Shirakawa T

References (9)

Title : Genetic polymorphisms and lung cancer susceptibility: a review - Kiyohara_2002_Lung.Cancer_37_241
Author(s) : Kiyohara C , Otsu A , Shirakawa T , Fukuda S , Hopkin JM
Ref : Lung Cancer , 37 :241 , 2002
Abstract : Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Cigarette smoking is an established risk factor for lung cancer although a possible role for genetic susceptibility in the development of lung cancer has been inferred from familial clustering of the disease and segregation analyzes. Everyone may have a unique combination of polymorphic traits that modify genetic susceptibility and response to drugs, chemicals and carcinogens. Developments in molecular biology have led to growing interest in investigation of biological markers, which may increase predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an individual could be determined easily. As there are the great number of carcinogen-activating and -detoxifying enzymes, the variation in their expression and the complexity of exposures to tobacco carcinogens, the existence of multiple alleles at loci of those enzymes may result in differential susceptibilities of individuals. This review summarize data addressing the relationships of lung cancer to markers of genetic susceptibility genes, including metabolic polymorphisms other than well-investigated cytochrome P450s or glutathione S-transferases, DNA repair genes and the p53 tumor suppressor gene. Among genetic polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His) were significantly associated with lung cancer risk. As lung cancer is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for lung cancer. Hopefully, in the future we will be able to screen for lung cancer susceptibility by using specific biomarkers.
ESTHER : Kiyohara_2002_Lung.Cancer_37_241
PubMedSearch : Kiyohara_2002_Lung.Cancer_37_241
PubMedID: 12234692

Title : The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma - Kruse_2000_Am.J.Hum.Genet_66_1522
Author(s) : Kruse S , Mao XQ , Heinzmann A , Blattmann S , Roberts MH , Braun S , Gao PS , Forster J , Kuehr J , Hopkin JM , Shirakawa T , Deichmann KA
Ref : American Journal of Human Genetics , 66 :1522 , 2000
Abstract : The platelet-activating factor (PAF) represents a phospholipid with complex biological functions, including involvement in inflammatory processes. The degrading enzyme PAF acetylhydrolase (PAFAH) represents a candidate for asthma and other atopic diseases. Two loss-of-function mutations of PAFAH are associated with severe asthma in Japanese individuals. Our aim was to look for further PAFAH variants in white populations, their possible association with atopic and asthmatic phenotypes, and their functional importance. We picked up three common variants in the PAFAH gene: Arg92His (exon 4), Ile198Thr (exon 7), and Ala379Val (exon 11). The known loss-of-function mutations were not seen. The variant allele Thr198 was found to be highly associated with total IgE concentrations in an atopic population (P=.009) and with "atopic asthma" in an asthmatic population (P=.008). The variant allele Val379 was found to be highly associated with "specific sensitization" in the atopic population (P=.002) and with "asthma" in the asthmatic population (P=.003). By use of recombinant PAFAH enzymes, the variant Val379 showed increased (14 microM) and Thr198 markedly increased (42 microM) KM values compared to the wild type (7 microM); furthermore, Vmax of Val379 was highly increased (132%). Thr198 and Val379 influence plasmatic PAFAH toward lower substrate affinities and therefore are very likely to prolong the activities of PAF. At the same time, they are associated with an increased risk to develop asthma and atopy. Thus, two PAFAH variants seem to play a key role in atopic and asthmatic processes in Caucasian populations.
ESTHER : Kruse_2000_Am.J.Hum.Genet_66_1522
PubMedSearch : Kruse_2000_Am.J.Hum.Genet_66_1522
PubMedID: 10733466
Gene_locus related to this paper: human-PLA2G7

Title : Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157-associated hemolytic uremic syndrome - Xu_2000_Am.J.Kidney.Dis_36_42
Author(s) : Xu H , Iijima K , Shirakawa T , Shiozawa S , Miwa M , Yamaoka K , Kawamura N , Nakamura H , Yoshikawa N
Ref : Am J Kidney Dis , 36 :42 , 2000
Abstract : Platelet-activating factor (PAF) may be involved in the pathogenesis of Escherichia coli O157-associated hemolytic uremic syndrome (HUS). PAF is degraded to inactive products by PAF acetylhydrolase. In this study, we investigated whether a PAF acetylhydrolase gene mutation (G-->T transversion at position 994) is involved in HUS in Japanese children. A point mutation in the PAF acetylhydrolase gene (G994T) was identified using polymerase chain reaction in 50 Japanese children with E coli O157-associated HUS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G994T gene mutation and clinical features of HUS. There was no difference in genotype and allele frequencies between patients with HUS and healthy controls. The mean duration of oligoanuria was significantly longer in patients with the GT genotype than in those with the GG genotype (P = 0.012). Although 11 of 15 patients (73%) heterozygous for the mutant allele (GT) required dialysis, only 13 of the 35 wild-type homozygotes (GG; 37%) required dialysis (P = 0. 030). Mean plasma PAF acetylhydrolase activity was significantly less in patients with the GT genotype than in those with the GG genotype (P < 0.0001). In conclusion, we have shown an association between the G994T PAF acetylhydrolase gene mutation and the severity of renal damage in E coli O157-associated HUS. Our study suggests that analysis of the PAF acetylhydrolase gene mutation in Japanese children with E coli O157-associated HUS may allow the prediction of the severity of HUS.
ESTHER : Xu_2000_Am.J.Kidney.Dis_36_42
PubMedSearch : Xu_2000_Am.J.Kidney.Dis_36_42
PubMedID: 10873870
Gene_locus related to this paper: human-PLA2G7

Title : Role of platelet-activating factor acetylhydrolase gene mutation in Japanese childhood IgA nephropathy - Tanaka_1999_Am.J.Kidney.Dis_34_289
Author(s) : Tanaka R , Iijima K , Xu H , Inoue Y , Murakami R , Shirakawa T , Nishiyama K , Miwa M , Shiozawa S , Nakamura H , Yoshikawa N
Ref : Am J Kidney Dis , 34 :289 , 1999
Abstract : Platelet-activating factor (PAF) is a potent mediator of inflammatory injury in renal diseases. PAF is degraded to inactive products by PAF acetylhydrolase. Recently, a point mutation (G to T transversion) of the PAF acetylhydrolase gene was observed at position 994, and this mutation was found to contribute to the variability in plasma PAF levels, with undetectable plasma PAF acetylhydrolase activity occurring in homozygous patients (TT genotype) and reduced levels of activity in heterozygous patients (GT genotype). Therefore, we investigated the effect of the PAF acetylhydrolase gene mutation on the pathogenesis and progression of immunoglobulin A (IgA) nephropathy. Genomic DNA was obtained from 89 children with IgA nephropathy and 100 controls. We identified the PAF acetylhydrolase gene mutation (G994T) by polymerase chain reaction. There was no significant difference in genotypic frequency between patients and controls. However, urinary protein excretion at the time of biopsy was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. The percentage of glomeruli with mesangial cell proliferation was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. These results indicate the PAF acetylhydrolase gene mutation may influence the degree of proteinuria and the extent of mesangial proliferation in the early stage of childhood IgA nephropathy.
ESTHER : Tanaka_1999_Am.J.Kidney.Dis_34_289
PubMedSearch : Tanaka_1999_Am.J.Kidney.Dis_34_289
PubMedID: 10430976
Gene_locus related to this paper: human-PLA2G7

Title : Platelet-activating factor acetylhydrolase gene mutation in Japanese nephrotic children - Xu_1998_Kidney.Int_54_1867
Author(s) : Xu H , Iijima K , Shiozawa S , Tanaka SS , Inoue Y , Shirakawa T , Nishiyama K , Miwa M , Nakamura H , Yoshikawa N
Ref : Kidney Int , 54 :1867 , 1998
Abstract : BACKGROUND: Platelet-activating factor (PAF) may be involved in the pathogenesis of steroid-responsive nephrotic syndrome (SRNS). PAF is degraded to inactive products by PAF acetylhydrolase. We have investigated whether PAF acetylhydrolase gene mutation is involved in SRNS in Japanese children.
METHODS: We identified a point mutation in the PAF acetylhydrolase gene (G994T) using the polymerase chain reaction in 101 Japanese children with SRNS and 100 healthy Japanese.
RESULTS: There was no difference in the genotype and allele frequencies between patients with SRNS and normal controls. The mean number of relapses during the first year after onset was significantly higher in the 26 patients who were heterozygous for the mutant allele (GT) than in 75 wild-type homozygotes (GG) (2.61 +/- 1.98 vs. 1.33 +/- 1.35; P = 0.0019).
CONCLUSIONS: We conclude that analysis of the PAF acetylhydrolase gene mutation at position 994 in Japanese children with SRNS allows the identification of patients who are more likely to have a disease relapse.
ESTHER : Xu_1998_Kidney.Int_54_1867
PubMedSearch : Xu_1998_Kidney.Int_54_1867
PubMedID: 9853251
Gene_locus related to this paper: human-PLA2G7

Title : Synergism between cellular messengers and agonist combinations in pepsinogen secretion - Matsumoto_1987_Am.J.Physiol_253_G557
Author(s) : Matsumoto H , Dickinson KE , Shirakawa T , Komiyama K , Hirschowitz BI
Ref : American Journal of Physiology , 253 :G557 , 1987
Abstract : The esophagus of Rana catesbeiana yielded 20-40 X 10(6) peptic cells that were greater than 80% pure by immunostaining, greater than 90% viable, and had low basal pepsinogen and lactic dehydrogenase (LDH) release. Cellular responses to agents that bypass receptors and act directly on cell messenger systems have been compared with receptor-mediated activation. Pepsinogen secretion was stimulated dose dependently by A23187, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), and forskolin. The combination of any two or all three agents at optimum effective concentrations stimulated secretion to more than double the output of the sum of the individual responses. Incubation in Ca2+-free media reduced responses to A23187 and TPA but not forskolin. Ca2+ deprivation eliminated the synergism of messenger combinations. Secretory responses to combinations of the agonists bethanechol or bombesin with either A23187 or TPA were additive and were synergistic with forskolin. Isoproterenol plus bethanechol or bombesin produced synergistic responses that were significantly smaller than combinations of their putative messengers. The synergistic response to isoproterenol and bethanechol was dependent on extracellular Ca2+. These data suggest that although Ca2+ may function in peptic cells to stimulate secretion directly, it may also act as a gain control for synergistic interaction between other messenger pathways (protein kinase a and c).
ESTHER : Matsumoto_1987_Am.J.Physiol_253_G557
PubMedSearch : Matsumoto_1987_Am.J.Physiol_253_G557
PubMedID: 2444114

Title : Cellular messengers of stimulants of pepsinogen secretion from isolated frog esophageal mucosa - Shirakawa_1986_Am.J.Physiol_250_G361
Author(s) : Shirakawa T , Hirschowitz BI
Ref : American Journal of Physiology , 250 :G361 , 1986
Abstract : The messenger roles of Ca2+ and cyclic nucleotides in the stimulation of pepsinogen secretion by three classes of stimuli [muscarinic (bethanechol), peptidergic (bombesin), and adrenergic (isoproterenol)] were studied in vitro using the peptic gland-bearing esophageal mucosa from the American bullfrog, Rana catesbeiana. Pepsinogen secretion was stimulated in a dose-dependent manner by the calcium ionophore A23187, by dibutyryl cAMP (DBcAMP), and by isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor. Isoproterenol and bethanechol increased the tissue cAMP content in the presence of IBMX. IBMX, which by itself stimulated secretion, was potentiating in combination with bombesin, additive with bethanechol, and less than additive with isoproterenol. Omission of Ca2+ from the bathing medium did not alter basal pepsinogen secretion nor the response to maximally effective doses of isoproterenol but partly inhibited the secretory responses to bethanechol and bombesin. Ca2+-free medium with 1 mM EGTA reduced pepsinogen secretion under all basal and stimulated (including A23187- but not DBcAMP-stimulated) conditions, indicating a critical role for Ca2+ in the secretion of pepsinogen secretion. A23187 by itself produced only an initial (15-20 min) release of pepsinogen, whereas IBMX and DBcAMP produced a delayed sustained secretion. The combination of A23187 with either IBMX or DBcAMP mimicked the responses to bethanechol or bombesin. These results indicate that both calcium and cAMP may be obligatory and interacting intermediates in the full stimulation of pepsinogen secretion by frog esophageal peptic glands with at least cholinergic and peptidergic stimuli.
ESTHER : Shirakawa_1986_Am.J.Physiol_250_G361
PubMedSearch : Shirakawa_1986_Am.J.Physiol_250_G361
PubMedID: 2420209

Title : Seasonal fluctuations in pepsinogen secretion from frog esophageal peptic glands - Shirakawa_1986_Am.J.Physiol_250_G484
Author(s) : Shirakawa T , Hirschowitz BI
Ref : American Journal of Physiology , 250 :G484 , 1986
Abstract : The seasonal activity of pepsinogen secretion in the Rana catesbeiana was studied by use of peptic gland bearing esophageal mucosa mounted in a perfused double chamber. The amount of the basal pepsinogen secretion during hibernation (winter) and breeding (spring) periods was approximately 25 and 55% of basal secretion during the active (summer) period. The circumannual variation of basal secretion was highly correlated (r = 0.88, n = 37) with the pepsinogen content of the mucosa. The fractional rate of basal secretion (approximately 2% of content per hour) remained essentially constant, and pepsinogen as a fraction of total protein remained at between 20 and 25%. The results indicate that the decrease in absolute basal secretion from frog peptic glands during winter is a consequence of decreased content and hence synthesis of protein, including pepsinogen, by the mucosa. In addition, stimulated secretory responses to both bethanechol and bombesin, as a multiple of basal rate, were reduced during both hibernation and breeding periods, whereas the response to isoproterenol was entirely abolished during the hibernation period. By contrast, the secretory response to isobutylmethylxanthine remained constant (approximately 200% of basal) through all seasons, suggesting that mechanisms responsible for enzyme translocation and secretion remained intact. Reduced basal and secretagogue-stimulated secretion during hibernation and breeding seasons is thus likely due to a combination of reduced protein synthesis and decreased number or function of agonist receptors in peptic cells of the frog.
ESTHER : Shirakawa_1986_Am.J.Physiol_250_G484
PubMedSearch : Shirakawa_1986_Am.J.Physiol_250_G484
PubMedID: 2421586

Title : Interaction between stimuli and their antagonists on frog esophageal peptic glands - Shirakawa_1985_Am.J.Physiol_249_G668
Author(s) : Shirakawa T , Hirschowitz BI
Ref : American Journal of Physiology , 249 :G668 , 1985
Abstract : The peptic glands, which are located in the mucosa of the distal esophagus in the frog, respond to multiple stimuli. In vitro studies were performed, using mucosal sheets of the esophagus of Rana catesbeiana, during the summer months when the glands are fully responsive to determine whether the receptors for the stimuli [cholinergic, beta-adrenergic, and peptidergic (bombesin but not cholecystokinin)] are specific to the stimuli. Through the use of three classes of antagonist, we found that 1) atropine defined the muscarinic nature of the bethanechol stimulation, 2) propranolol defined the beta-adrenergic nature of stimulation by isoproterenol, and 3) the substance P analogue [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P was specific for the peptide bombesin. No cross-inhibition was seen, and dibutyryl cGMP did not inhibit any of the three stimuli. Moreover, any two of the three stimuli in combination stimulated more pepsinogen than either alone but the same as the sum of the two individual responses. Both lines of evidence indicate that there are at least three independent receptor pathways for stimulation of pepsinogen secretion in these glands.
ESTHER : Shirakawa_1985_Am.J.Physiol_249_G668
PubMedSearch : Shirakawa_1985_Am.J.Physiol_249_G668
PubMedID: 2417491