Search PubMed⌕ Search

Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 163 records · Page 9Linked to original sources
PubMed2003

The role of nitric oxide after a short period of liver ischemia-reperfusion.

BACKGROUND: Liver ischemia-reperfusion injury is a serious problem during liver resection and transplantation. Nitric oxide (NO) has been suggested to have a cytoprotective effect for microcirculation, while the interaction of active oxygen species and NO produces peroxynitrite anion. The present study attempts to clarify the role of NO in liver ischemia-reperfusion injury. METHODS: Wistar male rats were subjected to 30 min of hepatic ischemia followed by reperfusion. The model rats were divided into the three following groups: a control group that was not administered NO synthase inhibitors, and two experimental groups that were administered either N(omega)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine. In each group, we examined active oxygen species and nitric oxide production, and investigated liver function by measuring serum transaminase levels. In addition, we conducted histopathologic examinations and microcirculation examinations using intravital videomicroscopy. RESULTS: In the control group, NO concentrations in the plasma increased with time after reperfusion. A decrease in NO production was detected in the groups administered NO synthase inhibitors. Elevated serum transaminase levels became more prominent after L-NAME administration, while aminoguanidine administration reduced its level. The degree of microcirculation failure was found to be more prominent in the L-NAME-administered group over both the control group and the aminoguanidine-administered group. A significantly lower survival rate was observed at 6 h after reperfusion in the L-NAME-administered group over that of the other groups. CONCLUSIONS: A reduction of the ischemia-reperfusion injury is important in inhibiting the production of high-output NO and peroxynitrite, and in maintaining NO levels necessary for maintenance of microcirculation.

Animals↗
PubMed2003

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition.

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

Animals↗
PubMed2003

Sialyl Lewis X analog attenuates gastric microcirculatory disturbance and gastric mucosal erosion induced by thermal injury in rats.

BACKGROUND AND AIM: We hypothesize that selectins, which are adhesion molecules, are involved in the pathogenesis of stress-induced gastropathy. We therefore investigated whether the novel Sialyl Lewis X (SLex) analog, which is a clinically available antagonist of selectins, attenuate gastric mucosal lesions induced by thermal injury. METHODS: Male Wistar rats were anesthetized and a 30% full-skin thickness dorsal burn was inflicted on each rat. The SLex analog was administrated into the jugular vein 30 min before and 2.5 h after the thermal injury. Saline was administered to the vehicle group. The distribution of E-selectin immunoreactivity on the luminal side of the gastric mucosal microvascular network was observed by immunohistochemical methods. Active oxygen species were measured by the chemiluminescence method. Rolling leukocytes and endothelial damage, investigated by using Monastral Blue B (MBB), of the gastric mucosal microvascular network were observed through an intravital microscope. RESULTS: A high intensity of E-selectin fluorescence was observed on the luminal surface of the venular endothelial cells 5 h after thermal injury in the vehicle group. However, E-selectin-associated fluorescence was almost negligible in the non-injury group and in the SLex analog group. The SLex analog also attenuated the rolling of leukocytes in the venules, venular deposits of MBB, luminol-dependent chemiluminescence activities, and gastric mucosal lesion formation. CONCLUSION: It is suggested that the selectin family is involved in gastric microcirculatory disturbance and the pathogenesis of gastric mucosal lesions after thermal injury. A novel preventive therapy using the SLex analog is considered to effectively protect both gastric microcirculation and the gastric mucosa in rats with thermal injury.

Animals↗
PubMed2003

Bilirubin rinse: A simple protectant against the rat liver graft injury mimicking heme oxygenase-1 preconditioning.

Heme oxygenase (HO)-1 preconditioning through genetic or pharmacologic interventions was shown experimentally to improve posttransplant outcome of liver grafts. However, its clinical application requires careful consideration because of the complexity and economic costs of the procedures. This study aimed to examine if graft preconditioning with HO-1 could be substituted by a simple treatment with heme-degrading products such as bilirubin. Rats were pretreated with or without hemin, an HO-1 inducer for preconditioning. Their livers were harvested as grafts in University of Wisconsin (UW) solution for 16 hours at 4 degrees C and followed by reperfusion ex vivo or by transplantation in vivo. The control grafts were also treated with a rinse buffer containing varied concentrations of unconjugated bilirubin with different time intervals. The HO-1-preconditioned grafts ex vivo exhibited a marked improvement of bile output and cell injury that was cancelled by blocking HO with zinc protoporphyrin-IX. The aggravation of the graft viability by the inhibitor was repressed by supplementation of bilirubin but not by that of carbon monoxide. Furthermore, a short-term rinse treatment with micromolar levels of bilirubin attenuated biliary dysfunction and cell injury of the grafts both ex vivo and in vivo even without HO-1 preconditioning. The protective effects of HO-1 preconditioning or bilirubin rinse appeared to involve its inhibitory effects on lipid peroxidation in hepatocytes. In conclusion, these results suggest that bilirubin rinse serves as a simple strategy to ameliorate hyperacute oxidative stress and hepatobiliary dysfunction of the transplanted grafts, mimicking effects of HO-1-mediated preconditioning.

Adenosine↗
PubMed2003

Balloon-catheter-assisted endoscopic snare papillectomy for benign tumors of the major duodenal papilla.

BACKGROUND: Adenomas of the major duodenal papilla are considered premalignant and should be resected completely. Endoscopic snare papillectomy has been recognized as a safe and feasible treatment. An endoscopic snare papillectomy technique was devised using a balloon catheter inserted into the common bile duct to more efficiently resect papillary tumors en bloc. METHODS: Two patients with benign adenoma of the major duodenal papilla were included in this study. A balloon catheter linked to a snare was inserted into the bile duct via the accessory channel of a duodenoscope, and snare resection was performed after pulling the expanded balloon toward the duodenal lumen. RESULTS: En bloc papillectomy was successfully performed, leaving the lateral margin free of tumor as confirmed microscopically. No complications were observed in either case. CONCLUSIONS: Given an appropriate indication, balloon-catheter-assisted endoscopic snare papillectomy is a useful technique for the treatment of tumors of the major duodenal papilla.

Adenoma↗
PubMed2003

Histological complete response in a case of advanced gastric cancer treated by chemotherapy with S-1 plus low-dose cisplatin and radiation.

A 76-year-old male was diagnosed with stage IV (cT4, cN2, cP0, cH0, cM0) gastric carcinoma with a type 3 tumor in the cardia with lymph node metastases, determined by gastrofiberscope and abdominal computed tomography (CT). The patient was treated with chemotherapy consisting of S-1 and low-dose cisplatin (CDDP) during the first cycle (3 weeks). S-1 was orally administered at a dose of 100 mg/day (60 mg/m(2)/day) on days 1-21. CDDP was infused at a dose of 10 mg/day (6 mg/m(2)/day) on days 1-5, 8-12 and 15-19. After this cycle, the clinical response was evaluated as no change (NC). In the second cycle, radiation therapy (2 Gy/day for 5 days/week) was initiated along with the chemotherapy. The CDDP dose was decreased to 7.5 mg/day because of the grade 3 thrombocytopenia and grade 2 leukocytopenia that occurred during the first cycle. The second cycle was stopped at a total radiation dose of 48 Gy due to grade 3 thrombocytopenia and grade 2 leukocytopenia. Examination after this treatment showed remarkable reduction of tumor volume in the primary lesion and lymph nodes, which was defined as a partial response (PR). The patient then underwent total gastrectomy with D1 lymph node dissection. The postoperative course was uneventful without surgical complications. At this time, no gastric cancer cells were detected in the resected specimen, including the primary lesion and lymph nodes, confirming a pathological complete response (CR grade 3). Thus, the chemo-radiation treatment regimen described here may be a potent tool to control advanced gastric carcinoma.

Aged↗
PubMed2003

Short-term surgical outcomes of laparoscopic colonic surgery in octogenarians: a matched case-control study.

This study was undertaken to evaluate the short-term surgical outcomes of laparoscopic surgery for colonic carcinoma in octogenarians and compare them with those for a younger group of patients who underwent the same surgical procedures. This matched case-control study involved 17 octogenarian patients with colonic carcinoma who underwent laparoscopic surgery between 1996 and 2001. The results were compared with those for 34 matched patients aged 60 years or less who underwent the same surgical procedures during the same period. Both groups were well matched for clinical characteristics. However, the American Society of Anesthesiology status was significantly higher in the octogenarian group (P = 0.001). There were no significant differences between the two groups in terms of the incidence of complications, the interval before resumption of liquid or solid food intake, or length of hospitalization. There were no deaths in either group. Advanced age should not be regarded as a contraindication for laparoscopic colonic surgery.

Adult↗
PubMed2003

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray.

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.

Antineoplastic Agents↗
PubMed2003

Gene expression in colorectal cancer and in vitro chemosensitivity to 5-fluorouracil: a study of 88 surgical specimens.

To predict the sensitivity of colorectal cancer to 5-fluorouracil (5-FU), we compared the gene expression of surgically obtained colorectal cancer specimens with chemosensitivity to 5-FU as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Eighty-eight patients with advanced and/or metastatic colorectal cancer provided written informed consent and entered the trial from September 2000 to October 2001. Fresh surgical specimens were used for the MTT assay, and sensitivity to 5-FU was evaluated at a cutoff concentration of 50 microg/ml and 48-h incubation time. Frozen samples were stored at - 80 degrees C until mRNA analysis of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), es-nucleoside transporter (NT), and E2F1 by real-time RT-PCR. The correlations between the variables were analyzed, and the predictive value of these mRNAs was assessed statistically using a receiver operating characteristic (ROC) curve. NT and DPD, TP and DPD, and TP and NT mRNA expression levels correlated significantly, while TS and E2F1 showed no correlations. High NT expression was associated with low sensitivity to 5-FU (P < 0.013), as were high DPD and E2F1 expression (P < 0.022 for both). High TP mRNA expression correlated with low sensitivity to 5-FU (P < 0.034), although high TS mRNA expression did not. ROC curves indicated that DPD and NT mRNAs were possible predictors of sensitivity to 5-FU, with cutoff values of 0.6 and 0.4, respectively. The sensitivity of colorectal cancer to 5-FU may be regulated by DPD, the rate-limiting enzyme of catabolism, and NT, an important transmembrane transporter of nucleosides.

Antimetabolites, Antineoplastic↗
PubMed2003

Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy. RESULTS: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008). CONCLUSIONS: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Adenocarcinoma↗
PubMed2003

Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 protein and messenger RNA in primary biliary cirrhosis.

OBJECTIVE: This study examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the autoimmune process of bile duct destruction in the early stages of primary biliary cirrhosis (PBC). MATERIALS AND METHODS: Ten PBC liver samples and five control samples were studied. Immunohistochemical studies of ICAM-1 and LFA-1, and Western blot of ICAM-1 were performed. Immunoelectron microscopy was conducted using immunoglobulin-gold and silver staining. Human ICAM-land LFA-1 peptide nucleic acid probes were used for in situ hybridization. RESULTS: In PBC liver samples, immunohistochemistry showed aberrant ICAM-1 expression on bile duct epithelial plasma membrane and also luminal sites of endothelial plasma membrane of terminal portal venules. Western blot confirmed ICAM-1 protein expression. LFA-1-positive lymphocytes were associated with epithelial cells of septal and interlobular bile ducts. Immunoelectron microscopy localized ICAM-1 on the luminal and basal surfaces as well as on lymphocytes around damaged bile duct epithelial cells, and LFA-1 on lymphocytes around damaged bile ducts. Messenger RNA expression of ICAM-1 was demonstrated in bile ducts, and LFA-1 in lymphocytes around bile ducts. CONCLUSION: De novo expression of ICAM-1 and LFA-1 at protein and mRNA levels in PBC may imply an inductive role of ICAM-1 through binding with its ligand LFA-1 in the extravasation of activated lymphocytes and lymphocyte-mediated bile duct destruction.

Adult↗
PubMed2003

[Standardization of cancer treatment and legal medical standards].

Legal medical standards are usually applied in two ways in Japanese medical malpractice cases. One application is a judgment on the quality of medical treatment, and the other is an evaluation of the validity of informed consent. Legal medical standards are not equivalent in all medical institutions. If physicians in a medical institution are expected to be aware of the most recent medical knowledge, that becomes the medical standard of the institution. For physicians in major metropolitan medical institutions, such knowledge constitutes the medical standard even before it is published in the guidelines of a committee of an established national medicoprofessional society. The standardization of cancer treatment may be used as evidence in medical malpractice suits brought by cancer patients based on both the quality of treatment and valid informed consent. In addition, it is possible that the validity of informed consent may be given more weight by the courts than the following of a course of standardized treatment by individual physicians/medical institutions in cases where patients have done extensive research on and exhibit informed knowledge of new treatment modalities.

Humans↗