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  • 1
    ISSN: 1432-0738
    Keywords: Fungal cyclic peptide ; Mycotoxin ; Cyclochlorotine ; Periportal liver necrosis ; Cytochrome p-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sequential morphological changes in murine liver induced by cyclochlorotine (CC), a secondary metabolite of Pencicillium islandicum were investigated by transmission electron microscopy and scanning electron microscopy. Within 15 min after the administration of CC there was a marked dilatation of Disse's space around the portal triads, and the exudates then poured out into the space which was formed by the invagination of the hepatocyte plasma membrane. Shortly after the invagination was completed, the connection between Disse's space and the invaginated space was pinched off, so that this space became a membrane-bound vacuole. After dehydration, the vacuoles became granular. The liver injuries induced by CC were influenced by various pretreatments. The results indicate that drug-metabolizing systems mediated by cytochrome p-450 in the hepatocytes may play an important role in the hepatotoxicity of CC.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-0832
    Keywords: Emestrin ; mycotoxin ; mycotoxicosis ; Emericella striata ; mouse liver ; mouse lymphoid tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of emestrin (EMS), a secondary metabolite of the Emericella species, on male ICR mice were examined. The intraperitoneal LD50 values of EMS were 17.7 and 13.0 mg/kg at 24 and 48 hr, respectively. The target organs of EMS were the heart, liver and thymus. In doses over 30 mg/kg the experimental animals died from cardiac failure shortly after the injections. Several survivors that were given EMS in doses under 20 mg/kg showed severe centrilobular necrosis in the liver at 24 hr. Marked degeneration of mitochondria was seen in electron micrographs of both cardiac muscle cells and hepatocytes. In the degenerated hepatocytes, prominent proliferation of RER, membrane-limited inclusions containing both ribosome-like granules and RER, and fenestrated lamella-like structures were observed. Massive necrosis of lymphocytes was always observed in the cortical layer of the thymus of the survivors within 24 hr, while bilateral adrenalectomized mice showed no discernible pathomorphological changes in the lymphoid tissues. Pretreatment of mice with diethyl maleate increased the incidence and severity of hepatic necrosis, whereas that with either cysteine or CoCl2 reduced the severity of centrilobular necrosis of the liver. Pretreatment with phenobarbital had no significant effect on EMS-induced hepatic lesions.
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  • 4
    ISSN: 1573-0832
    Keywords: Nocardia otitidiscaviarum ; exotoxin poisoning ; RER ; autophagic vacuole ; nocardiosis ; fatty liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs.
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  • 5
    ISSN: 1573-0832
    Keywords: Candida albicans ; cyclosporin ; cyclophosphamide ; FK506 (tacrolimus) ; immunosuppressive agents ; infection ; pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of the immunosuppressive agents FK506 (tacrolimus) and cyclosporin (CyA) on Candida albicans infection in mice were compared with those of cyclophosphamide. FK506 and CyA did not exacerbate C. albicans infection in mice when the effects were determined on the basis of survival ratio and colony forming units (CFU) in the kidney, although cyclophosphamide (CY) impaired the host defence mechanisms of mice against C. albicans infection. The effects of FK506 and CyA on the body weight of mice, histopathological changes of lymphoid tissues and formation of granulomas in kidney were also studied in comparison with those of CY.
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  • 6
    ISSN: 1573-0832
    Keywords: Human PMN ; H. capsulatum ; fungicidal resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The basis for resistance of yeast form of Histoplasma capsulatum to antifungal activity of human neutrophils was studied. In limiting dilution assays and short term coculture assays human neutrophils were ineffective in killing H. capsulatum whereas Candida albicans was readily killed. By contrast, in a cell free hydrogen peroxide-peroxidase-halide system H. capsulatum was as sensitive to killing as C. albicans. Moreover, lysate of human neutrophils effectively substituted for horse-radish peroxidase in a cell free system for killing H. capsulatum. H. capsulatum elicited significant products of the oxidative burst in human neutrophils as detected by luminol-enhanced chemiluminescence. However, the response was two-fold less (p〈0.05) than that induced by C. albicans. Transmission electron microscopy studies showed that phagosome-lysosome fusion took place when neutrophils phagocytosed C. albicans or H. capsulatum. Taken together, these findings indicate that, even though H. capsulatum elicits an oxidative burst and phagosome-lysosome fusion within the phagosome, it is capable of evading damage in short term assays.
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  • 7
    Publication Date: 2020-11-17
    Description: Introduction: The progression of dilated cardiomyopathy (DCM) mainly involves genetic mutations or ischemia at the cellular level, leading to microvascular dysfunction associated with cell death, interstitial fibrosis, and high wall stress. Radical treatment of DCM requires how to ameliorate its microcirculation and integrate cardiomyocytes created ex vivo into recipient myocardium. Hypothesis: The induced pluripotent stem cell derived cardiomyocyte sheets (iPS-sheet) has therapeutic potential by the improvement of microcirculation in a porcine DCM model. Methods: The iPS-sheets were generated from clinical grade human iPS cells. A DCM model was created by tachycardia pacing, and iPS-sheet was transplanted with immunosuppressive agents 1 month after the initiation of the pacing. We compared the therapeutic efficacy functionally and pathologically between the iPS-sheet transplant group (iPS-group) and the sham group after 1 month of transplantation. Results: On echocardiography, the iPS group showed a significant improvement in contractility compared to the sham group (LVEF 4 weeks after transplantation iPS vs. sham 49.0±6.5% vs. 36.4±3.3%, p
    Print ISSN: 0009-7322
    Electronic ISSN: 1524-4539
    Topics: Medicine
    Published by Ovid Technologies on behalf of American Heart Association.
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  • 8
    Publication Date: 2020-11-17
    Description: Background: Although Cardiomyogenesis therapy using iPS cells for heart failure should overcome immune rejection because of allogenic cell source, appropriate protocol of immunosuppressant to promise efficacy and safety has not been fully elucidated. In this study, we investigated the duration of immunosuppressant administration that could promise the efficacy of human iPS cell derived cardiomyocytes (hiPSCs-CM) patch transplantation as well as safety. Methods: The hiPSCs-CM patch were transplanted to myocardial infarction model rats with normal immune function in immunosuppressant treatment groups. Control were underwent sham operation and treated with no immunosuppressant (Group1). Immunosuppressant treatment groups were divided into three groups as follows: treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PSL) for 1month and 1 month tapering period (Group2); treated with TAC, MMF, and PSL for 2month and 1 month tapering period (Group3); and treated with TAC, MMF, and PSL for 3month and 1 month tapering period (Group4). After 6 months, cardiac function and histology were analyzed. Results: hiPSC-CM patch transplantation showed significant improvement cardiac fraction compared to the Group1 (ΔLVEF; Group2 22 ± 3 %, Group3 28 ± 5 %, Group4 23 ± 4 % versus Group1 -15 ± 8 %, P 〈 0.05) and did not show any differences in immunosuppressant treated groups. The hiPSCs-CM patch were detected for 2 months post-transplant and Improved Cardiac functions were maintained for at least 6 months despite disappearance of the transplanted patch. Fibrosis and cardiomyocyte size were significantly ameliorated in Group2-4 compared with Group1, however, there were significant differences in immunosuppressant treated groups. Furthermore, the Group 2, 3 and 4 showed a greater amount of structurally mature blood vessels compared with Group1, however, there were no significant in immunosuppressant treated groups. Tumor formation was not observed 6 months after transplantation in the Group 2, 3 and 4. Conclusion: 2 months administration of immunosuppressive agent may promise the safety and efficacy of hiPSCs-CM patch transplantation for rat ischemic heart failure model, proposing appropriate recipe of immunosuppressant in clinical trial.
    Print ISSN: 0009-7322
    Electronic ISSN: 1524-4539
    Topics: Medicine
    Published by Ovid Technologies on behalf of American Heart Association.
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  • 9
    Publication Date: 2020-11-17
    Description: Although hypertrophic cardiomyopathy (HCM) is a major hereditary heart disease, unknown underlying basic pathology make it difficult for physicians to heal this disease. We hypothesized that the disease specific iPS derived cardiomyocytes from HCM with the myosin binding protein C (MYBPC3) mutation represent the pathophysiological phenotype, and editing the mutation would cancel the diseased phenotype to check the role in the mutation gene. We established iPS cells with heterozygous frameshift mutation (WT/MT-iPS) from patient and performed genome editing to generate cells with repair of mutation (WT/WT-iPS) and homozygous mutation (MT/MT-iPS) using CRISPER-Cas9. Droplet digital PCR revealed that the transcript of the mutant allele was about 30% in WT/MT-iPS derived cardiomyocytes (CMs) compared to the WT allele and also WT/WT-iPSCMs and MT/MT-iPSCMs expressed only the transcript of WT allele and MT allele, respectively. The RNA expression of MYBPC3 was restored in WT/WT-iPSCMs and decreased in MT/MT-iPSCMs assessed by quantitative real-time PCR. Sarcomeric disarray was observed in WT/MT-iPSCMs, and was more prominently expressed in MT/MT-iPSCMs assessed by immunofluorescence staining. Cell motion analyzer revealed that relaxation velocity was significantly decreased and relaxation duration was significantly increased in WT/MT-iPSCMs and MT/MT-iPSCMs compared to WT/WT-iPSCMs. Moreover significant increase in contraction end velocity was observed in MT/MT-iPSCMs compared to WT/MT and WT/WT-iPSCMs. Established disease specific iPS-CMs with MYBPC3 mutation reproduces pathophysiology in HCM, providing important clues that elucidate true nature in patient’s hereditary diseases.
    Print ISSN: 0009-7322
    Electronic ISSN: 1524-4539
    Topics: Medicine
    Published by Ovid Technologies on behalf of American Heart Association.
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