PubMed Health⌕ Search

Biomedical subjects

S Hiraoka

Publications and source records attributed to S Hiraoka.

At least 19 recordsLinked to original sources
PubMed2006

Therapeutic efficacy of leukocytapheresis in a pregnant woman with severe active ulcerative colitis.

Leukocytapheresis has recently been used to induce remission in patients with ulcerative colitis (UC) who fail to respond to corticosteroids. We could not find a report in the literature on leukocytapheresis for UC with gestational exacerbation. We have recently encountered this unique condition and report the details here. A 30-year-old Japanese woman with left-sided severe UC was corticosteroid-dependent and had recurrence of the active disease during tapering of corticosteroid. She declined any dose increase and the use of any immunosuppressive agent because she was in the 13th week of pregnancy. Then, concomitant leukocytapheresis was performed without increasing the corticosteroid dose. Recovery was rapid and dramatic. Mucous and bloody stool decreased after the first session, and she had remission 2 weeks later. She underwent a total of four sessions without complications. After 6 weeks, she was discharged from our hospital and underwent maintenance treatment as an outpatient with mesalazine and corticosteroid tapering. Subsequently, she gave birth to a healthy baby girl by an uncomplicated vaginal delivery while keeping the remitted stage of UC.

Adult↗
PubMed2003

A developmentally regulated and psychostimulant-inducible novel rat gene mrt1 encoding PDZ-PX proteins isolated in the neocortex.

Single or repeated exposure to psychostimulants such as amphetamines and cocaine after postnatal week 3 leads to an enduring enhancement in the psychotomimetic responses elicited by a subsequent challenge of a stimulant in rodents. This behavioral sensitization phenomenon has been considered to be the neural consequences of stimulant-induced alterations in gene expression in the brain after a critical period of postnatal development. Using a differential cloning technique, RNA arbitrarily primed PCR, we have now identified from the rat neocortex a novel and developmentally regulated methamphetamine (MAP)-inducible gene mrt1 (MAP responsive transcript 1). mrt1 encodes two major types of PDZ- and PX-domains containing proteins of approximately 62 kDa in size with different carboxy termini, Mrt1a and Mrt1b. The mrt1 mRNAs for Mrt1a, mrt1a, and for Mrt1b, mrt1b, are predominantly expressed in various brain regions and the testes, respectively. Acute MAP injection upregulated mrt1b expression in the neocortex after postnatal week 3 in a D1 receptor antagonist-sensitive manner without affecting mrt1a expression. This upregulation was mimicked by another stimulant, cocaine, whereas pentobarbital and D1 antagonist failed to change the mrt1b transcript levels. Moreover, repeated daily treatment of MAP, but not MAP plus D1 antagonist, for 5 days caused an augmentation of the basal expression of mrt1b 2 and 3 weeks after the drug discontinuation. These late-developing, cocaine-crossreactive, D1 antagonist-sensitive and long-term regulations of mrt1b by MAP are similar to the pharmacological profiles of stimulant-induced behavioral sensitization, and therefore may be associated with the initiation and/or maintenance of the long-term neuronal adaptation.

Aging↗
PubMed2003

Gastrin activates nuclear factor kappaB (NFkappaB) through a protein kinase C dependent pathway involving NFkappaB inducing kinase, inhibitor kappaB (IkappaB) kinase, and tumour necrosis factor receptor associated factor 6 (TRAF6) in MKN-28 cells transfected with gastrin receptor.

BACKGROUND: We previously reported that gastrin induces expression of CXC chemokines through activation of nuclear factor kappaB (NFkappaB) in gastric epithelial cells that express gastrin receptor. AIMS: To clarify gastrin receptor mediated signals leading to activation of NFkappaB. METHODS: MKGR26 cells were created by transfecting gastrin receptor cDNA into MKN-28 cells. Degradation of inhibitor kappaB (IkappaB) and phosphorylation of protein kinase C (PKC)-delta were both detected by western blot analysis. NFkappaB activation was determined by luciferase assay and electrophoretic mobility shift analysis. RESULTS: Gastrin induced degradation of IkappaB-alpha and activation of NFkappaB, which was abolished by the selective gastrin receptor antagonist L-740,093 and the general PKC inhibitor GF109203X. Gastrin induced phosphorylation of PKC-delta, and its inhibitor rottlerin partially suppressed NFkappaB activation. However, the mitogen activated protein kinase (MAPK) kinase inhibitor PD98059, p38 MAPK inhibitor SB203580, and tyrphostin AG1478 had no effect on NFkappaB activation. Introduction of the dominant negative mutant of IkappaB kinase, of NFkappaB inducing kinase, and of tumour necrosis factor receptor associated factor 6 (TRAF6), but not that of TRAF2, inhibited gastrin induced activation of NFkappaB. CONCLUSIONS: Gastrin activates NFkappaB via a PKC dependent pathway which involves IkappaB kinase, NFkappaB inducing kinase, and TRAF6.

Animals↗
PubMed2001

PPARgamma agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF-like growth factors in ras-transformed rat intestinal epithelial cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits the growth of several types of cancer cells. However, the mechanisms by which this occurs are poorly understood. The goal of the present study was to investigate the effects of PPARgamma on mutated ras-induced cell growth, activation of transcription factors and expression of genes associated with cellular transformation in rat intestinal epithelial cells. A human PPARgamma cDNA was introduced to the activated H-ras-transfected IEC-6 cells (IECras) and 1 clone (IECrasPR82) that stably expresses both activated ras and PPARgamma was obtained. Thiazolidinedione derivatives such as troglitazone and rosiglitazone, selective ligands for PPARgamma, inhibited the cellular growth of IECrasPR82 cells in a time-dependent manner and induced G1 cell cycle arrest. Treatment with troglitazone (20 microM) decreased the expression of cyclin D1, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin and suppressed the promoter activities of cyclin D1 and HB-EGF. Furthermore, a luciferase assay and an electrophoretic mobility shift assay showed that thiazolidinedione derivatives suppressed the transcriptional activities of AP-1 and Ets, both of which play crucial roles in the expression of cyclin D1 and HB-EGF. These findings suggest that reduction of EGF-like growth factors and cyclin D1 through the suppression of AP-1 and Ets may be 1 mechanism whereby PPARgamma inhibits their growth.

Animals↗
PubMed2001

Mesyloxy-group migration as the stereoselective preparation method of various functionalized olefins and its reaction mechanism.

[structure: see text]. It was demonstrated that mesylation of appropriate gamma,gamma-difluorinated allylic alcohols under usual conditions furnished the corresponding alpha,alpha-difluorinated allylic mesylates, possibly by way of 1,3-mesyloxy-group migration after formation of the expected "normal" intermediates, gamma,gamma-difluorinated allylic mesylates. This rearrangement was conveniently applied to the construction of trisubstituted allylic alcohols, alpha,beta-unsaturated esters, amides, or ketones in good to excellent chemical yields with exclusive E selectivities.

Journal Article↗
PubMed2001

Performance of a shaking vessel with current pole.

To improve solid particle suspensions in liquids in a shaking vessel, a pole was installed at the axis of the shaking vessel, which was referred to as the "current pole". The performance of a shaking vessel with current pole at its central axis was examined experimentally with respect to particle dispersion, power consumption, mixing time and solid-liquid mass transfer coefficient. The current pole improved the particle suspension without an increase in power consumption and reduced the critical circulating frequency for complete suspension. The current pole was very effective in eliminating the stagnation point on the vessel bottom and to decrease the mixing time. The mass transfer coefficient with a current pole had the same value as that without a current pole above the critical circulating frequency for complete suspension. As the diameter of the current pole increased, the mixing time decreased. A pole diameter of 5% of the vessel diameter was effective for suspension.

Journal Article↗
PubMed2001

Epidermal growth factor receptor mediates stress-induced expression of its ligands in rat gastric epithelial cells.

BACKGROUND & AIMS: Epidermal growth factor (EGF)-like growth factors are induced after acute gastric injury and may play an important role in mucosal repair. However, the mechanisms that trigger these growth factors are poorly understood. We determined the role of EGF receptor (EGFR) in stress-induced expression of heparin-binding EGF-like growth factor (HB-EGF) in a rat gastric epithelial cell line (RGM1 cells). METHODS: RGM1 cells were transfected with a plasmid containing complementary DNA encoding a dominant-negative human EGFR (HERCD533). Cells were treated with hydrogen peroxide (0-400 micromol/L) or sorbitol (600 mmol/L). Tyrosine phosphorylation of EGFR was determined by immunoprecipitation and Western blotting with an antiphosphotyrosine antibody. HB-EGF messenger RNA and protein were determined with Northern and Western blotting, respectively. Cell growth was evaluated by cell number and [(3)H]thymidine incorporation. RESULTS: Oxidative stress and osmotic stress induced tyrosine phosphorylation of EGFR within 2 minutes, followed by a marked increase in HB-EGF and amphiregulin transcripts in RGM1 cells. Introduction of HERCD533 into the cells inhibited not only tyrosine phosphorylation of EGFR but also growth response to EGF. Furthermore, oxidative stress-induced HB-EGF messenger RNA expression was impaired in HERCD533-expressing cells. CONCLUSIONS: EGFR plays a crucial role in the stress-induced expression of EGF-like growth factors in gastrointestinal epithelial cells.

Amphiregulin↗
PubMed2001

Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappaB.

Although hypergastrinemia is frequently observed in individuals with a chronic Helicobacter pylori infection, its pathophysiological significance in gastric mucosal inflammation is unclear. The present study was designed to determine if gastrin induces the expression of CXC chemokines in gastric epithelial cells. Human and rat gastric epithelial cells, transfected with gastrin receptor, were stimulated with gastrin. The expression of mRNAs for human interleukin-8 (IL-8) and rat cytokine-induced neutrophil chemoattractant-1 and release of human IL-8 protein were then determined by Northern blot analysis and ELISA, respectively. Gastrin not only induced the expression of mRNAs for these chemokines but also stimulated IL-8 protein release. A luciferase assay using IL-8 promoter genes showed that nuclear factor (NF)-kappaB is absolutely required and activator protein-1 (AP-1) is partly required for the maximum induction of IL-8 by gastrin. An electrophoretic mobility shift assay revealed that gastrin is capable of activating both NF-kappaB and AP-1. In addition, the inhibition of NF-kappaB abrogated gastrin-induced chemokine expression. These results suggest that gastrin is capable of upregulating CXC chemokines in gastric epithelial cells and therefore may contribute to the progression of the inflammatory process in the stomach.

Animals↗
PubMed2000

Polymorphisms in FcepsilonRI beta chain do not affect IgE-mediated mast cell activation.

Genetic polyymorphisms that result in three amino acid changes in FcepsilonRI beta chain (Ile(181)-->Leu, Val(183)-->Leu, and Glu(237)-->Gly) have been identified as candidates that associate with allergic disorders such as atopy and asthma. To elucidate the biological significance of these polymorphisms in regulating the expression and function of FcepsilonRI, we generated four types of transfectants that express wild-type or mutant mouse beta chains corresponding to these human variants by retrovirus-mediated gene transfer into beta chain-deficient mouse-derived mast cells. No significant functional differences between the wild-type beta chain transfectant and any of the mutant beta chain transfectants were observed in beta-hexosaminidase release, intracellular calcium mobilization, or cytokine and leukotriene C(4) production in response to FcepsilonRI crosslinking. Our results suggest that these polymorphisms in FcepsilonRI beta chain do not affect FcepsilonRI-mediated mast cell activation at least in our mouse in vitro system.

Animals↗
PubMed2000

Met/HGF receptor modulates bcl-w expression and inhibits apoptosis in human colorectal cancers.

The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor. In the present study, we investigated the role of met expression on the modulation of apoptosis in colorectal tumours. The gene expressions of c-met and the anti-apoptotic bcl-2 family, including bcl-2, bcl-x(L)and bcl-w, were analysed in human colorectal adenomas and adenocarcinomas by using a quantitative polymerase chain-reaction combined with reverse transcription. In seven of 12 adenomas and seven of 11 carcinomas, the c-met gene was overexpressed. The bcl-w, bcl-2 and bcl-x(L)genes were over-expressed in nine, five and six of 12 adenomas and in five, two and seven of 11 carcinomas, respectively. The c-met mRNA level in human colorectal adenomas and carcinomas was correlated with bcl-w but not with bcl-2 or with bcl-x(L)mRNA level. The administration of c-met-antisense oligonucleotides decreased Met protein levels in the LoVo human colon cancer cell line. In the case of c- met -antisense-treated cells, apoptotic cell death induced by serum deprivation was more prominent, compared to control or c-met -nonsense-treated cells. Treatment with c-met-antisense oligonucleotides inhibits the gene expression of bcl-w in LoVo cells. On the other hand, the gene expression of bcl-2 or bcl-x(L)was not affected by treatment with c-met-antisense oligonucleotides. These findings suggest that Met expression modulates apoptosis through bcl -w expression in colorectal tumours.

Adenocarcinoma↗
PubMed2000

Quality of life in adult patients after stem cell transplantation.

Many articles pertaining to quality of life (QOL) following stem cell transplantation have been published in the US and western Europe. However, since the actions of health insurance systems and overall cultural aspects are strongly associated with QOL, investigations into QOL should be carried out within all countries. Therefore, we have investigated the QOL of adult patients following stem cell transplantation at 31 hospitals in Japan. The survivors, who were surveyed by mail questionnaire, were 20 years or older at the time of this study. The underlying diseases were acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, myelodysplastic syndrome, and multiple myeloma. Median age at the time of the study was 36 years, and median interval after transplantation was 35.3 months. Of 383 patients surveyed, 282 (73.6%) responded to the questionnaire. One hundred and ninety-two patients were treated with an allogeneic-related transplantation, 52 with allogeneic-unrelated, and 38 with an autologous transplantation. Our data revealed that the length of time since transplantation and the diagnosis of chronic GVHD were associated with QOL. When unrelated and related transplantation recipients were compared, ratings on relief from pain, stability in weight, and confidence in dealing with daily life were lower among unrelated transplantation patients.

Adolescent↗
PubMed1999

PPARgamma inhibits the expression of c-MET in human gastric cancer cells through the suppression of Ets.

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) is shown to inhibit the growth of MKN-45 cells, a human gastric cancer cell line, which overexpresses c-Met tyrosine kinase. The aim of the present study was to investigate whether PPARgamma regulates the expression of c-Met. Two days after the activation of PPARgamma by troglitazone, a potent and selective PPARgamma ligand, a dramatic reduction of c-MET transcripts and the c-Met protein in MKN45 cells was observed. The luciferase assay showed that the activation of PPARgamma suppressed -249 to +330 c-MET promoter activity, driven by cotransfection of ETS-1 expression vector. These data demonstrate that PPARgamma activation is capable of suppressing Ets-induced c-MET gene transcription. Thus, it is possible that the growth inhibitory effect of PPARgamma on MKN-45 cells is related to the suppression of c-MET transcription.

Cell Division↗
PubMed1999

DNA sequence comparison considering both amino acid and nucleotide insertions/deletions because of evolution and experimental error.

Amino acid similarity often needs to be considered in DNA sequence comparison to elucidate gene functions. We propose a Smith-Waterman-like algorithm which considers amino acid similarity and insertions/deletions in sequences at the DNA level and at the protein level in a hybrid manner. The algorithm is applied to cDNA sequences of Oryza sativa and those of Arabidopsis thaliana. The results are compared with the results of application of NCBI's tblastx program (which compares the sequences in the BLAST manner after translation). It is shown that the present algorithm is very helpful in discovering nucleotide insertions/deletions originating from experimental errors as well as amino acid insertions/deletions due to evolutionary reasons.

Algorithms↗
PubMed1999

Endoscope disinfection using acidic electrolytic water.

BACKGROUND AND STUDY AIMS: The aim of the present study was to evaluate a new endoscope disinfector (WM-1) that uses acidic electrolytic water (AEW). MATERIALS AND METHODS: AEW was produced by electrolysis of a 0.05% NaCl-water mixture, with a redox potential greater than 1000 mV and a pH lower than 2.7. In the first study, an endoscope artificially contaminated with 15 species of bacteria and four strains of viruses was treated using the WM-1. In the second study, endoscopic contamination after clinical use was examined by culture for Helicobacter pylori and other bacteria, and by polymerase chain reaction for the H. pylori urease gene and hepatitis C virus. The extent of contamination was then examined after exposing the WM-1 to AEW. The safety of AEW was examined using both in vivo and in vitro studies. RESULTS: All of the bacteria and viruses were destroyed or inactivated after the instrument had been exposed to AEW. Clinical contamination was detected from the instrument in 19 of 30 endoscopic procedures, whereas no bacteria or viruses were detected after five minutes' exposure to AEW. AEW was found to be nonirritant, nontoxic to cells, and nonmutagenic. CONCLUSION: The WM-1 successfully and safely disinfected the endoscopes. With running costs of yen 24 per day ($0.21 per day), the WM-1 provides an effective and inexpensive alternative to conventional disinfection equipment.

Acids↗
PubMed1999

Fc receptor beta subunit is required for full activation of mast cells through Fc receptor engagement.

The high-affinity IgE receptor (Fc epsilonRI) and the low-affinity IgG receptor (Fc gammaRIII) on mast cells are the key molecules involved in triggering the allergic reaction. These receptors share the common beta subunit (FcRbeta) which contains an immunoreceptor tyrosine-based activation motif and transduces the signals of these receptors' aggregation. In rodents, FcRbeta is essential for the cell surface expression of the Fc epsilonRI. In humans, the FcRbeta gene was reported to be one of the candidate genes causing atopic diseases. However, the role of FcRbeta in vivo still remains ambiguous. To elucidate the functions of FcRbeta, we developed the mice lacking FcRbeta [FcRbeta(-/-)]. The FcRbeta(-/-) mice lacked the expression of the Fc epsilonRI on mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) was not induced in FcRbeta(-/-) mice as was expected. In these mice, the expression of IgG receptors on mast cells was augmented but the IgG-mediated PCA reaction was attenuated. Although with bone marrow-derived cultured mast cells from FcRbeta(-/-), adhesion to fibronectin and Ca2+ flux upon aggregation of IgG receptors were enhanced, mast cells co-cultured with 3T3 fibroblasts exhibited impaired degranulation on receptor aggregation. These observations indicate that FcRbeta accelerates the degranulation of mature mast cells via the IgG receptor in connective tissues.

3T3 Cells↗
PubMed1998

Calphostin C induces expression of amphiregulin mRNA via reactive oxygen species in IEC-6 cells.

Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial cells. In this work, we determined the effect of calphostin C on AR mRNA expression in IEC-6 cells, a rat intestinal epithelial cell line, and unexpectedly found that this compound enhanced the TPA-induced expression of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pretreatment with N-acetylcysteine. These results suggest that calphostin C can upregulate expression of AR mRNA via reactive oxygen species.

Acetylcysteine↗