Biomedical subjects

Hiroshi Ikeda

Publications and source records attributed to Hiroshi Ikeda.

At least 19 recordsLinked to original sources

PubMed2006

BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth.

We have previously shown that heat shock protein (Hsp) 27 or its upstream activator p38 mitogen-activated protein kinase (MAPK) confers resistance to bortezomib and dexamethasone (Dex) in multiple myeloma (MM) cells. This study examined anti-MM activity of a novel p38 MAPK inhibitor, BIRB 796, alone and in combination with conventional and novel therapeutic agents. BIRB 796 blocked baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. The Hsp90 inhibitor 17-allylamino-17-demethoxy-geldanamycin (17-AAG) upregulated protein expression and phosphorylation of Hsp27; conversely, BIRB 796 inhibited this phosphorylation and enhanced 17-AAG-induced cytotoxicity. Importantly, BIRB 796 inhibited Hsp27 phosphorylation induced by 17-AAG plus bortezomib, thereby enhancing cytotoxicity. In bone marrow stromal cells (BMSC), BIRB 796 inhibited phosphorylation of p38 MAPK and secretion of interleukin-6 (IL-6) and vascular endothelial growth factor triggered by either tumour necrosis factor-alpha or tumour growth factor-beta1. BIRB 796 also inhibited IL-6 secretion induced in BMSCs by adherence to MM cells, thereby inhibiting tumour cell proliferation. These studies therefore suggest that BIRB 796 overcomes drug-resistance in the BM microenvironment, providing the framework for clinical trials of a p38 MAPK inhibitor, alone and in combination with bortezomib, Hsp90 inhibitor, or Dex, to improve patient outcome in MM.

Antineoplastic Agents, Hormonal↗

PubMed2006

Association between polycystic ovary syndrome and female-to-male transsexuality.

BACKGROUND: The aim of this study is to understand the relationship between polycystic ovary syndrome (PCOS), altered hormonal characteristics and insulin resistance in female-to-male (FTM) transsexual patients. METHODS: We studied 69 Japanese FTM cases, aged 17-47 years, who were seen in the Gender Identity Disorder Clinic of Sapporo Medical University Hospital between December 2003 and May 2006. The subjects had never received hormonal treatment or sex re-assignment surgery. Prior to treatment, they received physical examinations entailing measurement of anthropometric, metabolic and endocrine parameters, after which we compared the values obtained according to the presence or absence of PCOS and/or obesity. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS. Of the 49 for whom HOMA-IR was calculated, 15 (30.6%) also showed insulin resistance, whereas of the 59 for whom adiponectin was measured, 18 (30.5%) showed hypoadiponectinaemia. Of 69 for whom androgens were measured, 29 (39.1%) showed hyperandrogenaemia. Insulin resistance was associated with obesity but not with PCOS. In contrast, hyperandrogenaemia was associated with both PCOS and obesity. CONCLUSION: FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.

Adiponectin↗

PubMed2006

High photobiological hydrogen production activity of a Nostoc sp. PCC 7422 uptake hydrogenase-deficient mutant with high nitrogenase activity.

We describe a strategy to establish cyanobacterial strains with high levels of H(2) production that involves the identification of promising wild-type strains followed by optimization of the selected strains using genetic engineering. Nostoc sp. PCC 7422 was chosen from 12 other heterocystous strains, because it has the highest nitrogenase activity. We sequenced the uptake hydrogenase (Hup) gene cluster as well as the bidirectional hydrogenase gene cluster from the strain, and constructed a mutant (Delta hupL) by insertional disruption of the hupL gene. The Delta hupL mutant produced H(2) at 100 mumoles mg chlorophyll a (-1) h(-1), a rate three times that of the wild-type. The Delta hupL cells could accumulate H(2) to about 29% (v/v) accompanied by O(2) evolution in 6 days, under a starting gas phase of Ar + 5% CO(2). The presence of 20% O(2) in the initial gas phase inhibited H(2) accumulation of the Delta hupL cells by less than 20% until day 7.

Amino Acid Sequence↗

PubMed2006

Mutational analysis of the mechanism of negative regulation by SRC homology 2 domain-containing protein tyrosine phosphatase substrate-1 of phagocytosis in macrophages.

Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) is a transmembrane protein predominantly expressed in macrophages. The binding of CD47 on RBCs to SHPS-1 on macrophages is implicated in inhibition of phagocytosis of the former cells by the latter. We have now shown that forced expression in mouse RAW264.7 macrophages of a mutant version (SHPS-1-4F) of mouse SHPS-1, in which four tyrosine phosphorylation sites are replaced by phenylalanine, markedly promoted Fc gammaR-mediated phagocytosis of mouse RBCs or SRBCs. Forced expression of another mutant form (SHPS-1-deltaCyto) of mouse SHPS-1, which lacks most of the cytoplasmic region, did not promote such phagocytosis. Similarly, forced expression of a rat version of SHPS-1-4F, but not that of rat wild-type SHPS-1 or SHPS-1-deltaCyto, in RAW264.7 cells enhanced Fc gammaR-mediated phagocytosis of RBCs. Tyrosine phosphorylation of endogenous SHPS-1 as well as its association with Src homology 2 domain-containing protein tyrosine phosphatase-1 were not markedly inhibited by expression of SHPS-1-4F. Furthermore, the attachment of IgG-opsonized RBCs to RAW264.7 cells was markedly increased by expression of SHPS-1-4F, and this effect did not appear to be mediated by the interaction between CD47 and SHPS-1. These data suggest that inhibition by SHPS-1 of phagocytosis in macrophages is mediated, at least in part, in a manner independent of the transinteraction between CD47 and SHPS-1. In addition, the cytoplasmic region as well as tyrosine phosphorylation sites in this region of SHPS-1 appear indispensable for this inhibitory action of SHPS-1. Moreover, SHPS-1 may regulate the attachment of RBCs to macrophages by an as yet unidentified mechanism.

Animals↗

PubMed2006

Chiral recognition by fluorescent chemosensors based on N-dansyl-amino acid-modified cyclodextrins.

Four kinds of N-dansyl-amino acid-modified beta-cyclodextrins (beta-CDs) were prepared as fluorescent chemosensors for chiral discrimination. The use of an amino acid as a spacer improved binding affinities and chiral discrimination abilities of the chemosensors. N-dansyl-l-Phe-modified beta-CD showed high d-selectivity for norbornane derivatives and N-dansyl-d-Phe-modified beta-CD showed high l-selectivity for menthol. Microcalorimetric titration results indicate that the chemosensors selectively accommodate the enantiomer that induces the least unfavorable entropy change on making an inclusion complex.

Amino Acids↗

PubMed2006

Synaptic amplifier of inflammatory pain in the spinal dorsal horn.

Inflammation and trauma lead to enhanced pain sensitivity (hyperalgesia), which is in part due to altered sensory processing in the spinal cord. The synaptic hypothesis of hyperalgesia, which postulates that hyperalgesia is induced by the activity-dependent long-term potentiation (LTP) in the spinal cord, has been challenged, because in previous studies of pain pathways, LTP was experimentally induced by nerve stimulation at high frequencies ( approximately 100 hertz). This does not, however, resemble the real low-frequency afferent barrage that occurs during inflammation. We identified a synaptic amplifier at the origin of an ascending pain pathway that is switched-on by low-level activity in nociceptive nerve fibers. This model integrates known signal transduction pathways of hyperalgesia without contradiction.

Animals↗

PubMed2006

Evaluation of morphological and molecular variation in Plantago asiatica var. densiuscula, with special reference to the systematic treatment of Plantago asiatica var. yakusimensis.

Morphological and molecular variations in Plantago asiatica L. var. densiuscula Pilg. were analyzed to evaluate the genetic basis for recognizing the dwarf variety P. asiatica var. yakusimensis (Masam.) Ohwi. Considerable variation in the leaf size of P. asiatica var. densiuscula was observed, and no morphological discontinuities were found between the dwarf types of P. asiatica var. densiuscula and P. asiatica var. yakusimensis. Morphological analysis of plants grown under standardized conditions revealed that both environmental plasticity and genetic differentiation contributed to the dwarfisms. Molecular phylogenetic analysis of rDNA internal transcribed spacer (ITS) regions and the SUC1 locus encoding a sucrose transporter revealed that P. asiatica var. yakusimensis was genetically unique although the differentiation level was low. From the above results, we concluded that P. asiatica var. yakusimensis should be reduced to a form of P. asiatica var. densiuscula. Furthermore, the geographic distribution of the SUC1 genotype suggested multiple origins of dwarves, and possible hypotheses for the origins of dwarves are discussed.

Base Sequence↗

PubMed2006

Déjà vu experiences in patients with schizophrenia.

To investigate whether déjà vu experiences are psychopathologic phenomena, we studied the frequency and characteristics of déjà vu experiences in patients with schizophrenia. One hundred thirteen patients with schizophrenia and 386 nonclinical control subjects were evaluated with the Inventory of Déjà vu Experiences Assessment. The frequency and features of déjà vu experiences were compared between the 2 groups. The patients with schizophrenia had déjà vu experiences less frequently (53.1%) than did the nonclinical subjects (76.2%). The frequency of déjà vu experiences did not correlate significantly with age at evaluation or education level among the patients with schizophrenia. Most characteristics of déjà vu experiences of the patients were comparable with those of the control subjects. However, the experiences of the patients tended to be longer and more monotonous. The patients often felt alert, oppressed, and disturbed by the experiences. They appeared to have the experiences under unpleasant mental or physical states. Their déjà vu experiences are not primarily different in nature from those of the nonclinical subjects. The decreased frequency of the experiences in the patients may suggest déjà vu experiences as nonpathologic phenomena.

Adult↗

PubMed2006

Electron-transfer fluorescence quenching of aromatic hydrocarbons by europium and ytterbium ions in acetonitrile.

To make the effects of molecular size on photoinduced electron-transfer (ET) reactions clear, the ET fluorescence quenching of aromatic hydrocarbons by trivalent lanthanide ions M3+ (europium ion Eu3+ and ytterbium ion Yb3+) and the following ET reactions such as the geminate and free radical recombination were studied in acetonitrile. The rate constant k(q) of fluorescence quenching, the yields of free radical (phi(R)) and fluorescer triplet (phi(T)) in fluorescence quenching, and the rate constant k(rec) of free radical recombination were measured. Upon analysis of the free energy dependence of k(q), phi(R), phi(T), and k(rec), it was found that the switchover of the fluorescence quenching mechanism occurs at deltaG(fet) = -1.4 to -1.6 eV: When deltaG(fet) < -1.6 eV, the fluorescence quenching by M3+ is induced by a long-distance ET yielding the geminate radical ion pairs. When deltaG(fet) > -1.4 eV, it is induced by an exciplex formation. The exciplex dissociates rapidly to yield either the fluorescer triplet or the geminate radical ion pairs. The large shift of switchover deltaG(fet) from -0.5 eV for aromatic quenchers to -1.4 to -1.6 eV for lanthanide ions is almost attributed to the difference in the molecular size of the quenchers. Furthermore, it was substantiated that the free energy dependence of ET rates for the geminate and free radical recombination is satisfactorily interpreted within the limits of the Marcus theory.

Acetonitriles↗

PubMed2006

Depression of presynaptic excitation by the activation of vanilloid receptor 1 in the rat spinal dorsal horn revealed by optical imaging.

In this study, we show that capsaicin (CAP) depresses primary afferent fiber terminal excitability by acting on vanilloid receptor 1 (TRPV1 channels) of primary afferent fibers in adenosine 5'-triphosphate (ATP)- and temperature-dependent manner using two optical imaging methods. First, transverse slices of spinal cord were stained with a voltage-sensitive dye and the net excitation in the spinal dorsal horn was recorded. Prolonged treatment (>20 min) with the TRPV1 channel agonist, CAP, resulted in a long-lasting inhibition of the net excitation evoked by single-pulse stimulation of C fiber-activating strength. A shorter application of CAP inhibited the excitation in a concentration-dependent manner and the inhibition was reversed within several minutes. This inhibition was Ca(++)-dependent, was antagonized by the TRPV1 channel antagonist, capsazepine (CPZ), and the P(2)X and P(2)Y antagonist, suramin, and was facilitated by the P(2)Y agonist, uridine 5'-triphosphate (UTP). The inhibition of excitation was unaffected by bicuculline and strychnine, antagonists of GABA(A) and glycine receptors, respectively. Raising the perfusate temperature to 39 degrees C from 27 degrees C inhibited the excitation (-3%/ degrees C). This depressant effect was antagonized by CPZ and suramin, but not by the P(2)X antagonist, 2', 3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP). Second, in order to record the presynaptic excitation exclusively, we stained the primary afferent fibers anterogradely from the dorsal root. CAP application and a temperature increase from 27 degrees C to 33 degrees C depressed the presynaptic excitation, and CPZ antagonized these effects. Thus, this study showed that presynaptic excitability is modulated by CAP, temperature, and ATP under physiological conditions, and explains the reported central actions of CAP. These results may have clinical importance, especially for the control of pain.

Adenosine Triphosphate↗

PubMed2006

Multiple endocrine neoplasia type I and Cushing's syndrome due to an aggressive ACTH producing thymic carcinoid.

Thymic carcinoid in multiple endocrine neoplasia type 1 (MEN 1) is previously reported as a non-ACTH producing tumor. The present case is a 39-year-old man with mortal outcome from thymic carcinoid and Cushing's syndrome with high plasma ACTH. The symptom was first observed at age 29 and was relieved after extended thymectomy, with reduction of ACTH level. The tumor was positive for ACTH, Grimelius silver staining and Chromogranin A. The finding of primary hyperparathyroidism, pituitary adenoma, and a novel germline nonsense mutation (W423X) established the diagnosis of MEN 1. Cushing's syndrome due to ACTH producing thymic carcinoid should be also considered as one phenotype of the MEN 1 spectrum.

ACTH Syndrome, Ectopic↗

PubMed2006

Direct assay for alpha-amylase using fluorophore-modified cyclodextrins.

A simple assay method for alpha-amylase was developed based on fluorophore-modified cyclodextrins (CDs). Four kinds of CD derivatives bearing a 4-amino-7-nitrobenz-2-oxa-1,3-diazole (NBD-amine) moiety were prepared as artificial substrates for the assay method. The fluorescence intensity of all the NBD-amine-modified CDs decreased upon addition of Aspergillus oryzae alpha-amylase, indicating a reduction in hydrophobicity near the NBD-amine moiety induced by hydrolysis of the CD ring. NC4gammaCD, having a gamma-CD and an amino-tetramethylene spacer, was the most sensitive substrate for the alpha-amylase assay. The initial rate of hydrolysis of NC4gammaCD displayed a liner correlation to the concentration of the alpha-amylase. NC4gammaCD was sensitive to the alpha-amylase but was not sensitive to guest compounds that were accommodated by the native CDs.

Aspergillus oryzae↗

PubMed2006

Prospective trial of radiotherapy for patients 80 years of age or older with squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the safety and efficacy of external beam radiotherapy for elderly patients with esophageal cancer. METHODS AND MATERIALS: A trial testing external beam radiotherapy (66 Gy within 6.5 weeks) as a single-modality treatment was performed for biopsy-proven squamous cell carcinoma of the thoracic esophagus clinically staged as Stage I and IIA (T1-T3N0M0, International Union Against Cancer, 1987) in patients aged > or =80 years. RESULTS: From January 1999 through December 2002, 51 evaluable patients (35 men and 16 women) with a median age of 83 years (range, 80-91 years) were enrolled from 22 institutions. Of the 51 patients, 18 (35%) had Stage T1 and 33 (65%) had Stage T2-T3 disease. Radiotherapy could be completed in 47 patients (92%) within 43-58 days (median, 49). The actuarial incidence of Grade 3 or worse cardiopulmonary complications at 3 years was 26%, with 3 early deaths, and correlated significantly with the size of the anteroposterior radiotherapy portals. The median survival time and overall survival rate at 3 years was 30 months and 39% (95% confidence interval, 25-52%), respectively. CONCLUSION: The results of high-dose radiotherapy in octogenarians are comparable to those in younger patients, but meticulous treatment planning and quality control is required.

Aged, 80 and over↗

PubMed2006

Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C.

In contrast to the United States, Japanese patients with chronic hepatitis C currently treated with interferon are generally 10 to 15 years older. Older patients, however, tend to experience more frequent adverse events. This study was conducted to clarify the effect of patient age on the efficacy and safety of combination therapy. We consecutively enrolled 208 patients with naïve chronic hepatitis C. Patients were classified into three groups according to age: younger than 50 years of age (n = 52); 50 to 59 years old (n = 83); and 60 years of age or older (n = 73). Interferon alpha-2b therapy was administered daily for 2 weeks, followed by 3 times per week for 22 weeks, while ribavirin was administered daily. Of the 208 study patients, discontinuation of therapy or dose reduction was required in 116 (56%) and was more frequent in older patient groups: 38%, 48%, and 77% for the < 50, 50-59, and > or = 60-year-old patient groups, respectively (P < .001). Multivariate analysis showed patient age to be independently associated with adherence to therapy. A sustained virological response was achieved in 77 (37%) patients, with genotype, viral load, and adherence to therapy associated with this achievement. A tendency toward a lower sustained virological response rate was seen in the older patients. In conclusion, patient age is an important factor contributing to the safety of combination therapy. Thus, treatment schedule should be modified, or other therapeutic modalities should be considered for older patients with chronic hepatitis C.

Adult↗

PubMed2006

Randomized prospective study on prophylactic antibiotics in clean orthopedic surgery in one ward for 1 year.

BACKGROUND: At present in Japan, there are neither reports on antibiotic prophylaxis regardless of underlying diseases nor precise guidelines on prophylactic antibiotics in orthopedic surgery. Therefore, the preventive effect of antimicrobial agents on surgical site infection (SSI) after clean orthopedic surgery was studied to control the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in our ward and to reduce SSI caused by MRSA. METHODS: Regardless of the type of operation or underlying disease, a regimen of prophylaxis that is of shorter duration than before was conducted in 419 patients admitted to our orthopedic ward (one ward) and who underwent clean orthopedic surgery between 2001 and 2002. RESULTS: The annual usage of beta-lactam antibiotics in the ward decreased by 960.9 g, the isolation rate of MRSA in the ward decreased to 50% (the lowest isolation rate in the past 4 years), and SSIs caused by MRSA were found in 3 of 419 (0.71%) patients in one year compared with 6 of 470 (1.28%) during the previous year. Comparison of two antibiotics revealed that SSI caused by MRSA did not occur in any of the 187 patients receiving sulbactam/ampicillin as prophylaxis but did occur in 1.29% (3/232) patients receiving cefazolin. Concerning all SSIs caused by any organisms, they occurred in 0.53% of patients receiving sulbactam/ampicillin and in 2.16% of patients receiving cefazolin. The difference in the SSI rates between the two groups was not statistically significant. CONCLUSIONS: Although there is statistically no significant difference in the incidence of SSI caused by MRSA, we were able to decrease the isolation rates of MRSA and prevent MRSA from spreading owing to the reduced antibiotic usage in this study. Sulbactam/ampicillin can be recommended, as well as cefazolin, for antibiotic prophylaxis in clean orthopedic surgery.

Adolescent↗

PubMed2006

Nitric oxide-dependent long-term potentiation revealed by real-time imaging of nitric oxide production and neuronal excitation in the dorsal horn of rat spinal cord slices.

Nitric oxide (NO) is thought to be involved in the central mechanism of hyperalgesia and allodynia at the spinal level. Recently, we reported that NO played an important role in the induction of long-term potentiation (LTP) of synaptic strength in spinal dorsal horn, which is believed to underlie hyperalgesia and allodynia. In this study, to elucidate the relationship of NO to LTP in spinal dorsal horn, we measured the spatiotemporal distribution of NO signal with the NO-sensitive dye, DAR-4M, and neuronal excitation with the voltage-sensitive dye, RH482, in rat spinal cord slices, elicited by dorsal root stimulation. In superficial dorsal horn, neuronal excitation evoked by C fiber-activating dorsal root stimulation was potentiated for more than 2 h after low-frequency conditioning stimulation (LFS, 240 pulses at 2 Hz for 2 min). In the same slices that exhibited LTP, NO was produced and distributed in the superficial dorsal horn during the delivery of LFS, and the amplitude of LTP and amount of NO production showed close correlation from slice to slice. LTP and production of NO were inhibited in the presence of the NO synthase inhibitors and an inhibitor of heme oxygenase, the synthetic enzyme for carbon monoxide (CO). These results suggest that production and distribution of NO is necessary for the induction of LTP in spinal dorsal horn, and that CO contributes to the LTP induction and NO production by LFS.

Animals↗

PubMed2006

[Sources of leader's confidence in organizations].

The purpose of this study was to examine the sources of confidence that organization leaders had. As potential sources of the confidence, we focused on fulfillment of expectations made by self and others, reflection on good as well as bad job experiences, and awareness of job experiences in terms of commonality, differentiation, and multiple viewpoints. A questionnaire was administered to 170 managers of Japanese companies. Results were as follows: First, confidence in leaders was more strongly related to fulfillment of expectations made by self and others than reflection on and awareness of job experiences. Second, the confidence was weakly related to internal processing of job experiences, in the form of commonality awareness and reflection on good job experiences. And finally, years of managerial experiences had almost no relation to the confidence. These findings suggested that confidence in leaders was directly acquired from fulfillment of expectations made by self and others, rather than indirectly through internal processing of job experiences. Implications of the findings for leadership training were also discussed.

Adult↗

PubMed2006

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell differentiation determined by immunohistochemical staining for chromogranin A (Cg A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A total of 50 patients diagnosed as having bone metastatic prostate cancer were studied. The period of observation was between 6.9 and 79.4 months (median 48.7 months). Cg A was detected by immunostaining using the labeled streptavidin biotin method. Cg A-positivity was defined as the presence of immunostained cells in 10% or more of the tumor. All statistical analyses were carried out using the Statistical Package for Social Sciences Software, version 10.0 for Windows. Eleven patients (22%) were classified into the Cg A-positive group. There were no significant differences in clinical data between the Cg A-positive and Cg A-negative groups. The 5-year cause-specific survival rate was 34.1% for the Cg A-positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non-recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A-negative group, and this difference was significant (p=0.0253). The 3-year cause-specific survival rates after recurrence were 38.4% and 42.3% respectively (p=0.8125). We consider that NE cell differentiation of the primary tumor in cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

Aged↗