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Y Ninomiya

Publications and source records attributed to Y Ninomiya.

At least 271 records · Page 15Linked to original sources
PubMed1987

Ion specificity of rat chorda tympani fibers to chemical and electrical tongue stimulations.

Responses of rat single chorda tympani fibers to ionic chemical stimuli and anodal tongue stimulations with ionic bathing solutions were examined. Fourteen out of 30 fibers showed the highest sensitivities to NaCl for both chemical and electrical stimulations, whereas the remaining 16 fibers showed almost no ion specificity for electrical stimulation even though most of them have the highest sensitivities to HCl for chemical stimulation. Ion specificity for electrical stimulation was significantly smaller than that for chemical stimulation.

Animals↗
PubMed1987

Structure of the glycosaminoglycan domain in the type IX collagen-proteoglycan.

Type IX collagen represents 5-20% of the total collagen in hyaline cartilage. The molecules of this collagen are composed of three genetically distinct polypeptide subunits. One of these subunits, alpha 2(IX), contains covalently bound glycosaminoglycan (chondroitin sulfate or dermatan sulfate). We report here on the structure of the glycosaminoglycan attachment site of type IX collagen-proteoglycan. We show, by a combination of cDNA and peptide sequencing, that the attachment region contains the sequence Gly-Ser-Ala-Asp, located within the noncollagenous domain NC3 of the alpha 2(IX) chain. By comparing the exons encoding the NC3 domain in the alpha 2(IX) and alpha 1(IX) genes, we find that the exon coding for the glycosaminoglycan attachment site in the alpha 2(IX) gene is 48 base pairs long, whereas the homologous alpha 1(IX) exon is 33 base pairs. The NC3 domain is, therefore, five amino acid residues longer in alpha 2(IX) than in alpha 1(IX). The extra sequence in alpha 2(IX), Val-Glu-Gly-Ser-Ala, provides a simple explanation for the kink observed at the NC3 domain of type IX molecules when examined by electron microscopy. The inserted block of amino acid residues also provides the NC3 domain of alpha 2(IX) chains with a serine residue, not present in alpha 1(IX) that serves as attachment site for a glycosaminoglycan side chain. Our data show that the amino acid sequence that surrounds the glycosylated serine residue in type IX collagen-proteoglycan differs from glycosylated sequences in noncollagenous core proteins. The data also provide strong evidence that glycosylation of type IX collagen is not a chance glycosylation of a serine residue in a noncollagenous domain, but is a specific post-translational modification of this unusual collagen molecule.

Amino Acid Sequence↗
PubMed1987

[Antitumor effects of 5'-deoxy-5-fluorouridine (5'-DFUR) against various murine tumors in combination with recombinant interferon alpha or cytostatics].

Antitumor effects of oral fluorinated pyrimidines including 5'-DFUR and their combination with recombinant interferon (rIFN) alpha A/D (Bgl) or cytostatics were investigated using various tumor models in mice. 5'-DFUR was more effective against Colon 26 than tegafur and 5-FU as a single agent, and their therapeutic indices were 14.7, 2.3 and 1.2, respectively. In combination with various cytostatics, 5'-DFUR as well as 5-FU and tegafur showed better efficacy against mouse Colon 26, Meth A fibrosarcoma and A755 adenocarcinoma than any other single agents. Combination therapy with 5'-DFUR and rIFN-alpha A/D also showed better efficacy against all seven murine tumors tested than their single therapy. In these combination therapies, increased toxicities measured by a body weight change and the incidence of toxic death were also observed to some extent. Among combinations with fluorinated pyrimidines, those with 5'-DFUR showed the toxicities at a lesser degree than those with 5-FU or tegafur. These results indicate that 5'-DFUR would be useful for the multiple combination chemotherapy like 5-FU and tegafur.

Animals↗
PubMed1987

[A case report of an advanced ovarian cancer (stage T4) treated with a total amount of 1815 mg of CDDP].

A case is reported of a 34-year-old female who complained of an adult head-sized tumor in the pelvis and was treated with a high dose of CDDP. On the first look operation, it was found impossible to perform reduction surgery because of severe adhesion and peritonitis carcinomatosa. To introduce a high concentration of an anti-cancer agent into the tumor tissue, we administered CDDP intravenously, intraperitoneally and intra-arterially to the total amount of 1815 mg. After this high dose combination chemotherapy, a second look operation was performed and the tumor was seen to be reduced. The patient is now in remission and is being followed up as an out-patient. The clinical course of this case had decided for us which route would be the most effective and would have the least side effect, also, how much of a dosage can be administered as a maximum adoptive dose of an anti-cancer agent, and what kind of a second-line chemotherapy is effective against resistant cancer cells.

Adult↗
PubMed1987

[Intraperitoneal high-dose cisplatinum chemotherapy (CDDP-ip) in patients with carcinomatous peritonitis].

Immediately after CDDP-ip, the level of free Pt in ascites reached nearly 100 micrograms/ml, and the AUC (area under the curve) for ascites was 20-140 times greater than that for serum. The free Pt in serum following CDDP-ip administration was detected for several hours, and interestingly, the AUC for serum after ip therapy was 0.4-2.2 times greater than that after iv therapy. As a result, free Pt was found to act on cancer cells in the abdominal cavity directly at a high concentration. At the same time, the possibility of an antitumor effect from the vascular side of the tumor was also suggested. On the other hand, cases of ovarian cancer had various levels of peritoneal clearance (CLp), which depended on the severity of their carcinomatous peritonitis. The CLp had a great influence on the peak plasma concentration and on the AUC of free Pt in serum. In particular, the peak plasma concentration produced by CDDP-ip was 40-80% of the plasma concentration produced by CDDP-iv. These findings indicate that high-dose CDDP-ip is possibly effective and useful for advanced ovarian cancer, producing only very mild side effects.

Ascitic Fluid↗
PubMed1987

The study of placental L-ascorbate (vitamin C) transport mechanism (using microvillous membrane vesicles).

To investigate the placental L-ascorbate (Vitamin C) transport mechanism, the uptake of L-ascorbate into microvillous membrane vesicles prepared from human term placenta was studied using the rapid filtration technique. The uptake of L-ascorbate into microvillous membrane vesicles was osmotically sensitive. This finding indicated that the uptake of L-ascorbate into microvillous membrane vesicles represented transport into the vesicles. The uptake of L-ascorbate into microvillous membrane vesicles was not dependent on sodium electrochemical gradient. The initial rate of uptake was not changed when the intravesicular space was rendered electrically more negative by membrane diffusion potential induced by the use of highly permeant anions. The initial rate of L-ascorbate transport exhibited saturation kinetics with respect to the L-ascorbate concentration; an apparent Km of 1.33 mM and Vmax of 47p mol/mg protein/20 sec was calculated. The uptake of L-ascorbate into microvillous membrane vesicles was competitively inhibited by D-isoascorbate. These results indicated that transport of L-ascorbate across the placental microvillous membrane vesicles was carrier mediated and was passive transport.

Ascorbic Acid↗
PubMed1986

Peptide-specific antibodies identify the alpha 2 chain as the proteoglycan subunit of type IX collagen.

Type IX collagen is a recently characterized product of chondrocytes. The molecules of this collagen are heterotrimers of three genetically distinct polypeptide chains. One of the three chains contains chondroitin and/or dermatan sulfate glycosaminoglycan chains, giving the molecule a proteoglycan character. In fact, Type IX collagen has been identified with the proteoglycan Lt (PG-Lt), first isolated by Noro, A., Kimata, K., Oike, Y., Shinomura, T., Maeda, N., Yano, S., Takahashi, N., and Suzuki, S. (1983) J. Biol. Chem. 258, 9323-9331 from chick embryonic tibia and femur. Based on amino acid sequences predicted from the nucleotide sequences of cDNA and genomic clones specific for two of the chains of Type IX collagen, we have synthesized oligopeptides representing portions of the two chains. In addition, an oligopeptide has been made based on a partial amino acid sequence of the third chain. Antibodies against the synthetic peptides have been generated in rabbits, and the polyclonal sera have allowed identification of the three genetically distinct polypeptide subunits of Type IX collagen. In addition, labeling with [35S]sulfate and treatment with chondroitinase ABC demonstrates that glycosaminoglycan chains are present on the subunit that has been given the designation alpha 2(IX).

Amino Acid Sequence↗
PubMed1986

The developmentally regulated type X collagen gene contains a long open reading frame without introns.

Type X collagen is a recently discovered product of hypertrophic chondrocytes that is localized to presumptive mineralization zones of hyaline cartilage. Thus, in the epiphyseal growth plate of long bones it is present only in the zone of hypertrophic chondrocytes and absent in the resting and rapidly growing cartilage and in bone. Type X collagen represents, therefore, a transient and developmentally regulated collagen which is synthesized by a subpopulation of chondrocytes. We report here the isolation and characterization of cDNA and genomic clones specific for the chicken protein. The results demonstrate that the polypeptide chains of this collagen contain three distinct domains: a short non-collagenous, amino-terminal region, a collagenous domain of 460 amino acid residues, and a non-collagenous, carboxyl-terminal domain of 170 amino acid residues. The nucleotide sequence of the gene shows that these domains are encoded by a long open reading frame that is not interrupted by introns. Examination of the amino acid sequence derived from this nucleotide sequence reveals the presence of a hydrophobic segment localized 10 amino acid residues upstream from the translational stop codon. The length and sequence characteristics of this segment raise the intriguing possibility that Type X collagen polypeptides may contain a transmembrane segment.

Amino Acid Sequence↗
PubMed1986

Differential localization of mRNAs of collagen types I and II in chick fibroblasts, chondrocytes, and corneal cells by in situ hybridization using cDNA probes.

We have employed a highly specific in situ hybridization protocol that allows differential detection of mRNAs of collagen types I and II in paraffin sections from chick embryo tissues. All probes were cDNA restriction fragments encoding portions of the C-propeptide region of the pro alpha-chain, and some of the fragments also encoded the 3'-untranslated region of mRNAs of either type I or type II collagen. Smears of tendon fibroblasts and those of sternal chondrocytes from 17-d-old chick embryos as well as paraffin sections of 10-d-old whole embryos and of the cornea of 6.5-d-old embryos were hybridized with 3H-labeled probes for either type I or type II collagen mRNA. Autoradiographs revealed that the labeling was prominent in tendon fibroblasts with the type I collagen probe and in sternal chondrocytes with the type II collagen probe; that in the cartilage of sclera and limbs from 10-d-old embryos, the type I probe showed strong labeling of fibroblast sheets surrounding the cartilage and of a few chondrocytes in the cartilage, whereas the type II probe labeled chondrocytes intensely and only a few fibroblasts; and that in the cornea of 6.5-d-old embryos, the type I probe labeled the epithelial cells and fibroblasts in the stroma heavily, and the endothelial cells slightly, whereas the type II probe labeled almost exclusively the epithelial cells except for a slight labeling in the endothelial cells. These data indicate that embryonic tissues express these two collagen genes separately and/or simultaneously and offer new approaches to the study of the cellular regulation of extracellular matrix components.

Animals↗
PubMed1986

Molecular basis of drug resistance to new antirhinovirus agents.

The modes of action of antirhinovirus agents and mechanisms of resistance to the agents are compared. Chalcone Ro 09-0410, 4',6-dichloroflavan (DCF) and RMI-15,731, which were active against rhinoviruses, inactivated the virus directly. Inactivation was associated with the binding of the agents to the virus particles, since the infectivity, reduced by exposure to the compounds, was restored to the original level by extraction of the agents with chloroform. The binding of [3H]chalcone to rhinovirus type 2 was inhibited by any of the three unlabelled agents. Furthermore, virus sublines selected for resistance to both dichloroflavan and RMI-15,731 showed cross-resistance to chalcone and vice versa. These findings indicate that the three agents exert their activities through the same mode of action (namely binding to or interaction with a specific site on the viral capsid protein) and that the binding or interaction sites for these three agents are either the same or very close to each other. Since the sublines resistant to chalcone and to RMI-15,731 have little or no capability to bind to chalcone, the resistance to these agents is conferred by changes in the viral capsid protein. On the other hand, flavone Ro 09-0179 and enviroxime, which were active widely against picornaviruses, had no ability to inactivate the virus directly, and their antiviral activity was not associated with the capsid protein.

Benzimidazoles↗
PubMed1986

[Pharmacokinetics of adriamycin vaginal suppository in uterine cervical cancer].

Vaginal suppositories of Adriamycin (ADM, 5 mg), for reducing the capacity for repair from sublethal damage of X-ray-irradiated cells, were prepared using Wipepsol S-55 as the vehicle, and were intravaginally administered to patients with advanced uterine cervical cancer, and their pharmacokinetics and clinical effects were studied. The ADM concentration in the uterine cervical cancer tissues indicated high levels (17 to 566 micrograms/g), and migration into the cardinal ligament and regional lymph nodes was noted. However, little ADM was detected in serum (0 to 0.14 micrograms/g), probably because of its molecular weight and excellent tissue absorbance, and no side effects, such as cardiotoxicity and myelosuppression due to consecutive administration were detected. Histologically, the effect obtained when administered alone was limited, administration in combination with radiotherapy being more effective. Accordingly, radiotherapy of advanced uterine cervical cancer with concomitant administration of ADM vaginal suppositories seems to bring about a more powerful antitumoral effect with fewer systemic side effects.

Cervix Uteri↗
PubMed1985

Construction and characterization of cDNA encoding the alpha 2 chain of chicken type IX collagen.

We have isolated and characterized a cDNA encoding the carboxy-terminal half of one of the polypeptide subunits of a novel disulfide-bonded collagen found in hyaline cartilage. This collagen has been given the type assignment type IX, and it has several unusual characteristics. First, the polypeptide subunits are shorter than alpha-chains of the fibrillar collagens types I, II, and III. Second, type IX molecules are heterotrimers of three genetically distinct polypeptide subunits. Third, type IX molecules contain three triple-helical collagenous domains interspersed with noncollagenous domains. When chicken cartilage collagens are extracted with pepsin, type IX collagen is cleaved and gives rise to the triple-helical fragments HMW and LMW. The identification of the cDNA reported here is based on a comparison of the amino acid composition of tryptic peptides derived from LMW with the composition of tryptic peptides predicted from the nucleotide sequence of the cDNA. We also show that the amino-terminal sequence of one of the subunits of LMW is identical with the sequence predicted from the nucleotide sequence of the cDNA. Finally, we demonstrate that the amino-terminal amino acid sequence of a tryptic peptide isolated from one of the subunits of HMW is identical with a sequence predicted from the cDNA. We have given the polypeptide chain encoded by the cDNA reported here the name alpha 2(IX), and we show that it is homologous to the alpha 1(IX) chain previously characterized by us.

Amino Acid Sequence↗
PubMed1985

The structure of type IX collagen.

We present a detailed analysis both of tryptic peptides and amino-terminal sequences of the subunits of two collagenous fragments (HMW and LMW) previously isolated from pepsin extracts of chicken cartilage (Reese, C.A., and Mayne, R. (1981) Biochemistry 20, 5443-5448). This analysis and a comparison with the nucleotide sequence of the cDNApYN1738 (Ninomiya, Y., and Olsen, B.R. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 3014-3018) shows that HMW and LMW are pepsin-resistant fragments of a unique collagen composed of molecules with three different polypeptide chains (alpha-chains). This collagen has been assigned the type number IX, and the alpha-chain encoded by pYN1738 has been given the designation alpha 1 (IX). Type IX collagen contains three triple-helical domains and at least two sets of interchain disulfide bridges. At the amino and carboxyl ends are noncollagenous domains which do not appear to be homologous to amino and carboxyl propeptides of interstitial collagens.

Amino Acid Sequence↗