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Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats.

Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation.

Adipocytes↗
PubMed2001

Restoration of endogenous wild-type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis.

p53 protein is a transcription factor involved in multiple tumor-suppressor activities including cell cycle control and apoptosis. TP53 gene is frequently mutated in glioblastoma, suggesting the importance of inactivation of this gene product in gliomagenesis. Restoration of p53 function in glioblastoma cell lines deficient for p53 has shown that p53 induces growth arrest or apoptosis depending on the cell line and vector used to transduce wild-type TP53 alleles. Considering that astrocytes grow and express p53, it is not clear whether these results reflect physiologic responses or the result of p53 overexpression in combination with cellular responses to viral vector infection. Here, we reassessed this issue using a glioblastoma cell line (LN382) that expresses an endogenous temperature-sensitive mutant p53. This cell line expresses TP53 alleles (100% as determined by a p53 transcriptional assay in yeast) mutated at codon 197 GTG (Val) > CTG (Leu). We found that the p53 protein in these cells acted as an inactive mutant at 37 degrees C and as a functional wild-type p53 below 34 degrees C as demonstrated by several lines of evidence, including (i) restoration of transactivating ability in yeast, (ii) induction of p53-modulated genes such as CDKN1(p21) and transforming growth factor-alpha, (iii) disappearance of accumulated p53 protein in the nucleus and (iv) decrease in steady state p53 protein levels. This temperature switch allowed p53 levels, which were close to physiological levels to dramatically reduce LN382 cell proliferation by inducing a G(1)/S cell cycle block, but not to induce apoptosis. The lack of apoptosis was considered to be a result of the low level p53 expression, because increasing wild-type p53 levels by adenoviral-mediated gene transfer caused apoptosis in these cells. The LN382 cell line will be extremely useful for investigations into the roles of p53 in cellular responses to a variety of stimuli or damages.

Apoptosis↗
PubMed2001

Embryonic and paralarval development of the central nervous system of the loliginid squid Sepioteuthis lessoniana.

The embryonic development of the central nervous system (CNS) in the oval squid Sepioteuthis lessoniana is described. It has three distinct phases: (1) The ganglionic accumulation phase: Ganglionic cell clusters develop by ingression, migration, and accumulation of neuroblasts. (2) The lobe differentiation phase: Ganglia differentiate into lobes. The phase is identified by the beginning of an axogenesis. During this phase, neuropils are first formed in the suboesophageal mass, then in the basal lobe system, and finally in the inferior frontal lobes and the superior frontal-vertical lobe systems. (3) The neuropil increment phase: After the shape of the lobes reached its typical form, neuropil growth occurs, specifically in the vertical lobe. The paralarval central nervous system (CNS) is characterized by neuronal gigantism of the giant fibers and some suboesophageal commissures and connectives. The neuropil formation in the CNS of S. lessoniana occurs somewhat earlier than in Octopus vulgaris, although the principal developmental plan is quite conservative among the other coleoids investigated. Some phylogenetic aspects are discussed based on the similarities in the morphologic organization of their brains.

Animals↗
PubMed2001

Endothelium-dependent relaxation by cilostazol, a phosphodiesteras III inhibitor, on rat thoracic aorta.

The relaxation effect of cilostazol, a phosphodiesterase III inhibitor, on the thoracic aorta was investigated. Cilostazol induced the relaxation of the thoracic aorta precontracted by phenylephrine in a concentration-dependent manner. The concentration-dependent relaxation was shifted to the right in the endothelium denuded aorta compared with that of intact endothelium, suggesting that this relaxation was partly dependent on endothelium. Cilostazol-induced relaxation of thoracic aorta tone was reversed by treatment with N(G)-nitro L-arginine (L-NNA), a competitive inhibitor of nitric oxide (NO) synthase. Cilostazol also significantly increased the NO level in the porcine thoracic aorta. In rats treated with cilostazol, the urinary excretion of nitrites, a stable metabolite of NO, and basal production of NO of the aortic ring were significantly greater than in those without treatment. These findings indicate that cilostazol-induced vasodilation of the rat thoracic aorta was dependent on the endothelium, which released NO from aortic endothelial cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

An isomer prediction model for PCNs, PCDD/Fs, and PCBs from municipal waste incinerators.

Isomer patterns of polychlorinated naphthalenes (PCNs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzofurans (PCDFs) from municipal waste incinerators (MWIs) were predicted by a model based on symmetry numbers and preferential chlorination positions. Fly ash isomer patterns from five stoker and seven fluidized bed incinerators were compared to validate the prediction model. The isomer patterns of the highly chlorinated PCN homologues from stoker type incinerators were successfully predicted. The relative equilibrium concentrations of tetrachloronaphthalenes (TeCNs), calculated by an ab initio method, cannot explain the field isomer patterns. Formation pathways involving chlorophenol precursor condensation reactions should be examined to see whether these isomer patterns provide a better fit to the field PCDD data. The PCB isomer patterns were fit reasonably well, but this finding could merely be an artifact of the limited data and the large number of isomers. The prediction equations of PCDFs, revised from prior work to include a symmetry number for each isomer, represented the field data patterns for the higher chlorinated isomers very well. Successful prediction of isomer patterns for partial homologue ranges suggests that these patterns are determined by a mechanism governed by Cl-position-specific preferences.

Benzofurans↗
PubMed2001

Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes.

CsOH- or Ag(2)O-mediated cycloalkylation of (alkylidene)bisperoxides 3 and 1,n-dihaloalkanes (n = 3-8) provided the corresponding medium-sized 1,2,4,5-tetraoxacycloalkanes 4-8 in moderate yields. Subsequent evaluation of the antimalarial activity of the cyclic peroxides 4-8 in vitro and in vivo revealed that 1,2,6,7-tetraoxaspiro[7.11]nonadecane 4a has considerable potential as a new, inexpensive, and potent antimalarial drug.

Animals↗
PubMed2001

Magnetic resonance imaging system for three-dimensional conformal radiotherapy and its impact on gross tumor volume delineation of central nervous system tumors.

PURPOSE: We developed an MRI system for three-dimensional planning in radiotherapy. Its contribution on gross tumor volume (GTV) delineation of central nervous system (CNS) diseases was evaluated. METHODS AND MATERIALS: The MRI system, with corrected distortion, was registered on computed tomography (CT) by means of fiducial/anatomic landmarks. In 41 consecutive patients with various CNS diseases, GTVs determined by MRI/CT registration (MR/CT-GTV) and CT alone (CT-GTV) were compared. Hard copies of diagnostic MRI were shown to doctors when CT-GTV was determined to simulate a conventional planning situation. Multi-observer volumetric analysis was conducted, assessing interobserver deviations among four radiation oncologists and intermethodological deviations between MR/CT-GTV and CT-GTV. RESULTS: Overall, the mean of geometric distortion was significantly reduced from 1.08 mm to 0.3 mm by distortion correction (p < 0.0001). The contribution of the correction was apparent at >12.0 cm radius from the center of the magnetic field. Interobserver deviation was significantly reduced by MR/CT registration (p = 0.005). The improvement was significant for acoustic neurinoma (p = 0.038), astrocytomas (p = 0.043), and lesions at the cerebellum/brainstem (p = 0.008). The regression coefficient between MR/CT-GTV and CT-GTV was <0.9 for cerebellum/brainstem lesions, suggesting that MRI/CT-GTV was smaller than CT-GTV. CONCLUSIONS: This system is feasible for three-dimensional planning and was shown to reduce interobserver deviations in GTV delineation for CNS diseases.

Brain Neoplasms↗
PubMed2001

Diffusion-weighted MR imaging of Carmofur-induced leukoencephalopathy.

Carmofur (1-hexylcarbamyl-5-fluorouracil), a derivative of 5-fluorouracil (5-FU), has been widely used in Japan as a postoperative adjuvant chemotherapy agent for colorectal and breast cancer. Periventricular hyperintensity on T2-weighted MR images in carmofur-induced leukoencephalopathy confront the physician with a broad range of differential diagnoses. We describe two cases of carmofur-induced leukoencephalopathy in which diffusion-weighted MR imaging revealed periventricular hyperintensity. We compared their findings with those of age-related periventricular hyperintensity in five patients and found discrepancies in signal intensity of periventricular areas. Our results suggest that diffusion-weighted MR imaging may be useful to differentiate carmofur-induced leukoencephalopathy from age-related periventricular hyperintensity.

Adult↗
PubMed2001

Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions.

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.

Aged↗
PubMed2001

Intracellular processing of aggregated tau differs between corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are sporadic neurodegenerative diseases with intracytoplasmic aggregates of the microtubule-associated protein, tau, in neurons and glial cells. Immunoblot analysis of detergent-insoluble brain extracts of patients with CBD and PSP shows distinctive patterns of tau fragments. These results suggest differing intracellular processing of aggregated tau in these two diseases despite an identical composition of tau isoforms. Such biochemical differences may be related to the neuropathological features of these diseases.

Aged↗
PubMed2001

Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs.

An effective method for determination of the levels of newly discovered 31-amino acid endothelins [ETs(1-31)] as well as big ETs and 21-amino acid ETs [ETs(1-21)], in human lungs has been developed. About 85% of ETs in human lung homogenates were recovered on acid extraction 8 times. Most of the published protocols for the determination of tissue ETs involve a reverse-phase minicolumn to separate proteins from peptides, after which the levels of ETs are directly determined by enzyme immunoassay. The levels determined, however, include fairly high amounts of non-bioactive ET metabolites in tissues and the data reported are diverse. We established an effective methods for the extraction and the separation of nine different muscle constricting ETs from their metabolites on a reverse-phase C18 column. Using this protocol, the levels of ETs in human lungs were determined by means of a sandwich-enzyme immunoassay specific for each ET derivative. The levels of ET-2(1-21) were the highest among those of ETs, and the levels of ETs(1-31) were in a similar range to those of big ETs but were lower than those of ETs(1-21). This method can be utilized to assess the pathophysiological roles of ETs(1-31) in various human organs.

Chromatography, High Pressure Liquid↗
PubMed2001

New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels.

The thrombopoietic status of patients with uremia remains unclear. This issue was addressed with particular reference to marrow megakaryocytopoiesis and endogenous thrombopoietin (TPO) levels. A study was conducted in 114 patients on hemodialysis, 43 patients on continuous ambulatory peritoneal dialysis, and 48 age-matched controls. Reticulated platelets, a marker of marrow megakaryocytopoiesis, were measured by flow cytometry. Serum TPO levels, platelet-associated IgG (PAIgG) levels, and hepatitis C virus (HCV) antibody titers were also measured by enzyme-linked immunosorbent assay. Circulating and reticulated platelet counts were significantly lower in the patients on dialysis than in the controls. Thrombocytopenia (less than 150 x 10(9)/L) was most frequent in the HCV-positive hemodialysis patients, who had a higher incidences and higher PAIgG titers. The following results were obtained in the HCV-negative dialysis patients: (1) platelet counts chronologically decreased with years on hemodialysis; (2) platelet counts were associated with the reticulated platelet counts; (3) serum TPO levels were significantly elevated in the dialysis patients, responding to the decrease of reticulated platelets; (4) hematocrits had a positive correlation with serum TPO levels, and serum TPO levels were significantly higher in the patients on hemodialysis who did not require recombinant human erythropoietin therapy than in the other patients. In conclusion, thrombocytopenia is a frequent finding in patients on dialysis. The failure of megakaryocyte production could be the principal cause of the platelet reduction, and the peripheral destruction and sequestration of platelets may be concomitantly involved. Elevation of serum TPO may in part serve as an aid to erythropoiesis in dialysis patients.

Adult↗
PubMed2001

A second susceptibility gene for developing rheumatoid arthritis in the human MHC is localized within a 70-kb interval telomeric of the TNF genes in the HLA class III region.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a multifactorial genetic basis. However, pathogenic genes for RA other than the human leukocyte antigen (HLA)-DRB1 gene have yet to be identified. Here, we investigated whether there is a second susceptibility locus for RA within the human major histocompatibility complex using 18 microsatellite markers distributed from the centromeric (HSET) to the telomeric end (P5-15) of the 3.6-Mb HLA region. Statistical studies of associated alleles on each microsatellite locus showed that one pathogenic gene for RA in the HLA region is localized in the DRB1 gene, as expected. Further, a second susceptibility gene of RA was suggested to be present in the HLA class III region, narrowed to 70 kb, that is just telomeric of the TNF gene cluster (TNFA and LTA) and that is located between the microsatellites TNFa and C1-2-A. In this critical segment, four expressed genes have been thus far identified, NFKBIL1 (IkappaBL), ATP6G, BAT1, and MICB, all of which are candidate genes for determining susceptibility to RA. These results exclude the possibility of involvement of the TNFA genes (TNF-alpha) in the development of RA, which was suggested previously to be a strong candidate for RA in the class III region.

Alleles↗
PubMed2001

Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study.

A 62-year-old woman initially presented with slowly progressive nonfluent aphasia with minimal intellectual involvement. Echolalia and personality change were prominent whereas parkinsonian features and signs suggesting parietal lobe dysfunctions were not present. The patient's language deficit was consistent with transcortical motor aphasia. She did not manifest extrapyramidal signs. The patient was diagnosed as having Pick's disease or frontal lobe dementia. She died at age 65, 2 years and 9 months following disease onset. Neuropathological findings including cytoskeletal abnormalities, however, were clearly distinct from those of classical Pick's disease and were consistent with those reported in corticobasal degeneration (CBD). The distribution of her cortical lesions was accentuated in the frontal language-related area. The clinical manifestations in CBD are diverse, and primary progressive nonfluent aphasia should be considered as an initial symptom of CBD. Neuropathological examination of such patients should include cytoskeletal abnormality studies.

Aphasia, Primary Progressive↗
PubMed2001

Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro.

We investigated the extent to which NO participates in the developmental competence (oocyte maturation, fertilization and embryo development to blastocyst) using an in vitro culture system adding sodium nitroprusside (SNP), NO donor, and NOS inhibitor (N-omega-nitro-L-arginine methyl ester, L-NAME). We also assessed the effects of NO/NOS system on blastocyst implantation using an in vitro trophoblast outgrowth assay. The treatment of low concentrations of SNP (10(-7) M) significantly stimulated meiotic maturation to metaphase II stages in cumulus enclosed oocytes. In contrast, 10(-3) and 10(-5) M L-NAME demonstrated a significant suppression in resumption of meiosis. This inhibition was reversed by the addition of SNP. No development beyond the four-cell stage was observed by the addition of high concentration of SNP (10(-3) M). Inhibition of embryo development, especially the conversion of morulae to blastocysts, was also observed in the treatment of lower doses of SNP (10(-5) and 10(-7) M). Similarly, inhibition of NO by NOS inhibitor resulted in the dose-dependent inhibition of embryo development and hatching rates, but the concomitant addition of SNP with L-NAME reversed the inhibitory effect by each SNP or L-NAME treatment. Furthermore, low concentration of SNP (10(-7) M) but not high concentration of SNP (10(-3) M) significantly stimulated trophoblast outgrowth, whereas the addition of L-NAME suppressed the spreading of blastocysts in a dose-dependent manner. These results suggest that NO may have crucial roles in oocyte maturation and embryogenesis including the process of implantation. The observed differences in required amount of NO and the sensitivity to cytotoxicity of NO in each developmental stage embryos may also suggest that NO/NOS system is tightly regulated in developmental stage specific manner.

Animals↗
PubMed2001

Familial X centromere variant resulting in false-positive prenatal diagnosis of monosomy X by interphase FISH.

Interphase fluorescent in situ hybridization (FISH) analysis performed on uncultured amniotic fluid cells from a female fetus revealed a single signal using an X chromosome alpha-satellite probe, and the absence of any signal using a Y chromosome alpha-satellite probe. This result was initially interpreted as monosomy for the X chromosome in the fetus. Subsequent chromosome analysis from the cultured amniotic fluid cells showed two apparently normal X chromosomes. FISH using the X alpha-satellite probe on metaphase spreads revealed hybridization to both X chromosomes, although one signal was markedly reduced compared to the other. The same hybridization pattern was observed in the mother of the fetus. This is the first report of a rare familial X centromere variant resulting in a false-positive diagnosis of monosomy X by interphase FISH analysis for prenatal diagnosis.

Adult↗