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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 145 records · Page 8Linked to original sources
PubMed2001

[A case of ileal conduit stenosis 13 years after construction].

A 63-year-old male was admitted to our hospital with the complaint of bilateral hydronephroses. Total cystectomy and ileal conduit construction were performed because of bladder tumor (TCC, G2, pT2N0M0) in 1985. The patient remained asymptomatic, but bilateral hydronephroses was observed by ultrasonography in 1997. DTPA renogram showed the delayed excretion. Conduitgraphy and antegrade pyelography revealed that the conduit was narrow like a pinhole at 2 cm distal region from the anastomotic site of the urinary duct. The stenotic region was inflated by a 24 Fr inflation-balloon-catheter. Chronic inflammation, which was thought to be caused by infection, was detected at the stenotic conduit by biopsy. Hydronephroses disappeared after the operation and the postoperative course was uneventful.

Catheterization↗
PubMed2001

[Hyperdense renal cyst associated with papillary adenoma: a case report].

An abnormal shadow in the chest of a 57-year-old male was detected during a medical checkup and careful investigation revealed a left posterior mediastinal tumor (neurinoma) and a clearly demarcated homogenous mass with dimensions of 16 x 12 mm and computed tomographic (CT) value of 79 H.U. in the superior pole of the right kidney. The content solution was sticky and blackish-green. Neoplastic degenerations of 8 x 4 and 5 x 5 mm were seen in the cyst. Partial nephrectomy, which included the cystic section, was conducted and papillary adenoma was pathologically diagnosed. Nine years after the operation, the patient is alive and neither relapse nor other abnormalities were detected.

Adenoma↗
PubMed2001

Analyses by comparative genomic hybridization of genes relating with cisplatin-resistance in ovarian cancer.

Cisplatin has played a key-role in the management of ovarian cancer patients. Since the mechanisms of cisplatin-resistance have been reported to be multifactorial, it is quite difficult to predict effectiveness of cisplatin-based chemotherapy. In the present study, we have screened abnormal chromosomal regions in cisplatin-resistant and paclitaxel-resistant human ovarian cancer cell lines using comparative genomic hybridization (CGH). Increased copy number at 6q21-25 and decreased copy number at 7q21-36 and 10q12-15 were observed in the cisplatin-resistant cell line. Increased copy number at 7q11.2-21 was observed in paclitaxel-resistant cell lines. Messenger RNA of MDR1 located on chromosomal region of 7q11.2-21 was overexpressed in the paclitaxel-resistant cell lines and recognized as a potential mechanism of acquired paclitaxel-resistance. In CGH analyses of 28 primary epithelial ovarian cancer patients, gains of 1q21-22 (p = 0.0183) and 13q12-14 (p = 0.0407) were observed in significantly high abundance in the cisplatin-resistant tumor group, compared with the cisplatin-sensitive tumor group. These genetic alterations were suggested to be potential indicators for drug resistance.

Chromosome Aberrations↗
PubMed2001

Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray.

Gene expression profiles were analyzed by using cDNA microarray for a cisplatin-sensitive cell line (KF), and three- and thirty-fold cisplatin-resistant ovarian cancer cell lines (KFr and KFrP200) both showing no p53 mutation within exon 5, 6, 7, 8 and no pglycoprotein overexpression. Expression of GST-pi mRNA increased as the level of resistance to cisplatin became high. Microarray analysis revealed that DNA repair associated genes, i.e., XRCC5, XRCC6, ERCC5, hMLH1 were over-expressed in three-fold cisplatin-resistant cell line, KFr as compared to cisplatin-sensitive parental cell line, KF. Apoptosis inhibitors, i.e., IGFR type I and II were over-expressed, and apoptosis inducer, i.e., caspase 3 and BAK were underexpressed in highly cisplatin-resistant cell line, KFrP200 as compared to KFr. As for clinical cases, cDNA microarray was used to compare gene expression profiles directly between two groups, i.e., the chemotherapy (CAP) sensitive group (n = 2) and the resistant group (n = 2). Six genes such as beta tubulin, high-mobility group (nonhistone chromosomal) protein 1, connective tissue growth factor, insulin-like growth factor binding protein 2, alpha tubulin, and RAS-related gene were overexpressed in CAP therapy resistance group, whereas seven genes such as CD9 antigen, alpha-2-macroglobulin, caveolin 2, interleukin 1 receptor antagonist, Rho GTPase activating protein 1, reticulon 3, cyclin-dependent kinase 10, keratin 7 were underexpressed in CAP therapy resistance group. By increasing clinical case number and gene number of microarray to be used in the analysis of expression profile of gene cluster affecting anticancer drug resistance and sensitivity of the ovarian cancer, it would be possible to apply microarray analysis to personalization of chemotherapy such as selection of effective chemotherapy protocol and prediction of therapeutic effect in the near future.

Cisplatin↗
PubMed2000

Calcium channel blockers verapamil and diltiazem impaired rubratoxin B-caused toxicity in HL60 cells.

The effects of calcium channel blockers (CCBs) verapamil and diltiazem on the toxicity of rubratoxin B in HL60 cells were investigated. Treatment of rubratoxin B caused a considerable rate of blebbing, fragmentation and condensation of cells. The rate of this morphological change was much lower in the concomitant rubratoxin B and CCBs-treated cells than in the cells treated only with rubratoxin B. Cell viability was determined by measuring mitochondrial succinic dehydrogenase activity and the rate of cell proliferation. The results of these assays were of the same tendency as that of the morphological study. CCBs attenuated rubratoxin B's toxicity on cell viability because of their protective action. Rubratoxin B induced apoptosis in the presence of internucleosomal fragmentation. In contrast, concomitant rubratoxin B and CCBs treatment did not. Taken together, the above results indicated that CCBs impaired the toxicity including morphological change, cell viability and apoptosis caused by rubratoxin B.

Apoptosis↗
PubMed2000

A new alternative to the mannich reaction: tandem radical addition-cyclization reaction for asymmetric synthesis of gamma-butyrolactones and beta-amino acids

The radical addition-cyclization reaction of substrates having two different radical acceptors such as acrylate and aldoxime ether moieties was studied. This new free radical-mediated Mannich-type reaction proceeded smoothly via a tandem C-C bond-forming process. Furthermore, the diastereoselective tandem reaction provides the novel method for asymmetric synthesis of gamma-butyrolactones and beta-amino acid derivatives.

Journal Article↗
PubMed2000

The antinociceptive effect induced by FR140423 is mediated through spinal 5-HT2A and 5-HT3 receptors.

The involvement of 5-HT receptors in the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]py razole, was investigated in mice by means of the tail-pinch test. The antinociceptive effect of FR140423 injected i.t. was completely abolished by co-administration of the non-selective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonist methysergide, the 5-HT2A receptor antagonist ketanserin and the 5-HT3 receptor antagonist MDL-72222 (3-tropanyl-3,5-dichlorobenzoate) but not by the 5-HT2B receptor antagonist SB-204741 (N-(1-methyl-5-indolyl)-N'-(3-methylisothiazol-5-yl)urea) or the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yloxy)pyridin-3-y l]indolin e-1-carboxamine). The antinociceptive effect of FR140423 administered orally was abolished by i.t., but not by i.c.v., injection of methysergide, ketanserin and MDL-72222. These data indicate that FR140423, unlike morphine, exerts its antinociceptive effect against a mechanical noxious stimulus, such as in the tail-pinch test, by activation of spinal 5-HT2A and 5-HT3 receptors.

Analgesics↗
PubMed2000

Large isoform of hepatitis delta antigen activates serum response factor-associated transcription.

Hepatitis delta virus infection sometimes causes severe and fulminant hepatitis as a coinfection or superinfection along with the hepatitis B virus. To elucidate the underlying mechanism of injury caused by hepatitis delta virus, we examined whether two isoforms of the hepatitis delta antigen (HDAg) had any effect on five well defined intracellular signal transduction pathways: serum response factor (SRF)-, serum response element (SRE)-, nuclear factor kappaB-, activator protein 1-, and cyclic AMP response element-dependent pathways. Reporter assays revealed that large HDAg (LHDAg) activated the SRF- and SRE-dependent pathways. In contrast, small HDAg (SHDAg) did not activate any of five pathways. LHDAg enhanced the transcriptional ability of SRF without changing its DNA binding affinity in an electrophoretic mobility shift assay. In addition, LHDAg activated a rat SM22alpha promoter containing SRF binding site and a human c-fos promoter containing SRE. In conclusion, LHDAg, but not SHDAg, enhances SRF-associated transcriptions. Despite structural similarities between the two HDAgs, there are significant differences in their effects on intracellular signal transduction pathways. These results may provide clues that will aid in the clarification of functional differences between LHDAg and SHDAg and the pathogenesis of delta hepatitis.

Animals↗
PubMed2000

Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability.

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, and hepatocellular carcinoma. Since there are several reports indicating that some viruses influence the tumor suppressor p53 function, we determined the effects of HCV proteins on p53 function and its mechanism determined by use of a reporter assay. Among seven HCV proteins investigated (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only core protein augmented the transcriptional activity of p53 and increased the expression of p21(waf1) protein, which is a major target of p53. Core protein increased both DNA-binding affinity of p53 in electrophoretic morbidity shift assay and transcriptional ability of p53 itself in a reporter assay. The direct interaction between core protein and C terminus of p53 was also shown by glutathione S-transferase fusion protein binding assay. In addition, core protein interacted with hTAF(II)28, a component of the transcriptional factor complex in vivo and in vitro. These results suggest that HCV core protein interacts with p53 and modulates p53-dependent promoter activities during HCV infection.

3T3 Cells↗
PubMed2000

Lesser reduction in bone mineral density by the immunosuppressant, FK506, compared with cyclosporine in rats.

BACKGROUND: Posttransplantation osteopenia leading to osteoporosis induced commonly by treatment with immunosuppressants including cyclosporine (CsA) is a severe complication and results in lowering the quality of life in patients receiving organ transplantation. FK506 is a newly developed immunosuppressant and is currently being used for the prevention of rejection after organ transplantation. In this study, to investigate whether FK506 as well as CsA would cause osteopenia or not, we evaluated the effect of FK506 on bone mineral density and several parameters relevant to bone metabolism in comparison with that of CsA using normal rats. METHODS: Ten-week-old male Sprague-Dawley rats were treated with FK506 (vehicle, 1 mg/kg, and 3.2 mg/kg) or CsA (vehicle, 10 mg/kg, and 32 mg/kg) by daily oral gavage for 28 days. Bone mineral density of the femur, plasma insulin-like growth factor I (IGF-I), and urinary deoxypyridinoline were determined by peripheral quantitative computerized tomography, radioimmunoassay, and enzyme-linked immunosorbent assay, respectively. RESULTS: The reduction in bone mineral density of the femur was observed in both FK506- and CsA-treated rats. The reduction in CsA-treated rats, however, was statistically significant and strikingly severe, whereas that in FK506-treated rats was much less severe than CsA. Plasma IGF-I levels were significantly elevated in FK506-treated rats but not in CsAtreated rats. Urinary deoxypyridinoline levels were unchanged in FK506-treated rats but elevated in CsA-treated rats. CONCLUSIONS: Compared with CsA, FK506 does not appear to induce severe osteopenia by high-turnover bone metabolism in the rat by mediating via IGF-I induction in part. The results suggest that FK506 may exert favorable effects on bone metabolism in patients with organ transplantation compared with CsA. To assess this idea, further clinical investigations focused on bone metabolism will be required.

Amino Acids↗
PubMed2000

FK506 suppresses neutrophil chemoattractant production by peripheral blood mononuclear cells.

To understand the mechanism of action of FK506 (Tacrolimus) on neutrophil chemotaxis, we examined its effect on human neutrophil chemotaxis and neutrophil chemoattractant production by peripheral blood mononuclear cells. FK506 and cyclosporin A had no direct suppressive effect on neutrophil chemotaxis induced by interleukin-8, leukotriene B(4), complement 5a (C5a), zymosan-activated serum and formyl-Met-Leu-Phe (fMLP). FK506 and cyclosporin A only slightly suppressed the chemotactic activity of platelet-activating factor (PAF). Dexamethasone did not inhibit the chemotactic activity of any chemoattractant. The supernatant of peripheral blood mononuclear cells stimulated with anti-CD3 and CD2 antibodies induced neutrophil chemotaxis. FK506 and cyclosporin A suppressed the chemotactic activity of the supernatant in parallel to the suppression of interleukin-8 production by peripheral blood mononuclear cells. Anti-interleukin-8 antibody completely suppressed the chemotactic activity of the supernatant without drugs. These studies indicate that FK506 may exert a beneficial effect on human inflammatory diseases by suppressing neutrophil chemotaxis secondary to inhibition of chemoattractant (for example, interleukin-8) production by leukocytes.

Cells, Cultured↗
PubMed2000

Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes.

The 26S proteasome is a multisubunit protein- destroying machinery that degrades ubiquitin-tagged proteins. To date only a single species of Rpn10, which possibly functions as a multiubiquitin chain-binding subunit, has been identified in various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single gene by developmentally regulated, alternative splicing. Rpn10a is ubiquitously expressed, whereas Rpn10e is expressed only in embryos, with the highest levels of expression in the brain. Both forms of Rpn10 are components of the 26S proteasome, with an apparently similar affinity for multiubiquitylated [(125)I]lysozyme in vitro. However, they exert markedly divergent effects on the destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome occurs in at least two functionally distinct forms: one containing a ubiquitously expressed Rpn10a and the other a newly identified, embryo-specific Rpn10e. While the former is thought to perform proteolysis constitutively in a wide variety of cells, the latter may play a specialized role in early embryonic development.

Alternative Splicing↗
PubMed2000

The antinociceptive effect of FR140423 in mice: involvement of spinal alpha(2)-adrenoceptors.

We investigated the role of the spinal noradrenergic system in the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]py razole, by using the tail-pinch test in mice and various adrenoceptor antagonists. The antinociceptive effect of FR140423 injected i.t. was completely abolished by co-administration of the non-selective alpha-adrenoceptor antagonist phentolamine and the alpha(2)-adrenoceptor antagonist yohimbine but not by the alpha(1)-adrenoceptor antagonist prazosin or the beta-adrenoceptor antagonist propranolol. Oral administration of FR140423, at doses of 5-80 mg/kg, produced a dose-dependent antinociceptive effect with an ED(50) value of 19 mg/kg. This antinociception was abolished by i.t., but not i.c.v., injection of phentolamine and yohimbine (10 microg/mouse). These results suggest that alpha(2)-adrenoceptors in the spinal cord are involved in the antinociceptive effect of FR140423 against mechanical noxious stimulus as they are in the effect of morphine and clonidine.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Simultaneous analysis of anthranilic acid derivatives in pharmaceuticals and human urine by high-performance liquid chromatography with isocratic elution.

A high-performance liquid chromatographic (HPLC) method for simultaneous determination of mefenamic acid (MFA), flufenamic acid (FFA) and tolfenamic acid (TFA) is presented for application to pharmaceuticals and human urine. Isocratic reversed-phase HPLC was employed for quantitative analysis using tetra-pentylammonium bromide (TPAB) as an ion-pair reagent. Urine samples were purified by solid-phase extraction using a silica-based strong anion-exchanger, Bond-Elut SAX cartridge. The HPLC assay was carried out using a Wakosil ODS 5C18 column (5 microm, 150x4.6 mm I.D.). The mobile phase consisted of 1.9 g of TPAB dissolved in 1:1 of a mixture of acetic acid-sodium acetate buffer solution, pH 5.0, and acetonitrile (11:9, v/v). The calibration curves of MFA, FFA and TFA showed good linearity in the concentration range of 33-167 microg/ml with a wavelength of 280 nm for pharmaceuticals, and in the low concentration range (1.7-30.1 microg/ml) with a wavelength of 230 nm for biological fluids. The correlation coefficients were better than 0.9999 in all cases. The lower limits of detection (defined as a signal-to-noise ratio of about 3) were approximately 2 ng for MFA, 3.5 ng for FFA and 2.5 ng for TFA. The procedure described here is rapid, simple, selective and is suitable for routine analysis of pharmaceuticals and pharmacokinetic studies in human urine samples.

Calibration↗
PubMed2000

In vitro processing of human immunodeficiency virus type 1 Gag virus-like particles.

Human immunodeficiency virus (HIV) Gag proteins are assembled into virus particles and then cleaved by the virion-associated HIV protease. Concomitant with Gag processing, doughnut-like HIV particles (the immature form) are converted to particles containing condensed cores (the mature form). Here we describe the in vitro processing of immature HIV Gag virus-like particles (VLP) by exogenously added HIV protease. Following delipidization, sequential processing of immature VLP showed that the matrix (MA)/capsid (CA) junction was cleaved faster than the CA/nucleocapsid (NC) junction, an altered order of processing when compared with authentic processing. When the in vitro processed VLP were analyzed on density gradients, most of the MA, CA-p15 intermediate, and NC were detected as a highly multimeric form, equivalent to the unprocessed VLP. In contrast, CA was found as a monomer dissociated from the multimeric CA-p15 following cleavage of the CA/NC junction. Electron microscopy revealed that the in vitro processing was accompanied by conversion of the doughnut-like particles to particles containing condensed cores and spherical outer shells. The cores, however, lacked core shells, which are normally observed for authentic HIV, suggesting that the in vitro processing of immature VLP failed to produce core shells.

Animals↗
PubMed2000

'Double-Drugs'--a new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker.

We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components.

Anti-HIV Agents↗
PubMed2000

delta-catenin is a nervous system-specific adherens junction protein which undergoes dynamic relocalization during development.

delta-catenin is a member of the Armadillo repeat family and component of the adherens junction discovered in a two-hybrid assay as a bona fide interactor with presenilin-1 (Zhou et al., [1997], NeuroReport 8:2085-2090), a protein which carries mutations that cause familial Alzheimer's disease. The expression pattern of delta-catenin was mapped between embryonic day 10 (E10) and adulthood by Northern blots, in situ hybridization and immunohistochemistry in the mouse. In development, delta-catenin is dynamically regulated with respect to its site of expression. It is first expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the mouse, delta-catenin mRNA is expressed by E10, increases and peaks at postnatal day (P)7, with lower levels in adulthood. In the developing neocortex, delta-catenin mRNA is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, delta-catenin protein forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By E18, delta-catenin expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood. The dynamic relocalization of delta-catenin expression during development, taken together with previously published data which described a role for delta-catenin in cell motility (Lu et al., [1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that delta-catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil.

Animals↗