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151.
M Ohkubo K Kojiri H Kondo S Tanaka H Kawamoto T Nishimura I Nishimura T Yoshinari H Arakawa H Suda H Morishima S Nishimura 《Bioorganic & medicinal chemistry letters》1999,9(9):1219-1224
6-N-Amino analogues of NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione] (3b) were synthesized and tested with respect to topoisomerase inhibition, cytotoxicity and anticancer effects. Among them, a 1,3-dihydroxypropane analogue (J-109,404, 5t) showed more than ten times more potent anticancer activity in MKN-45 human stomach cancer cells implanted in mice than NB-506. 相似文献
152.
Akihiro Ochi Tatsuro Hifumi Takanori Ueno Yoshinari Katayama 《BMC veterinary research》2017,13(1):384
Background
Capillaria hepatica is a zoonotic parasite in humans and animals and has a worldwide distribution. However, infections in mammals apart from rodents, which are natural hosts of the parasite, have rarely been reported. This report describes the first known case of C. hepatica infection in a horse in Japan.Case presentation
A 3-year-old filly without clinical signs was presented at a slaughterhouse in Japan. Gross examination revealed white to tan nodules 0.5 to 1.5 cm in diameter in the parenchyma of the liver. Histologically, the nodules had mature fibrous capsules and consisted of multifocal to coalescing granulomatous inflammations with numerous nematode eggs. The eggs were barrel shaped with an opercular plug on each end and double-layered shells; these findings are consistent with the features of C. hepatica eggs.Conclusions
To our knowledge, this is the first case of C. hepatica infection in a horse in Japan. The pathological findings confirmed the presence of this pathogen in this part of the world, and they highlight the importance of this nematode in the differential diagnosis of hepatic granulomatous lesions in horses.153.
Yasushi Iwasaki Keiko Mori Masumi Ito Yoshinari Kawai Ken-ichiro Hoshino Yuko Kawabata 《朊病毒》2017,11(3):186-194
Patients with prion diseases can live for long periods of time in a state of akinetic mutism given appropriate management of their symptoms. To study symptom support in these cases, we performed gastrostomies on 3 patients with V180I genetic Creutzfeldt-Jakob disease (CJD) who had become akinetic and mute, and compared them to 14 other similar patients being fed by tube. In the 3 gastrostomy cases, there were no direct complications due to the gastrostomy or tube feeding, nor were there episodes of discontinuation of tube feeding or initiation of continuous drip infusion due to severe complications. Antibiotics were administered for mild infections, a complication of CJD, with 0.2% and 8.8% of the total time after gastrostomy being used for intravenous or transluminal administration, respectively. We compared the present patient series with that of our previous report statistically, and found that patients undergoing gastrostomy required significantly fewer discontinuations of tube feeding than those who did not. No significant difference in antibiotic administration was found between groups, however. It is our conclusion that gastrostomy should be allowed for symptom support in akinetic patients with prion disease, but adequate informed consent must be provided to the patient's family. 相似文献
154.
Ayumi Tanaka Mohamed O. Radwan Akiyuki Hamasaki Asumi Ejima Emiko Obata Ryoko Koga Hiroshi Tateishi Yoshinari Okamoto Mikako Fujita Mitsuyoshi Nakao Kazuo Umezawa Fuyuhiko Tamanoi Masami Otsuka 《Bioorganic & medicinal chemistry letters》2017,27(16):3862-3866
Protein prenylation such as farnesylation and geranylgeranylation is associated with various diseases. Thus, many inhibitors of prenyltransferase have been developed. We report novel inhibitors of farnesyltransferase with a zinc-site recognition moiety and a farnesyl/dodecyl group. Molecular docking analysis showed that both parts of the inhibitor fit well into the catalytic domain of farnesyltransferase. The synthesized inhibitors showed activity against farnesyltransferase in vitro and inhibited proliferation of the pancreatic cell line AsPC-1. Among the compounds with farnesyl and dodecyl groups, the inhibitor with a farnesyl group was found to have stronger and more selective activity. 相似文献
155.
Yamamoto K Sakamoto Y Irie M Ohmori S Yoshinari M Kaçaniku G 《Journal of physiological anthropology》2008,27(1):43-50
The aim of this study was to examine the relationship between psychosocial stress and intraocular pressure among apparently healthy subjects. Psychosocial stress among 1,461 public school workers (883 men and 578 women) was measured using the inventory to measure psychosocial stress (IMPS) and intraocular pressure was measured using a non-contact tonometer (Topcon CT-90). After controlling for the effects of likely confounding variables such as age, body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, alcohol consumption, smoking status, and exercise, partial correlations and hierarchical multiple regression analysis were performed in order to test the hypothesis that IMPS-measured stress score was associated with intraocular pressure. IMPS-measured stress score was found to correlate positively with intraocular pressure in women after controlling for the effects of confounding variables, whereas this relationship was not found in men. Hierarchical multiple regression analysis indicated that IMPS-measured stress score was positively associated with intraocular pressure in women independent of confounding variables, but not in men. Perturbations of the hypothalamic-pituitary-adrenal (HPA) axis associated with stress are considered to be partly responsible for an increase in intraocular pressure among people suffering from psychosocial stress. Further research is needed to elucidate the relationship between this stress-associated increase in intraocular pressure and open-angle glaucoma. 相似文献
156.
157.
Yoshinari Shoyama Chitomi Sugawa Hiroyuki Tanaka Satoshi Morimoto 《Plant signaling & behavior》2008,3(12):1111-1112
Cannabis sativa is well known to produce unique secondary metabolites called cannabinoids. We recently discovered that Cannabis leaves induce cell death by secreting tetrahydrocannabinolic acid (THCA) into leaf tissues. Examinations using isolated Cannabis mitochondria demonstrated that THCA causes mitochondrial permeability transition (MPT) though opening of MPT pores, resulting in mitochondrial dysfunction (the important feature of necrosis). Although Ca2+ is known to cause opening of animal MPT pores, THCA directly opened Cannabis MPT pores in the absence of Ca2+. Based on these results, we conclude that THCA has the ability to induce necrosis though MPT in Cannabis leaves, independently of Ca2+. We confirmed that other cannabinoids (cannabidiolic acid and cannabigerolic acid) also have MPT-inducing activity similar to that of THCA. Moreover, mitochondria of plants which do not produce cannabinoids were shown to induce MPT by THCA treatment, thus suggesting that many higher plants may have systems to cause THCA-dependent necrosis.Key words: cannabinoid, Cannabis sativa, cylophilin D, mitochondrial permeability transition, necrosisCannabis sativa produces unique secondary metabolites consisting of alkylresorcinol and monoterpene groups.1 These metabolites called cannabinoids are well known to show a variety of interesting pharmacological activities including psychoactive effect and analgesic effect. Therefore, cannabinoids have attracted a great deal of attention, whereas why C. sativa produces such metabolites has long remained unclear. However, we have recently obtained evidences indicating the physiological function of THCA in Cannabis leaves.2We discovered that THCA is stored in capitate-sessile glands on Cannabis leaves and that secretion of this cannabinoid into leaf tissues causes cell death. When the properties of THCA were examined using cultured Cannabis cells, this cannabinoid induced plasmamembrane shrinkage and DNA degradation. These responses are regarded as the features of apoptotic cells, but were not suppressed by apoptosis inhibitors. In contrast, the necrosis inhibitor cyclosporine A significantly inhibited both plasmamembrane shrinkage and DNA degradation in Cannabis cells. Therefore, we assumed that THCA induces necrotic cell death in Cannabis cells and leaves.Necrosis in plants and animals is usually triggered by MPT though opening of MPT pores.3,4 MPT is known to cause mitochondrial dysfunction by mitochondrial swelling and loss of mitochondrial membrane potential (ΔΨm),5,6 and we also confirmed that THCA induces mitochondrial swelling and ΔΨm reduction in mitochondria isolated from Cannabis cells and that pretreatment with cyclosporine A inhibits both responses. Based on these evidences, we concluded that THCA has the activity to induce MPT-dependent necrosis.As described above, MPT pores play an important role in necrosis induction, whereas the mechanism of their opening in higher plants has not been fully understood. However, binding of cyclophilin D (a protein present in mitochondrial matrix) to MPT pores is shown to be essential for their opening in plants as well as animal.7–9 In animal mitochondria, Ca2+ mediates this binding reaction, leading to opening of MPT pores. Wheat mitochondria are also shown to undergo swelling through opening of MPT pores in response to Ca2+,9 whereas MPT pores of oats,10 Arabidopsis thaliana11 and C. sativa2 do not open by Ca2+ treatment. In contrast, THCA catalyzed opening of Cannabis MPT pores in the absence of Ca2+, suggesting that THCA directly mediates binding of cyclophilin D to MPT pores (Fig. 1). In addition, we have now confirmed that THCA causes dysfunction though MPT in mitochondria of plants (rice, soybean, A. thaliana and Scutellaria baicalensis) lacking cannabinoid-producing ability (data not shown). Therefore, many higher plants may have the systems to induce THCA-dependent necrosis.Open in a separate windowFigure 1A model depicting the opening mechanism of MPT pores in mitochondria. CYD, cyclophilin D; CN, cannabinoid.Furthermore, we investigated whether other cannabinoids and their related compounds can mediate MPT in Cannabis mitochondria. When the MPT-inducing activity of each sample was measured by monitoring both ΔΨm reduction (Fig. 2) and mitochondrial swelling (data not shown), we confirmed that cannabinoids tested here (cannabidiolic acid and cannabigerolic acid) possess the activities similar to those of THCA. On the other hand, olivetolic acid (the akylresorcinol moiety of cannabinoid) and geraniol (the monoterpene moiety of cannabigerolic acid) showed neither ΔΨm reduction nor mitochondrial swelling (Fig. 2). These results suggested that the structures (cannabinoid skeleton) where monoterpene and olivetolic acid are coupled to each other seem essential for opening of MPT pores. Therefore, we assumed that plant cyclophilin D and MPT pores have the cannabinoid-binding site.Open in a separate windowFigure 2Change of ΔΨm by treatment with various compounds (A) and their chemical structures (B). The isolated mitochondria were stained with the ΔΨm-indicating reagent (tetramethylrhodamine methylester, TMRM) and then incubated with 200 µM of each compound for 60 min. The intensity of TMRM fluorescence was measured using a fluorescence microplate reader. A decrease of the fluorescence intensity indicates ΔΨm reduction. CBDA, cannabidiolic acid; CBGA, cannabigerolic acid; OLA, olivetolic acid.Plant cell death is shown to participate in important physiological responses such as leaf senescence, somatic embryogenesis and defense against microbial pathogens.12,13 Based on its induction mechanism, plant cell death is largely classified into apoptosis and necrosis. Although the molecular mechanism of apoptosis has been extensively investigated, there is little precise information on plant necrosis. However, our study would provide important insight into necrosis-inducing mechanisms in higher plants. 相似文献
158.
Iwase M Tashiro K Uchizono Y Goto D Yoshinari M 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,280(6):R1601-R1605
Anesthesia affects general hemodynamics and regulation of organ perfusion. We used colored microspheres to measure pancreatic islet blood flow in conscious rats at two time points, during either hyperglycemia or hypoglycemia. This method, using black and green microspheres, was validated by comparison with previous microsphere experiments and by lack of effect of a nonmetabolizable glucose analog, 3-O-methylglucose, on islet perfusion. Basal and glucose-stimulated islet blood flow levels were similar in pentobarbital sodium-anesthetized and conscious rats. However, the basal distribution of pancreatic blood flow was altered by anesthesia (fractional islet blood flow 5.8 +/- 0.4% in conscious rats, 7.9 +/- 0.8% in pentobarbital-anesthetized rats, P < 0.05). Insulin-induced hypoglycemia significantly increased whole pancreatic blood flow in conscious rats, whereas islet blood flow remained unchanged and fractional islet blood flow was decreased (5.8 +/- 0.5% in the basal state, 4.2 +/- 0.4% during hypoglycemia, P < 0.001). Methylatropine pretreatment significantly increased islet blood flow during hypoglycemia by 181%. This result suggests that prevention of hypoglycemia-induced increase in islet perfusion may be mediated, at least in part, by a cholinergic, vagal muscarinic mechanism. 相似文献
159.
In order to evaluate population-level effects of p-nonylphenol on a cladoceran zooplankton (Daphnia galeata), the chronic effects on survival and reproduction were estimated with partial life table tests, which examined responses in life history characters until 3 weeks after birth. The observed responses in survival and reproduction were converted to reductions of the intrinsic rate of natural increase r. The population level EC50, which is defined as the exposure concentration that reduces r by 50%, was estimated as 16.1 g l–1. In order to examine the extent to which the population-level effect in terms of r is influenced by extra mortality in nature, which is induced by predation, starvation, etc., sensitivity (elasticity) measures of the intrinsic rate of natural increase to reductions in age-specific survival and reproduction were calculated under hypothetical predation schemes. The sensitivities of the intrinsic rate to changes in survival and reproduction invariably decline rapidly after the onset of reproduction irrespective of predation schemes. This implies that partial life cycle tests until 21 days after birth can provide reliable estimates of the population-level effects. 相似文献
160.
Applicability of tetrazolium salts for the measurement of respiratory activity and viability of groundwater bacteria 总被引:5,自引:0,他引:5
Hatzinger PB Palmer P Smith RL Peñarrieta CT Yoshinari T 《Journal of microbiological methods》2003,52(1):47-58
A study was undertaken to measure aerobic respiration by indigenous bacteria in a sand and gravel aquifer on western Cape Cod, MA using tetrazolium salts and by direct oxygen consumption using gas chromatography (GC). In groundwater and aquifer slurries, the rate of aerobic respiration calculated from the direct GC assay was more than 600 times greater than that using the tetrazolium salt 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride (INT). To explain this discrepancy, the toxicity of INT and two additional tetrazolium salts, sodium 3'-[1-(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzenesulfonic acid hydrate (XTT) and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), to bacterial isolates from the aquifer was investigated. Each of the three tetrazolium salts was observed to be toxic to some of the groundwater isolates at concentrations normally used in electron transport system (ETS) and viability assays. For example, incubation of cells with XTT (3 mM) caused the density of four of the five groundwater strains tested to decline by more than four orders of magnitude. A reasonable percentage (>57%) of cells killed by CTC and INT contained visible formazan crystals (the insoluble, reduced form of the salts) after 4 h of incubation. Thus, many of the cells reduced enough CTC or INT prior to dying to be considered viable by microscopic evaluation. However, one bacterium (Pseudomonas fluorescens) that remained viable and culturable in the presence of INT and CTC, did not incorporate formazan crystals into more than a few percent of cells, even after 24 h of incubation. This strain would be considered nonviable based on traditional tetrazolium salt reduction assays. The data show that tetrazolium salt assays are likely to dramatically underestimate total ETS activity in groundwater and, although they may provide a reasonable overall estimate of viable cell numbers in a community of groundwater bacteria, some specific strains may be falsely considered nonviable by this assay due to poor uptake or reduction of the salts. 相似文献