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C Nishimura

Publications and source records attributed to C Nishimura.

At least 73 records · Page 4Linked to original sources
PubMed1990

Proton nuclear magnetic resonance study of human interleukin 6: chemical modifications and partial spectral assignments for the aromatic residues.

Partial assignments for the 1H-NMR resonances of the aromatic residues in human interleukin 6 (IL-6) are reported. The homonuclear Hartmann-Hahn spectrum clearly shows all connectivities for the histidine, tyrosine and tryptophan residues that exist in IL-6. Using a deuterium exchange method, the imidazole proton resonances of His-16 and His-165 have been assigned. Iodination of the tyrosine residues led to the assignment of Tyr-32. Photo-chemically induced dynamic nuclear polarization data have shown that His-16, Tyr-32 and Trp-158 are exposed to solvent, whereas His-165, Tyr-98 and Tyr-101 are buried. Iodination of Tyr-32 gave no significant effect on IL-6 activity, suggesting that Tyr-32 is not responsible for IL-6 activity.

Binding, Competitive↗
PubMed1990

Cloning and expression of human aldose reductase.

The complete amino acid sequence of human retina and muscle aldose reductase was determined by nucleotide analysis of cDNA clones isolated using synthetic oligonucleotide probes based on partial amino acid sequences of purified human psoas muscle aldose reductase. The cDNA sequence differs substantially in the noncoding and coding regions of recently published sequences of this enzyme. The mRNA for aldose reductase was abundantly expressed in HeLa cells, but only scarcely in a neuroblastoma cell line. Recombinant baculovirus containing one of the muscle cDNA clones was constructed and used to infect Spodoptera frugiperda (SF9) cells. A prominent protein with an apparent molecular size of 36 kDa was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the culture medium as well as in the homogenate of SF9 cells after 2 days of infection. Culture medium or the supernatant fraction of cell homogenates containing this protein had high aldose reductase activity which showed characteristics of the reported human enzyme. These findings indicate that the amino acid sequence reported in this paper represents human retina and muscle aldose reductase and that functional human aldose reductase can be expressed in large amounts in a baculovirus expression system. The result should facilitate refined structural analysis and the development of new specific aldose reductase inhibitors for the treatment of diabetic complications.

Aldehyde Reductase↗
PubMed1990

Characteristic changes between core and peripheral surface temperature related with postanesthetic shivering following surgical operations.

The relationship between changes in the core and the surface temperature and postanesthetic shivering was studied in 100 patients who underwent general anesthesia. Patients were classified into four groups by the patterns of change in the core and peripheral surface temperature. Type II and type IV groups of patients showed a decrease in surface temperature during the major operation such as gastrectomy and radical mastectomy. Type I and type III groups of patients showed no lowered peripheral surface temperature and with low temperature difference between core and surface temperature during the operation. The patients in type II and IV groups showed increased difference between core and surface temperature. The postanesthetic shivering occurred at significantly higher rate compared to the other two groups. As possible reasons of the shivering, operation of long duration and insufficient circulating blood volume were considered. Shivering reduces the temperature difference in the thermoregulatory homeostasis. However, in patients in type I and III, the rate of shivering was low. Evaluation of the difference between core and peripheral surface temperature may be important to manage body temperature at a steady level during the operation. The monitoring of body temperature difference between core and peripheral surface during the operation may be useful for predicting to occurrence of postanesthetic shivering.

Journal Article↗
PubMed1990

Induction of aldose reductase expression in rat kidney mesangial cells and Chinese hamster ovary cells under hypertonic conditions.

Rat kidney cortex mesangial cells (MES) and Chinese hamster ovary cells (CHO) responded to hypertonicity (600 mosmol/kg) in culture by accumulating sorbitol. The accumulation of sorbitol was due to increased aldose reductase (AR) activity, apparently brought about by increased levels of AR mRNA and protein. The levels of AR mRNA increased approximately 60-fold in MES cells and 30-fold in CHO cells by 24 h in culture media (300 mosmol/kg supplemented with 150 mM NaCl, 600 mosmol/kg total). AR activity also markedly increased (14- to 16-fold above control), but MES took 4 days and CHO 6 days to reach this maximum. Other osmolytes, raffinose and sorbitol (at concentrations of 250 to 300 mM) elicited the same response as that of 150 mM NaCl. These data show that AR expression is induced in MES and CHO cells under hypertonic conditions. Of special interest is the induction of large amounts of AR in rat kidney cortex mesangial cells, a target tissue of diabetes and a site where excessive accumulation of sorbitol is suspected to be a critical factor in diabetic nephropathy.

Aldehyde Reductase↗
PubMed1990

Effect of acyl substituents of synthetic lipid A-subunit analogues on their immunomodulating antiviral activity.

A chemically synthesized lipid A-subunit analogue, GLA-60, 2-deoxy-4-O-phosphono-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)- 3- tetradecanoyloxytetradecanoyl]-D-glucose, has many of the activities of endotoxin but has little toxicity. Then, compounds with various lengths of acyl side chain of the acyloxyacyl group at the 3-O position of GLA-60 were synthesized and evaluated for interferon (IFN)-inducing activity, natural killer (NK) cell activation and antiviral activity. The compounds with acyl side chains between C8 and C15 exhibited significant antiviral activity (inhibition of pox tail lesion formation in vaccinia virus-infected mice), serum IFN-inducing activity and NK cell activation. However, the compound carrying a C2 or a C16 acyl side chain did not exhibit these activities. The compounds with a C13 or C14 acyl side chain showed strong protective against herpes simplex virus type 1 in cyclophosphamide-immunosuppressed mice.

Acylation↗
PubMed1990

Enhancement of nonspecific resistance to microbial infections of synthetic lipid A-subunit analogues of GLA-27 modified at the C1 position of the glucosamine backbone.

The C1 position of lipid A-subunit analogue GLA-27, 4-O-phosphono-D-glucosamine carrying N-3-tetradecanoyloxytetradecanoyl(C14-O-(C14)) and 3-O-tetradecanoyl (C14) groups, was S-acetylated, thiolated or phosphorylated. Enhancement of nonspecific resistance to Pseudomonas aeruginosa and vaccinia virus infections of these chemically modified compounds were investigated. Thiolation augmented the nonspecific resistance to P. aeruginosa infection. Protective activity against vaccinia virus infection was reduced by all the chemical modifications. NK cell activity was found not to be effected by S-acetylation, but to be decreased slightly by thiolation or phosphorylation. IFN-inducing activity was reduced remarkably by thiolation or S-acetylation, or completely diminished by phosphorylation, compared with that of GLA-27.

Animals↗
PubMed1990

[Protective activities of a Chinese medicine, hochu-ekki-to, to impairment of hematopoietic organs and to microbial infection].

Effect of Hochu-ekki-to (HET) on the number of peripheral leukocytes (PL) and their functions in cyclophosphamide (CY)-treated or gamma ray-irradiated mice was investigated. By treatment of mice with anticancer agent CY or gamma ray irradiation, unfavorable side effects usually occurred to impair hematopoietic organs, causing bone marrow disorder. However, it was significantly protected by oral administration of HET (1 g/kg/d) to CY-treated or gamma ray-irradiated mice. The numbers of neutrophils and monocytes in PL were restored to the normal level, and colony-stimulating factor (CSF) was induced in the sera of mice by HET in a dose-dependent manner. The induction of serum CSF reached a peak at 3h after HET administration. Colony-forming unit of bone marrow cells in the spleen adoptively transferred into syngeneic mice, that is defined as CFU-S, was extremely reduced by CY-treatment. However, when HET was orally administered, CFU-S of CY-treated mice was markedly stimulated, suggesting that bone marrow cells were reactivated for further proliferation and mobilization. HET enhanced other leukocyte functions in CY-treated mice; i.e., superoxide production of neutrophils and phagocytic activity of macrophages. Thus, oral administration of HET to CY-treated mice enforced protection against Pseudomonas aeruginosa infection.

Administration, Oral↗
PubMed1990

Non-specific protective activity of synthetic lipid A-subunit analogs against microbial infections is influenced by their 2-N- and 3-O-linked acyl substituents in the D-glucosamine backbone.

Non-specific protective activities against vaccinia virus (VV) and Pseudomonas aeruginosa infections as well as interferon (IFN)-inducing, natural killer (NK) cell and macrophage activation activities of chemically synthesized lipid A-subunit analogs were investigated. The analogs are 4-O-phosphono-D-glucosamine derivatives carrying different 2-N- and 3-O-linked acyl substituents such as (R)-3-tetradecanoyloxytetradecanoyl (C14-O-(C14)), (R)-3-hydroxytetradecanoyl (C14-OH) and tetradecanoyl (C14) groups. Compounds GLA-59 and GLA-60, which possess C14-OH and C14-O-(C14) groups as their acyl substituents, showed stronger IFN-inducing and anti-vaccinia virus activities than GLA-27 and GLA-68, which possess a C14 group instead of the C14-OH group in GLA-59 and GLA-60, although NK cell activation activity was similarly high in all of these compounds. In protective activity against P. aeruginosa infection and macrophage activation activity, GLA-60 and GLA-68, which carry a C14-O-(C14) group at the 3-O-position, expressed higher activities than GLA-27 and GLA-59, which carry the acyloxyacyl group at the 2-N-position. These results indicate that the acyl substituent (whether the counterpart of the C14-O-(C14) group is a C14 or a C14-OH group) and the binding position of the acyloxyacyl group at the 2-N- or the 3-O-position strongly influence the manifestation of antimicrobial and immunomodulating activities in different ways depending on the activity. Among the compounds, GLA-60 satisfied the structure requirements for protection against both VV and P. aeruginosa infections. This compound is a hopeful immunomodulator for prevention against broad microbial infections.

Adjuvants, Immunologic↗
PubMed1990

Restoration of hematopoietic activity by lipid A analogue GLA-60 in cyclophosphamide-treated immunosuppressed mice.

Administration of GLA-60, a synthetic lipid A-subunit analogue, significantly increased the numbers of macrophages, lymphocytes and polymorphonuclear leukocytes (PMN) in the peritoneal cavity of cyclophosphamide (CY)-treated immunosuppressed mice. Colony-stimulating factors (CSFs) were induced by GLA-60 in sera of both normal and CY-treated mice in a dose-dependent manner. The CSFs induced in mouse sera stimulated growth of bone marrow stem cells (BMC) which derived from either CY-treated or untreated mice in CSF assay. Three different colonies were formed in CSF assay consisting of granulocytes (G), macrophages (M) and mixed population. Addition of serum CSFs as well as exogenous addition of interleukin 3 (IL-3) or G-CSF to BMC taken from mice 1 day after CY-treatment induced high activity to stimulate the proliferation of those cells. Production of interleukin 1 (IL-1) was also stimulated in sera of CY-treated and untreated mice by administration of GLA-60. These results indicate that restoration of hematopoietic activity by GLA-60 in CY-immunosuppressed mice is due to induction of CSFs and IL-1, which synergistically act on proliferation and differentiation of pluripotential stem cells in bone marrow.

Animals↗
PubMed1989

Bleomycin hydrolase is a unique thiol aminopeptidase.

Bleomycin hydrolase, which hydrolyzes the carboxamide bond in the pyrimidoblamic acid moiety of the bleomycin molecule, also cleaved several p-nitroanilide substrates with a neutral or basic amino acid residue and dipeptide substrates such as L-leucyl-glycine. The activity of bleomycin hydrolase was inhibited by two thiol protease inhibitors, E-64 and leupeptin, as well as by N-ethylmaleimide. These results suggest that bleomycin hydrolase is a thiol aminopeptidase. Magnesium ion, sodium chloride, ethylenediaminetetraacetic acid and 1,2-dihydroxybenzene-3,5-disulfonic acid specifically activated the enzymatic hydrolysis of L-arginine-p-nitroanilide, but did not that of L-leucine-p-nitroanilide. Lineweaver-Burk plots showed that Km values of the enzymatic activity for L-arginine-p-nitroanilide were altered by these reagents, although Vmax values were almost unaltered.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1989

Intracellular degradation of bleomycin hydrolase in two Chinese hamster cell lines in relation to their peplomycin susceptibility.

The Chinese hamster lung (V79) cell was intrinsically 10-times more resistant to peplomycin, a bleomycin-related antitumor antibiotic, than the Chinese hamster ovary (CHO) cell. This may be associated with the 3-times higher levels of recovery of bleomycin hydrolase activity of the V79 cell. The degradation of bleomycin hydrolase molecules in both V79 and CHO cells was examined using a monoclonal antibody specific for the enzyme. Labelling experiments showed that the bleomycin hydrolase in CHO cells was less stable than the comparable enzyme in V79 cells, and that 48 kDa subunits comprising bleomycin hydrolase (a homohexameric enzyme) molecules were degraded into 31 kDa forms in both cell lines. The 105,000 X g pellet (microsomes) fraction obtained after subcellular fractionation of CHO cells contained both 48 kDa subunit and 31 kDa forms of bleomycin hydrolase, while the 105,000 X g supernatant cytosol fraction yielded only 48 kDa subunit forms of the enzyme. Moreover, bleomycin hydrolase activity of both V79 and CHO cells was almost entirely recovered from the cytosol fraction. These results suggest that degradation of the 48 kDa subunit form of bleomycin hydrolase in these two lines of cultured cells into the 31 kDa form occurs on the plasma membrane or the endoplasmic reticulum, with which the resulting large number of bleomycin hydrolase molecules or degraded forms of the enzyme that have lost enzymatic activity are associated.

Animals↗
PubMed1989

Polyol and vacuole formation in cultured canine lens epithelial cells.

Polyol accumulation and myo-inositol depletion were accompanied by extensive vacuole formation in cultured canine lens epithelial cells that were incubated for up to 96 hr in growth medium supplemented with 30 mM D-galactose or 30 mM D-glucose. These changes did not occur in cells incubated in a hypergalactosemic or hyperglycemic medium which also contained an aldose reductase inhibitor (20 microM sorbinil). In addition, these changes were not observed in lens cells incubated in growth medium supplemented with either 30 mM mannitol, which is known to enter cells only slowly, or in 30 mM L-galactose, which is not a substrate for aldose reductase. The vacuoles were visible at the ultrastructural level after 6 hr of incubation in 30 mM D-galactose and increased in both number and size with time. These vacuoles had a unique fine structure. They did not result from swelling of mitochondria or other cell organelles. As demonstrated cytochemically, they did not represent either lysosomes or Golgi saccules. The proliferation pattern of cells incubated with 30 mM D-galactose was clearly different from that of control cells, but approached normal when an aldose reductase inhibitor was added to the incubation medium. Together these findings suggest that vacuole formation and altered cell proliferation were caused by polyol accumulation and/or myo-inositol loss, both of which result from aldose reductase activity.

Aldehyde Reductase↗
PubMed1989

Aldose reductase and polyol in cultured pericytes of human retinal capillaries.

Aldose reductase has been found in several tissues involved in the various complications of long-term diabetes. Since the loss of intramural pericytes is typical of early microangiopathy of the diabetic retina, the presence of aldose reductase and its activity were investigated in pericytes cultured from capillaries of human retinas. Verification that contaminating cells had been removed was made on the basis of the pericytes' distinctive appearance in culture, inability to internalize acetylated-low-density lipoprotein, and immunoreactivity for muscle actin. Using pure cultures of human pericytes, the presence of aldose reductase was demonstrated immunohistochemically with antibodies directed against human placental aldose reductase, and aldose reductase activity was shown biochemically by monitoring the accumulating of xylitol in cells incubated with xylose. Xylitol accumulation was inhibited by the inclusion of an aldose reductase inhibitor in the xylose-containing medium.

Adult↗
PubMed1989

A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes.

Aldose reductase (AR) is implicated in some of the disabling complications of diabetes, including neuropathy, retinopathy and cataracts. Our studies are aimed at further clarifying the role of AR in diabetes and facilitating the design of new classes of potent, specific AR inhibitors by gaining an understanding of the protein structure of AR. To this end, we have determined the complete protein sequence of rat lens AR using cDNA analysis and primer extension of mRNA. By comparing protein sequences, we have found that the structural relatedness (41% to 57%) among the vertebrate proteins, aldose reductase, aldehyde reductase, prostaglandin F synthase and the frog lens protein rho-crystallin can now be extended to prokaryotes by the inclusion of Corynebacterium 2,5-diketo-D-gluconate reductase. This more distantly related protein shares 30-40% identity with the vertebrate enzymes. Sequence alignments reveal that 18% of the amino acids are completely conserved in all members of the superfamily, many of them in clusters, suggesting that they mark important structural features such as the nucleotide binding site and substrate binding site. rho-Crystallin, which is structurally related to this superfamily of NADPH-dependent reductases, does not appear to reduce PGH2, PGD2, xylose or glyceraldehyde to any appreciable extent. It does, however, bind NADPH.

Aldehyde Oxidoreductases↗
PubMed1989

Activation of murine peritoneal macrophages by saikosaponin a, saikosaponin d and saikogenin d.

Macrophage activation by saikosaponins and saikogenins was investigated and compared with that by other saponins and macrophage stimulants. Saikosaponins a and d induced a marked cell accumulation in the peritoneal cavity when administered intraperitoneally. Among saikosaponins and saikogenins tested, saikosaponin d significantly activated peritoneal macrophages in terms of enhancement of phagocytic activity, increased level of cellular lysosomal enzyme (acid phosphatase), induction of cytostatic activity and expression of Ia antigen on the cell surface. The activities of saikosaponin d were much stronger than those of typical saponins ginsenoside Rg1 and glycyrrhizin and almost comparable with or somewhat weaker than those of lipopolysaccharide, a streptococcal preparation OK-432 and formalin-killed Propionibacterium acnes, indicating that saikosaponin d is a potent macrophage activator.

Animals↗
PubMed1989

Localization of aldose and aldehyde reductase in the kidney.

The distribution of NADPH-dependent reductase activity in the rat cortex, outer medulla and inner medulla was investigated through biochemical and histochemical methods. Biochemical studies revealed reductase activity to be present in all three regions of the kidney with the highest specific activity observed in the inner medulla, followed by the cortex and the outer medulla. Activity in all three regions was inhibited by the aldose reductase inhibitors sorbinil, tolrestat and 7-hydroxychromone-2-carboxylic acid. Based on substrate utilization and response to sulfate on the inhibitors, the inner medulla contains primarily aldose reductase (EC 1.1.1.21) while the cortex contains primarily aldehyde reductase (EC 1.1.1.2). The outer medulla contains a mixture of both enzymes. This distribution was confirmed by a radioimmunoassay for aldose reductase. Immunohistochemical investigations of the rat kidney with antibodies against rat lens aldose reductase and rat kidney aldehyde reductase revealed a similar distribution of these enzymes. Aldehyde reductase was immunohistochemically detected only in the cortex where it was localized in the proximal convoluted tubules. Immunoreactive aldose reductase was detected in Henle's loop at both the inner stripe of the outer medulla and in the inner medulla, and in the collecting tubules and the epithelial cell lining the pelvis of the inner medulla near the papilla. No specific immunohistochemical staining for aldose reductase was observed in the cortex. A similar immunohistochemical distribution of aldose reductase was also observed in the human kidney with antibodies against human placental aldose reductase.

Alcohol Dehydrogenase↗
PubMed1989

Inhibition of intracellular bleomycin hydrolase activity by E-64 leads to the potentiation of the cytotoxicity of peplomycin against Chinese hamster lung cells.

N-(N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl)-agmatine (E-64), a thiol protease inhibitor, potentiated the cytotoxicity of peplomycin against the Chinese hamster lung (V79) cell. After the treatment of the cells with E-64 (50 micrograms/ml) for 12 h, bleomycin hydrolase activity of the cells was almost completely inhibited. V79 cells treated with [3H]peplomycin for 24 h in the presence of E-64 (50 micrograms/ml) accumulated twice as much [3H]peplomycin and five times less [3H]desamidopeplomycin compared with V79 cells treated in the absence of E-64. These results suggest that E-64 increases the sensitivity of V79 cells to peplomycin probably by inhibiting the intracellular bleomycin hydrolase activity.

Animals↗