Biomedical subjects

Akira Hara

Publications and source records attributed to Akira Hara.

At least 19 recordsLinked to original sources

PubMed2004

Embryonic stem cells are capable of generating a neuronal network in the adult mouse retina.

The integration of embryonic stem (ES) cells as well-differentiated neuronal cells into the retinas of adult mice was investigated. ES cells were transplanted in adult mouse retinas by intravitreal injections. Neuronal differentiation of the ES cells was investigated by morphological and immunohistochemical examinations on post-operative days 5 and 30. ES cell apoptosis was examined by in situ terminal dUTP-biotin nick end labeling of DNA fragments. Differentiated ES cells growing along the retinal surface developed fine neuronal cell processes around cell nuclei and generated neuronal networks into the retinal inner plexiform layer (IPL) 30 days after transplantation. The differentiated ES cells expressed retinal and neuronal markers. Many apoptotic cells were recognized in transplanted ES cells at day 5 but not at day 30 after transplantation. ES cells may be useful for neural tissue regeneration in the adult mammalian retina.

Animals↗

PubMed2004

Overexpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signalling pathways in Chinese-hamster ovary cells.

To examine the roles of PLD (phospholipase D) in the regulation of the apoptotic process, PLD1 and PLD2 were stably overexpressed in S1P3-CHO cells [CHO (Chinese-hamster ovary) cells expressing the S1P (sphingosine 1-phosphate) receptor S1P3]. Treatment of S1P3-CHO cells with ActD (actinomycin D) induced apoptosis, as shown by the occurrence of nuclear fragmentation and the caspase-dependent proteolytic cleavage of PARP [poly(ADP-ribose) polymerase] and protein kinase Cd. Overexpression of either PLD1 or PLD2 protected S1P3-CHO cells from ActD-induced apoptosis, as demonstrated by an increased number of viable cells and inhibition of PARP and protein kinase Cd cleavage. However, in the early phase of apoptosis, ActD induced an increase in PLD activity and activation of key factors in the cell-survival signalling pathways, such as PI3K (phosphoinositide 3-kinase), Akt, p70S6K (p70 S6 kinase) and ERK (extracellular-signal-regulated kinase). Furthermore, the ActD-induced activation of these survival signalling enzymes was potentiated by overexpression of either PLD1 or PLD2. The PI3K inhibitor LY294002 inhibited the ActD-induced activation of Akt and p70S6K, and completely abolished the effects of PLD1 or PLD2, whereas inhibition of ERK activity by the MEK inhibitor U0126 had a milder effect. The ActD-induced activation of p70S6K and ERKs was blocked by 1-butanol, but not by t-butanol; similar to S1P, exogenous PLD suppressed the ActD-induced events in the apoptosis signalling pathways. These results show that, in S1P3-CHO cells, increased expression of PLDs prevents ActD-induced apoptosis by enhanced activation of the PI3K signalling pathways.

Animals↗

PubMed2003

Effect of acoustic stress on glucocorticoid receptor mRNA in the cochlea of the guinea pig.

As a first step toward elucidating the mechanism underlying the therapeutic effect of glucocorticoids on acute noise-induced hearing loss, we used semiquantitative reverse transcription polymerase chain reaction to study the level of glucocorticoid receptor (GR) mRNA in the cochlea of the guinea pig after acoustic overstimulation. The cochleas were dissected and divided into three portions (lateral portion, medial portion and modiolus). In the lateral portion, the glucocorticoid receptor mRNA level was significantly decreased 2 h after exposure to a 120 dB SPL sound and both 2 and 6 h after exposure to a 130 dB SPL sound. To determine where in the cochlea the changes in glucocorticoid receptor mRNA levels occur, in situ hybridization histochemistry was performed with digoxigenin-labeled sense and antisense RNA probes complementary to guinea pig glucocorticoid receptor mRNA. Glucocorticoid receptor mRNA was demonstrated in the spiral ligament, stria vascularis, spiral limbus and spiral ganglion. Moreover, the glucocorticoid receptor mRNA level was decreased in the spiral ligament, especially in the spiral prominence of the basal turn, 2 h after exposure to the 130 dB SPL sound. These results could imply that the therapeutic effect of glucocorticoids in the cochlea might be mediated in the spiral ligament, particularly in the spiral prominence.

Acoustic Stimulation↗

PubMed2003

Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis.

Major etiologic factors associated with human hepatocellular carcinomas (HCCs) include infection with hepatitis C (HCV) and hepatitis B virus (HBV), excess alcohol intake and aflatoxin B(1) exposure. While the G-->T p53 mutation at codon 249 has been identified as a genetic hallmark of HCC caused by aflatoxin B(1), the genetic profile associated with other etiologic factors appears to be less distinctive. In our study, we screened HCCs resulting from HCV infection (51 cases), HBV infection (26 cases) or excess alcohol intake (23 cases) for alterations in genes involved in the RB1 pathway (p16(INK4a), p15(INK4b), RB1, CDK4 and cyclin D1), the p53 pathway (p53, p14(ARF) and MDM2) and the Wnt pathway (beta-catenin, APC). Alterations of the RB1 pathway, mainly p16(INK4a) methylation, loss of RB1 expression and cyclin D1 amplification, were most common (69-100% of cases). There was a significant correlation between loss of RB1 expression and RB1 methylation. All 24 HCCs with RB1 promoter methylation lacked RB1 expression, while none of the 67 cases with RB1 expression exhibited RB1 methylation (p < 0.0001), suggesting that promoter methylation is a major mechanism of loss of RB1 expression in HCCs. Alterations of the p53 pathway consisted mostly of p53 mutations or p14(ARF) promoter methylation (20-48%). Mutations of the p53 gene were found at a similar frequency (13-15%) in all etiologic groups, without any consistent base change or hot spot. Mutations of beta-catenin were found in 13-31% of cases, while no APC mutations were detected in any of the HCCs analyzed. With the exception of only 3 of 39 cases (8%), cyclin D1 amplification and beta-catenin mutations were mutually exclusive, supporting the view that cyclin D1 is a target of the Wnt signaling pathway. Overall, the RB1, p53 and Wnt pathways were commonly affected in HCCs of different etiology, probably reflecting common pathogenetic mechanisms, i.e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection.

Biomarkers, Tumor↗

PubMed2003

Tetrahydrobiopterin is synthesized from 6-pyruvoyl-tetrahydropterin by the human aldo-keto reductase AKR1 family members.

Tetrahydrobiopterin (BH(4)) is a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase. The biosynthesis includes two reduction steps catalyzed by sepiapterin reductase. An intermediate, 6-pyruvoyltetrahydropterin (PPH(4)) is reduced to 1(')-oxo-2(')-hydroxypropyl-tetrahydropterin (1(')-OXPH(4)) or 1(')-hydroxy-2(')-oxopropyl-tetrahydropterin (2(')-OXPH(4)), which is further converted to BH(4). However, patients with sepiapterin reductase deficiency show normal urinary excretion of pterins without hyperphenylalaninemia, suggesting that other enzymes catalyze the two reduction steps. In this study, the reductase activities for the tetrahydropterin intermediates were examined using several human recombinant enzymes belonging to the aldo-keto reductase (AKR) family and short-chain dehydrogenase/reductase (SDR) family. In the reduction of PPH(4) by AKR family enzymes, 2(')-OXPH(4) was formed by 3 alpha-hydroxysteroid dehydrogenase type 2, whereas 1(')-OXPH(4) was produced by aldose reductase, aldehyde reductase, and 20 alpha-hydroxysteroid dehydrogenase, and both 1(')-OXPH(4) and 2(')-OXPH(4) were detected as the major and minor products by 3 alpha-hydroxysteroid dehydrogenases (types 1 and 3). The activities of aldose reductase and 3 alpha-hydroxysteroid dehydrogenase type 2 (106 and 35 nmol/mg/min, respectively) were higher than those of the other enzymes (0.2-4.0 nmol/mg/min). Among the SDR family enzymes, monomeric carbonyl reductase exhibited low 1(')-OXPH(4)-forming activity of 5.0 nmol/mg/min, but L-xylulose reductase and peroxisomal tetrameric carbonyl reductase did not form any reduced product from PPH(4). Aldose reductase reduced 2(')-OXPH(4) to BH(4), but the other enzymes were inactive towards both 2(')-OXPH(4) and 1(')-OXPH(4). These results indicate that the tetrahydropterin intermediates are natural substrates of the human AKR family enzymes and suggest a novel alternative pathway from PPH(4) to BH(4), in which 3 alpha-hydroxysteroid dehydrogenase type 2 and aldose reductase work in concert.

Alcohol Oxidoreductases↗

PubMed2003

Structural determinant for cold inactivation of rodent L-xylulose reductase.

L-Xylulose reductase (XR) is a homotetramer belonging to the short-chain dehydrogenase/reductase family. Human XR is stable at low temperature, whereas the enzymes of mouse, rat, guinea pig, and hamster are rapidly dissociated into their inactive dimeric forms. In order to identify amino acid residues that cause cold inactivation of the rodent XRs, we have here selected Asp238, Leu242, and Thr244 in the C-terminal regions of rodent XRs and performed site-directed mutagenesis of the residues of mouse XR to the corresponding residues (Glu, Trp, and Cys) of the human enzyme. Cold inactivation was prevented partially by the single mutation of L242W and the double mutation of L242W/T244C, and completely by the double mutation of D238E/L242W. The L242W and L242W/T244C mutants existed in both tetrameric and dimeric forms at low temperature and the D238E/L242W mutant retained its tetrameric structure. No preventive effect was exerted by the mutations of D238E and T244C, which were dissociated into their dimeric forms upon cooling. Crystallographic analysis of human XR revealed that Glu238 and Trp242 contribute to proper orientation of the guanidino group of Arg203 of the same subunit to the C-terminal carboxylate group of Cys244 of another subunit through the neighboring residues, Gln137 and Phe241. Thus, the determinants for cold inactivation of rodent XRs are Asp238 and Leu242 with small side chains, which weaken the salt bridges between Arg203 and the C-terminal carboxylate group, and lead to cold inactivation.

Animals↗

PubMed2003

Involvement of p38 mitogen-activated protein kinase in heat shock protein 27 induction in human neutrophils.

We investigated whether tumor necrosis factor-alpha (TNF-alpha) stimulates the induction of heat shock protein 27 (HSP27) in human neutrophils and the mechanism underlying this induction. In intact neutrophils, almost no HSP27 was detected. Stimulation of neutrophils by TNF-alpha increased the levels of HSP27 in the presence, but not in the absence, of cycloheximide. Reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that TNF-alpha also induced HSP27 mRNA in the presence of cycloheximide. TNF-alpha induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TNF-alpha was significantly suppressed by 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) or 4-(4-fluorophenyl)-2-(4-nitrophenyl)-5-(4-pyridyl)-1H-imidazole (PD169316); both are specific inhibitors of p38 MAP kinase, but not by 2'-amino-3'-methoxyflavone (PD098059, a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase). The accumulation of HSP27 induced by TNF-alpha plus cycloheximide was also suppressed by pretreatment with a specific protein kinase C (PKC) inhibitor. Furthermore, phorbol myristate acetate (PMA), a PKC stimulant, but not dibutyryl cyclic AMP, a protein kinase A stimulant, stimulated the accumulation of HSP27. Interestingly, SB203580 did not inhibit PMA-stimulated HSP27 induction. These results strongly suggest that TNF-alpha may act as the regulator of HSP27 induction in neutrophils. p38 MAP kinase (but not p44/p42 MAP kinase) and PKC take part in TNF-alpha-stimulated HSP27 induction in human neutrophils.

Apoptosis↗

PubMed2003

Structure-based design of inhibitors of human L-xylulose reductase modelled into the active site of the enzyme.

The program GRID was used to design potential inhibitors of human L-xylulose reductase based on a model of the holoenzyme in complex with n-butyric acid. The inclusion of phosphate or carboxylate functional groups in the ligand suggested an increase in the net binding energy of the complex up to 2.8- and 4.0-fold, respectively. This study may be useful in the development of potent and specific inhibitors of the enzyme.

Amino Acid Sequence↗

PubMed2003

Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone.

Neuroactive steroids, such as 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) and 3alpha,5alpha-tetrahydrodeoxycorticosterone have been shown to be synthesized from progesterone in animal brains. Comparison of kinetic constants for the neuroactive steroids and their precursors among four human 3(20)alpha-hydroxysteroid dehydrogenases (AKR1C1-AKR1C4) suggests that AKR1C1 and AKR1C2 are involved in the catabolism and synthesis, respectively, of the neuroactive steroids in the human brain. In our efforts to identify agents that would specifically inhibit the two enzymes, benzbromarone and 3',3",5',5"-tetrabromophenolphthalein were found to be relatively selective and potent inhibitors of AKR1C1. Kinetic analyses in the oxidoreduction catalyzed by AKR1C1 in the presence of the inhibitors suggest that the inhibitors bind to the enzyme-NADP(H) complex (K(i)=0.7 nM) in the ordered bi-bi pathway, including an isomerization step. The inhibitors effectively also decreased the reduction of 3alpha,5alpha-THP to its 20alpha-hydroxy metabolite in HepG2 cells treated with ethacrynic acid.

20-Hydroxysteroid Dehydrogenases↗

PubMed2003

Cloning, expression and tissue distribution of a tetrameric form of pig carbonyl reductase.

In this study, we isolated a cDNA for tetrameric carbonyl reductase (CR) from pig heart. The pig CR showed high amino acid sequence identity (81%) with rabbit NADP(+)-dependent retinol dehydrogenase (NDRD). The purified recombinant pig CR and NDRD were about 100-kDa homotetramers and exhibited high reductase activity towards alkyl phenyl ketones, alpha-dicarbonyl compounds and all-trans-retinal. The identity of NDRD with the tetrameric CR was verified by protein sequencing of CR purified from rabbit heart. Both tetrameric CR and its mRNA were ubiquitously expressed in pig and rabbit tissues. The pig and rabbit enzymes belonged to the short-chain dehydrogenase/reductase family, and their sequences comprise a C-terminal SRL tripeptide, which is a variant of the type 1 peroxisomal targeting signal, SKL. Transfection of HeLa cells with vectors expressing pig CR demonstrated that the enzyme is localized in the peroxisomes. Thus, the tetrameric form of CR represents the first mammalian peroxisomal enzyme that reduces all-trans-retinal as the endogenous substrate.

Alcohol Oxidoreductases↗

PubMed2003

Identification of amino acid residues involved in substrate recognition of L-xylulose reductase by site-directed mutagenesis.

L-Xylulose reductase (XR) catalyzes the oxidoreduction between xylitol and L-xylulose in the uronate cycle. The enzyme has been shown to be identical to diacetyl reductase, an enzyme that reduces alpha-dicarbonyl compounds. XR belongs to the short-chain dehydrogenase/reductase family, and shows high sequence identity with mouse lung carbonyl reductase (MLCR), an enzyme that reduces 3-ketosteroids but not sugars. In this study, we have confirmed the roles of Ser136, Tyr149 and Lys153 of XR as the catalytic triad by drastic loss of activity resulting from the mutagenesis of S136A, Y149F and K153M in rat XR. We have also constructed several mutant XRs, in which putative substrate binding residues from rat XR were substituted with those found in the corresponding positions of MLCR, in order to identify amino acids responsible for the different substrate recognition of the enzymes. While single mutants at positions 137, 143, 146, 190 and 191 caused little or moderate change in substrate specificity, a double mutant (N190V and W191S) and triple mutant (Q137M, L143F and H146L) resulted in almost loss of activity for only the sugars. In addition, the triple mutant exhibited 3-ketosteroid reductase activity, which was further enhanced by quintuple mutagenesis of the above five residues. These results suggest the importance of the size and hydrophobicity of the five residues for substrate recognition by XR and MLCR. Furthermore, the mutant enzymes containing a Q137M mutation were stable against cooling, which provides a structural mechanism of the cold inactivation that is a characteristic of the rodent XR.

Aldehyde Reductase↗

PubMed2003

Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphoinositide 3-kinase or Akt, in Chinese hamster ovary cells.

Available evidence suggests the involvement of phospholipase D (PLD) in cell proliferation and survival. Phosphoinositide 3-kinase (PI 3-kinase)/Akt and extracellular signal-regulated kinases (ERKs) are signalling molecules that have essential roles in cell proliferation and survival. We previously demonstrated that sphingosine 1-phosphate (S1P)-induced PLD activation via the G-protein-coupled receptor endothelial differentiation gene (EDG) 3/S1P(3) was involved in S1P-induced stimulation of PI 3-kinase and Akt. In the present study, we examined the involvement of two PLD isozymes, PLD1 and PLD2, in insulin-like growth factor (IGF)-I receptor tyrosine kinase-mediated stimulation of PI 3-kinase/Akt and ERKs. IGF-I and to a lesser degree S1P stimulated PI 3-kinase activity in Chinese hamster ovary cells overexpressing EDG3/S1P(3). IGF-I-induced ERK phosphorylation was suppressed by butan-1-ol, but not butan-2-ol, whereas no effect of butanol was observed in IGF-I-induced Akt activation in S1P(3)-overexpressing Chinese hamster ovary cells. Overexpression of wild-type PLD1 and PLD2 substantially potentiated S1P-, but not IGF-I-, induced activation of PI 3-kinase and Akt, whereas overexpression of the catalytically inactive mutant of PLD1 or PLD2 did not affect the responses to either agonist. On the other hand, overexpression of wild-type PLD1 and PLD2 potentiated IGF-I- and, to much smaller extents, S1P-induced ERK stimulation. ERK activation by IGF-I as well as S1P was dependent on Ras, but Akt activation by IGF-I was not dependent on Ras. These results suggest that PLDs are involved in growth factor regulation of at least two signalling pathways, PI 3-kinase/Akt and ERKs, depending on the class of cell-surface receptors.

Animals↗

PubMed2003

Glucocorticoids and dehydroepiandrosterone sulfate ameliorate ischemia-induced injury of the cochlea.

This study aimed to evaluate the effects of steroidal drugs on the functional recovery of the cochlea after transient ischemia. Albino guinea pigs were subjected to transient cochlear ischemia of 30 min duration, and the threshold shifts of the compound action potential (CAP) from the pre-ischemic values were evaluated 4 h after ischemia. Pre-ischemic administration of a glucocorticoid, prednisolone or methylprednisolone, significantly ameliorated the post-ischemic CAP threshold shifts as compared with control animals at a relatively wide range of doses. Post-ischemic administration of these glucocorticoids also exhibited protective effects. Pre-ischemic administration of dehydroepiandrosterone sulfate significantly decreased the post-ischemic CAP threshold shifts 4 h after ischemia. The present results indicate that glucocorticoids and dehydroepiandrosterone sulfate possess therapeutic effects against ischemic injury of the cochlea, such as idiopathic sudden sensorineural hearing loss.

Action Potentials↗

PubMed2003

Nevoid basal cell carcinoma syndrome: report of an aggressive case with ethmoid sinus invasion.

Nevoid basal cell carcinoma syndrome, also referred to as Gorlin-Goltz syndrome, is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar or plantar pits, ectopic calcification of the falx cerebri, and various skeletal developmental abnormalities. A minority of basal cell carcinomas demonstrate aggressive behavior and involve the craniofacial bones in nevoid basal cell carcinoma syndrome. A non-familial case of nevoid basal cell carcinoma syndrome with a basal cell carcinoma of the eyelid invading to the ethmoid sinus is reported.

Aged↗

PubMed2003

Carcinoid tumor in the female urethral orifice: rare case report and a review of the literature.

We experienced an extremely rare tumor in the female urethral orifice in a 57-year-old Japanese woman. To our knowledge, only two cases of primary urethral carcinoid tumor have been reported. The previous reports of urethral carcinoid tumor were recognized in the male middle urethra and penile urethra. The present case was resected, and diagnosed as a carcinoid tumor by histological, immunohistochemical and ultrastructural findings. The tumor cells were stained by chromogranin A, synaptophsin and neuron-specific enolase, and neurosecretory granules were confirmed with electron microscopy. The patient did not complain of any symptoms until 5 years after the resection of the tumor. Therefore, the case we describe here is the first known report of carcinoid tumor in the Japanese female urethra.

Biomarkers, Tumor↗

PubMed2003

Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells.

Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelial dysfunction in diabetes. To clarify whether glucose-modified HDL affects the function of endothelial cells, we first examined herein the level of H(2)O(2) generation from cultured human aortic endothelial cells (HAECs) exposed to a glycated oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation for 48 hours with 100 microg/mL of gly-ox-HDL induced significant release of H(2)O(2) from cells and gly-ox-HDL-induced H(2)O(2) formation was inhibited in the presence of diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, stimulation of HAECs with gly-ox-HDL for 48 hours elicited a marked downregulation of catalase and Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD), suggesting H(2)O(2) formation by gly-ox-HDL to be due to a disturbance involving oxidant and antioxidant enzymes in the cells. Treatment of HAECs with gly-ox-HDL attenuated the expression of endothelial nitric oxide synthase (eNOS), but not inducible nitric oxide synthase (iNOS), and this was followed by decreased production of nitric oxide (NO) by the cells. Furthermore, in vitro experiments with glycated HDL (gly-HDL) in the presence of 2 mmol/L EDTA and Cu(2+)-oxidized HDL suggested the effect of gly-HDL on endothelial function to be possibly potentiated by additional oxidative modification. Taking all of the above findings together, gly-ox-HDL may lead to the deterioration of vascular function through altered production of reactive oxygen species and reactive nitrogen species in endothelial cells.

Blotting, Western↗

PubMed2003

beta-Catenin mutation is selected during malignant transformation in colon carcinogenesis.

Activating mutations in the beta-catenin gene is thought to be responsible for the excessive beta-catenin signaling involved in the majority of colon carcinomas in rodent models. Our recent study which indicated that beta-catenin mutations are present frequently in early dysplastic lesions of rat colon induced by a colon-specific carcinogen, azoxymethane led us to perform more specifically a comparative study regarding types of the beta-catenin mutation as well as K-ras mutations between such early appearing lesions and colon tumors. Male F344 rats, 6 weeks old, received s.c. injections of azoxymethane (15 mg/kg body weight) once a week for 3 weeks, and were killed at 16 and 46 weeks of age. Colons of animals killed at 16 weeks of age were processed for early altered lesions. Colon tumors from animals killed at 46 weeks of age were evaluated histopathologically. Laser capture microdissection system was used to obtain DNA of epithelial cells in both intramucosal lesions and colon tumors. After amplification of exon 3 of the beta-catenin gene and exon 1 of the K-ras gene, the products were then sequenced directly in both directions. Mutations in the exon 3 of beta-catenin gene were detected in 22 of 56 early lesions (39.3%) and 21 of 37 colon cancers (56.8%). Remarkably, all beta-catenin mutations detected in the colon tumors converged at codons encoding functionally important residues that may directly mediate beta-catenin degradation, whereas mutations in the early appearing lesions were found to be scattered in the exon 3 of the gene. K-ras mutations were also detected in 24 of 56 early lesions (42.9%) and 11 of 37 colon cancers (29.7%). All K-ras mutations converged at codon 12 and codon 13, even in the early lesions. The results of this study provide evidence for the first time that beta-catenin mutation is selected during the colon carcinogenesis. Our results also suggest that the activation of beta-catenin signaling pathway is not only an initiating event, but also plays a pivotal role in the promotion stage of colorectal carcinogenesis.

Animals↗

PubMed2003

Structures of the mating-type loci of Cordyceps takaomontana.

Nucleotide sequences of the mating-type loci MAT1-1 and MAT1-2 of Cordyceps takaomontana were determined, which is the first such report for the clavicipitaceous fungi. MAT1-1 contains two mating-type genes, MAT1-1-1 and MAT1-1-2, but MAT1-1-3 could not be found. On the other hand, MAT1-2 has MAT1-2-1. A pseudogene of MAT1-1-1 is located next to MAT1-2.

Base Sequence↗