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1.
Int J Syst Evol Microbiol ; 70(2): 1158-1165, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833830

RESUMO

Two yeast strains isolated from soil collected in Hokkaido, Japan, were found to secrete two extracellular lipases that exhibited activities at both 25 and 4 °C. Both strains could utilize olive oil, rapeseed oil, lard and fish oil as sole carbon sources. The similarity of the D1/D2 domain of the large subunit ribosomal RNA (LSU rRNA) sequence of these yeast strains to that of other yeasts in the GenBank database was very low (<96 %). The phylogenetic trees based on the LSU rRNA sequences and translation elongation factor-1-α (tef1-α) sequences indicated that both strains represented a member of the Wickerhamomyces /Candida clade. Sexual reproduction was not observed. The name Wickerhamomyces psychrolipolyticus f.a., sp. nov is proposed for this newly described yeast species producing cold-active lipases. This novel species is distinguishable from the type strains of other related species, Wickerhamomyces alni, Candida ulmi and Candida quercuum due to their abilities to grow at 4 to 30 °C, to produce lipase that is active also at 4 °C and to assimilate soluble starch.


Assuntos
Filogenia , Saccharomycetales/classificação , Microbiologia do Solo , Composição de Bases , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Japão , Lipase , Técnicas de Tipagem Micológica , Fator 1 de Elongação de Peptídeos/genética , Subunidades Ribossômicas Maiores/genética , Saccharomycetales/isolamento & purificação , Análise de Sequência de DNA , Temperatura
2.
Oncotarget ; 9(53): 30053-30065, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30046387

RESUMO

Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to mediate many tumours'chemoresistance. We investigated the role of miR-363 in the chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX cells, and introduction of miR-363 into sensitive ovarian cancer cells confers TX-resistance and significantly inhibited the expression of the Hippo member, LATS2, as indicated by viability, clonogenic assay and expression analysis. Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, which also confers TX-resistance to the ovarian cancer cells. On the other hand, specific inhibitor against miR-363 restored the response to TX in the resistant cells. In addition, miR-363 was found to bind to the 3'-UTR of LATS2 mRNA, confirming that miR-363 directly targets LATS2 as indicated by dual luciferase assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours revealed its upregulation in most of the tumour tissues identified as resistant while it was downregulated in most of the tissues identified as sensitive ones. Moreover, higher levels of miR-363 in human ovarian cancer specimens were significantly correlated with TX chemoresistance. Taken together, our study reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in ovarian cancers, raising the possibility that combination therapy with a miR-363 inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.

3.
Adv Perit Dial ; 32: 7-10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28988582

RESUMO

Peritoneal dialysis (PD)-related infections (PDIs) such as peritonitis, exit-site infection, and tunnel infection are serious complications affecting patients on PD. Because patients with diabetes (DM) and of older age have increased in number in Japan, the number of patients with visual impairment is estimated also to have increased. Near vision is necessary for performing proper PD daily care. However, no studies have reported whether visual impairment is likely to increase the risk of PDIs.Our study included 31 PD patients (16 men, 15 women; mean age: 61.5 ± 11.8 years; mean PD duration: 27.3 ± 20.3 months; 38.7% with DM; 54.8% wearing glasses) who performed their own PD care. At our facility and related facilities, we used a standard near-vision test chart, which classifies vision into 12 grades, from 0.1 (poor) to 1.5 (clear), to assess near-vision binocular visual acuity in those patients between March 2015 and September 2015. In addition, we retrospectively examined the medical records of the patients to determine their history of PDIs. We then evaluated the correlation between near-vision acuity and the incidence of PDIs.Mean measured near-vision acuity was 0.61 ± 0.29, and we observed no significant difference in the visual acuity of patients with and without DM (0.55 ± 0.31 vs. 0.63 ± 0.26 respectively, p = 0.477). In addition, we observed no significant difference in the incidence of PDIs between patients with and without DM (1.298 ± 1.609 per year vs. 1.164 ± 0.908 per year respectively, p = 0.804). We did not find a correlation between near-vision acuity and the incidence of PDIs (r = -0.071, p = 0.795).


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Hiperopia/epidemiologia , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritonite/epidemiologia , Acuidade Visual , Idoso , Estudos de Coortes , Feminino , Humanos , Hiperopia/fisiopatologia , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/instrumentação , Estudos Retrospectivos
4.
Adv Perit Dial ; 31: 7-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26714380

RESUMO

Few studies have attempted to evaluate the relationship between peritoneal permeability and fluid status in peritoneal dialysis (PD). The aim of the present study was to clarify the relationship between change in the dialysate-to-plasma ratio of creatinine (D/P Cr) and change in fluid status as evaluated by natriuretic peptides. We studied 49 PD patients (29 men, 62 ± 11 years, 36.7% with diabetes) who underwent a peritoneal equilibration test at least twice after PD initiation. We evaluated correlations between the rate of change in the D/P Cr (R C-D/P Cr), the rate of change in a human atrial natriuretic polypeptide (RC-αhANP), and the rate of change in brain natriuretic peptide (RC-BNP). The RC-αhANP was strongly correlated with RC-BNP (r = 0.637, p < 0.001). In contrast, the RC-D/P Cr was not correlated with RC-αhANP (r = 0.041, p = 0.781) or with RC-BNP (r = 0.114, p = 0.435). However, positive correlations between RC-D/P Cr and RC-αhANP (r = 0.530, p = 0.006) and between RC-D/P Cr and RC-BNP (r = 0.625, p = 0.001) were observed in patients with increased D/P Cr The present study showed a positive correlation between change in peritoneal transport characteristics and change influid status in patients whose D/P Cr increased.


Assuntos
Fator Natriurético Atrial/sangue , Creatinina/sangue , Soluções para Diálise/metabolismo , Peptídeo Natriurético Encefálico/sangue , Diálise Peritoneal , Peritônio/metabolismo , Insuficiência Renal/terapia , Idoso , Transporte Biológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Insuficiência Renal/metabolismo , Estudos Retrospectivos
6.
Clin Nephrol ; 84(1): 50-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25997505

RESUMO

CASE PRESENTATION: A 62-year-old man was diagnosed with peritoneal dialysis (PD)-related peritonitis following diarrhea and determination of a dialysate leukocyte count of 10,224/µL. We cultured peritoneal effluent and started intraperitoneal antibiotic therapy. Peritonitis immediately improved. Peritoneal effluent culture yielded Aeromonas hydrophila. The medical interview revealed that the patient kept goldfish as pets. We suspected that the fish tank water was the source of the infection, considering the association of A. hydrophila with aquatic environments. Culturing of tank water confirmed the presence of Aeromonas. Furthermore, we observed that one of the goldfish was suffering from lepidorthosis, which is commonly caused by Aeromonas, and we then confirmed that the fish's infection was caused by an aeromonad. CONCLUSION: Aeromonas species have rarely been identified as the pathogens in PD-related peritonitis; to our knowledge, there hitherto have been no reports identifying the source of this organism. We present here the process of this infection as elucidated through investigation of the living environment of the patient.


Assuntos
Aeromonas hydrophila/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Animais , Antibacterianos/uso terapêutico , Carpa Dourada , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Falência Renal Crônica/microbiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Peritonite/tratamento farmacológico , Animais de Estimação , Microbiologia da Água
9.
Adv Perit Dial ; 30: 11-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25338415

RESUMO

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.


Assuntos
Infecções Relacionadas a Cateter/terapia , Cateterismo/métodos , Falência Renal Crônica/terapia , Diálise Peritoneal , Tela Subcutânea , Adulto , Idoso , Cateteres de Demora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do Tratamento
10.
PLoS One ; 9(4): e95560, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24751978

RESUMO

Intracytoplasmic sperm injection (ICSI), an important method used to treat male subfertility, is applied in the transgenic technology of sperm-mediated gene transfer. However, no study has described successful generation of offspring using ICSI in the common marmoset, a small non-human primate used as a model for biomedical translational research. In this study, we investigated blastocyst development and the subsequent live offspring stages of marmoset oocytes matured in vitro and fertilized by ICSI. To investigate the optimal timing of performing ICSI, corrected immature oocytes were matured in vitro and ICSI was performed at various time points (1-2 h, 2-4 h, 4-6 h, 6-8 h, and 8-10 h after extrusion of the first polar body (PB)). Matured oocytes were then divided randomly into two groups: one was used for in vitro fertilization (IVF) and the other for ICSI. To investigate in vivo development of embryos followed by ICSI, 6-cell- to 8-cell-stage embryos and blastocysts were nonsurgically transferred into recipient marmosets. Although no significant differences were observed in the fertilization rate of blastocysts among ICSI timing after the first PB extrusion, the blastocyst rate at 1-2 h was lowest among groups at 2-4 h, 4-6 h, 6-8 h, and 8-10 h. Comparing ICSI to IVF, the fertilization rates obtained in ICSI were higher than in IVF (p>0.05). No significant difference was noted in the cleaved blastocyst rate between ICSI and IVF. Following the transfer of 37 ICSI blastocysts, 4 of 20 recipients became pregnant, while with the transfer of 21 6-cell- to 8-cell-stage ICSI embryos, 3 of 8 recipients became pregnant. Four healthy offspring were produced and grew normally. These are the first marmoset offspring produced by ICSI, making it an effective fertilization method for marmosets.


Assuntos
Callithrix/embriologia , Diferenciação Celular , Oócitos/metabolismo , Injeções de Esperma Intracitoplásmicas/métodos , Animais , Animais Recém-Nascidos , Blastocisto/citologia , Transferência Embrionária , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Feminino , Marcadores Genéticos , Humanos , Masculino , Repetições de Microssatélites/genética , Corpos Polares/citologia , Gravidez
11.
Adv Perit Dial ; 29: 43-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24344490

RESUMO

The proportion of elderly people requiring renal replacement therapy has been increasing in Japan. Although several studies have shown the benefits of peritoneal dialysis (PD) in the elderly, few have reported on outcomes, including prognosis, in elderly PD patients, especially those more than 80 years of age. The purpose of the present study was to evaluate clinical outcomes in elderly (more than 80 years of age) PD patients. We retrospectively evaluated the medical records of elderly PD patients who commenced PD between 2007 and 2011. The frequency of perioperative complications, rate of PD-associated peritonitis, technique survival, overall survival, and utilization of nursing-care insurance systems were investigated as clinical outcomes. The 12 patients eligible for this study (7 men, 5 women; mean age: 85 +/- 3 years) had a median duration of follow-up of 1.2 years (interquartile range: 0.65-1.74 years). Perioperative complications were not observed in any of the patients. The frequency of PD-associated peritonitis was 1 episode in 56 months. During follow-up, 6 patients died, and 3 patients switched to hemodialysis because of tunnel infection or lack of family support. The overall survival rate at 12 months was 83%. Nursing-care insurance was used by 63% of patients. In elderly patients, it is important to predict the potential short-term issues at the initiation of PD to facilitate implementation of social services, such as home-visit nursing-care services, at the time of worsening general condition.


Assuntos
Diálise Peritoneal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Peritonite/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
12.
Adv Perit Dial ; 28: 148-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23311233

RESUMO

The incidence of metabolic syndrome is about 50% in peritoneal dialysis (PD) patients. The positive association of metabolic syndrome with lower physical activity (PA) has been reported in the general population, but the effect of PA in PD patients has not been clarified. The purpose of the present study was to evaluate PA in PD patients and to clarify the correlations between PA and various clinical parameters in PD patients. We assessed 38 PD patients (22 men; age: 63.9 +/- 10.8 years; body mass index: 24.0 +/- 3.9; 15 with diabetes) who had been treated with PD at least for 3 months. We defined PA as the average number of steps per day measured using a pedometer for 1 month. Blood biochemical findings and dialysis adequacy were measured as clinical parameters. Of the 38 patients, only 11 (29%) reached the steps per day of healthy individuals. In addition, steps per day were significantly correlated with serum albumin (r = 0.45, p = 0.01), C-reactive protein (r = -0.33, p = 0.04), and age (r = -0.34, p = 0.04). Multiple regression analysis showed that serum albumin was the only variable that significantly correlated with steps per day (beta = 0.42, p = 0.01). Our study showed that PA declines significantly in PD patients, which might correlate with malnutrition-inflammation-atherosclerosis syndrome.


Assuntos
Exercício Físico , Diálise Peritoneal , Albumina Sérica/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade
13.
Clin Exp Hypertens ; 33(4): 255-63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21699452

RESUMO

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Rim/fisiopatologia , Albuminúria/urina , Anticolesterolemiantes/farmacologia , Anti-Hipertensivos/farmacologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/etiologia , Ácidos Graxos Monoinsaturados/farmacologia , Feminino , Fluvastatina , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/epidemiologia , Indóis/farmacologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Análise de Regressão , Tetrazóis/farmacologia , Valina/análogos & derivados , Valina/farmacologia , Valsartana
14.
Environ Sci Technol ; 43(14): 5236-41, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19708347

RESUMO

In Japan, N-nitrosodimethylamine (NDMA) formation associated with ozonation at a relatively high concentration has been reported only at a small number of water treatment plants (WTPs) in the western part of Japan for which the source water is the Yodo River. In the present study, the formation of relatively high concentrations of NDMA was found upon ozonation of water samples taken from sewage treatment plants (STPs) located upstream of the water intake points of the WTPs in the Yodo River basin. NDMA concentrations before and after ozonation were 16-290 and 14-280 ng/L, respectively. At least some of the STPs investigated receive industrial effluents. At one STP in this area, an extremely high concentration of NDMA (10,000ng/L) was found in one influent water sample after ozonation. To identify potential NDMA precursors upon ozonation in the influent at this STP, the concentrated extracts of the influent were fractionated by high-performance liquid chromatography (HPLC). Ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS) identified 4,4'-hexamethylenebis(1,1-dimethylsemicarbazide) (HDMS) and 1,1,1',1'-tetramethyl-4,4'-(methylene-di-p-phenylene)disemicarbazide (TMDS) as precursors of NDMA on ozonation of the influent. Both HDMS and TMDS are used as antiyellowing agents in polyurethane fibers and as light stabilizers in polyamide resins. Their contributions to NDMA production on ozonation of water samples at STPs were up to 17%. The remaining unidentified NDMA precursors may be hydrophilic compounds that were not trapped by the cartridges used for extraction of the water samples. HDMS and TMDS were frequently present in surface waters and STP effluents in the Yodo River basin and were also detected in surface waters from several other areas in Japan.


Assuntos
Dimetilnitrosamina/química , Ozônio/química , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Monitoramento Ambiental , Água Doce/análise , Humanos , Japão , Estrutura Molecular , Rios , Semicarbazidas/química
16.
Clin Exp Nephrol ; 13(2): 123-129, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19057979

RESUMO

BACKGROUND/AIMS: The present study evaluated the clinical efficacy and pharmacokinetics of microemulsion cyclosporine A (ME-CyA) with modification from postprandial to preprandial administration in adult patients with refractory nephrotic syndrome. METHODS: We investigated 19 patients with refractory nephrotic syndrome who had been switched from the postprandial administration of ME-CyA to preprandial administration. The pharmacokinetics of ME-CyA were also evaluated before and 6 months after switching from postprandial to preprandial administration by serial measurement of the blood CyA concentration in 10 patients. RESULTS: This study showed that 16 of 19 patients (84%) displayed an improvement in their clinical condition or continued to maintain remission after switching from post- to preprandial administration. In particular among 14 patients with minimal change nephrotic syndrome (MCNS) in this study, 13 patients maintained or achieved remission under preprandial ME-CyA administration. Only three of 10 patients with postprandial administration showed a peak concentration> 500 ng/ml within 1-2 h after administration, while with preprandial administration, nine of 10 patients showed this good absorption profiles. This effectiveness of preprandial administration seems to be dependent on the improved pharmacokinetics with the increase of area under the curve from 0-4 h (AUC(0-4)) and peak concentration. There were no statistical differences in the mean daily doses of ME-CyA between both administration periods. No ME-CyA-induced nephrotoxicity or other harmful events were encountered throughout the study. CONCLUSION: The preprandial administration of ME-CyA results in a good pharmacokinetic profile and is useful for management of refractory nephrotic syndrome in adults, particularly in patients with MCNS.


Assuntos
Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Absorção Intestinal , Nefrose Lipoide/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Ciclosporina/sangue , Emulsões , Humanos , Imunossupressores/sangue , Pessoa de Meia-Idade , Período Pós-Prandial , Adulto Jovem
17.
J Mol Biol ; 373(1): 141-52, 2007 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-17804014

RESUMO

CueO is a multicopper oxidase (MCO) that is involved in the homeostasis of Cu in Escherichia coli and is the sole cuprous oxidase to have ever been found. Differing from other MCOs, the substrate-binding site of CueO is deeply buried under a methionine-rich helical region including alpha-helices 5, 6, and 7 that interfere with the access of organic substrates. We deleted the region Pro357-His406 and replaced it with a Gly-Gly linker. The crystal structures of a truncated mutant in the presence and in the absence of excess Cu(II) indicated that the scaffold of the CueO molecule and metal-binding sites were reserved in comparison with those of CueO. In addition, the high thermostability of the protein molecule and its spectroscopic and magnetic properties due to four Cu centers were also conserved after truncation. As for functions, the cuprous oxidase activity of the mutant was reduced to ca 10% that of recombinant CueO owing to the decrease in the affinity of the labile Cu site for Cu(I) ions, although activities for laccase substrates such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), p-phenylenediamine, and 2,6-dimethoxyphenol increased due to changes in the access of these organic substrates to the type I Cu site. The present engineering of CueO indicates that the methionine-rich alpha-helices function as a barrier to the access of bulky organic substrates, which provides CueO with specificity as a cuprous oxidase.


Assuntos
Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Oxirredutases/química , Oxirredutases/metabolismo , Estrutura Terciária de Proteína , Sítios de Ligação , Cobre/metabolismo , Cristalografia por Raios X , Estabilidade Enzimática , Proteínas de Escherichia coli/genética , Concentração de Íons de Hidrogênio , Modelos Moleculares , Dados de Sequência Molecular , Oxirredutases/genética , Dobramento de Proteína , Especificidade por Substrato , Temperatura
18.
Shinrigaku Kenkyu ; 78(1): 17-24, 2007 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-17511243

RESUMO

The purpose of this study is to show that expectations of generalized reciprocity within one's own group are responsible for in-group trust. To test this hypothesis, an allocator choice game in the minimal group situation was used. We assigned the role of a recipient in a dictator game to all 81 subjects, and measured whether they chose to be a recipient of either an in-group or an out-group "allocator" who freely allocate a fixed reward between him/her and a recipient. The results indicate that in-group trust occurs only in the condition in which recipients know that allocators make a reward allocation knowing the group membership of their recipient; recipients show no preference for either an in-group or an out-group allocator when allocators make the decision without knowing the group membership of their recipient. It is thus shown that participants' in-group trust is derived from the general belief that people treat in-group members more favorably than out-group members-a belief about generalized reciprocity within groups.


Assuntos
Relações Interpessoais , Preconceito , Confiança/psicologia , Adolescente , Adulto , Feminino , Processos Grupais , Humanos , Masculino , Recompensa
19.
Nihon Jinzo Gakkai Shi ; 49(2): 125-9, 2007.
Artigo em Japonês | MEDLINE | ID: mdl-17375621

RESUMO

A 71-year-old man was admitted to our hospital because of fever and rapidly progressive renal insufficiency over a month. He had depression and Alzheimer's disease as complications. On admission, his serum creatinine was 5.4 mg/dL, and the serum CRP and MPO-ANCA were 18.2 mg/dL and 285 EU, respectively. A computed tomographic chest scan showed pericardiac effusion and fibrosis in both lower lung fields. Although microscopic polyangiitis(MPA)was inferred from a positive MPO-ANCA, renal biopsy could not be carried out. The initial therapy was started with pulse methylprednisolone therapy, followed by oral administration of prednisolone at the dose of 1 mg/kg(60 mg/day). As a result, his fever and inflammatory findings disappeared, and renal insufficiency was ameliorated with a smooth recovery and the pericardial effusion was markedly diminished. However, on the 18th hospital day, chest radiography revealed a nodular shadow in the right lung. Fungus infection was suspected because his serum beta-D-glucan level was extremely high (above 999 pg/mL). Mikafungin, therefore, was started at a dose of 75 mg/day and then, the dose was increased up to 300 mg/day. Nevertheless, he finally died of respiratory failure on the 26th hospital day. The autopsy findings revealed a cavity of 4.0 x 3.0 x 3.0 centimeters in size in the upper lobe of the right lung. There was a great number of fungal threads with a septal wall branched in a Y-shaped figure around the cavity, thus indicating pulmonary aspergilloma. Intranuclear inclusion bodies staining positive for cytomegalovirus were observed in all the lung fields, suggestive of a cytomegalovirus infection. In the kidney, a cellular crescent formation was noted in the majority of glomeruli showing crescentic glomeluronephritis, compatible with MPA.


Assuntos
Aspergilose/etiologia , Infecções por Citomegalovirus/etiologia , Pneumopatias Fúngicas/etiologia , Pneumonia Viral/etiologia , Vasculite/patologia , Idoso , Doença de Alzheimer/complicações , Anticorpos Anticitoplasma de Neutrófilos , Aspergilose/patologia , Infecções por Citomegalovirus/patologia , Glomerulonefrite/complicações , Glomerulonefrite/patologia , Humanos , Pneumopatias Fúngicas/patologia , Masculino , Metilprednisolona/administração & dosagem , Peroxidase/imunologia , Pneumonia Viral/patologia , Prednisolona/administração & dosagem , Pulsoterapia , Vasculite/complicações , Vasculite/tratamento farmacológico
20.
Pharmacotherapy ; 25(1): 52-8, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15767220

RESUMO

STUDY OBJECTIVE: To compare the absorption profile of cyclosporine after preprandial administration with that after postprandial administration, and to determine which administration time resulted in a more stable absorption profile and the timing of the drug concentration that was the most reliable marker for monitoring drug absorption. DESIGN: Prospective analysis. SETTING: University teaching hospital in Japan. PATIENTS: Sixteen patients with refractory nephrotic syndrome. INTERVENTION: Thirteen patients received cyclosporine after breakfast (postprandial group) and eight received the drug 30 minutes before breakfast (preprandial group). MEASUREMENTS AND MAIN RESULTS: Blood cyclosporine concentration was measured 5 times serially: before administration (C 0 ) and at 1-hour intervals until 4 hours after administration of cyclosporine (C 1 -C 4 ). Also, area under the concentration-time curve from 0-4 hours (AUC 0-4 ) was calculated. Of the 13 patients in the postprandial group, six (46%) showed fair absorption and exhibited a peak concentration at C 1 or C 2 (high-absorption pattern); seven (54%) showed poor absorption and did not reach the peak concentration within the 4-hour period (low-absorption pattern). Five of the seven patients with the low-absorption pattern were switched from postprandial to preprandial administration. All patients in the preprandial administration group showed a high-absorption pattern and reached the peak cyclosporine concentration at C 1 . The C 2 value showed the best correlation with AUC 0-4 in both groups, and the C 0 parameter did not correlate with AUC 0-4 in either group. CONCLUSION: Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC 0-4 , we concluded that C 2 , and not C 0 , is a reliable marker for monitoring cyclosporine exposure.


Assuntos
Ciclosporina/farmacocinética , Jejum , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Período Pós-Prandial , Índice de Gravidade de Doença , Absorção , Área Sob a Curva , Ciclosporina/administração & dosagem , Ciclosporina/metabolismo , Esquema de Medicação , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Síndrome Nefrótica/fisiopatologia , Estudos Prospectivos , Fatores de Tempo
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