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Biomedical subjects

K Takata

Publications and source records attributed to K Takata.

At least 181 records · Page 10Linked to original sources
PubMed1989

Scavenger receptor of human monocytic leukemia cell line (THP-1) and murine macrophages for nonenzymatically glycosylated proteins.

Long-term incubation of proteins with glucose undergo a series of nonenzymatic reactions to form advanced glycosylation end product (AGE) with fluorescence and brown color. The receptor for AGE-proteins was demonstrated in murine macrophages (Vlassara et al. (1985) Proc. Natl. Acad. Sci. USA 82. 5588). Our recent study with rat macrophages revealed that the receptor also recognized proteins modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, indicating its close identity to a scavenger receptor for aldehyde-modified proteins (Takata, K. et al. (1988) J. Biol. Chem. 263. 14819). This notion was tested in the present study with human monocytic leukemia cell line (THP-1 cells), human monocyte macrophages and murine peritoneal macrophages. Endocytic uptake of AGE-proteins and aldehyde-modified proteins was inhibited in a cross-competitive fashion. The receptor activities of THP-1 cells for AGE-albumin and aldehyde-modified proteins were induced synchronously by phorbol 12-myristate 13-acetate. Furthermore, upon reduction by NaBH4 of the Schiff base formed between proteins and glucose or aldehydes, no ligand activity was generated. However, once the ligand activity was generated, NaBH4 was no longer effective for the ligand activity. Thus, a structure in common between AGE-proteins and aldehyde-modified proteins may be crucial for recognition by the human macrophage receptor.

Animals↗
PubMed1989

Protective effect of lipoproteins containing apoprotein A-I on Cu2+-catalyzed oxidation of human low density lipoprotein.

Two apoprotein A-I (apoA-I)-containing lipoproteins, one containing apoA-I and apoA-II (LpA-I/A-II) and the other containing only apoA-I (LpA-I), were examined for their effect on Cu2+-mediated oxidation of low density lipoprotein (LDL). The presence of LpA-I or LpA-I/A-II prevented LDL oxidation when assessed by the electrophoretic mobility, apoprotein B fragmentation and amounts of thiobarbituric acid-reactive substances. The protection of LDL oxidation by these lipoproteins was effective for up to 6 h, with LpA-I being more active than LpA-I/A-II. Results from these in vitro model experiments raise a possibility that LpA-I may play a role in protecting LDL from Cu2+-mediated oxidation.

Apolipoprotein A-I↗
PubMed1989

Scavenger receptor-mediated recognition of maleylated albumin and its relation to subsequent endocytic degradation.

Rat sinusoidal liver cells take up maleylated bovine serum albumin (maleyl-BSA) and its demaleylated form (demaleyl-BSA) by scavenger receptor-mediated endocytosis. Cellular binding of maleyl-BSA and demaleyl-BSA and its quantitative relation to subsequent intracellular degradation were investigated. The binding affinities of these ligands were almost equal whereas the number of binding sites for maleyl-BSA was more than twice as large than that for demaleyl-BSA. However, no difference was observed in their endocytic degradation. The amounts of maleyl-BSA degraded were proportional to those bound to the cell surface up to a certain level. However, a further increase in cell-bound ligands did not affect the degradation of maleyl-BSA. Several polyanions such as fucoidin and dextran sulfate of Mr = 5000 inhibited the binding of maleyl-BSA but did not affect its degradation. In contrast, acetylated or oxidized low density lipoprotein had virtually no effect on cellular binding of maleyl-BSA but exhibited profound effects on its intracellular degradation. Similar results were obtained with rat peritoneal macrophages. Based on these data, we would propose that two binding sites are involved in the receptor-mediated ligand recognition; one is coupled to subsequent endocytic degradation, and the other serves as a binding site for polyanionic compounds.

Albumins↗
PubMed1989

Intracellular accumulation of cholesteryl esters suppresses production of lipopolysaccharide-induced interleukin 1 by rat peritoneal macrophages.

Interleukin 1 (IL-1) is a major cytokine of macrophages secreted by several stimulants such as lipopolysaccharide (LPS). Macrophages are known to possess the scavenger receptor for acetylated low density lipoprotein (acetyl-LDL) and maleylated albumin. In the present study we determined effects of these ligands on LPS-induced IL-1 production by rat peritoneal macrophages. These ligands themselves did not induce IL-1 production. However, upon short incubation with acetyl-LDL, LPS-induced IL-1 production was significantly suppressed. The extent of the suppression was proportional to cellular cholesteryl esters. Thus, intracellular accumulation of cholesteryl esters might be responsible for suppression of LPS-induced IL-1 production.

Albumins↗
PubMed1989

Regional ligand domain is involved in scavenger receptor-mediated recognition of maleyl-albumin by rat sinusoidal liver cells.

Scavenger receptor-mediated endocytosis of maleyl-albumin was studied with rat sinusoidal liver cells. Upon maleylation of greater than 28 mol lysine residues per protein, bovine serum albumin became an active ligand. Further modification of up to 37 mol lysine residues per protein resulted in a sharp increase in the ligand activity, reaching a maximum level thereafter. Removal of maleyl moieties from maleyl-albumin (demaleylation) from 53 mol to 14 mol lysine residues per protein did not affect the ligand activity. However, further demaleylation to less than 5 mol lysine residues per protein led to complete loss of the ligand activity. Thus, the covalently incorporated maleyl moieties are needed for the ligand activity. The ligand activity was also generated when two peptides (Frag N and Frag C) from cyanogen bromide-cleaved albumin were maleylated, indicating that the formation of an active ligand would not require a whole albumin molecule. Maleyl Frag C was further separated into three peptides; maleyl Frag C-1 (261 amino acid residues), maleyl Frag C-2 (102 residues) and maleyl Frag C-3 (36 residues). The cellular binding and endocytic degradation of maleyl-albumin or acetylated low density lipoprotein were effectively competed for by maleyl Frag C-1 and maleyl Frag C-2 but not by maleyl Frag C-3. Thus, regional domains might be involved in the ligand recognition by the scavenger receptor.

Albumins↗
PubMed1989

Studies on the panaxytriol of Panax ginseng C. A. Meyer. Isolation, determination and antitumor activity.

An antitumor-active substance was obtained from the residue of the ethyl acetate extract of red ginseng, a traditional Chinese medicine, by chromatography on a silica gel column. From the proton and carbon-13 nuclear magnetic resonance spectra, it was identified as heptadeca-1-ene-4,6-diyne-3,9,10-triol (panaxytriol). The panaxytriol contents of red ginseng and white ginseng, determined by gas chromatography after solvent extraction and formation of trimethylsilyl derivatives, were 0.38 and 0.25 mg/g, respectively. Panaxytriol showed a growth-inhibitory activity against several tumor cell lines.

Alkynes↗
PubMed1989

[An integrated control system for radioisotope facilities].

The authors developed an integrated system for managing the safe use of radioisotope laboratory facilities, users' access to controlled areas, and the control of air-conditioners. This system consisted of a personal computer, an access controller, an eye retinal verifier, magnetic card readers, hand foot cloth monitors, video tape recorders and a fire alarm system. The access controller was set as the central unit to operate the whole system including 13 gates and air-conditioners. Under this program, only registered persons were permitted to enter the laboratories; the exact records on access were easily obtained; and electricity and fuel expenses were largely reduced. We expect that the system would facilitate the safe use of radioisotopes and the utilization of laboratory facilities.

Facility Design and Construction↗
PubMed1989

[Hepatocellular carcinoma treated with a curative segmentectomy five years after complete remission of acute myeloblastic leukemia].

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male who had been known to carry a chronic hepatitis B surface antigen (HBsAg) from June, 1983. Prompt remission was achieved with combination chemotherapy of BHAC-DMP. Follow-up maintenance and an intensification of this chemotherapy had been given for five years. He was readmitted to our hospital in March, 1988 because a mass was detected in the right lobe of the liver by ultrasonography. His serum alpha fetoprotein (AFP) level was found to be 180.1 ng/ml, and was diagnosed as having a hepatocellular carcinoma though there was no evidence of liver cirrhosis. A curative right hepatectomy was performed in May, 1988 after transcatheter arterial embolization and portal embolization. After resection of the tumor, the AFP level decreased to 10.7 ng/ml and no HbsAg was detected in the serum.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Endocytic pathway of high density lipoprotein via trans-Golgi system in rat resident peritoneal macrophages.

Interaction of high density lipoprotein (HDL) with rat resident peritoneal macrophages was investigated by morphological and biochemical approaches. Binding studies at 0 degree C demonstrated saturable binding sites for 125I-HDL on the surface membrane. When cells were incubated with 125I-HDL at 37 degrees C, the cell-associated radioactivity increased with time, but intracellular degradation of HDL did not occur. Rather, the cell-associated 125I-HDL was released intact into the medium. Two morphological probes were employed to visualize the post-binding fate of HDL. Horseradish peroxidase and ferritin conjugates of HDL showed specific bindings to the coated pits of the plasma membranes and were internalized and delivered through receptosomes to a trans-Golgi system. They were then resecreted as secretory vesicles from the cells. Parallel experiments with transferrin-horseradish peroxidase conjugates revealed an endocytic pathway identical or very similar to that observed with HDL. These results provide evidence that internalization and subsequent nonlysosomal pathway via the trans-Golgi system are involved in receptor-mediated endocytosis of HDL by macrophages.

Animals↗
PubMed1989

Development of a new experimental model for total exclusion of the right heart without the aid of cardiopulmonary bypass.

A new experimental model for the total exclusion of the right heart was successfully developed in mongrel dogs without the use of cardiopulmonary bypass. A Y-shaped conduit was constructed with tube grafts spirally stented on the exterior (10 mm in diameter), and each upper limb of the conduit was provided with a 30F cannula. The foot of the conduit was anastomosed with the main pulmonary artery in an end-to-side way with a side clamp. After a closed atrioseptostomy was performed with a special knife of our design, the upper limbs of the graft were connected to the superior and inferior venae cavae by a cannulation method. The operative procedure was completed by tightening the occluding snares around the venae cavae and ligating the root of the pulmonary artery and azygos vein. Thus, without any use of the right atrium, venous blood from the venae cavae was totally diverted to the pulmonary circulation via the conduit, and only the coronary venous return was shunted to the left atrium. Five consecutive dogs tolerated the operative procedure. No pressure gradients were observed between the pulmonary arteries and venae cavae. The circulation with this model was able to be sufficiently sustained with mean pulmonary arterial pressures of about 25 mm Hg, and no significant changes were shown in the left ventricular pump function from the preoperative state. However, the decrease in the mean pulmonary artery pressure to 20 mm Hg resulted in severe circulatory failure, and two of the five dogs succumbed to this condition. Our new model will be useful for studying the hemodynamic characteristics of the circulation after operations that result in total exclusion of the right heart.

Animals↗
PubMed1988

Evidence against in vivo presence of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole, a major fluorescent advanced end product generated by nonenzymatic glycosylation.

The reaction of protein amino groups with glucose leads to the formation of a stable Amadori product via a Schiff base adduct, which is further converted to advanced glycosylation end products (AGE) with color and unique fluorescence characteristics. 2-(2-Furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) was recently identified as a major fluorescent compound (Ponger, S., Ulrich, P.C., Bencsath, F.A., and Cerami, A. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 2684-2688). Its in vivo and in situ presence was further demonstrated by radioimmunoassays (Chang, J.C.F., Ulrich, P.C., Bucala, R., and Cerami, A. (1985) J. Biol. Chem. 260, 7970-7974). In the present study the occurrence of FFI in AGE-proteins was reassessed. The radioimmunoassay using anti-FFI antibody and high performance liquid chromatography failed to detect FFI in AGE samples obtained from bovine serum albumin, poly-L-lysine, oligo-L-lysine, and L-lysine. Even after acid hydrolysis or proteinase K digestion, FFI was undetectable. To our surprise, however, the addition of ammonia to these acid hydrolysate led to the production of FFI, suggesting the importance of acid hydrolysis and subsequent reaction with ammonia for the generation of FFI. This observation was fully supported by model experiments using AGE-samples prepared by incubating glucose with monoaminocarboxylic acids such as beta-alanine, gamma-aminobutyric acid, and epsilon-aminocaproic acid. Thus, a nonfluorescent FFI precursor is produced by acid hydrolysis, and its conversion to fluorescent FFI occurs upon subsequent reaction with ammonia, the evidence against the presence of FFI in AGE-proteins.

Ammonia↗
PubMed1988

Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins.

Long term incubation of proteins with glucose, named the Maillard reaction (Maillard, L. C. (1912) C. R. Acad. Sci. (Paris) 154, 66-68), gives rise to advanced glycosylation end product (AGE) with fluorescence, color, as well as cross-linked properties. The receptor-mediated endocytosis of AGE-proteins by macrophages was reported (Vlassara, H., Brownlee, M., and Cerami, A. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5588-5592). The present study on the binding of AGE-bovine serum albumin (BSA) to rat peritoneal macrophages and sinusoidal liver cells demonstrated the presence of a saturable, high affinity receptor for AGE-BSA with Kd = 2.4 x 10(-7) M (macrophages) and 2.1 x 10(-7) M (sinusoidal cells). The cellular binding of AGE-BSA and its endocytic uptake by these cells were competitively inhibited by BSA preparations modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, ligands known to be specific for a scavenger receptor for aldehyde-modified proteins (Horiuchi, S., Murakami, M., Takata, K., and Morino, Y. (1986). J. Biol. Chem. 261, 4962-4966). These ligands also had a profound in vivo effect on the plasma clearance of 125I-AGE-BSA as well as its hepatic uptake. Thus, endocytic uptake of AGE-proteins by macrophages appeared to be mediated by a scavenger receptor for aldehyde-modified proteins. This provides evidence for the biological importance of the scavenger receptor in eliminating senescent macromolecules from the circulation.

Animals↗
PubMed1988

Phosphotyrosine-modified proteins are concentrated at the membranes of epithelial and endothelial cells during tissue development in chick embryos.

We have used high affinity polyclonal antibodies specific for phosphotyrosine (PTyr) residues to examine the localization in various chick embryonic tissues in situ of PTyr-modified proteins by immunocytochemical methods. During the period from 9 to 21 d of development, most tissues exhibit elevated levels of PTyr-modified proteins as determined by immunoblotting experiments of tissue extracts with the anti-PTyr antibodies (Maher, P. A., and E. B. Pasquale. 1988. J. Cell Biol. 106:1747-1755). By immunofluorescence labeling of semithin frozen sections, the highest concentrations of PTyr immunolabeling in all of the embryonic tissues examined were localized to the membranes of the epithelial and endothelial cells with other cells showing no detectable labeling. These results were confirmed by immunoelectron microscopic labeling, which showed particularly high concentrations of PTyr-modified proteins close to the membranes at the apical junctions. The corresponding adult tissues showed no labeling. It is proposed that these results reflect the molecular basis for the functional plasticity of epithelial and endothelial cell junctions during embryonic development.

Animals↗