Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 127 records · Page 7Linked to original sources

PubMed2000

Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Animals↗

PubMed2000

Functional analysis of human metaxin in mitochondrial protein import in cultured cells and its relationship with the Tom complex.

Metaxin is an outer membrane protein of mammalian mitochondria which is suggested to be involved in protein import into the organelle. RNA blot analysis showed that distribution of metaxin mRNA in human tissues differs from that of mRNA for the translocase component Tom20. Effect of overexpression of human metaxin on mitochondrial preprotein import and processing in COS-7 cells was studied. Overexpression of metaxin resulted in impaired mitochondrial import of natural and chimeric preproteins and in their accumulation. We previously reported that overexpression of Tom20 in cultured cells causes inhibition of import of mitochondrial preprotein. Coexpression of metaxin with Tom20 had no further effect on the preprotein import. Overexpression of the cytosolic domain of metaxin also caused inhibition of preprotein import, although less strongly than the full-length metaxin. In blue native PAGE, Tom40, Tom22, and a portion of Tom20 migrated as a complex of approximately 400 kDa, and the other portion of Tom20 migrated in smaller forms of approximately 100 and approximately 40 kDa. On the other hand, metaxin migrated at a position of approximately 50 kDa. These results confirm earlier in vitro results that metaxin participates in preprotein import into mammalian mitochondria, and indicates that it does not associate with the Tom complex.

Animals↗

PubMed2000

Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice.

The intake of citrus fruits has been suggested as a way to prevent the development of some types of human cancer. Nitric oxide (NO) is closely associated with the processes of epithelial carcinogenesis. We attempted a search for NO generation inhibitors in Citrus unshiu. The active constituent was traced by an activity-guiding separation. NO and superoxide (O2-) generation was induced by a combination of lipopolysaccharide and IFN-gamma in mouse macrophage RAW 264.7 cells, and by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocyte HL-60, respectively. Expression of inducible NO synthase and cyclooxygenase 2 proteins were detected by Western blotting. The in vivo anti-inflammatory and antitumor promoting activities were evaluated by topical TPA application to ICR mouse skin with measurement of edema formation, epidermal thickness, leukocyte infiltration, hydrogen peroxide production, and the rate of proliferating cell nuclear antigen-stained cells. As a result, nobiletin, a polymethoxyflavonoid, was identified as an inhibitor of both NO and O2- generation. Nobiletin significantly inhibited two distinct stages of skin inflammation induced by double TPA application [first stage priming (leukocyte infiltration) and second stage activation (oxidative insult by leukocytes)] by decreasing the inflammatory parameters. It also suppressed the expression of cyclooxygenase-2 and inducible NO synthase proteins and prostaglandin E2 release. Nobiletin inhibited dimethylbenz[a]anthracene (0.19 micromol)/TPA (1.6 nmol)-induced skin tumor formation at doses of 160 and 320 nmol by reducing the number of tumors per mouse by 61.2% (P < 0.001) and 75.7% (P < 0.001), respectively. The present study suggests that nobiletin is a functionally novel and possible chemopreventive agent in inflammation-associated tumorigenesis.

Animals↗

PubMed2000

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals↗

PubMed2000

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy.

BACKGROUND: Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear. OBJECTIVE: To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C. DESIGN: Retrospective cohort study. SETTING: 7 university hospitals and 1 national hospital in Japan. PATIENTS: 593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated. INTERVENTION: Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy. MEASUREMENTS: Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated. RESULTS: 183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (+/-SE) reduction in fibrosis score of -0.60+/-0.07 at less than 3 years of follow-up and -0.88+/-0.08 at 3 years or more of follow-up. The rate of fibrosis progression was -0.28+/-0.03 unit/y (regression) in patients with sustained response, 0.02+/-0.02 unit/y in patients with nonsustained response (P< 0.001), and 0.10+/-0.02 unit/y in untreated patients. CONCLUSION: Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.

Adult↗

PubMed2000

Modifying effects of carotenoids on superoxide and nitric oxide generation from stimulated leukocytes.

Excessive and prolonged generation of superoxide (O2-) and nitric oxide (NO) from inflammatory leukocytes is associated with several lifestyle-related diseases, including cancer. In the present study, we screened 19 natural carotenoids for their modifying effects on O2- and NO generation from differentiated human promyelocytic HL-60 cells and mouse macrophage RAW 264.7 cells, respectively. Of the carotenoids tested, halocynthiaxanthin, isolated from oysters, showed the highest suppressive effect on the generation of both free radicals. The inhibitory potencies of certain carotenoids on radical generation markedly exceeded that of beta-carotene. In addition, some important structural moieties regulating radical generation suppression are discussed.

Animals↗

PubMed2000

14-3-3tau associates with a translational control factor FKBP12-rapamycin-associated protein in T-cells after stimulation by pervanadate.

Proteins of the 14-3-3 family can associate with and/or modulate the activities of a variety of proteins, such as protooncogene and oncogene products, Cdc25 phosphatases and phosphatidylinositol 3-kinase, and thus are implicated in regulation of signaling pathways and the cell cycle. We report here that treatment of Jurkat T-cells with an inhibitor of protein tyrosine phosphatase, pervanadate, induces the association of 14-3-3tau with a translational control factor, FKBP12-rapamycin-associated protein (FRAP), with significant latter's autophosphorylation. Coimmunoprecipitation of various mutants of FRAP coexpressed with 14-3-3tau in COS-7 cells revealed that 14-3-3tau binds to the C-terminal side of FRAP at unknown site(s) different from the predicted binding motifs to date.

14-3-3 Proteins↗

PubMed2000

1,1-Dimethylallylcoumarins potently suppress both lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in mouse macrophage RAW 264.7 cells.

We investigated the suppressive effects of 16 coumarin-related compounds on both lipopolysaccharide (LPS)- and interferon (IFN)-gamma-induced nitric oxide (NO) generation in a mouse macrophage cell line, RAW 264.7. Notably, coumarins possessing prenyl unit(s) were found to be highly active, a tendency consistent with our previous study. Among the coumarins tested, 1,1-dimethylallylcoumarins showed the highest inhibitory activity. Western blotting analysis revealed that they inhibited NO generation by suppressing inducible NO synthase (iNOS) protein expression. Our ongoing studies suggest that coumarins are prominent natural compounds that attenuate excessive and prolonged NO generation at inflammatory sites.

Animals↗

PubMed2000

Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.

The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect disease-causing mutations, to clarify their frequency and distribution, to determine whether genotype correlates with phenotype, and to determine the rate of abnormal findings in heterozygotes for the WD gene. We analyzed 41 unrelated Japanese WD families, including 47 patients. Twenty-one mutations, including nine novel ones, were identified. 2871delC (15.9%), 1708-5T-->G (11. 0%), and Arg778Leu (13.4%) were the most common mutations. 2871delC was detected mainly in eastern Japan and 1708-5T-->G in western Japan. The homozygotes for the 1708-5T-->G, 2871delC, or Arg778Leu mutations did not show a correlation with their phenotypes. Ceruloplasmin and copper levels were abnormally low in 28.6% and 35. 0% of heterozygotes, respectively. When patients and their families are screened for WD, a high rate of abnormal laboratory data in heterozygotes must be taken into account.

Adenosine Triphosphatases↗

PubMed2000

Relation between stent expansion and arterial remodeling: a serial intravascular ultrasound study.

Previous studies suggested that stent area (SA) did not change after the Palmaz-Schatz stent implantation. Whether these findings apply to other types of stent, however, is unknown. This study assessed vascular response to stent implantation using intravascular ultrasound (IVUS) studies. Serial (pre-intervention to follow-up) IVUS imagings were used to study 57 native coronary lesions after the GFX stent or the Multilink stent implantation. The vessel area (VA) at lesion site increased at follow-up (16.92 +/- 3.67 mm(2) after intervention to 18.17 +/- 4.66 mm(2) at follow-up, P < 0.01). The SA also increased from 8.39 +/- 1.90 mm(2) after intervention to 8.80 +/- 2.08 mm(2) at follow-up (P = 0.02). Thirty-two percent of lesions showed late stent expansion. The stent expansion [Delta (after intervention to follow-up) SA] correlated significantly with the VA growth [Delta (after intervention to follow-up) VA] (r = 0.59, P < 0.0001). In conclusion, some lesions reveal late stent expansion after both the GFX stent and the Multilink stent implantation. Adaptive vessel remodeling may be followed by stent expansion.

Aged↗

PubMed2000

Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti-inflammatory polymethoxyflavonoid.

Citrus fruit intake is known to be associated with a reduction of cancer incidence. Free radicals, including superoxide (O2-) and nitric oxide (NO), are involved in some epithelial carcinogenesis processes. In the present study, we screened thirty-one citrus fruits for their suppressive activities toward three lines of free radical generating systems: 1) O2- generation by the xanthine (XA)-xanthine oxidase (XOD) system; 2) O2- generation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic HL-60 cells; and 3) NO generation in murine macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma. As a result, the inhibitory activities of peel parts were largely found to be higher than those of the corresponding juice sac parts. In particular, the peel portion of Dancy tangerine (Citrus tangerinia) showed marked anti-oxidative activities in these systems. In addition, nobiletin, a polymethoxyflavonoid isolated from C. nobilis, showed a higher anti-inflammatory activity than indomethacin in a TPA-induced edema formation test in mouse ears. These results indicate that citrus fruits could be notable sources of anti-oxidative, anti-inflammatory, and cancer preventive compounds.

Animals↗

PubMed2000

Cancer prevention by natural carotenoids.

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2000

Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery.

Nasal carriage of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) is associated with an increased risk for postoperative staphylococcal infection. This study was conducted to investigate the effect of preoperative nasal mupirocin treatment on the postoperative infections in patients undergoing upper gastrointestinal surgery. The intervention group consisted of 141 consecutive patients who underwent upper gastrointestinal surgery between March 1, 1997, and February 28, 1998. The patients in the intervention group were treated with intranasal mupirocin three times a day for 3 consecutive days before surgery. The incidence of postoperative staphylococcal infections in the intervention group was then compared with that of the historical control group. The control group consisted of 128 consecutive patients who underwent upper gastrointestinal surgery without mupirocin treatment between January 1, 1996 and December 31, 1996. The postoperative staphylococcal infection rate in the control group (11.7%) was significantly higher (P < 0.001) than in the intervention group (0.71%). The postoperative MRSA infection rate was significantly reduced by the intervention (control group 7.0% and intervention group 0%; P < 0.01). These results suggest that preoperative nasal eradication of S. aureus with mupirocin thus appears to be an effective measure to prevent postoperative staphylococcal infection in patients undergoing upper gastrointestinal surgery.

Administration, Intranasal↗

PubMed2000

Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6.

AIMS/HYPOTHESIS: Both endocrine and exocrine cells of the pancreas differentiate from epithelial cells of primitive pancreatic ducts, and four types of pancreatic islet cells (alpha, beta, delta, and PP cells) are derived from the common pluripotent precursor cells. Although Pa x 6 is expressed in all islet cells, Pa x 4 is detected only in beta cells. In homozygous Pa x 4-null mice, beta cells are absent, whereas the number of alpha cells is increased. Therefore, we hypothesized that the balance of Pa x 4 and 6 is one of the determinants by which the common progenitor cells differentiate into alpha or beta cells. METHODS: To change this balance, we generated transgenic mice overexpressing Pa x 6 driven by the insulin promoter or the PDX1 promoter. RESULTS: In both types of transgenic mice, normal development of beta cells was disturbed, resulting in apoptosis of beta cells and diabetes. In Insulin/Pa x 6-Tg mice, beta cells were specifically affected, whereas in PDX/Pa x 6-Tg mice, developmental abnormalities involved the whole pancreas including hypoplasia of the exocrine pancreas. Furthermore, PDX/Pa x 6-Tg mice experienced proliferation of both ductal epithelia and islet cells and subsequent cystic adenoma of the pancreas. CONCLUSION/INTERPRETATION: These findings suggest that Pa x 6 promotes the growth of ductal epithelia and endocrine progenitor cells and that the suppression of Pa x 6 is necessary for the normal development of beta cells and the exocrine pancreas.

Animals↗

PubMed2000

Appraisal of treatment strategy by staging laparoscopy for locally advanced gastric cancer.

More accurate preoperative staging is necessary to determine the treatment strategy for locally advanced gastric cancer. Thirty-two patients with T3 or T4 gastric cancer expected to undergo curative resection based on conventional examinations underwent staging laparoscopy. The disease stages determined were compared with those obtained by conventional methods. The discrepancy rate of disease staging was 16 of 32 (50.0%), with down-staging in 5 of 32 (15.6%) and up-staging in 11 of 32 (34.4%). Of the 32 patients, 13 (40.6%) were found to have unsuspected peritoneal dissemination. The positive predictive value for peritoneal metastasis by staging laparoscopy was 100%, whereas the negative predictive value was 89% (17/19). The accuracy rate was 94%. After laparoscopy, 15 of the 32 (46.9%) were diagnosed as candidates for curative resection. Of these 15 patients who underwent surgery, 13 (86.7%) underwent curative resection (1 R0 and 12 R1); the remaining two underwent R2 resection because of peritoneal metastasis that was undetected by staging laparoscopy. Patients with tumors judged noncurable by laparoscopy (n = 11) received neoadjuvant chemotherapy. In 7 of the 11 cases, salvage surgery was done (one R0, three R1, three R2 resections). A second staging laparoscopy was performed in four cases to determine the indication for salvage surgery. Three of the four were judged to be curable and underwent curative resection. Staging laparoscopy is an effective tool for detecting unsuspected peritoneal metastasis, and it can increase the curative resection rate and decrease unnecessary laparotomy for advanced gastric cancer. Second-look laparoscopy enables accurate assessment of the chemotherapeutic response, which can help in decisions about salvage surgery.

Adenocarcinoma↗

PubMed2000

A model of binocular stereopsis including a global consistency constraint.

The binocular correspondence problem was solved by implementing the uniqueness constraint and the continuity constraint, as proposed by Marr and Poggio [Marr D, PoggioT (1976) Science 194: 283-287]. However, these constraints are not sufficient to define the proper correspondence uniquely. With these constraints, random-dot stereograms (RDSs), consisting of the periodic textures in each image, are treated as a correspondence of surfaces composed of patches of alternating values of disparity. This is quite different from the surface we perceive through the RDSs, that is a surface characterized by a single depth. Because these constraints are local, they cannot produce the global optimum of correspondence. To obtain the global optimum of correspondence, we propose a model of binocular stereopsis in which a global measure of correspondence is explicitly employed. The model consists of two hierarchical systems. First, the lower system processes various correspondences based on the uniqueness constraint. Second, the higher system provides a global measure of correspondence for the disparity in question. The higher system uniquely determines the global optimum of correspondence in the lower system through the recurrent loop between hierarchical systems. The convergence of the recurrent loop is determined by the consistency between the hierarchical systems. The condition is termed the 'global consistency constraint.

Algorithms↗

PubMed2000

Emergent mechanisms in multiple pattern generation of the lobster pyloric network.

By using a hard-wired oscillator network, multiple pattern generation of the lobster pyloric network is simulated. The network model is constructed using a relaxation oscillator representing an oscillatory or quiescent (i.e. steady-state) neuron. Modulatory inputs to the network are hypothesized to cause changes in the dynamical properties of each pyloric neuron: the oscillatory frequency, the postinhibitory rebound property, and the resting membrane potential. Changes in each of these properties are induced by changing appropriate parameters of the oscillator. By changing seven parameters of the network as a whole, modulatory input-dependent patterns are successfully simulated.

Animals↗

PubMed2000

Nafamostat mesilate treatment during open heart operation in immune thrombocytopenic purpura.

A 58-year old woman with idiopathic thrombocytopenic purpura underwent mitral and aortic valve replacements and tricuspid annuloplasty. Preoperative therapeutic interventions including prednisone and immunoglobulin were successful in elevating the platelet count to 93,000/ mm2. Furthermore, we used nafamostat mesilate for coagulopathy prophylaxis during cardiopulmonary bypass. Postoperative bleeding was average and clinical course was uneventful. The perioperative management for patients with idiopathic thrombocytopenic purpura requiring cardiac operation is reviewed.

Anticoagulants↗