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T Shirai

Publications and source records attributed to T Shirai.

At least 361 records · Page 20Linked to original sources
PubMed1995

Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes.

OBJECTIVE: To determine whether apoptosis occurs in rheumatoid arthritis (RA) synoviocytes, and if this phenomenon is dependent on the Fas/Apo-1 pathway. METHODS: Apoptotic change in vivo was examined in RA synovial cells by several standard methods. The ability of cells to undergo Fas-induced apoptosis was determined in vitro. RESULTS: Typical apoptotic change was demonstrated in RA synovial cells by each method. Anti-Fas antibody induced apoptotic synovial cell death in vitro. CONCLUSION: This is the first reported study to demonstrate apoptosis in RA synovial cells. The findings indicate that rheumatoid synoviocytes undergo Fas-mediated apoptosis.

Antibodies↗
PubMed1995

Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule.

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce antigen-specific peripheral tolerance in organ transplantation and autoimmune disease. Recently, diversities between CD80 and CD86 in expression, regulation, and function have been reported in certain cell populations and murine experimental disease models. To investigate the possible differential role of CD80 and CD86 in the development of lupus, we treated lupus-prone NZB/W F1 mice with specific monoclonal antibodies (mAb) against CD80, CD86, or both. The treatment with a combination of anti-CD80 and CD86 mAb before the onset of lupus completely prevented autoantibody production and nephritis, and prolonged survival. Interestingly, we found that anti-CD86 mAb alone, but not anti-CD80 mAb, efficiently inhibited autoantibody production. Subclass study on IgG anti-double-stranded (ds) DNA antibody revealed that the treatment with anti-CD86 mAb almost completely inhibited both IgG1 and IgG2b, but not IgG2a production. The incomplete reduction of IgG2a anti-dsDNA antibody by anti-CD86 mAb was compensated by the addition of anti-CD80 mAb. A significant reduction of mRNA for interleukin (IL)-2, interferon-gamma, IL-4 and IL-6 was observed in mice treated with a combination of anti-CD80 and CD86 mAb or anti-CD86 mAb alone. Treatment with both mAb after the onset of lupus resulted in a significantly prolonged survival with reduction of autoantibody production. These results suggest that CD86 plays a more critical role in autoantibody production, and CD86, but not CD80, contributes to Th2-mediated Ig production. However, the blockade of both CD80 and CD86 are required for preventing the development and progression of lupus.

Animals↗
PubMed1995

Ki-ras mutations with frequent normal allele loss versus absence of p53 mutations in rat prostate and seminal vesicle carcinomas induced with 3,2'-dimethyl-4-aminobiphenyl.

We have developed a prostate carcinogenesis model in Fischer 344 rats using 3,2'-dimethyl-4-aminobiphenyl (DMAB) as a carcinogen to examine various potential modifying factors. In this study, mutational changes in the ras and p53 genes were assessed in DMAB-induced rat prostate and seminal vesicle carcinomas by single-strand conformation polymorphism analysis and subsequent direct DNA sequencing. Eight of 22 prostate adenocarcinomas (three of nine (33.3%) from the ventral lobe and five of 13 (38.5%) from the dorsolateral lobe, including three transplantable tumors) and one of 11 seminal vesicle adenocarcinomas (9.1%) demonstrated point mutations in the Ki-ras gene. One prostate malignant fibrohistiocytoma examined was negative. Among the positive cases, five (three ventral prostate carcinomas and two transplantable tumors) also showed loss of the normal allele. In contrast, other than one mutation in the p53 gene in the malignant fibrohistiocytoma, there were no mutations in the Ha-ras or p53 genes. These results indicate that mutational activation of the Ki-ras gene, but not of the Ha-ras or p53 genes may play a mechanistic role in prostate and seminal vesicle carcinogenesis by DMAB and that a loss of the normal allele of the Ki-ras gene may also be involved in the process.

Adenocarcinoma↗
PubMed1995

Lack of promoting activity of four pesticides on induction of preneoplastic liver cell foci in rats.

Four pesticides were examined for hepatopromoting activity using a medium-term bioassay based upon induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gave negative results, the numbers and areas of GST-P positive foci not exceeding the control values for animals given DEN alone. Indeed, a significant reduction of foci development was seen for EPN (75 ppm). These findings provide experimental evidence that the presently examined four pesticides do not have hepatocarcinogenic potential in rats.

Animals↗
PubMed1995

Abnormal T cell activation and skewed T cell receptor V beta repertoire usage in Japanese patients with idiopathic portal hypertension.

Idiopathic portal hypertension (IPH), a disorder of unknown etiology, is characterized by a noncirrhotic portal hypertension associated with splenomegaly, hypersplenism, and anemia. We examined the surface phenotypes of T cells and the T cell receptor V beta repertoire in patients with IPH. The T cells in peripheral blood samples and from spleens showed a marked increase in frequencies of HLA-DP(+)- and HLA-DR(+)-activated T cells and the observed high frequencies in the blood were to a considerable extent reduced after splenectomy. Thus, the continuous activation of T cells may occur initially in the spleen. Investigation of T cell receptor V beta repertoire revealed a significant skewing of V beta 9 and V beta 11 in both peripheral blood and splenic T cells and V beta 12 in splenic T cells. The IPH may be a disease mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.

Adult↗
PubMed1995

Flow threshold for enhanced phorbol ester binding in the ischemic gerbil brain.

The correlation between regional phorbol ester binding and cerebral blood flow (CBF) was evaluated in the gerbil brain after 2-hour unilateral common carotid artery occlusion. [3H]phorbol 12,13-dibutyrate (PDBu) was used as a specific ligand for estimating the translocation of protein kinase C (PKC), and CBF was determined by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted concurrent measurement of these two parameters in the same brain. In the ischemia group of the animals, statistically significant, inverse correlations were noted between the CBF and PDBu binding in the hippocampus (CA1 and CA3 regions and dentate gyrus), the caudate-putamen and lateral nuclei of the thalamus. In these regions, the PDBu binding increased progressively as CBF fell below 35-40 ml/100 g/min. On the other hand, the PDBu binding in the cerebral cortices did not show any significant changes even when CBF was decreased to below 35 ml/100 g/min. The above data suggest that (1) the translocation of PKC to the cell membrane may be regionally specific in response to ischemia, and may remain in the regions particularly vulnerable to ischemia such as the hippocampus, caudate-putamen and lateral nuclei of the thalamus in the early ischemic phase; (2) the threshold of CBF below which PKC begins to translocate to the cell membrane in the above regions, may be 35-40 ml/100 g/min in 2-hour ischemia.

Animals↗
PubMed1995

Tepid antegrade and retrograde cardioplegia.

To determine the optimal temperature for the combination of antegrade and retrograde cardioplegia, 42 patients undergoing coronary artery bypass grafting were randomized to receive cold (9 degrees C; n = 14), tepid (29 degrees C; n = 14), or warm (37 degrees C; n = 14) blood cardioplegia delivered continuously retrograde and intermittently antegrade. Myocardial oxygen utilization, lactate and acid metabolism, and coronary vascular resistance were measured during the operation and cardiac function was assessed postoperatively. Myocardial oxygen consumption, lactate release and acid release were greatest with warm, intermediate with tepid, and least with cold cardioplegia (p = 0.0001). However, washout of lactate and acid at the time of cross-clamp release was reduced (p = 0.022) with tepid or cold compared with warm cardioplegia. Early postoperative left ventricular function was best preserved (p = 0.01) after tepid than after cold or warm combination cardioplegia. These results suggest that tepid combination cardioplegia reduced metabolic demands but permitted immediate recovery of cardiac function. This technique may provide better myocardial protection than cold or warm combination cardioplegia.

Aged↗
PubMed1995

Myocardial protection for coronary bypass grafting: the Toronto Hospital perspective.

BACKGROUND: The contemporary results of coronary artery bypass grafting using a variety of myocardial preservation techniques are excellent. In recent years, the number of "high-risk" patients referred for operation has increased, thus necessitating continued advances in surgical myocardial protection. METHODS: In this article, we review recent advances in clinical myocardial protective techniques and emphasize studies conducted at The Toronto Hospital. Further, on the basis of promising current research, we speculate on future prospects for myocardial protection. RESULTS: At The Toronto Hospital, we converted from crystalloid to intermittent cold blood cardioplegia in 1985. We demonstrated that "continuous" cardioplegic strategies may help resuscitate the ischemic myocardium and reduce operative complications in high-risk patients. Further improvements in myocardial protection will require refinements in cardioplegic solution temperature, direction of delivery, and additives to "precondition" the myocardium against ischemic damage. CONCLUSIONS: Major advances that meet the requirements of an increasingly high risk patient population have been made in surgical myocardial protection in recent years. The future is bright for continued progress in this area.

Blood↗
PubMed1995

Atypical pemphigus associated with monoclonal IgA gammopathy.

We describe a 60-year-old woman with atypical pemphigus and IgA-lambda monoclonal gammopathy. Histopathologic study of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular IgG deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG anti-intercellular antibodies that recognized the 150 kd desmoglein (pemphigus foliaceus antigen) in bovine desmosome preparation. Immunoblot studies with human epidermal extract showed that the IgG of this patient exclusively reacted with the 140 kd protein (between the 150 kd human desmoglein and the 130 kd human pemphigus vulgaris antigen), the nature of which is currently unknown. The patient also had IgA anti-intercellular autoantibodies, which reacted with the desmoglein in the bovine desmosome sample but did not show any reactivity in human epidermal extract.

Antibodies, Anti-Idiotypic↗
PubMed1995

Effect of ingestion of 20 pesticides in combination at acceptable daily intake levels on rat liver carcinogenesis.

Exposure of agricultural workers and the general population to pesticides is a major concern, and possible summation or synergistic effects deserves particular attention. In this study, however, combined dietary administration of 19 organophosphorus compounds and one organochlorine pesticide, each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of 100 times ADI significantly increased the number and area of lesions. The results thus provide direct support for the present safety factor approach to the quantitative hazard evaluation of pesticides.

Administration, Oral↗
PubMed1995

Rat strain differences in catechol carcinogenicity to the stomach.

The carcinogenic potential of catechol was compared in male Wistar, WKY, Lewis and SD strains of rats. Groups of 30 animals were treated with powdered diet containing 0.8% catechol for 104 wk and then examined histopathologically. Induction of glandular stomach adenocarcinomas occurred in 67, 73 and 77% of Wistar, Lewis and SD animals, respectively, but in only 10% of WKY rats. In addition, catechol induced forestomach papillomas in 20% (P < 0.05), and squamous cell carcinomas in 3% of SD rats. The results thus indicate that Wistar, Lewis and SD rats are much more susceptible than WKY rats to induction of glandular stomach adenocarcinomas by 0.8% catechol, and that this phenolic antioxidant also possesses weak carcinogenic activity for the SD rat forestomach.

Adenocarcinoma↗
PubMed1995

Lack of carcinogenicity of monosodium L-glutamate in Fischer 344 rats.

Monosodium L-glutamate (MSG) was administered to groups of 50 male and 50 female Fischer 344 rats in the diet at levels of 0, 0.6, 1.25, 2.5 and 5.0% for a 2-yr period. Survival of dosed and control rats of both sexes was comparable, although animals receiving 5.0% MSG showed a trend towards (or significant) growth retardation. Urinary biochemistry values indicated increased pH and Na+ levels and decreased K+ in rats of both sexes given 2.5 or 5.0%. However, no significant increases in proliferative or neoplastic lesion development in the urinary tract were observed in any MSG-treated animals. In addition, occurrences of neoplastic lesions in other organs did not differ between treated and control groups. The present study thus did not demonstrate any long-term carcinogenic effect of MSG administered to rats at levels up to 5.0% in the diet.

Animals↗
PubMed1995

Analysis of the potential carcinogenicity of coffee and its related compounds in a medium-term liver bioassay of rats.

The potential carcinogenicity of coffee and related compounds was examined using a medium-term liver bioassay based on the induction of glutathione S-transferase placental form (GST-P)-positive foci in F344 rats. A total of 230 males were initially injected with diethylnitrosamine (200 mg/kg body weight, ip) or saline as controls and 2 wk later were fed on diet or drinking water supplemented as follows for 6 wk: 5% regular instant coffee; 5% decaffeinated instant coffee; freshly brewed coffee, 8 g in 140 ml water; 0.1% caffeine, 0.2% methylglyoxal, 0.2% glyoxal; or 0.3% theophylline in the drinking water (w/v); and 0.4% theobromine in the diet (w/w). All rats were subjected to two-thirds partial hepatectomy at wk 3 and killed at wk 8. The resultant values for GST-P-positive hepatic focus induction were slightly increased with methylglyoxal and decreased with glyoxal and theobromine compared with the corresponding controls. Although the increase in number of foci for methylglyoxal was statistically significant at P < 0.05, the value was within the historical control levels. Regular and decaffeinated instant coffee as well as fresh-brewed coffee, caffeine and theophylline exerted no effects on focus development. Thus, the coffee-related compounds examined demonstrated no obvious enhancing potential, and it is therefore concluded that coffee and its main constituents are not carcinogenic for the rat liver.

Administration, Oral↗
PubMed1995

Lack of carcinogenicity of pesticide mixtures administered in the diet at acceptable daily intake (ADI) dose levels in rats.

Carcinogenic effects of pesticide mixtures were examined with our medium-term carcinogenesis protocols using male F344 rats. In the 8-week liver model, combined dietary administration of 20 pesticides (19 organophosphorus compounds and 1 organochlorine), each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of 100 times ADI significantly increased the number and area of liver lesions. In the second experiment using a multi-organ carcinogenicity protocol of 28 weeks, mixtures of 40 pesticides (high volume compounds) and 20 pesticides (suspected carcinogens) added to the diet at their respective ADI levels did not enhance carcinogenesis in any organ initiated by 5 different known carcinogens in combination. These results provide support for the safety factor (usually 100) approach presently used for the quantitative hazard evaluation of pesticides.

Animals↗
PubMed1995

Adequate distribution of warm cardioplegic solution.

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the left anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardioplegic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the left ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone.

Adenine Nucleotides↗
PubMed1995

Differences in cell proliferation and apoptosis between reversible and irreversible mucosal lesions associated with uracil-induced urolithiasis in N-butyl-N-(4-hydroxybutyl)nitrosamine-pretreated.

Differences between the reversible papillomatosis and preneoplastic lesions of the urinary bladder of rats were investigated in terms of cell proliferation and apoptosis after cessation of uracil administration. Animals were given N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then uracil for 8 weeks in order to induce urinary bladder lesions. During this period and after cessation of treatment until week 20, subgroups of animals were killed to allow sequential assessment of cell kinetics and apoptosis. Labeling indices (LI) in papillomatosis showed a marked elevation after 2 weeks of uracil treatment with a rapid decline thereafter. In contrast, LI in dysplasias, papillomas and carcinomas gradually elevated during the uracil treatment. Cessation of the uracil stimulation resulted in a complete disappearance of labeled cells in areas of papillomatosis accompanied by significant appearance of apoptotic bodies in the epithelial cells and shrinkage of the lesions. In the focal dysplasias and papillomas, however, any reduction in LI was temporary and followed by a rapid reelevation. The number of apoptotic bodies were relatively few in neoplastic lesions. Thus, removal of growth-stimulating uracil-calculi resulted in return of hyperplastic epithelium to normal by a homeostatically controlled apoptotic mechanism. In contrast, preneoplasias and neoplasias demonstrated an autonomous growth ability.

Animals↗
PubMed1995

Strong anti-mutagenic activity of the novel lipophilic antioxidant 1-O-hexyl-2,3,5-trimethylhydroquinone against heterocyclic amine-induced mutagenesis in the Ames assay and its effect on metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-p-1).

Antimutagenic effects of a novel lipophilic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), and other known antioxidants against heterocyclic amine- or other mutagen-induced mutagenesis were examined in the Ames assay using Salmonella strain TA 98 to access the chemo-preventive effects of antioxidants on heterocyclic amine-induced carcinogenesis. Further the mechanisms of inhibition by HTHQ were accessed. HTHQ was shown to potently inhibit mutagenesis induced by all of 8 different heterocyclic amines at rates between 100% and 63% in the presence of S9 mix. When the protection of HTHQ against 2-amino-6- methyldipyrido[1,2-alpha:3',2'-d]imidazole (Glu-P-1)-induced mutagenesis was compared with known antioxidants t-butylhydroquinone, propyl gallate, BHA, BHT and alpha-tocopherol, HTHQ showed the greatest effect. Among hexyl, butyl, ethyl and methyl derivatives of 1-O-alkyl-2,3,5-trimethylhydroquinone, HTHQ was the most effective in inhibiting Glu-P-1-, 3-amino-1-methyl-5-H-pyrido[4,3-b]indole (Trp-P-2)- or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced mutagenesis. On the other hand, HTHQ did not inhibit mutagenic activity induced by other mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) and benzo[a]pyrene. HTHQ weakly inhibited that due to direct mutagen 2-nitro derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) only in the presence of S9 mix. No such influence on a 2-nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis, was observed with or without the S9 mix. HTHQ slightly inhibited mutagenesis induced by activated Glu-P-1, a direct acting proximate metabolite of Glu-P-1, in the absence of the S9 mix. HPLC analysis revealed activated Glu-P-1 to be formed by incubating Glu-P-1 with the S9 mix, but this was considerably decreased by the addition of HTHQ. These results indicate that HTHQ is a powerful antimutagenic compound and specifically acts against heterocyclic amines. Its antimutagenic activity appeared to exert by both inhibiting metabolic activation of heterocyclic amines and action on activated N-hydroxy species.

Amines↗