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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 235 records · Page 13Linked to original sources
PubMed2000

Chromosome cohesion, condensation, and separation.

The faithful segregation of genetic information requires highly orchestrated changes of chromosome structure during the mitotic cell cycle. The linkage between duplicated sister DNAs is established during S phase and maintained throughout G2 phase (cohesion). In early mitosis, dramatic structural changes occur to produce metaphase chromosomes, each consisting of a pair of compacted sister chromatids (condensation). At anaphase onset, a signal is produced to disrupt the linkage between sister chromatids (separation), allowing them to be pulled apart to opposite poles of the cell. This review discusses our current understanding of the three stages of large-scale structural changes of chromosomes in eukaryotic cells. Recent genetic and biochemical studies have identified key components involved in these processes and started to uncover hitherto unexpected functional links between mitotic chromosome dynamics and other important chromosome functions.

Adenosine Triphosphatases↗
PubMed2000

Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats.

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.

Animals↗
PubMed2000

Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine.

The superoxide dismutase (SOD) activity of iron(II) tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 microM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 10(6) M-1 S-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 10(5) M-1 S-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN-superoxide complex.

Antioxidants↗
PubMed2000

Degradation of bisphenol A by the lignin-degrading enzyme, manganese peroxidase, produced by the white-rot basidiomycete, Pleurotus ostreatus.

Degradation of 2,2-Bis(4-hydroxyphenyl)propane (bisphenol A, BPA), an endocrine-disturbing chemical, by the growing mycelia of the white-rot basidiomycete, Pleurotus ostreatus, was examined. About 80% of BPA initially present decreased in 12 days of culture with this fungus. By in vitro experiments using the lignin-degrading enzyme manganese peroxidase (MnP), BPA was metabolized to phenol, 4-isopropenylphenol, 4-isopropylphenol, and hexestrol. The degradation products of BPA were assumed to be formed by the one-electron oxidation of the substrate.

Air Pollutants, Occupational↗
PubMed2000

Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib.

It has been hypothesized that suppression of bone remodeling allows microdamage to accumulate, leading to increased bone fragility. This study evaluated the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties of cortical bone in the dog rib. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group (CNT) was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with risedronate (RIS) at a dose of 0.5 mg/kg per day or alendronate (ALN) at 1.0 mg/kg per day orally. After sacrifice, the right ninth rib was assigned to cortical histomorphometry or microdamage analysis. The left ninth rib was tested to failure in three-point bending. Total cross-sectional bone area was significantly increased in both RIS and ALN compared with CNT, whereas cortical area did not differ significantly among groups. One-year treatment with RIS or ALN significantly suppressed intracortical remodeling (RIS, 53%; ALN, 68%) without impairment of mineralization and significantly increased microdamage accumulation in both RIS (155%) and ALN (322%) compared with CNT. Although bone strength and stiffness were not significantly affected by the treatments, bone toughness declined significantly in ALN (20%). Regression analysis showed a significant nonlinear relationship between suppressed intracortical bone remodeling and microdamage accumulation as well as a significant linear relationship between microdamage accumulation and reduced toughness. This study showed that suppression of bone turnover by high doses of bisphosphonates is associated with microdamage accumulation and reduced some mechanical properties of bone.

Alendronate↗
PubMed2000

The hexapeptide KP-102 (D-ala-D-beta-Nal-ala-trp-D-phe-lys-NH(2)) stimulates growth hormone release in a cichlid fish (Ooreochromis mossambicus).

Abstract Studies in mammals have shown that synthetic Met-enkephalin derivatives, called growth hormone-releasing peptides (GHRPs), stimulate growth hormone (GH) release. The present study was conducted to determine whether the GHRP, KP-102, specifically stimulates GH release in a teleost. Tilapia (Oreochromis mossambicus) were given a single intraperitoneal injection of KP-102 (D-Ala-D-beta;-Nal-Ala-Trp-D-Phe-Lys-NH(2)) or bovine GHRH(1-29)-amide or vehicle and blood was sampled at 1, 6 and 12 h after injection. KP-102 was administered at two doses of 1 ng/g and 10 ng/g body weight, whereas GHRH (positive control) was administered at a single dose of 10 ng/g body weight. Plasma levels of tilapia GH and prolactins (tPRL(177) and tPRL(188)) were determined by radioimmunoassay. As expected, GHRH injection significantly (P<0.001) elevated plasma GH levels (ng/ml) in tilapia at 6 h post-injection. KP-102 also significantly elevated GH levels (at the low dose) at 6 (P<0.05) and 12 (P<0.01) hours post-injection. There were no significant effects on plasma PRL(s) levels, although mean levels of both PRLs were elevated at 6 h post-injection. These results show for the first time that GHRPs stimulate GH release in teleosts and suggest that the GHRP receptor and possibly a "Ghrelin-like" ligand are also present in lower vertebrates.

Analysis of Variance↗
PubMed2000

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD). Several recent studies have shown that some metalloproteinase mediates TNF-alpha and FasL processing. We examined the ameliorating effect of a hydroxamic acid-based metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a lethal acuteGVHD model in mice. The ameliorating effect of KB-R7785 was superior to that of anti-TNF-alpha antibody. We also examined the effect of KB-R7785, which we previously demonstrated a potent ameliorating effect on acute GVHD, on graft-versus-leukemia (GVL) effect of allogeneic bone marrow transplantation (BMT). Administration of KB-R7785 without bone marrow cells and spleen cells (BMS). significantly prolonged the survival of IgE-producing B53 hybridoma cell-inoculated (C57BL/6 x BALB/c) F1 (CBF1) mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in 50% survival of B53-inoculated CBF1 mice over 50 days without histological manifestations of acute GVHD or residual B53 cells. These results suggest that KB-R7785 could be a potent therapeutic agent for GVHD, and indicate the beneficial effects of KB-R7785 that inhibit tumor infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.

Animals↗
PubMed2000

Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors.

Gab1 and Gab2 (Grb2 associated binder 1 and 2) are scaffolding adapter molecules that display sequence similarity with Drosophila DOS (daughter of sevenless), which is a potential substrate for the protein tyrosine phosphatase, Corkscrew, Both Gab1 and Gab2, like DOS, have a pleckstrin homology domain and potential binding sites for SH2 and SH3 domains. Gab1 and Gab2 are phosphorylated on tyrosine upon the stimulation of various cytokines, growth factors, and antigen receptors, and interact with signaling molecules, such as Grb2, SHP-2, and PI-3 kinase. Overexpression of Gab1 or Gab2 mimics or enhances growth factor or cytokine-mediated biological processes and activates ERK MAP kinase. These data imply that Gab1 and Gab2 act downstream of a broad range of cytokine and growth factor receptors, as well as T and B antigen receptors, and link these receptors to ERK MAP kinase and biological actions.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Effects of the V(2)-receptor antagonist OPC-41061 and the loop diuretic furosemide alone and in combination in rats.

This study was conducted to characterize the diuretic effect of OPC-41061, a nonpeptide vasopressin V(2)-receptor antagonist, and furosemide by administering each alone and in combination in conscious male rats. OPC-41061 at 1 and 10 mg/kg and furosemide at 10 and 100 mg/kg dose-dependently increased urine volume to the same extent. The high dose of OPC-41061 (10 mg/kg) markedly elevated electrolyte-free water clearance (E-CH(2)o) to a positive value. In contrast to OPC-41061, furosemide elevated only electrolyte clearance but not E-CH(2)o. The differences in diuretic profile reflected the changes in serum sodium and hormone levels. OPC-41061 dose-dependently elevated serum sodium concentration, but furosemide tended to decrease it. The high dose of furosemide (100 mg/kg) significantly elevated serum renin activity and aldosterone concentration, indicating that furosemide activated the renin-angiotensin-aldosterone system (RAA-system). On the other hand, OPC-41061 did not affect these parameters. When OPC-41061 was administered concomitantly with furosemide, OPC-41061 significantly increased urine volume and E-CH(2)o, and decreased urinary osmolality compared with furosemide alone. OPC-41061 dose-dependently elevated serum osmolality and sodium concentration even when administered in combination with the high dose of furosemide. These results suggest that OPC-41061 produces aquaresis leading to increased serum sodium without affecting the RAA-system. On the other hand, furosemide produced natriuresis, leading to decreased serum sodium level and activation of the RAA-system. It was also demonstrated that OPC-41061 produced an additive diuretic effect and elevated serum sodium level in the presence of furosemide.

Aldosterone↗
PubMed2000

[Rapidly progressive, refractory eosinophilia with a 250,000/microliter eosinophil count].

A 31-year-old man had received corticosteroids for 20 months for treatment of a brain tumor, and his blood eosinophil count ranged from 100/microliter to 1,000/microliter. On June 24th, 1998, he was re-admitted because of dyspnea secondary to left massive pleural effusion. Peripheral blood examination revealed an eosinophil count of 48,000/microliter. The eosinophils were hypersegmented, with abnormal distribution of eosinophilic granules and formation of cytoplasmic vacuoles. Blasts and basophils were not increased, hemoglobin was 13.4 g/dl, and the platelet count was 79,000/microliter. Bone marrow was slightly hypercellular with 55% eosinophils and 0.2% blasts. The patient's karyotype was normal, and Wilms' tumor gene was not detected. Serum IgE was normal and serum vitamin B12 and soluble IL-2 receptor were elevated. Serum levels of eosinophilopoietic cytokines, IL-3, IL-5, and GM-CSF, were low. Specimens of pleural fluid contained many eosinophils. Because the eosinophil count increased to 110,000/microliter on July 2nd, hydroxyurea was started without effect. On July 16th, the eosinophil count reached 167,000/microliter, and vincristine was added. The eosinophil count rose to 253,000/microliter the next day, and cytarabine and daunorubicin were administered, but the patient died of septic shock. Although the clinical course suggested eosinophilic leukemia, monoclonal proliferation of eosinophils was not demonstrated. To our knowledge, this is the highest peripheral blood eosinophil count reported in the literature to date.

Adult↗
PubMed2000

[Molecular biological diagnosis].

Biological behavior of lung cancer was evaluated by basic study. Malignancy Associated Change is the concept that the nuclear features of normal cells in the vicinity of cancer show subtle morphological difference from those of healthy individuals. The difference was recognized by high resolution cytometry and the expression of MAC cells was correlated with the degree of abnormality of chest diseases. Comparative genomic hybridization and fluorescence in situ hybridization were performed to investigate genetic abnormality of. Multiple genetic abnormalities and chromosomal instability showed poor prognosis. Two dimensional electrophoresis was employed to detect the expression of the specific protein of lung cancer. TAO2 was proved to be specific to well differentiated adenocarcinoma. Also, metabolic analysis will be employed for cell analysis.

Biomarkers, Tumor↗
PubMed2000

Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.

Adult↗
PubMed2000

Relationship between chromosomal instability and intratumoral regional DNA ploidy heterogeneity in primary gastric cancers.

The purpose of this study was to elucidate the relationship between intratumoral regional heterogeneity in DNA ploidy and chromosomal instability (CIN) in primary gastric adenocarcinomas. In 45 sporadic gastric adenocarcinomas, we measured DNA ploidy and numerical aberrations for chromosomes 7, 11, 17, and 18 by laser scanning cytometry and fluorescence in situ hybridization, respectively, in small tissue specimens taken from 2 to 6 (on the average 4) different portions of the same tumor. A total of 231 specimens including 45 normal control specimens were examined. All 98 tumor specimens with DNA aneuploidy (DNA index > or = 1.2) showed large intercellular variations in chromosome copy number, indicating CIN. In contrast, 85 tumor specimens with (near) diploidy (1.0 < or = DNA index < 1.2) exhibited much small intercellular variations in chromosome copy number as compared with aneuploid specimens (P < 0.0001). The relationship between DNA ploidy and intercellular variation in chromosome copy number was true for tumors consisting of a mixture of (near) diploid and aneuploid subpopulations. These data indicate that DNA aneuploidy is associated with CIN but that (near) diploidy is not. Intratumoral regional DNA ploidy heterogeneity was conspicuous in 33 (92%) of 36 tumors with regions of DNA aneuploidy, and all aneuploid specimens showed great intercellular variation in chromosome copy number. Diploid regions were predominant in early stage cancers (intramucosal and submucosal cancers), and five of eight early cancers contained only diploid population. In contrast, all tumors without (near) diploid regions were advanced cancers. These observations suggest that CIN is a necessary prerequisite for developing intratumoral DNA ploidy heterogeneity with DNA aneuploidy.

Adenocarcinoma↗
PubMed2000

[Concomitant surgical treatment of valvular heart disease and coronary artery disease].

Concomitant valvular surgery and coronary artery bypass grafting were performed in 24 patients. Aortic valve replacement was carried out in 18 cases (A group), and mitral valve surgery (M group) was done in 6 cases (replacement in 3, and plasty in 3). There were two hospital deaths (11.1%) in the A group, and two (33.3%) in the M group of mitral valve replacement with Hancock II. One late death was observed in the M group. Aortic valve replacement with coronary revascularization resulted in satisfactory outcome. However, surgical management of concomitant mitral valve and coronary artery disease may need to be improved.

Aged↗
PubMed2000

The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke.

We studied 24 patients up to 51 hours after ischemic stroke using 18F-fluoromisonidazole positron emission tomography to determine the fate of hypoxic tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were detected on positron emission tomography in 15 patients, and computed tomography was available in 12 patients, allowing comparison with the infarct volume to determine the proportions of the hypoxic tissue volume that infarcted and survived. The proportion of patients with hypoxic tissue and the amount of hypoxic tissue detected declined with time. On average, 45% of the total hypoxic tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct volume was initially hypoxic. Most of the tissue "initially affected" proceeded to infarction. We correlated hypoxic tissue volumes with neurological and functional outcome assessed using the National Institutes of Health Stroke Scale, Barthel Index, and Rankin Score. Initial stroke severity correlated significantly with the "initially affected" volume, neurological deterioration during the first week after stroke with the proportion of the "initially affected" volume that infarcted, and functional outcome with the infarct volume. Significant reductions in the size of the infarct and improved clinical outcomes might be achieved if hypoxic tissue can be rescued.

Adult↗
PubMed2000

[Dubowitz syndrome].

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Abnormalities, Multiple↗
PubMed2000

Antidiuretic effects of a nonpeptide vasopressin V(2)-receptor agonist, OPC-51803, administered orally to rats.

OPC-51803 is the first nonpeptide vasopressin (AVP) V(2)-receptor-selective agonist. Its pharmacological profile, including antidiuretic action and receptor binding, was characterized using conscious Brattleboro rats with hereditary diabetes insipidus and Sprague-Dawley rats. In membrane preparations from the liver and kidney, OPC-51803 displaced the [(3)H]AVP binding to V(2)-receptors (K(i) = 49.8 +/- 8.1 nM) more greatly than that to V(1a)-receptors (K(i) = 1061 +/- 60 nM), showing a 21 times higher affinity for V(2)-receptors. At single oral doses of 0.003 to 0.3 mg/kg in female Brattleboro rats, OPC-51803 decreased urine volume (from 10.8 +/- 1.1 to 0.5 +/- 0.2 ml during 0-2 h postdosing) and increased urinary osmolality (from 114 +/- 9 to 432 +/- 114 mOsm/kg) in a dose-dependent manner. During the period of 4-week treatment with OPC-51803, significant and constant antidiuresis was observed. In male Sprague-Dawley rats with normal plasma AVP levels, OPC-51803 at 0.03 to 0.3 mg/kg also produced a dose-dependent antidiuretic action (urine volume: from 2.6 +/- 0.6 to 1.1 +/- 0.2 ml at 0-4 h postdosing). Few changes in urinary parameters, serum parameters, or plasma hormone levels were observed. OPC-51803 did not change blood pressure or heart rate, or inhibit AVP-induced pressor response even at 30 mg/kg p.o. These results demonstrate that OPC-51803 is a V(2)-selective agonist that produces a significant antidiuretic action after single and multiple oral dosing in AVP-deficient and normal AVP states. The data suggest that OPC-51803 is a useful therapeutic drug in the treatment of hypothalamic diabetes insipidus, nocturnal enuresis, and some kinds of urinary incontinence.

Administration, Oral↗