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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 217 records · Page 12Linked to original sources

Reading of Japanese Kanji (morphograms) and Kana (syllabograms): a magnetoencephalographic study.

Magnetoencephalograms were recorded from six healthy Japanese subjects in order to investigate the areas in the cortices which are involved in the recognition of Japanese characters (Kanji and Kana). Forty-four Kanji (morphograms), 44 Kana (syllabograms) and 20 alphabet letters were used as stimuli. They were presented randomly and the subjects were required to read each stimulus and count the number of letters. The magnetic responses were recorded with dual 37-channel SQUID (Superconducting Quantum Interference Device) gradiometers from the temporal, parietal and occipital areas of the brain. The magnetic responses to Kanji and Kana were similar and consequently the locations of equivalent current dipoles (ECDs) to Kanji and those to Kana did not differ at any recording site. In all the subjects, ECDs were found in the posterior inferior temporal (PIT) areas approximately corresponding to Brodmann area 37 in the latency range of 150-300 msec. These activities were found in both hemispheres without consistent laterality. The location of the ECD moved forward from posterior to anterior in the PIT area as the latency increased in all but one subject. Only one subject showed activities in the left angular gyrus. Since activities in PIT areas were also found in alphabet letters, the bilateral PIT areas are considered to play an essential role in reading.

Adult↗

Induction of furanocoumarin biosynthesis in Glehnia littoralis cell suspension cultures by elicitor treatment.

Cell suspension cultures were established from Glehnia littoralis plants belonging to two different geographic strains. When the cells were treated with yeast extract, they started to produce and excrete furanocoumarins into the culture medium; a major component, bergapten, and a minor one, xanthotoxin, were detected and identified by HPLC and GC/MS. Changes in phenylalanine ammonia-lyase (PAL) activity and furanocoumarin production after elicitor treatment were traced, showing that PAL activity increased rapidly, reached a maximum after 24 h, and then declined to the normal level after 96 h which preceded the induced bergapten production. The induced-PAL activity of the cultured cells established from an S-type plant which accumulated trace amounts of furanocoumarins was about 50% of that in the cultured cells from an N-type plant that accumulated more than 0.1% furanocoumarins in the underground parts. However, the elicited production of bergapten was about six times higher in the cell cultures from the S-type plant. Addition of the PAL inhibitor 2-aminoindan-2-phosphoric acid (AIP) at 10 microM suppressed the induction of PAL activity and furanocoumarin production.

5-Methoxypsoralen↗

Anthocyanin production of Glehnia littoralis callus cultures.

A stable callus line that produces anthocyanins was established from callus derived from a petiole of a Glehnia littoralis seedling and subcultured in the dark. The major anthocyanin which made up about 60% of the total anthocyanins was determined as cyanidin 3-O-(6-O-(6-O-(E)-feruloyl-beta-D-glucopyranosyl) -2-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) by chemical and spectroscopic analyses. Anthocyanin contents in the cells cultured on B5 basal medium containing NAA (1 mg l-1), kinetin (0.01 mg l-1) and 3% sucrose reached 14% (dry wt basis) and the productivity has been sustained for 5 years.

Anthocyanins↗

Switch of osteonectin and osteopontin mRNA expression in the process of cartilage-to-bone transition during fracture repair.

The process of cartilage-to-bone transition (CBT) is a key event for the achievement of rigid bone healing during fracture repair. Since mineralization of cartilaginous matrix is a prerequisite for the initiation of CBT, the genetic localization of mineralization-related bone matrix proteins in CBT was examined in this study. An in situ hybridization method used on decalcified sections with digoxigenin-11-UTP labelled probes identified the cellular localizations of these genes in CBT. Cessation of osteonectin mRNA together with induction of osteopontin mRNA in chondrocyte maturation was observed during the process of CBT in the fracture callus on day 12 after fracture; osteocalcin mRNA was absent in chondrocytes of the CBT area. Induction of osteopontin mRNA in maturated chondrocytes was followed by the expression of mRNAs for osteonectin, osteopontin and osteocalcin in osteogenic cells in the ossification front of CBT. The data suggest that the switch from osteonectin to osteopontin mRNA expression in chondrocyte maturation is one of the key events during CBT. Transcriptional disorders of the expression of these molecules may be linked to the failure of fracture repair, i.e. delayed or prevented hypertrophic osteosynthesis.

Animals↗

Inhibition of immediate type allergic reactions by the aqueous extract of Kum-Hwang-San.

We studied the effect of aqueous extract of Kum-Hwang-San (KHS) on mast cell-mediated immediate type allergic reactions. KHS (1-100 microg/site) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 (200 microg/site) in mice by both topical and intradermal application. KHS (0.1-100 microg/site) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. KHS also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, KHS had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) secretion from RPMC. These results indicate that KHS inhibits immediate type allergic reactions by inhibition of histamine release and TNF-alpha secretion from mast cells in vivo and in vitro.

Animals↗

Nitric oxide donor-induced p53-sensitive cell death is enhanced by Bcl-2 reduction in human neuroblastoma cells.

In human neuroblastoma SH-SY5Y cells, S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO)-donor, caused cell death accompanying p53 expression, nucleosomal DNA fragmentation and cell death. In addition, SNAP-induced cell death and DNA fragmentation were enhanced by pretreatment for 4 days with N6,2'-O-dibutyryl cyclic AMP (diBu-cAMP) or staurosporine, while those were not changed by pretreatment with phorbol 12-myristate 13-acetate (PMA). Protein level of Bcl-2 was decreased by pretreatment with diBu-cAMP or staurosporine, and, on the contrary, the level was increased by pretreatment with PMA. However, these pretreatments did not change Bax protein level and SNAP-induced p53 expression. However, SNAP-treatment did not change protein levels of Bcl-2 and Bax. These results suggest that SNAP-induced p53-sensitive apoptosis is enhanced by Bcl-2 reduction, and that Bcl-2 and Bax may act downstream of p53 in SH-SY5Y cells.

Animals↗

Kainic acid induction of heme oxygenase in vivo and in vitro.

Heme oxygenase, catalyses oxidation of the heme molecule in concert with NADPH-cytochrome P450 reductase and then specifically cleaves heme into biliverdin, carbon monoxide, and iron. Biliverdin and its product, bilirubin, are known to be strong antioxidants. Kainic acid is a potent neurotoxin, and induces selective neuronal loss in the rat hippocampus. Kainic acid acts on the kainate receptors, and kainic acid neurotoxicity may be in part mediated by oxidative stress. In this study, we examined whether or not heme oxygenase was activated in kainic acid-induced neurotoxicity. After intracerebroventricular injection of kainic acid, the heme oxygenase-1 protein level was strongly enhanced, although the constitutive heme oxygenase (heme oxygenase-2) protein level was not changed. One day after treatment, the protein level of heme oxygenase-1 reached a maximum and then gradually decreased over a period of three to seven days. In the rat hippocampus, cells expressing heme oxygenase-1 in vivo were predominately microglia and only a few astrocytes. In addition, heme oxygenase-1 immunoreactivity was predominantly co-localized with major histocompatibility complex class II-, and partly co-localized with class I-immunoreactive microglia. In cultured glial cells in vitro, heme oxygenase- protein was expressed in the microglia even with the vehicle treatment, and was strongly induced in astrocytes by kainic acid treatment. These results suggest that ameboid microglia, which express both heme oxygenase-1 and major histocompatibility complex antigens, may play a key role in a delayed episode of kainic acid-induced microglial activation and neurodegeneration.

Animals↗

Effect of insulin therapy on body fat distribution in NIDDM patients with secondary sulfonylurea failure: a preliminary report.

OBJECTIVE: To clarify the influence of insulin therapy on body weight and fat distribution, we compared these parameters in five non-insulin dependent diabetes mellitus (NIDDM) patients, with secondary sulfonylurea failure, before and after insulin therapy. Body weight increased significantly after instituting insulin treatment. However, the visceral to subcutaneous fat (V/S) ratio decreased significantly due to a marked increase in S-fat without a change in V-fat. Insulin therapy necessitated by sulfonylurea failure does not appear to accelerate the atherogenic process in NIDDM patients as there is no increase in visceral fat.

Adipose Tissue↗

Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells.

BACKGROUND: While mast cells have been previously shown to express both GATA-1 and GATA-2 mRNAs, individual functions for these related factors during their course of differentiation within the mast cell lineage have not yet been defined. To address this question, the expression of GATA-1 and GATA-2 mRNAs and proteins were examined in three mouse mast cell progenitor lines as well as in mast cells isolated from both wild-type and GATA-1-deficient mice. RESULTS: Both mast cell progenitor lines, as well as primary mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells (PMCs) were examined by RNA blotting and immunological analyses. GATA-2 protein was abundantly expressed in all three mast cell lines and in BMMCs, but only weakly in some of PMCs. In contrast, GATA-1 protein was expressed in PMCs and BMMCs after culture in the presence of IL3 and SCF. We also found the presence of Alcian blue staining-positive but berberine staining-negative mast cells in the skin of mice heterozygous to GATA-1 knock-down allele. CONCLUSION: These results suggest that the expression of GATA factor-dependent genes is regulated by GATA-2 during mast cell development and that GATA-1 is required for the specification of differentiated mast cell phenotypes.

Animals↗

c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.

AIMS: The c-erbB-2 proto-oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c-erbB-2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c-erbB-2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma. METHODS AND RESULTS: In this study, we evaluated immunoreactivity for the c-erbB-2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n = 6). In normal adult livers and fetal livers, expression of c-erbB-2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c-erbB-2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c-erbB-2 protein. Moreover, the biliary cell expression of the c-erbB-2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c-erbB-2 was found in 33/47 (70%) cholangiocarcinomas. The c-erbB-2 expression in cholangiocarcinomas did not correlate with Ki67 labelling index or p53 expression. CONCLUSIONS: These results indicate that aberrant expression of c-erbB-2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c-erbB-2 oncogene participates not only in cholangiocarcinogenesis but also in biliary cell proliferation in non-neoplastic conditions.

Adult↗

Induction of heme oxygenase-1 and major histocompatibility complex antigens in transient forebrain ischemia.

Recent studies strongly suggest that oxidative stresses participate in ischemia/reperfusion-induced neurodegeneration. In addition, heme oxygenase (HO) and major histocompatibility complex (MHC) antigens serve as functional molecules against oxidative stress and as self-recognition markers in the immune system, respectively. In this study, we examined the induction of HO and MHC antigens in the rat hippocampus after transient forebrain ischemia. The protein level of HO-1 was significantly enhanced after an episode of ischemia. After ischemia, HO-1 expression was observed early but transiently in the CA1 pyramidal neurons and later but continuously in glial cells. Glial cells expressing HO-1 were predominantly ameboid microglia, but not astrocytes. Ameboid microglia expressing HO-1 were predominantly localized with MHC class II antigens. These results indicate that (1) HO-1 expression in CA1 pyramidal neurons may be harmful, and (2) ischemia induces HO-1 in ameboid microglia that express MHC class II antigens, indicating a very specific microglial stress protein response.

Animals↗

Endothelin in liver cell injury and regeneration after 70% hepatectomy with portal ischemia.

Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a common problem in hepatobiliary surgery. Endothelin (ET) is a potent vasoconstrictor and is associated with IR injury. This study evaluated the effect of ET on liver cell injury and hepatic regeneration after hepatectomy with IR. The portal veins of rats were clamped for 20 min, then unclamped and a 70% partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)]. Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal cells were evaluated. ET-1 concentration increased after IR and was significantly higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes and hepatic blood flow did not change in the TAK(+) group. Changes in desmin staining showed that Ito cells might be related to IR injury. In conclusion, ET-1 was associated with IR injury and TAK-044 reduced but did not affect hepatocyte DNA synthesis after partial hepatectomy.

Animals↗

Expression and localization of ornithine decarboxylase in reversible papillomatosis induced by uracil in rat bladder.

Direct mechanical irritation by uracil calculi formed following feeding of 3% uracil in the diet to male rats produces severe papillary hyperplasia (papillomatosis, which is reversible) of bladder epithelium. To evaluate the mechanism of the appearance of uracil-induced papillomatosis, we examined the changes of the enzyme activity and the localization of ornithine decarboxylase (ODC), as well as polyamine biosynthesis, and epithelial proliferation, that accompany the sequential bladder epithelial changes following administration and withdrawal of uracil. Moreover, expression of ODC mRNA was investigated using northern blotting and localization of ODC mRNA was demonstrated using in situ hybridization. ODC activity during uracil administration was maintained at a high level compared to that in normal epithelium, but sharply decreased after cessation of uracil treatment. The accumulation of ODC protein was observed in the proliferating bladder epithelium by immunohistochemical examination and western blotting analysis, and even after cessation of treatment, the protein binding to anti-ODC antibody remained mildly elevated. Sequential changes of proliferating cell nuclear antigen (PCNA)-positive cells in the epithelium during the development and disappearance of papillomatosis correlated with ODC activity. ODC mRNA was expressed strongly in the proliferating epithelium in rats treated with uracil and weakly in normal epithelium, in accordance with the location of ODC protein. Consequently, our data demonstrate that cell proliferation in the development of papillomatosis is closely associated with polyamine metabolism, and moreover suggest that ODC activity is up-regulated at a post-translational step.

Animals↗

Plasma transforming growth factor-beta 1 concentrations in patients with chronic viral hepatitis.

Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.

Biomarkers↗

Disturbed pyloric motility in Ws/Ws mutant rats due to deficiency of c-kit-expressing interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) are believed to initiate the basic contractile activity of the gastrointestinal tract. Interstitial cells of Cajal express c-kit receptor tyrosine kinase and are deficient in Ws/Ws mutant rats with a small deletion of the c-kit gene. As Ws/Ws rats show remarkable bile reflux to the stomach, the contraction pressure of the pylorus was compared between Ws/Ws and control +/+ rats. The contraction pressure of the pylorus was measured using a microtransducer, which was inserted through a pin-hole in the anterior wall of the stomach under anesthesia. The magnitude of bile reflux was estimated by measuring the content of bile acids in the stomach. The c-kit messenger RNA-expressing cells were detected by in situ hybridization. Frequency and the maximum pressure of the contraction were comparable between Ws/Ws and +/+ rats, but the duration of the contraction was significantly shorter in Ws/Ws rats than in +/+ rats. The number of c-kit messenger RNA-expressing ICC in the pylorus of Ws/Ws rats was 1.7% that of +/+ rats. The bile reflux observed in Ws/Ws rats was attributed to the decrease in the duration of the pyloric contraction, which appeared to result from the deficiency of c-kit messenger RNA-expressing ICC.

Animal Feed↗

An autopsy case of ancient sarcoidosis associated with severe fibrosis in the liver and heart.

An autopsy case of ancient sarcoidosis with severe fibrosis in the liver and heart was reported. The patient was a 61-year-old female when she died, 12 years after the onset of sarcoidosis. Cervical lymph node biopsy at 49 years demonstrated non-necrotizing sarcoid granuloma, and laboratory data were compatible with sarcoidosis. Liver and heart failure were observed clinically, and because of heart failure a pacemaker was implanted. She died of septic shock at 61 years. At autopsy, the liver demonstrated cirrhotic severe fibrosis, cholestasis, and acute cholangitis without mechanical bile duct obstruction. In the heart, severe fibrosis was observed, and infectious foci of candida infection were observed on the cardiac valves. Although both liver and heart did not show typical sarcoid granuloma, fibrosis was thought to be due to sarcoidosis because no other causes of liver and heart fibrosis were identified clinically or pathologically. There were systemic foci of candida infection, and she died of sepsis due to candida infection. It was speculated that immunological impairment induced candida infection. This case seems to be a rare and important case of ancient sarcoidosis.

Autopsy↗

Expression of pancreatic alpha-amylase protein and messenger RNA in hilar primitive bile ducts and hepatocytes during human fetal liver organogenesis: an immunohistochemical and in situ hybridization study.

AIMS/BACKGROUND: This study was conducted to evaluate the expression of pancreatic digestive enzymes in hilar bile ducts and hepatocytes during human fetal liver organogenesis. METHODS: We investigated the expression of pancreatic alpha-amylase protein and messenger RNA (mRNA) in hilar primitive bile ducts and hepatocytes by immunohistochemistry and in situ hybridization techniques, using 11 human fetal livers of various gestational ages. The specificity of the immunohistochemistry and in situ hybridization procedures was confirmed by Western blot analysis and in situ hybridization using sense probes, respectively. RESULTS: Immunoreactivity of pancreatic alpha-amylase protein and expression of pancreatic alpha-amylase mRNA were present not only in the primitive ductal cells of the hilar region including the ductal plate, remodelling bile ducts and remodeled bile ducts but also in primitive hepatocytes of the hilar region, though the immunoreactivity and mRNA signals in the primitive hepatocytes disappeared in the third trimester. There was perfect correlation between immunohistochemistry and in situ hybridization. CONCLUSIONS: These results suggest that primitive biliary cells and hepatocytes of the hilar region in the human fetus do express pancreatic alpha-amylase protein and mRNA, and that the primitive biliary epithelial cells and hepatocytes in the hilar region share a common cell lineage with exocrine pancreatic cells.

Bile Ducts, Intrahepatic↗