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Biomedical subjects

H Miyoshi

Publications and source records attributed to H Miyoshi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195.

AIMS/HYPOTHESIS: Advanced glycation end products (AGEs) participate in the pathogenesis of diabetic nephropathy. We reported earlier that OPB-9195, a synthetic thiazolidine derivative and novel inhibitor of advanced glycation, prevented progression of diabetic glomerulosclerosis by lowering serum concentrations of advanced glycation end products and reducing their deposition in the glomeruli. Here, we examined their contribution and that of growth factors, such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF), to the progression of diabetic nephropathy. We also investigated the expression of type IV collagen in the kidneys of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model, after treatment with OPB-9195. METHODS: Using northern blots and immunohistochemical techniques, we determined the renal expression of TGF-beta and type IV collagen mRNAs and proteins in OLETF rats. We also examined OPB-9195's effects on renal expression of VEGF mRNA and protein. RESULTS: Concomitant increases in TGF-beta and type IV collagen expression were observed at each point in time in OLETF rats not given OPB-9195. In contrast, OPB-9195 treatment greatly suppressed the renal expression of TGF-beta, VEGF and type IV collagen mRNAs and proteins to that seen in non-diabetic rats. CONCLUSION/INTERPRETATION: Since OPB-9195, an AGE-inhibitor, prevented the progression of diabetic nephropathy by blocking type IV collagen production and suppressing overproduction of two growth factors, TGF-beta and VEGF, in diabetic rats, this compound warrants further investigation.

Animals↗
PubMed1999

Jumbled spine and ribs (Jsr): a new mutation on mouse chromosome 5.

Jumbled spine and ribs (Jsr) is an autosomal dominant mutation that results in malformation of the axial skeleton. The vertebrae of mutant mice (Jsr/+) are all shorter than those of normal mice (+/+) in the inbred line and show various abnormalities. In addition, several ribs are fused at their proximal region because of fusion of thoracic vertebrae. In this study, we localized the Jsr mutation on distal Chromosome (Chr) 5 and constructed a high-resolution map. Chromosomal mapping was performed with an inter-subspecific backcross of (CKH-Jsr/+ x MOG) F1 carrying the Jsr allele and CKH-+/+. The predicted gene order around Jsr was determined to be cen-(Epo, Pdgfa, D5Mit31, D5Mit374)-(Jsr, Nfe2u, D5Mit99, D5Mit247, D5Mit284, D5Mit292, D5Mit327)-D5Mit328-tel. Subsequently, high-resolution mapping concluded the Jsr localization to be cen-Nfe2u-1.0cM-Jsr-0.2cM-D5Mit247,292-tel . Jsr/Jsr homozygotes are alive, as the mutation is not lethal. Based on histological analysis of mutant embryos, Jsr is hypothesized to be caused by abnormal development of primordial cells in the axial skeleton.

Animals↗
PubMed1999

Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas.

BACKGROUND & AIMS: Cholestatic liver injury results from the intrahepatic accumulation of toxic bile salts. Toxic bile salt-induced hepatocyte apoptosis in vitro is Fas dependent. The aim of this study was to ascertain if hepatocyte apoptosis in vivo during cholestasis is Fas dependent. METHODS: Studies were performed in bile duct-ligated (BDL) Fas-deficient lpr (lymphoproliferation) and wild-type mice. RESULTS: Hepatocyte apoptosis was the predominant mechanism of cell death as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and trypan blue assays to quantitate apoptosis and necrosis. The mechanisms of hepatocyte apoptosis were dependent on the presence or absence of the Fas receptor and the duration of BDL. After BDL of 3 days' duration, increased hepatocyte apoptosis occurred only in wild-type but not lpr mice, indicating the apoptosis was Fas dependent. In contrast, after BDL of >/=7 days, hepatocyte apoptosis also occurred in lpr animals consistent with a Fas-independent mechanism of apoptosis. Hepatocyte apoptosis in BDL lpr mice was associated with an increase in Bax expression and Bax association with mitochondria. CONCLUSIONS: During extrahepatic cholestasis, hepatocyte apoptosis is mediated by Fas. However, in the absence of the Fas receptor, additional mechanisms of hepatocyte apoptosis occur. Inhibition of multiple apoptotic pathways is necessary to attenuate chronic cholestatic liver injury.

Animals↗
PubMed1999

Left gastric vein hemodynamics and variceal recurrence in patients undergoing prophylactic endoscopic ligation of high-risk esophageal varices.

BACKGROUND: Early recurrence of esophageal varices remains problematic after endoscopic variceal ligation. To evaluate the efficacy of prophylactic endoscopic ligation for esophageal varices at high risk for bleeding, the relationship between left gastric vein hemodynamics and variceal recurrence was investigated. METHODS: Thirty-five patients with cirrhosis underwent endoscopic variceal ligation. Angiography was performed in all patients before treatment and after eradication of varices to study left gastric vein hemodynamics. RESULTS: Before treatment, 12 patients had hepatopetal flow in the left gastric vein (type I), 17 had hepatofugal flow (type II), and 6 had hepatofugal flow with an extra-esophageal shunt (type III). In type I and III patients, the direction of blood flow in the left gastric vein did not change after eradication of varices. Type II patients showed bi-directional flow in the left gastric vein after treatment. Varices recurred in all but one type II patient and in one type I patient during follow-up (mean 36.7 months). The 2-year recurrence-free rate was higher in type I patients (p = 0.0001) and type III patients (p = 0.0002) than in type II patients. CONCLUSIONS: Prophylactic ligation seems to be a safe and useful procedure, especially in patients with type I or III hemodynamics in the left gastric vein before treatment.

Angiography, Digital Subtraction↗
PubMed1999

A case of multiple symmetrical lipomatosis (Madelung's disease).

Multiple symmetrical lipomatosis (Madelung's disease) is a rare disease with multiple symmetrical unencapsulated fatty accumulation diffusely involving the neck, the shoulders and the upper extremities (Kohan et al. Otolaryngol. Head Neck Surg. 1993;108:156-159). We describe a 48-year-old Japanese man with a history of alcoholism and liver cirrhosis who reported gradually enlarging masses in his cervical region for 4 years. MRI revealed large masses suggesting lipomas in the neck. The patient underwent a two-stage lipectomy. This patient is the 13th case reported in Japan since 1978, though over 200 cases have been reported since 1846 in Europe, most of them from the Mediterranean (Kitano et al. ORL 1994;56:177 180; Kaku et al. Endocrinol. Diabetol. 1997;4:103-106).

Adipose Tissue↗
PubMed1999

Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with HIV infection.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from lytic infection of oligodendrocytes by the papovavirus JC (JCV). PML has also been recognized as an AIDS-defining illness. The incidence of PML has increased since 1987 and it occurs in up to 4% of patients with AIDS. To date, there is no treatment available for PML and it usually results in death within 3-6 months of diagnosis. However, there are some reports of remission of PML after antiretroviral therapy. We report a 12-year-old child with hemophilia B and developing AIDS with the onset of PML. With highly active antiretroviral therapy, PML subsided with an increase of CD4 count from 10 to 300/microl in spite of about 1.0 X 10(4) human immunodeficiency virus (HIV)-1-RNA copies. He has survived more than 1 year without specific therapy against JCV. Highly active antiretroviral therapy appears to have improved his prognosis in HIV-associated PML.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children.

Thrombotic microangiopathy (TMA) is a serious complication of BMT. Several factors are important in the etiology of TMA, such as cyclosporin A, GVHD, irradiation, intensive conditioning chemotherapy and infection, which cause damage to vascular endothelial cells leading to activation of these cells. We describe two young children with TMA following high-dose chemotherapy with autologous BMT. Development of TMA was accompanied by reactivation of HHV-6, which was identified by both an increase in the copy number of HHV-6 DNA in the peripheral blood and a significant increase in antibody titers to HHV-6. Thus, it was suggested that reactivation of HHV-6 together with high-dose chemotherapy played an important role in the pathogenesis of TMA in these patients. Since HHV-6 is known to infect vascular endothelial cells, and CMV which is virologically closely related to HHV-6, has been reported to be a pathogen that causes TMA, infection with HHV-6 of vascular endothelial cells may induce TMA via damage and activation of these cells.

Bone Marrow Transplantation↗
PubMed1999

Immunosuppressive effects of the heat shock protein 90-binding antibiotic geldanamycin.

Ansamycin antibiotic, geldanamycin has a unique pharmacological effect to bind to heat shock protein 90 (hsp90) and deplete hsp90 substrates. We investigated the immunopharmacological effects of geldanamycin. Geldanamycin depleted cellular Raf-1 of rat splenic cells without affecting the steady state levels of hsp90 and downstream mitogen activated protein (MAP) kinases, ERK1 and ERK2. In parallel, it inhibited mitogen-induced nuclear factor-kappa B (NF-kappa B) activation in these cells. Geldanamycin also had a potent suppressive effect on recall antigen-induced T cell proliferation, with an IC50 value of 1 nM. In vivo, geldanamycin suppressed the progression of adjuvant-induced arthritis dose-dependently. These results suggest that geldanamycin exerts an immunosuppressive effect partly through destabilizing Raf-1, and raise a new strategy for the prevention of inflammatory diseases.

Animals↗
PubMed1999

Characterization of the ubiquinol oxidation sites in cytochromes bo and bd from Escherichia coli using aurachin C analogues.

Natural aurachin C is the most potent inhibitor of oxidation of ubiquinols by cytochromes bo and bd from Escherichia coli. To probe the structural properties of the substrate oxidation site in the ubiquinol oxidases, we synthesized a systematic set of aurachin C analogues (N-hydroxy-4-quinolone derivatives) and examined how their structure affects their activity towards cytochromes bo and bd, which are structurally unrelated. We found that the presence of the 3-methyl group of the 2-n-decyl and 2-n-undecyl derivatives increased the inhibitory potency towards both enzymes, probably due to a local steric congestion that allows favorable interaction of the alkyl tail with the enzyme. Increase in the chain length of the 3-alkyl tail of the 2-n-undecyl derivatives decreased the inhibitory potency only in cytochrome bo, indicating that the binding site for the alkyl tails of cytochrome bo is smaller than that of cytochrome bd. Based on these findings, we discuss the differences in the molecular mechanism of substrate oxidation by these two terminal ubiquinol oxidases.

Binding Sites↗
PubMed1999

Binding analysis of Xenopus laevis translation initiation factor 4E (eIF4E) in initiation complex formation.

A translation initiation factor, eIF4E, of Xenopus laevis was purified by affinity column chromatography after the gene expression as a full-length protein in a baculovirus-insect cell system. Interaction between X. laevis eIF4E and 4E-BP2 was analyzed by affinity column chromatography, gel permeation chromatography (GPC), and surface plasmon resonance (SPR). It was found that the interaction of eIF4E with an mRNA cap-analogue enhanced the binding activity of eIF4E with 4E-BP2. Furthermore, the SPR analysis showed that the eIF4E-cap-analogue interaction was very weak regardless of complex formation of 4E-BP2 with eIF4E; the dissociation constant of eIF4E for the cap-analogue was estimated to be 10(-2)-10(-4) M. These results suggest that the participation of another initiation factor is required for eIF4E to recognize the cap structure in vivo. The results reported in this paper support "the performed complex model" of Lee et al., in which eIF4E binds to the mRNA cap structure after the initiation factors have formed the initiation complex eIF4F.

Amino Acid Sequence↗
PubMed1999

Factors associated with increased extravascular lung water in cardiac tamponade and myocardial ischemia.

OBJECTIVE: To evaluate and compare the factors associated with pulmonary edema in cardiac tamponade and myocardial ischemia. DESIGN: Prospective, controlled laboratory study. SETTING: Animal research laboratory of a university hospital. SUBJECTS: Fourteen anesthetized dogs. INTERVENTION: Extravascular lung water (EVLW) was measured with thermal indocyanine green dye double-indicator dilution method and hemodynamic indices were determined by the pulmonary artery flotation catheter. Seven dogs were used in the tamponade model, and seven other dogs were used in the myocardial ischemia model. Furthermore, ten dogs were dedicated to measure plasma colloid osmotic pressure (COP) and blood gas analysis during cardiac tamponade and myocardial ischemia. MEASUREMENTS AND MAIN RESULTS: Mean right atrial pressure (MRAP) (7-->10 mm Hg), pulmonary capillary wedge pressure (PCWP) (10-->13 mm Hg), and EVLW (5.4-->10.1 mL/kg) increased during tamponade, but all of these indices returned to the control level after release of tamponade (MRAP, 7 mm Hg; mean PCWP, 11 mm Hg; mean EVLW, 5.2 mL/kg). Myocardial ischemia caused increases in PCWP (10-->14 mm Hg) and EVLW (5.6-->9.6 mL/kg). Although PCWP returned to the control level, EVLW remained elevated (9.2 mL/kg) after reperfusion. EVLW had good correlations with MRAP (r2 = .64, p < .05) and PCWP (r2 = .62, p < .05) during cardiac tamponade. Despite a fair correlation between EVLW and PCWP during ischemia (r2 = .73, p < .05), EVLW was not related to PCWP after reperfusion. COP decreased during myocardial ischemia and at the reperfusion period, but there was no significant change in COP in the cardiac tamponade model. CONCLUSIONS: In contrast to a close relation between hydrostatic pressure and EVLW in cardiac tamponade, hydrostatic pressure was not a determinant of pulmonary edema during the reperfusion period after myocardial ischemia.

Animals↗
PubMed1999

Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer.

Retinitis pigmentosa (RP) is the most common inherited retinal disease, in which photoreceptor cells degenerate, leading to blindness. Mutations in the rod photoreceptor cGMP phosphodiesterase beta subunit (PDEbeta) gene are found in patients with autosomal recessive RP as well as in the rd mouse. We have recently shown that lentivirus vectors based on human immunodeficiency virus (HIV) type 1 achieve stable and efficient gene transfer into retinal cells. In this study, we evaluated the potential of HIV vector-mediated gene therapy for RP in the rd mouse. HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes. One to three rows of photoreceptor nuclei were observed in the eyes for at least 24 weeks postinjection, whereas no photoreceptor cells remained in the eyes of control animals at 6 weeks postinjection. Expression of HA-tagged PDEbeta in the rescued photoreceptor cells was confirmed by two-color confocal immunofluorescence analysis using anti-HA and anti-opsin antibodies. HIV vector-mediated gene therapy appears to be a promising means for the treatment of recessive forms of inherited retinal degeneration.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas.

Cholestatic liver injury appears to result from the induction of hepatocyte apoptosis by toxic bile salts such as glycochenodeoxycholate (GCDC). Previous studies from this laboratory indicate that cathepsin B is a downstream effector protease during the hepatocyte apoptotic process. Because caspases can initiate apoptosis, the present studies were undertaken to determine the role of caspases in cathepsin B activation. Immunoblotting of GCDC-treated McNtcp.24 hepatoma cells demonstrated cleavage of poly(ADP-ribose) polymerase and lamin B1 to fragments that indicate activation of effector caspases. Transfection with CrmA, an inhibitor of caspase 8, prevented GCDC-induced cathepsin B activation and apoptosis. Consistent with these results, an increase in caspase 8-like activity was observed in GCDC-treated cells. Examination of the mechanism of GCDC-induced caspase 8 activation revealed that dominant-negative FADD inhibited apoptosis and that hepatocytes isolated from Fas-deficient lymphoproliferative mice were resistant to GCDC-induced apoptosis. After GCDC treatment, immunoprecipitation experiments demonstrated Fas oligomerization, and confocal microscopy demonstrated DeltaFADD-GFP (Fas-associated death domain-green fluorescent protein, aggregation in the absence of detectable Fas ligand mRNA. Collectively, these data suggest that GCDC-induced hepatocyte apoptosis involves ligand-independent oligomerization of Fas, recruitment of FADD, activation of caspase 8, and subsequent activation of effector proteases, including downstream caspases and cathepsin B.

Animals↗
PubMed1999

UK-2A,B,C and D, novel antifungal antibiotics from Streptomyces sp.517.02. V. Inhibition mechanism of bovine heart mitochondrial cytochrome bc1 by the novel antibiotic UK-2A.

UK-2A is a potent antifungal antibiotic isolated from Streptomyces sp. 517-02 and its structure is highly similar to that of antimycin A. We investigated the inhibition mechanism of bovine heart mitochondrial cytochrome bc1 complex by the UK-2A using antimycin A and myxothiazol as the reference inhibitors of ubiquinol oxidation (Qo) and ubiquinone reduction (Qi) sites, respectively. The inhibitory potency of UK-2A was about 3-fold less than antimycin A. On the basis of the effects of UK-2A on the reduction kinetics of b and c1 hemes, this compound appeared to be an inhibitor of the Qi site. However, since spectral changes of dithionite-reduced cytochrome b induced by UK-2A binding differed from that of antimycin A, the precise binding manner of UK-2A to the enzyme is not identical to that of antimycin A. It could be concluded that antimycin A binding to cytochrome b is primarily decided by structural specificity of the salicylic acid moiety.

Animals↗
PubMed1999

[Usefulness of DIC-CT in choledocholithiasis].

In order to assess the efficacy of helical CT in drip-infusion cholangiography (DIC-CT) for diagnosis of choledocholithiasis, 82 patients with biliary diseases, including 25 patients with a definite diagnosis of choledocholithiasis obtained by direct cholangiography, were investigated by DIC-CT and EUS. Comparative investigation showed that, of the 25 cases, 94.7% could be imaged by DIC-CT and 87.5% by EUS, with respective sensitivities of 94.7% and 87.5%. The specificities in both cases were 100% and accuracies were 97.8% with DIC-CT and 96% with EUS respectively. Therefore, in diagnosis the choledocholithiasis, DIC-CT displays similar diagnostic efficiency as EUS or ERC, and can be recognized as the non-invasive and useful procedure for pre-operative diagnosis of cholecystolithiasis.

Biliary Tract Diseases↗
PubMed1999

[Chronological study for solitary bone metastasis in the sternum from breast cancer with bone scintigraphy].

Since breast cancer is frequently associated with bone metastasis, bone scintigraphies have been performed to determine pre-operative staging and to survey postoperative bone metastasis. The sternum, in particular, is a site at which is difficult to differentiate between benign bone disease and bone metastasis, because of varied uptake and wide individual variations. In this study, chronological bone images were scintigraphied in six cases with solitary sternal metastasis and three cases with benign bone disease including two fracture cases and one arthritis case. On bone scintigrams in which solitary sternal metastasis appeared, increased uptake was found in five cases, and photon deficiency was observed in one case. During follow-up scintigraphies, abnormal accumulations, such as hot spots and cold lesions, increased in the bone metastasis while abnormal uptake disappeared or was unchanged in the benign bone disease cases. On CT, four cases showed osteolytic change, and one exhibited osteosclerotic change. These findings indicate that sternal metastasis usually shows osteolytic change, even if a hot lesion is recognized on bone scintigraphy. In solitary sternal metastasis, for which early diagnosis is difficult, both an integrated diagnosis using other imaging techniques and chronological bone scintigraphy are important.

Adult↗
PubMed1999

Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats.

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to approximately 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severity of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.

Abnormalities, Drug-Induced↗