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81.
Fuminori Abe Gregory Alvord Michinori Koyama Akira Matsuda James E. Talmadge 《Cancer immunology, immunotherapy : CII》1989,28(1):29-33
Summary Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2 and 12.8 min t1/2), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2s of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration×time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics.This research was supported by the National Cancer Institute, DHHS, under contract No. N01-23910 with Program Resources, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government 相似文献
82.
Gen Matsumoto Michinori Ichikawa Akira Tasaki Hiromu Murofushi Hikoichi Sakai 《The Journal of membrane biology》1983,77(2):77-91
Summary Effects of the reagents suppressing or supporting axoplasmic microtubule assembly were studied on the Na ionic current of squid giant axons by perfusing the axon internally with the solution containing the reagent. Among the reagents suppressing the assembly, colchicine, vinblastine, podophyllotoxin, sulfhydryl reagents such as DTNB and NEM, and chaotropic anions such as iodide and bromide, were examined. These reagents reduced maximum Na conductance and shifted the voltage dependence of steady-state Na activation in a depolarizing direction along the voltage axis. They also made the voltage dependence less steep, but did not affect sodium inactivation appreciably. Effects on Na ionic current of reagents which support microtubule assembly (Taxol, DMSO, D2O and temperature) were opposite the effects of those agents suppressing assembly. At the same time, we demonstrated that after Na currents were partially reduced, they could be restored by internally perfusing the axon with a solution containing microtubule proteins, 260K proteins and cAMP under conditions favorable for microtubule assembly. For full restoration, it was found that the following conditions were necessary: (1) The microenvironment within the axon is suitable for microtubule assembly. (2) Tubulins incorporated into microtubules are fully tyrosinated at their C-termini. (3) A peripheral protein having a molecular weight of 260,000 daltons (260K protein) is indispensable. These results suggest that axoplasmic microtubules and 260K proteins in the structure underlying the axolemma play a role in generating Na currents in squid giant axons. 相似文献
83.
Jun-ichi Kunitomo Yoshiko Murakami Megumi Oshikata Tetsuro Shingu Michinori Akasu Sheng-Teh Lu Ih-Sheng Chen 《Phytochemistry》1980,19(12):2735-2739
Five new alkaloids, dehydrocrebanine, 4,5-dioxodehydrocrebanine, stesakine, dehydrostesakine, bisaknadinine and four known alkaloids, lirodenine, lanuginosine, 1-tetrahydropalmatine, d-isocorydine with a few alkaloids of unknown structure were newly isolated from Stephania sasakii. The structures of the new alkaloids were determined from spectral data and chemical evidence. 相似文献
84.
Hapten-inhibition studies showed that 3-O-methyl-D-glucose andmethyl--D-mannopyranoside, which are strong sugar haptens ofhemagglutination by pea seed lectins, inhibited (a) bindingof pea seed lectins with Rhizobium leguminosarum J357 cells,(b) the precipitin reaction of pea seed lectins with a capsularpolysaccharide from J357 cells and (c) adsorption of J357 cellsto a pea root. When the capsular polysaccharide was absorb edby the lectins or oxidized by periodate to remove the precipitinreactivity with the lectin, the inhibitory activity of the capsularpolysaccharide towards the adsorption disappeared. I.ectins,which were isolated from the bathing solution of pea roots inacid buffer (pH 2.1), were similar to the seed lectins in sugar-bindingspecificity. The possible existence of lectins on pea root hairsurface was shown by the indirect imraunofluorescent antibodytechnique in combination with the biotin-avidin system. Theseresults suggest that host recognition in Rhizobium-pea. symbiosisis based on the interaction between rhizobial cells and hostlectins.
1Present address: Nodai Research Institute, Tokyo Universityof Agriculture, Setagaya-ku, Tokyo 156, Japan. (Received February 18, 1981; Accepted May 2, 1981) 相似文献
85.
Hiroki Yokoo Seiichi Chiba Kengo Tomita Michinori Takashina Hiroshi Sagara Saburo Yagisita Yasuo Takano Yuichi Hattori 《PloS one》2012,7(12)
Sepsis is a major clinical challenge and septic encephalopathy is its nasty complication. The pathogenesis and underlying mechanisms of septic encephalopathy are not well understood. This study sought to fully characterize sepsis-associated biochemical and histopathological changes in brains of mice after cecal ligation and puncture, regarded as a highly clinically relevant animal model of polymicrobial sepsis. Real-time PCR analysis showed that gene expression levels of proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly up-regulated in brain tissues from septic mice, but to a much lesser extent when compared with those in peripheral tissues such as lungs. Blood-brain barrier (BBB) permeability was significantly increased in septic mice, as determined by the measurement of sodium fluorescein and Evans blue content. Sepsis resulted in increases in NADPH oxidase activity and expression of p47phox and p67phox and up-regulation of inducible nitric oxide (NO) synthase in brains, indicating that superoxide, produced by NADPH oxidase, reacts with NO to form peroxynitrite, that maybe lead to the loss of BBB integrity. Light and electron microscopic examination of septic mouse brain showed serious neuronal degeneration, as indicated by hyperchromatic, shrunken, pyknotic, and electron-dense neurons. These histopathogical changes were prevented by treatment with the free radical scavenger edaravone. Together, these results suggest that sepsis can lead to rapid neurodegenerative changes in brains via free radical species production and possibly subsequent injury to the BBB. We may also provide a potentially useful therapeutic tool for treating septic encephalopathy. 相似文献
86.
Kohji Moriishi Michinori Terao Minako Koura Satoshi Inoue 《Microbiology and immunology》1998,42(2):129-132
The region encoding proline-rich units of actA genes was amplified from 24 strains of Listeria monocytogenes using polymerase chain reaction (PCR). PCR products of 13 strains showed the expected size of 623 bp, whereas those of 11 strains showed a short size of 518 bp. The shortening of these PCR products resulted from the deletion of one proline-rich unit. These results indicate that ActA proteins are divided into at least two different types which are unrelated to bacterial serotypes. 相似文献
87.
A Yoshimura T Yoshida T Seguchi M Waki M Ono M Kuwano 《The Journal of biological chemistry》1987,262(27):13299-13308
We have studied function and structure of the low density lipoprotein (LDL) receptors in a monensin-resistant (Monr-31) mutant isolated from Chinese hamster ovary (CHO) cells. To assay the ability of the receptor to bind LDL, we employed three methods, 125I-LDL binding to the cells at 4 degrees C, 125I-LDL binding to the receptor-phospholipid complex (Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1980) J. Biol. Chem. 255, 11442-11447), and ligand blotting (Daniel, T.O., Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1983) J. Biol. Chem. 258, 4606-4611). The LDL receptor number was similar in both CHO and Monr-31, but the binding affinity was reduced in the mutant. The semi-quantitative immunoblotting assay with an antibody directed against the COOH-terminal 14 amino acids and the ligand-blotting assay with LDL also showed that the relative steady-state level of the receptor in Monr-31 was comparable to that in CHO, whereas the binding capacity of the receptor in Monr-31 was lower than that in CHO. The precursor and degradation forms of the LDL receptors produced in the mutant cells were similar in size to those in the parental cells, but the apparent molecular mass of the mature receptor protein in sodium dodecyl sulfate-polyacrylamide gels was reduced about 5000 daltons in the mutant. These results suggest a structural change at the NH2-terminal LDL binding domain. Tests of the effects of tunicamycin, endo-alpha-N-acetylgalactosaminidase (O-glycanase), and sialidase (neuraminidase) on the molecular size of the mature receptors indicated that the reduced size of the receptor in the mutant cells resulted from altered oligosaccharide chain(s) linked to serine/threonine residues in the binding domain. We compared the molecular sizes and binding activity of human LDL receptors in several clones derived from CHO and Monr-31 cells which were transfected with human LDL receptor cDNA. The human LDL receptors produced in the transfected clones of Monr-31 were also smaller in molecular size and lower in binding capacity than those produced in the transfected clones of CHO. These results suggest that both structural and functional alteration of the LDL receptor of Monr-31 is not caused by a mutation in the structural gene of the LDL receptor but by altered processing or maturation of the receptor. The correlation of the decrease in molecular size and reduced binding capacity of the LDL receptor is discussed. 相似文献
88.
89.
Transmembrane molecules for phylogenetic analyses of pathogenic protists: Leishmania-specific informative sites in hydrophilic loops of trans- endoplasmic reticulum N-acetylglucosamine-1-phosphate transferase
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A sequence database was created for the Leishmania N-acetylglucosamine-1-phosphate transferase (nagt) gene from 193 independent isolates. PCR products of this single-copy gene were analyzed for restriction fragment length polymorphism based on seven nagt sequences initially available. We subsequently sequenced 77 samples and found 19 new variants (genotypes). Alignment of all 26 nagt sequences is gap free, except for a single codon addition or deletion. Phylogenetic analyses of the sequences allow grouping the isolates into three subgenera, each consisting of recognized species complexes, i.e., subgenus Leishmania (L. amazonensis-L. mexicana, L. donovani-L. infantum, L. tropica, L. major, and L. turanica-L. gerbilli), subgenus Viannia (L. braziliensis, L. panamensis), and one unclassified (L. enriettii) species. This hierarchy of grouping is also supported by sequence analyses of selected samples for additional single-copy genes present on different chromosomes. Intraspecies divergence of nagt varies considerably with different species complexes. Interestingly, species complexes with less subspecies divergence are more widely distributed than those that are more divergent. The relevance of this to Leishmania evolutionary adaptation is discussed. Heterozygosity of subspecies variants contributes to intraspecies diversity, which is prominent in L. tropica but not in L. donovani-L. infantum. This disparity is thought to result from the genetic recombination of the respective species at different times as a rare event during their predominantly clonal evolution. Phylogenetically useful sites of nagt are restricted largely to several extended hydrophilic loops predicted from hypothetical models of Leishmania NAGT as an endoplasmic reticulum transmembrane protein. In silico analyses of nagt from fungi and other protozoa further illustrate the potential value of this and, perhaps, other similar transmembrane molecules for phylogenetic analyses of single-cell eukaryotes. 相似文献
90.
Sekine Y Yamamoto C Kakisaka M Muromoto R Kon S Ashitomi D Fujita N Yoshimura A Oritani K Matsuda T 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(12):6194-6204
We found that an adaptor protein, signal-transducing adaptor protein (STAP)-2, is a new member of the Fas-death-inducing signaling complex and participates in activation-induced cell death in T cells. STAP-2 enhanced Fas-mediated apoptosis and caspase-8 aggregation and activation in Jurkat T cells. Importantly, STAP-2 directly interacted with caspase-8 and Fas, resulting in enhanced interactions between caspase-8 and FADD in the Fas-death-inducing signaling complex. Moreover, STAP-2 protein has a consensus caspase-8 cleavage sequence, VEAD, in its C-terminal domain, and processing of STAP-2 by caspase-8 was crucial for Fas-induced apoptosis. Physiologic roles of STAP-2 were confirmed by observations that STAP-2-deficient mice displayed impaired activation-induced cell death and superantigen-induced T cell depletion. Therefore, STAP-2 is a novel participant in the regulation of T cell apoptosis after stimulation. 相似文献