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Biomedical subjects

Y Terada

Publications and source records attributed to Y Terada.

At least 37 records · Page 2Linked to original sources

Cancer chemopreventive agents, serratane-type triterpenoids from Picea jezoensis.

Seven serratane-type triterpenoids isolated from the cuticle of Picea jezoensis (Sieb. et Zucc.) Carr. jezoensis (Pinaceae) and the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. hondoensis (Mayer) Rehder (Pinaceae) were studied their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All compounds showed strong inhibitory effects on the EBV-EA activation, being stronger than that of oleanolic acid, which exerts on cancer preventive activity in animal carcinogenesis models. Among these compounds, 13alpha, 14alpha-epoxy-3beta-methoxyserratan-21beta-ol and 3beta-methoxy-21alpha-hydroxyserrat-14-en-29-al were investigated for the inhibitory effects in a two-stage mouse skin carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene as initiator and TPA as promoter. 13alpha,14alpha-Epoxy-3beta-methoxyserratan-21beta-ol was found to exhibit the excellent anti-tumor promoting activity in the in vivo carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗

An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers.

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.

Adult↗

Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.

The vasopressin-regulated water channel aquaporin-2 (AQP2) is known to tetramerize in the apical membrane of the renal tubular cells and contributes to urine concentration. We identified three novel mutations, each in a single allele of exon 4 of the AQP2 gene, in three families showing autosomal dominant nephrogenic diabetes insipidus (NDI). These mutations were found in the C-terminus of AQP2: a deletion of G at nucleotide 721 (721 delG), a deletion of 10 nucleotides starting at nucleotide 763 (763-772del), and a deletion of 7 nucleotides starting at nucleotide 812 (812-818del). The wild-type AQP2 is predicted to be a 271-amino acid protein, whereas these mutant genes are predicted to encode proteins that are 330-333 amino acids in length, because of the frameshift mutations. Interestingly, these three mutant AQP2s shared the same C-terminal tail of 61 amino acids. In Xenopus oocytes injected with mutant AQP2 cRNAs, the osmotic water permeability (Pf) was much smaller than that of oocytes with the AQP2 wild-type (14%-17%). Immunoblot analysis of the lysates of the oocytes expressing the mutant AQP2s detected a band at 34 kD, whereas the immunoblot of the plasma-membrane fractions of the oocytes and immunocytochemistry failed to show a significant surface expression, suggesting a defect in trafficking of these mutant proteins. Furthermore, coinjection of wild-type cRNAs with mutant cRNAs markedly decreased the oocyte Pf in parallel with the surface expression of the wild-type AQP2. Immunoprecipitation with antibodies against wild-type and mutant AQP2 indicated the formation of mixed oligomers composed of wild-type and mutant AQP2 monomers. Our results suggest that the trafficking of mutant AQP2 is impaired because of elongation of the C-terminal tail, and the dominant-negative effect is attributed to oligomerization of the wild-type and mutant AQP2s. Segregation of the mutations in the C-terminus of AQP2 with dominant-type NDI underlies the importance of this domain in the intracellular trafficking of AQP2.

Amino Acid Sequence↗

Use of highly energetic (116 keV) synchrotron radiation for X-ray fluorescence analysis of trace rare-earth and heavy elements.

This study has revealed the advantages of the use of 116 keV X-rays as an excitation source of X-ray fluorescence (XRF) analyses. This technique is suitable for nondestructive multielemental analyses of heavy elements such as rare-earth elements. The lowest MDL value evaluated for the bulk analysis of a JG-1 standard reference sample (granite rock) was 0.1 ppm for W for a 500 s measurement. The spectrum of standard glass samples of SRM612 demonstrated clearly resolved K-line peaks of more than 30 elements, including all the existing rare-earth elements, at 50 ppm levels. The calibration curve for the determination of a rare-earth element shows a linear relation between the XRF intensity and concentrations from 10 to 0.03 ng. This powerful technique should be useful for nondestructive analyses of rare-earth and heavy elements in geological, geochemical and archaeological samples as well as industrial materials.

Metals, Rare Earth↗

Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k.

Through large-scale human genome mapping and sequencing of a region at chromosome 17q25.1 that is of particular interest because genes associated with breast, ovarian, and esophageal cancer are likely to be located there, we isolated the cDNA of a novel member of the family of ubiquitin-conjugating enzymes. The predicated peptide showed 97% identity in amino-acid sequence to murine ubiquitin-conjugating enzyme E2-230k (Mus UBE2-230k). The human cDNA consisted of 4878 nucleotides with an open reading frame encoding 1138 amino acids; the approximately 5 kb transcript was expressed predominantly in skeletal muscle and heart. The predicted UBE2-230k peptide contained a motif typical of the UBC domain that has been implicated in the ubiquitin-dependent proteolytic system and related pathways.

Amino Acid Sequence↗

Development of multipurpose laboratory XIEES spectrometer and its application to surface XAFS analysis of Al2O3 films.

A new laboratory spectrometer for X-ray Induced Electron Emission Spectroscopy (XIEES) has been developed. This spectrometer is suitable for measurements of X-ray Absorption Fine Structure (XAFS) spectrum in surface sensitive fluorescence and electron emission detection modes as well as in standard transmission mode. It is the advantage of this spectrometer that a wide range of x-ray energy scanning between 0.48 and 41 keV is available. At the Cu K-edge, a energy resolution of about 2 eV has been achieved. The spectrometer has been used to analyze the Al2O3 (40 A and 500 A)/Si(100) with total electron yield measurement.

Journal Article↗

Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells.

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.

Animals↗

Anaplastic meningioma with papillary, rhabdoid, and epithelial features: a case report.

A 74-year-old man manifested disturbed consciousness and right hemiparesis. Computed tomography revealed a left frontal parasagittal meningeal tumor with extensive peritumoral brain edema and skull invasion. Subtotal removal was performed. Five years later, he underwent two more operations of massive recurrences. Pathological studies revealed anaplastic meningioma with two different histological areas. One was an epithelial and meningothelial area, and the other was a papillary and rhabdoid area. In the papillary and rhabdoid area, small tumor cells with a high nucleus/cytoplasm ratio proliferated densely around the dilated central capillaries with a pseudopapillary pattern. Many rhabdoid cells (vimentin ++, cytokeratin AE1/AE3 +, epithelial membrane antigen [EMA] + +) tended to be distributed far from the central capillaries. There were many mitotic figures near the central vessels. Dense MIB1-positive nuclei were also observed near the central vessels. The trabecular pattern of the tumor cells in the epithelial area was quite different from the histological features of chordoid meningioma.

Aged↗

Topography and distribution of sympathetic nerve fibers in the rat temporomandibular joint: immunocytochemistry and ultrastructure.

The distribution and fine structure of nerve fibers containing neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal polypeptide (VIP) in the temporomandibular joint were investigated by both the avidin-biotin complex method and an indirect immunofluorescence technique. The innervation pattern of NPY- and TH-positive fibers differed from that of VIP-positive fibers. Specifically, the former was distributed in both the superficial and deep sublining layers, while the latter was mostly located in the deep sublining layer. NPY- and TH-immunoreactive fibers were largely confined to vascular elements; occasional fibers were observed in the synovial lining layer close to the joint cavity. More nerves with NPY and TH immunoreactivity were observed close to the upper joint compartment than near the lower compartment NPY and TH immunoreactivity was dramatically reduced in the TMJ of superior cervical ganglionectomized animals, indicating the sympathetic origin of these nerves. NPY immunoreactivity was found only in unmyelinated axons, which were located in the adventitia and adventitia-medial border of arteries or arterioles. Occasionally, axons were near the joint cavity, in areas free of vascular structures. These observations show that abundant sympathetic nerves supply the temporomandibular joint of the rat and provide a morphological basis for the involvement of different neuropeptides in vascular regulatory and modulatory functions in physiological and pathophysiological conditions.

Animals↗

Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population.

Genetic factors may play a major role in determining serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels in the general population. Cholesteryl ester transfer protein (CETP) is a strong genetic factor as a determinant of HDL-C levels in Japanese, whereas hepatic lipase (HL) plays a predominant role in Caucasian populations. We investigated the effects of HL gene promoter polymorphisms on HDL-C levels in a general population of Japanese men (n = 299). An HL promoter polymorphism of -514C/T explained a considerable variance of HDL-C (2.9%), as compared with CETP mutations of D442G and IVS14 + 1G > A (3.6% and 1.9%). HL promoter variation of the -514C/C genotype, reported to have high HL activity, had significant effects on decreasing HDL-C levels (-3.8mg/dl), but -514T allele carriers had a weak effect on increasing HDL-C levels. The frequency of the -514T allele was three times higher (0.50) in the Japanese than in Caucasian populations (0.15-0.19). Thus, the higher frequency of the HL -514T allele, along with CETP gene mutations, could explain about 9% of phenotypic variability of HDL-C. These genetic attributes may be among the many factors that contribute to the relatively higher serum HDL-C levels in Japanese subjects.

Adolescent↗

Molecular cloning, tissue expression, and chromosomal assignment of a novel gene encoding a subunit of the human signal-recognition particle.

Human cancers derived from breast, esophageal, or ovarian tissues frequently show allelic losses on chromosome band 17q25. Moreover, a locus responsible for hereditary focal nonepidermolytic palmoplantar keratoderma, a condition associated with esophageal cancer (TOC; tylosis with oesophageal cancer), has been mapped to the same band. During efforts to sequence, by shotgun methods, a 1-Mb target region that we had defined as the DNA segment harboring the putative tumor suppressor gene(s) involved in these events, we identified a novel cDNA. The full-length cDNA is 2495bp long and is expressed predominantly in skeletal muscle, heart, kidney, and placenta. The predicted product, a 627-amino-acid protein, exhibited significant sequence homology to the canine 68-kd subunit of the signal recognition particle that has been implicated in the transport of secreted and membrane proteins to the endoplasmic reticulum for proper processing. We confirmed the location of this gene at chromosome 17q25.1 by radiation-hybrid mapping and by fluorescence in situ hybridization.

Amino Acid Sequence↗

Nine novel single-nucleotide polymorphisms in the integrin beta4 (ITGB4) gene in the Japanese population.

We identified nine single-nucleotide polymorphisms (SNPs) in the human integrin beta4 (ITGB4) gene (17q24-q25), which encodes a cell-surface receptor, by screening all exons and exon-intron boundaries. Seven of these SNPs were present in coding regions and two in intronic sequences; four of the coding SNPs involved amino-acid substitutions. As the gene is implicated in the tumorigenesis of breast cancers, the polymorphic sites will serve as useful markers not only for distinguishing alleles in loss of heterozygosity (LOH) analyses but also for studying genetic susceptibility to malignancies in humans.

Antigens, CD↗

Finger-assisted laparoscopy to remove a noncommunicating uterine horn.

A 21-year-old-woman had a double uterus with noncommunicating right uterine horn and communicating left uterine horn. The pelvic cavity showed evidence of endometriosis and adhesions from previous laparotomy. A finger was inserted under laparoscopic observation without gas leakage through an iris access port in the lower abdominal wall, which required only a small incision. An index finger was adequate to separate and manipulate inflamed tissue and to assess a connection of horns.

Abnormalities, Multiple↗

Structure and stereochemistry of epoxyserratanes from the cuticle of Piceajezoensis var. jezoensis.

Three new epoxytriterpenes, 14 beta,15 beta-epoxy-21 beta-hydroxyserratan-3-one (1), 13 alpha,14 alpha-epoxy-21 alpha-methoxyserratan-3-one (2), and 13 alpha,14 alpha-epoxy-3 beta-methoxyserratan-21 beta-ol (3), were isolated together with two known triterpenoids, 21 alpha-methoxyserrat-13-en-3-one (4) and 21 beta-hydroxyserrat-14-en-3-one (5), from the cuticle of Picea jezoensis var. jezoensis. The structures of these new compounds were established on the basis of spectral data (NMR, MS) and single-crystal X-ray analyses (1 and 2) and partial synthesis (2 and 3).

Chromatography, Thin Layer↗

Caffeine promotes an ethanol-induced conditioned taste aversion: a dose-dependent interaction.

The present study examined whether caffeine administered within a dose range previously shown to promote ethanol drinking would also alter an ethanol-induced conditioned taste aversion (CTA). The results revealed a dose-dependent interaction between caffeine and ethanol where caffeine (2.5 and 10 mg/kg) promoted an ethanol-induced CTA at a low ethanol dose (1.0 g/kg) but had no effect in blocking CTA at the higher ethanol dose (1.5 g/kg). These results were found to be unrelated to an alteration in ethanol metabolism, as caffeine had no effect in altering blood ethanol levels at the doses tested. In agreement with the reward comparison hypothesis, the present results suggest that rather than attenuate ethanol's "aversive" effects, caffeine may have promoted an ethanol-induced CTA by increasing the reinforcing efficacy of ethanol.

Animals↗

Primary refractoriness to platelet transfusion caused by Nak(a) antibody alone.

BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion. RESULTS: The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count. CONCLUSION: Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.

Adult↗

Glucocorticoids stimulate p21(CIP1) in mesangial cells and in anti-GBM glomerulonephritis.

BACKGROUND: Glucocorticoids are widely used for the treatment of glomerulonephritis, but the mechanism of cell cycle inhibition by glucocorticoids is poorly understood at a molecular level. METHODS: The effects of dexamethasone on cell cycle progression were examined in rat mesangial cells. To investigate the mechanisms of cell cycle inhibition by dexamethasone, we transfected the -2.3 kb p21(CIP1) promoter-CAT construct to mesangial cells using an electroporation METHOD: We also examined whether glucocorticoids stimulate the expression of p21(CIP1) and inhibit cell proliferation in glomeruli of anti-glomerular basement membrane (GBM) glomerulonephritis in rats. RESULTS: Dexamethasone inhibited 3H-thymidine uptake and the percentages of S and G2/M phases in rat mesangial cells. Dexamethasone stimulated CAT activity of the p21(CIP1) promoter 4.5-fold. Deletion analysis of the p21(CIP1) promoter revealed that the glucocorticoid-responsive region (GRE) is present between -1.4 and -1.1 kb upstream of the transcription initiation site. Dexamethasone inducibility of p21(CIP1) promoter activity requires the presence of the C/EBP alpha DNA binding site in the GRE of the p21(CIP1) promoter and C/EBP alpha protein. Intravenous injection of anti-GBM antibody caused mesangial proliferation, crescent formation, and proteinuria in rats. Ten days of administration of prednisolone (1 mg/kg/day) reduced proteinuria and inhibited mesangial cell proliferation and crescent formation. The glomerular-sieving method revealed that prednisolone increased p21(CIP1) expression in glomeruli. CONCLUSION: These data suggest that the cell cycle arrest of mesangial cells is mediated by a functional link between the glucocorticoid receptor and the transcriptional control of p21(CIP1) not only in vitro but also in vivo. Our observations provide new insights into the molecular mechanisms of glucocorticoid action in glomerulonephritis.

Animals↗

Hyperosmolality activates Akt and regulates apoptosis in renal tubular cells.

BACKGROUND: The novel serine-threonine kinase Akt is a critical enzyme in cell survival. We investigated the roles of the Akt pathway and apoptotic signals in (1) Madin-Darby canine kidney (MDCK) cells in a hyperosmotic condition in vitro and (2) in the inner medulla of dehydrated rat in vivo. METHODS: The in vivo experiments were performed in 24- and 48-hour water-restricted rats. Hyperosmolality-stimulated Akt phosphorylation was examined in MDCK cells. Phosphatidylinositol 3-kinase (PI3-K) inhibitors, the dominant-negative mutant of PI3-K, the dominant-negative mutant of Akt, and the dominant-active form of Akt were used to examine the roles of the PI3-K/Akt pathways in renal tubular cell apoptosis. RESULTS: The amount of phosphorylated Akt protein was increased in the inner medulla of dehydrated rats. Hyperosmolality induced by the addition of NaCl, urea, and raffinose phosphorylated Akt in MDCK cells in an osmolality-dependent manner. PI3-K inhibitors and the dominant-negative mutant of PI3-K inhibited the hyperosmolality-induced phosphorylation of Akt. Raising the media osmolality from a normal level to 500 or 600 mOsm/kg H2O final osmolality elicited apoptotic changes such as nucleosomal laddering of DNA and an increment of caspase-3 activity and increased activity in the cell death enzyme-linked immunosorbent assay. Dominant-active Akt prevented the mild hyperosmolality-induced apoptosis, while inhibition of the PI3-K/Akt pathways promoted apoptosis. CONCLUSION: The Akt pathway is activated by hyperosmolality in vitro and in vivo, and activation of Akt prevents the mild hyperosmolality-induced apoptotic changes in MDCK cells. PI3-K/Akt pathways are involved in a hypertonic condition that confers the balance between cell survival and apoptosis.

Androstadienes↗