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1.
Anticancer Res ; 41(9): 4645-4650, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475093

RESUMO

BACKGROUND/AIM: Previous reports have indicated that increased expression of Jagged-1 (JAG1) may predict chemotherapy response and poor prognosis for patients with recurrent or metastatic colorectal cancer (CRC). This study aimed to investigate the clinical impact of JAG1 expression level in patients with CRC, including recurrence, especially in those diagnosed with lymph node-positive stage III CRC who underwent complete resection and appropriate adjuvant chemotherapy. PATIENTS AND METHODS: All patients were enrolled through a retrospective chart review, and only those for whom the clinical course and all clinical information were adequately determined according to the inclusion criteria were selected for retrospective review through medical records. Immunohistochemical staining of JAG1 was performed using paraffin-embedded tissue. JAG1 expression was determined by scoring for staining intensity and percentage of positively stained cells; the final JAG1 score was determined as the sum of both scores. RESULTS: Sixteen patients who experienced relapse and 15 without (for over 3 years) were selected. The protein expression level of JAG1 showed a tendency for being lower in the group without recurrence, although not statistically significantly (p=0.083); however, the mean JAG1 expression score was significantly lower in the group without recurrence (1.53 vs. 3.19; p=0.004). The patients were divided into two groups with low and high JAG1 expression. The results showed that high JAG1 expression was significantly associated with recurrence of stage III CRC (p=0.029). CONCLUSION: The expression of JAG1 may be a potential novel biomarker for predicting CRC recurrence.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Proteína Jagged-1/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Regulação para Cima , Idoso , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(27): e26616, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232219

RESUMO

ABSTRACT: There has been increased use of self-expandable metal stents (SEMS) in treating malignant colorectal obstruction (MCO). The aim of this study was to investigate factors that are associated with the outcomes of SEMS placement for MCO.Clinical data from patients who underwent SEMS placement for MCO at 6 hospitals in Honam province of South Korea between 2009 and 2018 were reviewed retrospectively. Eight hundred two patients were identified and their data were analyzed. Technical success, clinical success, complications, and predictors of outcome were included as main outcome measures.Technical and clinical success rates were 98.8% (792/802) and 90.1% (723/802), respectively. Complications including stent migration, stent occlusion due to tumor ingrowth and outgrowth, perforation, bacteremia/fever, and bleeding occurred in 123 (15.3%) patients. In multivariate regression analyses, procedure time was significantly associated with the technical success of SEMS placement (P = .001). Longer length of obstruction, the use of covered stent, and longer procedure time were significant independent predictive factors for the clinical success of SEMS placement (odds ratio [OR] 0.974 (95% confidence interval [CI] 0.950-0.990); P = .043, OR 0.255 (95% CI 0.138-0.471); P < .001, and OR 0.957 (95% CI 0.931-0.984); P = .002, respectively). Stage IV colorectal cancer and the use of covered stent were significant independent predictive factors for the development of complications after SEMS placement (OR 2.428 (95% CI 1.407-4.188); P = .001 and OR 3.329 (95% CI 2.060-5.378); P < .001, respectively).Longer length of obstruction, the use of covered stent, and longer procedure time were associated with lower clinical success rates. Having stage IV colorectal cancer and the use of covered stents were associated with an increased risk of complications.


Assuntos
Neoplasias Colorretais/complicações , Obstrução Intestinal/cirurgia , Cuidados Paliativos/métodos , Stents Metálicos Autoexpansíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Sensors (Basel) ; 21(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200890

RESUMO

With the rapid deployment of present-day mobile communication systems, user traffic requirements have increased tremendously. An ultra-dense network is a configuration in which the density of small base stations is greater than or equal to that of the user equipment. Ultra-dense networks are considered as the key technology for 5th generation networks as they can improve the link quality and increase the system capacity. However, in an ultra-dense network, small base stations are densely positioned, so one user equipment may receive signals from two or more small base stations. This may cause a severe inter-cell interference problem. In this study, we considered a coordinated multi-point scenario, a cooperative technology between base stations to alleviate the interference. In addition, to suppress the occurrence of severe interference at the cell edges, link formation was carried out by considering the degree of cell load for each cluster. After the formation of links between all the base stations and user equipment, a subcarrier allocation procedure was performed. The subcarrier allocation method used in this study was based on the location of base stations with clustering to improve the data rate and reduce the interference between the clusters. Power allocation was based on the channel gain between the base station and user equipment. Simulation results showed that the proposed scheme delivered a higher sum rate than the other resource allocation methods reported previously for various types of user equipment.

4.
Cell Cycle ; 19(15): 1952-1968, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32594826

RESUMO

Centrosomes are the primary microtubule-organizing centers that are important for mitotic spindle assembly. Centrosome amplification is commonly observed in human cancer cells and contributes to genomic instability. However, it is not clear how centrosome duplication is dysregulated in cancer cells. Here, we report that ATAD5, a replisome protein that unloads PCNA from chromatin as a replication factor C-like complex (RLC), plays an important role in regulating centrosome duplication. ATAD5 is present at the centrosome, specifically at the base of the mother and daughter centrioles that undergo duplication. UAF1, which interacts with ATAD5 and regulates PCNA deubiquitination as a complex with ubiquitin-specific protease 1, is also localized at the centrosome. Depletion of ATAD5 or UAF1 increases cells with over-duplicated centrosome whereas ATAD5 overexpression reduces such cells. Consistently, the proportion of cells showing the multipolar mode of chromosome segregation is increased among ATAD5-depleted cells. The localization and function of ATAD5 at the centrosomes do not require other RLC subunits. UAF1 interacts and co-localizes with ID1, a protein that increases centrosome amplification upon overexpression. ATAD5 depletion reduces interactions between UAF1 and ID1 and increases ID1 signal at the centrosome, providing a mechanistic framework for understanding the role of ATAD5 in centrosome duplication.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32492920

RESUMO

BACKGROUND: Evidence supports abdominal massage (AM) or electrical stimulation (ES) as effective in treating functional constipation (FC). Manual lymph drainage (MLD) may also be beneficial, however, it was not previously investigated or compared to ES and AM. METHODS: Sixteen college-aged males and 36 females were recruited. Participants were randomly assigned to MLD, AM or ES. Heart rate variability (HRV) measures for total power (TP), high frequency (HF), low frequency and LF/HF ratio assessed ANS outcomes. state-trait anxiety inventory (STAI) and stress response inventory (SRI) assessed psychological factors and bowel movement frequency (BMF) and duration (BMD) were recorded daily. RESULTS: MLD significantly improved all ANS measures (p≤0.01); AM significantly improved LF, HF and LF/HF ratios (p = 0.04); and ES significantly improved LF (p = 0.1). STAI measures improved, but not significantly in all groups. SRI improved significantly from MLD (p < 0.01), AM (p = 0.04) and ES (p < 0.01), but changes were not significant between groups. BMD improved significantly in all groups (p≤ 0.02). BMF improved significantly only following MLD and AM (p < 0.1), but differences between groups were not significant (p = 0.39). CONCLUSIONS: MLD significantly reduced FC symptoms and MLD had greater improvements than AM or ES.


Assuntos
Constipação Intestinal/terapia , Estimulação Elétrica , Drenagem Linfática Manual , Massagem , Feminino , Frequência Cardíaca , Humanos , Masculino , Adulto Jovem
6.
Nucleic Acids Res ; 48(13): 7218-7238, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32542338

RESUMO

R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflict (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX1, DDX5, DDX21 and DHX9 and increases the abundance of these helicases at replication forks to facilitate R-loop resolution. Depletion of ATAD5 or ATAD5-interacting RNA helicases consistently increases R-loops during the S phase and reduces the replication rate, both of which are enhanced by replication stress. In addition to R-loop resolution, ATAD5 prevents the generation of new R-loops behind the replication forks by unloading PCNA which, otherwise, accumulates and persists on DNA, causing a collision with the transcription machinery. Depletion of ATAD5 reduces transcription rates due to PCNA accumulation. Consistent with the role of ATAD5 and RNA helicases in maintaining genomic integrity by regulating R-loops, the corresponding genes were mutated or downregulated in several human tumors.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Ligação a DNA/metabolismo , Estruturas R-Loop , RNA Helicases DEAD-box/metabolismo , Células HEK293 , Células HeLa , Humanos , Antígeno Nuclear de Célula em Proliferação/metabolismo
8.
Fish Shellfish Immunol ; 92: 151-164, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31108176

RESUMO

IL-12 is an important cytokine that connects the innate and adaptive immune systems. The complete gene structure of olive flounder IL-12 and its characteristics have not yet been formally reported. Here, we report the complete sequences of both subunits of olive flounder IL-12 (IL-12p35 and IL-12p40). In addition, its function was analyzed by generating the single-chain rIL-12 of which subunits were fused by a GS linker and the rIL-12-specific mouse antibody. The cDNA sequences of IL-12p35 and IL-12p40 were 1059 nucleotides and 1319 nucleotides, respectively. The analyses of their gene structures, deduced amino acid sequences, protein model structures, and phylogenetic trees confirmed the accurate identification of olive flounder IL-12. The protein structure model suggested that an inter-subunit disulfide bond might be formed between the Cys177 of p35 and Cys74 of p40 to link the subunits. Olive flounder expressed IL-12p40 at higher levels than IL-12p35 in the various tissues under natural conditions although both expression levels were low. However, when infected by Edwardsiella tarda or stimulated by LPS, the flounder expressed both of the subunit genes at similar maximized levels in 6 h and gradually reduced thereafter. Olive flounder PBMC induced with the rIL-12 increased IFN-γ and TNF-α expression but decreased IL-10 expression as did treatment with LPS. However, when the LPS-treated PBMC were neutralized with the rIL-12-specific antibody, the pattern of cytokine expression was precisely reversed. In conclusion, we have formally identified the gene structure and function of olive flounder IL-12.


Assuntos
Imunidade Adaptativa/genética , Doenças dos Peixes/imunologia , Linguados/genética , Linguados/imunologia , Imunidade Inata/genética , Interleucina-12/genética , Interleucina-12/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Edwardsiella tarda/fisiologia , Infecções por Enterobacteriaceae/imunologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Linguado/genética , Linguado/imunologia , Perfilação da Expressão Gênica/veterinária , Interleucina-12/química , Lipopolissacarídeos/farmacologia , Filogenia , Alinhamento de Sequência/veterinária
9.
Curr Microbiol ; 73(1): 54-64, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27016238

RESUMO

Upon entering the human body, Vibrio vulnificus, a gram-negative marine bacterium, must withstand a temperature change (TC) from 25 to 37 °C. This bacterium acquires iron mainly via the vulnibactin receptor (VuuA)-mediated iron uptake system (IUS), which is under the positive control of cyclic AMP receptor protein (CRP), a global regulator responsible for catabolite repression. In this study, we examined the effect of TC on the expression of vuuA and crp, and the reciprocal relation between VuuA-mediated IUS and CRP under iron-limited conditions. Iron limitation increased vuuA expression but decreased crp expression. TC resulted in increased vuuA and crp expression. A crp or vuuA mutation reciprocally decreased vuuA or crp expression. TC could increase vuuA or crp expression even in a crp- or vuuA-mutated background. These results indicate that TC increases the expression of both vuuA and crp by facilitating metabolism under iron-limited conditions, and that CRP and VuuA-mediated IUS interact coordinately toward optimal metabolism in V. vulnificus.


Assuntos
Amidas/metabolismo , Proteínas de Bactérias/genética , Proteína Receptora de AMP Cíclico/genética , Regulação Bacteriana da Expressão Gênica , Oxazóis/metabolismo , Vibrio vulnificus/metabolismo , Proteínas de Bactérias/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Humanos , Temperatura , Vibrioses/microbiologia , Vibrio vulnificus/genética
10.
Korean J Spine ; 10(3): 174-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24757482

RESUMO

Although anterior approaches to the cervical spine are popular and safe, they cause some of complications. Esophageal perforation after anterior spinal fusion is a rare but potentially life-threatening complication. We present a rare case of delayed esophageal perforation caused by a cervical screw placed via the anterior approach. A 43-year-old man, who had undergone surgery for complete cord injury at another orthopedic department 8 years previously, was admitted to our institute due to painful neck swelling and dysphagia. Radiological studies revealed a protruding screw and esophageal perforation. The perforation was found during surgery and was successfully repaired. This case emphasizes the need for careful long-term follow-up to check for delayed esophageal perforation in patients that have undergone anterior cervical spine plating.

11.
J Microbiol ; 50(2): 320-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22538662

RESUMO

The ferrophilic bacterium Vibrio vulnificus can utilize the siderophore aerobactin of Escherichia coli for iron acquisition via its specific receptor IutA. This siderophore piracy by V. vulnificus may contribute to its survival and proliferation, especially in mixed bacterial environments. In this study, we examined the effects of glucose, cyclic AMP (cAMP), and cAMP-receptor protein (Crp) on iutA expression in V. vulnificus. Glucose dose-dependently repressed iutA expression. A mutation in cya encoding adenylate cyclase required for cAMP synthesis severely repressed iutA expression, and this change was recovered by in trans complementing cya or the addition of exogenous cAMP. Furthermore, a mutation in crp encoding Crp severely repressed iutA expression, and this change was recovered by complementing crp. Accordingly, glucose deprivation under iron-limited conditions is an environmental signal for iutA expression, and Crp functions as an activator that regulates iutA expression in response to glucose availability.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica , Vibrio vulnificus/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Proteína Receptora de AMP Cíclico/genética , Glucose/metabolismo , Ferro/metabolismo , Vibrio vulnificus/genética
12.
Korean J Lab Med ; 30(5): 507-10, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20890083

RESUMO

We identified 6 sucrose-fermenting Vibrio vulnificus strains and examined their virulence characteristics. They were all encapsulated, motile, capable of producing toxins and utilizing transferrin-bound iron, cytotoxic to cultured cells, and virulent enough to kill mice. They could be definitely identified only by genetic identification methods such as PCR, and not by conventional culture-based identification methods such as API 20E (bioMérieux, France). These results indicate that it is essential to adopt genetic approaches as early as possible in order to avoid misdiagnosis of such strains, especially in clinical situations.


Assuntos
Sacarose/metabolismo , Vibrio vulnificus/patogenicidade , Animais , Proteínas de Bactérias/genética , Fermentação , Camundongos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vibrio vulnificus/genética , Vibrio vulnificus/crescimento & desenvolvimento , Virulência
13.
J Microbiol Methods ; 69(3): 442-50, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17428560

RESUMO

A yeast transcriptional activator, Gcn4p, induces the expression of genes that are involved in amino acid and purine biosynthetic pathways under amino acid starvation. Gcn4p has an acidic activation domain in the central region and a bZIP domain in the C-terminus that is divided into the DNA-binding motif and dimerization leucine zipper motif. In order to identify amino acids in the DNA-binding motif of Gcn4p which are involved in transcriptional activation, we constructed mutant libraries in the DNA-binding motif through an innovative application of random mutagenesis. Mutant library made by oligonucleotides which were mutated randomly using the Poisson distribution showed that the actual mutation frequency was in good agreement with expected values. This method could save the time and effort to create a mutant library with a predictable mutation frequency. Based on the studies using the mutant libraries constructed by the new method, the specific residues of the DNA-binding domain in Gcn4p appear to be involved in the transcriptional activities on a conserved binding site.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Ligação a DNA/genética , Biblioteca Gênica , Mutagênese Sítio-Dirigida/métodos , Mutação Puntual , Reação em Cadeia da Polimerase/métodos , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae , Fatores de Transcrição/química , Sequência de Aminoácidos , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica/química , Proteínas de Ligação a DNA/química , Regulação Fúngica da Expressão Gênica , Dados de Sequência Molecular , Plasmídeos , Distribuição de Poisson , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética
14.
Biol Pharm Bull ; 29(11): 2295-300, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17077532

RESUMO

In order to determine whether Pseudomonas aeruginosa alkaline protease AprA is involved in facilitating siderophore-mediated iron-acquisition from human transferrins, we measured bacterial growth, the production of siderophore and AprA, iron-acquisition from transferrins, and the proteolytic cleavage of transferrins in an alkaline minimal medium (pH 8.3) containing human transferrins as an iron source and compared these on a time scale. The growth of P. aeruginosa was found to be stimulated in proportion to the iron-saturation levels of transferrins. AprA production and the proteolytic cleavage of transferrins began concomitantly with siderophore production from the early growth phase when P. aeruginosa was actively growing and consuming most iron for growth. However, the AprA-free, but siderophore-containing, culture ultrafiltrates could also remove iron from transferrin. These results indicate that alkaline protease AprA can facilitate the siderophore-mediated iron-uptake of P. aeruginosa via the proteolytic cleavage of transferrins. However, the proteolytic cleavage by AprA is not essentially required for iron-acquisition from transferrins.


Assuntos
Proteínas de Bactérias/metabolismo , Endopeptidases/metabolismo , Ferro/farmacocinética , Pseudomonas aeruginosa/enzimologia , Sideróforos/biossíntese , Transferrina/metabolismo , Anemia Ferropriva/metabolismo , Proteínas de Bactérias/genética , Transporte Biológico , Divisão Celular , Meios de Cultivo Condicionados/análise , Meios de Cultivo Condicionados/química , Endopeptidases/genética , Humanos , Concentração de Íons de Hidrogênio , Ferro/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
15.
J Microbiol ; 44(5): 537-47, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17082748

RESUMO

This study was designed to determine whether or not Vibrio vulnificus metalloprotease VvpE can promote iron uptake via the proteolytic cleavage of human hemoglobin. We found that V. vulnificus utilized hemoglobin as an iron source more efficiently via the vulnibactin-mediated iron-uptake system than via the HupA-mediated iron-uptake system and, of the proteases produced by V. vulnificus, VvpE was found to be the only protease capable of destroying hemoglobin. However, VvpE expression, on both the transcriptional and protein levels, was suppressed in iron-limited media. However, vvpE transcription, but not extracellular VvpE production, was reactivated by the addition of hemoglobin or inorganic iron into iron-limited media. Moreover, vvpE transcription began only in the late growth phase when V. vulnificus had already consumed most of the iron for growth. In addition, neither vvpE mutation nor in trans vvpE complementation affected the ability of V. vulnificus to acquire iron or to grow in iron-limited media or in cirrhotic ascites containing hemoglobin. Hemoglobin added into iron-limited media was not destroyed, but gradually formed an insoluble aggregate during culture; this aggregation of hemoglobin occurred regardless of vvpE mutation or complementation. These results indicate that VvpE is not required for efficient iron uptake from hemoglobin. On the contrary, hemoglobin or iron is required for efficient vvpE transcription. In addition, a discrepancy exists between vvpE transcription and extracellular VvpE production in iron-limited media containing inorganic iron or hemoglobin, which suggests that additional unknown posttranscriptional events may be involved in the extracellular production of VvpE.


Assuntos
Hemoglobinas/metabolismo , Ferro/metabolismo , Metaloproteases/metabolismo , Vibrio vulnificus/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Eletroforese em Gel de Poliacrilamida/métodos , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Ferro/farmacocinética , Metaloproteases/genética , Mutação/genética , Reação em Cadeia da Polimerase/métodos , Transcrição Genética/genética , Transcrição Genética/fisiologia , Vibrio vulnificus/genética , Vibrio vulnificus/metabolismo
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