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T Akasu

Publications and source records attributed to T Akasu.

At least 19 recordsLinked to original sources

Detection of cytokeratin 19 and 20 mRNA in peripheral and mesenteric blood from colorectal cancer patients and their prognosis.

To detect the presence of cancer cells in peripheral and mesenteric blood and to examine their relationship to prognosis in colorectal cancer patients undergoing curative surgery, we examined cytokeratin 19 and 20 mRNA in peripheral and mesenteric venous blood. Using reverse transcriptase polymerase chain reaction, cytokeratin 19 and 20 mRNA was amplified in peripheral and mesenteric blood samples obtained from 35 colorectal cancer patients who underwent curative surgery. Cytokeratin 19 or 20 mRNA in peripheral or mesenteric blood samples was detected in 18 of 35 cases (51%). There was no significant difference in Dukes' staging between the positive and negative groups. The median follow-up period was 56 months. In the positive group six patients (33%) showed recurrences. One patient (6%) showed recurrence in the negative group. The recurrence rate was significantly higher in the positive group than in the negative group. Five-year disease-free survival was significantly better in the negative group than in the positive group (94% vs. 65%). The detection of cytokeratin 19 or 20 mRNA in peripheral or mesenteric blood is thus associated with the prognosis for colorectal cancer patients undergoing curative surgery. Although the presence of these mRNAs in blood samples is a prognostic marker, the clinical utility of this assay is questionable because of the low recurrence rate in the positive group.

Adult↗

5-Hydroxytryptamine facilitates spatiotemporal propagation of optical signals in the hippocampal-septal pathway.

The role of 5-hydroxytryptamine (5-HT) on the propagation of neuronal excitation in the hippocampal-septal pathway was examined in a brain slice by optical and electrophysiological recording techniques. After electrical stimulation of the fimbrial pathway, optical signals first occurred at the caudal region of lateral septal nucleus (LSN), then propagated toward the rostral region of LSN. All of the evoked optical signals were blocked by tetrodotoxin (TTX). The optical signal that propagated to the LSN was blocked by either the removal of external Ca(2+) or bath-application of 6-cyano-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX). Bath-application of 5-HT (1-50 microM) to the LSN for 10 min produced an increase in the propagation area of the optical signal and prolonged the falling phase of the optical signal. Bicuculline blocked the 5-HT-induced facilitation of the optical signal. 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT), a selective 5-HT(1A) agonist, mimicked the facilitation of 5-HT. 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190), a 5-HT(1A) antagonist, blocked the facilitation induced by 5-HT. 5-HT enhanced the amplitude of the field potential in septal slices, where the optical signals had been enhanced. These results indicate that 5-HT increases the efficacy of excitatory synaptic transmission in the hippocampal-septal circuit via 5-HT(1A) receptors of LSN neurons.

2-Amino-5-phosphonovalerate↗

Activation of inhibitory pathways suppresses the induction of long-term potentiation in neurons of the rat lateral septal nucleus.

Long-term potentiation of the hippocampal-septal pathway was examined by intracellular recording techniques. High frequency stimulation (two 100-Hz 1-s trains with a 20-s interval between them) of the hippocampal CA3 area resulted in a transient depolarization in rat lateral septal nucleus neurons. High frequency stimulation was followed by a facilitation of fast and slow inhibitory postsynaptic potentials, lasting for more than 2 h, but not by a long-lasting increase in the excitatory postsynaptic potential in the normal solution. Long-term potentiation (>2 h) of the excitatory postsynaptic potential did not appear in 74% of neurons tested, even when the fast inhibitory postsynaptic potential was blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. High frequency stimulation produced long-term potentiation of the excitatory postsynaptic potential in the Mg(2+)-free solution containing bicuculline. When the fast and slow inhibitory postsynaptic potentials were blocked by GABA(A) and GABA(B) receptor antagonists (bicuculline and CGP 55845A respectively), high frequency stimulation produced a large and sustained depolarization followed by long-term potentiation of the excitatory postsynaptic potential. However, the excitatory postsynaptic potential was not enhanced by administration of these drugs after termination of high frequency stimulation. Pretreatment with 2-amino-5-phosphonopentanoate, a NMDA receptor antagonist, resulted in loss of long-term potentiation in both sets of experiments. Paired-pulse stimulation of the hippocampal CA3 region with interstimulus intervals between 200 and 800 ms depressed the second excitatory postsynaptic potential in the presence of bicuculline. CGP 35348, a GABA(B) receptor antagonist, reversed the depression of excitatory postsynaptic potentials to facilitation. These data suggest that high frequency stimulation of hippocampal CA3 neurons enhances the efficacy of GABAergic inhibitory circuits which, in turn, depress the ability of lateral septal nucleus neurons to express long-term potentiation.

Animals↗

Long-term outcome of urinary function after extended lymphadenectomy in patients with distal rectal cancer.

AIMS: Extended lymphadenectomy for rectal cancer has been superseded by autonomic nerve-sparing surgery, but it still has historical significance. It is useful to document the long-term outcome of urinary function in cases who had resection of the inferior hypogastric nerve plexus (pelvic nerve plexus). METHODS: The long-term urinary function following extended lymphadenectomy was studied retrospectively through the medical records of 83 patients who had been followed-up for more than 5 years after surgery. RESULTS: Forty-four per cent of the male patients and 17% of the female patients had to perform clean intermittent self-catheterization (CIC) for more than 1 year; these rates were almost the same at 3 years after the procedure. Urinary incontinence was reported in 34% of the male patients and 45% of the female patients. Complicated cystitis (eight patients), complicated pyelonephritis (two patients), bladder stones (five patients) that required surgical treatment, and chronic renal failure (two patients) were considered as adverse outcomes of extended surgery. In particular, one case needed to undergo urinary diversion. CONCLUSIONS: A surprisingly large proportion of patients suffered various urinary tract problems due to extended lymphadenectomy. The findings demonstrate the importance of selection of well-balanced operations that can encompass both radicality and quality of life. The extent of resection should be decided by the extent of the cancer and routine excision of the inferior hypogastric nerve plexus should not be performed.

Adult↗

Characterization of outward currents induced by 5-HT in neurons of rat dorsolateral septal nucleus.

Properties of the 5-hydroxytryptamine (5-HT)-induced current (I(5-HT)) were examined in neurons of rat dorsolateral septal nucleus (DLSN) by using whole cell patch-clamp techniques. I(5-HT) was associated with an increase in the membrane conductance of DLSN neurons. The reversal potential of I(5-HT) was -93 +/- 6 (SE) mV (n = 7) in the artificial cerebrospinal fluid (ACSF) and was changed by 54 mV per decade change in the external K(+) concentration, indicating that I(5-HT) is carried exclusively by K(+). Voltage dependency of the K(+) conductance underlying I(5-HT) was investigated by using current-voltage relationship. I(5-HT) showed a linear I-V relation in 63%, inward rectification in 21%, and outward rectification in 16% of DLSN neurons. (+/-)-8-Hydroxy-dipropylaminotetralin hydrobromide (30 microM), a selective 5-HT(1A) receptor agonist, also produced outward currents with three types of voltage dependency. Ba(2+) (100 microM) blocked the inward rectifier I(5-HT) but not the outward rectifier I(5-HT). In I(5-HT) with linear I-V relation, blockade of the inward rectifier K(+) current by Ba(2+) (100 microM) unmasked the outward rectifier current in DLSN neurons. These results suggest that I(5-HT) with linear I-V relation is the sum of inward rectifier and outward rectifier K(+) currents in DLSN neurons. Intracellular application of guanosine-5'-O-(3-thiotriphosphate) (300 microM) and guanosine-5'-O-(2-thiodiphosphate) (5 mM), blockers of G protein, irreversibly depressed I(5-HT). Protein kinase C (PKC) 19-36 (20 microM), a specific PKC inhibitor, depressed the outward rectifier I(5-HT) but not the inward rectifier I(5-HT). I(5-HT) was depressed by N-ethylmaleimide, which uncouples the G-protein-coupled receptor from pertussis-toxin-sensitive G proteins. H-89 (10 microM) and adenosine 3',5'-cyclic monophosphothioate Rp-isomer (300 microM), protein kinase A inhibitors, did not depress I(5-HT). Phorbol 12-myristate 13-acetate (10 microM), an activator of PKC, produced an outward rectifying K(+) current. These results suggest that both 5-HT-induced inward and outward rectifying currents are mediated by a G protein and that PKC is probably involved in the transduction pathway of the outward rectifying I(5-HT) in DLSN neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Optical recording of the spatiotemporal propagation of neuronal excitation in the rat hippocampal CA2-CA1 pathway.

Changes in the membrane potential of neurons in the hippocampal CA2 and CA1 regions were recorded by optical recording techniques. After stimulation of the Schaffer collaterals at the hippocampal CA2 region, excitatory optical signals first occurred adjacent stimulus electrode and then flamed-up signals spread toward the hippocampal CA1 region. The optical signal was blocked by tetrodotoxin (TTX) (1 microM). Propagation of the optical signal was blocked in an artificial cerebrospinal fluid (ACSF) containing 0 mM Ca2+ and 6 mM Mg2+. 6,7-Dinitroquinoxaline-2,3 (1H,4H)-dione (DNQX) (20 microM) also blocked the optical signals that spread to the hippocampal CA1 region. The time course of the optical signal recorded at a unit area (49 pixels) on the propagation pathway was characterized by fast and slow components. TTX (1 microM) blocked both fast and slow components of the optical signal. The slow component of the optical signal was preferentially depressed by either removal of external Ca2+ or by bath-application of DNQX (20 microM). When bicuculline (15 microM) was applied to the bath-solution, the intensity and propagation area of the optical signal were increased. The results indicate that stimulation of the Schaffer collaterals in the hippocampal CA2 region produces the propagation of the optical signal to the hippocampal CA1 region, and that the optical signal involves the action potential and excitatory and inhibitory postsynaptic potentials.

Action Potentials↗

[Surgical treatment of liver metastases from colorectal cancer patient selection and oncological outcome].

The indications for surgical resection of liver metastases from colorectal cancer remain controversial. Clinical, pathological, and outcome data for 418 consecutive patients undergoing hepatectomy between 1984 and 1998 were examined. The over-all 5-year survival rate was 42%, and the 10-year survival rate was 31%. The 5-year survival rate of patients with four or more nodules was 24%, with 20 patients surviving for more than 5 years. Five factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis. The preoperative scoring system reported by Fong et al was double-checked in our 418 patients and was found to be useful to predict long-term outcome after hepatectomy. It is clear that liver resection alone has limitations. Therefore clinical risk scoring (CRS) and effective intravenous systemic chemotherapy to prevent recurrence both in the remaining liver and lung should be established to improve survival outcome in patients with poor prognostic factors after liver resection.

Colorectal Neoplasms↗

Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited cancer-prone syndrome. Here, we describe a novel and efficient approach for screening mutations of two major HNPCC susceptibility genes, hMSH2 and hMLH1. The system consists of RNA extraction from whole blood treated with the translation inhibitor, followed by long RT-PCR of the entire coding regions combined with direct sequencing. In analysis of 15 kindreds suspicious for HNPCC, 8 samples were subjected to analysis after puromycin treatment and 7 samples were analyzed without puromycin treatment. Three deleterious mutations were detected in the kindreds with puromycin treatment, while none were observed in those without puromycin. Signals from mutated alleles were enhanced after puromycin treatment and easily distinguished from the wild-type allele, achieved by suppression of nonsense-mediated mRNA decay. Furthermore, 12 other mutations were detected in 15 kindreds. The system is considered to be a reliable and useful approach for detecting germline mutations of hMSH2 and hMLH1 in HNPCC kindreds.

Adaptor Proteins, Signal Transducing↗

En bloc surgery for colon cancer: report of a case.

We report herein the case of a 57-year-old woman in whom successful en bloc surgery was performed for locally advanced colon cancer. A fixed tumor was palpable in the right subcostal region, and computed tomography (CT) showed that it originated in the ascending colon and invaded the right kidney, duodenum, head of the pancreas, and liver. A right hemicolectomy with D3 lymphadenectomy was performed combined with resection of the right kidney, duodenum, head of the pancreas, and liver. On microscopic examination, well-differentiated adenocarcinoma of the ascending colon widely invaded the parenchyma of the kidney, the parenchyma of the pancreatic head, and the duodenal wall. Lymph node metastasis was found in one paracolic node. This case report outlines the procedures involved in this extended surgery.

Adenocarcinoma↗

Endorectal ultrasonography and treatment of early stage rectal cancer.

The purpose of this study was to evaluate the accuracy of preoperative staging by endorectal ultrasonography (EUS) and its contribution to treatment of early stage rectal cancer (ESRC). The results of EUS for 154 consecutive patients with ESRC (pTis to pT2) were compared prospectively with histologic findings, assessed according to the TNM classification. Results of treatment selection and long-term outcomes were analyzed retrospectively. There were 35 patients histologically staged as pTis, 8 as pT1-slight (invasion confined to the superficial one-third of the submucosa), 37 as pT1-massive (invasion extending to the deeper submucosa), and 74 as pT2. The equipment used was an echoendoscope GF-UM2 or GF-UM3 (Olympus, Tokyo, Japan). Sensitivity/specificity/overall accuracy rates for detection of slight submucosal invasion, massive submucosal invasion, and muscularis propria invasion were 99%/74%/96%, 98%/88%/97%, and 97%/93%/96%, respectively. Incidences of lymph node metastasis in pTis, pTis to pT1-slight, pT1, pT1-massive, and pT2 cases were 0%, 0%, 18%, 22%, and 30%, respectively. Incidences of lymph node metastasis in ESRCs staged by EUS (u) as uTis, uT1-slight, uT1-massive, uT2, and uT3 by EUS were 0%, 0%, 26%, 36%, and 64%, respectively. Sensitivity, specificity, and overall accuracy rates for detection of positive nodes in overall ESRCs were 53%, 77%, and 72%, respectively. Of the 43 patients with pTis to pT1-slight tumors, 22 underwent endoscopic polypectomy or local excision, 20 radical surgery, and 1 radical surgery after endoscopic polypectomy due to vascular invasion. All these patients are alive and all but one (who refused radical surgery due to vascular invasion after local excision and developed liver and lung metastases) are disease-free. Of the 37 patients with pT1-massive tumors, 34 underwent radical surgery and 3 transcoccygeal segmental resection. All these patients are alive disease-free except for one who died of peritoneal carcinomatosis after radical surgery. All patients with pT2 tumors underwent radical surgery. The overall 5-year survival rates for pTis, pT1, and pT2 cases were 100%, 98%, and 97%, respectively. EUS is an accurate method for evaluating invasion depth in ESRC. Patients with uTis or uT1-slight tumors staged by EUS are at low risk of positive nodes and good candidates for endoscopic polypectomy or local excision. Those with uT1-massive or uT2 lesions should be treated with a radical operation because of the high incidence of positive nodes.

Adenocarcinoma↗

Dermatomyositis accompanied by rectal cancer: report of a case.

Dermatomyositis (DM) is a rare inflammatory disorder of the skin and muscles associated with an increased incidence of malignancy. We describe herein the case of a 59-year-old woman with DM accompanied by rectal cancer. Following excision of the rectal cancer, the characteristic features of the skin rash such as the heliotrope eyelid rash and Gottron's papules, and proximal muscle weakness, improved. Moreover, the elevated preoperative serum levels of muscle-associated enzymes, including aspartate transaminase, creatine phosphokinase, lactate dehydrogenase, and aldolase, decreased from 38 to 16 (IU/1), 138 to 42 (IU/1), 672 to 515 (IU/1), and 32.2 to 4.3 (IU/1), respectively. The current concepts of the correlation between DM and malignancy are discussed with regard to the present case.

Adenocarcinoma↗

5-Hydroxytryptamine-induced outward currents mediated via 5-HT(1A) receptors in neurons of the rat dorsolateral septal nucleus.

Effects of 5-hydroxytryptamine (5-HT) on neurons of the rat dorsolateral septal nucleus (DLSN) were examined by intracellular and whole-cell patch-clamp recording techniques. An outward current was induced by 5-HT (1-100 microM) in a concentration-dependent manner. The EC(50) for 5-HT was 4.8 microM. Also, 8-OH-DPAT (10-100 microM) produced the outward current an EC(50) of 17 microM. Amplitudes of the outward currents produced by 5-HT (100 microM) and 8-OH-DPAT (100 microM) were 117+/-4 (n=6) and 58+/-8 pA (n=6), respectively. Fluvoxamine (200 nM), a specific serotonin re-uptake inhibitor, enhanced the 5-HT (1 microM)-induced outward current: the EC(50) for 5-HT was 0.5 microM in the presence of fluvoxamine (200 nM). L-694247 (100 microM) and CP 93129 (100 microM) also produced outward currents with amplitudes of 33+/-3 (n=4) and 18+/-5 pA (n=4), respectively in DLSN neurons. DOI (100 microM) and RS 67333 (100 microM) did not produce outward currents. NAN-190 shifted, in a parallel manner, the concentration-response relationship of 5-HT to the right. The Lineweaver-Burk plot of the concentration-response curve showed that NAN-190 depressed the 5-HT-induced current in a competitive manner. The current-voltage relationship indicates that the 5-HT-induced current reversed polarity at a potential close to the equilibrium potential of K(+). Ba(2+) (100 microM-1 mM) partially depressed the outward current produced by 5-HT. These results suggest that 5-HT induces multiple K(+) currents via 5-HT(1A) receptors in DLSN neurons.

Animals↗

Resection of synchronous liver metastases from colorectal cancer.

BACKGROUND: The prognosis for patients with liver metastases from colorectal cancer is still poor. Thus, patient selection for hepatic resection is essential to improve the poor results of the procedure. Some reports have shown that the prognosis for patients with synchronous liver metastases is worse than that for those with metachronous liver metastases. Therefore, determination of the factors that influence outcome after resection of synchronous liver metastases is more important than with metachronous liver metastasis. METHOD: We studied patients who had been followed for more than 5 years after undergoing resection of synchronous liver metastases from colorectal cancer. RESULTS: Among the 12 prognostic factors studied (age, gender, adjuvant chemotherapy, tumor site, CEA level, tumor differentiation, tumor size, regional lymph node metastatic status, distribution of liver metastases, number of liver metastases, tumor size and pathological margin), regional lymph node metastatic status and pathological margin were significant prognostic factors by univariate analysis (p = 0.0002 and 0.005, respectively). Regional lymph node metastatic status was a significant prognostic factor by multivariate analysis (p = 0.031). The survival curve of patients with six or more regional lymph node metastases was similar to that of patients with non-resectable liver metastasis. CONCLUSION: The resection of synchronous liver metastases in patients with six or more regional lymph node metastases is relatively contraindicated. For these patients, other treatment modalities should be considered.

Age Factors↗

Robotic surgery.

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General Surgery↗

Effects of corticosteroids on synaptic transmission in rat dorsolateral septal nucleus.

The effects of corticosteroids on synaptic transmission in the rat dorsolateral septal nucleus (DLSN) were examined, in vitro, by using intracellular and voltage-clamp recording methods. Prednisolone (100 microM) increased the amplitude of excitatory postsynaptic potential (EPSP) and depressed both fast and slow inhibitory postsynaptic potentials (IPSP). Under voltage-clamp conditions, prednisolone (100 microM) increased the amplitude of excitatory postsynaptic current (EPSC) and depressed the fast and slow inhibitory postsynaptic currents (IPSCs). Corticosterone (100 microM) mimicked the effects of prednisolone on the postsynaptic currents (PSCs). To examine the direct effects of prednisolone on the EPSC and slow IPSC, the fast IPSC was blocked by bicuculline (20 microM). Under these experimental conditions, prednisolone (100 microM) did not alter the isolated EPSC but depressed slow IPSC by 22 +/- 3% (n = 10). The fast IPSC was isolated by pretreatment with kynurenic acid and CGP55845A, where the EPSC and slow IPSC were blocked. Prednisolone (100 microM) depressed the isolated fast IPSC in DLSN neurons. Prednisolone (100 microM) did not change either the inward current produced by glutamate or the outward current produced by gamma-aminobutyric acid (GABA). The results suggest that corticosteroids facilitate excitatory synaptic transmission in the DLSN by reducing the release of GABA from the presynaptic nerve terminals of interneurons.

Action Potentials↗