Search PubMed⌕ Search

Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 19 recordsLinked to original sources
PubMed2003

Lewis type 1 antigen synthase (beta3Gal-T5) is transcriptionally regulated by homeoproteins.

The type 1 carbohydrate chain, Galbeta1-3GlcNAc, is synthesized by UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T). Among six beta3Gal-Ts cloned to date, beta3Gal-T5 is an essential enzyme for the synthesis of type 1 chain in epithelium of digestive tracts or pancreatic tissue. It forms the type 1 structure on glycoproteins produced from such tissues. In the present study, we found that the transcriptional regulation of the beta3Gal-T5 gene is controlled by homeoproteins, i.e. members of caudal-related homeobox protein (Cdx) and hepatocyte nuclear factor (HNF) families. We found an important region (-151 to -121 from the transcription initiation site), named the beta3Gal-T5 control element (GCE), for the promoter activity. GCE contained the consensus sequences for members of the Cdx and HNF families. Mutations introduced into this sequence abolished the transcriptional activity. Four factors, Cdx1, Cdx2, HNF1alpha, and HNF1beta, could bind to GCE and transcriptionally activate the beta3Gal-T5 gene. Transcriptional regulation of the beta3Gal-T5 gene was consistent with that of members of the Cdx and HNF1 families in two in vivo systems. 1) During in vitro differentiation of Caco-2 cells, transcriptional up-regulation of beta3Gal-T5 was observed in correlation with the increase in transcripts for Cdx2 and HNF1alpha. 2) Both transcript and protein levels of beta3Gal-T5 were determined to be significantly reduced in colon cancer. This down-regulation was correlated with the decrease of Cdx1 and HNF1beta expression in cancer tissue. This is the first finding that a glycosyltransferase gene is transcriptionally regulated under the control of homeoproteins in a tissue-specific manner. beta3Gal-T5, controlled by the intestinal homeoproteins, may play an important role in the specific function of intestinal cells by modifying the carbohydrate structure of glycoproteins.

Amino Acid Motifs↗
PubMed2003

Induction of indefinite survival of fully allogeneic cardiac grafts and generation of regulatory cells by intratracheal delivery of alloantigens under blockade of the CD40 pathway.

BACKGROUND: The authors previously showed that intratracheal delivery (ITD) of donor splenocytes induced prolonged survival of fully allogeneic cardiac grafts in mice. In this study, this treatment protocol was combined with blockade of the CD40 pathway in an attempt to induce operational tolerance. METHODS: CBA mice were given donor splenocytes (1x107) or Kb peptide (100 microg) by ITD with or without antibody specific for mouse CD40 ligand (MR1, 200 microg) 7 days before transplantation of a C57BL/10 heart. Also, splenocyte (5 x 107) from primary recipient CBA mice given ITD of donor splenocytes or Kb peptide plus MR1 were adoptively transferred into naive CBA secondary recipients 7 days after the pretreatment and C57BL/10 hearts were transplanted into those recipients the same day. RESULTS: ITD of donor splenocytes and Kb peptide induced prolonged survival of cardiac grafts (median survival time [MST], 74 and 56 days, respectively), whereas naive control mice and mice pretreated with syngeneic splenocytes had acute graft rejection (MST in both groups, 7 days). When MR1 was included, all grafts survived indefinitely (>200 days), but mice pretreated with MR1 alone had graft rejection (MST, 54 days). Mice bearing cardiac grafts had acceptance of skin grafts from C57BL/10 but not BALB/c mice, demonstrating that operational tolerance was induced. Secondary recipients given adoptive transfer of splenocytes from primary recipients of the combined treatment had acceptance of C57BL/10 grafts, suggesting that regulatory cells were generated within 7 days of pretreatment. CONCLUSIONS: ITD of donor splenocytes or Kb peptide under blockade of the CD40 pathway induced operational tolerance and generated regulatory cells.

Adoptive Transfer↗
PubMed2003

High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells.

BACKGROUND: The authors investigated whether antithrombin III (AT-III) could induce unresponsiveness to alloantigens. METHODS: CBA mice were given intravenous injection of 50 or 500 U/kg AT-III or control plasma the same day as transplantation of a heart from a C57BL/6 mouse. An adoptive transfer study and mixed leukocyte culture analysis were also performed. RESULTS: Naive CBA mice rejected C57BL/6 cardiac grafts acutely (median survival time [MST], 9 days). The 50-U/kg dose of AT-III induced a moderate increase in graft survival (MST, 25 days), whereas control mice rejected their graft acutely (MST, 7 days). With the 500-U/kg dose of AT-III, all grafts survived indefinitely (>100 days) and regulatory cells were generated. In vitro, AT-III suppressed proliferation of mixed leukocyte responses and generation of interleukin-2. CONCLUSION: AT-III can be not only an antithrombotic agent but also a strong immunomodulating agent when used at high dose.

Animals↗
PubMed2003

Chemosensitivity testing--present and future in Japan.

Radical surgery with extended lymph node dissection is the first and only curative treatment of gastrointestinal cancer. Although the combined cancer chemotherapy has achieved 30%-50% response rates, a controversy still remains over the significance of the adjuvant cancer chemotherapy after surgery. To break through this limitation, we have introduced the chemosensitivity test to evaluate the appropriate adjuvant cancer chemotherapy for advanced gastrointestinal cancer. Our plural studies indicated that the chemosensitivity test would be useful in evaluating the appropriated adjuvant chemotherapy by increasing survival in the sensitive group. Recently, the molecular targets have been clarified for the conventionally available antitumor agents, e.g., thymidylate synthetase for 5-fluorouracil, ATP-binding cassette transporters for anthracyclines, glutathione-related detoxification for platins, and topoisomerase I for CPT-11, which will be applied for dinical use in evaluating the appropriate cancer chemotherapy. The chemosensitivity test is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor in five institutes at present. Because complete dissection and chemosensitivity test-guided adjuvant chemotherapy will result in a survival benefit for patients with advanced gastrointestinal cancer, this test should be approved as "social insurance" for further wide clinical application.

Antineoplastic Agents↗
PubMed2003

Combined antitumor activity of 7-hydroxystaurosporine (UCN-01) and tamoxifen against human breast carcinoma in vitro and in vivo.

BACKGROUND: 7-Hydroxystaurosporine (UCN-01) was originally isolated as a protein kinase C inhibitor and has shown antitumor activity against several human cancer cell lines. UCN-01 inhibits cell cycle progression from the G1 to the S phase and is associated with inhibition of cyclin-dependent kinase (CDK) activity and induction of intrinsic CDK inhibitor p21, leading to dephosphorylation of retinoblastoma (Rb) protein. Tamoxifen (TAM) traps cancer cells in the G1 phase, suggesting that the mechanism of action of TAM is similar to that of UCN-01. The present study was conducted to assess the antitumor activity of UCN-01 combined with TAM against human breast carcinoma cells in vitro and in vivo. MATERIALS AND METHODS: MCF-7 cells were treated with UCN-01, TAM, or UCN-01 combined with TAM at various concentrations in vitro. The antitumor effect was evaluated as the inhibition rate (I.R.%) by MTT assay. Two human breast carcinoma xenografts in nude mice, MCF-7 and Br-10, were treated with UCN-01, TAM or both agents together. The expression of p21 and the phosphorylation status of Rb protein in MCF-7 cells were detected by Western blotting. RESULTS: UCN-01 or TAM alone inhibited the proliferation of MCF-7 cells in a concentration-dependent manner. Combined treatment with UCN-01 followed by TAM inhibited the growth of MCF-7 cells synergistically and no significant differences in cytotoxicity were observed between the different sequences of UCN-01/TAM and TAM/UCN-01. Combination treatment with UCN-01 and TAM against MCF-7 and Br-10 in vivo exhibited superior antitumor effects compared with either agent treatment alone. Although 0.1 microg UCN-01 per ml (I.R.: 48.1%) or 2 microM TAM (I.R.: 31%) induced p21 expression, phosphorylation of Rb protein was not inhibited. However, combination treatment with UCN-01 and TAM at the same concentrations resulted in an I.R. of 67% and dephosphorylation of Rb protein. CONCLUSION: The present study suggests that combining UCN-01 and TAM could result in augmented cytotoxicity because of their similar mechanism of action. This combination may have potential clinical applications for breast cancer treatment, by reducing the toxicity of UCN-01.

Animals↗
PubMed2003

Diffuse cavernous hemangioma of the rectum: report of a case.

Cavernous hemangioma of the rectum (CHR) is an uncommon benign vascular lesion, which mainly affects young adults. The rectosigmoid area is the most common site of cavernous hemangioma in the gastrointestinal tract. CHR is often misdiagnosed due to a lack of knowledge of the clinical features. We report a case of CHR, focusing on the clinical features, diagnostic procedures used, and treatments given. This patient was finally treated effectively with abdominoperineal resection. Thorough preoperative imaging is necessary to confirm the diagnosis and evaluate both the site and extent of the hemangioma. Magnetic resonance imaging (MRI) provides information about the dimensions of the tumor and involvement of the adjacent structures with its high resolution and multiplanar capability, without the use of contrast medium. Moreover, endorectal surface coil MRI depicts the five separate layers of the bowel wall and internal and external sphincter more clearly than the conventional body coil MRI.

Female↗
PubMed2003

Colorectal motility induction by sacral nerve electrostimulation in a canine model: implications for colonic pacing.

PURPOSE: This study investigated the role of the sacral nerves in the mechanism of defecation using adult mongrel dogs. The possibility of designing a colonic pacemaker as a new therapeutic device to treat defecation disturbances, such as fecal incontinence and severe constipation, is also discussed. METHODS: Colorectal motility during spontaneous defecation was monitored with force strain-gauge transducers implanted in the proximal, distal, and sigmoid colon, rectum, and internal anal sphincter. Under general anesthesia, the sacral nerve was stimulated electrically, and the colorectal motility response was examined. RESULTS: During spontaneous defecation, three characteristic motility patterns were observed: 1) giant migrating contractions of the colon were propagated to the rectum or anus; 2) the rectum relaxed before the giant migrating contractions were propagated; and 3) the internal anal sphincter was relaxed during the propagation of the giant migrating contraction. Sacral nerve stimulation elicited the following three unique responses: 1) contractile movements were propagated from the distal colon to the rectum; 2) a relaxation response was noted in the rectum; and 3) the internal anal sphincter exhibited a relaxation response. The duration and propagation velocity of the contractile responses and the duration of relaxation responses elicited by electrical stimulation of the sacral nerve were similar to those that occurred during spontaneous defecation, but their amplitudes were smaller. CONCLUSION: The coordinated processes of the colon and anorectum during defecation were affected by the sacral nerves. This suggests that it is possible to design a colonic pacemaker to control lower colonic and rectal movements.

Animals↗
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

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

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

[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↗