Search PubMed⌕ Search

Biomedical subjects

H Tanaka

Publications and source records attributed to H Tanaka.

At least 19 recordsLinked to original sources
PubMed1992

Differentiation-inducing activity of retinoic acid isomers and their oxidized analogs on human promyelocytic leukemia HL-60 cells.

Retinoidal activity of retinoic acid isomers [all-trans-retinoic acid (ATRA), 9-cis-retinoic acid (9CRA) and 13-cis-retinoic acid (13CRA)] and their oxidized derivatives [19-hydroxy and 19-oxo derivatives of ATRA (19-hydroxy-ATRA and 19-oxo-ATRA), 19-oxo derivative of 9CRA (19-oxo-9CRA), and 19-hydroxy derivative of 13CRA (19-hydroxy-13CRA)] was evaluated by means of a human promyelocytic leukemia HL-60 cell differentiation induction assay. All the compounds examined showed this activity with ED50 values of 2-30 nM, which are in accordance with their binding activity to nuclear retinoic acid receptors (RARs).

Binding, Competitive↗
PubMed1992

Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine (26-31) and 1-[(alkyloxy)methyl]-6-(arylthio)-2-thiouracil (32-45) derivatives was carried out on the basis of LDA lithiation of 1-[(alkyloxy)-methyl]thymine (9-14) and 1-[(alkyloxy)methyl]-2-thiouracil (15-25) followed by reaction with diaryl disulfides. The oxidative hydrolysis of the 2-thiouracil derivatives gave 1-[(alkyloxy)methyl]-6-(arylthio)uracil derivatives (46-57). 1-Alkyl-6-(phenylthio)thymine (59-61) derivatives were prepared on the basis of alkylation of 6-(phenylthio)thymine (58). Methylation of the hydroxyl group of HEPT did not affect the anti-HIV-1 activity of HEPT. Substitution of the 1-(2-hydroxyethoxy)methyl group by ethyl, butyl, methoxymethyl, (propyloxy)methyl, and (butyloxy)-methyl groups somewhat improved the original anti-HIV-1 activity of HEPT. Substitution with ethoxymethyl and (benzyloxy)methyl groups further potentiated the activity [EC50: 1-(ethoxy-methyl)-6-(phenylthio)thymine (27), 0.33 microM; 1-[(benzyloxy)methyl]-6-(phenylthio)thymine (31), 0.088 microM]. When the 5-methyl group of 27 and 31 was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity was improved remarkably [EC50: 5-ethyl-1-(ethoxymethyl)-6-(phenylthio)-uracil (46), 0.019 microM; 5-ethyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (52), 0.0059 microM; 5-isopropyl-1-(ethoxymethyl)-6-(phenylthio)uracil (55), 0.012 microM; 5-isopropyl-1-[(benzyloxy)methyl]-6-(phenylthio)uracil (56), 0.0027 microM]. Introduction of two m-methyl groups into the phenylthio ring also potentiated the activity.

Antiviral Agents↗
PubMed1992

Purification and characterization of a sialidase from Bacteroides fragilis SBT3182.

A sialidase from Bacteroides fragilis SBT3182 was purified 2,240-fold to apparent homogeneity by ammonium sulfate precipitation and sequential chromatographies on DEAE-Toyopearl 650M, Hydroxyapatite, MonoS and Superose6 columns. The N-terminal amino acid sequence of this sialidase, Ala-Asp-X-Ile-Phe-Val-Arg-Glu-Thr-Arg-Ile-Pro-, was determined. Substrate specificity of this enzyme using a variety of sialoglycoconjugates showed a 1.5- and 2.2-fold preference for sialyl alpha 2-8 linkages when compared with alpha 2-3 and alpha 2-6 bound sialic acids, respectively. The native sialidase had a molecular weight of 165kDa, as determined by Superose6 gel filtration chromatography and consisted of three subunits each of 55kDa by SDS-polyacrylamide gel electrophoresis. This enzyme had optimal activity at pH6.1 with colominic acid as substrate.

Amino Acid Sequence↗
PubMed1992

[MR angiography enhanced by sodium acetazolamide].

We tried to use sodium acetazolamide to enhance MR angiography (MRA). Sodium acetazolamide, one of carbonic anhydrase inhibitors, has an effect to increase regional cerebral blood flow. We made a direct comparison between pre and post enhanced MRA (both 3D-TOF and 3D-PC techniques). MRA after administration of sodium acetazolamide could depict more details of cortical branches without enhancement of back-ground. So we recommend this simple method to be used widely in any examination of MR angiography.

Acetazolamide↗
PubMed1992

Effect of Mn2+ on neonatal and adult rat heart: initial depression and late augmentation of contractile force.

In the present study, we examined the inotropic effect of Mn2+ on adult and neonatal rat myocardia, contraction of which is known to be highly dependent on Ca2+ release from the sarcoplasmic reticulum and trans-sarcolemmal Ca2+ influx, respectively. Mn2+ produced an initial negative inotropic effect followed by a late augmentation of contractile force in both neonatal and adult preparations, accompanied by marked prolongation of the contraction duration. The attenuation of the late augmentation by ryanodine was greater in the adult while the effect of nicardipine was greater in the neonate, which was similar to the effects of the two drugs in the absence of Mn2+. We tentatively concluded that Mn2+ produces late augmentation of the contractile force in neonatal and adult rat myocardia through some action on the general mechanism of force development, rather than by acting specifically on the sarcoplasmic reticulum.

Aging↗
PubMed1992

Amino acid substitution in the C-terminal arm domain of HU-2 results in an enhanced affinity for DNA.

Three mutants of the Escherichia coli hupA gene, encoding the HU-2 protein, were constructed by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The resulting HupAN10, HupAN11 and HupAN12 proteins contained Thr59-->Lys, Gln64-->Lys and Asn53-->Arg substitutions, respectively. These amino acid (aa) changes increased the positive charge of the N-terminal half of the two-strand, antiparallel beta-ribbon of the arm structure, which is believed to be a domain for DNA binding. The three mutant proteins bound to DNA more tightly than wild-type HU-2, and their affinities for DNA increased in the order of HupAN10, HupAN11, HupAN12. The mutant proteins showed a slightly increased HU activity for supporting Mu phage development. A mutant HU-2 protein with increased basicity, but with an altered aa sequence in the arm region due to a frameshift mutation, was also constructed. This mutant protein showed a reduced affinity to DNA and was unable to support Mu growth, suggesting that a unique aa sequence of the arm domain, rather than mere basicity of this domain, is required for efficient binding to DNA.

Amino Acid Sequence↗
PubMed1992

Ursodeoxycholic acid-dependent activation of the glucocorticoid receptor.

Therapeutic effectiveness of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis strongly indicates that UDCA possesses immunomodulatory activities. In order to further investigate mechanical background of such UDCA action, we first asked whether UDCA modulates glucocorticoid-mediated signal transduction. Using electrophoretic mobility-shift assay, we demonstrated that treatment with UDCA promoted the specific complex formation between the cytosol protein and the glucocorticoid-response element DNA in a dose-dependent fashion in vitro, and also nuclear translocation of the glucocorticoid receptor (GR) in vivo. Gene transfer experiments revealed that UDCA induced cellular CAT activities in a GR-dependent fashion, but rather weakly as compared to synthetic glucocorticoid dexamethasone.

Animals↗
PubMed1992

Molecular cloning of a cDNA clone for tobacco lipid transfer protein and expression of the functional protein in Escherichia coli.

A cDNA clone encoding a lipid transfer protein (LTP) was isolated from tobacco by screening a library with a PCR-amplified spinach LTP gene. DNA sequence analysis showed a large open reading frame (344 bp) encoding a polypeptide of 114 amino acids. The first 23 amino acids of the deduced protein have the characteristics of a signal peptide for protein secretion or targeting into dense microbody-like vesicles. The cDNA clone was then inserted into an expression vector, pMAL, and expressed in E. coli as a fusion with the maltose binding protein (MBP). The MBP-LTP fusion protein was purified to homogeneity and subjected to factor Xa cleavage to yield the LTP domain. A lipid transfer assay demonstrated that the resulting LTP was functional. The availability of the expression system in E. coli will facilitate the elucidation of in vivo function(s) of plant LTPs.

Amino Acid Sequence↗
PubMed1992

Establishment of the human BSMZ breast cancer cell line, which overexpresses the erbB-2 and c-myc genes.

A new cell line, designated BSMZ, was established from a malignant pleural effusion from a woman with breast cancer. This line has a doubling time of 27 h and has now been cultured for over 120 passages. The large, rounded BSMZ cells grow as both a monolayer and as aggregations in suspension. Intracytoplasmic lumen, a finding consistent with results from cells derived from mammary tissue, was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor was identical to the original BSMZ cells in microscopic and electron microscopic studies. These cells possess an average of 80 chromosomes. Expression of erbB-2 and c-myc genes was increased by 10-fold, while there was no detectable overexpression of the N-ras and c-myb genes. Southern analysis has revealed amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore provide a useful model for the study of human breast cancer and overexpression of the erbB-2 gene.

Adult↗
PubMed1992

Chimeric HU-IHF proteins that alter DNA-binding ability.

Chimeric proteins between Escherichia coli histone-like HU and IHF were constructed by genetic engineering, in which part of the arm region was replaced by the corresponding region of IHF alpha (designated as HupANhimA) or IHF beta (HupANhimD); alternatively, an alpha-helix 2-beta 1 region was replaced by the corresponding region of IHF alpha (HupAXhimA) or IHF beta (HupAXhimD) (symbols N and X indicate NotI and XhoI junctions). These proteins were synthesized in a hupA-hupB double-deletion mutant. HupANhimA exhibited marked reduction in nonspecific DNA binding in vitro, and a drastic loss of HU activity in replicative transposition of Mu phage in vivo. HupANhimD also showed a significant reduction in the ability for DNA binding, though this protein supported Mu phage development. In contrast, the other two chimeric HU proteins showed only slight changes in nonspecific DNA-binding ability: they retained activities for transposition of Mu phage in vivo. These observations confirm that the flexible arm of HU-2, a domain proposed for DNA binding [Tanaka et al., Nature 310 (1984) 376-381; Goshima et al., Gene 96 (1990) 141-145], plays an important role in the physiological function of this protein. The results indicate that a unique conformation of the arm structure of HU protein, particularly the N-terminal half of a two-strand antiparallel beta-ribbon of the structure, is important for the DNA-binding ability of this protein.

Amino Acid Sequence↗
PubMed1992

Polyclonal and monoclonal antibodies monospecific to MMTV LTR orf protein produced in E. coli.

Monoclonal and polyclonal antibodies specific to an open reading frame of the mouse mammary tumor virus long terminal repeat were generated using an open reading frame-beta-galactosidase fusion protein produced in E. coli. Both antibodies reacted with the open reading frame-beta-galactosidase fusion protein but not with beta-galactosidase alone using an immunoblotting technique. It is concluded that these antibodies were specific for the protein encoded by the open reading frame of the mouse mammary tumor virus long terminal repeat.

Antibodies, Monoclonal↗
PubMed1992

Levels of mRNA coding for motoneuron growth-promoting factors are increased in denervated muscle.

Partial denervation of skeletal muscle induces sprouting of axons remaining within the muscle, possibly as a result of increased synthesis by denervated muscle fibers of motoneuron growth-promoting factors. Direct verification of this hypothesis has not been possible because the molecules responsible are not unambiguously characterized. We used Xenopus oocytes as a functional assay for mRNAs coding for secreted growth factors: preparations of mRNA from innervated and denervated neonatal muscle were injected into oocytes. Three days later, oocytes injected with denervated muscle mRNA expressed increased levels of nicotinic acetylcholine receptor and voltage-dependent sodium channels at their membrane. Proteins secreted by the same oocytes were tested for their effects on (i) neurite outgrowth from embryonic chicken ventral spinal cord neurons; (ii) survival in mixed culture of embryonic chicken motoneurons identified using the SC1 antibody; and (iii) survival of embryonic motoneurons purified by panning on SC1 antibody. In all three assays, media conditioned by oocytes injected with mRNA from denervated muscle contained significantly higher levels of biological activity than did those from oocytes injected with innervated muscle mRNA or water. mRNA was prepared from muscle at different times after denervation: a maximal increase was obtained already after 1 day, consistent with an involvement in sprouting. Synthesis of motoneuron growth-promoting factors is thus regulated by denervation in a parallel fashion to that of other key components of the neuromuscular junction.

Animals↗
PubMed1992

[Evaluation of cleft lip and palate by computed tomography with 2 mm thin slice scanning--Part 2].

Computed tomography was performed on 104 patients of cleft lip and palate with continuous 2 mm slice scanning. The type of hard palate was classified into 3 groups, as normal, hypoplasia and aplasia, depending on its developmental degree. The shape of alveolus was also grouped into 3 groups as circular, triangular and asymmetric forms for the evaluation of the maxillary development. The hard palate development correlated with the shape of the alveolus, the diameter of maxillary and mandibular bone, and frequency of sinusitis and otitis media. Evaluation of the hard palate by thin slice scanning is useful in presumption of future facial development.

Adolescent↗