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N-formyl methionine (fMet)-containing proteins are produced in bacteria, eukaryotic organelles mitochondria and plastids, and even in cytosol. However, Nα-terminally formylated proteins have been poorly characterized because of the lack of appropriate tools to detect fMet independently of downstream proximal sequences. Using a fMet-Gly-Ser-Gly-Cys peptide as an antigen, we generated a pan-fMet-specific rabbit polyclonal antibody called anti-fMet. The raised anti-fMet recognized universally and sequence context-independently Nt-formylated proteins in bacterial, yeast, and human cells as determined by a peptide spot array, dot blotting, and immunoblotting. We anticipate that the anti-fMet antibody will be broadly used to enable an understanding of the poorly explored functions and mechanisms of Nt-formylated proteins in various organisms.
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Anticuerpos , Especificidad de Anticuerpos , N-Formilmetionina , Proteínas , Animales , Humanos , Conejos , Anticuerpos/análisis , Anticuerpos/inmunología , Bacterias/química , Citosol/metabolismo , Sueros Inmunes/análisis , Sueros Inmunes/inmunología , Immunoblotting , Mitocondrias/metabolismo , N-Formilmetionina/análisis , N-Formilmetionina/inmunología , Proteínas/análisis , Proteínas/química , Proteínas/inmunología , Proteínas/metabolismo , Saccharomyces cerevisiae/químicaRESUMEN
BACKGROUND: Medical narcotics must be administered under medical supervision because of their potential for misuse and abuse, leading to more dangerous and addictive substances. The control of medical narcotics requires close monitoring to ensure that they remain safe and effective. This study proposes a methodology that can effectively identify the overprescription of medical narcotics in hospitals and patients. METHODS: Social network analysis (SNA) was applied to prescription networks for medical narcotics. Prescription data were obtained from the Narcotics Information Management System in South Korea, which contains all data on narcotic usage nationwide. Two-mode networks comprising hospitals and patients were constructed based on prescription data from 2019 to 2021 for the three most significant narcotics: appetite suppressants, zolpidem, and propofol. Two-mode networks were then converted into one-mode networks for hospitals. Network structures and characteristics were analyzed to identify hospitals suspected of overprescribing. RESULTS: The SNA identified hospitals that overprescribed medical narcotics. Patients suspected of experiencing narcotic addiction seek treatment in such hospitals. The structure of the network was different for the three narcotics. While appetite suppressants and propofol networks had a more centralized structure, zolpidem networks showed a less centralized but more fragmented structure. During the analysis, two types of hospitals caught our attention: one with a high degree, meaning that potential abusers have frequently visited the hospital, and the other with a high weighted degree, meaning that the hospital may overprescribe. For appetite suppressants, these two types of hospitals matched 84.6%, compared with 30.0% for propofol. In all three narcotics, clinics accounted for the largest share of the network. Patients using appetite suppressants were most likely to visit multiple locations, whereas those using zolpidem and propofol tended to form communities around their neighborhoods. CONCLUSIONS: The significance of this study lies in its analysis of nationwide narcotic use reports and the differences observed across different types of narcotics. The social network structure between hospitals and patients varies depending on the composition of the medical narcotics. Therefore, these characteristics should be considered when controlling medication with narcotics. The results of this study provide guidelines for controlling narcotic use in other countries.
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Análisis de Redes Sociales , República de Corea , Humanos , Narcóticos/uso terapéutico , Zolpidem/uso terapéutico , Propofol/uso terapéuticoRESUMEN
BACKGROUND: As the misuse and abuse of medical narcotics are increasing in South Korea, an information system for the integrated information management of medical narcotic drugs across the nation is needed. This paper presents the development process of the Narcotics Information Management System (NIMS) for the monitoring of medical narcotics usage and the results of its implementation. METHODS: As the NIMS enforces that all narcotics handlers digitally report all information on handling medical narcotic drugs, the functional requirements of the NIMS have been identified in accordance with the Narcotics Control Act. In addition to the functional requirements, the non-functional requirements of the NIMS have been elicited by major narcotics handlers and their associations. The non-functional requirements include privacy, availability, connectivity, interoperability, and data integrity. The system design with entity-relationship diagrams and its implementation processes have been presented. RESULTS: The NIMS encompasses all narcotic handlers, which comprise exporting, importing, and pharmaceutical companies; wholesalers; hospitals and clinics; and pharmacies, collecting over 120 million cases annually. It enables transparent monitoring throughout the life cycle, from manufacturing, sales, purchase, and disposal of narcotics. As a result, the number of prescriptions for medical narcotics has been reduced by 9.2%. CONCLUSIONS: To the best of our knowledge, the NIMS is the world's first system to manage all information on the total life cycle of medical narcotics, including imports, production, distribution, use, and disposal of drugs. This system has enabled the safety management and monitoring of medical narcotic drugs. Additionally, it provides consistent and transparent information to physicians and patients, leading to the autonomous safety management of narcotics. The successful development of the NIMS can provide guidelines for implementing a narcotics management system in other countries.
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Narcóticos , Farmacias , Humanos , Narcóticos/uso terapéutico , Prescripciones de Medicamentos , Gestión de la Información , República de CoreaRESUMEN
PURPOSE: To investigate the factors associated with the development of glaucoma in the healthy eyes of unilateral glaucoma patients. MATERIALS AND METHODS: This was a retrospective observational case series study. All participants had unilateral primary open-angle glaucoma at the initial visit and were divided into two groups: one in which the fellow eyes developed glaucoma during the follow-up period and one in which the fellow eyes remained healthy. A complete ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, intraocular pressure measurement, retinal nerve fiber layer and optic disk photographs, a 30-2 visual field test, and optical coherence tomography with angiography, was performed over a follow-up period of at least 3 years. RESULTS: A total of fifty-six patients were enrolled, and over the course of the study period, 11 patients developed glaucoma in the fellow eyes, while the fellow eyes of 45 patients remained healthy. At the baseline, the glaucomatous eye had a larger area of beta parapapillary atrophy, lower parapapillary choroidal vascular density (pCVD) within the area, and a lower prevalence of microvascular dropout than normal fellow eyes (P < 0.001, 0.013, 0.001, respectively). In the multivariate analysis, a reduced pCVD in the gamma parapapillary atrophy (γPPA) region was significantly associated with the development of glaucoma in normal eyes (odds ratio, 0.566; 95% CI, 0.342, 0.935; P = 0.026). CONCLUSIONS: The pCVD within the γPPA region at baseline is the risk factor for the development of glaucoma in the normal fellow eye of patients with unilateral glaucoma.
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Glaucoma de Ángulo Abierto , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/patología , Presión Intraocular , Campos Visuales , Tomografía de Coherencia Óptica/métodos , Microvasos/patología , Atrofia/patología , BiomarcadoresRESUMEN
PURPOSE: The study aims to investigate the role of the lipid mediator resolvin D1 (RvD1) in bacterial keratitis in a murine model. METHODS: The effect of RvD1 on Pseudomonas aeruginosa-stimulated human corneal epithelial cells (HCECs) and mouse macrophages and dendritic cells (DCs) was assessed. C57BL/6 mouse corneas were abraded and treated with RvD1 after stimulation with P. aeruginosa, following which cytokine production level in the cornea and drainage lymph nodes was compared with that in controls. Corneal opacity and thickness were assessed using anterior segment photographs, and optical coherence tomography and corneal infiltrates were analyzed using immunohistochemistry for neutrophils. RESULTS: RvD1 significantly inhibited pro-inflammatory cytokine production in HCECs, mouse macrophages, and DCs. Corneal opacity and corneal thickness were reduced, and the development of corneal infiltrates, specifically neutrophils, was also significantly inhibited by RvD1 in response to stimulation with P. aeruginosa. CONCLUSIONS: RvD1 inhibits P. aeruginosa-induced corneal inflammation. This finding supports a potential therapeutic approach for patients with bacterial keratitis.
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Lesiones de la Cornea , Opacidad de la Córnea , Infecciones Bacterianas del Ojo , Queratitis , Infecciones por Pseudomonas , Animales , Citocinas , Ácidos Docosahexaenoicos/farmacología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/prevención & control , Humanos , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Queratitis/prevención & control , Ratones , Ratones Endogámicos C57BL , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosaRESUMEN
INTRODUCTION: To evaluate the safety and efficacy of atelocollagen in preventing the fibrotic change of human tenon tissue induced by transforming growth factor ß1 (TGFß1) Methods: Primary cultured human Tenon's fibroblasts (HTFs) were incubated with TGFß1 alone, and with a various concentrations of atelocollagen respectively. Cell viability was measured by cell counting kit-8 (CCK8). The mRNA levels of α-smooth muscle actin (α-SMA), vimentin, fibronectin, zonular occludens scaffolding protein (ZO-1), cellular communication network factor 2 (CCN2) and interleukin-6 (IL-6) were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescence analysis. Wound healing assay and collagen contraction assay were additionally evaluated for identifying the inhibitory effect of atelocollagen in HTFs. To elucidate the mechanism by which atelocollagen affects HTFs proliferation, the phospho-extracellular-signal-regulated kinases (pERK)/total-extracellular-signal-regulated kinases (tERK), phospho-focal adhesion kinase (pFAK)/total-focal adhesion kinase (tFAK), and pSmad3/tSmad3 protein expression ratios were measured by Western blot. RESULTS: The safety of atelocollagen in HTF was identified by CCK8 analysis. The expression of α-SMA and vimentin in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased at both mRNA and protein levels, while that of ZO-1 in 0.046% atelocollagen increased compared with TGFß1-treated cells. The protein expression of fibronectin, CCN2, and IL-6 in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased. Immunofluorescence microscopy of α-SMA and ZO-1 showed results similar to those of the western blot. In the wound scratch assays, cell migration was significantly attenuated in HTFs treated with 0.005% atelocollagen. Atelocollagen at 0.005, 0.011, and 0.023% significantly inhibited the gel contraction induced by TGFß1 at both 24 h and 48 h. The increase in pERK/tERK and pSmad3/tSmad3 protein expression ratios in TGFß1-treated HTFs significantly decreased after treatment with 0.023 and 0.046% atelocollagen. CONCLUSION: Since atelocollagen gel effectively suppresses the proliferation of HTFs in TGFß1 - induced transdifferentiation, it may be a potential therapeutic agent in glaucoma surgery.
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PURPOSE: To develop a deep learning method to predict visual field (VF) from wide-angle swept-source optical coherence tomography (SS-OCT) and compare the performance of three Google Inception architectures. METHODS: Three deep learning models (with Inception-ResNet-v2, Inception-v3, and Inception-v4) were trained to predict 24-2 VF from the macular ganglion cell-inner plexiform layer and the peripapillary retinal nerve fibre layer map obtained by SS-OCT. The prediction performance of the three models was evaluated by using the root mean square error (RMSE) between the actual and predicted VF. The performance was also compared among different glaucoma severities and Garway-Heath sectorizations. RESULTS: The training dataset comprised images of 2220 eyes from 1120 subjects, and the test dataset was obtained from another 305 subjects (305 eyes). In all subjects, the global prediction errors (RMSEs) were 4.44 ± 2.09 dB, 4.78 ± 2.38 dB, and 4.85 ± 2.66 dB for the Inception-ResNet-v2, Inception-v3, and Inception-v4 architectures, respectively, and the prediction error of Inception-ResNet-v2 was significantly lower than the other two (P < 0.001). As glaucoma progressed, the prediction error of all three architectures significantly worsened to 6.59 dB, 7.33 dB, and 7.79 dB, respectively. In the analysis of sectors, the nasal sector had the lowest prediction error, followed by the superotemporal sector. CONCLUSIONS: Inception-ResNet-v2 achieved the best performance, and the global prediction error (RMSE) was 4.44 dB. As glaucoma progressed, the prediction error became larger. This method may help clinicians determine VF, particularly for patients who are unable to undergo a physical VF test.
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Aprendizaje Profundo , Tomografía de Coherencia Óptica , Algoritmos , Estudios Transversales , Humanos , Presión Intraocular , Fibras Nerviosas , Células Ganglionares de la Retina , Pruebas del Campo Visual , Campos VisualesRESUMEN
BACKGROUND: Distinguishing lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has a tremendous therapeutic implication. Sometimes, the commonly used immunohistochemistry (IHC) markers fail to discriminate between them, urging for the identification of new diagnostic biomarkers. METHODS: We performed IHC on tissue microarrays from two cohorts of lung cancer patients to analyse the expression of beta-arrestin-1, beta-arrestin-2 and clinically used diagnostic markers in ADC and SCC samples. Logistic regression models were applied for tumour subtype prediction. Parallel reaction monitoring (PRM)-based mass spectrometry was used to quantify beta-arrestin-1 in plasma from cancer patients and healthy donors. RESULTS: Beta-arrestin-1 expression was significantly higher in ADC versus SCC samples. Beta-arrestin-1 displayed high sensitivity, specificity and negative predictive value. Its usefulness in an IHC panel was also shown. Plasma beta-arrestin-1 levels were considerably higher in lung cancer patients than in healthy donors and were higher in patients who later experienced a progressive disease than in patients showing complete/partial response following EGFR inhibitor therapy. CONCLUSIONS: Our data identify beta-arrestin-1 as a diagnostic marker to differentiate ADC from SCC and indicate its potential as a plasma biomarker for non-invasive diagnosis of lung cancer. Its utility to predict response to EGFR inhibitors is yet to be confirmed.
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Adenocarcinoma del Pulmón/diagnóstico , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Regulación hacia Arriba , beta-Arrestina 1/metabolismo , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/metabolismo , Estudios de Casos y Controles , Diagnóstico Diferencial , Progresión de la Enfermedad , Detección Precoz del Cáncer , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Logísticos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/metabolismo , Valor Predictivo de las Pruebas , Análisis de Matrices Tisulares , beta-Arrestina 1/sangreRESUMEN
BACKGROUND: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction. METHODS: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed. RESULTS: A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively. CONCLUSIONS: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention.
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Anafilaxia , Hipersensibilidad a las Drogas , Epinefrina/administración & dosificación , Hipersensibilidad a los Alimentos , Adolescente , Adulto , Factores de Edad , Anciano , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Anafilaxia/etiología , Hipersensibilidad a las Drogas/complicaciones , Hipersensibilidad a las Drogas/tratamiento farmacológico , Hipersensibilidad a las Drogas/epidemiología , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Masculino , Sistemas de Registros Médicos Computarizados , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Síncope/tratamiento farmacológico , Síncope/epidemiología , Síncope/etiologíaRESUMEN
TodS is a sensor kinase that responds to various monoaromatic compounds, which either cause an agonistic or antagonistic effect on phosphorylation of its cognate response regulator TodT, and controls tod operon expression in Pseudomonas putida strains. We describe a molecular sensing mechanism of TodS that is activated in response to toluene. The crystal structures of the TodS Per-Arnt-Sim (PAS) 1 sensor domain (residues 43-164) and its complex with toluene (agonist) or 1,2,4-trimethylbenzene (antagonist) show a typical ß2α3ß3 PAS fold structure (residues 45-149), forming a hydrophobic ligand-binding site. A signal transfer region (residues 150-163) located immediately after the canonical PAS fold may be intrinsically flexible and disordered in both apo-PAS1 and antagonist-bound forms and dramatically adapt an α-helix upon toluene binding. This structural change in the signal transfer region is proposed to result in signal transmission to activate the TodS/TodT two-component signal transduction system. Site-directed mutagenesis and ß-galactosidase assays using a P. putida reporter strain system verified the essential residues involved in ligand sensing and signal transfer and suggest that the Phe(46) residue acts as a ligand-specific switch.
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Proteínas Bacterianas , Pliegue de Proteína , Proteínas Quinasas , Pseudomonas putida , Transducción de Señal/fisiología , Tolueno , Transactivadores , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Cristalografía por Rayos X , Operón , Proteínas Quinasas/química , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Pseudomonas putida/química , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Tolueno/química , Tolueno/metabolismo , Transactivadores/química , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Mannosylphosphorylated glycans are found only in fungi, including yeast, and the elimination of mannosylphosphates from glycans is a prerequisite for yeast glyco-engineering to produce human-compatible glycoproteins. In Saccharomyces cerevisiae, MNN4 and MNN6 genes are known to play roles in mannosylphosphorylation, but disruption of these genes does not completely remove the mannosylphosphates in N-glycans. This study was performed to find unknown key gene(s) involved in N-glycan mannosylphosphorylation in S. cerevisiae. For this purpose, each of one MNN4 and five MNN6 homologous genes were deleted from the och1Δmnn1Δmnn4Δmnn6Δ strain, which lacks yeast-specific hyper-mannosylation and the immunogenic α(1,3)-mannose structure. N-glycan profile analysis of cell wall mannoproteins and a secretory recombinant protein produced in mutants showed that the MNN14 gene, an MNN4 paralog with unknown function, is essential for N-glycan mannosylphosphorylation. Double disruption of MNN4 and MNN14 genes was enough to eliminate N-glycan mannosylphosphorylation. Our results suggest that the S. cerevisiae och1Δmnn1Δmnn4Δmnn14Δ strain, in which all yeast-specific N-glycan structures including mannosylphosphorylation are abolished, may have promise as a useful platform for glyco-engineering to produce therapeutic glycoproteins with human-compatible N-glycans.
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Manosa/metabolismo , Proteínas de la Membrana/genética , Ingeniería Metabólica , Polisacáridos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Pared Celular/metabolismo , Humanos , Manosa/química , Manosa/genética , Manosafosfatos/metabolismo , Manosiltransferasas/deficiencia , Manosiltransferasas/genética , Manosiltransferasas/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/metabolismo , Fosforilación , Proteínas Recombinantes , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
UNLABELLED: Tumor suppressor p53 has been suggested to be a host restriction factor against HIV-1 replication, but the detailed molecular mechanism has remained elusive for decades. Here, we demonstrate that p53-mediated HIV-1 suppression is attributed to double-stranded RNA (dsRNA)-dependent protein kinase (PKR)-mediated HIV-1 trans-activator (Tat) phosphorylation and inactivation. p53 silencing significantly enhanced HIV-1 replication in infected cells. Ectopic expression of p53 suppressed Tat activity, which was rescued by PKR silencing. In addition, ectopic expression of PKR abolished Tat activity in p53(-/-) and eIF2α(CA) cells. Finally, we found that HIV-1 infection activates p53, followed by the induction and activation of PKR. PKR directly interacted with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues (T23, T40, S46, S62, and S68), which inhibits Tat-mediated provirus transcription in three critical steps: (i) phosphorylation near the arginine-rich motif (ARM) inhibits Tat translocation into the nucleus, (ii) accumulation of Tat phosphorylation abolishes Tat-Tat-responsive region (TAR) binding, and (iii) Tat phosphorylation at T23 and/or T40 obliterates the Tat-cyclin T1 interaction. These five Ser/Thr sites on Tat were highly conserved in HIV-1 strains prevalent in Europe and the United States. Taken together, our findings indicate that p53-derived host restriction of HIV-1 replication is likely attributable, at least in part, to a noncanonical p53/PKR/Tat phosphorylation and inactivation pathway in HIV-1 infection and AIDS pathogenesis. IMPORTANCE: HIV-1-mediated disease progression to AIDS lasts for years to decades after primary infection. Host restriction and associated viral latency have been studied for several decades. p53 has been suggested as an important host restriction factor against HIV-1 replication. However, the detailed molecular mechanism is still unclear. In the present study, we found that the p53-mediated HIV-1 restriction is attributed to a p53/PKR/Tat-inactivation pathway. HIV-1 infection activated p53, which subsequently induced PKR expression and activation. PKR directly phosphorylated Tat exclusively at five specific Ser/Thr residues, which was accompanied by significant suppression of HIV-1 replication. Accumulation of Tat phosphorylation at these sites inhibited Tat function by blocking Tat nuclear localization, Tat binding to TAR, and Tat-cyclin T1 interaction. Our findings provide a better understanding of the p53-derived host restriction mechanism against HIV-1 replication in AIDS pathogenesis and may contribute to further research focusing on the investigation of potential therapeutic targets for HIV-1.
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Infecciones por VIH/inmunología , VIH-1/inmunología , Proteína p53 Supresora de Tumor/metabolismo , Replicación Viral/inmunología , eIF-2 Quinasa/metabolismo , Secuencia de Bases , Western Blotting , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Línea Celular , Técnicas de Silenciamiento del Gen , VIH-1/fisiología , Humanos , Inmunohistoquímica , Inmunoprecipitación , Datos de Secuencia Molecular , Fosforilación , Análisis de Secuencia de ADN , Espectrometría de Masas en Tándem , Transactivadores/metabolismo , Proteína p53 Supresora de Tumor/genética , Técnicas del Sistema de Dos HíbridosRESUMEN
OBJECTIVES: To identify the clinical significance of primary tumour thickness (TT) and its direction in patients with oral tongue squamous cell carcinoma (OTSCC), we measured TT in all axial/coronal/sagittal views on magnetic resonance imaging (MRI) and evaluated their meaning. METHODS: A total of 53 OTSCC patients were analysed who had undergone preoperative three-dimensional MRI and had been surgically treated. TT measured on axial (mediolateral direction), coronal (superoinferior direction), and sagittal (anteroposterior direction) views was compared to that in pathologic specimens. The association between TT on MRI and other pathologic parameters was also evaluated. RESULTS: TT on MRI in each plane showed relatively high concordance rates with the histological measurements. TT in all three planes was significantly correlated with lymph node (LN) metastasis. Occult LN metastasis was found in 15 of 39 (38.5%) patients, and the cutoff value of TT in axial/coronal/sagittal MRI predicting occult LN metastasis was 6.7 mm, 7.2 mm, and 12.3 mm, respectively. TT on MRI did not show any significant association with recurrence and survival. CONCLUSIONS: TT on MRI in all three planes showed relatively high coincidence with TT on histopathology and presented a potential cut-off value as a predictive indicator for occult LN metastasis. KEY POINTS: Three-dimensional measurement of tumour thickness (TT) is important for oral cancer treatment. Magnetic resonance imaging (MRI) is a useful diagnostic tool for oral cancer. TT on MRI has a high coincidence with TT on histopathology. TT on MRI is a predictive marker for occult lymph node metastasis.
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Carcinoma de Células Escamosas/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Lengua/patología , Adulto , Anciano , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Imagenología Tridimensional , Metástasis Linfática , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios/métodos , Radioterapia Adyuvante , Neoplasias de la Lengua/radioterapia , Neoplasias de la Lengua/cirugía , Resultado del Tratamiento , Carga TumoralRESUMEN
In this study, we characterized the CpxRA two-component signal transduction system of the rumen bacterium Mannheimia succiniciproducens. The truncated form of the CpxA sensor kinase protein without its transmembrane domain was able to autophosphorylate and transphosphorylate the CpxR response regulator protein in vitro. We identified 152 putative target genes for the Cpx system in M. succiniciproducens, which were differentially expressed by more than twofold upon overexpression of the CpxR protein. Genes of a putative 16-gene operon related to the cell wall and lipopolysaccharide biosynthesis were induced strongly upon CpxR overexpression. The promoter region of the first gene of this operon, wecC encoding UDP-N-acetyl-D-mannosaminuronate dehydrogenase, was analyzed and found to contain a sequence homologous to the CpxR box of Escherichia coli. An electrophoretic mobility shift assay showed that the phosphorylated CpxR proteins were able to bind specifically to PCR-amplified DNA fragments containing the promoter sequence of wecC. Furthermore, a cpxR-disrupted mutant strain exhibited increased envelope permeability compared with a wild-type strain. These results suggest that the Cpx system of M. succiniciproducens is involved in the maintenance of the integrity of the cell envelope.
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Proteínas Bacterianas/metabolismo , Pared Celular/metabolismo , Mannheimia/metabolismo , Proteínas Quinasas/metabolismo , Rumen/microbiología , Animales , Proteínas Bacterianas/genética , Bovinos , Pared Celular/genética , Regulación Bacteriana de la Expresión Génica , Mannheimia/enzimología , Mannheimia/genética , Proteínas Quinasas/genéticaRESUMEN
PURPOSE: The aim of this study was to evaluate the effect of serum clot activator, silica (SiO 2 ), which may be used for making autologous serum eye drops, on human corneal fibroblasts. METHODS: Cultured human corneal fibroblasts were exposed to 10%, 20%, and 30% silica for 1, 6, and 24 hours; methyl thiazolyl tetrazolium-based colorimetric assay was performed to determine the survival rate of fibroblasts and lactate dehydrogenase leakage assay to assess the cytotoxicity. The apoptotic response was evaluated by flow cytometric analysis and fluorescence staining with Annexin V and propidium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. RESULTS: The survival rate of human corneal fibroblasts and cytotoxicity showed both dose-dependent and time-dependent responses. The fluorescent micrograph and flow cytometry showed that as the exposure time increased, more cells underwent apoptosis or necrosis after treatment with 30% silica. When observed with light and electron microscopy, the number of corneal fibroblasts decreased and they were more detached from the dish. In addition, damaged corneal fibroblasts showed degenerative changes after exposure to 30% silica. CONCLUSIONS: Silica showed dose-dependent and time-dependent toxicity in human corneal fibroblasts. It is safer to keep the blood in tubes without a clot activator when manufacturing autologous serum eye drops to prevent possible corneal cytotoxicity.
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Apoptosis , Córnea , Humanos , Soluciones Oftálmicas/farmacología , Células Cultivadas , Fibroblastos , Supervivencia CelularRESUMEN
[This corrects the article DOI: 10.1007/s11571-021-09728-4.].
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Young immature granule cells (imGCs) appear via adult neurogenesis in the hippocampal dentate gyrus (DG). In comparison to mature GCs (mGCs) (born during development), the imGCs exhibit two competing distinct properties such as high excitability (increasing activation degree) and low excitatory innervation (reducing activation degree). We develop a spiking neural network for the DG, incorporating both the mGCs and the imGCs. The mGCs are well known to perform "pattern separation" (i.e., a process of transforming similar input patterns into less similar output patterns) to facilitate pattern storage in the hippocampal CA3. In this paper, we investigate the effect of the young imGCs on pattern separation of the mGCs. The pattern separation efficacy (PSE) of the mGCs is found to vary through competition between high excitability and low excitatory innervation of the imGCs. Their PSE becomes enhanced (worsened) when the effect of high excitability is higher (lower) than the effect of low excitatory innervation. In contrast to the mGCs, the imGCs are found to perform "pattern integration" (i.e., making association between dissimilar patterns). Finally, we speculate that memory resolution in the hippocampal CA3 might be optimally maximized via mixed cooperative encoding through pattern separation and pattern integration.
RESUMEN
PURPOSE: The aim of this study is to investigate changes in intraocular pressure (IOP) and anterior-segment parameters before and after cataract surgery, vitrectomy, and combined surgery. METHODS: The records of patients who had undergone cataract surgery (cataract group), vitrectomy (vitrectomy group), or combined cataract surgery and vitrectomy (combined group) at our hospital were retrospectively examined. The vitrectomy group consisted of pseudophakic eyes. IOP and anterior-segment measurements, including anterior chamber depth (ACD), angle opening distance (AOD), trabecular-iris angle (TIA), and trabecular-iris space area (TISA), were measured using swept-source anterior-segment optical coherence tomography before and 6 months after surgery in 41, 15, and 40 eyes, respectively. RESULTS: In the cataract and combined groups, there was a decrease in IOP (cataract group: from 15.8 to 13.4 mmHg, p <0.001; combined group: from 15.8 to 14.2 mmHg, p = 0.002) and an increase in the central corneal thickness after surgery (p <0.001). The ACD increased in all groups, with a smaller increase in the vitrectomy group (p <0.03). Postoperative AOD, TIA, and TISA were significantly increased in the cataract and combined groups (p <0.02). Higher preoperative IOP and larger IOP reduction after surgery were correlated with smaller preoperative AOD, TISA, and TIA in cataract and combined groups (p <0.034). A small preoperative ACD was related to smaller preoperative AOD, TISA, TIA (r > 0.649, p <0.001), and postoperative IOP reduction in the cataract and combined groups (r = 0.377, p = 0.018 and r = 0.559, p = 0.001, respectively). CONCLUSIONS: Compared to the vitrectomy group, the cataract and combined groups showed reduced postoperative IOP and increased AOD, TISA, and TIA. In these two groups, patients with shallower preoperative ACDs showed greater changes in IOP after surgery. Changes in IOP after surgery are thought to be related to changes in the anterior segment caused by the removal of the crystalline lens.
Asunto(s)
Catarata , Oftalmopatías , Cristalino , Humanos , Presión Intraocular , Estudios Retrospectivos , Vitrectomía , Cámara Anterior/diagnóstico por imagen , Catarata/diagnóstico , Tomografía de Coherencia Óptica/métodosRESUMEN
Supracolloidal chains consisting of nano- or micro-scale particles exhibit anisotropic properties not observed in individual particles. The orientation of the chains is necessary to manifest such characteristics on a macroscopic scale. In this study, we demonstrate the orientation of supracolloidal chains composed of nano-scale micelles of a diblock copolymer through spin-coating. We observed separate chains coated on a substrate with electron microscopy, and analyzed the orientation and stretching of the chains quantitatively with image analysis software. In drop-casting, the chains were coated randomly with no preferred orientation, and the degree of stretching exhibited an intrinsic semi-flexible nature. In contrast, spin-coated chains were aligned in the radial direction, and the apparent persistence length of the chain increased, confirming the stretching of the chain quantitatively. Furthermore, by incorporating fluorophores into supracolloidal chains and confirming the oriented chains with confocal fluorescence microscopy, it is demonstrated that oriented chains can be utilized as a template to align functional materials.
RESUMEN
PURPOSE: This study compared the anti-pseudomonal effects between nephrite-impregnated contact lenses (CLs) and conventional and cosmetic CLs. METHODS: After inoculation with Pseudomonas aeruginosa (P.aeruginosa), we counted the number of bacteria on the CL surface and observed each surface using atomic force microscopy (AFM) and scanning electron microscopy (SEM). To estimate potential harm of nephrite-impregnated CLs, we conducted a safety test using a rabbit model, treated with all CL types. RESULTS: Both conventional and cosmetic CLs (n = 258 ± 2.9 × 104, 368 ± 2.2 × 104) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation (n = 134 ± 0.8 × 104, 238 ± 2.5 × 104, p < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite-impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved. CONCLUSIONS: Nephrite may be used as a next-generation substance to reduce infectious keratitis caused by P. aeruginosa when added to CLs.