Biomedical subjects

H Toyoda

Publications and source records attributed to H Toyoda.

At least 73 records · Page 4Linked to original sources

PubMed2000

Dijet production by double pomeron exchange at the fermilab tevatron

We report the first observation of dijet events with a double Pomeron exchange topology produced in &pmacr;p collisions at sqrt[s] = 1800 GeV. The events are characterized by a leading antiproton, two jets in the central pseudorapidity region, and a large rapidity gap on the outgoing proton side. We present results on jet kinematics and production rates, compare them with corresponding results from single diffractive and inclusive dijet production, and test factorization.

Journal Article↗

PubMed2000

Direct measurement of the W boson width in p&pmacr; collisions at radicals = 1.8 TeV

This Letter describes a direct measurement of the W boson total decay width, gamma(W), using the Collider Detector at Fermilab. The measurement uses an integrated luminosity of 90 pb(-1), collected during the 1994-1995 run of the Fermilab Tevatron p&pmacr; collider. The width is determined by normalizing predicted signal and background distributions to 49 844 W-->enu candidates and 21 806 W-->&mgr;nu candidates in the transverse-mass region M(T)<200 GeV and then fitting the predicted shape to the 438 electron events and 196 muon events in the high- M(T) region, 100<M(T)<200 GeV. The result is gamma(W) = 2.04+/-0.11(stat)+/-0.09(syst) GeV.

Journal Article↗

PubMed2000

sqv-3, -7, and -8, a set of genes affecting morphogenesis in Caenorhabditis elegans, encode enzymes required for glycosaminoglycan biosynthesis.

sqv (squashed vulva) genes comprise a set of eight independent loci in Caenorhabditis elegans required zygotically for the invagination of vulval epithelial cells and maternally for normal oocyte formation and embryogenesis. Sequencing of sqv-3, sqv-7, and sqv-8 suggested a role for the encoded proteins in glycolipid or glycoprotein biosynthesis. Using a combination of in vitro analysis of SQV enzymatic activities, sqv(+)-mediated rescue of vertebrate cell lines, and biochemical characterization of sqv mutants, we show that sqv-3, -7, and -8 all affect the biosynthesis of glycosaminoglycans and therefore compromise the function of one specific class of glycoconjugates, proteoglycans. These findings establish the importance of proteoglycans and their associated glycosaminoglycans in epithelial morphogenesis and patterning during C. elegans development.

Animals↗

PubMed2000

Search for second and third generation leptoquarks including production via technicolor interactions in p&pmacr; collisions at radicals = 1.8 TeV

We report the results of a search for second and third generation leptoquarks using 88 pb(-1) of data recorded by the Collider Detector at Fermilab. Color triplet technipions, which play the role of scalar leptoquarks, are investigated due to their potential production in decays of strongly coupled color octet technirhos. Events with a signature of two heavy flavor jets and missing energy may indicate the decay of a second (third) generation leptoquark to a charm (bottom) quark and a neutrino. As the data are found to be consistent with standard model expectations, mass limits are determined.

Journal Article↗

PubMed2000

Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes.

Mutations that disrupt developmental patterning in Drosophila have provided considerable information about growth factor signaling mechanisms. Three genes recently demonstrated to affect signaling by members of the Wnt, transforming growth factor-beta, Hedgehog, and fibroblast growth factor families in Drosophila encode proteins with homology to vertebrate enzymes involved in glycosaminoglycan synthesis. We report here the biochemical characterization of glycosaminoglycans in Drosophila bearing mutations in sugarless, sulfateless, and tout-velu. We find that mutations in sugarless, which encodes a protein with homology to UDP-glucose dehydrogenase, compromise the synthesis of both chondroitin and heparan sulfate, as would be predicted from a defect in UDP-glucuronate production. Defects in sulfateless, a gene encoding a protein with similarity to vertebrate N-deacetylase/N-sulfotransferases, do not affect chondroitin sulfate levels or composition but dramatically alter the composition of heparin lyase-released disaccharides. N-, 6-O-, and 2-O-sulfated disaccharides are absent and replaced entirely with an unsulfated disaccharide. A mutation in tout-velu, a gene related to the vertebrate Exostoses 1 heparan sulfate co-polymerase, likewise does not affect chondroitin sulfate synthesis but reduces all forms of heparan sulfate to below the limit of detection. These findings show that sugarless, sulfateless, and tout-velu affect glycosaminoglycan biosynthesis and demonstrate the utility of Drosophila as a model organism for studying the function and biosynthesis of glycosaminoglycans in vivo.

Amidohydrolases↗

PubMed2000

Search for scalar top quark production in p&pmacr; collisions at sqrt

We have searched for direct production of scalar top quarks at the Collider Detector at Fermilab in 88 pb(-1) of p&pmacr; collisions at sqrt[s] = 1.8 TeV. We assume the scalar top quark decays into either a bottom quark and a chargino or a bottom quark, a lepton, and a scalar neutrino. The event signature for both decay scenarios is a lepton, missing transverse energy, and at least two b-quark jets. For a chargino mass of 90 GeV/c(2) and scalar neutrino masses of at least 40 GeV/c(2), we find no evidence for scalar top production and present upper limits on the production cross section in both decay scenarios.

Journal Article↗

PubMed2000

Determination of N-acetyl- and N-glycolylneuraminic acids in gangliosides by combination of neuraminidase hydrolysis and fluorometric high-performance liquid chromatography using a GM3 derivative as an internal standard.

A highly sensitive method for quantification of sialic acids in gangliosides was developed. The sialic acids, released by hydrolysis of gangliosides, were converted to fluorescent derivatives with 1,2-diamino-4,5-(methylenedioxy)benzene (DMB) and separated on a reversed-phase C18 column with an isocratic elution. As little as 0.1-1.0 nmol of sialic acid in ganglioside was quantified. The use of acetate buffer instead of water in the mobile phase could prevent damage on the column and reduce background peaks derived from the reagents. When gangliosides were subjected to acid hydrolysis, the velocity of hydrolysis varied depending on their structures and a part of the sialic acid liberated decomposed with prolonged heating time. Therefore gangliosides were hydrolyzed by Arthrobacter ureafaciens neuraminidase in the presence of sodium cholate after addition of an internal standard. For the internal standard, GM3 with N-propionylneuraminic acid (GM3(NeuPr)) was synthesized from GM3(NeuAc) by N-deacylation followed by N-propionylation. Folch partition was used to decrease lipophilic materials included in the sample, and the sialic acids released were recovered from the upper phase. The present method has a satisfactory sensitivity in the simultaneous quantification of NeuAc and NeuGc in purified gangliosides as well as in crude lipid fractions containing a variety of gangliosides.

Carbohydrate Sequence↗

PubMed2000

Diffractive dijets with a leading antiproton in &pmacr;p collisions at sqrt

We report results from a study of events with a leading antiproton of beam momentum fraction 0.905 7 GeV. Using the dijet events, we evaluate the diffractive structure function of the antiproton and compare it with expectations based on results obtained in diffractive deep inelastic scattering experiments at the DESY ep collider HERA.

Journal Article↗

PubMed2000

Destabilization of tumor necrosis factor-alpha mRNA by 5-alpha dihydrotestosterone in Jurkat cells.

The effect of a male steroid hormone, 5DHT, on the expression of TNF-alpha was examined using a human leukemia T cell line, Jurkat. Cells were treated with 5DHT in the presence or absence of PHA, and RNA was isolated followed by a reverse transcriptase - mediated PCR (RT-PCR) to measure the steady state levels of TNF-alpha mRNA. The treatment of cells with 5DHT resulted in a 50% of decrease in the level of TNF-alpha mRNA compared to that in untreated conditions (basal level). A similar level of reduction of the message by 5DHT was also observed in PHA-stimulated cells. The reduction of the steady state levels of TNF-alpha mRNA in Jurkat cells was a result of destabilization of the gene as demonstrated by actinomycin D treatment; a half-life of TNF-alpha message in 5DHT treated cells and non-treated cells was 1 hr and 2.5 hr, respectively, whereas that in 5DHT/PHA and PHA-treated cells was 3hr and 6hr, respectively.

DNA Primers↗

PubMed2000

Production of Upsilon(1S) mesons from chi(b) decays in p&pmacr; collisions at sqrt

We have reconstructed the radiative decays chi(b)(1P)-->Upsilon(1S)gamma and chi(b)(2P)-->Upsilon(1S)gamma in p&pmacr; collisions at sqrt[s] = 1.8 TeV, and measured the fraction of Upsilon(1S) mesons that originate from these decays. For Upsilon(1S) mesons with p(Upsilon)(T)>8.0 GeV/c, the fractions that come from chi(b)(1P) and chi(b)(2P) decays are [27.1+/-6.9(stat)+/-4. 4(syst)]% and [10.5+/-4.4(stat)+/-1.4(syst)]%, respectively. We have derived the fraction of directly produced Upsilon(1S) mesons to be [50.9+/-8.2(stat)+/-9.0(syst)]%.

Journal Article↗

PubMed2000

Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes.

Epiregulin is a new member of the epidermal growth factor (EGF) family purified from conditioned medium of NIH-3T3 clone T7. Some EGF family growth factors play essential roles in human keratinocytes in an autocrine manner. We show here that epiregulin is another autocrine growth factor for human keratinocytes. Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. Immunoprecipitation of [(35)S]methionine-labeled conditioned medium revealed a 5-kDa band corresponding to epiregulin. Northern blot analysis detected a 4. 8-kilobase transcript of epiregulin, and the addition of epiregulin up-regulated epiregulin mRNA synthesis. Furthermore, an anti-epiregulin blocking antibody reduced DNA synthesis by 25%. Epiregulin up-regulated the mRNA levels of heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and TGF-alpha. In turn, the addition of EGF, HB-EGF, amphiregulin, and TGF-alpha increased epiregulin mRNA levels. These results demonstrate that epiregulin acts as an autocrine growth factor in human epidermal keratinocytes and is part of auto- and cross-induction mechanisms involving HB-EGF, amphiregulin, and TGF-alpha. The mRNA expression profile resulting from induction of differentiation with high calcium and fetal calf serum revealed the differential expression of epiregulin, HB-EGF, amphiregulin, and TGF-alpha in keratinocytes. This indicates that these four growth factors have distinct, non-redundant biological functions.

Amphiregulin↗

PubMed2000

Search for color singlet technicolor particles in p&pmacr; collisions at radicals = 1.8 TeV

We search for color singlet technirho and technipion production in p&pmacr; collisions at sqrt[s] = 1.8 TeV recorded with the Collider Detector at Fermilab. These exotic technimesons are present in a model of walking technicolor. The signatures studied are lepton plus two jets plus E(T) and multijet final states. No excess of events is seen in either final state. We set an upper limit on the technirho production cross section and exclude a region in the technipion mass versus technirho mass plane.

Journal Article↗

PubMed2000

Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo.

We have devised a sensitive method for the isolation and structural analysis of glycosaminoglycans from two genetically tractable model organisms, the fruit fly, Drosophila melanogaster, and the nematode, Caenorhabditis elegans. We detected chondroitin/chondroitin sulfate- and heparan sulfate-derived disaccharides in both organisms. Chondroitinase digestion of glycosaminoglycans from adult Drosophila produced both nonsulfated and 4-O-sulfated unsaturated disaccharides, whereas only unsulfated forms were detected in C. elegans. Heparin lyases released disaccharides bearing N-, 2-O-, and 6-O-sulfated species, including mono-, di-, and trisulfated forms. We observed tissue- and stage-specific differences in both chondroitin sulfate and heparan sulfate composition in Drosophila. We have also applied these methods toward the analysis of tout-velu, an EXT-related gene in Drosophila that controls the tissue distribution of the growth factor Hedgehog. The proteins encoded by the vertebrate tumor suppressor genes EXT1 and 2, show heparan sulfate co-polymerase activity, and it has been proposed that tout-velu affects Hedgehog activity via its role in heparan sulfate biosynthesis. Analysis of total glycosaminoglycans from tout-velu mutant larvae show marked reductions in heparan sulfate but not chondroitin sulfate, consistent with its proposed function as a heparan sulfate co-polymerase.

Animals↗

PubMed2000

The effect of retreatment with interferon-alpha on the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND: Interferon (IFN) has been reported to have beneficial long term effects that reduce the occurrence of hepatocellular carcinoma (HCC), even in patients who do not have complete responses to IFN. The authors evaluated the effect of retreatment with IFN-alpha on the long term prognoses of those with incomplete responses to their initial IFN-alpha treatment. METHODS: Among 271 patients with incomplete responses to initial IFN-alpha treatment who had received sufficient dose and duration (a total dose of more than 350 megaunits administered over a period longer than 12 weeks) between October 1989 and September 1997, 63 patients received retreatment and 208 did not. The authors retrospectively compared the incidence of HCC between patients who received retreatment and those who did not. RESULTS: There were no significant differences in the clinical characteristics between these two groups. The cumulative incidence of HCC was significantly lower among the patients who had retreatment, and retreatment with IFN-alpha was the only factor that correlated with the lower incidence of HCC in multivariate analysis. The results were similar when the 12 patients with complete responses to retreatment were excluded from the analysis. CONCLUSIONS: Retreatment with IFN-alpha appeared to have the additional effect of suppressing the development of HCC in patients who had incomplete responses to the initial treatment, even when the hepatitis C virus was not cleared (i.e., a complete response was not achieved) with retreatment. Further prospective study is required.

Adolescent↗

PubMed2000

Randomized trial of the usefulness of a bile leakage test during hepatic resection.

HYPOTHESIS: An intraoperative bile leakage test will assist in decreasing postoperative bile leakage in patients undergoing hepatic resection. DESIGN: Randomized controlled trial. SETTING: University hospital. PATIENTS: One hundred three consecutive patients who were scheduled for hepatic resection without biliary reconstruction. Associated cirrhosis was present in 49 patients (48%), and only 24 (23%) had normal livers. Patients were randomized to undergo (n = 51) or to not undergo (n = 52) a bile leakage test, according to age, liver function, and hepatectomy method. The 2 groups were similar in baseline demographics. INTERVENTION: A bile leakage test was carried out by injecting isotonic sodium chloride solution through the cystic duct, and interrupted suturing was taken for a bile leak on the transected liver surface. MAIN OUTCOME MEASURES: The incidence of postoperative bile leakage and the length of the postoperative hospital stay. Bile leakage was defined as continuous drainage, with a bilirubin level of 86 micromol/L or more (> or =5 mg/dL), beyond 1 week. RESULTS: Twenty-one patients (41%) in the test group showed a bile leak, and a median of 1 site (range, 1-6 sites) was closed during the test. Postoperative bile leakage was observed in 3 patients (6%) in the test group and in 2 (4%) in the control group (P = .99). The odds ratio of the event was 1.53 (95% confidence interval, 0.25-9.44). The median postoperative hospital stay lasted 17 (range, 13-47) and 18 (range, 12-41) days for the test and control groups, respectively (P =.98). CONCLUSION: This randomized trial suggested no advantage in using a bile leakage test during hepatic resection.

Adult↗

PubMed2000

Comparison of characteristics between patients with GB virus C/hepatitis G virus (GBV-C/HGV) RNA and those with GBV-C/HGV E2-antibody in patients with hemophilia.

We compared characteristics of patients with GB virus C/hepatitis G virus (GBV-C/HGV) RNA to those of patients with GBV-C/HGV E2-antibody. GBV-C/HGV RNA and GBV-C/HGV antibody were assayed in 83 persons with hemophilia using a reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, respectively. GBV-C/HGV RNA was detected in 19 (22.9%) patients and GBV-C/HGV antibody was detected in 17 (20.5%). The background characteristics between the patient groups did not differ with respect to age, severity of hemophilia based on the frequency of use of blood product, and both the initial age at the first use and years since the first use of blood products. There were no differences in coinfection with hepatitis C virus (HCV) and/or human immunodeficiency virus, except that infection with HCV subtype 1a was more prevalent in patients with GBV-C/HGV RNA (P = 0.0229). Human lymphocyte antigen (HLA) typing was conducted in 18 patients with GBV-C/HGV RNA and 15 patients with GBV-C/HGV E2-antibody; 13 of the patients with GBV-C/HGV antibody had either HLA DQ7, DR15, or DR8, whereas only 4 of the patients with GBV-C/HGV RNA did (P < 0. 001). It is concluded that the presumed age at the time of GBV-C/HGV infection, the frequency of exposure to GBV-C/HGV, and the time since the GBV-C/HGV infection were not associated with recovery from infection with GBV-C/HGV. Coinfection with HCV subtype 1a may be related to persistent GBV-C/HGV viremia, whereas HLA DQ7, DR15, or DR8 may be related to the clearance of GBV-C/HGV after infection.

Adolescent↗

PubMed2000

Activation-induced T cell death occurs at G1A phase of the cell cycle.

Peripheral negative selection of cycling T cells after TCR engagement and deletion of activated T cells after an immune response occur by an apoptotic process termed activation-induced cell death (AICD). The cross-linking of TCR-CD3 complex with anti-CD3 monoclonal antibody led to significant apoptotic cell death in peripheral blood T cells. To further define cell cycle restriction points for triggering AICD in T cells, we evaluated the association between cell cycle progression and death signal transduction. Simultaneous DNA / RNA quantification analysis revealed that T cells entering G1A phase of the cell cycle may acquire sensitivity to AICD. The activation of caspase-3 was induced when T cells entered G1A phase. Up-regulation of cyclin-dependent kinases (Cdk4 and Cdk6) and cyclin D3 was initiated in TCR-stimulated T cells entering G1A phase and expression of these markers steadily increased as T cells progressed from G1A into G1B phase. Interestingly, caspase-3 inhibitors could inhibit the up-regulation of these G1 cell cycle regulators and induce G0 / G1A arrest as well as the inhibition of AICD. On the basis of these results, AICD signals are most likely transduced into TCR-stimulated T cells entering G1A phase. T cells that fail to progress from G1A into G1B phase undergo AICD.

Apoptosis↗

PubMed2000

A new method to estimate rCBF using IMP and SPECT without any blood sampling.

We developed and evaluated a method to measure rCBF without any blood sampling by using iodine- 123 IMP and SPECT. An integral of arterial input function, the integral taken from the value 0 to T of the variable Ca(t)dt, can be expressed as TC(T)/CO, where TC(T) is radioactivity delivered to the body in T minutes and CO is cardiac output. If T is acceptably small, rCBF can be determined by means of a microsphere model analysis with IMP as Cb(T)/(TC(T)/CO), where Cb(T) is cerebral radioactivity at T minutes. We derived TC(T) and CO from a chest dynamic scan. The method was applied to 45 patients who underwent rCBF studies (58 studies) with arterial blood sampling (ABS). Data from the chest scan were analyzed in comparison with ABS data in the first 28 studies, and equations for correction yielding an accurate TC(T)/CO were derived. The validity of the proposed method was evaluated in the subsequent 30 studies. The method yielded rCBF (rCBF-test) which agreed well with rCBF obtained by a two-compartment model analysis of dynamic SPECT and ABS data (rCBF-ref) with the mean and SD of differences between rCBF-test and rCBF-ref being 1.0 and 2.7 ml/100 g/min, respectively. In eleven subjects who underwent more than two studies, a percentage change in rCBF-test between the studies also closely approximated that of rCBF-ref (y = 1.11 x + 2.63, r = 0.92). The method can be used with acceptable reliability to measure rCBF without any blood sampling.

Adult↗