Search PubMed⌕ Search

Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 91 records · Page 5Linked to original sources

Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor.

Recent studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) and elevation of COX-2-mediated synthesis of prostaglandin E(2) (PGE(2)) were observed in various cancers including esophageal cancer, but their roles in carcinogenesis of the esophagi still remain unclear. To address the issue, we observed the reduction of N:-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in rat esophagi via JTE-522 (4-[4-cyclohexyl-2-methyloxazol-5-yl]-2-fluorobenzenesulfonamide), a selective COX-2 inhibitor. In this study, 54 F344 male rats were divided into nine groups; JTE-522 (3, 9 and 30 mg/kg) was administered orally. We also examined the effects of JTE-522 on COX-2 mRNA and synthesis of PGE(2). In the group in which JTE-522 was administered intermittently at a daily dose of 30 mg/kg, the number of NMBA-induced esophageal tumors per rat significantly reduced, to 62% (P< 0.05), but the size of the tumors was not significantly inhibited. In the group in which JTE-522 was administered continuously five times weekly for 24 weeks at a daily dose of 9 mg/kg, both the number and size of tumors significantly reduced, to 29 and 44%, respectively (P<0.05). Furthermore, JTE-522 suppressed not only tumor formation but also developing carcinomas (P<0.0021) [corrected]. In this study, treatment with NMBA alone resulted in an approximately 5-fold rise in expression of COX-2 mRNA detected by semi-quantitative RT-PCR analysis and an approximately 7-fold increase in the production of PGE(2) measured by ELISA compared with the normal esophageal mucosa. The up-regulated COX-2 expression did not decrease with the treatment of JTE-522 at the 3, 9 and 30 mg/kg doses; however, the increased levels of PGE(2) synthesis were significantly decreased by administering JTE-522 (P<0.01). Our study suggests that COX-2-mediated PGE(2) is important in NMBA-induced esophageal tumorigenesis in rats, and therefore may be a promising chemotherapeutic target for the prevention and treatment of esophageal cancer, especially with selective COX-2 inhibitors.

Animals↗

Successful unrelated cord blood transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes and surgical resection: case report.

A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic leukemia developed pulmonary aspergillosis during severe neutropenia by re-induction therapy. She was treated by intravenous fluconazole, oral itraconazole with plasma level monitoring and surgical resection of the focus for 3 months after clinical diagnosis of fungal infection was made. Once she had recovered from surgery we attempted to induce remission with anti-fungal treatment. She developed fever and neutropenia and appeared unlikely to remit with conventional chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation was performed 2 months after the induction therapy. Her pulmonary aspergillosis was reactivated during subsequent conditioning. Anti-fungal drugs were switched to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte concentrates were transfused. She obtained engraftment and has maintained complete hematological and molecular remission without signs of aspergillus infection for 13 months so far after transplantation. Even very high-risk transplantation in pediatric patients could be successfully supported by carefully designed intense comprehensive medical care.

Amphotericin B↗

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

Adult↗

An experimental study on radiation streaming through a labyrinth in a proton accelerator facility of intermediate energy.

A radiation streaming experiment has been carried out at the Takasaki Ion Accelerator Facility for Advanced Radiation Application at the Japan Atomic Energy Research Institute in a room housing a Cu target irradiated with 68 MeV protons and in a labyrinth of three-legs having a total length of 29 m. In the experiment, neutron and gamma ray energy spectra, neutron reaction rates, and neutron and gamma ray dose equivalent rates were measured using various counters and dosimeters. The experimental data show the applicability of some empirical formulas for estimating the thermal neutron flux in a room and neutrons streaming in a labyrinth designed for a proton accelerator operating in the intermediate energy region. The data suggest that it is mandatory to estimate the gamma ray dose equivalent rate in a labyrinth, which is dominated by the secondary gamma rays due to the neutron capture reaction.

Academies and Institutes↗

Successful subcutaneous pancreatic islet transplantation using an angiogenic growth factor-releasing device.

INTRODUCTION: Although the subcutaneous tissue is considered as an attractive site for pancreatic islet transplantation, the success rate has been extremely low. AIMS: To use basic fibroblast growth factor (bFGF) to induce neovascularization and sufficient blood flow around the space formed for grafted islets in the subcutaneous tissue to improve the islet survival. METHODOLOGY: In the experimental group, two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue (back) of diabetic Lewis rats. One week after implantation, in the same site, isolated rat islets were syngeneically transplanted after the removal of the devices. In the control group, two devices without bFGF were implanted before subcutaneous islet transplantation of the same number of islets. RESULTS: One week after the implantation of the bFGF-releasing devices in the experimental animals, the devices induced angiogenesis by slow release of bFGF. After transplantation of islets, the neovascularized recipient rats showed significant decreases in nonfasting blood glucose concentration and maintained normoglycemia for more than 3 months. However, in the control group, all rats failed to achieve normoglycemia after transplantation in the absence of neovascularization. CONCLUSION: This study provides evidence that the subcutaneous tissue is a promising site for pancreatic islet transplantation, which suggests the acceptability of this treatment for diabetic recipients.

Animals↗

Rapid progression of hepatocellular carcinoma after transcatheter arterial chemoembolization and percutaneous radiofrequency ablation in the primary tumour region.

We report one patient who showed rapid progression of hepatocellular carcinoma (HCC) after undergoing transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (PRFA) for a small HCC measuring 2.5 cm in diameter. Enhanced magnetic resonance imaging (MRI) following treatment showed complete tumour necrosis and did not reveal the presence of a tumour around the treated area. Furthermore, the serum alpha-fetoprotein (AFP) level decreased at the completion of therapy. However, the HCC advanced in a very short time. Numerous tumours around the treated area were observed on enhanced computed tomography (CT) 50 days after PRFA. It is strongly suspected that the tumour was disseminated through the portal system because of the presence pattern of tumours. We believe this to be the first case illustrating a hepatic cancer that progressed rapidly following TACE and PRFA.

Aged↗

Case of metastatic breast cancer from esophageal cancer.

Metastasis to the breast from extramammary malignancies is rare. This is the third case report of metastatic breast cancer from esophageal cancer. We report the clinical, radiographic, and pathologic findings of a 57-year-old woman who underwent esophagectomy for esophageal cancer and developed metastatic cancer 2 years later. Pathologic examination of a resected specimen of the breast revealed squamous cell carcinoma invading the mammary glands. Estrogen receptor and axillary lymph node metastasis were negative with immunostaining. She is alive 6 months after the modified radical mastectomy.

Breast Neoplasms↗

Increased proportion of HLA-class-I-specific natural killer cell receptors (CD94) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.

In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMT). The proportion of CD94 expression on PBMC was higher in patients without chronic graft-versus-host disease (cGVHD) and also in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, the proportions of CD94+/CD3+ cells and CD94+/CD8+ cells were higher in cGVHD patients showing good response. In addition, the proportion of NKG2A-expressing cells was higher in patients without cGVHD than in patients with cGVHD. Therefore, chronic allostimulation after allo-BMT may augment the proportion of CD94/NKG2A-positive cells, and these cells may play some role in the regulation of alloresponse in some patients.

Antigens, CD↗

Thyrotropin receptors in brown adipose tissue: thyrotropin stimulates type II iodothyronine deiodinase and uncoupling protein-1 in brown adipocytes.

It has been demonstrated that TSH receptors are expressed not only in thyroid gland but also in extrathyroidal tissues. Brown adipose tissue of guinea pig has been reported to express TSH receptor messenger RNA (mRNA), but the physiological roles of TSH receptors in brown adipose tissue have not been understood. We studied the expression and function of TSH receptors in rat brown adipose tissue and cultured rat brown adipocytes. Northern analysis demonstrated the expression of TSH receptor mRNA in rat brown adipose tissue and cultured rat brown adipocytes. TSH receptor mRNA in rat brown adipose tissue was decreased by cold exposure of the rat, and its mRNA in cultured rat brown adipocytes was also decreased by incubation with TSH or (Bu)(2)cAMP. TSH increased the intracellular cAMP concentration in cultured rat brown adipocytes in a dose dependent manner. Type II iodothyronine deiodinase mRNA, its activity, and uncoupling protein-1 mRNA in cultured rat brown adipocytes were significantly increased by incubation with TSH in a dose-dependent manner. These results suggest the expression of functional TSH receptors in brown adipose tissue, which may be involved in regulation of the expression of type II iodothyronine deiodinase and uncoupling protein-1.

Adipose Tissue, Brown↗

Efficacy of the inflammatory cell infiltration inhibitor IS-741 on colitis induced by dextran sulfate sodium in the rat.

We examined the therapeutic effects of the inflammatory cell infiltration inhibitor IS-741 (N-(2-((ethylsulfonyl)amino)-5-(trifluoromethyl)-3-pyridinyl)-cyclohexanecarboxamide monosodium salt monohydrate) on a rat colitis model. As a result of its effects on leukocyte infiltration, IS-741 inhibits cell adhesion, alleviates symptoms and signs of pancreatitis and multiple organ failure and demonstrates a life-saving effect in a model of severe acute pancreatitis. A rat model was prepared by inducing colitis with 3% dextran sodium sulfate (DSS) and maintaining pathology with 1% DSS. Repeated oral administration of IS-741 at 1, 10 or 100 mg/kg per day was conducted for 2 weeks (during treatment with 1% DSS). IS-741 at each dose decreased the area of erosion in the large intestine, thickening of the wall of the large intestine and anemia caused by melena. Some effects of IS-741 were nearly equivalent to those of the control compound salazosulfapyridine. Furthermore, IS-741 markedly alleviated inflammatory cell infiltration into the intestinal wall. IS-741 improved lesions in a rat DSS model by inhibiting leukocyte infiltration, suggesting the possibility of clinical application of this drug for IBD.

Administration, Oral↗

Three-dimensional portography using multislice helical CT is clinically useful for management of gastric fundic varices.

OBJECTIVE: This study seeks to evaluate three-dimensional (3D) helical CT portography as a tool for examining patients with gastric fundic varices. SUBJECTS AND METHODS: We compared 3D helical CT portography and conventional angiographic portography in 30 consecutive patients with gastric fundic varices. We assessed whether 3D helical CT portography is useful in selecting patients and in evaluating the results of balloon-occluded retrograde transvenous obliteration. RESULTS: Three-dimensional helical CT portography simultaneously depicted second or third branches of the intrahepatic portal vein and provided images of entire portosystemic collaterals. On 3D helical CT portography, gastric fundic varices were seen in 30 patients (100%), left gastric veins in 19 (63%), posterior gastric veins or short gastric veins in 28 (93%), gastrorenal shunts in 27 (90%), paraumbilical veins in three (10%), and inferior phrenic veins in two patients (7%). Findings of 3D helical CT portography and conventional angiographic portography were in close agreement. However, in four patients, posterior gastric veins or short gastric veins were not seen on conventional angiographic portography images of the spleen, but they were clearly revealed on 3D helical CT portography. Treatment was successful in all patients except one. Three-dimensional helical CT portography could easily evaluate therapeutic results. CONCLUSION: Three-dimensional helical CT portography proved so effective that it can be considered a less invasive alternative than conventional angiographic portography in assessing portosystemic collaterals. CT portography is useful in selecting candidates from patients with gastric fundic varices for retrograde transvenous obliteration and also in evaluating therapeutic results.

Adult↗

Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma.

Angiogenesis is essential for tumor growth and metastasis. Some angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) are involved in increased angiogenic activity and disease progression in many carcinomas. However, there is little information regarding the association between angiogenic factors and leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable it to easily receive nutrition and medicinal components, chemotherapy cannot effectively treat leiomyosarcoma. This means the resistance to anticancer drugs in leiomyosarcoma is very strong. However, the resistant mechanism is still unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF, intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The findings of this study suggest that in leiomyosarcoma, angiogenic factors, such as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis, and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation might be related to chemoresistance mechanism.

Angiogenesis Inducing Agents↗

Polymorphism and allelic loss at the AS3 locus on 13q12-13 in esophageal squamous cell carcinoma.

Our previous studies of esophageal squamous cell carcinoma (ESC) revealed that frequent loss of heterozygosity (LOH) on 13q12-13 was associated with lymph node metastasis. These results suggest that 13q12-13 may harbor a tumor suppressor gene which regulates lymph node metastasis. Recently, a new tumor suppressor candidate, AS3, was identified in this region. We therefore examined AS3 alterations by PCR-SSCP and RT-PCR. Although polymorphisms were found in exon 10 and introns 21, 23, 25 and 29, a possible tumor specific mutation in exon 6 was identified in only one of 31 ESC-derived cell lines, indicating that the remaining allele of AS3 was rarely inactivated by mutational events. Interestingly, ESC patients with rare alleles frequently exhibited lymph node metastasis. These results suggest that polymorphic variation and LOH at the AS3 locus might be associated with lymph node involvement in ESC.

Alleles↗

[Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome].

We have experienced anesthetic management for mitral valve replacement in a 48-year-old female with idiopathic hypereosinophilic syndrome. Preoperative examination showed mild biventricular dysfunction. Anesthesia was induced and maintained with meticulous administration of fentanyl and midazolam in 66% oxygen. Administration of dopamine, dobutamine and prostaglandin E1 contributed to reducing afterload and maintaining cardiac output. The operative and postoperative courses were uneventful. Hypereosinophilic syndrome is one of the identified causes of restrictive cardiomyopathy. Anesthesia for patients with hypereosinophilic syndrome must be carried out carefully, because heart or respiratory failure is the most dangerous complication. In patients with hypereosinophilic syndrome requiring general anesthesia, perioperative steroid cover is advisable. This may reduce or prevent serious lung complications.

Anesthesia, General↗

[Experience of pediatric cardiac transplantation in the Cleveland Clinic Foundation].

Brain death was not approved on the patients under 6 years old in Japan now. It is impossible to perform cardiac transplantation on the small children. Between October 1997 and November 1998, cardiac transplantation was performed by pediatric cardiac surgical team in 11 children at the Cleveland Clinic Foundation. 7 patients were cardiomyopathy under 18 years old and 4 were congenital heart diseases in all ages. 8 were status 1 and 2 were requiring extracorporeal membrane support. Bicaval technique was exclusively utilized. There was one early death due to multiple organ failure. 10 patients underwent myocardial biopsy and the half of them had more than 3 A rejection. These acute rejections were controlled with steroid pulse therapy and OKT-3 treatment. We took part in the management of patients with pediatric cardiac transplantation at the Cleveland Clinic Foundation. Practical patient cares were described in this report.

Adolescent↗

Functional comparison of the single-layer agarose microbeads and the developed three-layer agarose microbeads as the bioartificial pancreas: an in vitro study.

In this study, the insulin secretory characteristics of the microencapsulated hamster islets were studied during long-term culture. The hamster islets were encapsulated as single-layer agarose microbeads or three-layer agarose microbeads with agarose and agarose containing poly(styrene sulfonic acid) (PSSa), respectively. The influence of PSSa on the function of the rat islets microencapsulted in three-layer microbeads was primarily monitored. The aim of this study was to examine the influence of the PSSa on the in vitro function of the islets encapsulated in the agarose/PSSa microbeads compared with single-layer agarose microbeads during long-term culture. The microbeads were cultured for 30 days in medium of Eagle's MEM at 37 degrees C in 5% CO2 and 95% air. The basal insulin secretion into the culture medium was measured daily during the first 12 days and two times per week until 30 days. The microbeads were subjected to static incubation test on the 10th, 20th, and 30th day during culture. The basal insulin secretion level of the agarose/PSSa microbeads was significantly higher than that of single-layer agarose microbeads. The static incubation tests revealed a similar pattern of insulin secretion from both microbeads when they were exposed to high glucose challenge. In the static incubation test, both could significantly increase insulin release to more than 6.61 times (stimulation index) in response to high glucose stimulation and could significantly decrease when glucose concentration returned from high glucose to low glucose on the 10th, 20th, and 30th day of culture. This study demonstrated that the hamster islets enclosed in agarose/PSSa hydrogel not only continuously secreted basal amounts of insulin, but also maintained their response to high glucose stimulation similar to the agarose microbeads. The above results together with those of our previous in vivo study suggest that the three-layer microbeads (agarose/PSSa) are well suitable for xenotransplantation of islets for the clinical application.

Animals↗

The influence of the anticomplement synthetic sulfonic polymers on the function of pancreatic islets: an in vitro study.

In a previous experiment, we demonstrated the anticomplementary efficacy of poly(stryrene sulfonic acid) (PSSa) and poly(2-acrylamido-2-methyl propane sulfonic acid) (PAMPS). The aim of this study was to examine their influence on the function of pancreatic islets in vitro. In this study, after culturing the rat islets with RPMI-1640 culture medium containing different concentrations of soluble PSSa or PAMPS for 24 h at 37 degrees C, we performed morphological and functional examination of the rat islets. We found that the islets maintained their normal morphology regardless of whether they were in the PSSa or PAMPS groups when the concentrations of soluble PSSa or PAMPS in the media were below 1 g/dl. In the static incubation study, the islets cultured in the PAMPS groups showed significantly high insulin secretory response to glucose challenge but those in the PSSa groups lost the response when the concentrations of soluble PSSa or PAMPS in the media were below 1 g/dl. The PAMPS not only had strong anticomplementry effect, but also maintained the good insulin secretory capacity of the islets. These results indicated that PAMPS is a promising bioartificial material for future clinical application of biohybrid artificial pancreas preparation. It is well suitable for xenotransplantation experiments.

Animals↗