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T Aikou

Publications and source records attributed to T Aikou.

At least 73 records · Page 4Linked to original sources
PubMed2000

Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats.

BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. MATERIALS AND METHODS: Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.

Animals↗
PubMed2000

Biological evaluation of undifferentiated carcinoma of the esophagus.

BACKGROUND: Patients with undifferentiated carcinoma of the esophagus (UEC) are rare and have a poor prognosis compared with those with differentiated squamous cell carcinomas (DECs). We compared clinicopathological and biological features of UEC and DEC, with emphasis on markers for epithelial cell origin, proliferation, and cell-cell adhesion. METHODS: Seven patients with UEC were compared with 21 with DEC. Immunohistochemical studies were performed by using monoclonal antibodies to cytokeratin, epithelial membrane antigen, p53, p21WAF1/CIP1, Ki-67, E-cadherin, desmoglein-1, and thrombomodulin. RESULTS: Patients with UEC had a poorer prognosis because of hematogenous metastasis at the time of presentation (mean survival, 6.5 +/- 6.2 vs. 35.5 +/- 28.9 months; P < .05). Immunohistochemical findings for cytokeratin and epithelial membrane antigen suggest that some UECs had epithelial origins. The following immunohistochemical profile of UEC was consistent with its highly malignant properties: (1) reduced or negative expression of cell-cell adhesion molecules such as E-cadherin, desmoglein-1, and thrombomodulin, (2) high positive rate for p53 and Ki-67, and (3) negative expression of p21WAF1/CIP1. CONCLUSIONS: The immunohistochemical findings for UEC showed its high cell-proliferative activity and a high potential for metastasis. Clinical features of UEC were supported by the results of immunohistochemical findings.

Adult↗
PubMed2000

Relation between effective utilization of exogenous fat emulsion as energy substrate and oxygen metabolism after surgery.

It is known that fat oxidation is increased in patients who have sustained surgical stress, but it is not clear whether fat emulsion should be administered during the early postoperative period. The aim of this study was to evaluate the utilization of exogenous fat emulsion after major surgery. Total parenteral nutrition composed of glucose/amino acids or glucose/amino acids/fat was administered for 6 days to 18 patients who had undergone esophagectomy. The caloric intake was significantly less than the resting energy expenditure (REE), and there was no difference in substrate utilization in either group up to postoperative day (POD) 2. After POD 4, fat utilization was significantly increased in the fat group. The total ketone body concentration was higher in the fat group than in the glucose group on POD 1 and 2. The arterial ketone body ratio (AKBR), which reflects the rate of turnover of the Krebs cycle, was positively correlated with the caloric intake/REE ratio. It was negatively correlated with the oxygen delivery index, oxygen consumption, and lactate concentration between POD 0 and POD 2. The lactate concentration was decreased and the AKBR was increased by POD 4. Fat emulsion was effectively utilized as energy substrate after POD 4, after the relative tissue hypoxia had improved and the AKBR had increased. The utilization of exogenous fat emulsion was closely related to deficient caloric intake and oxygen metabolism.

Aged↗
PubMed2000

Gastric acidity following pancreaticogastrostomy with pylorus-preserving pancreaticoduodenectomy.

Pancreaticogastrostomy (PG) has been reintroduced and employed occasionally as a useful alternative to pancreaticojejunostomy (PJ) after Whipple resection or pylorus-preserving pancreaticoduodenectomy (PPPD). Although the physiologic alteration in the stomach is important for the correlation between gastric and pancreatic functions, the actual intragastric pH profile after PG is still unclear. This study was conducted to investigate the physiologic changes in gastric pH and serum gastrin and secretin levels before and after PPPD reconstructed with PG (PPPD-PG) in humans. Twenty-four hour continuous intragastric pH and serum gastrin and secretin levels in the fasting state were examined in 25 patients who had undergone PPPD-PG. No peptic ulcer was detected after the operation. After PG, serum gastrin and secretin levels were unchanged. Twenty-four hour gastric pH monitoring revealed two distinct patterns during the nocturnal period before the operation: patients with acid-type secretion (n = 11) exhibited a persistent acid pH, whereas those with alkaline-type secretion (n = 14) had cyclic variations between an acid and an alkaline pH value. After PG, in both acid- and alkaline-type patients, median pH and percentages of time that the gastric pH was less than 4 (% pH < 4) and more than 6 (% pH > 6) did not change, and circadian pH patterns also remained unchanged. These results suggest that PPPD-PG has little influence on gastric acidity, and the neurohumoral relation between the stomach, duodenum, and pancreas is preserved after PG. Therefore, physiologically, PG can be recommended as a reconstructive procedure after PPPD.

Adult↗
PubMed2000

Ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery: experimental and clinical studies.

The ultrasonically activated scalpel, a new tool for cutting and coagulating tissue, uses high-frequency ultrasonic vibrations, and has been widely employed in the field of laparoscopic surgery. We evaluated its usefulness for cutting the pancreas in biliary-pancreatic surgery. We planned experimental and clinical studies using an ultrasonically activated scalpel (harmonic scalpel) for cutting the pancreas. The harmonic scalpel was set up at a power level of 3 (75% of full power) in the knife mode. In the experimental study, using dogs, cutting of the pancreas with the harmonic scalpel resulted in significantly less bleeding and significantly less histological tissue damage to the cut stumps than cutting of the pancreas with an electric or a regular scalpel. In the clinical study: (1) the hemostatic effect of the harmonic scalpel was excellent or good in any condition of the pancreas; (2) of 50 stumps of the main pancreatic duct cut with the harmonic scalpel, the stump was easily found in 48 (96%), while ultrasonography was necessary to find the remaining 2 stumps in soft pancreas; (3) in 41 anastomoses (29 soft and 12 hard pancreas) there were no postoperative pancreatic fistulae. These results indicate that the ultrasonically activated scalpel is an effective tool for cutting the pancreas in biliary-pancreatic surgery.

Animals↗
PubMed2000

Spindle cell carcinoma of the pancreas.

We experienced a rare case of spindle cell carcinoma of the pancreas. The patient was a 74-year-old man who complained of abdominal pain and loss of weight. Ultrasonographic scans revealed a hypoechoic solid mass in the head of the pancreas, 4 cm in diameter, with a high echoic spot suggestive of central necrosis or hemorrhage. The mass was hypodense on enhanced computed tomographic scans and hypovascular on angiograms. At laparotomy, the tumor had invaded to the mesocolon, but dissemination and distant metastasis were not found. We therefore performed pylorus-preserving pancreatoduodenectomy and ascending colectomy. The patient was discharged on postoperative day 26 after an uneventful recovery. Two months later, he was readmitted because of ascites, with positivity of spindle cells shown on cytology; he died on day 92 after surgery. In the resected specimen, the tumor had a mostly sarcomatous component, consisting of spindle-shaped cells, and a small glandular component. Immunohistochemically, both components were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and desmin. The tumor was diagnosed as a spindle cell carcinoma of the pancreas. Perineural invasion, lymphatic permeation, and blood vessel invasion were found, but lymph node metastasis was not found. Although a curative operation was performed, the outcome in this patient was very poor.

Aged↗
PubMed2000

Prospective evaluation of preoperative chemotherapy in resectable squamous cell carcinoma of the thoracic esophagus.

A prospective study was performed to clarify the surgical outcome of patients with esophageal carcinoma who would benefit from induction chemotherapy followed by surgery. Of 55 eligible patients, 42 (76.3%) agreed to randomization with either chemotherapy followed by surgery (n = 21) or surgery alone (n = 21). The other 13 refused. The chemotherapy consisted of cisplatin, 5-fluorouracil and leucovorin. All 55 patients underwent esophagectomy with two- or three-field resection, including two (3.6%) hospital mortalities. Of the 21 patients receiving chemotherapy, the response rate was 33.3% after the first course and 60% after the second course. A complete response was not obtained. Responders to the first course showed a prolonged survival, however time to treatment failure did not differ between patients treated with chemotherapy followed by surgery or surgery alone. This chemotherapy offered a worse surgical outcome for patients with pretreatment diagnosis of T3. Multivariate analysis identified a partial response to the first course of chemotherapy to be a favorable prognostic indicator. Preoperative chemotherapy does not give a survival benefit over surgery alone for patients with advanced tumor (T3). Initial response to the first dose of chemotherapy is deemed to be a prognostic factor for patients with less advanced tumor (T1/T2).

Aged↗
PubMed2000

Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation.

Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion and in cell-matrix interaction. We have examined the expression of galectin-3 in normal, adenomatous, and malignant thyroid tissues and also in metastatic lesions. Galectin-3 was rarely expressed in normal thyroid tissue but was abundant in the cytoplasm of the neoplastic lesions. Among neoplastic lesions, galectin-3 was expressed to a greater extent in follicular carcinomas than in follicular adenomas and was present in greater amounts in papillary carcinomas than in follicular adenomas or carcinomas. Primary lesions of papillary carcinoma with metastasis contained significantly higher concentrations of galectin-3 than tumors of this type without metastases. However, the expression of galectin-3 was significantly decreased in metastatic lesions in the lymph nodes compared with their primary lesions. From these results, we assumed that galectin-3 works in different ways at different stages of thyroid neoplasm proliferation. Among primary tumors, galectin-3 expression is significantly different in 3 histological types. However, the continuity of progression among these tumors is not yet proven. In later stages, decreased expression of galectin-3 may aid the release of cancer cells from the primary lesions for invasion and metastasis.

Adenocarcinoma, Follicular↗
PubMed2000

Serum midkine levels are increased in patients with various types of carcinomas.

The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.

Adult↗
PubMed2000

Reversal of P-glycoprotein and multidrug-resistance protein-mediated drug resistance in KB cells by 5-O-benzoylated taxinine K.

A newly synthesized taxoid originally from the Japanese yew Taxus cuspidata, 5-O-benzoylated taxinine K (BTK) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein (MRP)-mediated multidrug resistance. BTK reversed the resistance to paclitaxel, doxorubicin (ADM), and vincristine (VCR) of KB-8-5 and KB-C2 cells that overexpress P-gp by directly interacting with P-gp. BTK also moderately reversed the resistance to ADM of KB/MRP cells that overexpress MRP. However, BTK neither inhibited the transporting activity of MRP nor reduced intracellular glutathione levels in KB/MRP cells. BTK shifted the distribution of ADM in KB/MRP cells from punctate cytoplasmic compartments to the nucleoplasm and cytoplasm by inhibiting acidification of cytoplasmic organelles. These two functions of BTK make it able to reverse both P-gp- and MRP-mediated MDR. BTK in combination with ADM should be useful for treating patients with tumors that overexpress both P-gp and MRP.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Detection and clinical significance of lymph node micrometastasis determined by reverse transcription-polymerase chain reaction in patients with esophageal carcinoma.

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.

Carcinoembryonic Antigen↗
PubMed2000

Intranodal antitumor immunocyte infiltration in node-negative gastric cancers.

The status and role of immunocytes and dendritic cells in regional lymph nodes in patients with gastric cancer are examined in this study. Forty-nine patients with gastric cancer who underwent curative resection were enrolled in the present study. These patients had no lymph node metastases according to a histological examination. The infiltration of natural killer (NK) cells, dendritic cells, and MIB-1-positive immunocytes was investigated. Based on the Japanese Classification of Gastric Carcinoma, regional lymph nodes were divided into three compartments: (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and 16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1 lymph nodes in increased numbers compared with the lymph nodes of compartments 2 or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ significantly among the three compartments. The incidence of intranodal dendritic and MIB-1-positive cell infiltration in patients with submucosal gastric cancer was significantly higher than in patients with tumors that invaded beyond the muscularis propria. The decreased expression of these immunological markers correlated well with recurrent disease, regardless of tumor depth. The immunocyte level is higher in lymph nodes near the primary tumor (compartment 1) than in those that are distant from the tumor (compartments 2 and 3). This pertains to all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not correlate well with either lymph node compartment or the depth of tumor invasion. The degree of NK cell infiltration may be directly associated with antitumor effects, especially in compartment 1. A decrease in all three markers is associated with tumor recurrence.

Adult↗
PubMed2000

Down-regulation of E-cadherin by antisense oligonucleotide enhances basement membrane invasion of pancreatic carcinoma cells.

Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.

Adenocarcinoma↗
PubMed2000

Sensitivity of human pancreatic adenocarcinoma tumor lines to chemotherapy, radiotherapy, and hyperthermia.

BACKGROUND: Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test. METHODS: Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio). RESULTS: Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established. CONCLUSIONS: Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2000

N-acetyl cysteine inhibits cell cycle progression in pancreatic carcinoma cells.

The antioxidant N-acetyl cysteine (NAC) is a precursor of intracellular glutathione (GSH) and is also a well known as one of the chemopreventive agents which act through a variety of cellular mechanisms. We examined the effects of NAC on cell cycle progression in the pancreatic carcinoma cell lines, SW1990 and JHP1. Cells were incubated with or without NAC. Cell cycle distribution was analyzed by flow cytometry and immunoblotting. NAC suppressed cell proliferation in a concentration-dependent manner, whereas NAC increased intracellular glutathione content significantly in a dose-dependent manner. The percentage of cells in the G1 phase after treatment with NAC was significantly higher than the percentage seen for control cells. Cyclin D1 expression of carcinoma cells treated with NAC decreased remarkably compared with cells without NAC treatment. Thus, the antiproliferative effect of NAC by prolongation of the G1 phase in human pancreatic carcinoma cells shows its possible utility as an antitumor agent.

Acetylcysteine↗
PubMed1999

Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis.

BACKGROUND: Curative resection does not guarantee long term survival for the patient with extrahepatic bile duct carcinoma because of the possibility of metastases to the liver (LM). Expression of mucin core protein-1 (MUC1), sialyl-Le(x), and sialosyl-Tn in bile duct carcinoma was determined and compared with LM and prognosis. METHODS: Immunohistochemical expression of MUC1, sialyl-Le(x), and sialosyl-Tn in 73 extrahepatic bile duct tumors was analyzed using the DF3, FH6, and TKH2 monoclonal antibodies, respectively. Scoring was based on the percentage of immunoreactive cells: negative, low expression (</=25% immunoreactive cells), and high expression (>25%). RESULTS: High expression of MUC1, sialyl-Le(x), and sialosyl-Tn was observed in 68.5%, 34.2%, and 54.8%, respectively. of 73 cases. Patients with tumors showing high expression of MUC1 had a higher rate of LM (48.9%) and a significantly shorter survival period (median survival time, 17.8 months) compared with patients with tumors showing low (incidence of LM, 9.1%; median survival time, >100 months) or negative (incidence of LM, 11.1%; median survival time, 52.9 months) expression of MUC1 (P < 0.01). However, the survival period of patients with tumors showing high, low, or negative expression of sialyl-Le(x) or of sialosyl-Tn did not differ significantly. High MUC1 expression correlated with LM by logistic regression analysis and emerged as an independent prognostic factor in stepwise multivariate analysis. CONCLUSIONS: The results of the current study demonstrate that high expression of MUC1 correlates with LM and poor outcome in patients with extrahepatic bile duct carcinoma.

Adult↗
PubMed1999

Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells.

BACKGROUND: Lung resistance-related protein (LRP), the major vault protein in humans, is sometimes overexpressed in multidrug-resistant cells. Because cells transfected with the LRP gene did not express the multidrug-resistant phenotype, we investigated whether LRP is involved in multidrug resistance. METHODS: SW-620 cells, a human colon carcinoma cell line, alone or transfected with an expression vector carrying a LRP-specific ribozyme or with an empty vector, were treated with sodium butyrate to induce differentiation. Expression of P-glycoprotein, multidrug resistance protein, and LRP in the cells was examined by northern and western blotting, and the efflux of doxorubicin in the cells or isolated nuclei was examined by fluorescence microscopy. RESULTS: A 2-week treatment with sodium butyrate induced LRP and conferred resistance to doxorubicin, vincristine, etoposide, gramicidin D, and paclitaxel (Taxol) in SW-620 cells. Insertion of either of two LRP-specific ribozymes into SW-620 cells inhibited these activities. Levels of drugs accumulating in the cells were not decreased by sodium butyrate, suggesting that the adenosine triphosphate-binding cassette transporter is not involved in sodium butyrate-induced multidrug resistance. Doxorubicin was mainly located in the nuclei of untreated cells and in the cytoplasm of sodium butyrate-treated cells. Isolated nuclei from untreated cells or sodium butyrate-treated cells incubated with anti-LRP polyclonal antibodies contained more doxorubicin than the nuclei of sodium butyrate-treated cells alone. Efflux of doxorubicin was greater from the nuclei of sodium butyrate-treated cells than the nuclei of untreated cells or of sodium butyrate-treated cells transfected with a LRP-specific ribozyme and was inhibited by an anti-LRP polyclonal antibody. CONCLUSIONS: LRP is involved in resistance to doxorubicin, vincristine, etoposide, paclitaxel, and gramicidin D and has an important role in the transport of doxorubicin from the nucleus to the cytoplasm.

ATP Binding Cassette Transporter, Subfamily B, Mem↗