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1.
J Ultrasound Med ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045018

RESUMO

OBJECTIVES: We performed preoperative ultrasonography (US) to detect the anatomic course of the superficial radial nerve (SRN) and dominant pathologic tendon of the first extensor compartment in de Quervain tenosynovitis. METHODS: We prospectively studied 27 patients (29 wrists) with de Quervain tenosynovitis who underwent surgical release of the first extensor compartment. Preoperatively, US was performed to evaluate the presence of the dominant pathologic tendon and the septum in the subcompartment, number of SRNs in the area of the surgical incision, and anatomic running course of the SRN. These variables were also checked intraoperatively. Cohen κ statistics were calculated to investigate agreement between US and surgical field findings. RESULTS: There were 7 men and 20 women (mean age, 47.8 years; range, 26-67 years). For the dominant pathologic tendon, there were 2 cases (6.9%) of an abductor pollicis longus, 11 cases (37.9%) of an extensor pollicis brevis, and 16 cases (55.2 %) of a nondominant tendon (κ = 0.94). For the subcompartment, there were 10 cases (34.5%) without a septum, 8 (27.6%) with an incomplete septum, and 11 (37.9%) with a complete septum (κ = 0.95). Most SRNs crossed over the first extensor compartment (κ = 0.78). CONCLUSIONS: Preoperative US can be useful in detecting the anatomic running course of the SRN and dominant pathologic tendon before surgery for de Quervain tenosynovitis. Classifying the anatomic course of the SRN could be essential to planning surgery, and it could be helpful to prevent injury of the SRN during surgery.

2.
Histopathology ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985086

RESUMO

AIMS: We sought to determine Non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole section images of 489 cases of lung adenocarcinoma from the Cancer Genome Atlas (TCGA). TCGA data were classified into 426 of TRU type adenocarcinoma, 49 of IMA, and 14 of unclassifiable. Their RNA sequencing data was analyzed by DESeq2 and WGCNA R packages. Gene expression in patients' samples were measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10, and so on was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2, and VSIGI was increased > 15 fold in IMA. Immunohistochemistry of ANXA10, TFF2, and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed their predominant expression in IMA while they are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa were increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help to understand the pathogenesis of IMA and find therapeutic targets.

3.
BMC Musculoskelet Disord ; 21(1): 40, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954406

RESUMO

BACKGROUND: The purpose of this study was to investigate residual rotation of patients with forearm amputation and the contribution of involved muscle to residual rotation. METHODS: Testing was performed using five fresh-frozen cadaveric specimens prepared by isolating muscles involved in forearm rotation. Amputation was implemented at 25 cm (wrist disarticulation), 18 cm, or 10 cm from the tip of olecranon. Supination and pronation in the amputation stump were simulated with traction of involved muscle (supinator, biceps brachii, pronator teres, pronator quadratus) using an electric actuator. The degree of rotation was examined at 30°, 60°, 90°, and 120° in flexion of elbow. RESULTS: Average rotation of 25 cm forearm stump was 148° (SD: 23.1). The rotation was decreased to 117.5° (SD: 26.6) at 18 cm forearm stump. It was further decreased to 63° (SD 31.5) at 10 cm forearm stump. Tendency of disorganized rotation was observed in close proximity of the amputation site to the elbow. Full residual pronation was achieved with traction of each pronator teres and pronator quadratus. Although traction of supinator could implement residual supination, the contribution of biceps brachii ranged from 4 to 88% according to the degree of flexion. CONCLUSIONS: Close proximity of the amputation site to the elbow decreased the residual rotation significantly compared to residual rotation of wrist disarticulation. The preservation of pronosupination was 80% at 18 cm forearm stump. Although the pronator teres and the pronator quadratus could make a full residual pronation separately, the supinator was essential to a residual supination.

4.
Structure ; 28(3): 355-362.e4, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-31995743

RESUMO

Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding of the structure of IFs is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6-Å resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handed coiled coil, with participating α helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents an atomic-resolution visualization of 2B-2B interactions important to filament assembly and provides insight into the defects introduced by mutations in IF genes associated with human skin diseases.

6.
PLoS One ; 14(11): e0224430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31743333

RESUMO

The prognostic significance of tumor-infiltrating lymphocytes has been determined in cancers of the lung, colon and breast, though there is no standardized method for using this prognostic indicator for lung cancer. We applied a modified version of the method proposed by the International Immuno-Oncology Biomarkers Working Group to primary lung adenocarcinoma, which uses histologic findings of hematoxylin and eosin sections. The study included a total cohort of 146 lung adenocarcinoma patients who underwent lobectomy with lymph node dissection at two hospitals between 2008 and 2012. The full-face sections of hematoxylin and eosin-stained slides were reviewed, and we evaluated the level of tumor-infiltrating lymphocytes as a percentage of the area occupied out of the total intra-tumoral stromal area. Histopathologic factors include histologic grade, necrosis, extracellular mucin, lymphovascular invasion, lymph node metastasis, level of tumor infiltrating lymphocytes, tertiary lymphoid structures around the tumor, and the presence of a germinal center in tertiary lymphoid structures. The high level of tumor-infiltrating lymphocytes was found to be significantly correlated with the histologic grade (p = 0.023), necrosis (p = 0.042), abundance of tertiary lymphoid structures(p<0.001) and presence of a germinal center in tertiary lymphoid structures (p = 0.004). A high level of tumor-infiltrating lymphocytes was associated with better progression-free survival (p = 0.011) as well as overall survival (p = 0.049). On multivariable analysis, high tumor-infiltrating lymphocyte levels were a good independent prognostic factor for progression-free survival (Hazard ratio: 0.389, 95% confidence interval: 0.161-0.941, p = 0.036). Histologic evaluation of tumor-infiltrating lymphocytes level in lung adenocarcinoma with H&E sections therefore has prognostic value in routine surgical pathology.

7.
Int Immunopharmacol ; 77: 105945, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31644962

RESUMO

Ginsenoside Rg3 is a steroidal saponin abundant in Korean red ginseng that has high anti-inflammatory activity. Rg3 exerts an immunomodulatory effect in acute inflammatory conditions such as bacterial infections. In this study, we determined the effect of Rg3 on bacterial uptake by macrophages and the related intracellular signaling pathways. Rg3 increased macrophage phagocytosis of IgG-opsonized Escherichia coli and IgG-opsonized beads (IgGbeads), but not of non-opsonized beads. Rg3 also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (p38 MAPK), but not that of Akt. The inclusion of IgGbeads in macrophage cultures also increased the phosphorylation of ERK1/2 and p38, but co-culture of macrophages with non-opsonized beads did not affect the phosphorylation of ERK1/2 and p38. The Rg3-induced promotion of phagocytosis was inhibited by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. PD98059 inhibited Rg3-induced p38 MAPK phosphorylation, but SB203580 did not suppress ERK1/2 phosphorylation. Culture of macrophages with Rg3 increased actin polymerization, and this effect was inhibited by SB203580 and PD98059. The Rg3-induced increase in phagocytosis was also inhibited by NSC23766, a Rac1 inhibitor and CASIN, a Cdc42 inhibitor. Intraperitoneal injection of Rg3 increased the phosphorylation of ERK1/2 and p38 as well as the phagocytosis of bacteria by lung cells. These results demonstrate that ginsenoside Rg3 enhances macrophage phagocytosis of bacteria by activating the ERK1/2 and p38 MAPK pathways.

8.
BMC Pulm Med ; 19(1): 151, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31474222

RESUMO

BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. CASE PRESENTATION: A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. CONCLUSIONS: We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.


Assuntos
Neoplasias Brônquicas/patologia , Neoplasias Brônquicas/cirurgia , Mielolipoma/patologia , Mielolipoma/cirurgia , Adulto , Broncoscopia , Humanos , Terapia a Laser/métodos , Masculino , Tomografia Computadorizada por Raios X
9.
Transplant Proc ; 51(8): 2611-2614, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474447

RESUMO

BACKGROUND: The clinical benefit of rabbit antithymocyte globulin (Thymoglobulin) compared with basiliximab for induction therapy in kidney transplant (KT) resulting from acute kidney injury (AKI) donors remains controversial. In cases of severe AKI, the degree of kidney injury is too great to reveal influence of different induction therapies on clinical outcomes. We aimed to compare clinical outcomes of Thymoglobulin and basiliximab induction therapy in KTs from deceased donors (DDs) with mild to moderate AKI. METHODS: We retrospectively studied 147 patients who received KTs from DDs between 2009 and 2017 in our center; 91 patients received kidneys from AKI donors. The AKI severity was classified based on the Acute Kidney Injury Network (AKIN) staging, and patients with AKIN stage 3 (43 patients) were excluded. Clinical outcomes were compared according to the type of induction therapy. RESULTS: Thymoglobulin and basiliximab induction groups showed no significant differences in demographic and baseline characteristics except donor age and follow-up period. The Thymoglobulin group had lower incidences of acute rejection and a trend toward a lower incidence of delayed graft function and better graft survival than the basiliximab group. There was no significant difference in BK infection rate; however, cytomegalovirus infection rate showed a trend toward a lower incidence in the basiliximab group. CONCLUSIONS: In cases of KT from AKIN stage 1 and 2 donors, Thymoglobulin showed better clinical outcomes than basiliximab, although it had a somewhat high rate of cytomegalovirus infection. It seems beneficial to use Thymoglobulin induction therapy in KTs from DDs with mild to moderate AKI.


Assuntos
Lesão Renal Aguda , Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Doadores de Tecidos , Lesão Renal Aguda/etiologia , Adulto , Basiliximab/uso terapêutico , Infecções por Citomegalovirus/epidemiologia , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Estudos Retrospectivos
10.
Front Oncol ; 9: 652, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396480

RESUMO

Autophagy is a highly conserved cellular process in which cytoplasmic materials are degraded and recycled as energy sources when nutrient supplies are lacking. Established tumor cells require autophagy for cell growth and tumor promotion. In particular, the survival of pancreatic tumor cells appears to be strongly dependent on autophagy, referred to as autophagy addiction. This dependency of pancreatic tumor cells on autophagy may be a candidate target for pancreatic tumor therapy. EI24 (etoposide-induced gene 2.4 kb; PIG8, p53-induced gene 8) acts as a tumor suppressor, inhibiting cell growth and inducing apoptosis in breast, cervical, and prostate cancer cells. However, recent papers have reported that EI24 is an essential component of the autophagy pathway. This newly discovered role of EI24 as a component of autophagy may act as a tumor promoter, which is contradictory to its known role as a tumor suppressor. We investigated the role of EI24 as a component of autophagy in pancreatic tumor cell proliferation. Here, we demonstrated that knockdown of EI24 using siRNA in pancreatic tumor cells led to impaired autophagy at a late step (increase in LC3-II and accumulation of p62 and autolysosomes). EI24 deficiency in pancreatic tumor cell lines inhibited cell proliferation. We confirmed that loss of EI24 inhibited pancreatic cell proliferation using the CRISPR-Cas9 system. However, loss of EI24 in other cell lines did not affect cell proliferation. Taken together, our results suggest that EI24 acts as a tumor promoter in pancreatic tumor cells, and studying the role of EI24 in reference to its cellular context may lead to a useful therapeutic target.

11.
Clin Epigenetics ; 11(1): 116, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405379

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a genetic and epigenetic disease. There is growing evidence to suggest that environmental factors due to epigenetic changes can be involved in the OSCC pathogenesis. Although tumor suppressor genes (TSGs) are commonly inactivated by promoter hypermethylation in human cancers, the epigenetic changes and the mechanism of TSGs in human OSCC remain unclear. We therefore assessed the methylation status of the TSGs, which are associated with epigenetic silencing in human cancers, OSCC cell lines, primary tumors, and normal oral mucosa. RESULTS: We used 14 TSGs that were originally identified in colon cancer to investigate the aberrant hypermethylation of these genes associated with transcriptional silencing in 10 OSCC cell lines. We found three TSGs, TFPI2, SOX17, and GATA4, that are robustly hypermethylated and are associated with transcriptional silencing in OSCC cell lines. The re-expression of the three genes was induced by 5-aza-2'-deoxycytidine (5-aza-dC) in cells in which these genes were not expressed or had a lack of expression. In 33 cases of primary OSCC tumors, promoter hypermethylation was detected for the TFPI2, SOX17, and GATA4 genes at (32/33) 97%, (22/33) 67%, and (11/33) 33%, respectively. Eleven normal oral mucosa samples showed no promoter hypermethylation for all three genes, which suggests that this promoter hypermethylation is cancer-specific. Bisulfite sequencing analysis confirmed the cancer-specific methylation of the TFPI2, SOX17, and GATA4 promoters in the OSCC cell lines and tumors but not in the normal oral mucosa samples. More importantly, the methylation status of TFPI2, GATA4, and SOX17 was significantly associated with OSCC patients' overall survival through TCGA DNA methylation database. CONCLUSIONS: We identified that TFPI2, SOX17, and GATA4 are frequently hypermethylated in human OSCC cells in a cancer-specific manner and that the transcriptional expression of these genes is regulated by promoter hypermethylation in OSCC. Our results highlight the great potential used as a synergistic biomarker set to improve the prognosis and therapeutic treatment for patients with OSCC.

12.
Am J Sports Med ; 47(11): 2596-2607, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386550

RESUMO

BACKGROUND: Artificial meniscal scaffolds are being developed to prevent development of osteoarthritis after meniscectomy. Previously, it was reported that 3-dimensional (3D) anatomic scaffolds loaded with connective tissue growth factor (CTGF) and transforming growth factor ß3 (TGF-ß3) achieved meniscal regeneration in an ovine model. This was a relatively short-term study (3 months postoperative), and outcome analyses did not include magnetic resonance imaging (MRI). PURPOSE: To evaluate long-term outcome of meniscal replacement with growth factor-laden poly-ε-caprolactone (PCL) scaffolds. STUDY DESIGN: Controlled laboratory study. METHODS: Anatomically shaped ovine meniscal scaffolds were fabricated from PCL with a 3D printer based on MRI data. Skeletally mature sheep (N = 34) were randomly allocated to 3 groups: scaffold without growth factor (0-µg group), scaffold with CTGF microspheres (µS) (5 µg) + TGF-ß3 µS (5 µg) (5-µg group), and scaffold with CTGF µS (10 µg) + TGF-ß3 µS (10 µg) (10-µg group). Unilateral medial meniscal replacement was performed. Animals were euthanized at 6 or 12 months. Regenerated meniscus, articular cartilage status, and synovial reaction were evaluated quantitatively with gross inspection, histology, and MRI. Kruskal-Wallis and Dunn tests were used to compare the 3 groups. RESULTS: Remnants of the PCL scaffold were evident in the 6-month specimens and were decreased but still present at 12 months in most animals. There were no significant differences among groups in gross inspection, histology, or MRI for either meniscal regeneration or articular cartilage protection. All experimental groups exhibited articular cartilage degeneration as compared with control (nonoperated). In terms of synovitis, there were no clear differences among groups, suggesting that growth factors did not increase inflammation and fibrosis. MRI revealed that meniscal extrusion was observed in most animals (82.7%). CONCLUSION: Previously, the combination of CTGF and TGF-ß3 was shown to stimulate mesenchymal stem cells into a fibrochondrocyte lineage. CTGF and TGF-ß3 did not aggravate synovitis, suggesting no adverse response to the combination of 3D-printed PCL scaffold combined with CTGF and TGF-ß3. Further work will be required to improve scaffold fixation to avoid meniscal extrusion. CLINICAL RELEVANCE: A significant advantage of this technique is the ability to print custom-fit scaffolds from MRI-generated templates. In addition, average-size menisci could be printed and available for off-the-shelf applications. Based on the 1-year duration of the study, the approach appears to be promising for meniscal regeneration in humans.

13.
Sci Rep ; 9(1): 9505, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31239451

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

14.
Medicine (Baltimore) ; 98(14): e14972, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946323

RESUMO

Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays are widely used for complementary or companion diagnostic purposes during treatment with immune checkpoint inhibitors. However, limited information is available on the clinical reliability of the PD-L1 IHC assay using small biopsy samples.Participants included 46 patients with nonsmall cell lung cancer who underwent PD-L1 testing using 3 PD-L1 IHC assays (22C3, SP142, and SP263) for both small biopsy samples and surgical specimens from November 2017 to June 2018. The PD-L1 IHC assay results were analyzed with cut-off values of 1%, 5%, 10%, and 50%. The PD-L1 IHC results obtained from the surgical specimens were regarded as the reference values.The 22C3, SP142, and SP263 PD-L1 IHC assays were performed in 26 (57%), 20 (43%), and 46 (100%) patients, respectively. Biopsy methods included radial probe endobronchial ultrasound using a guide sheath, endobronchial ultrasound-guided transbronchial needle aspiration, bronchoscopic biopsy, and percutaneous needle aspiration in 26 (57%), 4 (9%), 12 (25%), and 4 (9%) patients, respectively. The 22C3, SP142, and SP263 PD-L1 assays had concordance rates of 73-96, 65-80, and 72%-91%, respectively, compared with the reference values.PD-L1 testing with 3 commercial PD-L1 IHC assays using small biopsy samples is reliable in patients with nonsmall cell lung cancer.


Assuntos
Bioensaio/métodos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Idoso , Biópsia , Biópsia por Agulha/métodos , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Testes Imunológicos/instrumentação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Manejo de Espécimes/métodos
15.
Sci Rep ; 9(1): 4871, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890732

RESUMO

This study aimed to evaluate the incidence rates of and risk factors for complex regional pain syndrome type 1 (CRPS-1) after surgery for distal radius fractures (DRFs). Using data from January 2007 to December 2014, we analysed the data from the Korean Health Insurance Review and Assessment (HIRA) service. After extracting the data of patients aged ≥18 years whose diagnostic and operation codes for DRFs were entered into the HIRA database, we analysed the incidence rates of and risk factors for CRPS-1. From 2007 to 2014, 172,194 DRFs were treated surgically. Within 1 year postoperatively, 1,103 CRPS-1 cases were diagnosed, with an incidence of 0.64%. On univariate and multivariate analyses, the risk factors that significantly correlated with the incidence of CRPS-1 included female sex, rheumatoid arthritis, open reduction, open fracture, and accompanying ulnar fracture, whereas old age, psychiatric disease, and external fixation were not statistically significant. The incidence of CRPS-1 after surgery for DRF was very low (0.64%) in South Korea. Careful monitoring is necessary for patients with complex fractures and rheumatoid arthritis who are at increased risk of developing CRPS-1.

16.
J Pathol Transl Med ; 53(3): 153-158, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813707

RESUMO

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50-60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

18.
Sci Rep ; 9(1): 2680, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804379

RESUMO

Among the genetic variations in the monoamine oxidase A (MAOA) gene, upstream variable number tandem repeats (uVNTRs) of the promoter have been associated with individual differences in human physiology and aggressive behaviour. However, the evidence for a molecular or neural link between MAOA uVNTRs and aggression remains ambiguous. Additionally, the use of inconsistent promoter constructs in previous studies has added to the confusion. Therefore, it is necessary to demonstrate the genetic function of MAOA uVNTR and its effects on multiple aspects of aggression. Here, we identified three MAOA alleles in Koreans: the predominant 3.5R and 4.5R alleles, as well as the rare 2.5R allele. There was a minor difference in transcriptional efficiency between the 3.5R and 4.5R alleles, with the greatest value for the 2.5R allele, in contrast to existing research. Psychological indices of aggression did not differ among MAOA genotypes. However, our electroencephalogram and electrocardiogram results obtained under aggression-related stimulation revealed oscillatory changes as novel phenotypes that vary with the MAOA genotype. In particular, we observed prominent changes in frontal γ power and heart rate in 4.5R carriers of men. Our findings provide genetic insights into MAOA function and offer a neurobiological basis for various socio-emotional mechanisms in healthy individuals.

19.
Eur J Pharmacol ; 852: 125-133, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30797785

RESUMO

Stearoyl lysophosphatidylcholine (sLPC) has protective effects against several lethal sepsis models, even after induction of sepsis, which is associated with sLPC-mediated inhibition of high mobility group box 1 (HMGB1) release. This study investigated the mechanism by which sLPC inhibits lipopolysaccharide (LPS)-induced extracellular secretion of HMGB1 after the onset of sepsis. sLPC increased AMPK phosphorylation and the binding of AMPK to calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß), one of the upstream signals of AMPK. Inhibition of CaMKKß activity decreased sLPC-mediated inhibition of HMGB1 release, and sLPC increased the concentration of intracellular calcium. Blocking of the macrophage G protein-coupled receptor G2A (G2A) suppressed AMPK phosphorylation, suppressed increases in the intracellular levels of calcium, and prevented the inhibition of HMGB1 release by sLPC. In particular, when macrophages were incubated with sLPC even after LPS treatment, sLPC increased the phosphorylation of AMPK and the binding of CaMKKß and AMPK, and suppressed the secretion of HMGB1. In addition, sLPC administered 1 h before or 4 h after establishment of sepsis significantly diminished circulating HMGB1 levels in mice. sLPC inhibited LPS-induced extracellular release of HMGB1 through the activation of the G2A/calcium/CaMKKß/AMPK pathway. These findings suggest that sLPC may be a potential anti-inflammatory agent for acute inflammatory conditions such as sepsis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Espaço Extracelular/efeitos dos fármacos , Proteína HMGB1/metabolismo , Lisofosfatidilcolinas/farmacologia , Receptores CCR10/metabolismo , Animais , Espaço Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Lisofosfatidilcolinas/uso terapêutico , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
PLoS One ; 14(2): e0212672, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30807604

RESUMO

BACKGROUND: Radial probe endobronchial ultrasound using a guide sheath (EBUS-GS) is used to diagnose peripheral lung cancer. The aim was to identify the accuracy of molecular analysis that were performed with EBUS-GS specimens in patients with non-small cell lung cancer (NSCLC). METHOD: From December 2015 to September 2017, we retrospectively studied 91 patients with peripheral NSCLC who underwent surgery after EBUS-GS. Epidermal growth factor receptor (EGFR) mutational and anaplastic lymphoma kinase (ALK) translocation status obtained from surgical specimens served as the references. RESULTS: Compared to the reference data, EGFR mutational testing of EBUS-GS specimens was in 97% agreement, and the κ coefficient was 0.931 (P< 0.001). In addition, on ALK translocation testing, the results of all 91 patients were in agreement with the reference data (concordance rate of 100%, κ coefficient 1.000; P< 0.001). CONCLUSION: We found that EBUS-GS could be used for molecular diagnosis, such as EGFR mutational and ALK translocation status, in patients with peripheral NSCLC.


Assuntos
Quinase do Linfoma Anaplásico , Brônquios , Carcinoma Pulmonar de Células não Pequenas , Endossonografia , Neoplasias Pulmonares , Proteínas de Neoplasias , Idoso , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Biópsia , Brônquios/diagnóstico por imagem , Brônquios/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estudos Retrospectivos
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