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Biomedical subjects

N Koide

Publications and source records attributed to N Koide.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis.

OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection is higher than in patients with hepatitis B virus (HBV)-related HCC in Japan, the long-term prognosis and prognostic factors of HCV-related HCC after hepatic resection are poorly understood. METHODS: The surgical outcome of HCV-related HCC in 172 consecutive patients who underwent hepatic resection between 1989 and 1997 was retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 23.2%, and 11 patients among that group had hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median overall survivals including hospital death after surgery were 41 months and 33 months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free survival rates after hepatic resection were 33%, 20%, and 15%, respectively. Multivariate analysis revealed that serum alpha-fetoprotein (AFP) of > or = 1000 ng/ml and the presence of vascular invasion were independent unfavorable prognostic factors affecting overall survival and that AFP of > or = 1000 ng/ml was an independently significant factor of poor disease-free survival. CONCLUSIONS: We found the postresection survival of patients with HCV-related HCC should be stratified by the high value of AFP and the presence of vascular invasion. AFP may be the most powerful predictor of the long-term prognosis and recurrence in such patients.

Aged↗
PubMed2001

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus.

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Apoptosis↗
PubMed2001

Flavonoids protect mice from two types of lethal shock induced by endotoxin.

The protective effect of flavonoids on two types of lethal endotoxic shock was studied. A lethal endotoxic shock was induced by administration of lipopolysaccharide (LPS) into D-galactosamine (D-GalN)-sensitized mice and another one was done by administration of a high dose of LPS into normal mice. Pretreatment with a series of flavonoids protected mice from two types of endotoxin lethality. Flavonoid pretreatment reduced the serum tumor necrosis factor-alpha (TNF-alpha) level in mice injected with D-GalN and LPS, but not in mice injected with a high dose of LPS. TNF-alpha-induced lethal shock in D-GalN-sensitized mice was also protected by pretreatment with flavonoids, suggesting that flavonoids augmented the resistance to TNF-alpha lethality. On the other hand, flavonoids reduced the plasma level of lipid peroxides in mice injected with a high dose of LPS, but not in D-GalN-sensitized mice. Taken together, these results indicated that flavonoids might protect mice from two types of endotoxin lethality. The protective mechanism of flavonoids in each endotoxin lethality is discussed.

Animals↗
PubMed2001

Inhibition of p38 mitogen-activated protein kinase augments lipopolysaccharide-induced cell proliferation in CD14-expressing Chinese hamster ovary cells.

CD14-expressing Chinese hamster ovary (CD14-CHO) cells, established by transfection of human CD14 DNA, acquired high responsiveness to lipopolysaccharide (LPS) through membrane-bound CD14 expression. LPS induced DNA synthesis and activated a series of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and c-Jun N-terminal kinase/stress-activated protein kinase, in CD14-CHO cells but not in mock-transfected CHO cells. Anti-CD14 antibody completely abrogated both LPS-induced DNA synthesis and LPS-induced phosphorylation of those MAP kinases, suggesting a critical role of membrane-bound CD14 in LPS signaling. A p38 MAP kinase inhibitor, SB203580, markedly augmented LPS-induced DNA synthesis in CD14-CHO cells, whereas an Erk1/2 inhibitor, PD98059, had no affect. On the other hand, SB203580 exhibited no effect on epidermal growth factor-induced DNA synthesis in CD14-CHO cells, although PD98059 inhibited it significantly. The activation and inactivation of p38 MAP kinase with dominant negative and dominant positive mutants also suggested the participation of p38 MAP kinase in LPS-induced DNA synthesis. It was therefore suggested that the activation of p38 MAP kinase can negatively regulate LPS-induced cell proliferation in CD14-CHO cells.

Animals↗
PubMed2001

Inhibition of caspase 3 abrogates lipopolysaccharide-induced nitric oxide production by preventing activation of NF-kappaB and c-Jun NH2-terminal kinase/stress-activated protein kinase in RAW 264.7 murine macrophage cells.

The effect of caspase inhibitors on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 267.4 murine macrophage cells was investigated. Pretreatment of RAW cells with a broad caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), resulted in a striking reduction in LPS-induced NO production. Z-VAD-FMK inhibited LPS-induced NF-kappaB activation. Furthermore, it blocked phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not that of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases. Similarly, a caspase 3-specific inhibitor, Z-Asp-Glu-Val-Asp-fluoromethylketone, inhibited NO production, NF-kappaB activation, and JNK/SAPK phosphorylation in LPS-stimulated RAW cells. The attenuated NO production was due to inhibition of the expression of an inducible-type NO synthase (iNOS). The overexpression of the dominant negative mutant of JNK/SAPK and the addition of a JNK/SAPK inhibitor blocked iNOS expression but did not block LPS-induced caspase 3 activation. It was therefore suggested that the inhibition of caspase 3 might abrogate LPS-induced NO production by preventing the activation of NF-kappaB and JNK/SAPK. The caspase family, especially caspase 3, is likely to play an important role in the signal transduction for iNOS-mediated NO production in LPS-stimulated mouse macrophages.

Amino Acid Chloromethyl Ketones↗
PubMed2001

The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells.

The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.

Animals↗
PubMed2001

Mouse B1 cell line responds to lipopolysaccharide via membrane-bound CD14.

The role of membrane-bound CD14 in the response of mouse B1 cell lines to lipopolysaccharide (LPS) was studied. The surface profile of mouse TH2.52 B cells was positive for CD5, IgM, B220, CD11b and F4/80, suggesting that TH2.52 cells carried the typical phenotype of B1 cells. Furthermore, TH2.52 B1 cells were found to express membrane-bound CD14, which plays a critical role in LPS recognition. TH2.52 B1 cells responded to a very low concentration of LPS and exhibited: (i) augmentation of DNA synthesis; (ii) activation of nuclear factor (NF)-kappaB; and (iii) phosphorylation of extracellular signal regulated kinase 1/2 (Erk1/2). They were markedly inhibited by anti-CD14 antibody. Therefore, the expression of membrane-bound CD14 was suggested to provide high sensitivity to LPS for TH2.52 B1 cells.

Animals↗
PubMed2001

The expression of membrane-bound CD14 renders mouse B-1 cells susceptible to LPS.

The surface expression of CD14 on mouse B-1 cells and its role on their response to lipopolysaccharide (LPS) were studied by using the murine TH2.52 B-1 cell line and peritoneal B-1 cells. TH2.52 cells with the B-1 phenotype were found to express membrane-bound CD14. Furthermore, CD14 was expressed on physiological peritoneal CD5+ B-1 cells. The stimulation of CD14-expressing TH2.52 cells with a low concentration of LPS resulted in the activation of nuclear factor (NF)-B and a mitogen-activated protein kinase (MAPK). The LPS-induced NF-B and MAPK activation was markedly inhibited by anti-CD14 antibody. These results suggest that B-1 cells may respond to LPS via membrane-bound CD14.

Animals↗
PubMed2000

Kinetics of expression of connective tissue growth factor gene during liver regeneration after partial hepatectomy and D-galactosamine-induced liver injury in rats.

Connective tissue growth factor (CTGF) is up-regulated by TGF-beta1 during wound healing. The present study examined the expression of CTGF during regeneration after 70% partial hepatectomy (PH) or d-galactosamine (GalN)-injured liver in rats. CTGF, TGF-beta1, and type I collagen mRNAs were semiquantified by a ribonuclease protection assay. After PH, TGF-beta1 and type I collagen were increased at 2-6 h and at 12-48 h. CTGF increased at 6 h and returned to the control level thereafter. The ribonuclease protection assay of cultured hepatic stellate cells (HSC) and in situ hybridization suggest that the cells express CTGF along sinusoid might be HSCs. After GalN administration, CTGF increased at 2-96 h with a shoulder peak at 6-12 h followed by a main peak at 24 h. TGF-beta1 and type I collagen were up-regulated with kinetics similar to those of CTGF. The different kinetics between PH and GalN regenerations indicate that regulation of CTGF in the two processes is different. Higher TGF-beta1 expression after inflammatory/necrotic process in the GalN regeneration may caused the prolonged CTGF expression.

Animals↗
PubMed2000

Big mitogen-activated kinase regulates multiple members of the MEF2 protein family.

Big mitogen-activated protein (MAP) kinase (BMK1), a member of the mammalian MAP kinase family, is activated by growth factors. The activation of BMK1 is required for growth factor-induced cell proliferation and cell cycle progression. We have previously shown that BMK1 regulates c-jun gene expression through direct phosphorylation and activation of transcription factor MEF2C. MEF2C belongs to the myocyte enhancer factor 2 (MEF2) protein family, a four-membered family of transcription factors denoted MEF2A, -2B, -2C, and -2D. Here, we demonstrate that, in addition to MEF2C, BMK1 phosphorylates and activates MEF2A and MEF2D but not MEF2B. The blocking of BMK1 signaling inhibits the epidermal growth factor-dependent activation of these three MEF2 transcription factors. The sites phosphorylated by activated BMK1 were mapped to Ser-355, Thr-312, and Thr-319 of MEF2A and Ser-179 of MEF2D both in vitro and in vivo. Site-directed mutagenesis reveals that the phosphorylation of these sites in MEF2A and MEF2D are necessary for the induction of MEF2A and 2D transactivating activity by either BMK1 or by epidermal growth factor. Taken together, these data demonstrate that, upon growth factor induction, BMK1 directly phosphorylates and activates three members of the MEF2 family of transcription factors thereby inducing MEF2-dependent gene expression.

Amino Acid Sequence↗
PubMed2000

Extracellular matrix components prevent lipopolysaccharide-induced bovine arterial endothelial cell injury by inhibiting p38 mitogen-activated protein kinase.

The effect of extracellular matrix components on lipopolysaccharide-induced vascular endothelial cell injury was studied by using lipopolysaccharide-susceptible bovine aortic endothelial cells. For evaluation of lipopolysaccharide-induced injury, we estimated DNA synthesis and cell detachment of bovine aortic endothelial cells in cultures using extracellular matrix components-coated plastic dishes. Among extracellular matrix components, matrigel almost completely inhibited the reduction in DNA synthesis and the enhancement in cell detachment of bovine aortic endothelial cells in cultures with lipopolysaccharide. The lipopolysaccharide-induced injury was also inhibited by coating with type IV collagen, gelatin, fibronectin, laminin, vitronectin, and heparin sulphate proteoglycan. Extracellular matrix components capable of preventing lipopolysaccharide-induced bovine aortic endothelial cells injury coincidentally inhibited the phosphorylation of p38 mitogen-activated protein kinase in lipopolysaccharide-treated bovine aortic endothelial cells. SB203580, a specific inhibitor of p38 mitogen-activated protein kinase, also prevented the reduction in DNA synthesis and the enhancement in cell detachment of bovine aortic endothelial cells in cultures with lipopolysaccharide. It was therefore suggested that extracellular matrix components might protect bovine aortic endothelial cells from lipopolysaccharide-induced injury through inhibiting the activation of p38 mitogen-activated protein kinase.

Animals↗
PubMed2000

Analysis of measles virus binding sites of the CD46 gene in patients with subacute sclerosing panencephalitis.

Measles virus (MV) binding sites of the CD46 gene were sequenced in patients with subacute sclerosing panencephalitis (SSPE) and in controls. There were 3 novel polymorphisms, including C/T at nucleotide position 38 (C/T38), G/A at position 176 (G/A176), and C/T at position 453 (C/T453), at allele frequencies of.97:.03, .99:.01, and.97:.03, respectively. The G/A176 polymorphism causes an Arg/Gln amino acid change within the essential binding sites of MV, whereas the C/A38 polymorphism causes a Ser/Phe change outside the MV binding sites. The C/T453 polymorphism does not produce an amino acid change. Two of the 40 SSPE patients and 2 of the 32 controls had both C/T38 and C/T453 polymorphisms in heterozygous patterns. One control subject, but no SSPE patients, had the G/A176 polymorphism in a heterozygous pattern. Thus, it is not likely that CD46 gene alteration has a role as a host susceptibility factor in the development of SSPE.

Adolescent↗
PubMed2000

Active intestinal tuberculosis with esophageal candidiasis due to idiopathic CD4(+) T-lymphocytopenia in an elderly woman.

We describe a case of intestinal tuberculosis and esophageal candidiasis in an 85-year-old Japanese woman with idiopathic CD4+ T-lymphocytopenia (ICL). The patient exhibited clinical symptoms of odynophagia, bloody diarrhea, and high fever. Physical examination on admission showed a poor nutritional status. Endoscopic examination of the upper digestive tract revealed the esophageal mucosa to be covered with yellowish-white plaque-like lesions. Colonoscopic examination revealed multiple annular ulcerations with bleeding. She was diagnosed with intestinal tuberculosis by polymerase chain reaction (PCR) and fecal culture. Her CD4+ T-lymphocyte count was 178/mm3 and no evidence of human immunodeficiency virus (HIV) infection was found. She was successfully treated with fluconazole and antituberculosis drugs. This case emphasizes the importance of opportunistic infections in elderly patients with predisposing conditions such as ICL.

Aged↗
PubMed2000

Four resections for hepatic metastasis from gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis.

In a patient with gastric cancer (GC) associated with one synchronous and three metachronous hepatic metastases (HM), who underwent four hepatectomies, we carried out histochemical investigations regarding cell proliferation, apoptosis, and angiogenesis in the GC and HM. Tissue samples were taken from the primary GC and four HM. Ki-67 immunostaining was performed to evaluate cell proliferation and determine the labeling index (Ki-67 LI; ie, the percentage of cancer cells with nuclei stained for Ki-67). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to evaluate apoptosis and determine the apoptotic index (ie, the percentage of TUNEL-positive cells), and immunostaining for factor VIII-related antigen was performed to evaluate angiogenesis and measure microvessel density (MVD). The Ki-67 LI was 43.2% in the primary GC and 39.9% in the synchronous HM, and the LI increased with the number of resections of metachronous HM. The apoptotic index was 3.36% in the primary GC, and 5.30% in the synchronous HM, and the index decreased after further resections of the metachronous HM. The MVD was 35 in the primary GC, and 22 in the synchronous HM, and it increased with the number of resections of metachronous HM. The primary GC in this patient may have strongly influenced the growth of HM through effects on cell proliferation, apoptosis, and angiogenesis.

Adenocarcinoma↗
PubMed2000

Co-occurrence of mucoepidermoid carcinoma and squamous cell carcinoma of the esophagus: report of a case.

A case of co-occurrence of a mucoepidermoid carcinoma (MEC) and a squamous cell carcinoma (SCC) in the esophagus is described. The present patient was a 61-year-old man who underwent a curative esophagectomy with a regional lymph node dissection for a MEC in the lower esophagus and a SCC near the esophagogastric junction. The two lesions were endoscopically and histologically divided by a normal esophageal mucosa. The MEC of the esophagus consisted of SCC cells and signet-ring cells, and a mucin product and carcinoembryonic antigen, which were found at high levels in the blood serum before surgery, were detected histochemically in the signet-ring cells. The follow-up survey of the patients with esophageal MEC previously reported in Japan showed that most of the patients died of either local recurrence or widespread metastasis after treatment; the overall 5-year survival rate was 24.4% in the total 25 cases, and 27.7% in the 22 resected cases. However, 6 patients who died of therapeutic complications were included among these patients; furthermore, the 5-year survival rate after surgery was 29.2% in the patients treated over the last decade (1989-1998). We expect that the clinical outcome of patients treated for esophageal MEC will therefore improve in the future.

Carcinoma, Mucoepidermoid↗
PubMed2000

Expression of vascular endothelial growth factor and angiogenesis in cardiac myxoma: a study of fifteen patients.

OBJECTIVE: To clarify the association between angiogenesis and the clinicopathologic features in cardiac myxoma, vascular endothelial growth factor expression in the myxoma was examined by using reverse transcriptase polymerase chain reaction and immunohistochemistry, and the microvessel density was determined by counting microvessels in the myxoma by using immunostaining for platelet endothelial cell adhesion molecule 1. METHODS: Seven fresh-frozen and 15 formalin-embedded tissues were analyzed by means of reverse transcriptase polymerase chain reaction and immunostaining for vascular endothelial growth factor, respectively. The microvessel density was measured in the 15 formalin-embedded tissues. Furthermore, immunostaining for proliferating cell nuclear antigen was performed, and the proliferating cell nuclear antigen-labeling index was calculated. RESULTS: All of the 7 analyzed myxomas were positive for vascular endothelial growth factor messenger RNA, as determined by means of reverse transcriptase polymerase chain reaction, whereas atrial septum and atrium tissues were negative. Positive immunohistochemical reaction for vascular endothelial growth factor was observed in the cells of all 15 myxomas. The size of myxomas with high vascular endothelial growth factor expression was smaller than that of myxomas with low vascular endothelial growth factor expression. The microvessel density in myxomas with high vascular endothelial growth factor expression was higher than that in myxomas with low vascular endothelial growth factor expression. There was an inverse correlation between the tumor size and the ratio of the microvessel density in the central part to the microvessel density in the peripheral part of myxomas. Furthermore, there was an inverse correlation between the proliferating cell nuclear antigen-labeling index and the tumor size, and the prolferating cell nuclear antigen-labeling index in myxomas with high vascular endothelial growth factor expression was higher than that in myxomas with low vascular endothelial growth factor expression. CONCLUSIONS: Cardiac myxomas produce vascular endothelial growth factor, which probably induces angiogenesis for tumor growth.

Adult↗
PubMed2000

Expression of membrane-type 1 matrix metalloproteinase in coronary vessels of allotransplanted primate hearts.

BACKGROUND: The mechanisms of intimal thickening in cardiac allograft vasculopathy (CAV) remain controversial after heart transplantation. Matrix metalloproteinase-2 (MMP-2) plays a crucial role in degrading extracellular matrix (ECM) during neointimal formation. Recently, it has been revealed that MMP-2 is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP). This process involves tissue inhibitor of MMP-2 (TIMP-2), forming an MT1-MMP/TIMP-2/pro-MMP-2 complex. In this study, we hypothesize that these components contribute to the pathogenesis of CAV. METHODS: Heterotopic cardiac allografting was performed in randomly paired Japanese monkeys with an immunosuppressive regimen of intravenous administration of antihuman CD18 monoclonal antibody. The donor hearts were harvested at Days 22, 28, 40, 41, and 95 posttransplantation. We examined expression of MMP-2, MT1-MMP, and TIMP-2 of graft vessels using immunohistochemistry and protein level by western blot analysis. RESULTS: Pathologically, various degrees of neointimal formation were observed. In the allografts harvested at Days 22, 28, 40, and 41, MT1-MMP was expressed in the endothelial cells and smooth muscle cells (SMCs) in media of some arteries without histological change, accompanied by expression of MMP-2 and TIMP-2. In the severely thickened neointima of the allograft harvested at Day 95, MMP-2 and faint MT1-MMP were expressed in SMCs of severely thickened neointima and media; TIMP-2 expression was seen only in noncollagenous tissue of severely thickened neointima. MMP-2 protein was more intensely expressed in the allograft harvested at Day 95 than in the allograft harvest at Day 41, while TIMP-2 protein level was almost same in the 2 samples. CONCLUSION: We observed the simultaneous expression of MMP-2, MT1-MMP, and TIMP-2. Thus, ECM degradation triggered by MT1-MMP/TIMP-2/pro-MMP-2 complex could be a novel mechanism of CAV.

Animals↗