[Molecular mechanism of action of ribotoxins].
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Animals↗
Biomedical subjects
Y Endo
Publications and source records attributed to Y Endo.
[Bleeding gastric varices associated with pancreatic arteriovenous malformation].
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Arteriovenous Malformations↗
Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA.
PURPOSE: Peritoneal dissemination is the most common cause of death associated with gastric cancer. In this study, we report the significance of molecular diagnosis of peritoneal dissemination by means of matrix metalloproteinase-7 (MMP-7) reverse transcriptase-PCR (RT-PCR) assay using preoperative peritoneal wash fluid. EXPERIMENTAL DESIGN: Preoperative peritoneal lavage by paracentesis was performed on 152 patients with gastric cancer. The peritoneal lavaged fluid was subjected to RT-PCR analysis with primers specific for MMP-7 and conventional cytological Papanicolaou examination. RESULTS: The MMP-7 RT-PCR assay was able to detect cancer cells at densities even lower than 10 cells/sample. There was no signal of MMP-7 mRNA from mesothelial cells, fibroblasts, peripheral blood, and lavaged fluid from patients with benign disease. Cytological examination and MMP-7 RT-PCR assay results were positive for 27 (18%) and 28 (18%) samples, respectively. The sensitivity for the prediction of peritoneal dissemination by cytology and MMP-7 RT-PCR assay were 46% and 33%, but the combination analysis using both parameters improved the sensitivity rate with 62%. Logistic regression analysis revealed that the cytological examination and MMP-7 RT-PCR assay are independent predictors of peritoneal dissemination. CONCLUSION: The combination of cytological examination and RT-PCR assay of preoperative peritoneal lavaged fluid is a highly efficient and reliable method for the selection of patients for adjuvant i.p. chemotherapy.
Adult↗
[Intermittent administration of 5-FU and isovorin to patients with advanced and recurrent colon cancer].
We attempted a new regimen of intermittent administration of 5-FU and low-dose Isovorin (F.I) to four patients with advanced and recurrent colon cancer. A partial response (PR) was achieved in two of four patients who had evaluable lesions for this treatment. We observed few side effects among these patients. Only one patient among four showed grade 1 neuropathy after two administrations of this chemotherapy. However, after a two-week pause in administration, the neuropathy disappeared and we could continue the therapy. This patient with multiple liver metastases achieved a partial response. Other patients had no side effects such as bone marrow suppression or digestive symptoms. This intermittent F.I treatment might be an effective and promising therapy with few side effects even for patients with poorer conditions.
Aged↗
Inhibition of peritoneal dissemination in human gastric cancer by MMP-7-specific antisense oligonucleotide.
MMP-7 is a matrix-degrading enzyme that is mainly produced from cancer cells, and has a great role in the invasion and metastasis of cancer. We have established a highly metastatic cell line (MKN-45-P) on the peritoneum of nude mice from MKN-45 by repeated intraperitoneal inoculation of intraperitoneal free cancer cells. By the precise screening of metastasis-related genes using reverse transcriptase-polymerase chain reaction (RT-PCR), MKN-45-P characteristically expressed more MMP-7 than the original cell line of MKN-45. In this study, we studied the effects of antisense oligonucleotides complementary to exon 3 of MMP-7 mRNA on the expression of MMP-7 and metastatic potential of MKN-45-P by using in vitro and in vivo experiments. RT-PCR and western blot analysis demonstrated that 10 microM antisense oligonucleotides suppressed MMP-7 expression at both the mRNA level (84%) and protein level (56%). Antisense oligonucleotides, specific for MMP-7 suppressed invasion by MKN-45-P cells without influencing proliferation. On the other hand, scrambling sequence control oligonucleotides did not show any inhibitory effects. In addition, survival of MKN-45-P bearing mice, which had been treated for 48 hrs with antisense oligonucleotides before intraperitoneal injection, was significantly better than that of control mice. In contrast, control oligonucleotides did not influence the survival of mice with the peritoneal dissemination model. These results strongly suggest that MMP-7 may have a great role in the formation of peritoneal dissemination in gastric cancer, and the molecular control of MMP-7 using antisense oligonucleotides may be a hopeful treatment modality for peritoneal dissemination.
Animals↗
[Tumor ablation with MRI navigation--a novel method of microwave coagulation therapy for hepatic tumor].
Fifty-eight patients with hepatic tumor which consisted of 22 hepatocellular carcinomas and 36 metastatic liver tumors were treated by microwave coagulation therapy with MRI navigation. The tumors were located in all segments of liver except S1. In 24 cases among them, the abdominal approach was difficult, because the tumors were located just below the diaphragm. These cases were selected for thoracoscope-assisted microwave ablation under MR-guidance across the diaphragm. All MR data were collected on a vertically oriented open MRI system (0.5 T SIGNA SP/i system: GE Medical Systems). The microwave electrode was introduced into the liver through a 14G needle via a percutaneous puncture with real-time MR image navigation. Microwave ablations at 60 W for 60 seconds were repeated several times depending on the tumor size. MR imaging may be employed as a reliable guide for percutaneous puncture. Moreover, sufficient safety margin could be obtained for hepatic tumor ablation. MR-guided microwave thermoablation therapy is a feasible method of treatment for hepatic tumors.
Carcinoma, Hepatocellular↗
Complement-dependent platelet degradation and anaphylactoid shock in mice induced by lipopolysaccharide carrying the mannose homopolymer.
Intravenous injection of specified bacterial lipopolysaccharides (LPSs) induced anaphylactoid shock in mice of various strains, including LPS-resistant C3H/HeJ. The reaction was accompanied by occasional mortality of mice within 1 h. Prior to shock, rapid accumulation of blood platelets in the lungs and liver followed by degradation of platelets (or release of their contents) and tissue destruction were observed. In this study, LPS specimens carrying mannose-homopolymer (MHP), which markedly activate the human complement system through the lectin pathway, induced marked platelet degradation and anaphylactoid shock in BALB/c mice. In contrast, in C5-deficient DBA/2 mice, the platelet degradation and anaphylactoid reactions did not occur. Anti-complement agent K-76 COOH (C5 inhibitor) protected BALB/c mice from mortality in the anaphylactoid reaction. K-76 COOH also inhibited platelet degradation, but not accumulation, induced by LPS in mice. Based on these findings, we postulated that strong complement activation by specified LPS preparations induced degradation of platelets that have accumulated in the lungs and liver, resulting in acute inflammation accompanied by severe tissue destruction, especially in the lungs, which in turn leads to anaphylactoid reaction.
Anaphylaxis↗
[Non-approved antidotes in Japan--Foreign antidotes imported for poisoning countermeasures at the Summit 2000].
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Antidotes↗
[A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system].
AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions.
Aged↗
Differential chromatin packaging of genomic imprinted regions between expressed and non-expressed alleles.
Chromosomal regions subject to genomic imprinting comprise a functional domain exhibiting parental-specific expression of genes and hence may take a unique chromatin structure. Here we have examined the chromatin packaging state of allelic sites in the Zfp127/Snrpn locus on mouse chromosome 7 and in the Igf2r locus on mouse chromosome 17 with an assay consisting of chromatin fractionation and allele-specific detection. The results showed that non-transcribed alleles of Igf2r are packaged more compactly than transcribed alleles in F(1) hybrid mice of both types of cross between C57BL/6 and MSM strains, whereas a non-imprinted gene, Sod-2, in the vicinity of Igf2r does not show such a difference. This indicates a close correlation between imprinting and the differential packaging of chromatin. On the other hand, the Zfp127/Snrpn locus showed such an allele-specific fractionation pattern only in F(1) hybrid mice of a cross but not in those of the reciprocal cross. Analysis of the congenic mice produced for this locus did not provide any difference. These results suggest that chromatin of imprinted domains in different compaction levels is affected by distinct blueprints in homologous chromosomes that are heritable through the germ line.
Alleles↗
Induction of histidine decarboxylase, the histamine-forming enzyme, in mice by interleukin-12.
Interleukin (IL)-12, a potent antitumour cytokine, has inflammatory side effects. We examined the effect of IL-12 on the histamine-forming enzyme, histidine decarboxylase (HDC). When injected intraperitoneally into C3H/HeN mice, IL-12 exhibited antitumour activity against squamous epithelial tumour cells (NR-S1 cells). At doses that produced this antitumour activity, IL-12 also enhanced HDC activity in the lung, liver, spleen and bone marrow. Compared with that induced by IL-1, the elevation of HDC activity induced by IL-12 was low and slow. However, daily injections of IL-12, but not of IL-1, produced a cumulative effect on HDC activities, an accumulation of exudate in the thorax, and death. Antagonists of H1 and H2 receptors and an inhibitor of HDC all failed to prevent the pulmonary exudation and death. These results suggest that IL-12 is an inflammatory cytokine capable of stimulating the synthesis of histamine, but that histamine itself may be not the direct cause of the pulmonary exudation and/or lethality induced by IL-12.
Animals↗
Polymethylcarborane as a novel bioactive moiety: derivatives with potent retinoid antagonistic activity.
4[(Deca-B-methyl-1,12-dicarba-closo-dodecaboran-1-yl)c arbamoyl]benzoic acid and its congeners showed potent antagonistic activity at concentrations of 10(-7)-10(-8) M on the differentiation-inducing action of retinoids towards human promyelocytic leukemia HL-60 cells. This is the first example of derivatives of polymethylcarborane, which resembles C60 in size, with biological activity.
Benzoates↗
Deactivation of neutrophil NADPH oxidase by actin-depolymerizing agents in a cell-free system.
The cell-free activation of human neutrophil NADPH oxidase (O(2)(-)-generating enzyme) is enhanced by actin [Morimatsu, Kawagoshi, Yoshida and Tamura (1997) Biochem. Biophys. Res. Commun. 230, 206--210]. In an attempt to elucidate the mechanism, we examined the effect of actin-depolymerizing agents on the duration of NADPH oxidase in a cell-free system. The addition of DNase I, an F-actin-depolymerizing protein, caused an accelerated deactivation of the oxidase. The deactivation was also facilitated by latrunculin A, a sponge toxin that depolymerizes F-actin. Exogenously added actin prevented the deactivation by DNase I or latrunculin A, whereas EDTA accelerated a dilution-induced deactivation of the oxidase and Mg(2+) ions retarded it. The stability in dilution was found to correlate well with free Mg(2+) concentration. Estimation of F-actin in the system showed that F-actin increased during the oxidase activation and that DNase I or EDTA decreased F-actin content in parallel with the activity. Treatment of the cell-free mixture with a chemical cross-linker prevented the deactivation and F-actin decrease by EDTA. Taken together, these results suggest that actin filaments which grow during the activation of NADPH oxidase prolong the lifetime of the oxidase.
Actins↗
Inhibitory effect of stromal cell derived factor-1 on the replication of divergent strains of feline immunodeficiency virus in a feline T-lymphoid cell line.
The effect of a CXC-chemokine, stromal cell derived factor-1 (SDF-1), on the replication of divergent strains of feline immunodeficiency virus (FIV) was examined in order to identify the mechanism of cell entry of FIV. A chemotaxis assay, using a modified Boyden chamber method, confirmed the biological activity of recombinant human (rh) SDF-1 for a feline T-lymphoid cell line (Kumi-1). The viral replication of FIV, as measured by the reverse transcriptase (RT) activity in the culture supernatant, was significantly suppressed by addition of rhSDF-1 in a dose-dependent manner in Kumi-1 cells. Furthermore, PCR analysis of the FIV proviral genome indicated that the inhibitory effect of rhSDF-1 on the replication of FIV in Kumi-1 cells was due to the inhibitory effect in the early event of replication. The inhibitory effect on viral replication by exogenous rhSDF-1 was shown for four divergent FIV isolates of subtypes A, B, and D in Kumi-1 cells.
Animals↗
A novel female-specific member of the CYP3A gene subfamily in the mouse liver.
Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we determined the primary structure of its cDNA and examined its expression profile. This cytochrome P450 consisted of 504 amino acids and showed 92, 68, 88, and 69% amino acid sequence identity with mouse CYP3A11, 3A13, 3A16, and 3A25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to those of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of animals of both sexes, but increased with age in females, whereas it was gradually reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicated that estradiol and testosterone were able to induce and suppress the expression of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not affect the level of CYP3A41 mRNA in the liver of either sex. On the other hand, pregnenolone 16alpha-carbonitrile and phenobarbital suppressed CYP3A41 level to half that of untreated female mice. These observations indicated that CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in the female mouse liver.
Amino Acid Sequence↗
Inhibition of adjuvant-induced inflammatory hyperalgesia in rats by local injection of neurotrophin-3.
The induction of nerve growth factor (NGF) in inflammatory tissue has been shown to be involved in hyperalgesia. In the present study, the role of neurotrophin-3 (NT-3) in the regulation of inflammatory hyperalgesia was analyzed. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) to the rat hind paw. NT-3 levels in the plantar skin were much higher than NGF levels (1.24 and 0.14 ng/g tissue, respectively) before CFA injection, but decreased significantly 6 h to 48 h after the injection while NGF was markedly induced at 6 h but decreased thereafter. When 1 microg of NT-3 was locally injected at 5 h after CFA injection at the time NT-3 levels decreased, hyperalgesia was reversed transiently but specifically. These results suggest an inhibitory role of NT-3 in the regulation of pain sensitivity.
Animals↗
Alteration of beta-catenin expression in esophageal squamous-cell carcinoma.
beta-catenin regulates cadherin-mediated cell-cell adhesion and also functions as a signaling molecule. In this study, we examined the expression pattern of E-cadherin, alpha-catenin and beta-catenin in 22 cases of esophageal squamous-cell carcinoma by Western-blot analysis. Expression of E-cadherin, alpha-catenin and beta-catenin was lower in carcinomas than in normal esophageal mucosa in 4 cases (18.2%) for E-cadherin, 6 cases (27.3%) for alpha-catenin and 9 cases (40.9%) for beta-catenin. Expression of beta-catenin was not always correlated with that of E-cadherin. Over-expression of beta-catenin was observed in 3 cases (13.6%). Of 3 cases that presented with over-expression of beta-catenin, 2 showed cytoplasmic staining by immunohistochemistry. Nuclear localization of beta-catenin was observed in one case that had higher beta-catenin level in tumor tissue (1.4-fold higher than normal mucosa). The genomic DNA sequences of the beta-catenin and the APC gene were analyzed. No mutation of the beta-catenin gene was observed in any cases. Silent mutation of the APC gene was found in all the cases that showed over-expression or nuclear localization of the beta-catenin protein. These results indicate that alterations of the cadherin-catenin complex may play an important role in a sub-set of esophageal carcinogenesis. Furthermore, it is suggested that beta-catenin over-expression is not caused by genetic alteration of either the beta-catenin or the APC gene.
Blotting, Western↗
Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease.
Both ficolins and mannose-binding lectin (MBL) are lectins characterized by the presence of collagen-like and carbohydrate-binding domains in a subunit, although their carbohydrate-binding moieties are quite different. A fibrinogen-like domain is in ficolins, and a carbohydrate recognition domain is in MBL. On binding to pathogens, human MBL activates the complement system via the lectin pathway in association with two types of MBL-associated serine proteases (MASP), MASP-1 and MASP-2 and its truncated form, small MBL-associated protein (sMAP, also called MAp19). We report here that ficolin/P35, a human serum ficolin, was found to copurify with MASPs and sMAP. MASPs that were complexed with ficolin/P35 exhibited proteolytic activities against complement components C4, C2, and C3. The ficolin/P35-MASPs-sMAP complex that was bound to Salmonella typhimurium activated complement. These findings indicate that ficolin/P35 is a second collagenous lectin capable of activating the lectin pathway and thus plays a role in innate immunity.
Biopolymers↗