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Biomedical subjects

S Oikawa

Publications and source records attributed to S Oikawa.

At least 217 records · Page 12Linked to original sources

Antitumor and immunomodulating activities of a beta-glucan obtained from liquid-cultured Grifola frondosa.

The effects of the beta-1,3-glucan, LELFD, obtained from liquid-cultured mycelium of Grifola frondosa, on the growth of syngeneic tumors and immune responses in mice were examined. In Meth A or IMC solid tumor systems, LELFD administered intraperitoneally (i.p.) or intralesionally (i.l.) exhibited significant antitumor effects. However, the growth of L1210 and P388 leukemias was unaffected by the injection of LELFD. The injection of LELFD i.p. enhanced the activities of natural killer cells and macrophages in mice. LELFD also enhanced the antibody response when it was injected i.p. with sheep red blood cells into mice. Furthermore, it was found that LELFD could activate the alternative complement pathway.

Adjuvants, Immunologic↗

Effect of eye-derived growth factors from rabbit retina on proliferation of endothelial cell from marginal vessels.

The biological activity of eye-derived growth factor(s) (EDGF) was studied in endothelial cells and other cell types. The endothelial cells of rabbit ears were aseptically collected from marginal vessels in a short time without contamination with other cell types. The cells were cultured in 10% FBS-MEM that possessed Factor VIII antigen and Weibel-Palade bodies, and showed monolayer cobble-stone formation. The retinal extracts from rabbits promoted not only endothelial cells but also fibroblasts and smooth muscle cells. Partially purified EDGF was obtained from retinal extracts by means of acetone precipitation and successive chromatographic separation with Heparin Sepharose and Sephadex G-200. The molecular weight was estimated at more than 150 kDa by gel filtration. The partially purified EDGF promoted proliferation of endothelial cells from rabbit ear marginal promoted vessels and bovine aorta, but did not affect smooth muscle cells, skin fibroblasts and Swiss albino 3T3 cells. Thus rabbit EDGF might be cell specificity in stimulating cell proliferation.

Animals↗

Effect of taurine administration on serum lipid and biliary lipid composition in man.

The effect of oral administration of taurine (3.2 g/day, 2 weeks) on the metabolism of lipids and bile acids was studied with healthy humans. Four male subjects were fed taurine. Another five male subjects were administered 1 g of cholesterol daily for two weeks and, at intervals of two weeks, cholesterol and taurine simultaneously. Serum lipoprotein and duodenal bile were analyzed. Oral administration of taurine resulted in the increase of taurine-conjugated bile acids. However, neither serum lipid nor biliary lipid composition was altered. Addition of taurine with cholesterol administration showed elevation of both the serum low density lipoprotein cholesterol level and the lithogenic index in bile. The ratio of glycine-to taurine-conjugated bile acids was changed from 4.1 to 0.63. The ratio of cholic acid/chenodeoxycholic acid was augmented from 0.57 to 0.81. The percentage of taurocholic acid, taurochenodexycholic acid and taurodeoxycholic acid were increased about 4-fold, 2.5-fold and 3-fold, respectively. Our results suggested that taurine administration alone did not influence the serum lipid level although taurine-conjugated bile acids were increased. The taurine intake would increase serum low density lipoprotein cholesterol and biliary cholesterol levels when excessive cholesterol is administered simultaneously.

Administration, Oral↗

Atrial natriuretic peptide gene expression and its secretion by pneumocytes derived from neonatal rat lungs.

Using a primary culture of pneumocytes derived from neonatal rat lungs, we investigated the synthesis and secretion at transcriptional and peptide levels of pulmonary rat(r) atrial natriuretic peptide (ANP). Total RNA extracted from pneumocytes contained a hybridizing RNA band of the same size as atrial rANP mRNA. Immunoreactive (IR)-rANP content in pneumocytes was 0.5% of that in atrial myocytes, and 8.6% of that in ventricular myocytes, while the secretory rate from pneumocytes was about 7% of atrial and ventricular myocytes. Triiodothyronine (T3, 5 x 10(-10) to 5 x 10(-8) M), dexamethasone and testosterone (5 x 10(-9) to 5 x 10(-8) M) significantly stimulated the synthesis of IR-rANP by pneumocytes in a dose-dependent manner. However, the stimulatory effect exerted by T3 on rANP synthesis, unlike in the case of cardiocytes, was much more potent than that of dexamethasone, as evidenced by the significant difference in potency at both transcriptional and peptide levels. The present study suggests that ANP secreted from lungs may at least in part contribute to circulating ANP pool, and that the tissue-dependent difference of sensitivity to thyroid hormone may play an important role in the regulation of developmental ANP gene expression in mammalian lungs.

Animals↗

Exon-intron organization of a gene for pregnancy-specific beta 1-glycoprotein, a subfamily member of CEA family: implications for its characteristic repetitive domains and C-terminal sequences.

A fragment of human gene for pregnancy-specific beta 1-glycoprotein(s), recently identified CEA family member(s), has been cloned. Analyses of nucleotide and deduced amino acid sequences revealed that it carried, from 5' to 3' direction, exons IA, IB, IIA, IIB, C3, C1 and C2, the first four encoding peptides distinct from but highly similar to domains of PS beta Gs. The lack of consensus 3' splice site sequence ahead of IB indicated that it was an abortive exon, which would explain the peculiar domain construction of PS beta Gs, i.e. N-IA-IIA-IIB-C1, 2 or 3. Apparently, the multiple C-terminal sequences for a PS beta G were generated by alternative splicing among C1, C2 and C3 exons. Furthermore, sequences which overlapped partly with Cexons, were found to be similar to parts of 3'-UTR of CEA and NCA, indicating further the close relationship of CEA/NCA and PS beta G subfamily genes.

Amino Acid Sequence↗

Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence.

A cDNA containing the entire coding region for a member of carcinoembryonic antigen (CEA) gene family has been cloned from cDNA library of HLC-1 cells by immunochemical screening with the antibody specific to nonspecific crossreacting antigen (NCA). The cDNA encodes a precursor form of a polypeptide consisting of a 34-residue signal sequence, a 108-residue N-terminal (N-) domain, a 178-residue domain (NCA-I domain) and a 24-residue domain rich in hydrophobic amino acids (M-domain). Each domain has a distinct but homologous amino acid sequence to that of the corresponding domain of CEA. Unlike the coding sequences, the 3'-untranslated sequences differ markedly in the NCA and CEA cDNAs facilitating the preparation of probes that will discriminate between nucleotide sequences for CEA and NCA.

Amino Acid Sequence↗

Compound 48/80 elicits cholinergic contraction through histamine release in the chick oesophagus.

1. The effects of compound 48/80 on cholinergic nerve transmission and on the liberation of histamine in the isolated chick oesophagus were investigated. 2. Compound 48/80 (0.2-1 microgram ml-1) potentiated the cholinergic nerve-induced contraction and caused the contraction of the oesophagus itself. The latter response was prevented by atropine, tetrodotoxin and mepyramine but not by metiamide. 3. Compound 48/80 released dose-dependently endogenous histamine from the isolated chick oesophagus. 4. These results suggest that the action of compound 48/80 is mediated by the release of histamine from an endogenous pool and that histamine released endogenously facilitates the release of ACh from the intrinsic cholinergic nerve in the chick oesophagus.

Acetylcholine↗

Intermolecular nuclear Overhauser effect and atomic pair potential approaches to wheat germ agglutinin-sugar binding.

The detailed binding mechanism of wheat germ agglutinin (WGA) with N-acetylglucosamine (GlcNAc) was investigated using intermolecular 1H-1H nuclear Overhauser effect (NOE) and atomic pair potential (APP) calculations. Negative NOE was observed on the 1H spectrum of 1-O-methyl derivative of GlcNAc in a solution containing WGA, when the aromatic region of the WGA spectrum was irradiated. Analyses of the time dependence of NOE revealed that H2 and the N-acetyl methyl protons of the sugar are in close proximity to the aromatic protons of WGA in the bound state. This was confirmed and further elucidated by the APP calculations. According to the calculation, the major binding force comes from a hydrogen-bonding between C3-OH of sugar and an acidic residue present in each of the two binding sites of WGA: Glu115 in site 1 and Asp29 in site 2. The binding is further assisted by the N-acetyl group which interacts with a few more polar amino acid residues in the binding sites. The optimized binding mode suggested by the APP calculations supports the NMR results in that H2 and a part of the N-acetyl methyl protons are within 4.5 A distance from protons of both Tyr64 and Tyr73 in site 1 and of Tyr159 in site 2.

Acetylglucosamine↗

Differential expression of carcinoembryonic antigen and nonspecific crossreacting antigen genes in human colon adenocarcinomas and normal colon mucosa.

The level of mRNA for carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in human colon adenocarcinomas and normal colon mucosa was analyzed by Northern blot hybridization using as probes 32P-labeled CEA cDNA and synthetic oligodeoxyribonucleotides specific to CEA and NCA mRNA sequences. The major 3.5-kb mRNA and a minor 4.2-kb mRNA are shown to be CEA-specific and expressed in both tissues, albeit at slightly different degrees, suggesting that the expression of CEA is regulated posttranscriptionally. Another minor mRNA of 2.9 kb is NCA-specific and expressed predominantly in cancerous tissues, suggesting its usefulness as a marker for colon cancer.

Adenocarcinoma↗

Distribution of grifolan NMF-5N (I/B), a chemically modified antitumor beta-glucan in mice.

The distribution of a 3H-labeled chemically modified antitumor beta-glucan, grifolan NMF-5N (I/B), in various tissues after an injection into mice was examined in order to obtain information on distribution of the parent antitumor beta-glucan, grifolan NMF-5N. Grifolan NMF-5N was treated with sodium metaperiodate and sodium borotritide to obtain tritium-labeled grifolan NMF-5N [3H-grifolan (I/B)]. When 3H-grifolan (I/B) was administered into normal mice by intraperitoneal (i.p.) or intravenous (i.v.) injection, radioactivity was detected in various mouse tissues. Next, 3H-grifolan (I/B) was injected into tumor-bearing mice 7 d after the tumor inoculation, which is the most effective administration timing for the antitumor effect of grifolan NMF-5N. The results indicated a strong radioactivity in spleens and tumor masses. These results suggested a close relationship between the antitumor activity and the distribution of grifolan NMF-5N in mice.

Animals↗

Apolipoprotein E phenotypes of normo- and hyperlipoproteinemia in Japanese.

Apolipoprotein E phenotypes of normo- and hyperlipoproteinemia in Japanese were examined by the disc gel isoelectric focusing technique, which was modified according to the method of Kashyap et al. (1981). Apoprotein E isoproteins were clearly separated by this method. Six phenotypes (E2/2, E3/3, E4/4, E2/3, E2/4 and E3/4) were determined in 107 cases of normolipoproteinemia and 75 cases of hyperlipoproteinemia. In normolipoproteinemia, apoE phenotype frequencies were similar to those of the Japanese and Caucasian populations which were reported previously. In hyperlipoproteinemia, a higher frequency of phenotype E2/2 and a lower frequency of E3/3 were observed. The apo E phenotypes of type IIa and IIb were distributed similarly to that of normal subjects. In contrast, only 27.8% of type IV patients had E3/3 phenotype. Among type V patients 64.3% was homozygous or heterozygous for E-4, and only 14.3% was homozygous for E-3 (E3/3). The results suggest that the apolipoprotein E phenotypes are similarly distributed among different human races and the apolipoprotein E phenotypes could be one of the etiological factors associated with some types of hyperlipoproteinemia.

Adult↗

Angiogenesis factors in ocular tissues of normal rabbits on chorioallantoic membrane assay.

Recent studies have shown that angiogenesis-stimulatory factors exist in ocular tissues and play a crucial role in the development of some eye disorders such as diabetic retinopathy. However, there are few reports that studied location of angiogenesis factors in ocular tissues of experimental animals. We studied angiogenesis factors in ocular tissues of normal rabbits by chorioallantoic membrane (CAM) assay. Extracts derived from the retina, iris-ciliary body and optic nerve showed an evident activity of angiogenesis. Retinal extracts at 10 micrograms showed a strong angiogenic activity in 50% of CAMs (p less than 0.01). On the other hand, bovine serum albumin which is heterogeneous protein showed only a slight angiogenic activity at a high concentration (1,000 micrograms). The iris-ciliary body and optic nerve showed also an angiogenic activity as did the retina. Extracts from the heart, liver and serum showed no activity of angiogenesis. Thus, angiogenic activity was strongly present in the ocular tissues, especially in retina of the normal rabbits.

Allantois↗

Molecular cloning of a gene for a member of carcinoembryonic antigen (CEA) gene family; signal peptide and N-terminal domain sequences of nonspecific crossreacting antigen (NCA).

A 2073-base pair DNA fragment containing a part of gene for a member of carcinoembryonic antigen (CEA) gene family, has been isolated from human DNA library after screening with 32P-labeled 53-mer oligodeoxyribonucleotide corresponding to N-terminal 18 amino acids of CEA gene family and cDNA encoding CEA (1,2). The fragment contains two exons; the one encodes the first 60% of signal peptide and the other the rest of it in addition to 107 amino acids which correspond to the N-terminal domain of CEA (1,2). Apparently, the second intron is inserted between the first and the second nucleotides of the codon for 108th amino acid. The presence of Ala instead of Val as the 21st amino acid of the N-terminal domain indicates that the exon encodes nonspecific crossreacting antigen (NCA).

Amino Acid Sequence↗

The carcinoembryonic antigen (CEA) contains multiple immunoglobulin-like domains.

The amino acid sequences of human carcinoembryonic antigen deduced from the cDNA sequences have been analysed. This antigen contains seven extracellular domains (previously recognized three highly repetitive domains are further divided into A and B subdomains each) which are strikingly homologous to each other and to immunoglobulin variable regions, poly-Ig receptor and Thy 1.1. The N-terminal domain lacks immunoglobulin-like fold but the other six domains have, suggesting that the CEA belongs to immunoglobulin superfamily.

Amino Acid Sequence↗

Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence.

The cDNAs corresponding to the mRNA encoding a polypeptide which is immunoreactive with the antisera specific to carcinoembryonic antigen (CEA) (1) are cloned. The amino acid sequences deduced from the nucleotide sequences of the cDNAs show that it is synthesized as a precursor with a signal peptide followed by 668 amino acids of the putative mature CEA peptide, whose N-terminal 24 amino acids and amino acids 286 to 295 exactly coincide with those known for N-terminal sequences of CEA (2) and NFA-1 (3), respectively. The first 108 N-terminal residues are followed by three very homologous repetitive domains of 178 residues each and then by 26 mostly hydrophobic residues which probably comprise a membrane anchor. Each repetitive domains contains 4 cysteines at precisely the same positions and as many as 28 possible N-glycosylation sites are found in the CEA peptide region agreeing with high carbohydrate content of purified CEA.

Amino Acid Sequence↗

Effect of low density lipoprotein on DNA synthesis of cultured human arterial smooth muscle cells.

Increased concentration of plasma low-density lipoprotein (LDL) is one of the risk factors in atherosclerosis. We studied how DNA synthesis of human arterial smooth muscle cells (SMC) was influenced in the culture added with or without small dose (25 micrograms of protein/ml) of LDL. LDL were ultracentrifugally obtained from normal subjects and diabetics. DNA synthesis was investigated at 6-h intervals during 36 h in the culture with or without LDL using [methyl-3H]thymidine. We found that DNA synthesis reached a maximum value at 24 h after addition of LDL. On the other hand sequential changes were not detectable in the culture without LDL addition. This effect of diabetic LDL was significantly (P less than 0.001) greater than that of normal LDL. These results suggested that LDL induces synchronization of the cultured SMC to synthesize DNA and diabetic LDL may play an atherogenic role more strongly than normal LDL in the arterial wall even in the normal range of LDL concentration.

Arteries↗