Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 433 records · Page 24Linked to original sources

PubMed1996

Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RAR alpha fusion gene.

The interaction of an exogenous PML/RAR alpha fusion gene associated with acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RAR alpha cDNA in the expression vector pGD and stable transformants (L1210PML/RAR alpha and MOLT-4PML/RAR alpha) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [3H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L121OPML/RAR alpha and MOLT-4PML/RAR alpha cells but not in control cells. The exogenous PML/RAR alpha fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.

Apoptosis↗

PubMed1996

Exposure of astrocytes to hypoxia/reoxygenation enhances expression of glucose-regulated protein 78 facilitating astrocyte release of the neuroprotective cytokine interleukin 6.

Astrocytes exposed to hypoxia (H) or hypoxia/ reoxygenation (H/R) maintain cell viability and display changes in protein biosynthesis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocytes exposed to H showed induction of an approximately 78-kDa polypeptide that demonstrated sequence identity with glucose-regulated protein (GRP) 78. Cell lysates from H/R astrocytes displayed induction of neuroprotective interleukin (IL) 6, which was present in a high-molecular-weight complex also containing GRP78, suggesting that GRP78 might be functioning as a chaperone during cellular stress consequent on H/R. Introduction of antisense oligonucleotide to GRP78 into astrocytes prevented expression of the protein and suppressed H/R-induced astrocyte release of IL-6 by approximately 50%. These data indicate that modulation of astrocyte properties during oxygen deprivation results, in part, from intracellular glucose depletion and subsequent expression of GRP78, which sustains generation of neuroprotective IL-6 under the stress of H/R.

Animals↗

PubMed1996

Induction of interleukin-6 by interferon alfa and its abrogation by a serine protease inhibitor in patients with chronic hepatitis C.

We investigated short-term alterations in plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) levels induced by interferon alfa (IFN-alpha) injection in 18 patients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN-alpha 2a (6 million units [MU]) significantly increased the plasma IL-6 level 6 hours after the injection (P < .05). On the other hand, the IFN-alpha injection did not affect the plasma TNF-alpha and IL-lbeta levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL-6 gene transcripts in peripheral blood mononuclear cells (PBMC) after IFN-alpha injection, indicating that IFN-alpha enhances IL-6 production at the messenger RNA level. The induction of IL-6 by IFN-alpha was completely suppressed by the intravenous administration of gabexate mesilate (GM), a serine protease inhibitor. The mechanism whereby GM suppresses the elevation in circulating IL-6 levels seems to be the inhibition of IL-6 production at the messenger RNA level. Elevations of both serum C-reactive protein (CRP) levels and body temperature after GM-suppressed IFN-alpha injection suggest that the administration of GM by suppressing IL-6 production, may attenuate the IL-6-related responses induced by IFN-alpha injection. In conclusion, we found that IL-6 was induced by IFN-alpha in vivo, and that this induction was completely abrogated by the administration of GM. Our results indicate that serine protease inhibitors may be useful for inhibiting IL-6-relating responses.

2',5'-Oligoadenylate Synthetase↗

PubMed1996

Biotin deficiency decreases ornithine transcarbamylase activity and mRNA in rat liver.

Biotin deficiency is well known as a cause of hyperammonemia, but there has been no report on the effect of biotin deficiency on hepatic ureagenesis. In this study, we examined the changes in the activities and gene expression of urea cycle enzymes using rats fed raw egg white as a model of biotin deficiency. All rats were made biotin-deficient by feeding them an avidin-containing diet for 6 wk. The rats were divided into two groups at the beginning of this experiment: biotin-deficient rats (BD rats) and biotin-supplemented rats (BS rats) which were treated with biotin once a day at a dose of 1 mg per rat intraperitoneally. The plasma ammonia concentration of the BD rats (92.8 +/- 12 mumol/L) was significantly higher than that of BS rats (63.9 +/- 16 mumol/L, P < 0.05). The activities of ornithine transcarbamylase (OTC) was significantly lower in the liver of the BD (110.2 +/- 5.5) rats than in the BS rats (154 +/- 3.8 U/mg protein, P < 0.01). Activities of the other urea cycle enzymes were not significantly different in the two groups. OTC gene expression in the liver of BD rats was 40% lower than in BS rats (P < 0.05). These data suggest that biotin deficiency decreases OTC activity and the amount of OTC mRNA.

Amino Acids↗

PubMed1996

Truncation of Vargula luciferase still results in retention of luminescence.

Significant amino acid sequence homology in two regions of Vargula hilgendorfii to one in apoaequorin was reported. The intra-amino acid homology in Vargula luciferase between residues 81-312 and 321-540 was 19.3%, and each of this intra-homologous region contained the region homologous to apoaequorin. In order to prove the possibility that only one of the homologous regions is sufficient for luminescence, we have produced a chimeric protein comprising of only the N-terminal homologous region of Vargula luciferase fused to protein A. Comparison of the luminescence of this truncate luciferase indicated that there was 38.5% retention in the bioluminescence of luciferase when compared to that of the mature form of luciferase. This fact may have interesting implications for further study of engineering luciferase.

Animals↗

PubMed1996

Effective renaturation of denatured and reduced immunoglobulin G in vitro without assistance of chaperone.

IgG is an oligomeric protein that consists of two heavy and two light chains. To form the oligomer, a highly concentrated protein would be required on renaturation. On the other hand, refolding of proteins at high concentration often led to aggregation. Therefore, denatured and reduced oligomeric protein scarcely refolded to the native structure. As was expected, the folding yield of the denatured and reduced IgG was below 5% under the condition employed in rapid dilution. The low folding yield was elucidated to be due to assembly or aggregation. Using a renaturation method previously developed to depress aggregation effectively by means of slow dialysis, the refolding yield of the denatured and reduced IgG at above 1 mg/ml was above 70%. Most of the refolded IgG was identical with the intact material based on analyses by affinity chromatography and SDS-PAGE.

Chromatography, Affinity↗

PubMed1996

Effect of additives on the renaturation of reduced lysozyme in the presence of 4 M urea.

Reduced lysozyme was renatured by sulfhydryl-disulfide interchange reactions at pH 8.0 in the presence of 4 M urea, with or without additives at 40 degrees C. In the absence of additives, the final folding yield of reduced lysozyme was approximately 40%. In the presence of sarcosine, glycerol, ammonium sulfate, N-acetyl glucosamine and glucose, its folding yields increased in all cases. In particular, yields increased up to 90% in the presence of 4 M sarcosine. On the other hand, the melting temperatures of lysozyme with or without additives in 0.02 M citrate buffer (pH 6.0) were evaluated using differential scanning calorimetry. In the absence of additive, the melting temperature of lysozyme was 73.8 degrees C. In the presence of additives, all melting temperatures were higher than that of lysozyme in the absence of additives. Moreover, there was a good correlation on addition of additives between an increase in the folding yield of reduced lysozyme with 4 M urea and an increase in the melting temperature without 4 M urea. Therefore, we conclude that additives, which stabilize native lysozyme, are effective at increasing the folding yield of reduced lysozyme in 4 M urea.

Acetylglucosamine↗

PubMed1996

Allergenicity of acid protease secreted by Candida albicans.

We have previously reported the cases of Candida albicans (C. alb) acid protease (CAAP)-induced atopic asthma. In this study, the allergenicity of the released enzyme CAAP was examined among asthmatic patients with positive immediate skin response to crude C. alb antigen. Among 49 patients with positive skin response to crude C. alb, anti-crude C. alb IgE antibodies were detected in 40 and anti-CAAP IgE antibodies were detected in 18. Moreover, anticrude C. alb IgE antibodies were detected in all of the patients in whom anti-CAAP IgE antibodies were detected. No correlations between IgG antibodies to both antigens or between IgE and IgG antibodies to CAAP were observed. CAAP induced significant T-cell proliferation in 20/28 patients showing positive T-cell proliferation response to crude C. alb antigen. Most of the patients showing positive conjunctival response to crude C. alb antigen also showed positive response to CAAP. Most of the patients showing high levels of serum IgE antibody and positive histamine-release response of peripheral blood leukocytes to CAAP showed positive conjunctival response. The results indicate that CAAP is an important allergen in C. alb-related mucosal allergy.

Allergens↗

PubMed1996

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome.

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2',5'-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of alpha l-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.

Brain↗

PubMed1996

Identification and mapping of functional domains on human T-cell lymphotropic virus type 1 envelope proteins by using synthetic peptides.

To identify the regions that are important in human T-cell leukemia virus type 1 (HTLV-1) envelope function, we synthesized 23 kinds of peptides covering the envelope proteins and examined the inhibitory effect of each peptide on syncytium formation induced by HTLV-1-bearing cells. Of the 23 synthetic peptides, 2, corresponding to amino acids 197 to 216 on gp46 and 400 to 429 on gp21, inhibited syncytium formation induced by HTLV-1-bearing cells but did not affect syncytium formation induced by human immunodeficiency virus type 1-producing cells. The peptide concentrations giving 50% inhibition of syncytium formation for gp46 197 to 216 and gp21 400 to 429 were 14.9 and 6.0 microM, respectively. A syncytium formation assay with overlapping synthetic peptides containing amino acids 175 to 236 and 391 to 448 of the envelope proteins showed that syncytium formation was inhibited by peptides that contained the amino acid sequences 197 to 205 (Asp-His-Ile-Leu-Glu-Pro-Ser-Ile-Pro) and 397 to 406 (Gln-Glu-Gln-Cys-Arg-Phe- Pro-Asn-Ile-Thr). These observations suggest that the two regions corresponding to amino acids 197 to 216 and 400 to 429 are involved] in HTLV-1 envelope function.

Amino Acid Sequence↗

PubMed1996

Endogenous atrial natriuretic peptide inhibits endothelin-1 secretion in dogs with severe congestive heart failure.

Atrial natriuretic peptide (ANP) has been shown to counteract the response of endothelin-1 (ET-1), but whether endogenous ANP actually inhibits the systemic release of ET-1 in vivo has not yet been determined. We administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled ANP receptor, to conscious dogs with severe congestive heart failure (CHF) produced by rapid right ventricular pacing (n = 5, for 22 days) at doses of 0.3, 1.0, and 3.0 mg/kg at 30-minutes intervals. In the present study, plasma ANP and ET-1 levels were significantly elevated in CHF(348 +/-58 and 4.54 +/- 0.60 pg/ml, respectively compared with those in control dogs (65 +/- 4, P < 0.01, 1.30 +/- 0.17 pg/ml, P < 0.001). HS inhibited plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a biological market of endogenous ANP activity, in a dose-dependent manner from 21.8 +/- 2.2 to 7.2 +/- 1.4 pmol/ml (P < 0.001), with concomitant significant increases in plasma ET-1 levels from 4.54 +/- 0.60 to 6.60 +/- 0.72 pg/ml (P < 0.05). There was a significant negative correlation between the decrease in plasma cGMP and the increment in plasma ET-1 (r = -0.64, P < 0.01). Despite these responses, mean arterial pressure and pulmonary arterial pressure did not change significantly. Plasma angiotensin II and arginine vasopressin levels, both of which have been reported to stimulate ET-1 secretion in vitro, also showed no significant changes. These results strongly suggest that endogenous ANP directly inhibits endogenous ET-1 secretion through a cGMP-mediated pathway in chronic severe CHF.

Animals↗

PubMed1996

Histamine augments VCAM-1 expression on IL-4- and TNF-alpha-stimulated human umbilical vein endothelial cells.

Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and CD49d molecules on eosinophils is thought to mediate the selective infiltration of eosinophils into inflamed tissues in allergic disease. IL-4 and TNF-alpha are associated with allergic conditions, and they have been shown to selectively augment VCAM-1 expression on endothelial cells, suggesting that they may be responsible for VCAM-1 expression in allergic disease. We used immunocytochemical staining analysis to examine the effect of chemical mediators, including histamine, leukotrienes and platelet-activating factor (PAF), on VCAM-1 expression in IL-4- and TNF-alpha-stimulated endothelial cells. Histamine, significantly augmented (p < 0.05 to p < 0.01) VCAM-1 expression in both IL-4- and TNF-alpha-stimulated endothelial cells. IL-4 and TNF-alpha were found to have a synergistic effect on endothelial cell VCAM-1 expression, when compared with the effect of stimulation with each of these cytokines separately, and the addition of histamine further increased VCAM-1 expression. This enhancing effect of histamine was inhibited by the presence of mepyramine and thioperamide but not by cimetidine. Another chemical mediator, PAF, failed to induce any increase in VCAM-1 expression, however, leukotrienes augmented it slightly in a narrow range of concentrations. The histamine-induced augmentation of VCAM-1 expression was reflected functionally by many more eosinophils attaching to endothelial cells than to cells stimulated with both cytokines. This attachment of eosinophils was inhibited by the presence of antibody to VCAM-1 and CD49d. Addition of histamine 10 h after stimulation with both cytokines still induced an increase in VCAM-1 expression. In addition, an inhibitor of RNA polymerase, alpha-amanitin, dose-dependently decreased this histamine-induced augmentation of VCAM-1 expression. These findings strongly suggest that histamine upregulates VCAM-1 expression at the transcriptional level through newly generated of mRNA in endothelial cells stimulated with IL-4 and TNF-alpha.

Amanitins↗

PubMed1996

Angiotensin-converting enzyme gene polymorphism in hypertensive individuals with parental history of stroke.

BACKGROUND AND PURPOSE: It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to stroke has not yet been proven. We investigated an association of ACE gene polymorphism with parental history of stroke (PHS) in patients with hypertension. METHODS: We studied 70 hypertensive patients (ambulatory blood pressure > 140/90 mm Hg; age, 59 +/- 11 years) with (n = 27) or without (n = 43) PHS, defined as either one or both parents having had a stroke before 60 years of age. The ACE genotype was analyzed by polymerase chain reaction. RESULTS: Casual blood pressure and mean ambulatory blood pressure levels were not significantly different between patients with and without PHS. The incidence of left ventricular hypertrophy also did not differ significantly between the two groups. However, the frequency of the D allele was significantly higher in patients with PHS (0.72) than in patients without PHS (0.52) (chi 2 = 5.472, P = .019). The frequency of the DD genotype of the ACE gene was also significantly higher in patients with than in those without PHS (DD, 63.0%; ID, 18.5%; II, 18.5% versus DD, 32.6%; ID, 39.5%; II, 27.9%; chi 2 = 6.395, P = .041). CONCLUSIONS: The DD genotype of the ACE gene is associated with PHS in patients with hypertension, which is independent of blood pressure levels or presence of cardiac hypertrophy.

Aged↗

PubMed1996

Inhibition of theophylline metabolism by aciclovir.

We report a case of side effects caused by the increase in plasma theophylline concentration after coadministration of aciclovir had been started during theophylline therapy. Interaction between theophylline and aciclovir has not previously been reported. Therefore, a study of the pharmacokinetic and metabolic interactions between theophylline and aciclovir was carried out in five healthy male volunteers. All subjects received a single oral dose of 320 mg theophylline (aminophylline, 400 mg) after they had taken oral aciclovir 800 mg five times daily for two consecutive days. The area under the curve from 0 to infinity of theophylline (AUC0-infinity) after coadministration of aciclovir was increased from 189.9 +/- 18.2 to 274.9 +/- 34.3 micrograms.h/ml (p < 0.01), and total body clearance was decreased from 28.4 +/- 2.9 to 19.8 +/- 2.5 ml/h/kg (p < 0.01). Further, there was a significant increase in urinary theophylline and decreases in urinary 1,3-dimethyluric acid and 1-methyluric acid after coadministration of aciclovir. The decrease in total body clearance is likely to have resulted from inhibition of metabolism via the oxidation pathway. The results indicated that with aciclovir therapy lower doses of theophylline might be necessary and careful monitoring of plasma concentrations was essential.

Acyclovir↗

PubMed1996

Immunotoxic effect of low dose cisplatin in mice.

The immunosuppressive effects of cisplatin at relatively low doses were investigated in CD-1 mice. Mice were injected intraperitoneally with 8, 40 and 200 micrograms/kg cisplatin for 10 days. A decrease in body and thymus weights was observed at 200 micrograms/kg. Though there were no dose-related effects on the IgM antibody response to sheep erythrocytes, a statistically significant reduction of the contact hypersensitivity response (CHR) was seen at 200 micrograms/kg. In vivo and in vitro effects of cisplatin on T- and B-lymphocyte function were assessed by proliferative response to concanavalin A and lipopolysaccharide, respectively. Cisplatin inhibited splenic T-lymphocyte function more than splenic B-lymphocyte function. These data indicate that a relatively low dose of cisplatin induce immunosuppressive effects in mice with a greater effect on T-lymphocytes than the B-lymphocytes.

Animals↗

PubMed1996

[Antigenicity tests of a new antineoplastic agent S-1].

The antigenicity was tested of a new antineoplastic agent S-1 (a combination of tegafur (FT), CDHP and potassium oxonate (Oxo)) in mice and guinea pigs. 1. Male BALB/c or C3H/He mice were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and human serum albumin (HSA). S-1 was administered by oral gavage, and the other compounds were administered intraperitoneally with adjuvant (alum). In the heterologous passive cutaneous anaphylaxis (PCA) test, using Sprague-Dawley rats as recipients, no IgE antibodies against S-1, CDHP, or Oxo were detected to any serum obtained from the sensitized mice, and no eliciting antigenicities were seen for CDHP or Oxo. 2. Male Hartley guinea pigs were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and HSA. S-1 was administered by oral gavage, and the other compounds were administered subcutaneously with Freund's complete adjuvant (FCA). The homologous PCA test, active systemic anaphylaxis test, and passive hemagglutination test showed no production of antibodies against S-1, CDHP, or Oxo in any sensitized guinea pig, and no eliciting antigenicities for CDHP or Oxo. 3. Female Hartley guinea pigs were sensitized with S-1 subcutaneously with FCA. The active cutaneous anaphylaxis test revealed that S-1 did not induce cell-mediated delayed type hypersensitivity. 4. These results indicated that S-1, Oxo, and CDHP were not antigenic in mice and guinea pigs.

Administration, Oral↗

PubMed1996

[Mutagenicity study of a new antineoplastic agent S-1, and its components, CDHP, and Oxo].

S-1 is a new antineoplastic agent of a fluorinated pyrimidine derivative containing tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1 with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) and reducing its dose-limiting gastrointestinal toxicity. As a part of the safety evaluation of S-1, reverse mutation tests using bacteria and chromosomal aberration tests using cultured cells, CHL/IU, were conducted to test the in vitro mutagenicity of S-1, CDHP and Oxo. All S-1 doses are expressed as the content of FT. 1. The reverse mutation tests were carried out on S-1 at 1.02-520 micrograms/plate, on CDHP at 39.1-5000 micrograms/plate, and on Oxo at 78.1-5000 micrograms/plate using Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA. None of the test compounds induced a significant increase over solvent controls in the number of mutant colonies in any tester strains in either system, with or without mammalian metabolic activation (S9 Mix). 2. For the in vitro chromosomal aberration tests, Chinese hamster lung cells (CHL/IU), were treated with S-1 at 27.5-220 micrograms/ml for 24 hr or at 6.88-27.5 micrograms/ml for 48 hr without S9 Mix, and at 110-880 micrograms/ml with S9 Mix, with CDHP at 365-1460 micrograms/ml (10 mM), and with Oxo at 122-1950 micrograms/ml (10 mM), with and without S9 Mix. S-1 with and without S9 Mix, and Oxo only for 48 h treatment without S9 Mix, induced chromosomal aberrations, while CDHP did not. 3. The present study indicates that S-1 was nonmutagenic in bacteria, but clastogenic in vitro. CDHP had no in vitro mutagenic or clastogenic activity. Oxo was positive in the in vitro chromosomal aberration test, but negative in the reverse mutation test.

Animals↗

PubMed1996

[Immunotoxic effects of a new antineoplastic agent S-1 in mice--comparison with S-1, UFT and 5-FU].

The immunotoxicity of S-1, which is a new antineoplastic agent, was investigated in BALB/c mice. S-1 contains tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molecular ratio of 1:0.4:1. 5-fluorouracil (5-FU) and UFT were used as reference drugs. S-1 and reference drugs were administered by oral gavage for 7 days. The high dose employed in this study was determined as the maximally tolerated dose of a 9-day repeated-dose study in sarcoma 180-bearing mice. Decreased body weight was observed in mice treated with 5-FU and UFT but not in those treated with S-1. A significant decrease in thymus and spleen weight was observed in S-1-, UFT- and 5-FU-treated mice, and the degree was same for the three drugs. Though the number of white blood cells decreased dose-dependently for the three drugs, S-1 had the weakest effect. The number of red blood cells also decreased, but the effect was not dose-dependent, and its magnitude was the same for the 3 drugs. S-1 induced a dose-dependent decrease in the IgM antibody PFC response to sheep erythrocytes. The delayed type hypersensitivity response used a footpad reaction method was significantly suppressed at the highest dose of S-1. 5-FU and UFT suppressed humoral and cell-mediated immunity in almost the same manner as S-1. The degree of suppressive effects was greater on the humoral immune response than on the cell-mediated immune response. The number of CFU-GM colonies was significantly decreased in the highest dose group of each drug and in a lower group as well in S-1-treated mice. This finding might reflect the fact that S-1 induced continuous high levels of 5-FU in the blood. Under these experimental conditions, S-1 induced immunosuppressive effects in BALB/c mice, and the degree of suppression was almost same as that induced by 5-FU and UFT.

Animals↗