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Biomedical subjects

Hisao Tajiri

Publications and source records attributed to Hisao Tajiri.

At least 19 recordsLinked to original sources
PubMed2007

Streptococcal preparation OK-432 promotes fusion efficiency and enhances induction of antigen-specific CTL by fusions of dendritic cells and colorectal cancer cells.

Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various types of cancer but has not yet been standardized. Antitumor activity can be modulated by different mechanisms such as dendritic cell (DC) maturation state. This study addressed optimal strategies for FC preparations to enhance Ag-specific CTL activity. We have created three types of FC preparations by alternating fusion cell partners: 1) immature DCs fused with autologous colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK-432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK-FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short-term culture of fusion cell preparations promoted the fusion efficiency. Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T cells capable of high levels of IFN-gamma production and cytolysis of autologous tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs retained stimulatory capacity for inducing antitumor immunity. These results suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have the potential applicability to the field of antitumor immunotherapy and may provide a platform for adoptive immunotherapy in the clinical setting.

Antigens, CD↗
PubMed2007

Usefulness of magnifying endoscopy with narrow band imaging for the detection of specialized intestinal metaplasia in columnar-lined esophagus and Barrett's adenocarcinoma.

BACKGROUND: Barrett's esophagus with specialized intestinal metaplasia (SIM) from columnar-lined esophagus is difficult to distinguish with routine endoscopy. OBJECTIVE: To examine the values of fine mucosal patterns and the capillary patterns observed by magnifying endoscopy with narrow band imaging (MENBI) for the detection of SIM in columnar-lined esophagus and superficial Barrett's adenocarcinoma. We also undertook a histologic investigation regarding whether the capillary pattern observed by MENBI corresponds to the 3-dimensional (3D) structure of the capillary as depicted by using a confocal laser-scanning microscope (CLSM). DESIGN: To compare the findings of MENBI, at 217 sites of columnar-lined esophagus, with histologic findings. Capillaries of the superficial mucosal layer were observed and were analyzed by 3D with a CLSM in 45 biopsied specimens. PATIENTS: Fifty-eight patients, including 4 with superficial Barrett's adenocarcinoma. SETTING: Jikei University Hospital, Tokyo, Japan. RESULTS: Upon observation, all 6 adenocarcinoma sites were classified as irregular patterns in both the fine mucosal patterns and capillary patterns. The most characteristic endoscopic patterns of SIM were revealed to be the cerebriform fine mucosal pattern (sensitivity, 56%; specificity, 79%; odds ratio, 4.78) and ivy- or deoxyribonucleic acid (DNA)-like capillary pattern (sensitivity, 77%; specificity, 94%; odds ratio, 51.6). The addition of capillary patterns to fine mucosal patterns improved the accuracy of diagnosing SIM (P < .0001). CONCLUSIONS: MENBI was able to precisely visualize the structure of capillaries in the superficial mucosal layer. The addition of capillary patterns to fine mucosal patterns appeared to improve the diagnostic value for detecting SIM and superficial Barrett's adenocarcinoma upon observation by MENBI.

Adenocarcinoma↗
PubMed2006

Is metallic stenting worthwhile for biliary obstruction due to lymph node metastases?

BACKGROUND: The indications for metallic stents have widened from primary hepatobiliary cancers to the other diseases such as lymph node metastases from distant organs. The present study aimed to evaluate the results and establish the efficacy of metallic stenting in patients with obstructive jaundice due to metastatic lymph nodes. METHODS: Stent patency, survival and cost per patient until death were retrospectively compared between patients with primary carcinoma of the biliary tract (PC group; n = 71) and lymph node metastases from the gastric and colorectal carcinomas. (LN group; n = 26). RESULTS: Stent occlusion occurred in 17 patients in the PC group (24%). In contrast, stent occlusion was significantly more frequent in the LN group (P = 0.0293), occurring in 13 patients (50%). Cumulative stent patency was also significantly shorter in the LN group than that in the PC group (P = 0.0016). However, survival was almost the same between the two groups. The mean medical fee was 27% higher for the LN group than for the PC group, which was attributable to additional treatment for stent occlusion. DISCUSSION: The indications for metallic stent placement for biliary obstruction caused by lymph node metastases from the gastrointestinal tract seem limited. Further investigation of the treatments alternative to metallic stents would be required.

Aged↗
PubMed2006

Preferential involvement of Tim-3 in the regulation of hepatic CD8+ T cells in murine acute graft-versus-host disease.

Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses. We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor- and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number, and infiltration of lymphocytes in the liver. IFN-gamma expression by splenic and hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in aGVHD augmented the activation of effector T cells expressing IFN-gamma or exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in the regulation of CD8+ T cells responsible for the maintenance of hepatic homeostasis and tolerance.

Animals↗
PubMed2006

A Japanese case of familial Mediterranean fever with onset in the fifties.

The patient was a 63-year-old woman with attacks of fever and abdominal pain, starting from the age of 53 years and recurring every month. Despite various examinations at another hospital, the etiology remained unclear. She was under symptomatic treatment, and was referred to our department for further evaluation. Although she had onset in middle age, the clinical symptoms and examination findings suggested familial Mediterranean fever, and administration of colchitine inhibited the attacks completely. Therefore, the patient was diagnosed as having the disease. We were not able to analyze the entire MEFV gene, but detected only a heterozygous M694I mutation. Amyloidosis did not develop as a complication. The disease is rare in Japan, and its onset in the fifties is extremely rare in the world.

Abdominal Pain↗
PubMed2006

New approach to diagnosing ampullary tumors by magnifying endoscopy combined with a narrow-band imaging system.

BACKGROUND: A newly developed narrow-band imaging (NBI) system, which uses modified optical filters, can yield clear images of microvessels and surface structure in gastric and colonic diseases. In the present study, we investigated the ability of magnifying endoscopy with NBI (MENBI) to diagnose and differentiate between benign and malignant ampullary tumors. METHODS: Fourteen patients, whose ampullas were noted to be significantly enlarged or protruding with conventional endoscopy, were enrolled in the study. Specimens, which were obtained by forceps biopsy, endoscopic papillectomy, and/or surgery, were retrieved for histopathological examination. The correlation between MENBI images and histopathological findings was investigated. MENBI findings were classified as I, oval-shaped villi; II, pinecone/leaf-shaped villi; or III, irregular/nonstructured. In addition, tortuous, dilated, and network-like vessels noted on the ampullary lesions with MENBI were defined as abnormal vessels. RESULTS: In 6 of 14 patients, the ampullary changes were proven to be inflammatory in forceps biopsy specimens, without any evidence of malignancy after more than 1 year of follow-up. In five patients, ampullary lesions were treated by endoscopic papillectomy, and in three, by pancreatoduodenectomy. All adenomas and adenocarcinomas had type II and/or type III surface structures, and patients whose ampulla had a type I surface structure had only inflammatory or hyperplastic changes. In addition, abnormal vessels were seen only in adenocarcinomas and never in adenomas. CONCLUSIONS: MENBI has the ability and potential to predict histological characteristics of ampullary lesions.

Adenocarcinoma↗
PubMed2006

Placement of a metallic stent across the main duodenal papilla may predispose to cholangitis.

BACKGROUND: Cholangitis is a major complication after metallic stent placement to treat biliary obstruction, and it may impair quality of life. Whether transpapillary stent placement contributes cholangitis is still controversial. OBJECTIVES: The present study aimed to determine risk factors for acute cholangitis after metallic biliary stent placement. DESIGN: Retrospective cases series. PATIENTS: A total of 108 patients with malignant biliary obstruction were treated with metallic stents, resulting in 12 cases of cholangitis. MAIN OUTCOME MEASUREMENTS: A multiple logistic regression model was performed with clinical parameters, including stent placement across the main duodenal papilla. RESULTS: By multiple logistic regression model, age; lower location; and Wallstent, Ultraflex stent, and covered stent were negatively associated with cholangitis. Restenosis and placement across the main duodenal papilla were positively associated with the occurrence of cholangitis. Transpapillary stent placement was the most significant risk factor. In this logistic model, the area under a receiver operating characteristics curve was computed as 0.92: sensitivity, 0.92 (95% confidential interval (CI), 0.62-1.00); specificity, 0.86 (95% CI, 0.78-0.93); positive predictive value, 0.46 (95% CI, 0.26-0.67); and negative predictive value, 0.99 (95% CI, 0.94-1.00). CONCLUSIONS: Disruption of the sphincter mechanism by transpapillary placement may be the most important etiologic factor in the propensity for cholangitis after metallic stent placement for malignant biliary obstruction.

Acute Disease↗
PubMed2006

Endoscopic full-thickness resection: circumferential cutting method.

BACKGROUND: Endoscopic full-thickness resection (EFTR) at flexible endoscopy might allow less-invasive removal of more deeply penetrating cancers that have not spread to the serosal surface and more complete histologic examination of the excised tissue. OBJECTIVE: A method for closure of full-thickness defects in the stomach wall would be valuable for other endosurgical applications. SETTING: A method that uses an end cap and band-ligation without prior injection of saline solution to perform EFTR gave good results and was safe in pig studies. There is a size limitation of cancers that can be resected en bloc when using this method. The depth of resection was also variable. DESIGN AND INTERVENTIONS: EFTR was achieved by circumferential cutting with a sphincterotome and a snare. A prototype bidirectional cutter was tested. Sutured closure was accomplished by using a sheathed needle, a metal tag, and a thread at the tip, passed through a 2.8-mm accessory channel. Knot-tying devices secured the sutured defect. MAIN OUTCOME MEASUREMENTS: EFTR was studied in non-survival (n = 4) and survival (n = 8) experiments in pigs. RESULTS: Full-thickness specimens were resected from the gastric wall (100%, 12/12), and the defects were closed by using sewing and knot-tying devices (100%, 12/12). LIMITATIONS: A healing ulcer at the suturing site was evident at follow-up endoscopy in the survival experiments. Bleeding, which was stopped by suturing, occurred in 1 pig (8.3%, 1/12). All pigs survived these experiments without complications (100%, 8/8). CONCLUSIONS: Circumferential EFTR was feasible and appeared safe in survival experiments. This method might allow larger and deeper resection of tumors in the gastric wall.

Animals↗
PubMed2006

New generation argon plasma coagulation in flexible endoscopy: ex vivo study and clinical experience.

BACKGROUND AND AIM: A new argon plasma coagulation (APC) system was developed to improve the conduction characteristics of existing systems and to achieve a true non-contact procedure. We evaluated the new system in an ex vivo experiment and in two different clinical cases. METHODS: Swine gastric walls were cauterized at various current settings and time intervals. The diameter and penetration depth of the cauterized areas were measured. We also describe the use of this method to treat patients with gastric hemorrhagic hereditary telangiectasias and a mucosal gastric cancer. RESULTS: The ex vivo study revealed an improved maintenance of current conduction and greater control of the extent and penetration depth of the cauterization effects on tissue using the new APC system. In the clinical cases, hemorrhagic telangiectasias and an early stage gastric cancer were treated successfully without relapse using the new system. CONCLUSIONS: Improved current conduction and controllability of cauterization corresponding to emission time were demonstrated for the new APC. The new system allows expeditious superficial cauterization of a wide area without any contact with tissue. The therapeutic effect appeared favorable compared with previous APC devices for gastrointestinal applications.

Aged↗
PubMed2006

[A case of extrahepatic portal vein aneurysm with the remarkably bent bile duct by its displacement].

A 50-year-old man with type B liver cirrohosis was admitted with jaundice and ascites. He had undergone an operation for esophageal variceal rupture at another hospital. Abdominal CT scan and ultrasonography showed cystic dilatation of the extrahepatic portal vein, and Doppler ultrasonography showed it to be a portal vein aneurysm. After admission, jaundice progressed, and not only liver failure but also biliary tract obstruction was suspected as its etiology. Therefore, endoscopic retrograde cholangiography was performed, and it showed a remarkably bent extrahepatic bile duct thought to be caused by extrinsic compression. By combining the finding of endoscopic ultrasonography, we considered that the portal vein aneurysm had displaced the bile duct. We suspected that it also caused cholestasis and cholangitis.

Aneurysm↗
PubMed2005

Dendritic cells fused with allogeneic colorectal cancer cell line present multiple colorectal cancer-specific antigens and induce antitumor immunity against autologous tumor cells.

The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2(-)/HLA-24(-)), carcinoembryonic antigen (CEA)(+), and MUC1(+) as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2(+) and/or HLA-A24(+)) and allogeneic COLM-6 resulted in MHC class I- and MHC class II-restricted proliferation of CD4(+) and CD8(+) T cells, high levels of IFN-gamma production in both CD4(+) and CD8(+) T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.

Antigens, Neoplasm↗
PubMed2005

Prediction of recurrence of esophageal varices-special reference to a role for endoscopic ultrasonography.

The fate of esophageal varices (EV) depends largely on variables of hemodynamics in portal venous system, which has long been studied using various diagnostic modalities. Recent studies have mainly focused on relationship of portal hemodynamics and recurrence of esophageal varices after endoscopic treatment. In particular, there is increasing number of studies using endosonography because it is less invasive and provides high-resolution images of collaterals surrounding the lower esophagus and the upper stomach, which includes left gastric veins and its branches, submucosal vessels in the cardia, paraesophageal collaterals and perforating veins. On basis of those studies, the range of changes to those vessels seems to depend on treatment techniques and the role of each vessel in preventing the elevation of portal pressure following treatment and in recanalization of variceal channels greatly varies. Thus, the underlying pathophysiology of variceal recurrence has been gradually understood. Further studies could enable us to identify the patients, in whom varices would rapidly recur and to choose optimal treatment for each treatment.

Journal Article↗
PubMed2005

Endoscopic full-thickness resection with sutured closure in a porcine model.

BACKGROUND: Some early gastric cancers might be advantageously staged and treated by full-thickness resection if secure methods for closing the defect were available. The aim of this study was to test the feasibility of full-thickness gastric resection. METHODS: Full-thickness gastric resections were performed by using a ligating device without submucosal injection in survival studies in pigs (n = 8). The defects were closed by using new methods for suturing, locking, and cutting thread through a 2.8-mm accessory channel. Stitches (n = 2-4) were placed close to the target area before resection. OBSERVATIONS: Full-thickness resections (n = 8) were performed. The pigs survived without incident for 21 to 28 days. Healing of the suture site was evident at follow-up endoscopy. Suture sites were water tight. The pull-out force with stitches by using this new sewing method was significantly higher than with endoscopic clips (20.3 N +/- 0.94 vs. 2.2 N +/- 0.42, p < 0.05). CONCLUSIONS: Endoscopic full-thickness resection with sutured defect closure was feasible and appeared safe in these survival experiments.

Animals↗
PubMed2005

Development of a navigation function for an endosocopic robot surgery system.

An endoscopic robot system that we reported at MMVR11 is able to perform various surgical procedures in the stomach by using two manipulators. However, it is difficult for surgeons to recognize the 3D location and the direction of the endoscope's tip in the abdominal region during robotic surgery. In this research, we have developed a navigation function that enables image-guided surgery by superimposing the patient's abdominal organ structure onto the endoscopic image. In this paper, we describe the overview of the navigation for the robot system and the result of an animal experiment done while applying the system.

Endoscopy↗