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T Shirai

Publications and source records attributed to T Shirai.

At least 91 records · Page 5Linked to original sources
PubMed2000

Early detection of carcinogenic substances and modifiers in rats.

Over the past 20 years, we have been developing in vivo medium-term bioassay systems in rats for detecting carcinogenic and modifying effects of test compounds. The systems are based on the two-step hypothesis of carcinogenesis. In a liver model, male F344 rats are initially given a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and starting 2 weeks later are treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy at week 3. Carcinogenic potential is scored by comparing the numbers and areas per cm(2) of induced glutathione S-transferase placental form (GST-P) positive foci in the livers of groups of about 15 rats with those of corresponding control groups given DEN alone. A positive response is defined as a significant increase in the quantitative values of GST-P-positive foci, such a negative response as no change or a decrease. The results obtained have been compared with reported Salmonella/microsome and long-term carcinogenicity test findings for the same compounds. Of the liver carcinogens, 30 out of 31 (97%) mutagenic and 29 out of 33 (88%) non-mutagenic compounds gave positive results. Carcinogens other than hepatocarcinogens gave a lower proportion of positive results (9 out of 42, 21%). This bioassay also provides information concerning inhibitory potential. The practical utility and benefits of a multi-organ medium-term experimental protocol for early detection of carcinogenic agents and modifiers acting at sites other than the liver are also discussed.

Animals↗
PubMed2000

Experimental prostate carcinogenesis - rodent models.

A number of rodent models of prostate carcinoma development have been established to study mechanisms and modifying potential. All except for transgenic mouse models need long experimental periods for generation of a high yield of cancers. Spontaneous prostate tumor models, while not practical in terms of time and tumor incidences, allow the natural course of multistep neoplasia to be followed without a need for chemical exposure. Carcinogens, especially in combination with testosterone, can induce prostate carcinomas in rats, but none are prostate-specific, so that tumor development in other organs is a complicating factor. Induction of invasive prostate carcinomas in the rat frequently requires long-term administration of a pharmacological dose of testosterone with or without application of a chemical carcinogen. While there are several transgenic mouse models, each also has strong and weak points, and it is therefore necessary to select the best model for the purpose of any experimental study.

Aminobiphenyl Compounds↗
PubMed2000

Cloning and molecular characterization of calpain, a calcium-activated neutral proteinase, from different strains of Schistosoma japonicum.

cDNA coding for calpain of Schistosoma japonicum were cloned and sequenced, and serological basis of host responses to calpain were analyzed. cDNA of calpain from S. japonicum of two different isolates, Yamanashi strain (Sj-J) and Hunan strain (Sj-C), were 2, 468 bp and 2, 465 bp in length, including the same number (2, 274) of open reading frame. Nucleotide sequence and amino acid sequence between the two calpains are 99.1% and 98.8% identity, respectively. Sj-J and Sj-C calpains were considered to be translated as a preproenzyme, and a 746-amino acid mature enzyme contains eight motifs without a signal peptide at the N-terminal based on the deduced amino acid sequences. mRNA for calpain were detectable in different developmental stages, however, sera obtained from mice immunized with recombinant calpain showed enhanced binding to cercarial antigen. Human sera from S. japonicum-infected individuals recognized the large subunit of schistosomal calpain, and light-infected sera showed stronger reactivities to the recombinant calpain than moderate/high infection cases. When we tested synthetic peptides, there were four common human B cell epitopes in schistosomal calpain, all of which are shared with S. mansoni. Together with these results, calpain of S. japonicum seems to be not only a vaccine candidate, but also a target antigen for immunodiagnosis of human schistosomiasis.

Amino Acid Sequence↗
PubMed2000

Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB).

The objective of this study was to determine the effects of androgen depletion by 5alpha-reductase inhibitor (eg epristeride), pure antiandrogen (eg casodex) or C17-20 lyase inhibitor (eg YM116) on rat prostate carcinogenesis induced by administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB). DMAB was subcutaneously administered on male F344 rats for the first 20 weeks. Epristeride (10 and 50 mg/kg, three times per week), casodex (15 and 30 mg/kg, three times per week) or YM116 (15 and 30 mg/kg, three times per week) were administered orally for 40 consecutive. Then, all accessory sex organs were studied for the formation of neoplastic lesions by histological examination. All carcinoma lesions were produced only in the ventral lobe of the prostate. The incidence of carcinoma developing in the ventral lobe of the prostate was 9.5% in the control group on which DMAB alone was administered, whereas it was 31.6% in the epristeride 10 mg/kg group. 45.0% in the epristeride 50 mg/kg group, 47.8% in the casodex 15 mg/kg group, 63.2% in the casodex 30 mg/kg group, 10.5% in the YM116 15 mg/kg group and 5.0% in the YM116 30 mg/kg group. The incidences of carcinoma in the epristeride 10 mg/kg group, casodex 15 mg/kg group and casodex 30 mg/kg group were significantly higher than that of the control group. In this experimental model, all ventral prostate carcinomas were in situ adenocarcinomas that did not form palpable nodules or distant metastasis. Epristeride and casodex showed a dose-dependent promoting effect on rat ventral prostate carcinogenesis. These results were contradictory to the results of our previous studies; exogenous testosterone in combination with DMAB produced palpable, and metastatic tumors in other portions of accessory sex organs of F344 rats but no carcinoma in ventral prostate, and those invasive carcinomas were significantly inhibited by 5alpha-reductase inhibitor and nonsteroidal anti-androgen. The action mechanisms of androgen and the effects of androgen-regulatory drugs on prostate carcinogenesis should be further studied. Prostate Cancer and Prostatic Diseases (2000) 3, 115-119

Journal Article↗
PubMed2000

Development of systemic sclerosis in a patient with systemic lupus erythematosus and topoisomerase I antibody.

We describe a patient with systemic lupus erythematosus (SLE) associated with topoisomerase I (topo I, Scl-70) antibody, a specific marker for systemic sclerosis (SSc). SSc patients who produce this antibody have severe cutaneous and visceral involvement, and eventually have a poor prognosis. It is rare to find this antibody in patients with other collagen diseases. Only four SLE patients have been reported in the English language literature who were topo I antibody-positive but had no clinical evidence of scleroderma. The serum of our patient with SLE had precipitating topo I antibody from the onset of his disease. Twelve years after the onset of SLE, he developed proximal scleroderma and pulmonary fibrosis. This case reconfirms the prognostic significance of topo I antibody as a predictive marker, and indicates that SLE patients with topo I antibody require careful follow-up for future development of scleroderma.

Adult↗
PubMed2000

Guillain-Barré syndrome in a child with systemic lupus erythematosus and anti-Ro/SSA and anti-La/SSB autoantibodies.

We report a 9-year follow-up of a girl with systemic lupus erythematosus (SLE) and probable Sjögren's syndrome. At the age of 7 years, the patient developed a chilblain-like eruption with features of SLE, including leucopenia, oral ulcers, positive rheumatoid and antinuclear antibodies and positive anti-dsDNA, anti-Ro/SSA and anti-La/SSB antibodies. At the age of 13 years she developed Guillain-Barré syndrome, which completely resolved with aggressive treatment, including high-dose corticosteroids and the use of plasma exchange followed by intravenous gammaglobulin.

Autoantibodies↗
PubMed2000

Protective mechanisms against the intestinal nematode Strongyloides venezuelensis in Schistosoma japonicum-infected mice.

Mice infected with Schistosoma japonicum were resistant to the intestinal nematode, Strongyloides venezuelensis. The numbers of adult S. venezuelensis recovered from mice were significantly decreased when infections were given from 6 weeks after S. japonicum infection. Larval recovery from the lungs showed that significant numbers of subcutaneously inoculated S. venezuelensis larvae were eliminated by 3 days in S. japonicum-infected mice (P < 0.0001), while histology revealed that this was associated with massive eosinophilic infiltration in the lungs. In addition, adult S. venezuelensis worms implanted in the duodenum of S. japonicum-infected mice could not establish in the intestine. This failure was associated with mucosal mastocytosis. Activation of eosinophils and intestinal mast cells was correlated with elevated expression of mRNA for interleukin (IL)-3, IL-4, and IL-5 in S. japonicum-infected mice. Sera from S. japonicum-infected mice recognized S. venezuelensis larva antigens as strongly as those from S. venezuelensis-infected mice, although transfer of sera from S. japonicum-infected mice to normal recipient mice did not protect them from S. venezuelensis challenge infection. It was concluded that the mechanisms for larval killing and adult worm expulsion of S. venezuelensis in S. japonicum-infected mice were identical to those seen in infections with S. venezuelensis only.

Animals↗
PubMed2000

Genetic classification of combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (combined HCC/ CC) is a rare form of liver neoplasms showing both hepatocellular (HCC) and bile duct differentiation (CC). In an attempt to clarify the clonality and genetic/phenotypic relationships in the evolution of these neoplasms, we microdissected multiple HCC and CC foci and studied allelic status of chromosome arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. Overall, the highest frequency of loss of heterozygosity (LOH) was seen on 4q and 17p, followed by 8p and 16q. Of the 11 cases studied, 3 cases did not show any of the identical allelic losses between HCC and CC foci, indicating the biclonal nature. The remaining 8 cases showed multiple allelic losses shared between both components, strongly suggestive of a single clonal derivation. Moreover, 4 of the 8 cases showed additional or divergent allelic losses at more than 1 chromosomal locus only in HCC and/or CC foci. Thus, this heterogeneity was shown to affect the phenotypic diversity of the tumor. Summarizing the genetic patterns, combined HCC/CC could be classified into the following 3 possibilities: (1) collision tumor in which 2 independent neoplastic clones develop at close proximity; (2) single clonal tumor with homogeneous genetic background in both components--histological diversity is thus a manifestation of divergent differentiation potential of a single clone; (3) single clonal process in which genetic heterogeneity in the process of clonal evolution within the tumor parallels histologic diversity; therefore, the tumor in this category is mainly composed of mosaics of closely related subclones.

Aged↗
PubMed2000

A case of ileocolic intussusception from renal cell carcinoma.

We report a case of ileal metastasis of renal cell carcinoma (RCC) in a 58-year-old male. The patient had a history of radical nephrectomy for a right RCC, and 2 years later underwent bilateral partial pneumonectomy for metastatic disease of the lung. A period of 1 year after the partial pneumonectomy, he developed bloody stools. Colonoscopy revealed an ileocolic intussusception caused by a polypoid tumor in the ileum, and the tumor was observed to be protruding into the ascending colon. The histological features of the tumor biopsy specimen confirmed the diagnosis of metastatic RCC. Metastasis of RCC in the small bowel is a rare disease clinically. To our knowledge, this is the first reported case with ileal metastasis of RCC, which has been definitively diagnosed by colonoscopy.

Biopsy↗
PubMed2000

Epidemiology and etiology of premalignant and malignant urothelial changes.

Bladder neoplasms are common around the world. Incidences are particularly high in the Nile River Valley secondary to schistosomiasis, which is frequently associated with the development of squamous cell carcinoma similar to that of other chronic inflammatory processes of the lower urinary tract. However, elsewhere, most bladder tumors are of the urothelial (transitional) cell type. There is a marked male predominance and there are extensive racial differences. It is predominantly a neoplasm that occurs in patients aged >50 years. Urothelial carcinomas comprise two distinct diseases both biologically and molecularly: a low-grade papillary tumor which frequently recurs; and a high-grade malignancy which can present as dysplasia or carcinoma in situ, but frequently presents as invasive disease. However, epidemiological investigations of urothelial malignancies have generally not distinguished between preneoplastic and invasive neoplasms or between these two types of urothelial neoplasms. It is recommended that future studies should distinguish between these entities. The most common etiologic factor of urothelial malignancies besides schistosomiasis is cigarette smoking. In addition, numerous specific chemicals have been identified as bladder carcinogens in humans, some relating to specific occupational exposures. Bladder carcinogens include aromatic amines and amides, such as 4-aminobiphenyl, benzidine, 2-naphthylamine and phenacetin-containing analgesics, and certain cancer chemotherapeutic agents, such as phosphoramide mustards. More recently, occupational exposure to various combustion gases, such as diesel exhaust, has been related to an increased risk of developing bladder neoplasms. Also, exposure to chlorination by-products in drinking water and to arsenic has been suggested as increasing the risk of bladder neoplasia. As numerous specific chemicals appear to be related to the development of bladder tumors, various polymorphisms of enzymes involved in their metabolism have been suggested as affecting the susceptibility to their carcinogenicity. This has been particularly true with respect to the role of acetyltransferases in relation to aromatic amine carcinogenesis. Dietary influences have also been suggested as affecting bladder neoplasia susceptibility. Various heterocyclic amines generated by pyrolysis of food have been suggested as potential dietary factors increasing the risk of bladder cancer, particularly in relation to the ingestion of red meat. Despite the existence of several identifiable factors that increase or decrease the risk of bladder cancer, many patients have no known carcinogens or risk factors.

Adenocarcinoma↗
PubMed2000

Aberrant expression of p27(Kip1) is associated with malignant transformation of the rat urinary bladder epithelium.

Alteration in cell cycle regulators is considered to play an important role in carcinogenesis. In order to cast light on changes in reversible hyperplastic and irreversible tumorigenic lesions in the rat urinary bladder, expression of p27(Kip1), cyclin D1 and cyclin E proteins was sequentially compared. In the first study, 3% uracil was fed for 4 weeks to cause urinary calculi and consequent hyperplasia and papillomatosis, both regressing after withdrawal of the insult. Compared with normal bladder epithelium, in papillomatosis at week 4, the BrdU index and immunohistochemical positivities for cyclin D1 and cyclin E were significantly elevated, whereas values for p27(Kip1) tended to be reduced. One week after withdrawal of uracil, the BrdU index and positivities for cyclin D1 and cyclin E were decreased to below the control levels, while positivity for p27(Kip1) was dramatically increased, with a strong staining intensity. In a second study, rats were initiated with a bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine for 4 weeks, then fed 3% uracil for 8 weeks. During this latter period, expression of cyclin D1, cyclin E and p27(Kip1) in hyperplastic urothelium were comparable with those in the first study. One week after withdrawal of uracil, most urothelial lesions regressed, showing high p27(Kip1) and low cyclin D1 and cyclin E staining. Two weeks after uracil withdrawal, transitional cell carcinomas, with a low p27(Kip1) and high cyclin D1 and cyclin E staining pattern, could be easily distinguished from surrounding regressing epithelium. These data indicate that during regression of papillomatosis after cessation of a proliferative stimulus, expression of p27(Kip1)is elevated, accompanied by a lowering of cyclin D1 and cyclin E. In irreversible tumorous bladder lesions, on the other hand, persistent low expression of p27(Kip1) and elevated cyclin D1 and cyclin E are characteristic.

Animals↗
PubMed2000

Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone new zealand black mice.

New Zealand Black (NZB) mice spontaneously produce anti-erythrocyte autoantibodies (AEA) in association with splenomegaly, thus serving as a model for autoimmune hemolytic anemia. Although these autoimmune traits are inherited as a dominant fashion, expression in F(1) hybrids of NZB and most non-New Zealand strains is suppressed due to the contribution of wild-type modifying genes present in the latter strains. Using chromosomal microsatellite markers in the (C57BL/6 x NZB)F(1) x NZB backcross progeny, we mapped C57BL/6 modifying loci for AEA production and splenomegaly. Generation of AEA was found to be down-regulated by a combined effect of two major independently segregating dominant alleles-one linked to D7MIT30 on chromosome 7 and the other linked to D10MIT42 on chromosome 10. Splenomegaly was modified mainly by a single C57BL/6 allele linked to D4MIT58 on chromosome 4. Thus, the autoimmune hemolytic anemia in the NZB strain is under multigenic control and a combined action of not only susceptibility but also modifying alleles with suppressive activities affects the outcome of disease features in the progeny. There are potentially important candidate genes which may be linked to the regulation of AEA and splenomegaly.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

EmPLiCS: an empirical approach for structure-based design of natural peptide drugs.

The computer implementation of a peptide drug-design strategy has been developed. The system is named EmPLiCS (Empirical Peptide Ligand Construction System) according to the strategy of the system, which searches for peptide-ligand structures by referring to empirical rules that are derived from known protein 3D structures. The system was tested on several known peptide-protein complexes. The results demonstrated the ability of this system to detect key residues of peptides that are crucial for interaction with their specific proteins. The system also showed the ability to detect the main chain trace of these peptides. Some of the main chain atoms were detected even though the complete primary structures were not reproduced, suggesting that main chain structure is important in peptide-protein recognition. The results of the present study demonstrated that the empirical rules-based system can generate significant information for use in the design of natural peptide drugs.

Algorithms↗
PubMed2000

Polymorphisms of HLA-DR and -DQ genes in Japanese patients with bullous pemphigoid.

Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP-associated HLA-DR and -DQ genes among Japanese patients. We analyzed HLA-DR and -DQ genes among 23 Japanese BP patients based on the polymerase chain reaction-restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA-DRB1*04 or DRB1*1101, with significant increases in HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p < 0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA-DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.

Aged↗
PubMed2000

Immunohistochemical detection of carcinogen-DNA adducts in normal human prostate tissues transplanted into the subcutis of athymic nude mice: results with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 3,2'-dimethyl-4-aminobiphenyl (DMAB) and relation to cytochrome P450s and N-acetyltransferase activity.

Human prostate tissue transplanted into nude mice was examined immunohistochemically for DNA adducts formed after administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Positive staining for DMAB- or PhIP-DNA adducts was evident in 70-95% of both epithelial and stromal cells in human prostate xenografts. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a normal human prostate epithelial cell line (PrEC) to express both cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) mRNA, while a normal human prostate fibroblast cell line (NHPF) expressed NAT2, but not CYP1A2 mRNA. In addition, NAT2 and to a lesser extent CYP1A2 mRNAs were also found in four cases of normal human prostate tissues. The results suggest that initial activation of chemicals by liver CYP1A2 and subsequent metabolism by prostate NAT2 is a major pathway of DNA adduct formation in human prostate cells. Thus, the data suggest that human prostate has the potential to be targeted by environmental carcinogens.

Aged↗
PubMed2000

Suppressive effects of dietary genistin and daidzin on rat prostate carcinogenesis.

High intake of phytoestrogens through soybeans and their products is thought to be associated with low incidences of prostate and / or breast cancer in Asian countries. Possible chemopreventive effects of genistin or daidzin on rat prostate carcinogenesis were therefore investigated. Male F344 rats were given 10 biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks. Other groups of rats given DMAB were treated with genistin or daidzin together with a high dose of testosterone propionate (TP). Both genistin and daidzin reduced the numbers of ventral prostate carcinomas (P < 0.05), with a tendency for decrease in incidence. Invasive carcinomas which developed in the anterior prostate and seminal vesicles with TP were, however, not influenced by the two isoflavones. Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epidemiological findings.

Aminobiphenyl Compounds↗
PubMed2000

A clinicopathological study of postoperatively upgraded early squamous-cell carcinoma of the uterine cervix.

OBJECTIVE: To investigate the clinicopathological backgrounds and diagnostic problems of postoperatively upgraded early squamous-cell carcinomas of the uterine cervix. PATIENTS AND METHODS: A total of 23 patients with postoperatively upgraded early squamous-cell carcinomas who were treated at the Saitama Cancer Center during the period of January 1, 1976, through December 31, 1991, were analyzed clinicopathologically. We reexamined the Pap smears (ectocervix, endocervix), colposcopic findings, punch biopsies, and histological findings of the operative specimens. All patients were divided into one of 3 groups based on each patient's main location of the carcinoma of the cervix: Type A: ectocervical type; Type B: endocervical type; or Type C: combined (ectocervical and endocervical) type. Clinical staging of the uterine cervical carcinomas was done in accordance with the 1994 FIGO rules. RESULTS: The numbers of patients were: Type A, 2; Type B, 10; Type C, 11. Of the 23 patients, 21 (91.3%) had lesions in the endocervical portion at least. Fifteen patients (65.2%) complained of atypical vaginal bleeding. Colposcopic findings suggesting an invasive carcinoma appeared for only 6 patients (26.1%). A cytological reevaluation revealed that the endocervical findings were much stronger than the ectocervical ones in 10 (66.7%) of 15 patients whose smears of both sites could be rechecked. CONCLUSIONS: Even if the preoperative diagnosis was early cervical carcinoma, CIS or Stage Ia1, the signs of atypical vaginal bleeding suggested that the final clinical stage would be upgraded after an operation. Furthermore, when the endocervical cytological findings were much more exaggerated than the ectocervical ones, the possibility of deeply invaded endocervical lesions should be considered.

Adult↗