Biomedical subjects

M Tateno

Publications and source records attributed to M Tateno.

At least 37 records · Page 2Linked to original sources

PubMed2000

Predicting the risk of pre-eclampsia and a small-for-gestational-age infant by quantitative assessment of the diastolic notch in uterine artery flow velocity waveforms in unselected women.

OBJECTIVES: To develop a new quantitative index, the notch depth index (NDI), to evaluate its association with the risk of pre-eclampsia and a small-for-gestational-age (SGA) infant and to compare its clinical usefulness with that of the uterine artery resistance index (RI) and the peak systolic to early diastolic velocity (A/C) ratio. METHODS: Uterine artery color Doppler ultrasound was performed in 288 consecutive healthy pregnant women at 20.2 +/- 2.0 (range 16.0-23.9) weeks of gestation. The NDI represents the depth of the early diastolic notch divided by the maximal diastolic velocity. RESULTS: Nine (3.1%) of the 288 women developed pre-eclampsia and 18 women (6.3%) delivered an SGA infant. The NDI was associated with subsequent onset of pre-eclampsia. The optimal cutoff value for the NDI in predicting pre-eclampsia was 0.14, giving a sensitivity, specificity and a positive predictive value (PPV) of 67, 92, and 22%, respectively. The PPV of the NDI was the largest of the three indices evaluated (12% for the RI and 16% for the A/C ratio). The relative risk for pre-eclampsia in women with values equal to or greater than the optimal cutoff values of the RI, A/C ratio and the NDI was 9.7 (95% confidence interval, 2.5-3.7), 19.2 (4.2-91), and 19.2 (5.1-71), respectively. The NDI of 0.14 improved the PPV of 18% determined by the presence of notches in bilateral uterine arteries. The optimal cutoff value of 0.14 for the NDI in predicting an SGA infant yielded a higher PPV (22%) than those for the RI (9%) and A/C ratio (12%). CONCLUSIONS: The NDI value in the second trimester is associated with the later onset of pre-eclampsia, and is clinically more useful in predicting pre-eclampsia than the two conventional indices.

Adult↗

PubMed2000

Liver dysfunction due to apoptosis in a patient with systemic lupus erythematosus.

We report on a 23-year-old Japanese female with a 13-year history of systemic lupus erythematosus (SLE), and two episodes of deterioration followed by treatment with high dose prednisolone. Although she had been recently treated with prednisolone (12.5 mg daily), her liver function became worse in July 1998. Results of a liver biopsy revealed multi-focal hepatic cell death in a severe fatty liver, without any inflammatory cell invasion. The biopsy also showed a positive TUNEL (Tdt-catalysed DNA nick end labelling) reaction indicating apoptosis. Her liver function recovered rapidly following steroid pulse therapy. Serum soluble Fas ligand (sFasL) was found to be elevated to a concentration of 0.395 ng/ml at the time of liver damage, but was less than 0.03 ng/ml before liver damage and after prednisolone treatment. The liver damage in this case appeared to be involved with apoptosis induced by sFasL. Although hepatitis associated with SLE is rare, apoptosis directly related to elevated sFasL levels might cause this complication.

Adult↗

PubMed2000

Bacterial artificial chromosome libraries for mouse sequencing and functional analysis.

Bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) libraries providing a combined 33-fold representation of the murine genome have been constructed using two different restriction enzymes for genomic digestion. A large-insert PAC library was prepared from the 129S6/SvEvTac strain in a bacterial/mammalian shuttle vector to facilitate functional gene studies. For genome mapping and sequencing, we prepared BAC libraries from the 129S6/SvEvTac and the C57BL/6J strains. The average insert sizes for the three libraries range between 130 kb and 200 kb. Based on the numbers of clones and the observed average insert sizes, we estimate each library to have slightly in excess of 10-fold genome representation. The average number of clones found after hybridization screening with 28 probes was in the range of 9-14 clones per marker. To explore the fidelity of the genomic representation in the three libraries, we analyzed three contigs, each established after screening with a single unique marker. New markers were established from the end sequences and screened against all the contig members to determine if any of the BACs and PACs are chimeric or rearranged. Only one chimeric clone and six potential deletions have been observed after extensive analysis of 113 PAC and BAC clones. Seventy-one of the 113 clones were conclusively nonchimeric because both end markers or sequences were mapped to the other confirmed contig members. We could not exclude chimerism for the remaining 41 clones because one or both of the insert termini did not contain unique sequence to design markers. The low rate of chimerism, approximately 1%, and the low level of detected rearrangements support the anticipated usefulness of the BAC libraries for genome research.

Animals↗

PubMed2000

[A pilot trial of high dose CEP (cyclophosphamide, epirubicin, cis-platinum) therapy in patients with advanced and recurrent ovarian cancer].

We evaluated the feasibility of high-dose CEP (cyclophosphamide 750 mg/m2, epirubicin 90 mg/m2, cis-platinum 70 mg/m2) therapy, with granulocyte colony-stimulating factor support every 21 days, in 18 patients with advanced and recurrent ovarian cancer. Ten patients (56%) received 6 cycles of this regimen as planned. Toxicities more than grade 3/4 on' the WHO scale of neutropenia and thrombocytopenia were observed in all cases. Nausea, vomiting, mucositis, malaise, alopecia, hepatotoxicity, and fever were common adverse effects. The average relative dose intensity of cyclophosphamide, epirubicin, cis-platinum was 0.77, 0.77, 0.79 respectively, and each RDI decreased in the last two cycles. These data suggest that this regimen could be performed safely with careful consideration on hepatotoxicity and thrombocytopenia.

Adult↗

PubMed1999

Increased specificity of reverse transcription priming by trehalose and oligo-blockers allows high-efficiency window separation of mRNA display.

We have developed a method for high-efficiency window separation of cDNA display by increasing the specificity of priming in reverse transcription. In the conventional method, two-base anchored oligo(dT) primers (5'dT16VN3', where N is any base and V is G, A or C) are used to make windows for the display of transcripts. However, reverse transcriptase often extends misprimed oligonucleotides. To avoid mispriming from dT16VN primers, we have developed two new technologies. One is higher temperature priming with reverse transcriptase thermoactivated by the disaccharide trehalose. The other is the use of competitive oligonucleotide blockers that hybridize to the non-selectively primed mRNAs, preventing the mispriming from the VN site. These methods were combined to improve restriction landmark cDNA scanning (RLCS), resulting in the elimination of the redundant signals that appear in different windows. This was achieved by the increased specificity of initiation of reverse trans-cription from the beginning of poly(A) sites. This method paves the way for the precise visualization of transcripts to allow expression profiles in individual tissues and at each developmental stage to be understood.

Animals↗

PubMed1999

Nuclear magnetic resonance and molecular dynamics studies on the interactions of the Ras-binding domain of Raf-1 with wild-type and mutant Ras proteins.

The Ras protein and its homolog, Rap1A, have an identical "effector region" (residues 32-40) preceded by Asp30-Glu31 and Glu30-Lys31, respectively. In the complex of the "Ras-like" E30D/K31E mutant Rap1A with the Ras-binding domain (RBD), residues 51-131 of Raf-1, Glu31 in Rap1A forms a tight salt bridge with Lys84 in Raf-1. However, we have recently found that Raf-1 RBD binding of Ras is indeed reduced by the E31K mutation, but is not affected by the E31A mutation. Here, the "Rap1A-like" D30E/E31K mutant of Ras was prepared and shown to bind the Raf-1 RBD less strongly than wild-type Ras, but slightly more tightly than the E31K mutant. The backbone 1H, 13C, and 15N magnetic resonances of the Raf-1 RBD were assigned in complexes with the wild-type and D30E/E31K mutant Ras proteins in the guanosine 5'-O-(beta,gamma-imidotriphosphate)-bound form. The Lys84 residue in the Raf-1 RBD exhibited a large change in chemical shift upon binding wild-type Ras, suggesting that Lys84 interacts with wild-type Ras. The D30E/E31K mutant of Ras caused nearly the same perturbations in Raf-1 chemical shifts, including that of Lys84. We hypothesized that Glu31 in Ras may not be the major salt bridge partner of Lys84 in Raf-1. A molecular dynamics simulation of a model structure of the Raf-1 RBD.Ras.GTP complex suggested that Lys84 in Raf-1 might instead form a tight salt bridge with Asp33 in Ras. Consistent with this, the D33A mutation in Ras greatly reduced its Raf-I RBD binding activity. We conclude that the major salt bridge partner of Lys84 in Raf-1 may be Asp33 in Ras.

Amino Acid Sequence↗

PubMed1999

Successful stenting of congenital bronchial stenosis in infancy.

UNLABELLED: Recently, stent implantation has become the treatment of choice for patients with tracheobronchial stenosis due to malignant tumours, tuberculosis and recurrent stenosis following lung transplant. However, reports on this procedure in infants with congenital bronchial stenosis are extremely rare. We report successful stent implantation in an infant with congenital left bronchial stenosis followed by rapid improvement in his respiratory condition. CONCLUSION: The use of a stent in infants is still controversial because size mismatch will take place with growth. However, we believe that implantation of a metallic stent can be the preferred treatment of congenital bronchial stenosis even in small infants.

Bronchial Diseases↗

PubMed1999

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

Animals↗

PubMed1999

The identity determinants required for the discrimination between tRNAGlu and tRNAAsp by glutamyl-tRNA synthetase from Escherichia coli.

We previously elucidated the major determinant set for Escherichia coli tRNAGlu identity (U34, U35, C36, A37, G1*C72, U2*A71, U11*A24, U13*G22**Alpha46, and Delta47) and showed that the set is sufficient to switch the identity of tRNAGln to Glu [Sekine, S., Nureki, O., Sakamoto, K., Niimi, T., Tateno, M., Go, M., Kohno, T., Brisson, A., Lapointe, J. & Yokoyama, S. (1996) J. Mol. Biol. 256, 685-700]. In the present study, we attempted to switch the identity of tRNAAsp, which has a sequence similar to that of tRNAGlu, and consequently possesses many nucleotide residues corresponding to the Glu identity determinants (U35, C36, A37, G1*C72, and U11*A24). A simple transplantation of the rest of the major determinants (U34, U2*A71, U13*G22**Alpha46, and Delta47) to the framework of tRNAAsp did not result in a sufficient switch of the tRNAAsp identity to Glu. To confer an optimal glutamate accepting activity to tRNAAsp, two other elements, C4*G69 in the middle of the acceptor stem and C12*G23**C9 in the augmented D helix, were required. Consistently, the two base pairs, C4*G69 and C12*G23, in tRNAGlu had been shown to exist in the interface with glutamyl-tRNA synthetase (GluRS) by phosphate-group footprinting. We also found the two elements in the framework of tRNAGln, and determined that their contributions successfully changed the identity of tRNAGln to Glu in the previous study. By the identity-determinant set (C4*G69 and C12*G23**C9 in addition to U34, U35, C36, A37, G1*C72, U2*A71, U11*A24, U13*G22**Alpha46, and Delta47) the activity of GluRS was optimized and efficient discrimination from the noncognate tRNAs was achieved.

Acylation↗

PubMed1999

De novo synthesis of sphingolipids is required for cell survival by down-regulating c-Jun N-terminal kinase in Drosophila imaginal discs.

Mitogen-activated protein kinase (MAPK) is a conserved eukaryotic signaling factor that mediates various signals, cumulating in the activation of transcription factors. Extracellular signal-regulated kinase (ERK), a MAPK, is activated through phosphorylation by the kinase MAPK/ERK kinase (MEK). To elucidate the extent of the involvement of ERK in various aspects of animal development, we searched for a Drosophila mutant which responds to elevated MEK activity and herein identified a lace mutant. Mutants with mild lace alleles grow to become adults with multiple aberrant morphologies in the appendages, compound eye, and bristles. These aberrations were suppressed by elevated MEK activity. Structural and transgenic analyses of the lace cDNA have revealed that the lace gene product is a membrane protein similar to the yeast protein LCB2, a subunit of serine palmitoyltransferase (SPT), which catalyzes the first step of sphingolipid biosynthesis. In fact, SPT activity in the fly expressing epitope-tagged Lace was absorbed by epitope-specific antibody. The number of dead cells in various imaginal discs of a lace hypomorph was considerably increased, thereby ectopically activating c-Jun N-terminal kinase (JNK), another MAPK. These results account for the adult phenotypes of the lace mutant and suppression of the phenotypes by elevated MEK activity: we hypothesize that mutation of lace causes decreased de novo synthesis of sphingolipid metabolites, some of which are signaling molecules, and one or more of these changes activates JNK to elicit apoptosis. The ERK pathway may be antagonistic to the JNK pathway in the control of cell survival.

Acyltransferases↗

PubMed1999

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in a 50% survival of B53-inoculated CBF1 mice over 50 d without histological manifestations of acute GVHD or residual B53 cells. These results indicate the beneficial effects of KB-R7785 that inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.

Animals↗

PubMed1998

A novel mode of DNA recognition by a beta-sheet revealed by the solution structure of the GCC-box binding domain in complex with DNA.

The 3D solution structure of the GCC-box binding domain of a protein from Arabidopsis thaliana in complex with its target DNA fragment has been determined by heteronuclear multidimensional NMR in combination with simulated annealing and restrained molecular dynamic calculation. The domain consists of a three-stranded anti-parallel beta-sheet and an alpha-helix packed approximately parallel to the beta-sheet. Arginine and tryptophan residues in the beta-sheet are identified to contact eight of the nine consecutive base pairs in the major groove, and at the same time bind to the sugar phosphate backbones. The target DNA bends slightly at the central CG step, thereby allowing the DNA to follow the curvature of the beta-sheet.

Amino Acid Sequence↗

PubMed1998

An improved approach for construction of bacterial artificial chromosome libraries.

Presented here are improved methodologies that enable the generation of highly redundant bacterial artificial chromosome/P1-derived artificial chromosome libraries, with larger and relatively uniform insert sizes. Improvements in vector preparation and enhanced ligation conditions reduce the number of background nonrecombinant clones. Preelectrophoresis of immobilized high-molecular-weight DNA removes inhibitors of the cloning process, while sizing DNA fragments twice within a single gel effectively eliminates small restriction fragments, thus increasing the average insert size of the clones. The size-fractionated DNA fragments are recovered by electroelution rather than the more common melting of gel slices with subsequent beta-agarase treatment. Concentration of the ligation products yields a 6- to 12-fold reduction in the number of electroporations required in preparing a library of desirable size. These improved methods have been applied to prepare PAC and BAC libraries from the human, murine, rat, canine, and baboon genomes with average insert sizes ranging between 160 and 235 kb.

Animals↗

PubMed1998

Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies.

Both tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti-TNFalpha monoclonal antibody (MoAb) in a lethal acute GVHD model in mice. Whereas the treatment with either anti-FasL or anti-TNFalpha MoAb alone significantly delayed the mortality and improved the body weight, a complete protection was achieved by the administration of both MoAbs. Pathological examination indicated differential effects of anti-FasL or anti-TNFalpha MoAb on GVHD-associated pathologies. Hepatic lesion was improved by anti-FasL but not anti-TNFalpha MoAb. In contrast, intestinal lesion was improved by anti-TNFalpha but not anti-FasL MoAb. Cutaneous and splenic lesions were improved by either MoAb. The combination of both MoAbs improved all these lesions. These results indicate that FasL and TNFalpha differentially contribute to the GVHD pathologies and a complete protection from mortality can be achieved by neutralization of both FasL and TNFalpha.

Animals↗

PubMed1998

Enzyme structure with two catalytic sites for double-sieve selection of substrate.

High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain.

Adenosine Monophosphate↗

PubMed1998

Immunoglobulin-A and -G responses against virus-like particles (VLP) of human papillomavirus type 16 in women with cervical cancer and cervical intra-epithelial lesions.

Immunoglobulin-A and -G (IgA and IgG) responses against HPV-16-like particles (VLP) were tested by ELISA in 104 women with cervical abnormalities, 26 atypical cells of undetermined significance (ASCUS) and 14 cytologically normal women with HPV DNA. As controls, 130 age-matched cytologically normal women with no HPV DNA were selected from the population in which the cases were generated. The existence of HPV DNA in cervical samples was tested by a PCR-based method. The normal women positive with HPV-16 DNA were followed up at 4- to 7-month intervals for 16 to 24 months. IgA and IgG antibodies against HPV-16 VLP were frequently detected in these women repeatedly positive with HPV-16 DNA, suggesting that persistent HPV infection is crucial for effective antibody responses against the viruses. IgA response appears earlier and persists longer than IgG response. Women with HPV DNA of types 16, 31/33/35, 58 and unknown types showed significantly higher seropositivity for both IgA and IgG antibodies than the controls (p < 0.05 for both). No significant seropositivity for IgA or IgG was detected in the HPV-18/45-DNA-positive group. HPV 31/33/35, 58 appear to be types close to HPV 16, whereas HPV 18/45 appears to be distinct from HPV 16 in antigenicity. IgA and IgG responses against HPV-16 VLP were more frequently observed in women with normal cervices with HPV DNA, ASCUS, HSIL and cervical cancer than in the controls. Strong IgA and IgG responses depended on HPV-16 infection in HSIL and cervical cancer, but there was no correlation between the serological responses and the status of HPV DNA in ASCUS and LSIL. Antibody positivity reflects persistent viral infection that may increase the risk for malignant progression of the cervix. This serological assay using HPV-16 VLP may therefore be useful as a new diagnostic tool supplementing cervical cytological tests.

Adult↗

PubMed1998

CMV retinitis after cessation of ganciclovir therapy for CMV antigenemia in an unrelated BMT recipient.

An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.

Anemia, Aplastic↗

PubMed1998

Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor II.

A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61-year-old man with frequent hypoglycemia. Endocrinological analyses showed high serum levels of insulin-like growth factor II (IGF-II) and suppressed secretion of insulin. After the removal of a pleural tumor, which weighed 3150 g, serum IGF-II levels returned to normal and hypoglycemic attacks ceased. The tumor was composed of uniform spindle cells arranged in bundles, and fascicles with varying amounts of collagen and reticulin fibers. Mitotic figures at the rate of 6/10 high-power fields, and frequent foci of necrosis and hemorrhage were seen. Almost all of the tumor cells were immunohistochemically positive for vimentin and CD34. Electron microscopy revealed the immature mesenchymal or myofibroblastic nature of the tumor cells. These findings are consistent with malignant SFT of the pleura. Moreover, the tumor produced IGF-II mRNA as demonstrated by northern blot analysis. Thus, hypoglycemia of this patient was induced by SFT through the production and secretion of IGF-II.

Antigens, CD34↗