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T Kurahashi

Publications and source records attributed to T Kurahashi.

At least 19 recordsLinked to original sources
PubMed2006

BRAF mutations and phosphorylation status of mitogen-activated protein kinases in the development of flat and depressed-type colorectal neoplasias.

Although some molecular differences between flat-depressed neoplasias (FDNs) and protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF mutations or the status of phosphorylated mitogen-activated protein kinase (p-MAPK) are different between theses two groups. We evaluated the incidence of BRAF and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the immunohistochemical status of p-MAPK in the nonserrated neoplasias (46 FDNs and 57 PNs). BRAF mutations were detected in four FDNs (9%) and none of PNs (P=0.0369 by Fisher's exact test). KRAS mutations were observed in none of FDNs and in 14 PNs (25%; P=0.0002 by Fisher's exact test). MSI-H was detected in seven out of 44 FDNs (16%) and in one out of 52 of PNs (2%) (P=0.022 by Fisher's exact test). Type B and C immunostaining for p-MAPK was observed in 34 out of 46 FDNs (72%), compared with 24 out of 55 PNs (44%; P=0.0022 by chi(2) test). There was no significant difference in the type B and C immunostaining of p-MAPK between FDNs with and without BRAF mutations. BRAF and KRAS mutations are mutually exclusive in the morphological characteristics of colorectal nonserrated neoplasia. Abnormal accumulation of p-MAPK protein is more likely to be implicated in the tumorigenesis of FDNs than of PNs. However, this abnormality in FDNs might occur via the genetic alteration other than BRAF or KRAS mutation.

Adenocarcinoma↗
PubMed2004

Pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth.

We sought to clarify pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth. Colorectal carcinomas resected at Showa University Hospital in Tokyo included 86 with characteristics of polypoid growth (PG) and 21 with those of nonpolypoid growth (NPG). Mutations of APC, Ki-ras, and p53 genes, as well as microsatellite instability (MSI), were analysed using fluorescence-based polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). Carcinomas with an NPG pattern were smaller than PG tumours (P<0.0001). Carcinomas with a PG pattern were more likely to harbour Ki-ras mutations (36%) than NPG tumours (0%; P<0.0001). Mutation types in the APC gene differed significantly between PG and NPG carcinomas (P=0.0189), including frameshift mutations in 66% of PG carcinomas but no NPG carcinomas. Presence of a p53 mutation at a 'hot spot' also was more likely in PG carcinomas (37%) than in NPG carcinomas (0%; P=0.0124). No significant difference in presence of MSI was evident between carcinomas with PG and NPG patterns. In conclusion, significant genetic differences were evident between carcinomas with PG and NPG patterns. Genetic changes in NPG carcinomas differed from those of the conventional adenoma-carcinoma sequence. Assuming that some nonpolypoid growth lesions transform rapidly into advanced carcinomas, 20% of all colorectal carcinomas may progress in this manner.

Adult↗
PubMed2004

Study of hot electrons by measurement of optical emission from the rear surface of a metallic foil irradiated with ultraintense laser pulse.

Hot electrons and optical emission are measured from the rear surface of a metallic foil. The spectra of the optical emission in the near infrared region have a sharp spike around the wavelength of the incident laser pulse. The optical emission is ascribed to coherent transition radiation due to microbunching in the hot electron beam. It is found that the optical emission closely correlates with the hot electrons accelerated in resonance absorption.

Journal Article↗
PubMed2003

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus.

We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

Adult↗
PubMed2001

Tumor imprint cytology of ovarian ependymoma. A case report.

BACKGROUND: Ependymoma is a tumor that usually develops in the central nervous system and is extremely rare in the ovary. The first case of ovarian ependymoma was reported by Kleinman et al. (Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol 1984;15:632-8.) in 1984, and only eight cases have been reported since then. Criteria for the histopathologic diagnosis of ependymoma are already established, but there has been no investigation of the cytologic diagnosis of ovarian ependymoma. METHODS: An imprint cytologic specimen was obtained from a recurrent ovarian ependymoma. The imprint cytologic features were compared with the findings of histologic examination, immunostaining, and electron microscopy. RESULTS: Imprint cytology revealed clusters of small cells with tapering cytoplasmic processes and a round nucleus. On the basis of these features, a neurogenic tumor could be included in the differential diagnosis. Furthermore, many rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes, characteristic of ependymoma, were found. The presence of ependymal rosettes and perivascular pseudorosettes also were confirmed by the histopathologic examination. Together with positive immunostaining for glial fibrillary acidic protein, this led to the diagnosis of ependymoma, which also was supported by the electron microscopic findings. CONCLUSIONS: Careful observation of the imprint cytologic specimen of an ovarian ependymoma should reveal numerous rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes. In addition, if we remember that ependymoma can develop in the ovary and find cells with tapering processes that suggest a neurogenic tumor, it may be possible to detect histologic features characteristic of ependymoma by the imprint cytology. To our knowledge, this is the first report on the imprint cytologic diagnosis of ependymoma originating in the ovary.

Adult↗
PubMed2001

Extensive investigations on oxidized amino acid residues in H(2)O(2)-treated Cu,Zn-SOd protein with LC-ESI-Q-TOF-MS, MS/MS for the determination of the copper-binding site.

The ESI (electrospray ionization)-Q-TOF (tandem quadrupole/orthogonal-acceleration time-of-flight) mass spectrometer combined with the nano-HPLC (high performance liquid chromatography) system was utilized to pinpoint the Cu-binding site in Cu,Zn-SOD (superoxide dismutase) protein. Cu,Zn-SOD was treated with hydrogen peroxide, intended to specifically oxidize histidine residues coordinated to the copper ion as a mass spectrometric probe. The oxidized Cu,Zn-SOD was then fragmented with the successive treatment of endoproteinase Asp-N and DTT (dithiothreitol). Separation of the peptide mixture with the nano-HPLC and the on-line ESI-Q-TOF MS analysis revealed that only two peptide fragments were oxidized to a significant extent. Further analyses of oxidized peptide fragments with LC-ESI-Q-TOF-MS/MS disclosed that three out of four Cu-coordinated histidine residues were specifically oxidized by action of a redox-active copper ion and hydrogen peroxide, demonstrating the copper-catalyzed oxidation of amino acid ligands could be a versatile tool for the mass spectrometric determination of the copper-binding site. In addition, proline and valine residues in the proximity of the Cu ion were found to be oxidized upon H(2)O(2) treatment.

Amino Acid Sequence↗
PubMed2001

Physiology of morphologically identified cells of the bullfrog fungiform papilla.

Voltage-gated ionic current and the response to quinine were studied on the four types of morphologically identified taste cells of the bullfrog fungiform papilla by whole-cell patch clamp recording with a Lucifer yellow-filled pipette. Dye-coupled type Ia cells (mucous cells) did not show voltage-activated currents. Type Ib cells (wing cells) characterized by the fin-like processes, type II cells (rod cells) having a thick straight dendrite running to the surface and type III cells with a thin dendrite had voltage-gated sodium (INa) and potassium currents (IK) and generated action potentials. The amplitude of INa was significantly larger in type Ib and II cells than in type III cells. Type Ib and II cells responded to quinine but Type III cells did not.

Action Potentials↗
PubMed2001

Primary ependymoma of the ovary, in which long-term oral etoposide (VP-16) was effective in prolonging disease-free survival.

BACKGROUND: Ovarian ependymoma is an extremely unusual teratoma of the ovary with only eight cases previously reported in the literature worldwide. CASE: A 26-year-old woman presented in 1992 with a sensation of abdominal fullness. The laparotomy revealed ovarian cancer (stage III), which proved to be an ependymoma pathologically. Three courses of the PVP regimen (cisplatin, vinblastine, peplomycin) and pelvic irradiation were administered postoperatively. Oral administration of etoposide (VP-16) was initiated after the residual tumor began to proliferate, and the tumor decreased in size and never regrew during etoposide administration for a total of 5 years and 8 months. The recurrent tumor was observed soon after the drug was discontinued. CONCLUSION: Oral administration of etoposide was effective in prolonging disease-free survival.

Administration, Oral↗
PubMed2001

Prognostic value of p53 mutations in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy.

PURPOSE: A significant correlation has been found between p53 mutation and response to chemotherapy or radiotherapy. To determine the prognostic value of p53 mutation in patients with locally advanced esophageal carcinoma treated with definitive chemoradiotherapy, p53 mutation was analyzed using the biopsied specimens taken for diagnosis. METHODS: Concurrent chemoradiotherapy was performed for 40 patients with severe dysphagia caused by esophageal squamous cell carcinoma associated with T3 or T4 disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil, combined with an infusion of cisplatinum. Radiation treatment of the mediastinum was administered concomitantly with chemotherapy. The p53 gene mutation was detected by fluorescence-based polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) methods. DNA sequences were determined for DNA fragments with shifted peaks by SSCP methods. RESULTS: Of the 40 patients, 15 had T3 disease and 25 had T4 disease; 11 patients had M1 lymph node (LYM) disease. Of the 40 patients, 13 (33%) achieved a complete response. The median survival time was 14 months, and the 2-year survival rate was 20%. Among the 40 tumor samples, p53 mutation was detected in 24 tumors (60%). The survival rate in the 24 patients with p53 mutation did not differ significantly from that in the 16 patients without p53 mutation. In contrast, the 15 patients with T3 disease survived longer than the 25 patients with T4 disease (P = 0.016); however, the survival rate in the 11 patients with M1 LYM disease did not differ significantly from that in the 29 patients without M1 LYM disease. CONCLUSION: Concurrent chemoradiotherapy is potentially curative for locally advanced esophageal carcinoma, but p53 genetic abnormality has no impact on prognosis.

Aged↗
PubMed2001

Case report of serous ovarian tumor of borderline malignancy (Stage Ic) in a pregnant woman.

We encountered a case of Stage Ic ovarian serous borderline malignancy in the first trimester of pregnancy. At laparotomy, spontaneous rupture of the capsule and a small amount of serous ascites was observed. Because of the laparotomy during pregnancy, correct staging of the tumor might not be performed. This case presented a major problem in deciding the treatment strategy, which are reported here together with some discussion of the literature on the preservation of fertility in borderline ovarian malignancy.

Adult↗
PubMed2001

[A case of esophageal carcinoma with multiple liver metastases successfully treated with nedaplatin (NDP) and 5-fluorouracil (5-FU) combined with radiotherapy].

A 78-year-old male patient had esophageal carcinoma with multiple liver metastases. Chemoradiotherapy was performed. The chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU), combined with infusion of nedaplatin (NDP). Radiation of the mediastinum was administered concomitantly with chemotherapy. The patient showed a complete response (CR) of the primary lesion and a partial response (PR) of the liver metastasis for 11 months. Since liver metastasis recurred after initial treatment, chemotherapy consisting of NDP infusion combined with vindesine sulfate (VDS) infusion was performed. The patient again showed PR. Grade 3 leukocytopenia occurred during treatment, but there were no major toxicities such as thrombocytopenia, nausea, renal dysfunction or esophagitis. Survival time was one year and 7 months. In conclusion, concurrent chemoradiotherapy including NDP is effective and safe for patients with esophageal carcinoma accompanied by multiple liver metastasis. This nonsurgical approach may be an option for standard care in such cases.

Aged↗
PubMed2000

Detection of mutation of the p53 gene with high sensitivity by fluorescence-based PCR-SSCP analysis using low-pH buffer and an automated DNA sequencer in a large number of DNA samples.

Detection of mutations in genes responsible for hereditary diseases or tumors is important clinically. It is necessary to establish a simple technique for screening mutations in large numbers of samples. The polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method has proved to be a useful technique for analyzing mutations or DNA polymorphisms. Non-radioisotopic versions using fluorescent dye and an automated DNA sequencer have also been exploited to extend this technique into the clinical field. We have examined mutations of exons 5-9 of the p53 gene in 112 colorectal, 28 esophageal and 33 hepatocellular carcinomas by fluorescence-based PCR-SSCP (F-SSCP) under various conditions. We found 64 types of mutations in 63, 17 and 12 cases of colon, esophageal and hepatocellular carcinomas by F-SSCP. We determined the sequence of all samples, and confirmed that all mutations were successfully detected by F-SSCP. With the low-pH buffer system, 61 types of mutants were detected, while 51 types were detected by TBE and 57 types were detected by TBE with glycerol gel. The polyacrylamide gel in TME or TBE without glycerol was tough and could be used repeatedly, but the glycerol containing gel was fragile and could not stand repeated use. Thus, use of a low-pH buffer in the electrophoresis of F-SSCP is simpler and better at detecting mutations than the conventional TBE buffer system. We believe that low-pH F-SSCP analysis is an efficient and powerful technique for examination of a large number of samples, in particular clinical specimens obtained by biopsy or surgery.

DNA Mutational Analysis↗
PubMed2000

Functional outcome of stapled ileal pouch-anal canal anastomosis versus handsewn pouch-anal anastomosis.

This study was conducted to determine whether stapled ileal pouch-anal canal anastomosis (IACA) preserving the anal transitional zone (ATZ) or hand-sewn ileal pouch-anal anastomosis with mucosectomy (IPAA) is more beneficial in achieving disease eradication and better postoperative function. IACA was performed in 10 patients with ulcerative colitis (UC) and 10 patients with familial adenomatous polyposis (FAP), 15 of whom were examined proctoscopically. IPAA was performed in 4 patients with UC and 8 patients with FAP. The mean maximum resting pressure (MRP) was 55 mmHg in the IACA group and 34 mmHg in the IPAA group (P < 0.01). The anorectal inhibitory reflex was positive in 18 patients (90%) from the IACA group and 5 (42%) from the IPAA group (P < 0.05). The pre- and postoperative MRPs were 61 mmHg and 55 mmHg, respectively, in the IACA group vs 63 mmHg and 34 mmHg, respectively, in the IPAA group (P < 0.01). Whereas 16 (80%) of the 20 IACA patients could discriminate feces from gas, only 4 (33%) of the 12 IPAA patients could (P < 0.05). The mean observation period was 2.3 years, the mean length of the columnar cuff was 2.8 cm, and no case of dysplasia or adenoma was seen. Postoperative function is more favorable following IACA than following IPAA, both physiologically and symptomatically. However, long-term surveillance of the residual mucosa is necessary before making a final recommendation.

Adenomatous Polyposis Coli↗
PubMed2000

Growth patterns of superficially elevated neoplasia in the large intestine.

BACKGROUND: The growth pattern and malignant potential of superficially elevated neoplastic lesions remain controversial. A flat adenoma is classified as a superficially elevated neoplasm that characteristically demonstrates high-grade dysplasia despite its small size. In contrast, a nodule-aggregating (NA) tumor, which consists of multiple small aggregated nodules, can also be classified as superficially elevated neoplasia. METHODS: In this prospective study, 2720 consecutive patients undergoing total colonoscopy were examined for superficially for elevated lesions. Clinicopathologic characteristics, Ki-ras mutational status, and overexpression of p53 protein were compared in 25 NA tumors and 55 flat adenomas without a central depression (flat tumor). RESULTS: All flat tumors had a tubular pattern, whereas 21 of 25 NA tumors showed a villotubular or tubulovillous pattern. Ki-ras mutation was observed in 44% of NA tumors but in none of the flat tumors. Overexpression of p53 protein was found in 12% of NA tumors and 7% of flat tumors. CONCLUSIONS: NA tumors and flat tumors have different clinicopathologic and genetic characteristics, although both types of tumor are classified as superficially elevated lesions.

Adenocarcinoma↗
PubMed1999

Activation by bitter substances of a cationic channel in membrane patches excised from the bullfrog taste receptor cell.

1. The response to bitter-tasting substances was recorded in outside-out membrane patches excised from the taste receptor cell of the bullfrog fungiform papilla. 2. Application of a bitter-tasting substance, quinine or denatonium, induced channel openings under conditions in which none of the second messenger candidates or their precursors (e.g. cyclic nucleotide, inositol 1,4,5-trisphosphate, Ca2+, ATP and GTP) were present on either side of the membrane. The response could be recorded > 10 min after excision of the patch membrane. These data suggest that the channel was directly gated by the bitter-tasting substances. 3. No change in response was detected upon addition to the cytoplasmic side of either GDPbetaS (1 mM) or GTPgammaS (1 mM), suggesting that the G protein cascade has no direct relation to response generation. 4. The quinine-induced current was dose dependent. The lowest effective concentration was approximately 0.1 mM, and the saturating concentration was near 1 mM. The dose-response curve was fitted by the Hill equation with a K of 0.52 mM and a Hill coefficient of 3.8. 5. The single channel conductance measured in 120 mM NaCl solution was 10 pS. The channel was cation selective, and the ratio of the permeabilities for Na+, K+ and Cs+ (PNa : PK : PCs) was 1 : 0.48 : 0.39. The unitary conductance was dependent on the extracellular Ca2+ concentration ([Ca2+]o); 9.2 pS in a nominally Ca2+-free solution, and 4.5 pS in 1. 8 mM [Ca2+]o. 6. The dose dependence, the ion selectivity and the dependence of the unitary conductance on [Ca2+]o were almost identical to those of the quinine-induced whole-cell current reported previously, indicating that the channel activity observed in the excised membrane is the basis of the whole-cell current. 7. The present observations suggest the new possibility that the cationic channel directly gated by bitter substances is involved in the bitter taste transduction mechanism.

Animals↗
PubMed1999

Adrenaline enhances odorant contrast by modulating signal encoding in olfactory receptor cells.

Olfactory perception is influenced by hormones. Here we report that adrenaline can directly affect the signal encoding of olfactory receptor cells. Application of adrenaline suppressed action potentials near threshold and increased their frequency in response to strong stimuli, resulting in a narrower dynamic range. Under voltage-clamp conditions, adrenaline enhanced sodium current and reduced T-type calcium current. Because sodium current is the major component of spike generation and T-type calcium current lowers the threshold in olfactory receptor cells, the effects of adrenaline on these currents are consistent with the results obtained under current-clamp conditions. Both effects involved a common cytoplasmic pathway, cAMP-dependent phosphorylation. We suggest that adrenaline may enhance contrast in olfactory perception by this mechanism.

Action Potentials↗
PubMed1997

Mechanism of odorant adaptation in the olfactory receptor cell.

Adaptation to odorants begins at the level of sensory receptor cells, presumably through modulation of their transduction machinery. The olfactory signal transduction involves the activation of the adenylyl cyclase/cyclic AMP second messenger system which leads to the sequential opening of cAMP-gated channels and Ca2+-activated chloride ion channels. Several reports of results obtained from in vitro preparations describe the possible molecular mechanisms involved in odorant adaptation; namely, ordorant receptor phosphorylation, activation of phosphodiesterase, and ion channel regulation. However, it is still unknown whether these putative mechanisms work in the intact olfactory receptor cell. Here we investigate the nature of the adaptational mechanism in intact olfactory cells by using a combination of odorant stimulation and caged cAMP photolysis which produces current responses that bypass the early stages of signal transduction (involving the receptor, G protein and adenylyl cyclase). Odorant- and cAMP-induced responses showed the same adaptation in a Ca2+-dependent manner, indicating that adaptation occurs entirely downstream of the cyclase. Moreover, we show that phosphodiesterase activity remains constant during adaptation and that an affinity change of the cAMP-gated channel for ligands accounts well for our results. We conclude that the principal mechanism underlying odorant adaptation is actually a modulation of the cAMP-gated channel by Ca2+ feedback.

Adaptation, Physiological↗