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1.
AMIA Jt Summits Transl Sci Proc ; 2024: 249-257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827054

RESUMO

In the rapidly evolving field of healthcare, the integration of artificial intelligence (AI) has become a pivotal component in the automation of clinical workflows, ushering in a new era of efficiency and accuracy. This study focuses on the transformative capabilities of the fine-tuned KoELECTRA model in comparison to the GPT-4 model, aiming to facilitate automated information extraction from thyroid operation narratives. The current research landscape is dominated by traditional methods heavily reliant on regular expressions, which often face challenges in processing free-style text formats containing critical details of operation records, including frozen biopsy reports. Addressing this, the study leverages advanced natural language processing (NLP) techniques to foster a paradigm shift towards more sophisticated data processing systems. Through this comparative study, we aspire to unveil a more streamlined, precise, and efficient approach to document processing in the healthcare domain, potentially revolutionizing the way medical data is handled and analyzed.

2.
Int J Surg ; 110(6): 3433-3439, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489664

RESUMO

BACKGROUND: Infections following postmastectomy implant-based breast reconstruction (IBR) can compromise surgical outcomes and lead to significant morbidity. This study aimed to discern the timing of infections in two-stage IBR and associated risk factors. METHOD: A review of electronic health records was conducted on 1096 breasts in 1058 patients undergoing two-stage IBR at Seoul National University Hospital (2015-2020). Infections following the first-stage tissue expander (TE) insertion and second-stage TE exchange were analyzed separately, considering associated risk factors. RESULTS: Over a median follow-up of 53.5 months, infections occurred in 2.9% (32/1096) after the first stage and 4.1% (44/1070) after the second stage. Infections following the first-stage procedure exhibited a bimodal distribution across time, while those after the second-stage procedure showed a unimodal pattern. When analyzing risk factors for infection after the first-stage procedure, axillary lymph node dissection (ALND) was associated with early (≤7 weeks) infection, while both ALND and obesity were independent predictors of late (>7 weeks) infection. For infections following the second-stage procedure, obesity, postmastectomy radiotherapy, a history of expander infection, ALND, and the use of textured implants were identified as independent risk factors. Postmastectomy radiotherapy was related to non-salvaged outcomes after infection following both stages. CONCLUSION: Infections following first and second-stage IBR exhibit distinct timelines reflecting different pathophysiology. Understanding these timelines and associated risk factors will inform patient selection for IBR and aid in tailored postoperative surveillance planning. These findings contribute to refining patient suitability for IBR and optimizing personalized postoperative care strategies.


Assuntos
Implantes de Mama , Mastectomia , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Mastectomia/efeitos adversos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/cirurgia , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Implante Mamário/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Dispositivos para Expansão de Tecidos/efeitos adversos , Idoso , República da Coreia/epidemiologia , Fatores de Tempo
3.
Cell Genom ; 4(2): 100499, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38359788

RESUMO

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.


Assuntos
Rearranjo Gênico , Translocação Genética , Humanos , Animais , Camundongos , Mutação , Genômica , Inversão Cromossômica , Mamíferos
4.
Cells ; 12(14)2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37508518

RESUMO

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.


Assuntos
Criocirurgia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Criocirurgia/métodos , Neoplasias Pulmonares/patologia , Pulmão/patologia , Organoides/patologia
5.
Med Image Anal ; 89: 102886, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37494811

RESUMO

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Inteligência Artificial , Prognóstico , Fluoruracila/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
6.
Medicine (Baltimore) ; 100(46): e27731, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797298

RESUMO

RATIONALE: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States. Painkillers and fever antipyretics are the most common cause of DILI. Hepatic injury can be provoked by DILI as hepatocellular or cholestatic type. PATIENT CONCERNS: A 48-year-old woman presented jaundice accompanied by nausea and vomiting. The patient was an inactive hepatitis B carrier with low viral titer and was diagnosed renal cell carcinoma (RCC) with hepatic metastasis requiring pazopanib treatment. Prior to administration of pazopanib, tenofovir administration was started to prevent exacerbation of hepatitis B. The patient was referred to clinic of gastroenterology department due to sudden elevation of bilirubin after 5 weeks of pazopanib treatment. DIAGNOSES: Abdominal ultrasound and computed tomography showed non-specific finding other than metastatic nodule in the liver and liver cirrhosis. After then, the patient was performed liver biopsy, and the biopsy result was acute cholestatic hepatitis with centrilobular area necrosis and portal inflammation. Therefore, considering the clinical history and biopsy results, the patient was diagnosed as DILI due to pazopanib. INTERVENTIONS: After the biopsy, empirical steroid therapy was initiated and after 7 weeks of pazopanib discontinuation. OUTCOMES: The total bilirubin level returned to normal from peak level of 24.61 to 1.52 mg/dL. LESSONS: In patients with renal cell carcinoma, pazopanib treatment requires clinical caution as it causes rare complications such as severe jaundice and acute cholestatic hepatitis.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Indazóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Bilirrubina/sangue , Biópsia , Carcinoma de Células Renais/patologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Feminino , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Humanos , Indazóis/uso terapêutico , Icterícia/diagnóstico , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Náusea/etiologia , Pirimidinas/uso terapêutico , Esteroides/uso terapêutico , Sulfonamidas/uso terapêutico , Tomografia Computadorizada por Raios X , Ultrassonografia , Estados Unidos , Vômito/etiologia
7.
Sci Rep ; 11(1): 18576, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535723

RESUMO

Contradictory findings exist about association of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) with lung cancer development. This was a retrospective observational cohort study that used data from 7 hospitals in Korea, converted to the Observational Medical Outcomes Partnership Common Data Model. The primary outcome was occurrence of lung cancer. A total of 207,794 patients across the 7 databases was included in the final analysis; 33,230 (16%) were prescribed ACEi and 174,564 (84%) were prescribed ARB. Crude analysis adjusted for sex and age showed higher incidence of lung cancer in the ACEi group compared to the ARB group (hazard ratio [HR], 1.46; 95% confidence rate [CI], 1.08-1.97). After propensity-score matching, 30,445 pairs were generated, and there was no difference in incidence of lung cancer between the two groups (HR, 0.93; 95% CI, 0.64-1.35). Patients prescribed ACEi showed no difference in incidence of lung cancer development compared to those using ARB. This finding provides evidence on the association between ACEi and occurrence of lung cancer.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Adulto , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos
8.
BMC Med Inform Decis Mak ; 21(1): 114, 2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33812383

RESUMO

BACKGROUND: Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists. METHODS: Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists' workload, AI-assisted annotation was established in collaboration with university AI teams. RESULTS: A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models. DISCUSSION: Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition. CONCLUSIONS: Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.


Assuntos
Inteligência Artificial , Neoplasias , Algoritmos , Humanos , Masculino
9.
Med Image Anal ; 67: 101854, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091742

RESUMO

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.


Assuntos
Inteligência Artificial , Neoplasias Hepáticas , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/diagnóstico por imagem , Carga Tumoral
10.
Genomics ; 112(2): 1208-1213, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31295546

RESUMO

Interpretation of noncoding disease variants, which comprise the vast majority of Genome-wide association studies (GWAS) hits, remains a momentous challenge due to haplotype structure and our limited understanding of the mechanisms and physiological contexts of noncoding elements. GWAS have identified loci underlying human diseases, but assigning the causal nucleotide changes still remain a controversial issue. Here we addressed these issues through the combination of high-density genotyping and epigenomic data using a random forest model to discover the noncoding causal variants. Focusing on autoimmune diseases, we triaged putative causal variants for atopic dermatitis and inflammatory bowel diseases. Making a filtering pipeline, we found three interesting single nucleotide polymorphisms (rs1800630, rs1799964 and rs4796793) in the upstream site of TNF and STAT3 genes, two frequent genes shared in some autoimmune diseases, and show how those variants affect on TNF and STAT3 expression levels. All data and source codes related to this manuscript are available at https://github.com/jieunjung511/Autoimmune-research.


Assuntos
Dermatite Atópica/genética , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/genética , Fator de Necrose Tumoral alfa/genética , Sequências Reguladoras de Ácido Nucleico
11.
J Pain Res ; 12: 1615-1619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190971

RESUMO

OBJECTIVE: Combined spinal-epidural (CSE) anesthesia is a widely used neuraxial anesthetic technique. In clinical practice, failed dural puncture during needle-through-needle technique occasionally occurs, with incidence of 5%-29%. We radiologically evaluated four cases of failed dural puncture during needle-through-needle CSE anesthesia. CASE SERIES: Four patients received CSE anesthesia for elective orthopedic surgery. CSE procedures were performed in the same manner using a CSE device for needle-through-needle technique. An epidural needle was inserted in midline at L4/5 interspaces using loss of resistance to air whilst patients lay in the lateral decubitus position. The spinal needle was then inserted through the epidural needle for subarachnoid block, however, negative cerebrospinal flow was identified. Subsequently, radiographic imaging using C-arm fluoroscopy was performed to evaluate the status of needles. We found that epidural needles were considerably deviated from the midline, while spinal needles exited epidural needles, not through back holes, but through the Tuohy curve in three patients. In one patient, when the spinal needle was inserted to 12 mm, the anesthesiologist felt the needle touching the bony structure. The spinal needle was in contact with the superior articular process of the fifth lumbar vertebra, which was confirmed by C-arm radiography. CONCLUSION: Excessive paramedian deviation of the epidural needle may affect dural puncture during needle-through-needle CSE technique. Moreover, wrong passage of the spinal needle through Tuohy curve instead of the back hole, may contribute to failure of dural puncture.

12.
BMC Med Inform Decis Mak ; 18(1): 29, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29783980

RESUMO

BACKGROUND: Pathology reports are written in free-text form, which precludes efficient data gathering. We aimed to overcome this limitation and design an automated system for extracting biomarker profiles from accumulated pathology reports. METHODS: We designed a new data model for representing biomarker knowledge. The automated system parses immunohistochemistry reports based on a "slide paragraph" unit defined as a set of immunohistochemistry findings obtained for the same tissue slide. Pathology reports are parsed using context-free grammar for immunohistochemistry, and using a tree-like structure for surgical pathology. The performance of the approach was validated on manually annotated pathology reports of 100 randomly selected patients managed at Seoul National University Hospital. RESULTS: High F-scores were obtained for parsing biomarker name and corresponding test results (0.999 and 0.998, respectively) from the immunohistochemistry reports, compared to relatively poor performance for parsing surgical pathology findings. However, applying the proposed approach to our single-center dataset revealed information on 221 unique biomarkers, which represents a richer result than biomarker profiles obtained based on the published literature. Owing to the data representation model, the proposed approach can associate biomarker profiles extracted from an immunohistochemistry report with corresponding pathology findings listed in one or more surgical pathology reports. Term variations are resolved by normalization to corresponding preferred terms determined by expanded dictionary look-up and text similarity-based search. CONCLUSIONS: Our proposed approach for biomarker data extraction addresses key limitations regarding data representation and can handle reports prepared in the clinical setting, which often contain incomplete sentences, typographical errors, and inconsistent formatting.


Assuntos
Biomarcadores , Tomada de Decisão Clínica , Imuno-Histoquímica , Modelos Teóricos , Processamento de Linguagem Natural , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/cirurgia , Biomarcadores/metabolismo , Humanos
13.
Bioinorg Chem Appl ; 2016: 6374721, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27965526

RESUMO

The purpose of this study was to compare fracture resistances of K3 nickel-titanium files made from different thermal treatments. K3 (SybronEndo, Orange, CA), K3XF (SybronEndo), and experimentally heat treated K3 (K3H) were used. For the cyclic fatigue test, the samples were rotated with up-and-down motion in the artificial canal with the curvature of 60 degrees until the fracture occurred. The number of cycles to fracture (NCF) was measured. For the torsional fracture test, the samples were tightly bound and rotated until the fracture occurred. Elastic modulus (EM), ultimate torsional strength (UTS), and angle of rotation to fracture (ARF) were measured. The results were statistically analyzed by one-way ANOVA. The NCF of K3H was higher than those of K3 and K3XF (P < 0.05). The EM of K3XF and K3H was lower than that of K3 (P < 0.05). There was no significant difference in UTS. The ARF of K3XF was higher than that of K3 (P < 0.05). K3XF and K3H showed more flexibility than K3. The maximum torsional angle of K3XF was higher than that of K3, but there was no significant difference on the UTS in all three groups.

14.
Blood ; 128(17): 2117-2129, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27605510

RESUMO

MicroRNAs (miRNAs) have emerged as important regulators of the immune system. However, despite this prominence, our understanding of the function of miRNAs in the early hematopoietic stages is incomplete. In this study, we found that miR-139-5p negatively regulated the proliferation of hematopoietic stem cells and progenitor cells and that downregulation of miR-139-5p expression was associated with hematopoietic malignancy, such as chronic myeloid leukemia (CML). Knockdown of miR-139-5p resulted in myeloid-biased differentiation with expansion of myeloid progenitor cells. In contrast, miR-139-5p expression inhibited the proliferation of hematopoietic progenitors and resulted in the remission of a CML-like disease that is induced by breakpoint cluster region-Abelson (BCR-ABL) transformation. We also found that Brg1 is a functional target of miR-139-5p and that Brg1 is involved in BCR-ABL-induced leukemogenesis. Thus, our results identify miR-139-5p as a key regulator of cellular proliferation during early hematopoiesis and suggest that it is a potent antileukemic molecule.


Assuntos
Carcinogênese/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Células-Tronco Hematopoéticas/citologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , MicroRNAs/metabolismo , Animais , Separação Celular , Regulação para Baixo , Citometria de Fluxo , Proteínas de Fusão bcr-abl/genética , Técnicas de Silenciamento de Genes , Humanos , Immunoblotting , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
J Am Soc Nephrol ; 26(6): 1426-33, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25343954

RESUMO

Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m(2) were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval [95% CI], 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.


Assuntos
Causas de Morte , Glomérulos Renais/fisiopatologia , Estilo de Vida , Insuficiência Renal Crônica/mortalidade , Adulto , Fatores Etários , Idoso , Antropometria , Índice de Massa Corporal , Comorbidade , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Glomérulos Renais/metabolismo , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/fisiopatologia , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/epidemiologia , Análise de Sobrevida
16.
Eur J Immunol ; 45(1): 167-79, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25348202

RESUMO

Foxp3(+) Treg cells are crucial for maintaining T-cell homeostasis, but their role in B-cell homeostasis remains unclear. Here, we found that Foxp3 mutant scurfy mice had fewer B-lineage cells and progenitors, including common lymphoid progenitors and lymphoid-primed multipotent progenitors, but higher myeloid-lineage cell numbers in BM compared with WT littermates. Homeostasis within the HSC compartment was also compromised with apparent expansion of long- and short-term HSCs. This abnormality was due to the lack of Treg cells, but not to the Treg-cell extrinsic functions of Foxp3 or cell-autonomous defects. Among cytokines enriched in the BM of scurfy mice, IFN-γ affected only B lymphopoiesis, but GM-CSF, TNF, and IL-6 collectively promoted granulopoiesis at the expense of B lymphopoiesis. Neutralization of these three cytokines reversed the hematopoietic defects on early B-cell progenitors in scurfy mice. Treg cells ensured B lymphopoiesis by reducing the production of these cytokines by effector T cells, but not by directly affecting B lymphopoiesis. These results suggest that Treg cells occupy an important niche in the BM to protect B-lineage progenitor cells from excessive exposure to a lymphopoiesis-regulating milieu.


Assuntos
Linfócitos B/citologia , Células da Medula Óssea/citologia , Fatores de Transcrição Forkhead/imunologia , Granulócitos/citologia , Células-Tronco/citologia , Linfócitos T Reguladores/citologia , Animais , Anticorpos Neutralizantes/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Linhagem da Célula/imunologia , Proliferação de Células , Fatores de Transcrição Forkhead/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Homeostase/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Cultura Primária de Células , Células-Tronco/efeitos dos fármacos , Células-Tronco/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
17.
J Craniofac Surg ; 24(2): 554-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23524740

RESUMO

Persistent macroglossia affects speech, swallowing, and the dentofacial skeleton. A range of tongue reduction methods have been proposed to preserve the mobility and sensation of the tongue. However, recent reports have shown that speech or esthetic problems still exists, even after a comprehensive glossectomy in early childhood. Because a large volume reduction of the anterior tongue in young growing children might result in a short tongue tip with functional difficulties, it is important to select the appropriate tongue reduction method considering the growth of the tongue.In the current report, a staged tongue reduction was planned to minimize the functional and esthetic problems after surgery. A 3-year-old girl visited our clinic because of congenital macroglossia, phonation problems, and prognathic appearance of the mandible. The tongue was first reduced by a central glossectomy. The speech intelligibility, tongue movement, and skeletal growth pattern were improved after the first surgery. The secondary peripheral tongue reduction was performed 6 years later to achieve an esthetically pleasing tongue appearance.This 2-stage partial glossectomy, central tongue reduction first followed later by a peripheral tongue reduction, ensures functional integrity of the tongue and can provide an esthetically pleasing result in growing children. The results demonstrated that this strategic combination of a staged tongue reduction can be a successful treatment option for macroglossia.


Assuntos
Glossectomia/métodos , Macroglossia/congênito , Pré-Escolar , Estética , Feminino , Humanos , Macroglossia/cirurgia , Prognatismo/complicações , Inteligibilidade da Fala
18.
Brain Tumor Res Treat ; 1(2): 111-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24904903

RESUMO

Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. The clinical presentation of meningeal irritation is very rare. Nonetheless, if present and associated with fever, pituitary apoplexy may be misdiagnosed as a meningitis. We experienced a case of pituitary apoplexy masquerading as a meningitis. A 42-year-old man presented with meningitis associated symptoms and initial imaging studies did not show evidence of intra-lesional hemorrhage in the pituitary mass. However, a follow-up imaging after neurological deterioration revealed pituitary apoplexy. Hereby, we report our case with a review of literatures.

19.
J Immunol ; 188(8): 3791-803, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22427636

RESUMO

During the process of B cell development, transcription factors, such as E2A and Ebf1, have been known to play key roles. Although transcription factors and chromatin regulators work in concert to direct the expression of B lineage-specific genes, little is known about the involvement of regulators for chromatin structure during B lymphopoiesis. In this article, we show that deletion of Srg3/mBaf155, a scaffold subunit of the SWI/SNF-like BAF complex, in the hematopoietic lineage caused defects at both the common lymphoid progenitor stage and the transition from pre-pro-B to early pro-B cells due to failures in the expression of B lineage-specific genes, such as Ebf1 and Il7ra, and their downstream target genes. Moreover, mice that were deficient in the expression of Brg1, a subunit of the complex with ATPase activity, also showed defects in early B cell development. We also found that the expression of Ebf1 and Il7ra is directly regulated by the SWI/SNF-like BAF complex. Thus, our results suggest that the SWI/SNF-like BAF complex facilitates early B cell development by regulating the expression of B lineage-specific genes.


Assuntos
Diferenciação Celular/imunologia , Cromatina/imunologia , Proteínas Cromossômicas não Histona/imunologia , Células Precursoras de Linfócitos B/imunologia , Fatores de Transcrição/imunologia , Proteínas E2 de Adenovirus/genética , Proteínas E2 de Adenovirus/imunologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Diferenciação Celular/genética , Linhagem da Célula/imunologia , Cromatina/genética , Proteínas Cromossômicas não Histona/deficiência , Proteínas Cromossômicas não Histona/genética , DNA Helicases/deficiência , DNA Helicases/genética , DNA Helicases/imunologia , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Poli I-C/farmacologia , Células Precursoras de Linfócitos B/citologia , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/imunologia , Transdução de Sinais , Transativadores/genética , Transativadores/imunologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
20.
Biochem Biophys Res Commun ; 418(3): 512-7, 2012 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-22285184

RESUMO

The murine SWI/SNF-like BAF complex is an ATP-dependent chromatin remodeling complex that functions as a transcriptional regulator in cell proliferation, differentiation and development. The SWI/SNF-like BAF complex consists of several components including core subunits such as BRG1, BAF155/SRG3, BAF47/SNF5/INI1, and BAF170. We have previously shown that the interaction between SRG3/mBAF155 and other components of the complex stabilizes them by attenuating their proteasomal degradation. However, it has not been known how the major components of the SWI/SNF-like BAF complex such as BRG1, SNF5, and BAF60a are targeted for the ubiquitination and degradation, and how SRG3/mBAF155 protects them from the degradation process. Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Animais , Células COS , Chlorocebus aethiops , DNA Helicases/metabolismo , Estabilidade Enzimática , Humanos , Camundongos , Proteínas Nucleares/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose , Proteólise , Proteína SMARCB1 , Fatores de Transcrição/genética
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