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Biomedical subjects

K Tamada

Publications and source records attributed to K Tamada.

At least 37 records · Page 2Linked to original sources

Ropeway-type bile duct biopsy forceps with a side slit for a guidewire.

BACKGROUND: Transpapillary procurement of bile duct biopsy specimens is an effective diagnostic technique in cases of biliary structure. The utility of new ropeway-type bile duct biopsy forceps with a side slit for a guidewire was investigated in this study. METHODS: The 12 patients in this study had bile duct cancer (n = 3), cancer of the head of the pancreas (n = 4), gallbladder cancer (n = 1), and benign bile duct stenosis (n = 4). After endoscopic retrograde cholangiography, a guidewire was placed in the bile duct across the stenosis. The new forceps (1.8-mm diameter clamshell-type biopsy forceps without needle) was then introduced through the intact papilla along the guidewire. RESULTS: In all patients, sufficient tissue for histopathologic evaluation was obtained without complication. In one patient, biopsy specimens were selectively obtained of the left hepatic duct, which was impossible with conventional forceps. In another patient, histologic examination of specimens obtained by using this new forceps showed adenocarcinoma, whereas specimens obtained with a conventional forceps did not contain adenocarcinoma. However, in another patient, biopsy specimens obtained with a conventional forceps contained adenocarcinoma that was not evident in specimens obtained with the new forceps. Dislodgement of the guidewire during procurement of biopsy specimens occurred in 1 patient. In the other 11 patients, an endoscopic biliary drain was inserted over the guidewire. CONCLUSION: The new ropeway-type biopsy forceps is useful for selectively obtaining biopsy specimens of the bile duct. With this system, access for subsequent endoscopic biliary drainage is maintained.

Aged↗

Epstein-Barr virus nuclear antigen-1-dependent and -independent oriP-binding cellular proteins.

OBJECTIVE: Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and the replication origin, oriP, are essential for the replication and maintenance of latent EBV DNA in cells, but no enzymatic activity has been associated with EBNA-1 protein alone. In this study, we have searched for host cellular proteins that interact with EBNA-1 protein in various B cell lines latently infected with EBV, including a recently EBV growth-transformed cell line. METHODS: By using gel shift analysis, we investigated the interactions of an oligonucleotide containing a single EBNA-1 recognition site, derived from the family of repeats (FR) element of oriP, with protein from cell extracts. RESULTS: The FR oligonucleotide bound a (72-kD) cellular protein in the absence of EBNA-1 and without induction of the previously reported 'anti-EBNA-1 proteins'. The FR oligonucleotide formed complexes with additional proteins from EBNA-1-synthesizing cell lines; these complexes were abolished or supershifted by anti-EBNA-1 monoclonal antibodies. SDS-PAGE analyses of 35S-Met-labeled proteins that bound to a biotin- conjugated FR oligonucleotide, fractionated by a glycerol gradient centrifugation and affinity-purified with streptavidin, showed three major bands, a 72-kD protein, the FR binding of which seemed to be independent of EBNA-1, a 64-kD protein in both EBNA-1-transfected and latently EBV-infected cell lines, and a 45-kD protein in EBV-infected cell lines, which was most prominent in a recently EBV growth-transformed cell line. CONCLUSIONS: The FR element forms complexes with cellular proteins in the absence and presence of EBNA-1. These 72-, 64- and 45-kD cellular proteins might be involved in the function of the oriP and EBNA-1 system.

Binding Sites↗

The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT.

Costimulatory molecules on antigen-presenting cells (APCs) play an important role in T cell activation and expansion. However, little is known about the surface molecules involved in direct T-T cell interaction required for their activation and expansion. LIGHT, a newly discovered TNF superfamily member (TNFSF14), is expressed on activated T cells and immature dendritic cells. Here we demonstrate that blockade of LIGHT activity can reduce anti-CD3-mediated proliferation of purified T cells, suggesting that T cell-T cell interaction is essential for this proliferation. To test the in vivo activity of T cell-derived LIGHT in immune homeostasis and function, transgenic (Tg) mice expressing LIGHT in the T cell lineage were generated. LIGHT Tg mice have a significantly enlarged T cell compartment and a hyperactivated peripheral T cell population. LIGHT Tg mice spontaneously develop severe autoimmune disease manifested by splenomegaly, lymphadenopathy, glomerulonephritis, elevated autoantibodies, and severe infiltration of various peripheral tissues. Furthermore, the blockade of LIGHT activity ameliorates the severity of T cell-mediated diseases. Collectively, these findings establish a crucial role for this T cell-derived costimulatory ligand in T cell activation and expansion; moreover, the dysregulation of T cell-derived LIGHT leads to altered T cell homeostasis and autoimmune disease.

Animals↗

Multiple bile duct biopsies using a sheath with a side port: usefulness of intraductal sonography.

OBJECTIVE: We clarified the number of biopsies required to determine malignancy of the biliary tract on the basis of the type of bile duct tumor. SUBJECTS AND METHODS: Patients with a biliary tract malignancy (n = 33) and a benign biliary stenosis (n = 3) underwent biopsy via the percutaneous transhepatic route. We performed intraductal sonography using a 20-MHz probe with a 2.0-mm diameter. The sonographic findings were prospectively classified as polypoid, circular, or semicircular. The tip of a long 9-French sheath with a side port was wedged into the stenosis, and six specimens were obtained with a 1.8-mm-diameter forceps with serrated cups. RESULTS: When cholangiography or intraductal sonography showed a polypoid lesion, the sensitivity of two biopsies was 100% (6/6). When cholangiography showed a stenotic lesion, the sensitivity of nine biopsies (96%, 26/27) was superior to that of two biopsies (74%, 20/27; p < 0.05). When intraductal sonography showed a circular lesion, the sensitivity of three biopsies (100%, 14/14) was superior to that of a single biopsy (64%, 9/14; p < 0.05). When it showed a semicircular lesion, the sensitivity of nine biopsies (92%, 12/13) was superior to that of two biopsies (54%, 7/13; p < 0.05). CONCLUSION: Bile duct biopsy using a sheath with a side port has a high sensitivity. However, the number of biopsies required depends on the cholangioscopic and intraductal sonographic appearance of the tumor.

Aged↗

Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS.

This report describes a new human B7-like gene designated B7-H2. Cell surface expression of B7-H2 protein is detected in monocyte-derived immature dendritic cells. Soluble B7-H2 and immunoglobulin (Ig) fusion protein, B7-H2Ig, binds activated but not resting T cells and the binding is abrogated by inducible costimulator Ig (ICOSIg), but not CTLA4Ig. In addition, ICOSIg stains Chinese hamster ovary cells transfected with B7-H2 gene. By suboptimal cross-linking of CD3, costimulation of T-cell proliferation by B7-H2Ig is dose-dependent and correlates with secretion of interleukin (IL)-2, whereas optimal CD3 ligation preferentially stimulates IL-10 production. The results indicate that B7-H2 is a putative ligand for the ICOS T-cell molecule. (Blood. 2000;96:2808-2813)

Abatacept↗

LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response.

LIGHT is a recently identified member of the TNF superfamily and its receptors, herpesvirus entry mediator and lymphotoxin beta receptor, are found in T cells and stromal cells. In this study, we demonstrate that LIGHT is selectively expressed on immature dendritic cells (DCs) generated from human PBMCs. In contrast, LIGHT is not detectable in DCs either freshly isolated from PBMCs or rendered mature in vitro by LPS treatment. Blockade of LIGHT by its soluble receptors, lymphotoxin beta receptor-Ig or HVEM-Ig, inhibits the induction of DC-mediated primary allogeneic T cell response. Furthermore, engagement of LIGHT costimulates human T cell proliferation, amplifies the NF-kappaB signaling pathway, and preferentially induces the production of IFN-gamma, but not IL-4, in the presence of an antigenic signal. Our results suggest that LIGHT is a costimulatory molecule involved in DC-mediated cellular immune responses.

Amino Acid Sequence↗

In vitro growth inhibition of a broad spectrum of tumor cell lines by activated human dendritic cells.

Dendritic cells (DCs) are critical subsets of leukocytes providing antigen presentation for initiation of humoral and cellular immune responses. Their role as effector cells in tumor resistance, however, is less known. We report here that human DCs generated by culturing plastic-adherent peripheral blood monocytes in the presence of granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin-4 have potent growth-inhibition activity in vitro on a wide spectrum of human tumor lines of different tissue origin. Proinflammatory stimuli lipopolysaccharide (LPS) and interferon-gamma, but not tumor necrosis factor-alpha and CD40 signaling, can further enhance DC-mediated inhibition of tumor growth. The growth inhibition requires contact between DCs and tumor cells while LPS treatment enhances the antitumor activity in DC culture supernatants. Our results suggest that in addition to their predominant role as regulatory cells, activated DCs are also potential effector cells in tumor immunity.

Cell Adhesion↗

Local injections of OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of Th1-type cytokines and CXC3 chemokines.

The effect of local injections with streptococcal preparation OK432 on the antitumor effect induced by adoptive immunotherapy (AIT) was investigated. Draining lymph node cells on day 14 after B7-P815 inoculation were used for AIT after in vitro stimulation. AIT on days 7 and 10 showed no effect on the growth of s.c. established P815 mastocytoma, but local injections with OK432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitumor effect. On the other hand, the combination therapy significantly suppressed tumor growth, and the tumor-bearing mice survived longer than those receiving only one of the treatment modalities. The significant infiltration of CD4+ or CD8+ T cells and multiple necrosis in the tumor sites were observed only when the tumor-bearing mice were treated with the combination therapy. In addition, a transfer experiment using labeled effector cells revealed these infiltrated CD8+ T cells and CD4 T cells to be derived from the donor and the host respectively. More importantly, the combination therapy clearly led to higher expression of the mRNA for Th1-type cytokines and CXC3 chemokines in the tumor sites than resulted from each of the treatment modalities alone. Collectively, these results indicate that local injections with OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of the Th1-type cytokines and CXC3 chemokines.

Animals↗

Intraductal ultrasonographic assessment of coagulation depth during endoscopic microwave coagulation therapy in a canine model.

In order to examine the feasibility of endoscopic microwave coagulation therapy (MCT) for the treatment of common bile duct cancer in humans, we investigated the safety and effectiveness of endoscopic MCT with the assistance of intraductal ultrasonography (IDUS). We performed MCT in the canine small intestine as a model because of its similarity in size to the obstructed human common bile duct. Multiple coagulation lesions were made in anesthetized dogs, with the endoscope inserted through a jejunostomy. Under condition "A", the tip of the MCT probe was kept in a fixed position in contact with the mucosa of the intestine, and coagulation was performed with an output of 30 or 50 W for 30 or 10 s, respectively. Under condition "B", the tip of the MCT probe was moved along the intestinal mucosa, and coagulation was performed with an output of 50, 40, or 30 W, all for 10 s. After coagulation, a thin-caliber ultrasonic probe was inserted endoscopically for observation of the effects of coagulation. Each coagulation under condition "A" resulted in degeneration of all layers of the intestine. Coagulation under condition "B" resulted in more localized degeneration, extending from the mucosal layer to the proper muscle layer. By comparison with histologic observations, the accuracy of IDUS in assessing depth of degeneration was 87.5%. Endoscopic microwave coagulation was considered safe and effective, and IDUS was able to accurately assess the effects of microwave coagulation.

Animals↗

Diagnosis and non-surgical treatment of bile duct carcinoma: developments in the past decade.

In the past decade, ultrasonography and magnetic resonance cholangiography have become useful modalities for the screening of bile duct cancer. Intraductal ultrasonography, using a thin-caliber (2.0 to 2.4 mm in diameter) and high-frequency (15 to 20 MHz) probe, has become a promising modality in assessing locoregional staging. For interventional therapy of unresectable bile duct carcinoma, metallic stents also became an excellent modality. However, tumor ingrowth and overgrowth into the mesh of stents are problems to be solved, and external radiation therapy is widely conducted to control the tumor. To improve the limitations of external radiation, brachytherapy, photodynamic therapy, and microwave coagulation therapy are conducted. However, these modalities are available in only a limited number of institutions even now. To predict the prognosis of the patients, approaches using molecular biology must be established.

Bile Duct Neoplasms↗

Limitations of three-dimensional intraductal ultrasonography in the assessment of longitudinal spread of extrahepatic bile duct carcinoma.

We investigated the utility and limitations of three-dimensional intraductal ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight patients with extrahepatic bile duct carcinoma. 3D-IDUS was used to assess longitudinal cancer extension to the hepatic side prior to resection. When the linear dimension of 3D-IDUS showed bile duct wall thickening that was connected to the tumor and which became thin at a point, it was determined to be the front formation of longitudinal cancer extension. The findings were examined in relation to histologic information from the resected specimen. Although 3D-IDUS showed front formation of wall thickening in two patients, it accurately reflected the histological margin of the longitudinal cancer extension in only one patient. In the other patient, the wall thickening was longer than the histological margin. When 3D-IDUS showed bile duct wall thickening without front formation (n = 2), the wall thickening was longer than the histological margin of the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening (n = 4), one of these patients showed cancer spread histologically. As a result, the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%. Even if the linear dimension of 3D-IDUS demonstrated front formation of thickening of the bile duct, it reflected not only cancer extension but also inflammatory wall thickening.

Aged↗

Percutaneous recanalization of the bile duct along an endoscopic naso-biliary catheter.

Percutaneous recanalization of the bile duct is essential for placing biliary stents and carrying out other interventions. This prospective study was performed to establish safe approaches for percutaneous recanalization of the bile duct when it had previously resulted in failure. Between July 1995 and July 1999, percutaneous recanalization of the bile duct was attempted in 58 patients with a malignant biliary stenosis. When recanalization failed, an endoscopic naso-biliary drainage (ENBD) catheter was placed across the stenosis. The procedure was again attempted along the ENBD catheter. In the period of the study, four patients underwent successful recanalization after ENBD, although attempts prior to ENBD had been unsuccessful. As a result, the success rate of recanalization in the period was 100% (58/58). When recanalization fails, the use of an ENBD catheter may provide access to the biliary tree, and the biliary stenosis can be recanalized safely.

Abdominal Neoplasms↗

Placement of endoscopic naso-biliary drainage does not preclude subsequent percutaneous transhepatic biliary drainage.

We prospectively investigated whether the placement of endoscopic naso-biliary drainage (ENBD) precluded percutaneous transhepatic biliary drainage (PTBD). In 40 patients, the caliber of the intrahepatic bile duct was measured prior to ENBD by ultrasonography. When PTBD was required after ENBD, the ENBD catheter was clamped for 1 to 2 h before PTBD, and its caliber was again measured at the time of PTBD. When PTBD was performed within 7 days (mean, 1.8 days) after ENBD (n = 27), the size of the intrahepatic bile duct was 5.0 +/- 2.3 mm before and 4.6 +/- 2.3 mm after ENBD. There was no significant difference between these values (P > 0.5). When PTBD was performed 8 to 40 days (mean, 17.8 days) after ENBD (n = 13), the bile duct diameter was significantly reduced, from 4.2 +/- 1.5 mm (pre-ENBD) to 1.8 +/- 1.7 mm (post-ENBD) (P < 0.05). When PTBD was conducted within 7 days (mean, 1.8 days) after ENBD, previous ENBD did not induce collapse of the bile duct, if the ENBD catheter was clamped for 1 to 2 h before the puncture of the bile duct.

Bile Ducts, Intrahepatic↗

Intraductal US in assessing the effects of radiation therapy and prediction of patency of metallic stents in extrahepatic bile duct carcinoma.

BACKGROUND: We assessed the local effects of radiation therapy using intraductal ultrasonography (US) to predict the subsequent patency of metallic stents in bile duct carcinoma. METHODS: Data from 16 patients with extrahepatic-suprapancreatic bile duct carcinoma were prospectively analyzed. Thin-caliber US probes (2.0 mm diameter/20 MHz frequency and 2.8 mm diameter/10 MHz frequency) were inserted into the bile duct via a percutaneous transhepatic approach pre- and postradiation therapy to evaluate the effects of treatment. When intraductal US showed a reduction in bile duct wall thickness of 30% or greater or showed a lessening of vessel (portal vein or right hepatic artery) invasion, radiation therapy was judged to be effective. Noncovered metallic stents were then inserted, and their patency was evaluated over time. RESULTS: When radiation therapy was effective (n = 7), the metallic stent was patent for 522 +/- 571 days. When radiation was ineffective (n = 9), the metallic stent was patent for only 188 +/- 159 days. When radiation therapy was ineffective, stent obstruction occurred in 6 of 9 (66.7%) patients during this period, significantly more frequently than when radiation therapy was effective (14.3%, p < 0.05). CONCLUSIONS: Assessment of local radiation effects by intraductal US is useful for predicting patency of metallic stents in bile duct cancer.

Aged↗

T lymphocyte costimulatory molecules in host defense and immunologic diseases.

BACKGROUND: Costimulation is an essential component for the optimal induction of T cell-mediated immune responses. Manipulation of the costimulatory pathway with antibodies or genetically-engineered fusion proteins is an important strategy to treat immune-related diseases including allergy, asthma, transplantation and cancer. Recent advances have revealed several new costimulatory molecules, and the functional characteristics of each costimulatory pathway are now becoming clearer. LEARNING OBJECTIVES: In this review, we summarize basic outlines of the costimulatory systems in terms of molecular structure, expression kinetics and immunological function. We further discuss involvement and therapeutic manipulation of costimulation in several clinical diseases. DATA SOURCE: The MEDLINE database was used to review the literature related to costimulation. CONCLUSION: Costimulatory pathways play an essential role in the activation and regulation of T cell immune responses and the induction of T cell tolerance. Therapeutic manipulation of the costimulatory system demonstrates beneficial effects to treat immunological diseases in murine models as well as some clinical situations.

Animals↗

Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway.

LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma interferon and granulocyte-macrophage colony-stimulating factor. Gene transfer of LIGHT induced an antigen-specific cytolytic T-cell response and therapeutic immunity against established mouse P815 tumor. In contrast, blockade of LIGHT by administration of soluble receptor or antibody led to decreased cell-mediated immunity and ameliorated graft-versus-host disease. Our studies identify a previously unknown T-cell co-stimulatory pathway as a potential therapeutic target.

Amino Acid Sequence↗