Biomedical subjects

T Hatta

Publications and source records attributed to T Hatta.

At least 73 records · Page 4Linked to original sources

PubMed1997

[Antisense nucleic acid therapy of influenza virus].

We have demonstrated that Antisense phosphodiester (ODNs) and phosphorothioate oligonucleotides (S-ODNs) inhibit CAT (chloramphenicol acetyltransferase) protein expression in the clone 76 cell line, which is a derivative of the murine C127 cell line. This cell line expresses the influenza virus RNA polymerase and nucleoprotein (NP) genes in response to treatment with dexamethasone. Phosphodiester, phosphorothioate, and liposomally encapsulated oligonucleotides with four target sites (PB1, PB2, PA, and NP) were synthesized and tested for inhibitory effects by a CAT-ELISA assay using the clone 76 cell line. The liposomally encapsulated ODNs and S-ODNs complementary to the sites of the PB2-AUG and PA-AUG initiation codons showed highly inhibitory effects. On the other hand, the inhibitory effect of the S-ODNs targeted to PB1 was considerably decreased in comparison with the other three target sites. Liposome encapsulation afforded oligomer protection in serum-containing medium and substantially improved cellular accumulation. The liposomally encapsulated oligonucleotides exhibited higher inhibitory activity than the free oligonucleotides. Liposomal preparations of oligonucleotides facilitate release from endocytic vesicles, and thus, cytoplasmic and nuclear localization are observed following cell treatment. The activities of the unmodified oligonucleotides are effectively enhanced by using the liposomal carrier. In the observation of the endocapsulated antisense phosphodiester oligonucleotide, FITC-ODN-PB2-as treated clone 76 cells by a confocal laser scanning microscope, diffuse fluorescence was apparently observed in the cytoplasm. Interestingly, the endocapsulated antisense phosphorothioate oligonucleotide, FITC-S-ODN-PB2-as accumulated in the nuclear region of clone 76 cells. However, weak fluorescence was observed on the endosomes and in the cytoplasmes of the free antisense phosphorothioate oligonucleotides treated clone 76 cells.

DNA, Antisense↗

PubMed1997

[A case of IAHS (infection associated hemophagocytic syndrome) successfully treated with etoposide].

This report details a case of infection associated hemophagocytic syndrome (IAHS). A 20-year-old female was admitted to our hospital with persistent high fever in July, 1994. Physical examination revealed high body temperature (40 degrees C), marked hepatosplenomegaly and no superficial lymph node swelling. Laboratory examination revealed leukopenia and abnormal liver function on admission. Serum ferritin levels were surprisingly elevated. The coagulation tests showed high FDP and D-dimer. Specific viral antibody titers were not elevated such as Epstein-Barr virus or Cytomegalovirus. Bone marrow examination revealed histiocytic hyperplasia with hemophagocytosis, and the histiocytes were well matured. We diagnosed IAHS. Corticosteroids were administered on the 3rd hospital day (methylprednisolone 1 g/day, 3 days), but persistent high fever and laboratory findings did not improve. So we tried etoposide (etoposide 200 mg/day, 5 days) therapy on the 13th hospital day. After administration of etoposide, she failed to recover from severe leukopenia and suffered from meningitis. We administered G-CSF, gamma-globulin and antibiotics for intensive supportive therapy. As the leukocyte count increased, her symptoms and laboratory data improved. There was no hemophagocytosis in her bone marrow before discharge. Recently, etoposide is said to be effective for reactive monocytic proliferation. Administration of etoposide was very effective for IAHS, although corticosteroids, were ineffective.

Adult↗

PubMed1997

Synthesis and anti-influenza virus-A activity of circular dumbbell RNA DNA chimeric oligonucleotides.

We have designed a new type of antisense oligonucleotide, containing two hairpin loop structures with RNA/DNA base pairs (sense (RNA) and antisense (DNA)) in the double helical stem (nicked and circular dumbbell DNA/RNA chimeric oligonucleotides). The reaction of the nicked and circular dumbbell DNA/RNA chimeric oligonucleotides with RNase H gave the corresponding anti-DNA together with the sense RNA cleavage products. These oligonucleotides were more resistant to exonuclease attack. We also describe the anti-Fluv activities of circular dumbbell DNA/RNA chimeric oligonucleotides.

Antiviral Agents↗

PubMed1996

Inhibition of influenza virus RNA polymerase and nucleoprotein genes expression by unmodified, phosphorothioated, and liposomally encapsulated oligonucleotides.

We have demonstrated that antisense phosphodiester (ODNs) and phosphorothioate oligonucleotides (S-ODNs) inhibit CAT (chloramphenicol acetyltransferase) protein expression in the clone 76 cell line, which is a derivative of the murine C127 cell line. This cell line expresses the influenza virus RNA polymerase and nucleoprotein (NP) genes in response to treatment with dexamethasone. Phosphodiester, phosphorothioate, and liposomally encapsulated oligonucleotides with four target sites (PB1, PB2, PA, and NP) were synthesized and tested for inhibitory effects by a CAT-ELISA assay using the clone 76 cell line. The ODNs and S-ODNs complementary to the sites of the PB2-AUG and PA-AUG initiation codons showed highly inhibitory effects. On the other hand, the inhibitory effect of the S-ODNs targeted to PB1 was considerably decreased in comparison with the other three target sites. Liposome encapsulation afforded oligomer protection in serum-containing medium and substantially improved cellular accumulation. The liposomal encapsulated oligonucleotides exhibited higher inhibitory activity than the free oligonucleotides. The activities of the unmodified oligonucleotides are effectively enhanced by using the liposomal carrier.

Animals↗

PubMed1996

Interhemispheric cooperation of left- and right-handers in mental calculation tasks.

Relations between handedness and interhemispheric processing in cognitive tasks were examined. Thirty six right-handers and thirty left-handers (familial and nonfamilial left-handers) were asked to add two numbers which were presented tachistoscopically. Two numbers were displayed either to one visual field, or one to the left and one to the right visual field simultaneously. In Experiment 1, the numbers were displayed in Arabic numerals, and in Experiment 2 one of the numbers was displayed in Kanji and one in Arabic numerals. The results of Experiment 1 showed a bilateral advantage, however no subject group difference was shown in the performance of the three (left unilateral, right unilateral, and bilateral) presentation conditions. Though familial left-handers showed a weaker tendency to different patterns than right and non-familial left-handers, the results of Experiment 2 were largely similar to those of Experiment 1. These findings suggest that interhemispheric processing may not differ between left- and right-handers.

Journal Article↗

PubMed1996

Identification of an alternative 2,3-dihydroxybiphenyl 1,2-dioxygenase in Rhodococcus sp. strain RHA1 and cloning of the gene.

Gram-positive Rhodococcus sp. strain RHA1 possesses strong polychlorinated biphenyl-degrading capabilities. An RHA1 bphC gene mutant, strain RDC1, had been previously constructed (E. Masai, A. Yamada, J. M. Healy, T. Hatta, K. Kimbara, M. Fukuda, and K. Yano, Appl. Environ. Microbiol. 61:2079-2085, 1995). An alternative 2,3-dihydroxybiphenyl 1,2-dioxygenase (2,3-DHBD), designated EtbC, was identified in RDC1 cells grown on ethylbenzene. EtbC contained the broadest substrate specificity of any meta cleavage dioxygenase identified in a Rhodococcus strain to date, including RHA1 BphC. EtbC was purified to near homogeneity from RDC1 cells grown on ethylbenzene, and a 58-amino-acid NH2-terminal sequence was determined. The NH2-terminal amino acid sequence was used for the identification of the etbC gene from an RDC1 chromosomal DNA 2,3-DHBD expression library. The etbC gene was successfully cloned, and we report here the determination of its nucleotide sequence. The substrate specificity patterns of cell extract and native nondenaturing polyacrylamide gel electrophoresis analysis identified the coexpression of two 2,3-DHBDs (BphC and EtbC) in RHA1 cells grown on either biphenyl or ethylbenzene. The possible implication of coexpressed BphC extradiol dioxygenases in the strong polychlorinated-biphenyl degradation activity of RHA1 was suggested.

Amino Acid Sequence↗

PubMed1996

Effects of handedness and script types on visual-field differences in the mental addition task.

The effects of handedness and script types on the difference in performance in a mental addition task by visual field were examined. Right-handers, nonfamilial left-handers, and familial left-handers who were all native speakers of Japanese were asked to add two numbers presented in the visual half-fields tachistoscopically. The two numbers were displayed either to one visual field (left or right visual field) or to the center. The numbers were displayed in Arabic, in Kanji, or in Arabic and Kanji numerals (one in Arabic and the other in Kanji: Mixed stimuli). The subjects were asked to add the two numbers and to state the sum orally. In the right-handers group, a right visual-field advantage was found for the Arabic condition but not for the Kanji or Mixed stimuli. On the other hand, in the nonfamilial and familial left-handers group, no visual-field difference in any of the conditions was found. These findings suggest that pattern of cerebral lateralization for familial and nonfamilial left-handers is the same but it is different from that of right-handers.

Adult↗

PubMed1996

[Three cases of secondary acute myeloid leukemia after long-term treatment with oral etoposide].

Three cases of secondary acute myeloid leukemia (AML) that developed after long term treatment with oral etoposide were reported. Case 1 was a 72-year-old male in whom small cell lung cancer was diagnosed in January 1987. He developed AML (M4) in February 1993 after long-term treatment with oral etoposide (total dose 14,650 mg) t(9; 11) (p21; q23) with rearrangement of MLL genes was recognized. Case 2 was a 68-year-old female non-Hodgkin's lymphoma (NHL) was diagnosed in February 1989. AML (M4Eo) with inv(16) (p13q22) developed in March 1994 after long-term treatment with oral etoposide (total dose 5,100 mg). Case 3 was a 39-year-old male in whom NHL was diagnosed in January 1991. He developed AML(M2) with t(11; 19) (q23; p13) in May 1994 after long-term treatment with oral etoposide (total dose 20,450 mg). These three cases suggest that long-term treatment with oral etoposide may be associated with a risk of developing a secondary AML in patient with malignancies.

Administration, Oral↗

PubMed1995

Hen-egg-white lysozyme modified with histamine. State of the imidazolylethyl group covalently attached to the binding site and its effect on the sugar-binding ability.

The chemical modification of Asp101 which is located at the upper end-most site (site A) of the binding cleft of hen egg white lysozyme affects the sugar residue binding of the midmost site (site C) in addition to that of site A, and results in the considerable decrease in the enzymic activity [Fukamizo, T., Hayashi, K. & Goto, S. (1986) Eur. J. Biochem. 158, 463-467]. In the present study, Asp101 was modified with histamine and converted to [2-imidazol-4(5)-ylethyl]asparagine. Contrary to the findings described above, the specific activity of the modified lysozyme was higher than that of the native lysozyme by a factor of about two, and the loss of sugar residue binding ability caused by the modification was found to be restricted to site A. From the H-NMR spectra of the modified lysozyme, the pKa value of the imidazolylethyl group covalently attached to Asp101 was 7.1, and was higher than that of N-acetylhistidinemethylamide (6.65). This indicates that the imidazolylethyl moiety is not exposed to the solvent but adheres to the surface of the lysozyme molecule in an unidentified manner. When N-acetylglucosamine trisaccharide [GlcNAc)3] was added to the modified lysozyme, the 1H-NMR signals of H2 and H4 of the imidazolylethyl group were strongly affected. This indicates that the imidazolylethyl moiety is located near (GlcNAc)3 binding region. When the H gamma signal of Ile98 was saturated, nuclear Overhauser effects were observed on H2 and H4 resonances of the imidazolylethyl moiety. NOE was also observed on the signal of Trp63 H6 upon the saturation of the H4 signal of the imidazolylethyl moiety. Thus, the imidazolylethyl moiety should be located near Trp63 and Ile98, which are in the hydrophobic box most proximal to the sugar binding cleft. This situation of the imidazolylethyl moiety did not result in steric hindrance to the sugar residue binding at sites B and C. The modification affected only the sugar residue binding at site A, and resulted in the enhanced activity.

Acetylglucosamine↗

PubMed1995

Phosphorothioate oligonucleotides block reverse transcription by the Rnase H activity associated with the HIV-1 polymerase.

We demonstrate the degradation of RNA bound to an antisense oligonucleotide by a reverse transcriptase enzyme-associated RNase H activity. We found that phosphorothioate oligonucleotides inhibit the RNase H activity by binding to AMV RT, rather than to the template RNA, whereas the RNase H activity of HIV-1 RT is not affected by the antisense phosphorothioate oligonucleotide. Selective inhibition of HIV-1 gene expression involves the degradation of the template RNA bound to the antisense phosphorothioate oligonucleotide by the RNase H activity associated with the HIV-1 polymerase.

Avian Myeloblastosis Virus↗

PubMed1995

Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus.

Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3'- and 5'-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.

Antiviral Agents↗

PubMed1995

Patterns of handedness in modern Japanese: a cohort effect shown by re-administration of the H.N. Handedness Inventory after 20 years.

The H.N. Handedness Inventory, originally administered to a sample of 1199 Japanese students in 1973, was administered to a new sample of 1700 Japanese students 20 years later. It was found that the population of left-handed and ambidextrous females had increased. The incidence of inverted left-hand writers was very small. Comparison of the two sets of data demonstrates the effects of non-biological factors upon lateral preference.

Adult↗

PubMed1995

Multiple Polychlorinated Biphenyl Transformation Systems in the Gram-Positive Bacterium Rhodococcus sp. Strain RHA1.

The cloned bphA gene of the polychlorinated biphenyl (PCB) degrader Rhodococcus sp. strain RHA1 was expressed in Rhodococcus erythropolis IAM1399 cells, resulting in the transformation of di-, tri-, and tetrachlorobiphenyls. Disruption of the bphA1 gene in RHA1 resulted in a lack of growth on biphenyl and a loss of PCB transformation activity. However, the bphA1 insertion mutant of RHA1, designated RDA1, retained the ability to transform PCB congeners when grown on ethylbenzene as its carbon source. It also transformed 4-chlorobiphenyl to 4-chlorobenzoate, although it was suspected to be deficient in bphB and bphC gene activities as well as bphA. This suggested that an alternative PCB degradation system distinct from the one encoded by the cloned bph genes was present.

Journal Article↗

PubMed1995

Characterization of biphenyl catabolic genes of gram-positive polychlorinated biphenyl degrader Rhodococcus sp. strain RHA1.

Rhodococcus sp. strain RHA1 is a gram-positive polychlorinated biphenyl (PCB) degrader which can degrade 10 ppm of PCB48 (equivalent to Aroclor1248), including tri-, tetra-, and pentachlorobiphenyls, in a few days. We isolated the 7.6-kb EcoRI-BamHI fragment carrying the biphenyl catabolic genes of RHA1 and determined their nucleotide sequence. On the basis of deduced amino acid sequence homology, we identified six bph genes, bphA1A2A3A4, bphB, and bphC, that are responsible for the initial three steps of biphenyl degradation. The order of bph genes in RHA1 is bphA1A2A3A4-bphC-bphB. This gene order differs from that of other PCB degraders reported previously. The amino acid sequences deduced from the RHA1 bph genes have a higher degree of homology with the tod genes from Pseudomonas putida F1 (49 to 79%) than with the bph genes of Pseudomonas sp. strains KF707 and KKS102 (30 to 65%). In Escherichia coli, bphA gene activity was not observed even when expression vectors were used. The activities of bphB and bphC, however, were confirmed by observing the transformation of biphenyl to a meta-cleavage compound with the aid of benzene dioxygenase activity that complemented the bphA gene activity (S. Irie, S. Doi, T. Yorifuji, M. Takagi, and K. Yano, J. Bacteriol. 169:5174-5179, 1987). The expected products of the cloned bph genes, except bphA3, were observed in E. coli in an in vitro transcription-translation system. Insertion mutations of bphA1 and bphC of Rhodococcus sp. strain RHA1 were constructed by gene replacement with cloned gene fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

A Novel Transformation of Polychlorinated Biphenyls by Rhodococcus sp. Strain RHA1.

We have characterized a biphenyl degrader, Rhodococcus sp. strain RHA1. Biphenyl-grown cells of strain RHA1 efficiently transformed 45 components in the 62 major peaks of a polychlorinated biphenyl (PCB) mixture of Kanechlors 200, 300, 400, and 500 within 3 days, which includes mono- to octachlorobiphenyls. Among the intermediate metabolites of PCB transformation, di- and trichlorobenzoic acids were identified. The gradual decrease of these chlorobenzoic acids during incubation indicated that these chlorobenzoic acids would also be degraded by this strain. The effect of the position of chlorine substitution was determined by using PCB mixtures that have chlorine substitutions mainly at either the ortho or the meta position. This strain transformed both types of congeners, and strong PCB transformation activity of RHA1 was indicated. RHA1 accumulated 4-chlorobenzoic acid temporally during the transformation of 4-chlorobiphenyl. The release of most chloride in the course of 2,2(prm1)-dichlorobiphenyl degradation was observed. These results suggested that RHA1 would break down at least some PCB congeners into smaller molecules to a considerable extent.

Journal Article↗

PubMed1995

[Inhibition of gene expression by antisense DNA].

We demonstrated that unmodified and modified (phosphorothioate) oligonucleotides prevent cDNA synthesis by AMV, MMLV, or HIV reverse transcriptases. Antisense oligonucleotide/RNA hybrids specifically arrest primer extension. The blockage involves the degradation of the RNA fragment, bound to the antisense oligonucleotide, by reverse transcriptase associated RNase H activity. However, the phosphorothioate oligomer inhibited polymerization, by binding to the AMV- and MMLV-RTs, rather than to the template RNA, whereas there was no competitive binding of the phosphorothioate oligomer on the HIV RT during reverse transcription. Furthermore, the RNase H activity of HIV-RT was only slightly affected by the phosphorothioate oligonucleotide. The anti-HIV activities of phosphorothioate- or 5'-linked lipid-oligonucleotides are also described and some of the problems that still need to be solved are pointed out.

Avian Myeloblastosis Virus↗

PubMed1995

[Nineteen multiple primary cancer cases of 100 patients undergoing lung cancer resection].

In our department, half of 100 consecutive lung cancer resection cases were over the age of 70 years. In the same 100 patients, nineteen cases had multiple primary cancers. Sixteen cases had double, two cases had triple, one case had quadruple primary cancers. The incidence rate of multiple primary cancers involving the lung was 19%. This incidence of 19% is higher than the others ever reported in Japan. It was concluded, when lung cancer patients were elder, that there was increasment in the frequency of multiple cancer cases involving lung, and there was a high possibility of the occurrence of 2nd and 3rd primary cancers.

Adult↗

PubMed1995

Inhibition of influenza virus RNA polymerase and nucleoprotein of gene expression by antisense oligonucleotides.

We demonstrated that unmodified and modified (phosphorothioate) antisense oligonucleotides inhibit CAT (chloramphenicol acetyltransferase) protein expression in the clone 76 cell line. This cell line expresses the influenza virus RNA polymerase and nucleoprotein (NP) genes in response to dexamethasone. Antisense oligonucleotides with four target sites (PB1, PB2, PA, and NP) were synthesized and tested for the their inhibitory effects by a CAT-ELISA assay. Antisense phosphorothioate oligonucleotides (S-ODNs) complementary to the sites of the PB2-AUG and PA-AUG initiation codons showed a high inhibitory effect. On the other hand, the inhibitory effect of the S-ODNs targeted to PB1 was considerably decreased in comparison with the other three target sites.

Base Sequence↗