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Biomedical subjects

K Higashiyama

Publications and source records attributed to K Higashiyama.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Surgical treatment of T3N0M0 non-small cell lung cancer].

From January 1982 to June 1995, 45 patients underwent operation at our department for T3N0M0 non-small cell lung cancer. Tumors invaded chest wall in 38 patients (parietal pleura in 17, subpleural fat tissue in 10, and rib in 11), diaphragm in 3, mediastinum in 3, and pericardium in 1. Extrapleural dissection was performed in 17 patients and en bloc resection of chest wall and lung was performed in 21. Complete resection was possible in 43 patients (96%). Operative mortality was 2.2%. The actuarial overall 5-year survival rate was 63% for the patients with parietal pleura invasion, 45% for those with subpleural invasion, 45% for those with rib invasion, and 56% for those with diaphragm, mediastinal pleura or pericardial invasion. Recurrence at the resected margin was observed in 5 patients with chest wall invasion (subpleural tissue in 3, rib in 2) and 1 with diaphragmatic invasion. In conclusion, we recommend an en bloc resection of the chest wall with enough surgical margin for peripheral tumors firmly adherent to the parietal pleura.

Adult↗
PubMed1997

Antinociceptive effects of (+)-matrine in mice.

The antinociceptive potency of matridin-15-one ((+)-matrine) was examined using the acetic acid-induced abdominal contraction test and the tail-flick test in mice. (+)-Matrine, at doses of 1 to 10 mg/kg, s.c., produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal contractions in mice. The antinociceptive effect of (+)-matrine in the acetic acid-induced abdominal contraction test in mice was identical to that of pentazocine. Indeed, there was no significant difference in the ED50 (mg/kg with 95% confidence limits) values for the inhibition of acetic acid-induced abdominal contractions between (+)-matrine (4.7 (4.1-5.3)) and pentazocine (3.3 (2.2-5.0)). Furthermore, in the tail-flick assay, (+)-matrine at doses of 10 and 30 mg/kg, s.c., again produced a dose-dependent antinociceptive effect. When nor-binaltorphimine (20 mg/kg, s.c.), a selective kappa-opioid receptor antagonist, was administered 3 h before treatment with (+)-matrine, the antinociceptive effect of (+)-matrine was markedly antagonized. Furthermore, the antinociceptive effect of (+)-matrine was partially antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Naltrindole, a selective delta-opioid receptor antagonist, had no effect on the antinociceptive effect of (+)-matrine. In conclusion, (+)-matrine produced an antinociceptive effect mainly through the activation of kappa-opioid receptors and partially through mu-opioid receptors.

Abdomen↗
PubMed1996

Characterization of the constituent polypeptides of the extracellular hemoglobin from Lumbricus terrestris: heterogeneity and discovery of a new linker chain L4.

The extracellular hemoglobin of Lumbricus terrestris comprises four oxygen binding chains, a, b, c, d, and three linker chains L1, L2, L3 as major components. A stoichiometry of the whole molecule has been proposed on the basis of these chains, with a total number of 216 chains: forty-eight chains of each oxygen binding chain and eight molecules of each linker chain. We have isolated additional minor components by HPLC and two-dimensional gel electrophoresis. The following biochemical characterizations have been made. (i) All components so far reported, the heme-containing chains a, b, c, d, and linker chains L1, L2, L3 and a new minor polypeptide, L4, were mapped on a two-dimensional gel. Their estimated isoelectric points were between 4.7 and 5.9. (ii) The sequences of several peptides including the unique N-terminal peptide from linker L4 show that it can be considered as a duplicated gene product with a similar mass. (iii) Chain d2 was isolated and found to correspond to the minor chain previously pointed out by Shishikura et al. (J. Biol. Chem. 262 (1987) 3123-3131). (iv) The major chain d1 has serine at position 7 from the N-terminus. This is not consistent with previously reported glycine (Shishikura et al., J. Biol. Chem. 262 (1987) 3123-3131).

Amino Acid Sequence↗
PubMed1996

Isolation and amino acid sequence of a cystatin-type cysteine proteinase inhibitor from bovine hoof.

A low molecular mass cysteine proteinase inhibitor was found and isolated from bovine hoof. Purification of the inhibitor to homogeneity was performed by carboxymethyl-papain-sepharose affinity and DE-52 ion exchange chromatographies. From 15 g of bovine hoof, 0.25 mg of cysteine proteinase inhibitor was isolated. It had 100 amino acid residues and molecular mass of 11 406 Da, and its N-terminus was blocked. The amino acid sequence of the inhibitor demonstrated high similarity with that of the family 1 group, especially bovine thymus-derived cystatin. Thus, in summary, bovine hoof contains a cystatin-type cysteine proteinase inhibitor, presumably a family 1 cystatin.

Amino Acid Sequence↗
PubMed1996

Induction of c-fos protooncogene transcription and apoptosis by delta 12-prostaglandin J2 in human Pl-21 myeloid leukemia and RC-K8 pre-B lymphoma cells.

delta 12-prostaglandin J2 (PGJ2) is a dehydration product of PGD2 and thought to be the most potent antitumor agent among prostaglandin compounds. We examine the cytotoxic effects of PGJ2 on the cell growth of leukemia/lymphoma cells. PGJ2 inhibited the growth of both human PL-21 myeloid leukemia and RC-K8 pre-B lymphoma cells in culture in a dose-dependent manner with fragmentation of nucleus and formation of apoptotic body. Agarose gel electrophoresis revealed DNA ladder formation in the cells treated with PGJ2. Furthermore, PGJ2 induced a rapid and transient expression of apoptosis-related protooncogene, c-fos, in both cells. The gene transcriptional rate was remarkably increased approximately 3.3-fold in PGJ2 treated cells, but the stability of c-fos mRNA was not significantly changed. Inhibition of de novo protein synthesis with cycloheximide increased c-fos mRNA stability but not abrogated PGJ2-induced c-fos transcription. These data suggest that PGJ2 can induce apoptosis of human leukemia/lymphoma cells and the rapid activation of c-fos protooncogene transcription in which de novo protein synthesis is not required.

Antineoplastic Agents↗
PubMed1996

The amino acid sequences of two alpha chains of hemoglobins from Komodo dragon Varanus komodoensis and phylogenetic relationships of amniotes.

To elucidate phylogenetic relationships among amniotes and the evolution of alpha globins, hemoglobins were analyzed from the Komodo dragon (Komodo monitor lizard) Varanus komodoensis, the world's largest extant lizard, inhabiting Komodo Islands, Indonesia. Four unique globin chains (alpha A, alpha D, beta B, and beta C) were isolated in an equal molar ratio by high performance liquid chromatography from the hemolysate. The amino acid sequences of two alpha chains were determined. The alpha D chain has a glutamine at E7 as does an alpha chain of a snake, Liophis miliaris, but the alpha A chain has a histidine at E7 like the majority of hemoglobins. Phylogenetic analyses of 19 globins including two alpha chains of Komodo dragon and ones from representative amniotes showed the following results: (1) The a chains of squamates (snakes and lizards), which have a glutamine at E7, are clustered with the embryonic alpha globin family, which typically includes the alpha D chain from birds; (2) birds form a sister group with other reptiles but not with mammals; (3) the genes for embryonic and adult types of alpha globins were possibly produced by duplication of the ancestral alpha gene before ancestral amniotes diverged, indicating that each of the present amniotes might carry descendants of the two types of alpha globin genes; (4) squamates first split off from the ancestor of other reptiles and birds.

Amino Acid Sequence↗
PubMed1996

Inhibitory effect of a synthetic prostacyclin analogue, beraprost, on urokinase-type plasminogen activator expression in RC-K8 human lymphoma cells.

Plasminogen activation by urokinase-type plasminogen activator (uPA) is implicated in tumor invasion and metastasis by the breakdown of extracellular matrix. We have recently demonstrated the inhibitory effect of cAMP on uPA gene transcription in RC-K8 human lymphoma cells (Biochim Biophys Acta 1268: 293-9, 1995). Prostacyclin produced by endothelial cells is shown to increase cellular cAMP levels by activating adenylate cyclase. We, therefore, examined the effect of a stable analogue of prostacyclin, Beraprost, on uPA production in RC-K8 cells. uPA activity gradually increased in the conditioned medium with time. Beraprost (0.1 nM-1.0 microM) inhibited uPA accumulation in a dose-dependent manner without affecting cell viability. Fibrinzymography demonstrated that high and low molecular forms of uPA were present in the conditioned medium and that after Beraprost-treatment all forms of uPA decreased and no PA/PA inhibitor complex was present. Northern blot analysis revealed that after exposure to Beraprost, uPA mRNA levels increased transiently and then rapidly decreased to below control levels. Treatment with Beraprost resulted in a rapid activation of cellular cyclic AMP-dependent protein kinase (PKA). Beraprost completely negated uPA gene expression induced by phorbol myristate acetate, an activator of protein kinase C (PKC). These results suggest that Beraprost inhibits uPA production by suppressing uPA gene expression through the PKA pathway and that PKA-mediated signals are dominant in uPA gene expression as compared to those medicated by PKC. This inhibition of uPA expression by a prostacyclin analogue may be an important fact to explain the mechanism of anti-metastatic effects of prostacyclin.

Enzyme Inhibitors↗
PubMed1992

The enhancement of specific antibody production rate in glucose- and glutamine-controlled fed-batch culture.

The concentration effects of certain amino acids (Asp, Ile, Leu, Lys, Met, Val, Phe and Gln which were highly consumed during cultivation), and glucose on cell growth and antibody productivity were investigated using dish culture. From these experiments, it was found that only glutamine enrichment enhanced the specific antibody production rate. The other amino acids described above did not affect either the specific growth rate or specific antibody production rate. Thus we investigated the quantitative effects of glutamine concentration in the range of 0.4-33.3 mmol.l-1 on kinetic parameters in fed-batch culture which kept both glucose and glutamine concentration constant. As a result the specific growth rate decreased with increase in glutamine concentration in the range larger than 20 mmol.l-1. The specific antibody production rate had a maximum value at about 25 mmol.l-1 glutamine concentration.

Animals↗
PubMed1990

Enhancing effect of piperidone derivatives on the percutaneous absorption of indomethacin.

Following our previous demonstration that Azone and 2-n-alkylcyclohexanones enhanced the percutaneous absorption of indomethacin, six 1-n-alkylpiperidones were prepared and examined as potential transdermal absorption enhancers. In vitro skin experiments showed that indomethacin absorption enhancement was related to the lipophilicity of the enhancer, and that 1-n-dodecyl piperidone caused the greatest enhancement. The structure of this piperidone is similar to that of Azone, and both compounds had similar lipophilicity and drug absorption enhancement activity. We suggest that they act in the same way by decreasing diffusional resistance in the stratum corneum, and so modifying the hard barrier of the stratum corneum.

Animals↗
PubMed1989

Promoting effect of 2-n-alkylcyclohexanones on the percutaneous absorption of indomethacin.

We previously evaluated the promoting effects of 2-tert-butylcyclohexanone and its analogues on the percutaneous absorption of indomethacin (IMC), and showed that the 2-position of the cyclohexanone ring plays an important role in drug permeability through the skin. The present study investigates the in vitro penetration enhancement of IMC by five 2-n-alkylcyclohexanone derivatives. 2-n-Octylcyclohexanone was the most effective enhancer, but the other four enhancers also had significant promoting actions on skin permeability of IMC. Maximum absorption enhancement was associated with a defined range of enhancer lipophilicity. We propose that the enhancer penetrates into the stratum corneum and improves skin permeability of a drug by dissolving some of the hard lipid components or modifying the dense lipid stratum corneum.

Animals↗
PubMed1987

Expression of pancreatic secretory trypsin inhibitor in various cancer cells.

We demonstrated by immunoperoxidase staining that a half of cancer tissues surgically resected contained pancreatic secretory trypsin inhibitor-immunoreactive cells. Immunoreactivity in cancer tissues was detected in both early and advanced cancers. Human cell lines (BxPC-3, MIA PaCa-2, PANC-1, KATO-III, COLO 201, SW 403, WIHOVCAR 3, HeLa Ohio, A549 and SK X HEp-1) expressed pancreatic secretory trypsin inhibitor.

Aprotinin↗
PubMed1985

Evidence for involvement of cytochrome P-450-linked oxygenase system in the conversion of C21-steroids to delta 16-C19-steroids catalyzed by pig testicular microsomes.

Formation of androstadienone or androstadienol, a delta 16-C19-steroid, from progesterone or pregnenolone is catalyzed by the so-called delta 16-C19-steroid synthesizing enzyme in the pig testicular microsomes. The enzyme activity was also present in the testicular microsomes prepared from neonatal pig. The enzyme activity was considerably inhibited by CO, and such cytochrome P-450 inhibitors as SU 8000, SU 10603, and metyrapone. delta 16-C19-Steroid synthesizing enzyme activity was extracted from the testicular microsomes by sodium cholate in potassium phosphate buffer, pH 7.4, containing EDTA and dithiothreitol, and the solubilized enzyme activity was partially purified by DEAE-cellulose column chromatography. It was shown by reconstitution of the enzyme activity that delta 16-C19-steroid synthesizing enzyme is a cytochrome P-450-linked oxygenase system dependent on cytochrome P-450-reductase and cytochrome b5. In particular, cytochrome b5 was an essential component for the activity of delta 16-C19-steroid synthesizing enzyme.

Animals↗