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Shunsuke Yamamoto

Publications and source records attributed to Shunsuke Yamamoto.

14 recordsLinked to original sources

[A case of stage IV gastric cancer treated sequentially for over two years by TS-1, paclitaxel, and CPT-11].

We report a patient with advanced stage IV gastric cancer treated by chemotherapy for over two years. The patient was a 69-year-old man with paraaortic lymph node metastasis of gastric cancer. He underwent a distal gastrectomy in non-curative resection. After surgery, chemotherapy with TS-1 (100 mg/body/day) was performed. At 7 months after surgery, progression of lymph node metastasis in porta hepatis was recognized, and paclitaxel was administered at a weekly dose of 80 mg/m(2) for 3 weeks followed by one week rest. He remained stable for 12 months under paclitaxel treatment. At 26 months after surgery, progression of lymph node metastasis in porta hepatis was recognized again, and CPT-11 was administered at a bi-weekly dose of 80 mg/m(2). Although the patient died two years seven months after surgery, the chemotherapy with sequential administration of TS-1, paclitaxel and CPT-11 was thought to be effective for advanced gastric cancer.

Adenocarcinoma↗

Longterm outcomes after endoscopic mucosal resection for early gastric cancer.

BACKGROUND: Despite the widespread use of endoscopic mucosal resection (EMR) in patients with early gastric cancer (EGC), its longterm outcomes have not been fully evaluated. Our aim was to evaluate longterm survival after complete EMR for EGC. METHODS: From patients who underwent EMR between 1978 and 1996 at our center, we enrolled 131 patients with differentiated mucosal EGCs less than 2 cm (without ulcerative change) that had been completely removed by EMR. The vital status of the patients at the end of December 1998 was confirmed by the hospital cancer registry, which is linked to the Osaka Cancer Registry. RESULTS: A total of 124 patients (95%) were completely followed-up. Two patients (1.5%) died of gastric cancer and 26 died of other causes during the mean observation period of 58 months. The overall 5- and 10-year survival rates were 84% and 64%, respectively. The disease-specific 5- and 10-year survival rates were 99% and 99%. CONCLUSION: En bloc EMR ensured an excellent prognosis, and should be the first choice of treatment in patients with small differentiated mucosal EGC. Careful histological examination and longterm endoscopic surveillance are important.

Adenocarcinoma↗

[A case of primary duodenal cancer near the papilla of Vater which had initial symptoms of obstructive jaundice].

A 63-year-old man visited our hospital complaining of brown urine. A physical examination showed jaundice of the skin and conjunctiva bulbar. Blood tests showed elevated serum levels of bilirubin and hepatobiliary enzymes. A type 2-like mass lesion was found near the papilla of Vater during the endoscopic retrograde cholangiopancreatography and was histologically proven to be a well-differentiated adenocarcinoma. A diagnosis of obstructive jaundice due to primary duodenal cancer arising near the papilla of Vater was made. After the jaundice was decreased by endoscopic biliary stenting, a pancreatoduodenectomy was performed. A histopathological examination of the resected specimen concerning the location and manner of invasion of cancer cells revealed that the cancer arose from the duodenal mucosa near the papilla of Vater.

Adenocarcinoma↗

Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta.

Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least two steps that requires inducible IkappaBzeta.

Adaptor Proteins, Signal Transducing↗

Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes.

The mechanism of the liver damage and lethality in Propionibacterium acnes (P. acnes)-LPS system remains obscure. To examine the role of CD14 in the system, M14M mice, in which CD14 was expressed heterotopically under the control of the metallothionein promoter were used. The production of soluble CD14 (sCD14) was increased by both P. acnes - priming and LPS challenge (1 microg per mouse) in both nontransgenic and M14M mice, although the plasma level was much higher in M14M nontransgenic than mice. The size of granulomas induced by an intraperitoneal administration of P. acnes in M14M mice 7 days after priming was smaller than that in nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in hepatocytes in nontransgenic mice but not in M14M mice. The challenge dose resulted in almost 90% lethality in nontransgenic mice but not in M14M mice 24h after challenge. TNF-alpha, IFN-gamma, IL-12, IL-18 and inducible nitric oxide synthase (iNOS) mRNA expressions produced by LPS challenge in M14M mice were low compared with those in nontransgenic mice. IL-18 mRNA expression was upregulated in P. acnes-primed nontransgenic mice but not in M14M mice. These results suggest that the high sCD14 concentration may account for less marked liver damage in M14M mice. Increase in the challenge dose of LPS (2 microg per mouse) resulted in increased lethality of M14M mice without liver damage. The levels of endothelial cell leukocyte adhesion molecule (ELAM)-1 mRNA expression in several organs in M14M mice 1-3h after LPS challenge were, however, lower than those in nontransgenic mice. The high sCD14 concentration may stimulate endothelial cell activation, which may account for lethality without liver damage in M14M mice. Thus, CD14 is involved in both the priming and induction phases as well as lethality in P. acnes-LPS system.

Animals↗

The roles of soluble osteopontin using osteopontin-transgenic mice in vivo: proliferation of CD4+ T lymphocytes and the enhancement of cell-mediated immune responses.

We generated transgenic mice expressing osteopontin (OPN) under the control of the alpha(1)-antitrypsin promoter. These mice (OPN-T mice) expressed OPN mRNA in liver and kidney, and released a large amount of plasma OPN, which increased after stimulation with turpentine oil. Before sensitization, the number of CD4+ T cells in lymph nodes was significantly higher in OPN-T than nontransgenic mice, and that in spleen was slightly higher, whereas that of CD8+ T cells was no different between OPN-T and nontransgenic mice. After sensitization, the CD4+ T cell numbers in spleen increased significantly, while there were almost no changes in the CD8+ T cells in lymph nodes and spleen. The intensity of contact hypersensitivity responses to 2,4-dinitrofluorobenzene (DNFB) was obviously enhanced in OPN-T mice. In the delayed-type hypersensitivity (DTH) model elicited by DNFB, the number of CD8+ T cells among DNFB-2,4,6-trinitrobenzenesulfonic acid (TNBS)-peritoneal exudate cells was significantly higher in OPN-T than nontransgenic mice, while there was almost no difference in that of CD4+ T cells. Adoptive transfer experiments revealed that the enhanced reactivity is carried by CD4+ and CD8+ T cells, respectively, although the ability of transferring DTH was significantly lower in CD8+ than in CD4+ T cells. The enhancement of CD8+ T cell migration was observed in OPN-T mice. These results suggest that OPN induces a proliferation of effector CD4+ and CD8+ cells in cell-mediated reactions and plays a role in the migration of CD8+ T cells.

Adoptive Transfer↗

Expression of splice variants of the human ADAM15 gene and strong interaction between the cytoplasmic domain of one variant and Src family proteins Lck and Hck.

OBJECTIVE: The aim of the present study was to show variant species of ADAM15 and unique Src homology 3 (SH3)-binding motifs, which strongly bound Src family proteins compared with ADAM15. METHODS AND RESULTS: RT-PCR using primers for the cytoplasmic domain revealed the presence of different species, designated ADAM15v1 and ADAM15v2, which had characteristic SH3-binding class I and class II motifs. The mRNA of ADAM15v1 and ADAM15v2 was mainly found in peripheral blood mononuclear cells, T lymphocytes and monocytic cell lines. ADAM15v2 protein interacted more strongly with the Src family proteins Lck and Hck than did ADAM15 protein, as examined by pull-down analysis and immunoprecipitation followed by immunoblot analysis. The binding with Lck and Hck was enhanced by the phosphorylation of ADAM15v2 protein. CONCLUSIONS: These results suggest that the cytoplasmic domain of ADAM15v2 strongly interacts with Lck and Hck and regulates leukocyte function.

ADAM Proteins↗

Involvement of CD14 in lipopolysaccharide- induced liver injury in mice pretreated with Propionibacterium acnes.

OBJECTIVE: The aim of this study was to elucidate the role of CD14 in the Propionibacterium acnes-lipopolysaccharide (LPS) system. METHODS AND RESULTS: CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed decreased responses to LPS in vivo, were used. Seven days after priming, the size of granulomas induced by an intraperitoneal administration of P. acnes in the M14M mice was smaller than that in the nontransgenic mice. The number of CD14-positive cells in granulomas was also decreased in the M14M mice compared to the nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in hepatocytes in the nontransgenic mice but not in the M14M mice. Seven days after priming, tumor necrosis factor-alpha expression was found in monocytic cells in granulomas and Kupffer cells in the nontransgenic mice and was significantly upregulated after LPS injection, whereas the expression was very weak in these cells in the M14M mice. CONCLUSIONS: CD14 plays a role in the P. acnes-LPS system in both priming and induction phases.

Animals↗

[Pneumothorax during retroperitoneoscopic nephrectomy: a case report].

A 54-year-old female patient was scheduled for retroperitoneoscopic nephrectomy. Anesthesia was induced with propofol and maintained with nitrous oxide/sevoflurane and epidural anesthesia. One hour after the start of the surgery, arterial oxygen saturation suddenly decreased from 99% to 94%. Because her oxygenation gradually improved and hemodynamics was stable, the operation was continued. After the end of the surgery, left pneumothorax was found on a chest X ray. The patient was extubated following thoracocentesis that had improved her pneumothorax and oxygenation. There is no report of pneumothorax in retroperitoneoscopic nephrectomy, as far as we know, although several cases have been reported in laparoscopic nephrectomy. We must be careful of pneumothorax in both laparoscopic and retroperitoneoscopic nephrectomy.

Anesthesia, Epidural↗

Structure and expression of the murine ADAM 15 gene and its splice variants, and difference of interaction between their cytoplasmic domains and Src family proteins.

The murine cell surface antigen ADAM 15 is a transmembrane glycoprotein that is expressed in a variety of cells including monocytic and T cell lines and consists of a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, and an epidermal growth factor (EGF)-like domain in the extracellular region. The cytoplasmic domain comprises 103 amino acids containing proline-rich endophilin I, Src homology 3 (SH3), and phox homology domain-containing protein (SH3PX1) binding motifs. The ADAM15 gene is composed of 21 exons and 20 introns and spans approximately 10 kb. The transcription initiation site of the ADAM15 gene was defined by an oligonucleotide-capping method. Reverse transcription (RT)-PCR using primers of the cytoplasmic domain of ADAM15 revealed the presence of different ADAM15 species designated ADAM15v1 and ADAM15v2, respectively, that had characteristic SH3-binding class I and/or class II motifs. The ADAM15v1 and ADAM15v2 genes consist of an extra one exon and two exons, respectively, which exist in intron 19 of the ADAM15 gene. The expression of ADAM15v1 and ADAM15v2 mRNA was found in T lymphocyte and monocyte lines. ADAM15v2 protein interacted more strongly with the Src family proteins Lck and Src than ADAM15 protein, when examined by pull-down and immunoprecipitation followed by immunoblot analysis using a T lymphocyte line. Phosphorylation of ADAM15v2 protein markedly enhanced the binding with Lck. These results suggest that the cytoplasmic domain of ADAM15v2 strongly interacts with Lck and plays an important role in T lymphocytes.

ADAM Proteins↗

Possible involvement of toll-like receptor 4 in endothelial cell activation of larger vessels in response to lipopolysaccharide.

Toll-like receptors (TLRs) serve as recognition and signaling elements for bacterial substances. To examine the role of TLRs in endothelial cells of larger vessels in lipopolysaccharide (LPS)-induced signaling, the expression and function of TLRs in human umbilical vein endothelial cells (HUVEC) were analyzed. A high level of TLR4 mRNA expression was found in HUVEC, human peripheral blood mononuclear cells (PBMC) and human monocyte cell line THP-1 cells. Little or no TLR2 mRNA expression was observed in HUVEC. In contrast, strong TLR2 mRNA expression was observed in PBMC and THP-1 cells. Moderate and high levels of TLR1 mRNA expression were found in HUVEC, PBMC and THP-1 cells, respectively. TLR3 mRNA expression was moderate in PBMC but weak in HUVEC and THP-1 cells. Little or no TLR5 and RP105 mRNA expression was observed in HUVEC, whereas a moderate level was detected in PBMC and THP-1 cells. The LPS-induced E-selectin expression in HUVEC was significantly inhibited by pretreatment with an anti-TLR4 mAb. Preincubation of HUVEC with an anti- TLR4 mAb significantly reduced the LPS-induced IL-6 production. LPS induced E-selectin and IL-6 production by HUVEC only in the presence of human serum, suggesting the involvement of soluble CD14. Anti-CD14 mAb strongly inhibited the LPS-induced E-selectin and IL-6 production by HUVEC. The inhibition with the concomitant treatment with anti-TLR4 and anti-CD14 mAbs was stronger than that with anti-CD14 mAb only, although it was slight. These results show that TLR4 in the presence of soluble CD14 plays a major role in the signaling of LPS in endothelial cells of larger vessels.

Blotting, Northern↗

CD156 transgenic mice. Different responses between inflammatory types.

CD156 (ADAM8) is part of the ADAM family of proteins with the catalytic site consensus sequence of metalloprotease and disintegrins. To examine the role of CD156 in vivo, we generated mutant CD156 (eCD156) transgenic mice expressing the ectodomain of CD156 under the control of the alpha1-antitrypsin (AT) promoter. One of the transgenic mice designated ATMS2-TG18 expressed a 1.84 kb mRNA which was predicted to be a truncated CD156. The expression of the transgenic CD156 mRNA in ATMS2-TG18 mice was abundant in the liver and slight in kidney. Turpentine oil (TO) and lipopolysaccharide (LPS) markedly upregulated the expression. Soluble CD156 (sCD156) was produced constitutively, and increased after the treatment with TO. Casein-induced peritoneal leukocyte infiltration was significantly less extensive in ATMS2-TG18 than non-transgenic mice. The expression of L-selectin in neutrophils (PMN) from peripheral blood leukocytes (PBL) was more strongly downregulated in ATMS2-TG18 than non-transgenic mice, suggesting that L-selectin in PMN from ATMS2-TG18 mice was shed by sCD156. In contrast, oxazolone (Ox)-induced contact hypersensitivity reactions (CHR) were more marked in ATMS2-TG18 than non-transgenic mice. The expression of E-selectin mRNA was detected in inflammatory skin sites from ATMS2-TG18, but not non-transgenic mice, suggesting that sCD156 may activate the endothelial cells and lead to the upregulation of E-selectin. These results suggest that CD156 regulates leukocyte infiltration directly or indirectly.

ADAM Proteins↗

Expression of murine N-MYC by insertion of retrovirus sequences in a murine macrophage cell line (RAW264).

RAW264 cells, reported to be originated from Abelson-virus-induced B lymphomas, are widely used as a murine monocyte cell line. We found that RAW264 show enhanced expression of murine N-MYC. Murine cDNA clones associated with N-MYC were separated from (lambda)gt11 cDNA library constructed by using mRNA from the macrophage cell line, RAW264 cells. Sequencing analysis of the longest cDNA clone N-MYCL showed that the length of the coding region was 18 bases shorter than that of the predicted full length N-MYC cDNA, and the 3' untranslated region had the 5' long terminal repeat (LTR) sequence of the Moloney-like proviral sequence, suggesting the expression of N-MYC by insertion of the proviral sequence. This suggests that expression of N-MYC plays a role in the establishment of macrophage cell line RAW264. Integration of LTR and overexpression of the N-MYC gene might have existed in the parental lymphoma cells, playing a role in the development of lymphoma or in the establishment of macrophage cell line.

Amino Acid Sequence↗