the formation of a more toxic compound during hemorrhagic shock (HS). NO reacts at a very high rate constant with superoxide to give peroxynitrite, a potentially toxic molecule. In this study, we investigated whether or not peroxynitrite contributed to tissue injury in the liver during HS. METHODS: Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. In addition to the time course of tissue injury and inducible NO synthase (iNOS) messenger RNA (mRNA) expression in the liver during HS, we investigated the effect of N6-(iminoethyl)-L-lysine(LNIL) (a specific inhibitor of iNOS) and also that of uric acid (a natural scavenger of peroxynitrite) on tissue injury and nitrotyrosine formation (a footprint of peroxynitrite) in the liver. RESULTS: The liver injury, evaluated by plasma aminotransferase levels and histology, became evident at the end of the shock period and had significantly increased 1 hour after the start of resuscitation (Shock-1 h). There was no iNOS mRNA expression in the liver at baseline, and it had clearly increased by Shock-1 h. Treatment with LNIL or uric acid significantly attenuated the tissue injury with a prominent reduction in nitrotyrosine formation in the liver. CONCLUSIONS: These lines of evidence suggest that one of the mechanisms by which NO production causes liver injury during HS may be its reaction with superoxide to form peroxynitrite.

Animals↗
PubMed2000

Polo-like kinase expression in normal human endometrium during the menstrual cycle.

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% +/- 4.98%) and the early secretory phase (19.28% +/- 4.99%) than in the early proliferative phase (2.60% +/- 2.33%) or the late secretory phase (5.76% +/- 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.

Adult↗
PubMed2000

Inducible differentiation and apoptosis of the pre-B cell receptor-positive pre-B cell line.

The function of the pre-B cell receptor (pre-BCR) during B cell differentiation is not precisely defined. To investigate the pre-BCR receptor activity, we have established pre-BCR-positive pre-B cell lines that are able to differentiate into immature B cells in vitro. Antibody cross-linking of the pre-BCR induced apoptosis and differentiation accompanied with tyrosine phosphorylation. A specific tyrosine-phosphorylated 43 kDa protein (p43) was found down-stream of the pre-BCR. The results demonstrated the receptor function of pre-BCR, which indicates that a ligand-like molecule or a cross-linking structure on the cell surface is possibly present.

Animals↗
PubMed2000

An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-beta1 in uraemic rat kidneys.

BACKGROUND: An oral adsorbent (AST-120) delays the progression of chronic renal failure (CRF). The aims of the present study are to determine the effects of AST-120 on the localization of indoxyl sulphate in uraemic rat kidneys, and to examine whether AST-120 reduces the renal cortical gene expression of transforming growth factor (TGF)-beta1, tissue inhibitor of metalloproteinase (TIMP)-1 and pro-alpha1(I)collagen, and ameliorates glomerular and tubulointerstitial injuries in uraemic rats. METHODS: Two weeks after 5/6-nephrectomy, 10 rats were divided into pairs such that both rats in each pair exhibited almost the same levels of serum creatinine, blood urea nitrogen and creatinine clearance. One rat from each pair was assigned to a control uraemic group, the other to a uraemic group which received AST-120 everyday for 11 weeks. The localization of indoxyl sulphate was studied by immunohistochemistry using a monoclonal anti-indoxyl sulphate antibody we had developed. The renal cortical gene expression was studied by using northern blotting. RESULTS: Rats treated with AST-120 showed decreased levels of serum creatinine, blood urea nitrogen and urinary protein as well as increased levels of creatinine clearance as compared with control uraemic rats. AST-120 markedly decreased indoxyl sulphate levels in both serum and urine. Immunohistochemistry demonstrated that indoxyl sulphate was localized in the renal proximal tubular epithelial cells, especially of dilated tubules, and that AST-120 markedly reduced the tubular staining of indoxyl sulphate. AST-120 attenuated interstitial fibrosis, tubular injury as well as glomerular sclerosis, and reduced the renal gene expression of TGF-beta1, TIMP-1 and pro-alpha1(I)collagen. CONCLUSIONS: AST-120 reduces the gene expression of TGF-beta1, TIMP-1 and pro-alpha1(I)collagen in the kidneys, and delays the progression of CRF, at least in part, by alleviating the overload of indoxyl sulphate on remnant proximal tubular epithelial cells.

Adsorption↗
PubMed2000

Control of antibody-antigen interaction using anion-induced conformational change in antigen peptide.

The binding of a monoclonal antibody to an epitope peptide was controlled by the conformational change of the epitope peptide induced by anions. We synthesized peptides in which the epitope sequence DTYRYI for the monoclonal antibody AU1 is located between amphiphilic peptides (KKLL)n and (LLKK)n. In the absence of an appropriate anion, the peptide was in a random coil state and the epitope was linear. In contrast, in the presence of an appropriate anion, the peptide exhibited an anti-parallel alpha-helical structure and the epitope was subsequently 'bent'. In the presence of 41 microM triphosphate, the association constant between the antibody and the peptide was decreased by one order of magnitude in the case of n = 3 and at least three orders of magnitude in the case of n = 4 or 5. Oligo-DNAs, as anions, dissociated the antibody-peptide complex, whereas triphosphate did not. The DNA concentrations required for 50% dissociation of the antibody-peptide complex at pH 7.5 were 4x10(-8), 1x10(-7) and 6x10(-6) M for decamer, octamer and hexamer DNA, respectively.

Amino Acid Sequence↗
PubMed2000

Anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact canine heart.

The effects of the activation sequence on ventricular repolarization and its spatial gradient were examined in anesthetized open-chest dogs. Unipolar and bipolar electrograms were recorded from 47 epicardial sites on the anterior left ventricular wall using a mapping electrode. The local QT interval (QT) and the activation time (AT) at each site were measured on the unipolar and bipolar electrograms, respectively. The QT index (QTI) was defined as the QT minus AT interval, and was used as a measure of local repolarization. QTI was longer at each site during propagation that was longitudinal (L) (219+/-21 ms) than during propagation transverse (T) (202+/-22 ms, p<0.001) to the epicardial fiber orientation or during atrial pacing (165+/-20 ms, p<0.001). During L-propagation, the QTI shortened as a function of the distance from the stimulus. The spatial gradient was steeper during T-propagation (p<0.05). Monophasic action potentials (MAP) were also recorded simultaneously at 4 epicardial sites. The MAP duration during ventricular pacing was longer than during atrial pacing at sites within 1.5 cm of the pacing site. This difference disappeared at more distant sites and was attenuated by a simultaneous stimulus from a site symmetrically aligned along the fiber. These findings indicate that anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact heart. An electrotonic downstream effect appears to be the cause.

Animals↗