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1.
Mod Rheumatol ; 33(5): 936-943, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36190743

RESUMEN

OBJECTIVES: Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. METHODS: Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. RESULTS: Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). CONCLUSIONS: RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.


Asunto(s)
Artritis Reumatoide , Bronquiectasia , Infecciones por Mycobacterium no Tuberculosas , Humanos , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Estudios Transversales , Micobacterias no Tuberculosas , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico por imagen , Factor Reumatoide , Bronquiectasia/complicaciones , Bronquiectasia/diagnóstico por imagen
2.
Acta Radiol ; 63(7): 909-913, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34098754

RESUMEN

BACKGROUND: Chest radiography (CR) is employed as the evaluation of pneumoconiosis; however, we sometimes encounter cases in which computed tomography (CT) is more effective in detecting subtle pathological changes or cases in which CR yields false-positive results. PURPOSE: To compare CR to CT in the diagnosis of early-stage pneumoconiosis. MATERIAL AND METHODS: CR and CT were performed for 132 workers with an occupational history of mining. We excluded 23 cases of arc-welder's lung. Five readers who were experienced chest radiologists or pulmonologists independently graded the pulmonary small opacities on CR of the remaining 109 cases. We then excluded 37 cases in which the CT data were not sufficient for grading. CT images of the remaining 72 cases were graded by the five readers. We also assessed the degree of pulmonary emphysema in those cases. RESULTS: The grade of profusion on CR (CR score) of all five readers was identical in only 5 of 109 cases (4.6%). The CR score coincided with that on CT in 40 of 72 cases (56%). The CT score was higher than that on CR in 13 cases (18%). On the other hand, the CT score was lower than that on CR in 19 cases (26%). The incidence of pulmonary emphysema was significantly higher in patients whose CR score was higher than their CT score. CONCLUSION: CT is more sensitive than CR in the evaluation of early-stage pneumoconiosis. In cases with emphysema, the CR score tends to be higher in comparison to that on CT.


Asunto(s)
Neumoconiosis , Enfisema Pulmonar , Polvo , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neumoconiosis/diagnóstico por imagen , Neumoconiosis/patología , Enfisema Pulmonar/diagnóstico por imagen , Radiografía Torácica , Tomografía Computarizada por Rayos X/métodos
3.
BMC Infect Dis ; 19(1): 684, 2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31375066

RESUMEN

BACKGROUND: Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis. CASE PRESENTATION: The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica. To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication. CONCLUSIONS: We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted.


Asunto(s)
Botrytis/patogenicidad , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/microbiología , Biopsia , Botrytis/genética , Proteínas Fúngicas/genética , Humanos , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/cirugía , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
4.
Bioorg Med Chem ; 26(13): 3763-3772, 2018 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-30017113

RESUMEN

Synthesis of several 1,5-Anhydro-d-fructose (1,5-AF) derivatives to evaluate inhibitory activities of the inflammasome was carried out. Recently, 1,5-AF reported to suppress the inflammasome, although with only low activity. We focused on the hydration of 2-keto form of 1,5-AF and speculated that this hydration was the cause of low activity. Therefore, we synthesized some 1,5-AF derivatives that would not be able to form the dimer conformation and can be expected to have high activity against inflammasome, and then evaluated their inhibitory activities with respect to the NLRP3 inflammasome by using mouse bone marrow-derived macrophages and human THP-1 cells. As a result, some synthesized 2-keto form compounds had much higher inhibitory activities with respect to the NLRP3 inflammasome than did 1,5-AF.


Asunto(s)
Fructosa/análogos & derivados , Inflamasomas/metabolismo , Animales , Células Cultivadas , Fructosa/síntesis química , Fructosa/farmacología , Humanos , Inflamasomas/efectos de los fármacos , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Relación Estructura-Actividad
5.
J Plant Res ; 131(2): 271-284, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29273862

RESUMEN

All fine root systems consist of individual fine roots. Individual roots have morphological, anatomical, and functional heterogeneity (heterorhizy). Heterorhizy plays crucial roles in plant ecosystems. However, in many species, the heterorhizy and fine root system architecture based on individual root units are unclear. This study investigated heterorhizy along the root system architecture of Vaccinium virgatum Ait (rabbiteye blueberry) softwood-cuttings (propagated from annual shoots in growing season) using protoxylem groups (PGs), a classification according to the number of protoxylem poles, as an indicator of individual root traits. Individual roots of rabbiteye blueberry varied from monarch to heptarch. The frequency of roots with larger number of PGs decreased but those with smaller number of PGs increased from adventitious roots toward lateral roots with different branching levels. This architecture were stable among cultivars, collecting position of the cuttings, or indole acetic acids treatment. Individual root sizes and secondary growth were positively correlated with the PGs. These results indicate that branching itself strongly and broadly controls individual root traits. The individual roots were classified into two types: monarch and diarch roots with small size and lacking secondary growth (thought to be hair roots in core Ericaceae) and triarch or more PG roots with large size and showing secondary growth. These heterogeneous individual roots responded differently to the experimental factors. In particular, elongation of the large roots significantly contributed to increased total root length. These results mean that heterorhizic plasticity is a determinant of root system development and heterorhizic variation exists even under practical cutting condition. In conclusion, we demonstrated heterorhizy of rabbieye blueberry cuttings based on the strong relationships of PG, individual root morphology and growth potential, and root system architecture. This study also supports strong connection between root morphology and functional roles intermediated by the PG.


Asunto(s)
Arándanos Azules (Planta)/anatomía & histología , Raíces de Plantas/anatomía & histología , Arándanos Azules (Planta)/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Xilema/clasificación
6.
Jpn J Clin Oncol ; 47(4): 350-356, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28158568

RESUMEN

BACKGROUND: Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. METHODS: To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). RESULTS: ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. CONCLUSIONS: The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised.


Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Pemetrexed/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Enfermedades Pulmonares Intersticiales/patología , Masculino , Mesotelioma/tratamiento farmacológico , Persona de Mediana Edad , Vigilancia de Productos Comercializados , Factores de Riesgo
7.
Mol Genet Genomics ; 291(1): 65-77, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26159870

RESUMEN

To characterize the structure and expression of a large multigene family of α/ß-gliadin genes, 90 individual α/ß-gliadin genes harboring a promoter region were identified in the wheat cultivar Chinese Spring. These genes were classified into eleven groups by phylogenetic analysis, and the chromosomes they were derived from were determined. Of these genes, 50 had the basic α/ß-gliadin domains and six conserved cysteine residues and 16, 16 and 18 of them were, respectively, located on chromosome 6A, 6B and 6D. Six genes had an additional cysteine residue, suggesting that these α/ß-gliadins acquired the property of binding other proteins through intermolecular disulphide bands. Expression of α/ß-gliadin genes in developing seeds was measured by quantitative RT-PCR using group-specific primers over 3 years. Expression patterns of these genes on the basis of accumulated temperature were similar among gene groups, whereas expression levels differed for the 3 years. The expression of most α/ß-gliadin and other prolamin genes was correlated with the sunshine duration. On the other hand, although all α/ß-gliadin genes had a common E-box within the -300 promoter region, some genes showed a particular expression pattern with respect to the sunshine duration, similarly to gene encoding high-molecular weight glutenin subunits and endosperm enzymes. These observations suggested that expression of each α/ß-gliadin gene is differentially regulated by multiple regulatory factors.


Asunto(s)
Gliadina/genética , Familia de Multigenes/genética , Triticum/genética , Secuencia de Aminoácidos , Cromosomas de las Plantas/genética , Endospermo/genética , Regulación de la Expresión Génica de las Plantas/genética , Genes de Plantas/genética , Glútenes/genética , Datos de Secuencia Molecular , Filogenia , Regiones Promotoras Genéticas/genética , Alineación de Secuencia
8.
Nihon Rinsho ; 74(10): 1634-1639, 2016 10.
Artículo en Japonés | MEDLINE | ID: mdl-30551273

RESUMEN

High-resolution computed tomography (HRCT) scan is a noninvasive technique that might be valuable for evaluating bronchial wall thickening and bronchiectasis as a result of chronic inflammation in patients with severe asthma. HRCT is also useful to diagnose the complications of asthma such as pulmonary emphysema and chronic eosinophilic pneumonia. In addition, HRCT will be able to demonstrate the tracheobronchial and parenchymal abnormality dis- tinctly, with the result that it will be helpful for making differential diagnosis in the patients with wheeze, including allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, bronchial tuberculosis and tracheal tumor.


Asunto(s)
Asma/diagnóstico por imagen , Humanos
9.
J AOAC Int ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38831620

RESUMEN

BACKGROUND: PCR-based genetic testing of agricultural products and foods is widely used for detecting various analytical targets such as genetically modified organisms and food allergens. However, it is difficult to obtain accurate genetic testing results from processed foods because DNA is fragmented by heat and pressure during food processing. Thus we previously developed an analytical method to quantitatively evaluate the degree of DNA fragmentation for the purpose of quality control of genetic testing for processed foods. OBJECTIVE: Our previous analytical method requires four PCR primer sets, resulting in high reagent costs and heavy analytical workloads. Therefore, we attempted to develop an easy-to-use test kit for quantifying the degree of DNA fragmentation and to evaluate its analytical performance. METHODS: To simplify the analysis procedure, we used only two primer sets. In addition, no-fragmentation control templates were prepared to obtain stable measurement results. The precision of the simplified analysis was evaluated through blind tests among laboratories. RESULTS: It was confirmed that plant species and extracted DNA concentrations had little effect on analysis with the newly developed test kit. In addition, the analytical values indicating the degree of DNA fragmentation exhibited small variability among laboratories. CONCLUSION: We confirmed the high practicality of the developed test kit. Because DNA fragmentation in cells is a universal phenomenon, we anticipate that the test kit will be used not only for quality control of genetic testing but also for food testing, medical diagnostics and other applications in a range of fields. HIGHLIGHTS: The newly developed test kit enables quantitative evaluation of the degree of DNA fragmentation in a simple manner.

10.
Radiology ; 266(3): 936-44, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23220902

RESUMEN

PURPOSE: To quantify observer agreement and analyze causes of disagreement in identifying honeycombing at chest computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this multiinstitutional HIPAA-compliant retrospective study, and informed patient consent was not required. Five core study members scored 80 CT images with a five-point scale (5 = definitely yes to 1 = definitely no) to establish a reference standard for the identification of honeycombing. Forty-three observers from various subspecialties and geographic regions scored the CT images by using the same scoring system. Weighted κ values of honeycombing scores compared with the reference standard were analyzed to investigate intergroup differences. Images were divided into four groups to allow analysis of imaging features of cases in which there was disagreement: agreement on the presence of honeycombing, agreement on the absence of honeycombing, disagreement on the presence of honeycombing, and other (none of the preceding three groups applied). RESULTS: Agreement of scores of honeycombing presence by 43 observers with the reference standard was moderate (Cohen weighted κ values: 0.40-0.58). There were no significant differences in κ values among groups defined by either subspecialty or geographic region (Tukey-Kramer test, P = .38 to >.99). In 29% of cases, there was disagreement on identification of honeycombing. These cases included honeycombing mixed with traction bronchiectasis, large cysts, and superimposed pulmonary emphysema. CONCLUSION: Identification of honeycombing at CT is subjective, and disagreement is largely caused by conditions that mimic honeycombing.


Asunto(s)
Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Fibrosis Pulmonar/diagnóstico por imagen , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
Genes Cells ; 16(7): 748-64, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21668587

RESUMEN

Terminal deoxynucleotidyltransferase (TdT) interacting factor 2 (TdIF2) is an acidic protein that binds to TdT. TdIF2 binds to DNA and core histones and contains an acidic-amino acid-rich region in its C-terminus. It has therefore been suggested to function as a histone chaperone within the nucleus. TdIF2 localized within the nucleolus in HEK 293T cells, and its N-terminal (residues 1-234) and C-terminal (residues 606-756) regions were crucial for the nucleolar localization. A chromatin immunoprecipitation (ChIP) assay showed that TdIF2 associated with the promoter of human ribosomal RNA genes (hrDNAP), and an in vitro luciferase assay system showed that it promoted hrDNAP activity. Using the yeast two-hybrid system with TdIF2 as the bait, we isolated the cDNA encoding HIV Tat interactive protein 60 (Tip60), which has histone acetyltransferase (HAT) activity, as a TdIF2-binding protein. TdIF2 bound to Tip60 in vitro and in vivo, inhibited the Tip60 HAT activity in vitro and co-localized with Tip60 within the nucleolus. In addition, TdIF2 promotes upstream binding factor (UBF) acetylation in vivo. Thus, TdIF2 might promote hrDNAP activity by suppressing Tip60's HAT activity and promoting UBF acetylation.


Asunto(s)
Proteínas Portadoras/metabolismo , Nucléolo Celular/metabolismo , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , ARN Ribosómico/genética , Animales , Proteínas Portadoras/química , Citoplasma/metabolismo , ADN Nucleotidilexotransferasa/metabolismo , Regulación hacia Abajo , Células HEK293 , Histona Acetiltransferasas/metabolismo , Humanos , Lisina Acetiltransferasa 5 , Proteínas Nucleares/química , Unión Proteica , Transporte de Proteínas , Proteínas de Unión al ARN , Alineación de Secuencia , Técnicas del Sistema de Dos Híbridos
13.
J Immunol ; 184(9): 4819-26, 2010 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20308631

RESUMEN

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19(Cre)/hVEGF-A(fl)) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses.


Asunto(s)
Linfocitos B/inmunología , Endotelio Linfático/inmunología , Ganglios Linfáticos/inmunología , Linfangiogénesis/inmunología , Factor A de Crecimiento Endotelial Vascular/fisiología , Vénulas/inmunología , Inmunidad Adaptativa/genética , Animales , Formación de Anticuerpos/genética , Antígenos CD19/biosíntesis , Antígenos CD19/genética , Linfocitos B/metabolismo , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Endotelio Linfático/metabolismo , Endotelio Linfático/patología , Humanos , Tolerancia Inmunológica/genética , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/fisiología , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Linfangiogénesis/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Ovalbúmina/administración & dosificación , Ovalbúmina/antagonistas & inhibidores , Ovalbúmina/inmunología , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genética , Vénulas/metabolismo , Vénulas/patología
14.
J Comput Assist Tomogr ; 36(5): 505-11, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22992597

RESUMEN

OBJECTIVES: To evaluate image quality of 320-detector row wide-volume (WV) computed tomography (CT) compared to 64-detector row helical CT from axial images and coronal multiplanar reformation (MPR). METHODS: Thirty-five patients with diffuse lung diseases were scanned using both 320-detector row WV CT (coneXact and volumeXact+) and 64-detector row helical protocols. Three blinded observers evaluated dislocation and heterogeneity of normal structures on 3 MPR patterns (WV scan with coneXact, WV scan with volumeXact+, and helical scan) using a 3-point scale from 1 (severe dislocation/heterogeneity) to 3 (no dislocation/heterogeneity). They also evaluated axial images of 2 scan patterns (WV with volumeXact+ and helical) using a 5-point scale from 1 (nondiagnostic) to 5 (excellent). Statistical analyses were performed with a post hoc test, Wilcoxon signed rank test, Mann-Whitney U test, or the Kendall W test. RESULTS: The WV scans with the coneXact algorithm had significantly lower quality scores than the WV scans with the volumeXact+ algorithm and the helical scans (P < 0.01) with MPR. Helical scans had significantly lower quality scores than the WV scans with volumeXact+ for heterogeneity on the mediastinal window setting with MPR (P < 0.01). There were no significant differences concerning total image quality of axial images between the WV scans with the volumeXact+ algorithm and the helical scans. CONCLUSIONS: The overall image quality of WV scans with the volumeXact+ algorithm was almost comparable to that of the helical scans on the lung window setting, but density homogeneity with helical scans was inferior to that of the WV scans with the volumeXact+ algorithm on the mediastinal window setting with MPR.


Asunto(s)
Enfermedades Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Interpretación de Imagen Radiográfica Asistida por Computador , Radiografía Torácica/métodos , Estadísticas no Paramétricas
15.
J AOAC Int ; 105(1): 159-166, 2022 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-34626115

RESUMEN

BACKGROUND: To provide the consumer with choices of genetically modified organisms (GMO) or non-GMO, official food labeling systems were established in many countries. Because the threshold GMO content values were set to distinguish between "non-GMO" and "GMO" designations, GMO content quantification methods are required for ensuring the appropriateness of labeling. OBJECTIVE: As the number of GMOs is continuously increasing around the world, we set out to develop a low-cost, simple and less biased analytical strategy to cover all necessary detection targets. METHODS: Digital PCR methods are advantageous compared to the conventional quantitative real-time PCR methods. We developed a digital PCR-based GMO quantification method to evaluate the GMO content in maize grains. To minimize the analytical workload, we adopted multiplex digital PCR targeting the 35S promoter and the nopaline synthase terminator, which are genetic elements commonly introduced in many GMOs. RESULTS: Our method is significantly simpler and more precise than the conventional real-time PCR-based methods. Additionally, we found that this method enables quantification of the copy number of GMO DNA without double counting multiple elements (35S promoter and nopaline synthase terminator) tandemly placed in a recombinant DNA construct. CONCLUSION: This is the first report on the development of a genetically modified maize quantification method using a multiplexed genetic element-specific digital PCR method. The tandem effect we report here is quite useful for reducing the bias in the analytical results. HIGHLIGHTS: Multiplexed genetic element-specific digital PCR can simplify weight-based GMO quantification and thus should prove useful in light of the continuous increase in the number of GM events.


Asunto(s)
Reacción en Cadena de la Polimerasa Multiplex , Zea mays , ADN , ADN de Plantas/genética , Plantas Modificadas Genéticamente/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Zea mays/genética
16.
Breast Cancer ; 28(3): 710-719, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33453015

RESUMEN

BACKGROUND: This study evaluated characteristics of patients treated with abemaciclib and diagnosed with interstitial lung disease (ILD), using 12-month post-marketing data from the real-world setting in Japan. METHODS: Spontaneous reports of adverse events in patients receiving abemaciclib were collected regularly from healthcare providers (HCPs) from November 30, 2018, to November 29, 2019. Detailed follow-up was requested on suspected ILD cases via questionnaires and/or interviews. Radiological images (when available) were reviewed by an ILD adjudication committee of specialists. The age distribution of patients prescribed abemaciclib in Japan was estimated based on insurance claims data. RESULTS: Of 4700 patients estimated to be exposed to abemaciclib, 82 cases of ILD were reported (46 serious, 13 fatal). Most (91%) had ≥ 1 symptom at diagnosis, commonly dyspnea/shortness of breath (59%), cough (44%), and/or fever (37%). The majority (68%) received steroid therapy (24 [56%] recovered/recovering; 5 [12%] not recovered; 13 [30%] deaths, 1 [2.3%] unknown). No specific imaging patterns or sites of predilection were identified, but a diffuse alveolar damage (DAD) pattern was observed at outcome in 3 of 4 evaluated fatal cases (16 in total evaluated). Features of fatal cases included advanced age, pre-existing interstitial change, and advanced Eastern Cooperative Oncology Group Performance Status. CONCLUSION: Advanced age and a DAD pattern were identified as potential risk factors for cases with poorer outcomes, as previously reported for drug-induced ILD. HCPs should consider the benefit-risk profile when prescribing abemaciclib, informing patients of risks and regularly monitoring treated patients to ensure early detection and treatment of ILD.


Asunto(s)
Aminopiridinas/efectos adversos , Antineoplásicos/efectos adversos , Bencimidazoles/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aminopiridinas/administración & dosificación , Antineoplásicos/administración & dosificación , Bencimidazoles/administración & dosificación , Femenino , Humanos , Japón/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/mortalidad , Persona de Mediana Edad , Vigilancia de Productos Comercializados , Tomografía Computarizada por Rayos X
17.
Eur J Radiol ; 142: 109866, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34365304

RESUMEN

PURPOSE: The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients. METHOD: The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed. RESULTS: Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814. CONCLUSIONS: Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Radiografía , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Capacidad Vital
18.
Asian J Endosc Surg ; 13(3): 279-286, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31691544

RESUMEN

INTRODUCTION: Laparoscopic surgery requiring longer operative times and artificial pneumoperitoneum may affect pulmonary function; its feasibility in patients with interstitial lung disease remains unknown. Therefore, we examined the feasibility of laparoscopic surgery in patients with interstitial lung disease. METHODS: We conducted a retrospective observational cohort study and examined the clinical data of patients with interstitial lung disease who had undergone abdominal surgery under general anesthesia. The primary end-point was the incidence of pulmonary complications. The secondary end-points were non-pulmonary complications and in-hospital mortality. RESULTS: Twenty-nine patients who had undergone abdominal surgery were diagnosed with interstitial lung disease after a review of their clinical and imaging records. Laparoscopic surgery and open surgery were performed in 11 and 18 patients, respectively. Acute exacerbation occurred in one (9%) patient in the laparoscopic group and three patients (17%) in the open group; all had undergone emergency surgery. Postoperative pneumonia did not occur in any patients. Non-pulmonary complications occurred in one patient (9%) in the laparoscopic group and two patients (11%) in the open group. One patient in each group died of acute exacerbation during hospitalization. CONCLUSION: Neither acute exacerbation nor pulmonary complications occurred after elective laparoscopic or open surgery in patients with interstitial lung disease. The risk of acute exacerbation after elective laparoscopic surgery may not be as high as that after elective thoracic surgery.


Asunto(s)
Laparoscopía , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/cirugía , Estudios Observacionales como Asunto , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos
19.
Br J Radiol ; 93(1115): 20200409, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32783627

RESUMEN

OBJECTIVE: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. METHODS: 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. RESULTS: ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. CONCLUSION: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. ADVANCES IN KNOWLEDGE: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.


Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Neoplasias/terapia , Neumonía/inducido químicamente , Neumonía/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Bronquiectasia/diagnóstico por imagen , Antígeno CTLA-4/antagonistas & inhibidores , Neumonía en Organización Criptogénica/inducido químicamente , Neumonía en Organización Criptogénica/diagnóstico por imagen , Femenino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Polisacáridos Bacterianos/sangre , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neumonitis por Radiación/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
20.
ERJ Open Res ; 6(4)2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33263023

RESUMEN

BACKGROUND: Chest computed tomography (CT) is commonly used to diagnose pneumonia in Japan, but its usability in terms of prognostic predictability is not obvious. We modified CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years) and A-DROP scores with CT information and evaluated their ability to predict mortality in community-acquired pneumonia patients. METHODS: This study was conducted using a prospective registry of the Adult Pneumonia Study Group - Japan. Of the 791 registry patients, 265 hospitalised patients with chest CT were evaluated. Chest CT-modified CURB-65 scores were developed with the first 30 study patients. The 30-day mortality predictability of CT-modified, chest radiography-modified and original CURB-65 scores were validated. RESULTS: In score development, infiltrates over four lobes and pleural effusion on CT added extra points to CURB-65 scores. The area under the curve for CT-modified CURB-65 scores was significantly higher than that of chest radiography-modified or original CURB-65 scores (both p<0.001). The optimal cut-off CT-modified CURB-65 score was ≥4 (positive-predictive value 80.8%; negative-predictive value 78.6%, for 30-day mortality). For sensitivity analyses, chest CT-modified A-DROP scores also demonstrated better prognostic value than did chest radiography-modified and original A-DROP scores. Poor physical status, chronic heart failure and multiple infiltration hampered chest radiography evaluation. CONCLUSION: Chest CT modification of CURB-65 or A-DROP scores improved the prognostic predictability relative to the unmodified scores. In particular, in patients with poor physical status or chronic heart failure, CT findings have a significant advantage. Therefore, CT can be used to enhance prognosis prediction.

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