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T Morii

Publications and source records attributed to T Morii.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of the sequence-selective DNA binding by peptide dimers with covalent and noncovalent dimerization domains.

Sequence-specific DNA binding proteins generally consist of more than two DNA-contacting regions to ensure the selectivity of recognition. The multiple DNA binding modules are connected either through the covalent linker or through the noncovalent dimerization domain. We have compared the DNA binding of peptide dimers with covalent and noncovalent dimerization domains to explore the potential advantage of each linkage on the sequence-specific DNA binding. Three sets of head-to-tail peptide dimers were synthesized by using the same basic region peptide to target the same DNA sequence; one dimer was assembled with a bridged biphenyl derivative as a covalent dimerization domain, and two other dimers were assembled with the cyclodextrin guest noncovalent dimerization domains. One of the noncovalent dimers was a heterodimer that consisted of cyclodextrin and guest peptides, while the other was a homodimer that consisted of peptides bearing both cyclodextrin and the guest molecule within the same chain. Both noncovalent dimers formed the specific DNA complexes within narrower ranges of peptide concentrations and showed higher sequence selectivity than the covalent dimer did. Among the three dimers, the noncovalent homodimer that can form an intramolecular inclusion complex showed the highest sequence selectivity. Because the noncovalent homodimer with the higher stability of the circular intramolecular inclusion complex exhibited the higher sequence selectivity, it was concluded that an equilibrium involving a conformational transition of a monomeric peptide effectively reduced the stability of its nonspecific binding complex, hence increasing the efficacy of cooperative dimer formation at the specific DNA sequence.

Adamantane↗
PubMed1999

Formation of 8-nitroguanine from 2'-deoxyguanosine by NO/O2 system.

We investigated the reaction of 2'-deoxyguanosine (dGuo) with NO/O2 gas mixture under physiological condition and detected 8-nitroguanine, which is known as a novel DNA lesion caused by peroxynitrite (ONOO-). The yield increased with increase in the ratio of O2 and pH. The reaction mechanism is discussed.

Deoxyguanosine↗
PubMed1999

Reactivity of 2'-deoxyoxanosine, a novel DNA lesion.

2'-Deoxyoxanosine (dOxo) is a novel DNA lesion produced from 2'-deoxyguanosine by the reaction with nitrous acid or nitric oxide. We found that dOxo reacted with glycine under physiological conditions. The product was identified by spectrometric data as an adduct between the six membered ring of dOxo and an amino group of glycine. The adduct was more stable than dOxo under physiological conditions. The incubation of an oligodeoxynucleotide containing dOxo with glycine gave also rise to the adduct. These results suggest that dOxo formed in DNA reacts with amino groups of various compounds around DNA in vivo resulting in the adduct.

Anti-Bacterial Agents↗
PubMed1999

[Successful lithium carbonate therapy for a patient with intractable and severe aplastic anemia].

A 16-year-old female patient who had been given a diagnosis of severe aplastic anemia underwent 2 courses of a combined regimen of corticosteroid pulse therapy and androgen therapy. This proved ineffective. Antilymphocyte globulin therapy was also ineffective. The patient was then given lithium carbonate at a dose of 600 mg/day in combination with an androgen derivative. This had a dramatic effect on her peripheral blood smear. Within 3 weeks after the first course of this treatment, she no longer required red blood cell transfusions. Also, once the lithium carbonate dose was increased to 1,200 mg/day, the patient no longer needed exogenous platelet transfusions. Approximately 6 months after the start of combination therapy, a peripheral blood smear showed entirely normal results. However, 2 months after lithium carbonate was discontinued probably as a result of drug-induced liver dysfunction, both leukocytopenia and thrombocytopenia reappeared. Therefore, lithium carbonate was readministered at a dose of 400 mg/day, and later at a dose of 800 mg/day. Again, the patient showed improvements in 3 blood components without any adverse effects. We concluded that lithium therapy was remarkably useful for this patient with intractable and severe aplastic anemia.

Adolescent↗
PubMed1999

[A case of leukemic lymphoma complicated by M-proteinemia: effectiveness of long-term daily administration of oral low-dose etoposide in continuing remission].

A 51-year-old man was admitted with systemic lymph node adenopathy. Hematological examination on admission revealed leukocytosis, and 35% of leukocytes were classified as pathologically abnormal. Moreover, increases in serum IgM (kappa type) and plasma viscosity were recognized. Following biopsy of the lymph node, a diagnosis of non-Hodgkin's lymphoma (diffuse, mixed type) was made. After the implementation of combination chemotherapy, the results of hematological and physical examinations improved. As the nadir receded, serum IgM increased once more, and nine courses of chemotherapy were necessary. In order to promote steady progress toward discharge, etoposide therapy was instituted. Subsequent low-dose etoposide therapy at 50 mg/day rarely resulted in an increase in serum IgM, subjective or objective adverse effects, except for mild lekopenia. After discharge the patient was placed on intermittent etoposide therapy and remained in a state of remission for approximately 11 months. Fortunately, his rehabilitation was successful, and he returned temporarily to his former position. The 2nd remission has continued for approximately seven months. Consequently, long-term low-dose etoposide therapy is speculated to be a significantly useful therapeutic technique for intractable malignant lymphoma.

Administration, Oral↗
PubMed1998

Kinetic studies of sequence-specific binding of GCN4-bZIP peptides to DNA strands immobilized on a 27-MHz quartz-crystal microbalance.

Specific protein-DNA interaction was studied quantitatively by using a highly sensitive 27-MHz quartz-crystal microbalance (QCM). Biotinylated DNA double strands (21 bp, having a CRE site of 5'ATGACGTCAT3') were immobilized on an avidin-bound QCM surface, and sequence-specific binding of bZIP 56-mer peptides (having both the basic region for binding and the leucine zipper region for dimerization) to the DNA strand on the QCM was observed. The binding amount (Deltam) at the nanogram level and kinetic parameters such as association constants (Ka) and binding and dissociation rate constants (k1 and k-1) could be obtained from time courses of QCM frequency decreases. A bZIP peptide as a dimer was observed to bind sequence-specifically to one DNA strand having a CRE site. Ka values of ss-bZIP, in which the leucine-zipper region of bZIP was substituted by a Cys-Cys linkage, were largely decreased, and the sequence selectivity also disappeared. Ka values obtained by the QCM method showed good agreement with those obtained from the conventional gel mobility shift assay or from circular dichroism spectrum changes. When the specific sequence of the CRE site of DNA strands was partly changed, Ka values decreased by about a half due to the increase of the dissociation rate constant (k-1) independent of the binding rate constant (k1).

Amino Acid Sequence↗
PubMed1998

[Mycobacterial infection in patients with hematologic disorders].

In patients with hematologic disorders, cellular immunity may be suppressed by the disease itself or by treatment with adrenal corticosteroids, immunosuppressants, or anticancer agents. Miliary tuberculosis developing in such compromised hosts is cryptic, and thus its diagnosis is difficult to make. Miliary tuberculosis will be fatal if it cannot be detected. Therefore, the possibility of mycobacterial infection should always be kept in mind when treating patients with hematologic disorders. However, such patients often have a poor prognosis, even if they have already been diagnosed with miliary tuberculosis. Prophylactic medication has been proved to be effective against mycobacterial infection with hematologic disorders. Thus, the importance of prophylactic medication should be emphasized.

Hematologic Diseases↗
PubMed1997

Functional expression on human trophoblasts of interleukin 4 and interleukin 7 receptor complexes with a common gamma chain.

The gamma chain in the high-affinity receptor complex for interleukin 2(IL-2) is used in receptor complexes for IL-4 and IL-7. We examined expression and function of the gamma chain in trophoblast cells. Flow cytometric studies demonstrated that the human placental cell line and choriocarcinoma cell lines expressed the IL-2R gamma chain. None of these cell lines expressed the IL-2R alpha and beta chains, whereas the alpha chains of IL-4R and IL-7R were present. The gamma chain and IL-4R and IL-7R mRNA were detected in human placental trophoblasts by the in situ hybridization method. The release of human chorionic gonadotropin by trophoblasts was accelerated by IL-4 and IL-7 in a concentration-dependent manner. These findings indicate that IL-4 and IL-7 are involved in trophoblast function.

Antigens, CD↗
PubMed1997

Selective recognition of tandemly repeated DNA sequences by homo- and heterodimers of short peptides.

The non-covalent and specific protein-protein interaction is critical to the specificity and the cooperativity of the DNA-binding by protein dimers. We have designed and synthesized three sets of peptide dimers with covalent- or noncovalent artificial dimerization modules to elucidate the structural and thermodynamic aspects for the sequence-specific DNA-binding by protein dimers. We have investigated the DNA binding of covalent dimer, noncovalent homodimer and noncovalent heterodimer with specific or nonspecific DNA sequences by gel mobility shift assay. Although the amino acid sequence of DNA-binding region of these peptide dimers are the same, the selectivity and the cooperativity of DNA binding by these peptide dimers were found to be different.

Adamantane↗
PubMed1996

Specific interaction with guanine residues of Z-form DNA by bleomycin-nickel(III) complex.

The Ni(III) complex of bleomycin (BLM) reacts with guanine residues of the oligomer duplex only under high salt condition (4.5 M NaCl) where the (dC-dG)6 sequence exists as the isolated Z-form segment. In addition, the (dC-dG)n inserts were subcloned into a plasmid so that reactivity of the BLM-Ni(III) complex with restriction fragments could be examined. Results are reported for two fragments: an EcoRI-DdeI fragment in which the (dC-dG)n insert is flanked at the 5' end by a segment of B-DNA and a HindIII-DdeI fragment in which the (dC-dG)n fragment is embedded at both ends by stable B-DNA forming segments. The BLM-Ni(III) complex does not bind to (dC-dG)5 sequence of pBRZ10 DNA fragment under any conditions, but to several guanine residues of (dC-dG)8 and (dC-dG)12 sequences of pBRZ16 and pBRZ24 DNA fragments in 4.5 M NaCl solution. In the fragments of pBRZ16 and pBRZ24 DNAs, the BLM-Ni(III) complex reacts with most of guanine bases of (dC-dG)8 and (dC-dG)12.

Base Sequence↗
PubMed1996

Interleukin 4 (IL-4) blocks the IL-2-induced increased in natural killer activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting expression of the IL-2 receptor alpha, beta, and gamma.

The natural killer (NK) activity and DNA synthesis of decidual CD16-CD56bright NK cells were markedly elevated by treatment with interleukin 2 (IL-2). IL-4 did not affect NK activity or DNA synthesis of decidual CD16-CD56bright NK cells, but inhibited the IL-2-induced NK activity and DNA synthesis in a dose-dependent manner. Flow cytometry of decidual mononuclear cells cultured in IL-2 or IL-4 or both IL-2 and IL-4 demonstrated IL-4 inhibition of the expression of the IL-2 receptor alpha (IL-2R alpha), IL-2R beta, and IL-2R gamma on decidual CD16-CD56bright NK cells. This suggests that IL-4 blocks the IL-2-induced NK activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting the expression of IL-2R alpha, IL-2R beta, and IL-2R gamma.

CD56 Antigen↗
PubMed1996

Expression of the interleukin-2 receptor gamma chain on cord blood mononuclear cells.

Lymphocytes in umbilical cord blood and neonatal peripheral blood have been shown to have less ability in an immune reaction. In our present experimental approach to address this issue, we made use of the cord blood of full-term birth infants to investigate the expression of the interleukin- 2 receptor gamma (IL-2Rgamma) chain that is shared with receptors for IL-4, IL-7, IL-9, and IL-15 as well as IL-2. The gamma chain expression in cord blood lymphocytes was about one-third that in the lymphocytes of adults, whereas no significant difference between cord blood and adult monocytes was observed. A reduced expression of the gamma chain was observed in all of the CD4+ T cells, CD8+ T cells, gamma-delta T cells, B cells, CD16+ natural killer (NK) cells, and CD56(bright) NK cells of the cord blood lymphocytes. The reduced gamma chain expression reached two-thirds of that in adults after 3 days of culture in vitro and in infants 3 days after birth, thus implying that the increase in the gamma chain may significantly contribute to the prevention of neonatal infection.

Adult↗
PubMed1996

Production of interleukin 10 during malaria caused by lethal and nonlethal variants of Plasmodium yoelii yoelii.

We investigated the induction of T-helper cell subsets during the course of lethal or nonlethal bloodstage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythrocytic parasites. C57BL/6 mice infected with the nonlethal variant (PyNL) showed a moderate level of parasitemia and resolution of primary acute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN-gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells obtained from mice infected with PyL within the 1st week of infection produced high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mice at the same time at which the in vitro IL-10 response peaked. In contrast, spleen cells from mice infected with PyNL failed to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice infected with the lethal variant were a major source of IL-10, although non T-cells were also involved in the production of IL-10 during this malaria infection. In addition, the initial burst of IL-10 in response to malaria antigens was seen concomitantly with the production of IFN-gamma within the 1st week of infection. These results indicate that both Th1 and Th2 subsets of T-helper lymphocytes are activated during infection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.

Animals↗
PubMed1996

Immunogenicity of Leucocytozoon caulleryi sporozoites and their reactivity with specific immune sera.

The immunogenicity of Leucocytozoon caulleryi sporozoites for chickens and their reactivity in vitro with specific immune sera were studied. Almost all of the chickens that had been immunized with the sporozoite antigens survived the sporozoite challenge. The degree of parasitemia observed in the immunized chickens was significantly lower than that found in the nonimmunized chickens. Specific antibodies against sporozoites were tested by the circumsporozoite precipitation (CSP) reaction. Antibodies were demonstrated in the sera of chickens that had been immunized with the sporozoite antigens or chickens that had recovered from a primary infection with L. caulleryi sporozoites. When viable mature sporozoites were incubated in vitro with serum from immune chickens, agglutination and a long, thread-like precipitate at one end of the sporozoite could be seen within a few minutes under a phase-contrast microscope. The effects of specific immune serum on the infectivity of sporozoites were examined by the sporozoite neutralization activity (SNA) test. Sporozoites that had been incubated in vitro with serum from immune chickens lost their infectivity to chickens. The CSP reaction and the SNA test in L. caulleryi infection were stage- and species-specific.

Animals↗
PubMed1995

Sequence-specific DNA binding by covalently constrained peptide dimers of the basic leucine zipper protein GCN4.

DNA binding of covalently bonded peptide dimers was studied by using enantiomeric and C2-symmetric templates as a dimerization module. Amino acid sequence of the peptide is derived from that of DNA contact region of the basic leucine zipper protein GCN4. These peptide dimers were designed to possess different constraints with respect to the orientation of two peptides. The basic region peptides were covalently linked to the enantiomeric template at the C-terminal ends. Two peptides are arranged either in a right-handed or left-handed geometry depending on the chirality of the template. The GCN4 basic region dimers with both right-handed and left-handed geometries show equal affinity to the native GCN4 binding DNA sequences, 5'-ATGACTCAT-3' and 5'-ATGACGTCAT-3', as revealed by the gel mobility shift assay. Specific recognition of the palindromic DNA sequence by the peptide dimers was confirmed by the DNase I footprinting. Circular dichroism spectroscopic study indicates that the basic region peptides bound the target DNA sequence in a helical conformation. The degree to which a chiral constraint effects may depend on the geometry of two DNA binding domains in the parent protein-DNA complex and on a position to apply the chiral constraint.

Base Sequence↗
PubMed1995

Sequence-specific DNA recognition by peptide heterodimers.

The DNA binding motif rich in basic amino acid residues is used by a variety of DNA binding proteins to recognize specific DNA sequences. We report here a sequence-specific DNA recognition by peptide heterodimers derived from the basic leucine zipper proteins. Specific hetero-dimerization is controlled by an artificial dimerization module consisting of a host-guest inclusion complex. Efficiency of the sequence discrimination by the peptide dimers depends on a stability of the half-matched binding complex. However, structures of the matched and half-matched binding complexes differ from one another.

Base Sequence↗
PubMed1995

DNA recognition by peptide oligomers.

It has been demonstrated that coupling a host-guest complex formation onto the DNA binding ability of short peptides gave raise a cooperative DNA binding by short peptide dimers. This strategy was extend to study the DNA binding by oligomers of short peptide. An amino acid bearing the adamantyl group was incorporated at the N-terminal of a peptide derived from the basic region of a yeast transcription activator GCN4, and beta-cyclodextrin was attached at the C-terminal cysteine residue in the same peptide chain. DNA binding of the peptide with both host and guest molecules to tandemly repeated DNA sequences was studied by gel shift assay.

Amino Acid Sequence↗