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Biomedical subjects

T Shirai

Publications and source records attributed to T Shirai.

At least 307 records · Page 17Linked to original sources
PubMed1996

Antegrade and retrograde cardioplegia: alternate or simultaneous?

UNLABELLED: Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 degrees C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 degrees C) and reduces the anaerobic metabolism seen with warm (37 degrees C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. METHODS: Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). RESULTS: Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. CONCLUSION: Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions.

Adult↗
PubMed1996

Medium-term liver and multi-organ carcinogenesis bioassays for carcinogens and chemopreventive agents.

To bridge the gap between long-term carcinogenicity tests and short-term screening assays such as the Ames test, several types of medium-term bioassay for rapid detection of carcinogenic agents have been developed using male F344 rats. The liver model, in which diethylnitrosamine initiation and acceleration of carcinogenesis by partial hepatectomy are essential components, requires only 8 weeks of animal experimentation and a few weeks for quantitative analysis of hepatic preneoplastic lesions. Using the model, a total of 250 chemicals have been analyzed and the efficacy of the system for hapatocarcinogens has thereby been well established. Other models are so-called multi-organ bioassays for detection of carcinogenic agents in multiple organs within relatively short periods. Among these, the DMBDD bioassay with 5 known carcinogens as initiators has been found to be most applicable and has now been introduced for practical use. Data from these bioassays and several single organ carcinogenesis systems have demonstrated that carcinogenic and modifying effects of individual exogenous agents may markedly differ from organ to organ. Therefore, research into chemoprevention should be based on a whole body level analysis. The present medium-term systems are very useful for this purpose.

Animals↗
PubMed1996

Chemically induced lung and forestomach neoplasias in transgenic mice carry mutant forms of the human c-Ha-ras transgene.

Susceptibility to lung carcinogens and genetic changes in neoplastic lesions were investigated in transgenic mice carrying a human hybrid c-Ha-ras gene, encoding a prototype p21 gene product. Nine-week-old male and female transgenic mice and non-transgenic littermates were injected i.p. with 6-nitrochrysene (6NC) three times biweekly or administered urethane in their drinking water for 3 weeks. Control mice were given dimethylsulfoxide (DMSO), the solvent for 6NC, alone. The incidences of lung adenocarcinomas were four out of seven female (57%) transgenic mice treated with 6NC and three out of three males (100%) and three out of three females (100%) receiving urethane. No adenocarcinomas were observed in control animals or non-transgenic mice. Adenomas developed in all treated groups, but the incidence and multiplicity were higher in transgenic animals than in their non-transgenic counterparts. In the 6NC-treated group, forestomach papillomas and squamous cell carcinomas were also observed in both male (25 and 50%) and female (56 and 33%) transgenic mice. PCR-SSCP and DNA sequence analysis of these induced lesions revealed point mutations at codon 61 of transgenic human c-Has-ras, from CAG (Gln) to CTG (Leu) or CAG (Gln) to AAG (Lyn) in lung hyperplasias (two out of three), an adenoma (one out of two), adenocarcinomas (five out of seven) and forestomach squamous cell carcinomas (four out of five). Mutations were not observed in forestomach papillomas. No changes in mouse Ha-ras or Ki-ras were found in any lesions. Furthermore, p21 overexpression was not evident in lung or forestomach tumors on immunohistochemical analysis. These findings indicate a high sensitivity to lung carcinogens in transgenic mice carrying the human c-Ha-ras gene and that this might be effected by mutational activation.

Animals↗
PubMed1996

Effects of transgenic mixed-haplotype MHC class II molecules A alpha d A beta z on autoimmune disease in New Zealand mice.

The MHC haplotype heterozygosity (H-2d/H-2z) acts as one major predisposing genetic element for autoimmune disease resembling systemic lupus erythematosus (SLE) in the F1 hybrid of NZB (H-2d) and NZW (H-2z) mice. To determine a possible role of mixed-haplotype A molecules, we introduced a transgene A beta z into H-2d/H-2d homozygous (NZB x NZW.H-2d)F1 mice, in which, compared with the original H-2d/H-2z heterozygotes, the incidence and titer of IgG anti-DNA antibodies, serum levels of nephritogenic retroviral gp70/anti-gp70 immune complexes (ICs) and the associated incidence of IC-type lupus nephritis were reduced. Evidence for the formation of mixed-haplotype A alpha d A beta z molecules in the transgenic mice was obtained by A beta z molecule expression on the cell surface of splenic B cells and macrophages, thymic epithelial cells and mature B cells in the bone marrow. A alpha d A beta z-restricted T cell clones showed good proliferative responses to spleen cells from the transgenic mice, to an extent much larger than seen in cells from the original (NZB x NZW)F1 mice, suggesting that the expression of functional A alpha d A beta z molecules on cells in transgenic mice is considerably high. Compared with findings in transgene-negative littermates and the original (NZB x NZW)F1 mice, the A beta z transgene to a greater extent promoted serum levels of IgM anti-double-stranded (ds) DNA antibodies and IgM anti-gp70/gp70 ICs in the transgenic mice. None the less, the production of IgG anti-dsDNA antibodies and IgG anti-gp70/gp70 ICs as well as the development of renal disease was markedly suppressed. Possible mechanisms of such effects of the transgene are discussed.

Animals↗
PubMed1996

Flow threshold for reduction of cyclic AMP binding in the hippocampus CA1 and other brain regions during stroke development in gerbils.

The flow threshold for alterations of the in vitro [3H]cyclic AMP (cAMP) binding, an indicator of the total amount of particulate cAMP-dependent protein kinase, was evaluated in the gerbil brain after 30 min, 2 h, and 6 h of unilateral common carotid artery occlusion, respectively. The autoradiographic method developed in our laboratory enabled us to measure the [3H]cAMP binding and local CBF in each region of the same brain. The ischemic flow thresholds for reduction of the cAMP binding in the hippocampus CA1 were 18, 34, and 49 ml 100 g-1 min-1 after 30-min, 2-h, and 6-h ischemia, respectively. These values were higher than those in other regions such as the hippocampus CA, and temporal cerebral cortex in each duration of ischemia. These findings indicate that (a) the ischemic flow threshold for perturbation of the cAMP system may be higher in the hippocampus CA1 than in other brain regions, suggesting that the hippocampus CA1 could be especially vulnerable to acute ischemic stress; and (b) the level of the aforementioned threshold may increase progressively during the time course of ischemia in particular regions such as the hippocampus CA1 and CA3, suggesting that the duration of ischemia exerts a definite influence on the viability of the ischemic neuronal cells in these regions.

Animals↗
PubMed1996

Pemphigus vulgaris exacerbated by exposure to sunlight.

We report two cases of pemphigus vulgaris who showed exacerbation of their bullous skin lesions after exposure to sunlight. These cases indicate that ultraviolet light is an aggravating factor, not only for pemphigus foliaceus, but also for pemphigus vulgaris.

Adult↗
PubMed1996

DNA-damaging agents induce the 72-kD heat shock protein in SV40 transformed normal human fibroblasts.

In order to elucidate the involvement of DNA damage in the induction of heat shock proteins (stress proteins), we examined the induction of 72-kD heat shock protein (HSP72) in an SV40-transformed human fibroblast cell line (WI38VA13) which was exposed to various DNA-damaging agents, including 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3 -nitro-methylmethane sulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline-N-oxide. Induction of HSP72 was detected by the indirect immunofluorescence method using a monoclonal antibody. All the DNA-damaging agents used in this study induced HSP72 on human fibroblasts. This result indicates that DNA damage is one trigger for the induction of HSP72.

Antineoplastic Agents↗
PubMed1996

Detection of autoantibody against 97-kD antigen by immunoblot, but not by indirect immunofluorescence, in a patient with linear IgA bullous dermatosis.

A case of linear IgA bullous dermatosis in an 85-year-old man is reported. Direct immunofluorescence (IF) of the lesional skin showed linear deposition of IgA and weak deposition of IgG at the basement membrane zone. Although no circulating autoantibody was detected by indirect IF, immunoblotting analysis using NaCl-separated normal human epidermal extracts revealed a circulating IgA antibody which bound to the 97-kD antigen.

Aged↗
PubMed1996

Pemphigoid and pemphigus foliaceus successfully treated with topical corticosteroids.

Six patients with pemphigoid and three patients with pemphigus foliaceus were successfully treated with topical corticosteroids. This was especially effective in cases of pretibial localized pemphigoid and in mild cases of bullous pemphigoid and pemphigus foliaceus with negative or low-titer circulating autoantibodies.

Administration, Topical↗
PubMed1996

Induction of the low-molecular-weight stress protein HSP27 in organ-cultured normal human skin.

To examine the inducibility of 27-kD-molecular-weight heat shock protein (HSP27) in human skin, an indirect immunofluorescence (IF) study was performed on organ-cultured normal human skin by using a monoclonal antibody specific for HSP27. After heat treatment at 45 degrees C for 1 h, nuclear IF was observed in the epidermal cells. When the organ-cultured skin explants were exposed to 10.0 micrograms/ml or 100.0 micrograms/ml 8-methoxypsoralen (8-MOP) for 1 h and then irradiated with UVA (320-400 nm), positive nuclear IF was also observed 6 h after UVA irradiation. Considering these results with the previous reports about HSP72, it appears that, in human skin, HSP27 as well as HSP72 plays an important role in resisting various environmental stresses.

Aged↗
PubMed1996

Expression of E-cadherin in skin carcinomas.

In this study, we investigated the expression of E-cadherin in 31 cases of human skin carcinoma including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Paget's disease, Bowen's disease (invasive type), and trichilemmal carcinoma, by immunohistochemical staining using a monoclonal antibody specific for E-cadherin. Similar to the E-cadherin expression in normal epidermis, E-cadherin was strongly expressed in all samples of BCC on the cell borders, whereas marked decrease or loss of E-cadherin expression was found in the tumor cells of SCC, Paget's disease, and Bowen's disease (invasive type). On the other hand, E-cadherin expression of trichilemmal carcinoma was slightly reduced. Considering the clinical and histological features of these skin carcinoma, the reduction of E-cadherin expression is considered to be associated with the invasion and metastasis of human skin carcinoma.

Adult↗
PubMed1996

Distribution of lectin UEA-I in trichilemmal carcinoma, squamous cell carcinoma, and other epithelial tumors of the skin.

Trichilemmal carcinoma (TLC) is a cutaneous appendage tumor. In some cases, the histological distinction between TLC and squamous cell carcinoma (SCC) is difficult with hematoxylin & eosin staining. In the present study, in order to establish a simple and reliable method for distinguishing between TLC and SCC, we examined the lectin Ulex europaeus agglutinin-I (UEA-I)-binding patterns of TLC (4 cases), SCC (10 cases), malignant proliferating trichilemmal cyst (MPTC) (3 cases), Bowen's disease (4 cases), Bowen's carcinoma (4 cases), actinic keratosis (4 cases), basal cell carcinoma (8 cases), and eccrine porocarcinoma (1 case). In normal skin samples, UEA-I was strongly positive in the outer root sheath cells of the hair follicle and weakly positive in the granular layers of the epidermis. UEA-I stained the tumor cells of TLC clearly and some MPTC and Bowen's disease cells weakly. This result indicates that histochemical staining with UEA-I is a simple and useful method for distinguishing between TLC and SCC of the skin.

Adult↗
PubMed1996

Histopathological analysis of invasive bladder carcinomas induced by 3,2'-dimethyl-4-aminobiphenyl in hamsters.

Histopathological characteristics of urinary bladder tumors induced in Syrian golden hamsters by 3,2'-dimethyl-4-aminobiphenyl (DMAB) were analyzed. DMAB was subcutaneously injected in corn oil at a concentration of 100 mg/kg once a week for 20 weeks and ethinyl estradiol (EE) was administered in the diet at a dose of 0.75 ppm throughout the experiment. A small group of animals was killed at week 20 and all survivors were killed at week 50. Urinary bladder carcinomas were induced in 14 of 18 hamsters (78%; 0.89/animal) in the DMAB+EE group and 11 of 17 (65%; 0.88/animal) in the DMAB alone group in males, and in 11 of 14 (79%; 0.79/animal) in the DMAB+EE group and 4 of 5 (80%; 0.80/animal) in the DMAB alone group in females examined between weeks 20 and 50. All were non-papillary invasive transitional cell carcinomas partly demonstrating glandular and/or squamous differentiation, and most carcinomas developed in the bladder neck. Degree of invasion was clearly correlated with degree of morphological atypism in the transitional cell carcinomas, but not with squamous or glandular differentiation. No sex difference or modifying effect of EE on DMAB urinary bladder carcinogenesis was evident. No bladder carcinomas were observed in non-DMAB-treated animals.

Aminobiphenyl Compounds↗
PubMed1996

Direct effects of testosterone, dihydrotestosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in castrated F344 rats.

The present experiment was carried out to explore the effect of endogenous androgen on rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP) or 5alpha-dihydrotestosterone (DHT) with or without ethinyl estradiol (EE). In order to eliminate the influence of endogenous androgen, F344 rats were orchiectomized just after initiation with the prostate carcinogen, DMAB, and then given TP, DHT, TP plus EE or DHT plus EE for 40 weeks. The results demonstrated that while administration of TP following DMAB treatment causes invasive carcinomas in the lateral and anterior prostate and seminal vesicles, DHT does not exhibit equivalent effects. Synergistic enhancement was also evident with TP plus EE, but not with DHT plus EE. The incidences of prostatic and seminal vesicle lesions in all groups of the present experiment, except for the group given castration without hormonal supplement, were equivalent to those previously found in non-castrated animals. Therefore, the present findings indicate that endogenous testosterone may not be required for promotion by TP/EE of DMAB-initiated prostate carcinogenesis and that it may not contribute to the actions of DHT.

Aminobiphenyl Compounds↗
PubMed1996

Lack of chemoprevention effects of the monoterpene d-limonene in a rat multi-organ carcinogenesis model.

Modifying effects of dietary administration of the monoterpene d-limonene were examined using a multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), 1,2-dimethylhydrazine (DMH, s.c.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) and dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) during the first 4 weeks (DMBDD treatment), and then d-limonene was administered in the diet, at the dose of 2.0, 1.0 or 0.5%. The maximal tolerable dose was 2.0% under the present conditions. Further groups were treated with DMBDD or 2.0% d-limonene alone as controls. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. The incidences and/or multiplicities of renal atypical tubules and adenomas were increased in animals fed 2.0% d-limonene. The immunohistochemical reactivity for alpha2u-globulin in the proximal tubules was greater in rats fed d-limonene than in the carcinogen alone group. No enhancing or inhibitory effect was noted for tumor development in other organs. The present results indicate a lack of any chemopreventive effect of d-limonene in any organ of male rats under the present experimental conditions.

1,2-Dimethylhydrazine↗
PubMed1996

Dose-dependent induction of mammary carcinomas in female Sprague-Dawley rats with 2-amino-1-methyl-6-phenylimidazol[4,5-b]pyridine.

The dose-dependence of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induction of mammary carcinomas was investigated in female Sprague-Dawley (SD) rats given PhIP in the diet for 48 weeks at concentrations of 0, 25, 100 and 200 ppm in experiment 1, and 0, 12.5, 50 in experiment 2. Yields of ductular lesions, including intraductal papillomas and carcinomas, as well as papillo-tubular and solid-tubular carcinomas, showed dependence on the dose, with the respective total incidences being 0, 4.8, 25, 72.2 and 0, 10 and 35%. There was thus no apparent carcinogen exposure threshold. The present results confirmed the carcinogenicity demonstrated in a previous study using F344 rats and revealed the SD rat strain to be more susceptible.

Adenocarcinoma↗