Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 134
Filtrar
1.
Genes Cells ; 29(8): 613-634, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38937957

RESUMO

Bacteria use several means to survive under stress conditions such as nutrient depletion. One such response is the formation of hibernating 100S ribosomes, which are translationally inactive 70S dimers. In Gammaproteobacteria (Enterobacterales), 100S ribosome formation requires ribosome modulation factor (RMF) and short hibernation promoting factor (HPF), whereas it is mediated by only long HPF in the majority of bacteria. Here, we investigated the role of HPFs of Comamonas testosteroni, which belongs to the Betaproteobacteria with common ancestor to the Gammaproteobacteria. C. testosteroni has two genes of HPF homologs of differing length (CtHPF-125 and CtHPF-119). CtHPF-125 was induced in the stationary phase, whereas CtHPF-119 conserved in many other Betaproteobacteria was not expressed in the culture conditions used here. Unlike short HPF and RMF, and long HPF, CtHPF-125 could not form 100S ribosome. We first constructed the deletion mutant of Cthpf-125 gene. When the deletion mutant grows in the stationary phase, 70S particles were degraded faster than in the wild strain. CtHPF-125 contributes to stabilizing the 70S ribosome. CtHPF-125 and CtHPF-119 both inhibited protein synthesis by transcription-translation in vitro. Our findings suggest that CtHPF-125 binds to ribosome, and stabilizes 70S ribosomes, inhibits translation without forming 100S ribosomes and supports prolonging life.


Assuntos
Proteínas de Bactérias , Comamonas testosteroni , Proteínas Ribossômicas , Ribossomos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ribossomos/metabolismo , Comamonas testosteroni/metabolismo , Comamonas testosteroni/genética
2.
Chembiochem ; : e202400352, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073256

RESUMO

Identifying target proteins that interact with bioactive molecules is indispensable for understanding their mechanisms of action. In this study, we developed a uniform ribosome display technology using equal-length DNAs and mRNAs to improve molecular display principle for target identification. The equal-length DNAs were designed to contain various coding sequences for full-length proteins with molecular weights of up to 130 kDa and were used to synthesize equal-length mRNAs, which allowed the formation of full-length protein-ribosome-equal-length mRNA complexes. Uniform ribosome display selections of dihydrofolate reductase and haloalkane dehalogenase mutant were performed against methotrexate and chlorohexane, respectively. Quantitative changes of proteins after each selection indicated that the target protein-displaying ribosomal complexes were specifically selected through non-covalent or covalent interactions with the corresponding bioactive molecules. Furthermore, selection of full-length proteins interacting with methotrexate or anti-DDX46 antibody from protein pools showed that only the target proteins could be precisely identified even though the molar amounts of equal-length mRNAs encoding them were adjusted to 1/20,000 of the total equal-length mRNAs. Thus, the uniform ribosome display technology enabled efficient identification of target proteins that interact with bioactive small and large molecules through simplified operations without deep sequencing.

3.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36834855

RESUMO

Ribosomal protein bL31 in Escherichia coli was initially detected as a short form (62 amino acids) using Kaltschmidt and Wittmann's two-dimensional polyacrylamide gel electrophoresis (2D PAGE), but the intact form (70 amino acids) was subsequently identified by means of Wada's improved radical-free and highly reducing (RFHR) 2D PAGE, which was consistent with the analysis of its encoding gene rpmE. Ribosomes routinely prepared from the K12 wild-type strain contained both forms of bL31. ΔompT cells, which lack protease 7, only contained intact bL31, suggesting that protease 7 cleaves intact bL31 and generates short bL31 during ribosome preparation from wild-type cells. Intact bL31 was required for subunit association, and its eight cleaved C-terminal amino acids contributed to this function. 70S ribosomes protected bL31 from cleavage by protease 7, but free 50S did not. In vitro translation was assayed using three systems. The translational activities of wild-type and ΔrpmE ribosomes were 20% and 40% lower than those of ΔompT ribosomes, which contained one copy of intact bL31. The deletion of bL31 reduces cell growth. A structural analysis predicted that bL31 spans the 30S and 50S subunits, consistent with its functions in 70S association and translation. It is important to re-analyze in vitro translation with ribosomes containing only intact bL31.


Assuntos
Escherichia coli , Proteínas Ribossômicas , Proteínas Ribossômicas/metabolismo , Escherichia coli/metabolismo , Ribossomos/metabolismo , Peptídeo Hidrolases/metabolismo , Aminoácidos/metabolismo
4.
Int J Mol Sci ; 24(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37958644

RESUMO

Cell-free molecular display techniques have been utilized to select various affinity peptides from peptide libraries. However, conventional techniques have difficulties associated with the translational termination through in-frame UAG stop codons and the amplification of non-specific peptides, which hinders the desirable selection of low-affinity peptides. To overcome these problems, we established a scheme for ribosome display selection of peptide epitopes bound to monoclonal antibodies and then applied genetic code expansion with synthetic X-tRNAUAG reprogramming of the UAG codons (X = Tyr, Trp, or p-benzoyl-l-phenylalanine (pBzo-Phe)) to the scheme. Based on the assessment of the efficiency of in vitro translation with X-tRNAUAG, we carried out ribosome display selection with genetic code expansion using Trp-tRNAUAG, and we verified that affinity peptides could be identified efficiently regardless of the presence of UAG codons in the peptide coding sequences. Additionally, after evaluating the photo-cross-linking reactions of pBzo-Phe-incorporated peptides, we performed ribosome display selection of low-affinity peptides in combination with genetic code expansion using pBzo-Phe-tRNAUAG and photo-irradiation. The results demonstrated that sub-micromolar low-affinity peptide epitopes could be identified through the formation of photo-induced covalent bonds with monoclonal antibodies. Thus, the developed ribosome display techniques could contribute to the promotion of diverse peptide-based research.


Assuntos
Código Genético , Ribossomos , Códon de Terminação/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Epitopos/metabolismo
5.
Genes Cells ; 25(8): 562-581, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32559334

RESUMO

When a cell is zinc-deficient, ykgM and ykgO, which encode paralogs of the zinc-binding ribosomal proteins L31 and L36, are expressed from the ykgM operon, which is ordinarily held inactive by the Zur repressor. In ribosomes lacking L31, ribosomal subunit association is weakened, resulting in reduced in vitro translation and the deletion mutants of rpmE, the gene encoding L31, forming small colonies. We isolated four suppressor mutants of ∆rpmE that formed normal colonies. All four mutation sites were located in zur, and ribosomes of zur mutant cells contained one copy of YkgM and had translational activities equivalent to those of ribosomes containing L31. L36 is highly conserved among bacteria, chloroplast and mitochondria. Analysis of a deletion mutant of rpmJ, which encodes L36, suggested that L36 is involved in late assembly of the 50S particle, in vitro translation and cell growth. In zur mutant cells lacking rpmJ, the paralog YkgO was expressed and took over the functions of L36. zur mutant cells contained four types of ribosomes containing combinations of L31 or YkgM, and L36 or YkgO. Copy numbers of L31 and YkgM, and L36 and YkgO, summed to 1, indicating that each paralog pair shares a binding site.


Assuntos
Proteínas de Escherichia coli/metabolismo , Proteínas Ribossômicas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Proteômica/métodos , Proteínas Ribossômicas/genética , Subunidades Ribossômicas/genética , Subunidades Ribossômicas/metabolismo , Ribossomos/metabolismo , Zinco/análise
6.
Genes Cells ; 22(5): 452-471, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28397381

RESUMO

Ribosomes routinely prepared from Escherichia coli strain K12 contain intact (70 amino acids) and short (62 amino acids) forms of ribosomal protein L31. By contrast, ribosomes prepared from ompT mutant cells, which lack protease 7, contain only intact L31, suggesting that L31 is cleaved by protease 7 during ribosome preparation. We compared ribosomal subunit association in wild-type and ompT - strains. In sucrose density gradient centrifugation under low Mg2+ , 70S content was very high in ompT - ribosomes, but decreased in the wild-type ribosomes containing short L31. In addition, ribosomes lacking L31 failed to associate ribosomal subunits in low Mg2+ . Therefore, intact L31 is required for subunit association, and the eight C-terminal amino acids contribute to the association function. In vitro translation was assayed using three different systems. Translational activities of ribosomes lacking L31 were 40% lower than those of ompT - ribosomes with one copy of intact L31, indicating that L31 is involved in translation. Moreover, in the stationary phase, L31 was necessary for 100S formation. The strain lacking L31 grew very slowly. A structural analysis predicted that the L31 protein spans the 30S and 50S subunits, consistent with the functions of L31 in 70S association, 100S formation, and translation.


Assuntos
Proteínas de Escherichia coli/metabolismo , Peptídeo Hidrolases/metabolismo , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Peptídeo Hidrolases/genética , Ligação Proteica , Biossíntese de Proteínas , Proteólise , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Subunidades Ribossômicas/química
7.
Proc Jpn Acad Ser B Phys Biol Sci ; 94(2): 129-138, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29434079

RESUMO

Strength, functionality and beauty are the three qualities identifying well-designed architecture. For buildings in earthquake-prone countries such as Japan, emphasis on seismic safety frequently leads to the sacrifice of functionality and beauty. Therefore, it is important to develop new structural technologies that can ensure the seismic performance of a building without hampering the pursuit of functionality and beauty. The moment-resisting frame structures widely used for buildings in Japan are likely to experience weak-story collapse. Pin-supported walls, which can effectively enhance the structural story-by-story integrity of a building, were introduced to prevent such an unfavorable failure pattern in the seismic retrofit of an eleven-story building on a university campus in Tokyo, while also greatly aesthetically enhancing the façade of the building. The slight damage observed and monitoring records of the retrofitted building during the 2011 Tohoku earthquake in Japan demonstrate that the pin-supported walls worked as intended, protecting the building and guaranteeing the safety of its occupants during the earthquake.


Assuntos
Indústria da Construção/métodos , Materiais de Construção , Desenho de Equipamento/métodos , Colapso Estrutural/prevenção & controle , Desastres , Terremotos , Meio Ambiente , Japão , Universidades
8.
Hepatol Res ; 47(3): E55-E63, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27062374

RESUMO

AIM: Psychiatric side-effects are the main reason for discontinuation of interferon (IFN)-based therapy. Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. We prospectively evaluated brain activation in 20 chronic hepatitis C patients with or without IFN-based therapy by using NIRS during a verbal fluency task (VFT). METHODS: The relative concentrations of oxygenated hemoglobin were measured while patients completed a questionnaire survey at the start of treatment and at 4 and 12 weeks during treatment, using NIRS. RESULTS: The VFT performance did not change among the two groups. Patients with IFN-based therapy showed significantly lower activation during VFT in frontal channels at 12 weeks than those at the start of treatment and control (P < 0.05). Their Center for Epidemiologic Studies Depression Scale scores were significantly higher at 12 weeks than those at the start of treatment, although major depressive symptoms were not found (8.3 ± 7.9 vs. 13.2 ± 6.0, P < 0.001). CONCLUSION: The decrease in oxygenated hemoglobin concentrations of the frontal lobe detected using NIRS in this study reflects hypofunction of the frontal lobe. This functional decline that was caused by IFN-based therapy may be associated with the prodromal phase of depression.

9.
Clin Lab ; 62(1-2): 81-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27012036

RESUMO

BACKGROUND: Plasma PTH levels are normally high during the night and early morning and lowest at approximately 10 am (the PTH circadian rhythm). Our objective was to examine the relationship between the PTH circadian rhythm and calcium-phosphorus metabolism in non-dialyzed, chronic kidney disease (CKD) patients. METHODS: The characteristics of twenty-eight subjects comprised: male, 23; diabetic patients, 16; mean age, 71.1 +/- 10.5 years; mean eGFR, 18.3 +/- 8.1 mL/min/1.73 m2. Under a protein-restricted diet, plasma intact PTH (iPTH) was measured at 7 am (iPTH7), 10 am (iPTH10), and 10 pm (iPTH22). Serum concentrations of calcium (Ca), phosphate (Pi), 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25[OH]2D), and fibroblast growth factor (FGF)-23 were measured at 7 am. A normal iPTH rhythm was defined as when both iPTH7 and iPTH22 exceeded iPTH10. When iPTH10 was equal to, or exceeded either iPTH7 or iPTH22, or both, the rhythm was considered abnormal. RESULTS: Median levels of iPTH7, iPTH10, and iPTH22 were 92.5 [IQR: 60.8-152.01, 85.5 [61.0-144.5], and 95.5 164.3-160.5] pg/mL, respectively. Sixteen subjects showed an abnormal iPTH rhythm. There was no significant difference between groups in age, eGFR, iPTH7, iPTH10, iPTH22, Pi, 25-OH1D, 1,25(OH)2D, or FGF-23. However, the abnormal group showed significantly higher mean levels of corrected Ca as compared to the normal group (9.50 +/- 0.42 vs. 9.18 +/- 0.28; p = 0.032). CONCLUSIONS: Abnormal diurnal patterns of PTH are associated with sustained mild hypercalcemia in nondialyzed chronic kidney disease patients. This abnormal rhythm was not associated with Pi or FGF-23, and this may be an independent risk factor for CKD-mineral and bone disorder.


Assuntos
Cálcio/sangue , Ritmo Circadiano , Hipercalcemia/sangue , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Taxa de Filtração Glomerular , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fósforo/sangue , Período Pós-Prandial , Valor Preditivo dos Testes , Prognóstico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Índice de Gravidade de Doença
10.
Clin Lab ; 62(12): 2349-2354, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28164555

RESUMO

BACKGROUND: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Continuous hemodiafiltration (CHDF) is often performed for the treatment of the aforementioned acute illnesses. We have previously reported that an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has a greater capacity for in vitro FGF-23 adsorption than polysulfone and polymethyl methacrylate membranes. However, reports related to the influence of AN69ST-CHDF on serum FGF-23 levels in acute illness are lacking. In this study, we investigated the effect of AN69ST-CHDF on circulating FGF-23 concentrations in clinical practice. METHODS: Subjects comprised six inpatients who underwent AN69ST-CHDF for an acute illness. Blood samples for the measurement of serum FGF-23 were collected at 0, 3, and 12 hours post-treatment. Blood samples were also drawn from the extracorporeal circuit at the inlet and outlet of the hemofilter 3 hours after CHDF initiation, in order to calculate the clearance of serum FGF-23. RESULTS: Three and 12 hours after the start of AN69ST-CHDF, circulating FGF-23 levels decreased from baseline values with a marginal statistical significance (p = 0.0625 and 0.0938, respectively). An FGF-23 clearance of 27.5 [interquartile range: 19.4 - 29.2] mL/minute 3 hours after the initiation of AN69ST-CHDF was achieved. CONCLUSIONS: Our results suggest that AN69ST-CHDF can be a novel FGF-23 lowering therapy for acute illnesses requiring acute blood purification.


Assuntos
Resinas Acrílicas/química , Acrilonitrila/análogos & derivados , Doença Aguda/terapia , Fatores de Crescimento de Fibroblastos/sangue , Hemodiafiltração/instrumentação , Membranas Artificiais , Acrilonitrila/química , Adsorção , Idoso , Biomarcadores/sangue , Regulação para Baixo , Desenho de Equipamento , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Propriedades de Superfície , Fatores de Tempo , Resultado do Tratamento
11.
Circ J ; 79(10): 2169-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26310781

RESUMO

BACKGROUND: Hemodialysis (HD) patients are reported to show poor clinical outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) compared with non-HD patients and their long-term prognosis remains unclear. METHODS AND RESULTS: We prospectively enrolled 489 consecutive patients undergoing PCI with SES and performed a retrospective analysis focusing on HD patients. Median follow-up was 7.0 years (interquartile range, 4.2-7.9) and the follow-up rate was 100%. At the 7-year follow-up, the cumulative incidences of all-cause death, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were significantly higher in HD patients than in non-HD patients (HD vs. non-HD=34.7% vs. 9.6%, 42.6% vs. 10.2% and 75.3% vs. 24.4%, respectively; log-rank P<0.001). Cox-proportional hazard analysis revealed that independent predictors of all-cause death were HD (hazard ratio [HR] 2.88, 95% confidence interval [CI]: 1.39-6.00), insulin-treated diabetes mellitus (HR 2.19, 95% CI: 1.17-4.11), heart failure (HR 2.58, 95% CI: 1.25-5.32) and older age (HR 1.06/1-age, 95% CI: 1.02-1.10). Moreover, HD was an independent predictor of TLR (HR 3.63, 95% CI: 1.85-7.11) and MACE (HR 3.54, 95% CI: 2.19-5.73). CONCLUSIONS: In the present study, Japanese HD patients undergoing PCI with SES showed poorer long-term clinical outcomes than non-HD patients. HD was a strong predictor of long-term adverse events after SES implantation.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea , Diálise Renal , Sirolimo , Fatores Etários , Idoso , Povo Asiático , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida
12.
Acta Neurochir (Wien) ; 157(5): 803-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25791694

RESUMO

BACKGROUND: We describe the details of our unique surgical procedures for microvascular decompression for hemifacial spasm. METHODS: A patient is just laid supine, skipping the complicated preparation for the lateral or park-bench position. The subfloccular approach from a small cranial window situated on the more lateral and basal side of the occipital cranium enables the surgeon to reach all the segments of the facial nerve root without cerebellar retraction by a spatula. CONCLUSIONS: We believe this approach is ideal for the safe and precise decompression of any part of the facial nerve root.


Assuntos
Descompressão Cirúrgica/métodos , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Humanos , Decúbito Dorsal
13.
Anal Chem ; 86(14): 6768-73, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24380432

RESUMO

The identification of target proteins of bioactive small molecules as bioprobe candidates or drug seeds is indispensable for elucidating their actions and predicting their side effects. To meet the current need, we developed a scheme for detection and identification of target proteins by using ribosome display and photo-cross-linking techniques, and demonstrated the feasibility. The mRNAs encoding full-length human proteins (FHPs) were constructed and translated in vitro to prepare pools of FHP-ribosome-mRNA complexes used for ribosome display selection. Expression levels of the FHPs were confirmed by Western blot analysis, and photo-cross-linked small-molecule beads were assessed through cell-free synthesized FHP binding assay. After ribosome display selection against photo-cross-linked small-molecule beads, RT-PCR using mRNAs recovered from the selected ternary complexes and electrophoresis of the PCR products allowed specific detection of the target proteins binding to the beads. In addition, a repeat of ribosome display selection enabled us to identify the target proteins even if the molar quantity was one ten-thousandth of that of the other proteins in a cell-free synthesized FHP pool. Therefore, these results showed that ribosome display using photo-cross-linked small-molecule beads and further extended FHP pool could be one of the powerful techniques for identification of unknown target proteins of bioactive small molecules.


Assuntos
Diazometano/química , Fotoquímica/métodos , Proteínas/metabolismo , Ribossomos/metabolismo , Códon de Terminação , Reagentes de Ligações Cruzadas/química , Cristalografia por Raios X , Humanos , Medições Luminescentes , Biblioteca de Peptídeos , Reação em Cadeia da Polimerase , Proteínas/análise , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Ribossomos/química , Tacrolimo/metabolismo , Proteína 1A de Ligação a Tacrolimo/genética , Proteína 1A de Ligação a Tacrolimo/metabolismo
14.
Genes Cells ; 18(7): 554-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23663662

RESUMO

In bacteria, 70S ribosomes (consisting of 30S and 50S subunits) dimerize to form 100S ribosomes, which were first discovered in Escherichia coli. Ribosome modulation factor (RMF) and hibernation promoting factor (HPF) mediate this dimerization in stationary phase. The 100S ribosome is translationally inactive, but it dissociates into two translationally active 70S ribosomes after transfer from starvation to fresh medium. Therefore, the 100S ribosome is called the 'hibernating ribosome'. The gene encoding RMF is found widely throughout the Gammaproteobacteria class, but is not present in any other bacteria. In this study, 100S ribosome formation in six species of Gammaproteobacteria and eight species belonging to other bacterial classes was compared. There were several marked differences between the two groups: (i) Formation of 100S ribosomes was mediated by RMF and short HPF in Gammaproteobacteria species, similar to E. coli, whereas it was mediated only by long HPF in the other bacterial species; (ii) RMF/short HPF-mediated 100S ribosome formation occurred specifically in stationary phase, whereas long HPF-mediated 100S ribosome formation occurred in all growth phases; and (iii) 100S ribosomes formed by long HPF were much more stable than those formed by RMF and short HPF.


Assuntos
Bactérias/química , Evolução Molecular , Ribossomos/química , Ribossomos/classificação , Bactérias/metabolismo , Proteínas Ribossômicas/análise , Proteínas Ribossômicas/química , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo
15.
Nephrol Dial Transplant ; 29(8): 1546-53, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24596084

RESUMO

BACKGROUND: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). METHODS: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. RESULTS: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. CONCLUSIONS: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Glomerulonefrite por IGA/terapia , Metilprednisolona/administração & dosagem , Tonsilectomia , Adulto , Biópsia , Feminino , Seguimentos , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Glucocorticoides/administração & dosagem , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Masculino , Pulsoterapia , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
16.
Psychiatry Clin Neurosci ; 68(3): 182-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24895734

RESUMO

AIM: The Fukushima disaster was caused by an earthquake that occurred on 11 March 2011. Following the serious damage caused by the earthquake and the subsequent tsunami, radioactive contamination occurred because of the meltdown accident at the Fukushima nuclear power plant. We investigated what mental disorders were likely to become exacerbated under these conditions. METHODS: We surveyed psychiatric outpatients at Fukushima Medical University Hospital for 1 month (31 days) from the day of the earthquake (March­April 2011). RESULTS: The survey revealed that bipolar I disorder was most likely to become exacerbated under the conditions and that the exacerbation exhibited was more likely to involve manic switches than depression. CONCLUSION: On the basis of the results of our study, particular care must be taken to follow up bipolar I disorder patients after a natural disaster. Our results also suggested the possible origin of bipolar I disorder.


Assuntos
Terremotos , Acidente Nuclear de Fukushima , Transtornos Mentais/diagnóstico , Tsunamis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Japão , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
17.
JAC Antimicrob Resist ; 6(1): dlad155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38384742

RESUMO

Objectives: In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals. Methods: The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe. Results: A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris. We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo. APC6 disrupted the biofilms formed by Candida species. Conclusions: This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis.

18.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674908

RESUMO

Postoperative sarcopenia is associated with poor outcomes in hospitalized patients. However, few studies have focused on short-term postoperative sarcopenia. Furthermore, the influence of nutritional management using amino acids (AAs) comprising a peripheral parenteral nutrition (PPN) solution and its combination with exercise (Exc) is unclear. Hence, we established a postoperative sarcopenic rat model to evaluate the effects of parenteral AA infusion combined with Exc on skeletal muscles and investigate the underlying mechanisms involved in the amelioration of muscle atrophy. Male F344 rats underwent surgery followed by hindlimb suspension (HS) for 5 days. The rats were divided into AA (-), AA (+), AA (-)-Exc, and AA (+)-Exc groups. They were continuously administered a PPN solution with or without AA at 98 kcal/kg/day. The Exc groups were subjected to intermittent loading for 1 h per day. Postoperative sarcopenic rats exhibited decreased muscle strength and mass and an upregulated ubiquitin-proteasome system, autophagy-lysosome system, and fast-twitch fiber-related genes, especially in the AA (-) group. The AA (+)-Exc group exhibited attenuated decreased muscle strength, increased gastrocnemius mass, and a suppressed upregulation of muscle atrophy- and fast-twitch fiber-related genes. Therefore, parenteral AA infusion combined with Exc may be effective in preventing postoperative sarcopenia in hospitalized patients.


Assuntos
Aminoácidos , Modelos Animais de Doenças , Músculo Esquelético , Condicionamento Físico Animal , Ratos Endogâmicos F344 , Sarcopenia , Animais , Sarcopenia/prevenção & controle , Sarcopenia/etiologia , Masculino , Aminoácidos/administração & dosagem , Ratos , Músculo Esquelético/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Atrofia Muscular/prevenção & controle , Atrofia Muscular/etiologia , Força Muscular , Infusões Parenterais , Nutrição Parenteral , Progressão da Doença , Autofagia
19.
Artigo em Inglês | MEDLINE | ID: mdl-39034338

RESUMO

The objective of the study is to investigate the safety, feasibility, and degradation profile of a novel Mg alloy-based bioresorbable coronary scaffold (JFK-PRODUCT BRS) with thin struts (110 µm). Polymer- or Mg alloy-based BRSs have not replaced nondegradable metal stents because of the higher prevalence of scaffold thrombosis and restenosis in clinical practice; these poor clinical outcomes were due to inadequate scaffold designs, including thick struts (more than 150 µm) and their inappropriate degradation processes. Fourteen healthy pigs received 17 JFK-PRODUCT BRSs in the coronary arteries and were sacrificed at 1, 6, 12, 18, and 26 months after implantation. Angiography, optical coherence tomography, microfocus X-ray computed tomography (µCT), scanning electron microscopy with energy-dispersive X-ray spectrometry (SEM-EDX), and histopathological evaluation were performed. The JFK-PRODUCT had a median percent late recoil of 11.28% at 1 month. The µCT observation confirmed that scaffold discontinuity reached 64.8% at 12 months with increased scaffold inner area thereafter, suggesting artery positive remodeling. The inflammation was mild, peaked at 18 months, and decreased thereafter. The SEM-EDX analysis demonstrated gradual degradation of the scaffold with formation of inorganic deposits, presumed to be calcium phosphates. It also revealed the disappearance of calcium phosphates at 26 months, achieving almost complete replacement of the scaffold by biocomponents. The current study demonstrated the safety and feasibility of JFK-PRODUCT with a lower acute recoil rate despite its thin struts. The scaffolds were almost completely disappeared at 26 months after implantation.

20.
Chembiochem ; 14(12): 1504-6, 2013 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-23893885

RESUMO

Celebrating a joint effort: The 2nd symposium of the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology recently took place in Wako, Japan. This report describes the collaboration behind this event and highlights the science presented over the three days.


Assuntos
Glicômica , Biologia de Sistemas/tendências , Tecnologia , Comportamento Cooperativo , Alemanha , Japão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA