PubMed Health⌕ Search

Biomedical subjects

C Nishimura

Publications and source records attributed to C Nishimura.

At least 109 records · Page 6Linked to original sources
PubMed1987

Purification of bleomycin hydrolase with a monoclonal antibody and its characterization.

We established a hybridoma clone that produced anti-bleomycin hydrolase antibody. The subclass of the monoclonal antibody was immunoglobulin M. The antibody significantly reacted with bleomycin hydrolase from rabbit tissues, mouse livers, sarcoma 180, and adenocarcinoma 755 but not significantly with that from MH 134 and Ehrlich carcinoma. The enzyme from L5178Y cells showed an intermediate reactivity. Bleomycin hydrolase was purified from rabbit liver by immunoaffinity with the monoclonal antibody and DEAE gel chromatography. Approximately 1300-fold-purified bleomycin hydrolase was obtained. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing on a polyacrylamide slab gel of purified bleomycin hydrolase showed a single band with an apparent Mr of 48K and an isoelectric pH of 5.2. The molecular weight of bleomycin hydrolase determined on gel filtration high-performance liquid chromatography was ca. 300K, suggesting a hexameric enzyme. The enzyme showed an optimum pH of 6.8-7.8 and gave a Vmax value of 6.72 mg min-1 mg-1 for peplomycin and 9.24 mg min-1 mg-1 for bleomycin B2 and a Km value of 0.79 mM for both substrates. The enzyme was inhibited by E-64, leupeptin, p-tosyl-L-lysine chloromethyl ketone, N-ethylmaleimide, Fe2+, Cu2+, and Zn2+ but was enhanced by dithiothreitol. The results suggest that bleomycin hydrolase is a thiol enzyme.

Animals↗
PubMed1987

Effect of stereospecificity of chemically synthesized lipid A-subunit analogues GLA-27 and GLA-40 on the expression of immunopharmacological activities.

Tumor necrosis factor (TNF)-inducing, mitogenic, polyclonal B cell activation (PBA), macrophage activation and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-40, were investigated. The structure of GLA-27 comprises 4-O-phosphono-D-glucosamine carrying tetradecanoyl and 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups as the 3-O- and 2-N-acyl substituents, respectively. GLA-40 is a 1-deoxy compound of GLA-27. The activities of stereoisomers, (R) and (S) forms at the C3 position of the C14-O-(C14) group, of both compounds were also investigated. TNF-inducing activity of the (S) isomers of GLA-27 and GLA-40 was stronger than that of the (R) isomers while the (R) isomers exhibited stronger mitogenic and PBA activities than the (S) isomers. With respect to macrophage activation such as phagocytosis, acid phosphatase and N-acetyl-beta-D-glucosaminidase activity as cellular lysosomal enzymes and cytostasis, peritoneal macrophages obtained from mice administered i.p. with test samples showed significant activities. Among stereoisomers of GLA-27, the (R) isomer exhibited somewhat stronger phagocytic and lysosomal enzyme activities than those of the (S) isomer while there was no appreciable difference in the activities between the isomers of GLA-40. Significant cytostasis-inducing activity was observed in stereoisomers tested. All of the isomers showed remarkable antiviral activity against vaccinia virus.

Animals↗
PubMed1987

Antiviral activity and inhibition of topoisomerase by ofloxacin, a new quinolone derivative.

The antiviral activity of ofloxacin, a new quinolone derivative, against vaccinia virus (VV), herpes simplex virus (HSV) and influenza virus (InfV) was evaluated in both in vitro and in vivo experiments. As a result, ofloxacin showed inhibitory activity against VV in cultured mammalian cells, and prevented formation of pox tail lesions in VV-infected mice. However, it was less effective against HSV and InfV than VV. The antiviral activity of ofloxacin assessed by VV tail-lesion test was strongest when administered to mice through the oral route daily for five consecutive days post-infection. Nalidixic acid and novobiocin, well-known gyrase inhibitors, showed only weak antiviral activity in both in vitro and in vivo tests against VV. It was also demonstrated that ofloxacin inhibited virus-specific DNA and RNA syntheses. It was more inhibitory to VV topoisomerase than cellular topoisomerases. Thus, ofloxacin has selectivity for VV.

Animals↗
PubMed1987

Depletion of myo-inositol and amino acids in galactosemic neuropathy.

A depletion of not only myo-inositol (MI) but also taurine and other amino acids was observed in the sciatic nerve of a galactosemic rat. Treatment of the galactosemic rats with sorbinil, an aldose reductase (AR) inhibitor, was found to block galactitol formation and protect against the loss of MI, taurine, and other amino acids. Incubation studies of sciatic nerve have revealed that [3H]MI and [3H]taurine were actively taken up and concentrated. Incubation of the nerve in a high-galactose medium showed a decrease in the accumulation of [3H]MI and [3H]taurine whereas the galactitol level increased. Time-course studies have shown that the galactitol level reached a plateau before a substantial decrease in the accumulation of [3H]MI and [3H]taurine occurred. The addition of AR inhibitors in the galactose medium significantly protected against the loss in the capacity of the nerve to accumulate [3H]MI and [3H]taurine. Hypertonicity of the galactose medium also seemed to have a protective effect similar to that of AR inhibitors.

Amino Acids↗
PubMed1986

Evaluation of liver weight changes following repeated administration of carbon tetrachloride in rats and body-liver weight relationship.

The proper method of evaluating liver weight changes resulting from the primary toxic effect of a chemical was studied. We used a pair-feeding method with carbon tetrachloride (CCl4), a chemical known to cause an increase in liver weight. Male rats were assigned to an untreated control group, CCl4-treated groups (daily dose of 10 microliter or 50 microliter of CCl4 in olive oil/100 g body wt), olive oil-treated plus feed-restricted groups, and feed-restricted groups. In the 2 types of feed-restricted groups the body weight changes of the CCl4-treated groups were duplicated by imposing restrictions on feeding. Absolute and relative liver weights were compared among the 4 types of groups after treatment for 14 or 25 days. Either absolute or relative liver weight of the treated group when compared to that of the feed-restricted group was the most reliable and sensitive toxicity indicator. In comparing the treated group with the untreated control group, relative liver weight was a more sensitive toxicity indicator than absolute liver weight. However, when liver weight data for about 200 normal male rats were plotted against body weight, and the 95% confidence limits of the regression line (y = ax) were estimated, most of the data for the feed-restricted rats were outside the lower confidence limit. This means that a comparison of the relative liver weights of the treated rats and untreated control rats is not strictly valid, because the body weight-liver weight relationships are not the same in the 2 groups.

Administration, Oral↗
PubMed1985

Immunopotentiator separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi).

The separation and properties of a new immuno-potentiator, Benincasa cerifera mitogen (BCM) fraction, were investigated. BCM fraction was separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi) by gel filtration using Sepharose 4B. BCM fraction is a heteropolymer consisting of uronic acid, neutral sugars, protein, and phosphorus. The proliferation and differentiation of murine B cells were markedly stimulated by BCM fraction. The in vitro development of peritoneal macrophages into antitumor macrophages was also activated by the addition of BCM fraction to cultures. BCM fraction augmented the IgM and IgG antibody responses against sheep erythrocytes (SRBC) and the induction of delayed-type footpad reaction against SRBC. The antitumor activity of BCM fraction was observed in terms of prolongation of the survival period of mice bearing Meth A fibrosarcoma. After hydrolysis with 1% acetic acid at 100 degrees C for 4 h, marked mitogenic activity was found in a precipitate composed of 29% neutral sugars, 50% uronic acid, 1% protein, and 0.1% phosphorus. The precipitate did not contain detectable amino sugar. The possibility that the biological activities of BCM fraction may be due to contamination by bacterial lipopolysaccharide was ruled out on the basis of the results of chemical analysis and of marked mitogenicity noted in C3H/HeJ spleen cell cultures.

Acetates↗
PubMed1985

Enhancement by muramyldipeptides of the activities of early-type inducers of interferon.

A synthetic muramyldipeptide (MDP) and two analogues, B30-MDP and MDP-Lys(L18), augmented serum interferon (IFN) production in mice by the inducers lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly I:C), and also augmented immune IFN production induced by purified protein derivative (PPD) in mycobacteria-sensitized mice. These compounds were most effective when administered to mice one day before the interferon inducer. By contrast, IFN production in mice by either oral tilorone or virus infection was not enhanced with these compounds. Since LPS and poly I:C are well known as early-type IFN inducers, and tilorone and virus infection are late-type inducers, we presume that MDP and its analogues are able to augment only early-type IFN production. This enhancing effect may be mediated by macrophage activation. In vivo antiviral activity of MDP and its analogues was further tested in mice infected with vaccinia virus (VV) using early-type inducers. When mice previously treated with MDP or its analogues were stimulated for IFN production with a low dose of LPS, protective activity against VV infection was markedly enhanced.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Enhancement of non-specific resistance to viral infection by muramyldipeptide and its analogs.

Antiviral activity of muramyldipeptide (MDP) and its lipophilic derivatives, B30-MDP and MDP-Lys(L18), was investigated in mice infected with vaccinia virus (VV) and herpes simplex virus type 2 (HSV-2). Mice administered these compounds subcutaneously or orally were protected against VV in tail lesion tests and against HSV-2 in skin lesion tests, respectively. Since in vitro antiviral activity was not demonstrated with these compounds in cultured mammalian cells infected with either VV or HSV-2, host-mediated defense mechanisms may play a role in the activity of the compounds. As for serum interferon (IFN) induction, MDP and its analogs showed no activity in mice, suggesting that IFN does not participate in the antiviral mechanisms against VV and HSV-2. An extrinsic antiviral activity was demonstrated when peritoneal macrophages from the mice administered these compounds were cocultivated with VV-infected 3T3 cells. The results indicate that macrophage activation by MDP and its analogs plays a role in the defense mechanisms against viral infection. This activity was not virus-specific. We also demonstrate that the introduction of lipophilic residue(s) into MDP enhances the antiviral activity of mice against VV and HSV-2.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Alterations in the retinal dopaminergic neuronal system in rats with streptozotocin-induced diabetes.

Neurochemical alterations, which may be associated with the development of diabetic retinal dysfunction, were investigated using streptozotocin (STZ)-induced hyperglycemia in rats. Young male Wistar rats, weighing 100-150 g, were made diabetic with daily intraperitoneal injections of STZ (30 mg/kg) for 5 days. This treatment caused a continuous hyperglycemia (400-600 mg/dl) and suppressed gain in body weight. Nine weeks after the STZ treatment, a significant increment in retinal valine and a decline in phenylalanine were noted, while the concentrations of other neuroactive amino acids, such as gamma-aminobutyric acid and aspartic acid, in the retina remained unchanged. On the other hand, the concentration of retinal dopamine (DA) was found to decrease significantly from the third week of hyperglycemia, when [3H]spiperone binding showed a tendency to increase in the retinal particulate fraction. However, the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase (AADC) and the uptake of [3H]tyrosine showed no alteration in the retina of diabetic rats. The accumulation rate of 3,4-dihydroxyphenylalanine (DOPA) in vivo in the retina of diabetic rats, measured following the administration of the AADC inhibitor m-hydroxybenzyl-hydrazine (100 mg/kg i.p.), was also unchanged. Although [3H]DA uptake by retinal tissue was similar in control and diabetic animals, the spontaneous efflux of [3H]DA from the retina was found to be significantly accelerated in STZ-treated animals. In addition, the release of preloaded [3H]DA, elicited by repeated photic stimulation, was significantly attenuated in retina from diabetic rats. These results suggest that an accelerated efflux of DA, possibly leading to the depletion of DA from the retinal DA system, may account for early retinal dysfunctions known to occur in diabetic subjects.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Lymphocyte activation by a polysaccharide fraction separated from hot water extracts of Angelica acutiloba Kitagawa.

The action of a polysaccharide fraction obtained from hot water extracts of Angelica acutiloba Kitagawa, termed as Angelica immunostimulating polysaccharide (AIP) fraction, on murine lymphocytes participating in antibody responses was investigated. When AIP fraction was injected concomitantly into mice immunized with antigens, immunoglobulin M (IgM) and IgG antibody responses against sheep erythrocytes (SRBC) increased significantly, but IgM response against T-independent antigens such as trinitrophenylated lipopolysaccharide (TNP-LPS) and TNP-Ficoll did not augment. Murine B lymphocytes were polyclonally activated in vitro and in vivo by AIP fraction to differentiate into antibody-forming cells as functionally matured cells. The differentiation of B lymphocytes to an intermediate stage capable of responding to helper T lymphocytes was also stimulated by the administration of AIP fraction into CDF1 and C3H/HeJ mice. A concomitant injection of AIP fraction with SRBC for carrier priming resulted in the increment of anti-TNP IgM antibody response in cultured reconstituted with unprimed B and SRBC-primed T lymphocytes, indicating that AIP fraction can stimulate T lymphocytes.

Animals↗
PubMed1985

Alteration of lipid peroxide and endogenous antioxidant contents in retina of streptozotocin-induced diabetic rats: effect of vitamin A administration.

Possible involvement of lipid peroxide (LPO) in the occurrence of diabetic retinal lesion was investigated using streptozotocin-induced diabetic rats. Young male Wistar rats weighing 100-150 g were made diabetic by daily intraperitoneal injection of 30 mg/kg streptozotocin (STZ) for 5 days. Five weeks after the termination of STZ-treatment, when animals maintained typical hyperglycemia, the tissue level of LPO, estimated by the thiobarbituric acid method in the presence of 0.5 mM EDTA, was found to be augmented in the kidney. At 7 to 9 weeks after the STZ-treatment, the content of LPO in the retina also exhibited a significant increase, while those in the serum, brain and peripheral nerves showed no alteration. This increment of LPO in the kidney and retina was accompanied by the concomitant reduction of fat-soluble antioxidants determined by the ferric chloride-bipyridyl reaction, and insulin treatment (10 u/rat/day, s.c.) completely eliminated the increased formation of LPO in these organs. When diabetic rats were treated with retinol acetate, which had an inhibitory effect on LPO formation in retinal homogenate, the increase in LPO content was found to be significantly suppressed, especially in the retina. These results suggest that the STZ-induced diabetic state may elicit an increased formation of LPO in the retina and kidney, both of which are known to be main organs having typical diabetic lesions.

Animals↗
PubMed1984

Mitogenic and polyclonal B cell activation activities of synthetic lipid A analogues.

The activation of murine B cells and macrophages by synthetic lipid A analogues, solubilized with triethylamine and complexed with bovine serum albumin, were investigated in vitro. The analogues used are nonphosphorylated, C-1 or C-4' monophosphorylated and C-1,4' diphosphorylated derivatives of beta-1,6-linked D-glucosamine disaccharide possessing both ester- and amide-bound fatty acid substituents. They were divided into 4 groups, A, B, C and D in terms of the fatty acid substitution. Ester- and amine-bound fatty acids of the analogues are both tetradecanoic acids (C14) in group A, C14 and (R)-3-hydroxytetradecanoic acids (C14-OH) in group B, both C14-OH in group C and C14-OH and (R)-3-tetradecanoyloxytetradecanoic acids in group D. Mitogenic activity was exhibited in spleen cells from C3H/HeN mice by the C-1 monophosphorylated analogues in groups A and B, and by the C-4' monophosphorylated analogues in groups B, C and D, but not in cells from C3H/HeJ mice. Nonphosphorylated analogues in groups A, B and C, and C-4' monophosphorylated analogue in group A showed negative mitogenic activity. Only the nonphosphorylated analogue in group D exhibited mitogenic activity in spleen cells from C3H/HeJ mice as well as those from C3H/HeN mice. None of the other analogues exhibited the activity in C3H/HeJ spleen cells. Polyclonal B cell activation activity was exhibited by the C-1 monophosphorylated analogues in groups A and B, and by the C-4' monophosphorylated analogues in groups C and D. Nonphosphorylated analogues in all groups and C-4' monophosphorylated analogues in groups A and B showed negative PBA activity. None of the analogues tested could induce any cytostatic macrophages from thioglycollate-elicited peritoneal macrophages.

Animals↗
PubMed1984

Activation of peritoneal macrophages by berberine-type alkaloids in terms of induction of cytostatic activity.

The antitumour alkaloids, berberine and coralyne were investigated in terms of their ability to induce chemiluminescent responses and cytostatic activity in macrophages against tumour cells in vitro. Berberine hydrochloride and sulfate, and coralyne chloride, which had no direct tumoristatic activities at a concentration of less than 0.15 micrograms/ml, activated macrophages to inhibit the incorporation of tritiated thymidine into EL4 leukemic cells. The activation of cytostatic macrophages by berberine was not augmented by the addition of a suboptimal dose of macrophage activating factor (MAF). Furthermore, a marked chemiluminescent response of macrophages was induced by treatment with berberine as well as with MAF or lipopolysaccharide. These results show that berberine and coralyne are potent macrophage activators for inducing cytostatic activity against tumour cells in vitro.

Animals↗