Search PubMed⌕ Search

Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 163 records · Page 9Linked to original sources
PubMed1999

Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Anaphylaxis↗
PubMed1999

Induction of inducible heme oxygenase (HO-1) in the central nervous system: is HO-1 helpful or harmful?

Heme oxygenase (HO) produced biliverdin and bilirubin, which are powerful antioxidants, therefore, it has been proposed as helpful against oxidative stress. In contrast, HO also produces iron, and it could increase oxidative stress if not handled property. To clarify the effect of HO, i.e., helpful or harmful, we examined the expression, localization, and induction mechanism of HO-1 in the rat hippocampus after transient forebrain ischemia and injection of kainic acid (KA). Following ischemia, HO-1 expression was observed early but transiently in the CA1 pyramidal neurons and later but continuously in glial cells. In addition, HO-1-expressing pyramidal neurons were colocalized well with phosphorylated c-Jun, which is a critical step in neuronal apoptosis. After injection of KA, HO-1 expression was observed only in glial cells but not neurons, and HO-1 expression was observed in predominantly ameboid microglia, along with a few astrocytes. HO-1-expressing ameboid microglia expressed major histocompatibility complex class II antigen, suggesting strong activation. These results suggested that HO-1 may have double-edged effects, and its effects may be depend on the cell type. This short review is intended to highlight on the effect of HO-1 in neurodegeneration.

Journal Article↗
PubMed1999

Kainic acid-induced activation of nuclear factor-kappaB in rat hippocampus.

Nuclear factor-kappaB (NF-kappaB) is known to play a key role in immune and inflammatory responses. To understand the mechanisms of inflammatory activation that accompany neuronal damage, we determined the cell type in which NF-kappaB was activated. NF-kappaB protein was detected in the cytosolic fraction of untreated and vehicle-treated rat hippocampus. After kainic acid (KA) treatment, NF-kappaB protein was significantly increased in both the cytosolic and particulate fractions. NF-kappaB immunoreactivity was observed in both brain blood vessels and glial cells after 1 day. Although NF-kappaB immunoreactivity in brain blood vessels disappeared after 3 days, this activity was maintained in glial cells for up to 7 days. In addition, double immunostaining indicates that NF-kappaB was activated in glial cells, such as microglia and astrocytes, after 3 days. Thus, NF-kappaB activation seems to be delayed and to occur continuously in microglia and astrocytes, suggesting that an inflammatory activation in glial cells participates in KA-induced neurodegeneration.

Animals↗
PubMed1999

Expression of bone matrix proteins in urolithiasis model rats.

Urinary calcium stones are a pathological substance, and they show similarities to physiological mineralization and other pathological mineralizations. The expression of messenger (m) RNAs of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and osteocalcin (OC) in bones and teeth has been described. We previously identified OPN as an important stone matrix protein. In addition, the spontaneous calcification of arteries and cartilage in mice lacking MGP was recently reported, a finding which indicates that MGP has a function as an inhibitor of mineralization. Here, we examined the mRNA expressions of OPN, MGP, ON, and OC in the kidneys of stone-forming model rats administered an oxalate precursor, ethylene glycol (EG) for up to 28 days. The Northern blotting showed that the mRNA expressions of OPN and MGP were markedly increased with the administration of EG, but their expression patterns differed. The OPN mRNA expression reached the maximal level at day 7 after the initiation of the EG treatment and showed no significant difference after 14 and 28 days, whereas the MGP mRNA expression rose gradually to day 28. The in situ hybridization demonstrated that the cell type expressing OPN mRNA was different from that expressing MGP. We suggest that OPN acts on calcification and MGP acts on suppression.

Animals↗
PubMed1999

Combination of transileocolic vein obliteration and balloon-occluded retrograde transvenous obliteration is effective for ruptured duodenal varices.

Duodenal varices are a rare site of hemorrhage in patients with portal hypertension, but their rupture is a serious and often fatal event. We report a 65-year-old woman who presented with hematemesis and melena. She was admitted to our department because of prolonged shock, despite having received transfusion of a large volume of blood. Upper gastrointestinal endoscopy revealed nodular varices with active bleeding in the second portion of the duodenum. Endoscopic injection sclerotherapy (EIS) was performed using a tissue adhesive agent, alpha-cyanoacrylate monomer, with only temporary benefit. However, anemia continued to progress after the procedure. Therefore, we combined transileocolic vein obliteration (TIO) with balloon-occluded retrograde transvenous obliteration (B-RIO), using 5% ethanolamine oleate with iopamidol to obliterate the varices. Complete hemostasis was achieved without complications. Neither recurrence of varices nor further bleeding has occurred for over 3 years. We conclude that combined TIO and B-RTO, which can obstruct both the feeding and the draining vessels of duodenal varices to retain the sclerosing agent completely in the varices, is a safe and effective hemostatic measure for ruptured duodenal varices, when EIS has failed to accomplish complete hemostasis.

Aged↗
PubMed1999

Ret/PTC3 is the most frequent form of gene rearrangement in papillary thyroid carcinomas in Japan.

Rearrangements of the RET and TRK proto-oncogenes, which generate fusion oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations. To determine the spectrum of gene rearrangements in Japanese patients, we systematically examined 40 papillary thyroid carcinomas for all possible types of gene fusion events involving RET or TRK genes. RET rearrangements were found in ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3 in six, and a novel RET rearrangement in the remaining patient. In this last patient, the 5' novel sequence was fused in-frame to the RET amino acid sequence; thus, the fusion gene may encode a protein with a RET kinase domain at the carboxy terminus. The RET gene was fused to 5' donor sequences at the beginning of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found in this panel of carcinomas. Our results indicated that constitutive activation of the RET by gene rearrangement is a frequent mechanism of papillary thyroid carcinogenesis in Japanese adults.

Adult↗
PubMed1999

Expression of heme oxygenase-1 mediated by non-NMDA and metabotropic receptors in glial cells: possible involvement of reactive oxygen species production and protein kinase C activation.

Heme oxygenase (HO) produces biliverdin and bilirubin which are physiological antioxidants and potent scavengers of oxygen radicals. Recently, we found that intracerebroventricular injection of kainic acid (KA) induced inducible HO (HO-1) predominantly in glial cells in the rat hippocampus in vivo. In this study, we examined the mechanism of HO-1 expression induced by agonists for glutamate receptors in cultured glial cells in vitro. The HO-1 protein level was significantly enhanced by several agonists for non-N-methyl-D-aspartate (non-NMDA) receptors and metabotropic glutamate receptors (mGluR) such as KA, quisqualic acid (QA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propanoic acid (AMPA), and trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid (ACPD). Among these agonists, QA had the greatest potency. KA-induced HO-1 expression was inhibited by the non-NMDA antagonist NBQX. In addition, KA induced the marked production of reactive oxygen species (ROS), and KA-induced HO-1 expression was also inhibited by the antioxidants allopurinol and ascorbic acid. ACPD-induced HO-1 expression was inhibited by the mGluR antagonist MCPG and the protein kinase C (PKC) inhibitor calphostin C. These results suggest that induction of HO-1 expression by the activation of non-NMDA receptors is mediated by ROS production, and that expression induced by mGluR activation is mediated by PKC activation in rat glial cells.

Animals↗
PubMed1999

Interferon-gamma plus lipopolysaccharide induction of delayed neuronal apoptosis in rat hippocampus.

Interferon-gamma and lipopolysaccharide (IFN-gamma/LPS) induce expression of inducible nitric oxide synthase (iNOS) protein both in cells in vitro and in the brain in vivo. In cultured cells, excessive production of nitric oxide (NO) induces neuronal cell death. However, it is still unclear whether IFN-gamma and LPS might induce neuronal cell death in vivo. In this study, we examined the neuronal cell death and induction of major histocompatibility complex (MHC) antigens after microinjection of IFN-gamma/LPS into the rat hippocampus. Although microglia appeared morphologically ramified in the normal and vehicle-injected hippocampus, microinjection of IFN-gamma/LPS immediately induced the ameboid type. From days 1-7, iNOS was expressed in ameboid microglia surrounding the site of the microinjection. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells appeared among the granular neurons of the dentate gyrus on day 3 and peaked about 7 days after microinjection. When the NOS inhibitor N(G)-nitro-L-arginine (L-NA) was intraperitoneally administered prior to the microinjection, the number of TUNEL-positive neurons decreased in a L-NA dose-dependent manner. These results suggest that IFN-gamma/LPS induces delayed neuronal apoptosis in the hippocampus in vivo, and it possibly involves excessive NO production by iNOS. Thus, this animal model may be one of neurodegenerative with extensive inflammatory activation in the hippocampus.

Animals↗
PubMed1999

Endogenous adenosine protects CA1 neurons from kainic acid-induced neuronal cell loss in the rat hippocampus.

CA3 pyramidal neurons in the rat hippocampus show selective vulnerability to the intracerebroventricular injection of kainic acid (KA). However, the mechanism of this selective neuronal vulnerability remains unclear. In this study, we examined the contribution of endogenous adenosine, a potent inhibitory neuromodulator, to the differences in the neuronal vulnerability of the hippocampus, using microtubule-associated protein (MAP)-2, phosphorylated c-Jun, and major histocompatibility complex (MHC) class II immunoreactivities as markers for neuronal cell loss, neuronal apoptosis and glial activation, respectively. Pretreatment with 8-cyclopenthyltheophylline (CPT), an A1 adenosine receptor antagonist, significantly exacerbated KA-induced neuronal cell loss in both the CA1 and CA3. Although c-Jun phosphorylation, a critical step in neuronal apoptosis, was not detected in the vehicle-injected rat hippocampus, c-Jun phosphorylation was induced in the CA3 by the injection of KA alone. Pretreatment with CPT induced c-Jun phosphorylation in both the CA1 and CA3. MHC class II antigen was also detected in the regions of c-Jun phosphorylation. Coadministration of N6-cyclopenthyladenosine (CHA), an A1 adenosine receptor agonist, attenuated the neuronal cell loss in the CA1 and CA3 with or without pretreatment with CPT. These results strongly suggest that endogenous adenosine has neuroprotective effects against excitotoxin-induced neurodegeneration in the CA1 through its A1 receptors.

Adenosine↗
PubMed1999

Vascular endothelial growth factor activates MAP kinase and enhances collagen synthesis in human mesangial cells.

UNLABELLED: Vascular endothelial growth factor activates MAP kinase and enhances collagen synthesis in human mesangial cells. BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial mitogen that is constitutively expressed in normal human glomeruli, but its role in the kidney is still unclear. In this study, we examined the effects of VEGF on human mesangial cells (HMCs). Methods and Results. Reverse transcription-polymerase chain reaction analysis demonstrated the presence of VEGF receptor mRNA (flt-1 and KDR) in HMCs. The treatment of HMCs with VEGF did not cause a change in 3H-thymidine incorporation or cell numbers. In contrast, VEGF caused a dose- and time-dependent increase in collagen synthesis, with threefold to fivefold increases in both cell-associated and secreted collagen synthesis seen after treatment with 200 ng/ml VEGF. The effects of VEGF were attenuated by treatment of HMCs with the tyrosine kinase inhibitor herbimycin A or the MEK inhibitor PD 98059, but not with the protein kinase C (PKC) inhibitor chelerythrine. VEGF treatment also caused a marked increase in p42/p44 mitogen-activated protein kinase (MAPK) activity, but had no significant effect on HMC superoxide production. Finally, an increase in collagen synthesis was also seen in rat mesangial cells treated with VEGF. CONCLUSIONS: These results suggest that VEGF is not a mitogenic signal in HMCs, but may be involved in the regulation of the mesangial matrix in humans by a MAPK-dependent mechanism.

Animals↗
PubMed1999

The pathophysiology of glossal pain in patients with iron deficiency and anemia.

BACKGROUND: It is well known that prolonged anemia causes atrophy of tongue papillae, glossal pain, and dysphagia, but it is uncertain whether iron (Fe) deficiency induces glossal pain without any objective manifestation. To resolve this matter, the relationship between Fe deficiency and glossal pain was examined. METHODS: Eighteen patients with Fe deficiency and 7 anemic patients manifesting spontaneous irritation or pain of the tongue without any objective abnormalities participated in this study. To ascertain the cause of glossal pain and the oral pathophysiology in Fe deficiency and anemia, peripheral blood was examined and the glossal pain threshold and salivary flow rates (SFRs) were estimated along with Candida albicans cell culture tests. RESULTS: Compared with patients with Fe deficiency, those with anemia had a longer history of tongue pain. In patients with anemia, painful areas of the tongue were more numerous than in patients with Fe deficiency. Pain thresholds were decreased in the painful portions, and both nonstimulated and stimulated SFRs were suppressed. Each patient was treated with oral Fe; within 2 months, most patients exhibited increased serum ferritin level (P< 0.02, paired t-test), pain threshold (P < 0.05) and salivation (P < 0.05) and glossal pain subsided. CONCLUSIONS: Fe deficiency causes glossal pain and the degree of glossal pain increases as Fe deficiency advances to anemia, manifesting hyposalivation and abnormalities of glossal papillae.

Adult↗
PubMed1999

Phosphorylation of c-Jun and its localization with heme oxygenase-1 and cyclooxygenase-2 in CA1 pyramidal neurons after transient forebrain ischemia.

Accumulating evidence on the molecular and cellular basis of ischemia/reperfusion-induced neurodegeneration suggests that oxidative stress is involved. Heme oxygenase (HO) and cyclooxygenase (COX) play physiologically important roles in the CNS. Conversely, HO and COX also can increase oxidative stress. Recent studies suggest that c-Jun phosphorylation is an important step in some forms of stress-induced neuronal apoptosis. In this study, the authors tried to clarify the association of HO and COX with c-Jun phosphorylation. Inducible forms of HO and COX (HO-1 and COX-2, respectively) were transiently induced in CA1 pyramidal neurons after ischemia. c-Jun also was induced in pyramidal neurons throughout the hippocampal formation, but its phosphorylation was limited to CA1. In contrast, these molecules were constitutively expressed at low levels. Most (84%) of the CA1 pyramidal neurons examined expressed HO-1, COX-2, or both, and such expression showed good co-localization with c-Jun phosphorylation. These results suggest the following: (1) c-Jun phosphorylation was associated with ischemia/reperfusion-induced neuronal apoptosis; (2) HO-1 and COX-2 were induced in CA1 pyramidal neurons, which undergo cell death; and (3) most CA1 pyramidal neurons expressed HO-1, COX-2, or both, which strongly suggests that these are candidates for neuron killers.

Animals↗
PubMed1999

Replication of GB virus C (hepatitis G virus) in interferon-resistant Daudi cells.

We previously reported that Daudi cells, a Burkitt's lymphoma cell line, were capable of supporting productive infection of hepatitis C virus (HCV). During continual cultivation after HCV infection, the culture became resistant to interferons (IFNs). This resistant cell line, coded as H-903, was used as host cells for replication of GB virus C (GBV-C), also known as hepatitis G virus. GBV-C RNA was detected in the culture by reverse transcription-PCR for more than 130 days after inoculation, while it was detected for 44 days but not later in the parental IFN-sensitive Daudi cells. Productive infection of GBV-C in the H-903 system was confirmed by serially inoculating supernatants from infected cultures into uninfected cells. The viral E2 antigen was detected by immunofluorescence in the cells inoculated with the fifth passage of GBV-C. The presumed capsid-coding region of the viral genome in the inoculum, in the serially passaged virus, or in the virus produced by a long-term culture was only 16 amino acids long, suggesting that the GBV-C with a short core sequence was replication competent.

Amino Acid Sequence↗
PubMed1999

Monoclonal antibodies against the minimal DNA-binding domain in the carboxyl-terminal region of human immunodeficiency virus type 1 integrase.

Integrase of human immunodeficiency virus type 1 (HIVIN) consists of 288 amino acids, and its minimum DNA-binding domain (MDBD) (amino acids [aa] 220 to 270) is required for the integration reaction. We produced and characterized four murine monoclonal antibodies (MAbs) to the MDBD of HIVIN (strain LAI). Immunoblot and enzyme-linked immunosorbent assays with truncated HIVINs showed that those MAbs recognized sequential epitopes within the MDBD (aa 228 to 236, 237 to 252, 253 to 261, and 262 to 270). Their binding to HIVIN inhibited terminal cleavage and strand transfer activities but not disintegration activity in vitro. This collection of MAbs is useful for studying the structure and function of the MDBD by complementing mutational analyses and other biochemical studies.

Animals↗
PubMed1999

Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene.

The xeroderma pigmentosum group G (XP-G) gene (XPG) encodes a structure-specific DNA endonuclease that functions in nucleotide excision repair (NER). XP-G patients show various symptoms, ranging from mild cutaneous abnormalities to severe dermatological impairments. In some cases, patients exhibit growth failure and life-shortening and neurological dysfunctions, which are characteristics of Cockayne syndrome (CS). The known XPG protein function as the 3' nuclease in NER, however, cannot explain the development of CS in certain XP-G patients. To gain an insight into the functions of the XPG protein, we have generated and examined mice lacking xpg (the mouse counterpart of the human XPG gene) alleles. The xpg-deficient mice exhibited postnatal growth failure and underwent premature death. Since XPA-deficient mice, which are totally defective in NER, do not show such symptoms, our data indicate that XPG performs an additional function(s) besides its role in NER. Our in vitro studies showed that primary embryonic fibroblasts isolated from the xpg-deficient mice underwent premature senescence and exhibited the early onset of immortalization and accumulation of p53.

Animals↗
PubMed1999

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.

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

Immediate causes of death in thyroid carcinoma: clinicopathological analysis of 161 fatal cases.

Most patients with thyroid carcinoma have a good prognosis. Due to the small number of fatal cases, it has not been clarified what conditions result in death for patients with thyroid carcinoma. To provide appropriate management for advanced thyroid carcinoma patients, we analyzed causes of death in 161 fatal cases. Clinical characteristics and immediate (final) causes of death based on pathological conditions were analyzed in 62 anaplastic carcinomas and 99 fatal differentiated carcinomas. Single fatal conditions could not be specified in 55 patients. In the remaining 106 patients, respiratory insufficiency (43%) was the most common specific fatal condition, followed by circulatory failure (15%), hemorrhage (15%), and airway obstruction (13%). Respiratory insufficiency due to remarkable pulmonary metastasis replacing lung tissue, massive hemorrhage and airway obstruction due to uncontrolled local tumors, and circulatory failure resulting from compression of the vena cava by extensive mediastinal or sternal metastases were found to be the most important immediate causes of death. Based on this knowledge, several palliative procedures may be worth considering to improve survival and quality of life in patients with advanced thyroid carcinoma.

Adenocarcinoma, Follicular↗