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Biomedical subjects

Y Saitoh

Publications and source records attributed to Y Saitoh.

At least 361 records · Page 20Linked to original sources

Blood and lymphatic vessel invasion as prognostic factors for patients with primary resected nonsmall cell carcinoma of the lung with intrapulmonary metastases.

BACKGROUND: The new classification of intrapulmonary metastases of lung cancer was proposed by the American Joint Committee on Cancer; however, the prognostic factors are heterogeneous and not yet fully clarified. In this study, the authors evaluated the prognostic factors for and the possible routes of intrapulmonary metastases. METHODS: The factors influencing the prognosis of primary resected nonsmall cell lung carcinomas with intrapulmonary metastasis in the resected specimens were evaluated according to the Cox proportional hazards model using a total of 66 nonsmall cell lung carcinomas. The possible routes of tumor spread via the blood or lymphatic vessels also were evaluated. RESULTS: The overall 5-year survival rate was 26.1%, and the statistical analysis of survival curves revealed a significant difference with regard to N classification (P = 0.042), site of intrapulmonary metastasis (P = 0.012), blood vessel invasion (P = 0.0046), and lymphatic vessel invasion (P = 0.0267); there were no significant differences in relation to age, sex, histology, differentiation, T classification, tumor size, stage, number of intrapulmonary metastases, or size of intrapulmonary metastasis. Multivariate analysis according to the Cox proportional hazards model identified a significant correlation between survival and blood vessel invasion (P = 0.044) and lymphatic vessel invasion (P = 0.042), suggesting independent prognostic significance. The correlation between site of intrapulmonary metastasis and the ratio of blood or lymphatic vessel invasion showed a significantly lower ratio of blood vessel invasion in cases with intrapulmonary metastases at sites central to the primary lesion or in different segment(s) compared with those in cases with intrapulmonary metastases at sites peripheral to the primary lesion or in ipsilateral different lobe(s), suggesting a possible lymphatic vessel route of tumor spread. CONCLUSION: Blood vessel and lymphatic vessel invasion are important clinical factors in evaluating prognosis and the route of tumor spread in primary resected nonsmall cell carcinoma with intrapulmonary metastasis.

Adult↗

Ischemic preconditioning improves cardiac functional recovery following preservation with University of Wisconsin solution.

Single or multiple brief periods of regional or global ischemia and reperfusion prior to a prolonged ischemic insult showed cardioprotective effects. Although this phenomenon (ischemic preconditioning [IPC]) has been described in ischemic reperfusion models, the effect of IPC on heart preservation has not been previously reported. We, thus, investigated the effect of IPC on heart preservation. Hearts isolated from male Wistar rats (250-350 g) were mounted on a Langendorff apparatus to estimate baseline function (aortic flow, coronary flow, cardiac output, heart rate, systolic pressure, and rate pressure product). All hearts were divided into 5 groups. In groups 1 and 4, the hearts were subjected to 8 and 12 hr of preservation, respectively. The hearts in group 2 were subjected to a single 2.5-minute cycle of normothermic global ischemic episode (IPC) before 8 hr of preservation. In groups 3 and 5, the hearts were subjected to two 2.5-min IPC cycles and stored for 8 or 12 hr. The hearts were arrested with University of Wisconsin solution and stored at 4 degrees C. Following storage, the hearts were reperfused and measured postpreservative function to assess cardiac functional recovery. Lactate and troponin-T leakage in the coronary perfusate was also measured. In group 3, the treatment of two 2.5-min IPC cycles significantly increased cardiac output, but the treatment of single 2.5-min IPC cycle did not affect the result. In the extended preservation group (group 5), the recovery (%) of both coronary flow and cardiac output were significantly increased compared with group 4. Furthermore, lactate leakage was significantly reduced in groups 2 and 3. These results suggest that IPC improves cardiac functional recovery following simple cold storage and has cardioprotective effects in rat heart preservation.

Adenosine↗

Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in Fc epsilon RI-mediated signal transduction.

Wortmannin inhibited phosphatidylinositol 3-kinase (P13-kinase) and Fc epsilon RI-mediated histamine secretion in RBL-2H3 cells to a similar degree, with IC50 values of 3 and 2 nM, respectively. Although P13-kinase is an acknowledged regulator of intracellular trafficking and secretion, wortmannin has proved to be a difficult drug to use in assessing the role of P13-kinase because it inhibits another important enzyme, myosin light-chain kinase (MLCK; IC50 = 200 nM). In the present study we synthesized a unique derivative of wortmannin, O-acetyl-delta 16-wortmannin-17-ol (KT7692), that has an inhibitory potency against PI3-kinase one-hundredth that of wortmannin, but retains a similar potency to wortmannin against MLCK. Histamine secretion was influenced 100-fold more by wortmannin than by KT7692.2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a structurally different PI3-kinase inhibitor from wortmannin, inhibited PI3-kinase with an IC50 of 2 microM but had little effect on MLCK activity in this concentration range. LY294002 also inhibited histamine secretion in RBL-2H3 cells with an IC50 of 5 microM. These results provide further evidence that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion after stimulation of Fc epsilon RI. Furthermore KT7692 in combination with wortmannin and LY294002 would be a powerful tool for clarifying the involvement of PI3-kinase as distinct from that of MLCK in signal transduction systems of various cellular responses.

Androstadienes↗

Limited TCR repertoire of infiltrating T cells in the kidneys of Sjögren's syndrome patients with interstitial nephritis.

To analyze the mechanism of interstitial nephritis in patients with Sjörgren's syndrome (SS), we examined the TCR repertoire of infiltration T cells in kidney, labial salivary glands, and PBLs using a PCR. The repertoire of the TCR V beta gene on infiltrating T cells from the kidneys of SS patients was more restricted than those on infiltrating T cells in labial salivary glands and PBL. The TCR V beta 2 gene was expressed predominantly in six of seven (86%) SS patients. Junctional sequences of cDNAs encoding the V beta 2 gene on infiltrating T cells in the kidneys of five SS patients showed that some of the cells expanded clonally, indicating Ag-driven stimulation rather than superantigen-induced proliferation. The same V beta 2 clones in the kidney were not detected in labial salivary glands of the same SS patients; the conserved amino acid (arginine at position 96) in the CDR3 region of the V beta 2 gene was found at a frequency of 48.0% in the kidney, whereas it was detected in only 15.4% of the clones in lips. In conclusion, these findings suggest the possibility that T cells that infiltrate the kidneys of SS patients with interstitial nephritis might recognize different autoantigens than those that infiltrate labial salivary glands.

Amino Acid Sequence↗

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells.

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.

Acute Disease↗

Serum concentrations of 5-fluorouracil achieved with nocturnal constant-rate infusion in patients with disseminated cancer.

Nocturnal infusion of 5-fluorouracil (FUra) was performed in nine patients with disseminated cancer. Three gastric, three colon and three breast cancer patients were administered 300 mg/m2 FUra continuously for 10 h per day from 2100 h to 0700 h for more than 20 consecutive days. In the first three patients, who were treated by drip infusion without the use of a volumetric pump, serum FUra concentrations ranged widely, from 27 to 130 ng/ml, even though the rate of administration was re-adjusted four times during the night. The last six patients were treated using a volumetric pump, and FUra concentrations in serum ranged from 175 to 378 ng/ml, and displayed no circadian rhythm. Although the dose intensity and area under the curve of FUra in these patients were high, neither myelosuppression nor other side effects were observed.

Adult↗

Fibrin glue sealing for the prevention of pancreatic fistulas following distal pancreatectomy.

OBJECTIVE: To evaluate the use of fibrin glue sealing of the pancreatic stump for the prevention of postoperative pancreatic fistulas. DESIGN: A prospective, randomized clinical trial. PATIENTS AND METHODS: Fibrin glue is a biologic adhesive consisting of highly concentrated human fibrinogen, thrombin, and factor VIII. Twenty-six of 56 patients who underwent distal pancreatectomy for gastric cancer or pancreatic disease were randomly assigned to the fibrin glue group. Fibrin glue was applied to the suture line of the pancreatic stump with the ligated main pancreatic duct. Pancreatic fistula was defined as a pancreatic fluid discharge for over 7 post-operative days diagnosed by local findings, with amylase concentration in the discharge fluid more than three times the serum amylase concentration, a level low enough that even a small pancreatic leakage could be diagnosed. RESULTS: The overall incidence of pancreatic fistula was 28.6%. Postoperative pancreatic fistulas occurred in four patients (15.4%) in the fibrin glue group and 12 (40.0%) in the control group (P = .04). The lower pancreatic fistula rate was seen in the fibrin glue group also when analyzing patients with gastric cancer or pancreatic disease only, although there was no statistically significant difference. CONCLUSIONS: Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.

Adult↗

Analysis of proliferative activity using antiproliferating cell nuclear antigen antibody in colorectal cancer.

Using anti-PCNA antibody (PC10), an immunohistochemical study of the expression of PCNA in formalin-fixed and paraffin-embedded materials of colorectal cancer patients was performed and correlation of PCNA expression with clinicopathological findings and DNA ploidy pattern was studied. PCNA labeling rate (PCNA LR) was estimated in the advancing margin of the tumor and ranged from 23.8% to 77.9%. There was a significant difference in lymphatic vessel invasion, liver metastasis and Dukes' stage between the groups with high (> 48.7) and low (< 48.7) PCNA LR (P < 0.05). No differences were seen in tumor size, histological type, lymph node metastasis or DNA ploidy pattern. In patients with younger age, infiltration to neighboring organs, a high degree of venous invasion, and peritoneal dissemination, the frequency of high PCNA LR tended to be higher (P < 0.1). The results above suggest that a high proliferative activity as defined by evaluation of the PCNA LR at the advancing margin of the tumor may be one of the parameters of malignant potential and helpful as a predictor of liver metastasis in colorectal cancer.

Antibodies, Monoclonal↗

Endothelial leukocyte adhesion molecule-1-mediated vasoinvasion of human pancreatic adenocarcinoma.

The sialyl Lewis antigens, the ligands of endothelial leukocyte adhesion molecule-1 (ELAM-1), have been used as important tumor markers for the digestive system. The expression of two sialyl Lewis antigens, sialyl Lewis A antigen (SLea) and sialyl Lewis X antigen, was examined in human pancreatic cancer cells. The expression of SLea was dominant, as shown by flow cytometric analysis. Furthermore, suppressive effects of anti-SLea antibody and anti-ELAM-1 antibody on human pancreatic cancer cell vasoinvasion were demonstrated using a new assay system, the vasoinvasion chamber. These results suggest the critical involvement of SLea and ELAM-1 molecules in human pancreatic cancer cell vasoinvasion.

Adenocarcinoma↗

Spontaneous splenic rupture during the course of a rubella infection: report of a case.

We report herein the case of a 26-year-old man who suffered a spontaneous splenic rupture during the course of a rubella infection. Initially, he presented with a high fever accompanied by a skin rash extending from the body trunk to the extremities and was admitted to hospital 3 days after onset for sudden upper abdominal pain radiating to both shoulders. On admission, he was pale and sweating with hypotension. An abdominal ultrasonographic study revealed a collection of fluid in the perisplenic space and exploratory laparotomy confirmed an intraabdominal hemorrhage from a ruptured spleen. The patient was treated by splenectomy and recovered uneventfully. The excised spleen was found to be moderately enlarged with a denuded capsule. Because the patient had no history of any external trauma and a positive serological test for rubella, we concluded that rubella contributed to the spontaneous splenic rupture in this case.

Adult↗

Protein kinase C alpha-, beta- and gamma-subspecies in basal granulated cells of rat duodenal mucosa.

Protein kinase C [cPKC: alpha, beta (beta I, beta II), gamma], a Ca(2+)- and phospholipid-dependent enzyme, has been thought to play a critical role in the synthesis and secretion of gut hormones in gastrointestinal mucosa. However, the localization of PKC has not yet been clarified at the cellular level in the gastrointestinal epithelium. The present study was made to identify cPKC-containing cells immunohistochemically in the rat duodenal epithelium by light and electron microscopy and by confocal laser scanning microscopy. Special attention was paid to the demonstration of cPKC in basal granulated cells. By light microscopy, some duodenal epithelial cells were demonstrated to be immunopositive for PKC alpha-, beta- and gamma-subspecies. Their distribution and incidence were almost similar to those of cells stained by the silver impregnation method of Grimelius. By electron microscopy, profiles of secretory granules were found at the basal region of the PKC-immunopositive epithelial cells. When the cells were double-immunostained for gastrin, serotonin or somatostatin and for PKC alpha-, beta- or gamma-subspecies, these gut hormones and PKC subspecies were shown to colocalize as examined by confocal laser scanning microscopy. These findings show that cPKC (alpha, beta, gamma) is present in basal granulated cells such as G-, EC- and D-cells, presumably playing some important role in regulation of gut hormones, including their synthesis and/or secretion.

Animals↗

The mechanism of growth-regulation of glioma cells by trapidil.

Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.

Blotting, Northern↗

Detection of point mutations in K-ras gene at codon 12 in bile from percutaneous transhepatic choledochal drainage tubes for diagnosis of biliary strictures.

Detection of K-ras mutations at codon 12 constitutes one modality for diagnosis of pancreatic tumors. We attempted to detect K-ras mutations in DNA from bile collected through percutaneous transhepatic choledochal drainage (PTCD) tubes as a diagnostic approach to biliary strictures. Since bile salts induce cell damage, we first investigated the degeneration of cells according to bile exposure time using cell lines. High-mol-wt DNA could be extracted from cells exposed to bile for 6 h, but not from those exposed for 12 h. However, DNA exposed to bile for up 12 h could be amplified by the polymerase chain reaction (PCR) method. Therefore, K-ras mutations in fresh bile specimens collected from 15 patients through PTCD tubes were examined using PCR with restriction enzyme digestion. K-ras mutations were found in five out of five (100%) pancreatic cancers, all of which were negative according to cytodiagnosis of the same bile. On the other hand, K-ras mutations were not detected in bile from biliary tract cancers or metastatic neoplasms, except for one bile duct carcinoma and one metastatic case. Thus, although K-ras mutation alone is not an absolute marker for cancer, detection of K-ras mutations in fresh bile from PTCD tubes is a useful adjunct for diagnosis of pancreatic carcinomas in cases of biliary tract strictures.

Aged↗

Optimal stimulating current for train-of-four stimulation in conscious subjects.

The purpose of this study was to determine the optimal stimulating current for train-of-four (TOF) monitoring with regard to the return of TOF response and the discomfort associated with TOF. Two variables were examined at 60, 50, 40, 30, and 20 mA: (1) times from administration of vecuronium 80 micrograms.kg-1 to returns of responses to TOF determined accelographically in 75 anaesthetised patients and (2) discomfort associated with TOF in 15 awake volunteers using visual analogue scale (VAS). Times to return of the first response to stimulation at 60, 50, 40, and 30 mA were not different (29.1 +/- 11.2, 30.1 +/- 12.0, 31.9 +/- 12.6, and 35.4 +/- 14.2 min, respectively, mean +/- SD). However, time to the return of the first response elicited at 20 mA (53.7 +/- 21.6) was longer than at higher currents (P < 0.05). Similarly, with regard to the second, third, and fourth responses, the time to the return at 20 mA was longer than at the other currents (P < 0.05). The VAS associated with TOF at 60, 50, 40, 30, and 20 mA were 7.3 +/- 1.9, 6.7 +/- 1.8, 6.0 +/- 2.0, 4.1 +/- 2.1, and 2.7 +/- 2.3, respectively. The VAS at 30 mA was less than at 60 and 50 mA (P < 0.05), and at 20 mA was less than at 60, 50, and 40 mA (P < 0.05). In conclusion it is suggested that, when testing conscious patients, 30 mA is the optimal stimulating current for TOF monitoring because it represents the best compromise of neuromuscular monitoring and patient discomfort.

Adult↗

Effects of calcium channel blockers on circulatory response to tracheal intubation in hypertensive patients: nicardipine versus diltiazem.

We studied the circulatory responses to laryngoscopy and tracheal intubation in 37 hypertensive patients who received nicardipine 30 micrograms.kg-1 iv (Group N, n = 12), diltiazem 0.3 mg.kg-1 (Group D, n = 12) or saline placebo (Group C, n = 13) 60 sec before the initiation of laryngoscopy. Anaesthesia was induced with thiopentone 5 mg.kg-1 iv, and succinylcholine 2 mg.kg-1 iv was used to facilitate tracheal intubation after precurarization with vecuronium 0.02 mg.kg-1 iv. In patients in Group C heart rate (HR) increased from 79 +/- 14 (baseline) to 110 +/- 12 (P < 0.05) associated with tracheal intubation; mean arterial pressure (MAP) increased from 116 +/- 8 to 140 +/- 77 (P < 0.05) and rate-pressure product (RPP) increased from 13385 +/- 2393 to 21251 +/- 3883 (P < 0.05). The changes from baseline values in HR and RPP after tracheal intubation in Group D were less than those in Groups C and N (P < 0.05). The increase in MAP following tracheal intubation in Groups N and D was lower than that in Group C (P < 0.05). We conclude that, compared with nicardipine, administration of diltiazem iv is associated with less circulatory response to tracheal intubation in hypertensive patients.

Adult↗

Post-tetanic burst count: a stimulating pattern for profound neuromuscular blockade.

The purpose of this study was to compare the pattern of recovery from vecuronium 0.07 mg.kg-1 induced neuromuscular blockade using post-tetanic burst count (PTBC)-(three short tetanic bursts of 0.2 msec duration every 20 msec given every second following a tetanus), and post-tetanic count (PTC)-(0.2 msec single twitch stimuli given every second following a tetanus) using an accelerometer in 60 adult patients during nitrous oxide-oxygen-isoflurane anaesthesia. In addition, the relationship among PTBC, PTC, and T1 (the 1st response in the train-of-four (TOF) stimulation) was examined to investigate whether the PTBC had an advantage over the PTC or TOF for evaluating intense neuromuscular blockade. The PTBC was greater than PTC during the 15-35 min after the administration of vecuronium (unpaired t test with Bonferroni's correction, P < 0.05). Time to the return of PTB response was shorter than that of PTT (17.7 +/- 3.2 vs 22.7 +/- 3.7 min, unpaired t test, P = 0.0005). Time from the return of PTB to that of T1 was longer than the time from the return of PTC to that of T1 (13.3 +/- 2.6 vs 9.2 +/- 2.8 min, unpaired t test, P = 0.0003). At the return of T1, PTBC was greater than PTC (14.3 +/- 6.9 vs 9.4 +/- 2.3, unpaired t test, P = 0.0153). These results suggest that, using PTBC, a more profound level of neuromuscular blockade can be evaluated than that using PTC.

Adult↗