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1.
Cancer Sci ; 115(1): 283-297, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37923364

RESUMO

Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. Moreover, these cells exhibited primary resistance to enzalutamide. Since AR signaling plays a significant role in the development of CRPC, PSA promoter sequences fused with GFP were introduced into AILNCaP14 cells to conduct GFP fluorescence-based chemical screening. We identified flavopiridol, a broad-spectrum CDK inhibitor, as a candidate drug that could repress AR transactivation of CRPC cells, presumably through the inhibition of phosphorylation of AR on the serine 81 residue (pARSer81 ). Importantly, this broad-spectrum CDK inhibitor inhibited the proliferation of AILNCaP14 cells both in vitro and in vivo. Moreover, a newly developed liver metastatic model using AILNCaP15 cells revealed that the compound attenuated tumor growth of CRPC harboring highly metastatic properties. Finally, we developed a patient-derived xenograft (PDX) model of CRPC and DCaP CR from a patient presenting therapeutic resistance to enzalutamide, abiraterone, and docetaxel. Flavopiridol successfully suppressed the tumor growth of CRPC in this PDX model. Since ARSer81 was found to be phosphorylated in clinical CRPC samples, our data suggested that broad-spectrum CDK inhibitors might be a potent candidate drug for the treatment of CRPC, including those exhibiting primary resistance to enzalutamide.


Assuntos
Benzamidas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antígeno Prostático Específico , Antagonistas de Androgênios/uso terapêutico , Androgênios , Resistencia a Medicamentos Antineoplásicos , Receptores Androgênicos/metabolismo , Nitrilas/uso terapêutico , Linhagem Celular Tumoral
2.
BMC Musculoskelet Disord ; 25(1): 430, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831297

RESUMO

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.


Assuntos
Marcha , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Marcha/fisiologia , Fatores de Tempo , Vértebras Cervicais/fisiopatologia , Vértebras Cervicais/lesões , Idoso , Medula Cervical/lesões , Medula Cervical/fisiopatologia , Adulto Jovem
3.
Knee Surg Sports Traumatol Arthrosc ; 32(2): 257-264, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38226718

RESUMO

PURPOSE: The aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all-inside device. METHODS: Eight Thiel-embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step-off (0: no step-off; 1: cross-sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all-inside repairs of the ramp lesions using all-inside devices were conducted. Dissection was performed to confirm the position of anchor fixation. RESULTS: As the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step-off grade decreased as the knee was extended, and the step-off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step-off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step-off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon. CONCLUSION: Suturing with an all-inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study. LEVEL OF EVIDENCE: Level IV.


Assuntos
Lesões do Ligamento Cruzado Anterior , Meniscos Tibiais , Humanos , Estudos Transversais , Meniscos Tibiais/cirurgia , Articulação do Joelho/cirurgia , Joelho , Cadáver , Lesões do Ligamento Cruzado Anterior/cirurgia
4.
BMC Bioinformatics ; 24(1): 135, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37020193

RESUMO

BACKGROUND: Population structure and cryptic relatedness between individuals (samples) are two major factors affecting false positives in genome-wide association studies (GWAS). In addition, population stratification and genetic relatedness in genomic selection in animal and plant breeding can affect prediction accuracy. The methods commonly used for solving these problems are principal component analysis (to adjust for population stratification) and marker-based kinship estimates (to correct for the confounding effects of genetic relatedness). Currently, many tools and software are available that analyze genetic variation among individuals to determine population structure and genetic relationships. However, none of these tools or pipelines perform such analyses in a single workflow and visualize all the various results in a single interactive web application. RESULTS: We developed PSReliP, a standalone, freely available pipeline for the analysis and visualization of population structure and relatedness between individuals in a user-specified genetic variant dataset. The analysis stage of PSReliP is responsible for executing all steps of data filtering and analysis and contains an ordered sequence of commands from PLINK, a whole-genome association analysis toolset, along with in-house shell scripts and Perl programs that support data pipelining. The visualization stage is provided by Shiny apps, an R-based interactive web application. In this study, we describe the characteristics and features of PSReliP and demonstrate how it can be applied to real genome-wide genetic variant data. CONCLUSIONS: The PSReliP pipeline allows users to quickly analyze genetic variants such as single nucleotide polymorphisms and small insertions or deletions at the genome level to estimate population structure and cryptic relatedness using PLINK software and to visualize the analysis results in interactive tables, plots, and charts using Shiny technology. The analysis and assessment of population stratification and genetic relatedness can aid in choosing an appropriate approach for the statistical analysis of GWAS data and predictions in genomic selection. The various outputs from PLINK can be used for further downstream analysis. The code and manual for PSReliP are available at https://github.com/solelena/PSReliP .


Assuntos
Estudo de Associação Genômica Ampla , Software , Animais , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Genoma , Fluxo de Trabalho
5.
Support Care Cancer ; 31(2): 115, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36640181

RESUMO

PURPOSE: Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety. METHODS: The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared. RESULTS: The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders. CONCLUSION: The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Gastrointestinais , Neoplasias Pulmonares , Humanos , Caquexia/tratamento farmacológico , Caquexia/etiologia , Estudos Retrospectivos , Força da Mão , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológico , Albuminas
6.
Surg Endosc ; 37(4): 2698-2705, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36443561

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. METHODS: This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30 min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50 kg were administered a 50 mg dose, while those weighing < 50 kg were administered a 25 mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. RESULTS: Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). CONCLUSIONS: The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP.


Assuntos
Diclofenaco , Pancreatite , Humanos , Diclofenaco/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Administração Retal , Estudos Retrospectivos , Pontuação de Propensão , Anti-Inflamatórios não Esteroides/uso terapêutico , Pancreatite/etiologia , Pancreatite/prevenção & controle , Pancreatite/tratamento farmacológico
7.
Surg Today ; 53(1): 135-144, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35780275

RESUMO

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tegafur , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Uracila , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
8.
Gan To Kagaku Ryoho ; 50(8): 913-915, 2023 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-37608420

RESUMO

A 67-year-old woman presented with a history of upper abdominal pain and weight loss. Physical examination revealed a lump in the right lower quadrant. She had undergone esophagogastroduodenoscopy at another hospital ten years ago, which showed a 15-mm elevated lesion in the duodenal bulb. The patient had not undergone further examinations or received treatment during the 10 years. Esophagogastroduodenoscopy conducted in our hospital revealed an enlarged tumor that was difficult to assess on the whole image. The tumor was diagnosed as a well-differentiated adenocarcinoma based on a biopsy specimen. Enhanced computed tomography revealed a hypervascular duodenal tumor with liver and lymph node metastases. The patient was treated with capecitabine plus oxaliplatin for the duodenal cancer. Lymph node metastases increased markedly after 2 courses of chemotherapy. The patient died 3 months after the initiation of chemotherapy. The natural history of sporadic non-ampullary duodenal epithelial tumors remains to be fully elucidated due to the low incidence rate. This case suggests that sporadic non-ampullary duodenal epithelial tumors have a biological potential for invasive malignancy.


Assuntos
Adenocarcinoma , Neoplasias Duodenais , Feminino , Humanos , Idoso , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/cirurgia , Metástase Linfática , Fígado , Duodeno
9.
Eur J Orthop Surg Traumatol ; 33(2): 435-440, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35092509

RESUMO

The Revelation Hip System is a cementless stem with a lateral flare concept. Stable fixation is achieved by fitting the stem to the medullary cavity of the proximal lateral femoral cortex. Patients who have undergone total hip arthroplasty using the Revelation Hip System show good postoperative clinical and radiographic outcomes. However, to the best of our knowledge, no study has reported the relationship between stem fitting and clinical or radiological outcomes after the surgery. In the present study, we investigated the relationship between stem fitting and clinical or radiological outcomes after total hip arthroplasty (THA) using the Revelation Hip System. In this study, 28 hips of 26 patients who were treated with the Revelation Hip System for osteoarthritis, osteonecrosis of the femoral head, rheumatoid arthritis, and rapidly destructive coxarthropathy and were followed up for > 5 y were enrolled. These patients were divided into two groups, including the rest fit group (11 hips, group R) and the control group (17 hips, group C), according to the results of the density mapping analysis. In group R, the lateral side of the stem fits on the medullary cavity of the proximal lateral femoral cortex, while in group C, the lateral side of the stem did not fit. Radiographic results showed no significant differences between the groups in terms of stem alignment, subsidence, and stress shielding around the cup. The incidence of stress shielding around the stem in zone 7 was not significant but tended to be higher in group R than in group C (p = 0.052). Clinical outcomes showed no significant differences between group R and group C in terms of the Harris hip score, the Japanese Orthopaedic Association (JOA) score, and the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) total score. However, pain complaints that were assessed by patient-reported outcomes using the 36-Item Short Form Health Survey (SF-36) bodily pain and vitality subscales and the JHEQ pain subscale were significantly higher in group R than in group C at the final follow-up. These results suggest that some patients had pain complaint even if the stems were inserted as per the concept after THA with the Revelation Hip System.Trial Registration911.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Prótese de Quadril/efeitos adversos , Seguimentos , Resultado do Tratamento , Cabeça do Fêmur , Dor , Desenho de Prótese , Estudos Retrospectivos
10.
Cancer Sci ; 113(1): 170-181, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34714577

RESUMO

The aryl hydrocarbon receptor (AHR) pathway modulates the immune system in response to kynurenine, an endogenous tryptophan metabolite. IDO1 and TDO2 catalyze kynurenine production, which promotes cancer progression by compromising host immunosurveillance. However, it is unclear whether the AHR activation regulates the malignant traits of cancer such as metastatic capability or cancer stemness. Here, we carried out systematic analyses of metabolites in patient-derived colorectal cancer spheroids and identified high levels of kynurenine and TDO2 that were positively associated with liver metastasis. In a mouse colon cancer model, TDO2 expression substantially enhanced liver metastasis, induced AHR-mediated PD-L1 transactivation, and dampened immune responses; these changes were all abolished by PD-L1 knockout. In patient-derived cancer spheroids, TDO2 or AHR activity was required for not only the expression of PD-L1, but also for cancer stem cell (CSC)-related characteristics and Wnt signaling. TDO2 was coexpressed with both PD-L1 and nuclear ß-catenin in colon xenograft tumors, and the coexpression of TDO2 and PD-L1 was observed in clinical colon cancer specimens. Thus, our data indicate that the activation of the TDO2-kynurenine-AHR pathway facilitates liver metastasis of colon cancer via PD-L1-mediated immune evasion and maintenance of stemness.


Assuntos
Antígeno B7-H1/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias do Colo/patologia , Dioxigenases/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Células-Tronco Neoplásicas/patologia , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Humanos , Cinurenina , Neoplasias Hepáticas/metabolismo , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Evasão Tumoral , Regulação para Cima , Via de Sinalização Wnt
11.
Biochem Biophys Res Commun ; 586: 93-99, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837838

RESUMO

Dysregulated activation of the WNT/ß-catenin signaling pathway is essential for the initiation and development of various cancers. E7386, a small-molecule compound, attenuates WNT signaling by blocking the interaction between ß-catenin and CREB-binding protein (CBP); hence, it is regarded as a therapeutic candidate for cancers with activated WNT signaling. In the present study, we evaluated the biological characteristics associated with E7386 sensitivity by using a panel of patient-derived colon cancer spheroids. An integrative approach that combined E7386 sensitivity and gene expression profiles revealed that the resistance of the cancer spheroids to E7386 was associated with the activation of the NF-κB pathway. NF-κB pathway inhibitors acted synergistically with E7386 to block proliferation and induce cell cycle arrest in E7386-resistant spheroids. These findings suggest a possibility that a combination of E7386 and NF-κB inhibition may effectively block the proliferation of a subset of colon cancer cells.


Assuntos
Proteína de Ligação a CREB/genética , NF-kappa B/genética , Fenilenodiaminas/farmacologia , Pirazinas/farmacologia , Esferoides Celulares/efeitos dos fármacos , Triazinas/farmacologia , beta Catenina/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Proteína de Ligação a CREB/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Cultura Primária de Células , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Via de Sinalização Wnt , beta Catenina/metabolismo
12.
J Infect Chemother ; 28(3): 413-419, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34973874

RESUMO

BACKGROUND: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis. METHODS: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020. RESULTS: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease. CONCLUSIONS: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis.


Assuntos
Colangite , Antibacterianos/uso terapêutico , Colangite/tratamento farmacológico , Colangite/epidemiologia , Hospitais , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
13.
Breed Sci ; 72(3): 257-266, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36408318

RESUMO

Wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) are widely cultivated temperate crops. In breeding programs with these crops in Japan, effective genomic-assisted selection was performed by selecting core marker sets from thousands of genome-wide amplicon sequencing markers. The core sets consist of 768 and 960 markers for barley and wheat, respectively. These markers are distributed evenly across the genomes and effectively detect widely distributed polymorphisms in the chromosomes. The core set utility was assessed using 1,032 barley and 1,798 wheat accessions across the country. Minor allele frequency and chromosomal distributions showed that the core sets could effectively capture polymorphisms across the entire genome, indicating that the core sets are applicable to highly-related advanced breeding materials. Using the core sets, we also assessed the trait value predictability. As observed via fivefold cross-validation, the prediction accuracies of six barley traits ranged from 0.56-0.74 and 0.62 on average, and the corresponding values for eight wheat traits ranged from 0.44-0.83 and 0.65 on average. These data indicate that the established core marker sets enable breeding processes to be accelerated in a cost-effective manner and provide a strong foundation for further research on genomic selection in crops.

14.
Plant Cell Physiol ; 61(12): 2087-2096, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539537

RESUMO

The Rice Core Collection of Japanese Landraces (JRC) consisting of 50 accessions was developed by the genebank at the National Agriculture and Food Research Organization (NARO) in 2008. As a Japanese landrace core collection, the JRC has been used for many research projects, including screening for different phenotypes and allele mining for target genes. To understand the genetic diversity of Japanese Landraces, we performed whole-genome resequencing of these 50 accessions and obtained a total of 2,145,095 single nucleotide polymorphism (SNPs) and 317,832 insertion-deletions (indels) by mapping against the Oryza sativa ssp. japonica Nipponbare genome. A JRC phylogenetic tree based on 1,394 representative SNPs showed that JRC accessions were divided into two major groups and one small group. We used the multiple genome browser, TASUKE+, to examine the haplotypes of flowering genes and detected new mutations in these genes. Finally, we performed genome-wide association studies (GWAS) for agronomical traits using the JRC and another core collection, the World Rice Core Collection (WRC), comprising 69 accessions also provided by the NARO genebank. In leaf blade width, a strong peak close to NAL1, a key gene for the regulation of leaf width, and, in heading date, a peak near HESO1 involved in flowering regulation were observed in GWAS using the JRC. They were also detected in GWAS using the combined JRC + WRC. Thus, JRC and JRC + WRC are suitable populations for GWAS of particular traits.


Assuntos
Variação Genética , Genoma de Planta/genética , Oryza/genética , Sequenciamento Completo do Genoma , Alelos , Estudo de Associação Genômica Ampla , Haplótipos , Japão , Fenótipo , Filogenia , Polimorfismo de Nucleotídeo Único/genética
15.
Spinal Cord ; 59(6): 626-634, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32782342

RESUMO

STUDY DESIGN: Retrospective epidemiological study. OBJECTIVES: Since the causes and incidences of traumatic spinal cord injury (TSCI) in each country change over time, up-to-date epidemiological studies are required for countermeasures against TSCI. However, no nationwide survey in Japan has been conducted for about 30 years. The purpose of this study was therefore to investigate the recent incidence and characteristics of TSCI in Japan. SETTING: Japan METHODS: Survey sheets were sent to all hospitals (emergency and acute care hospitals) that treated TSCI persons in Japan in 2018 and case notes were retrospectively reviewed. Frankel grade E cases were excluded from analysis. RESULTS: The response rate was 74.4% (2804 of 3771 hospitals). The estimated annual incidence of TSCI excluding Frankel E was 49 per million, with a median age of 70.0 years and individuals in their 70s as the largest age group. Male-to-female ratio was 3:1. Cervical cord injuries occurred in 88.1%. Frankel D was the most frequent grade (46.3%), followed by Frankel C (33.0%). The most frequent cause was fall on level surface (38.6%), followed by traffic accident (20.1%). The proportion of fall on level surface increased with age. TSCI due to sports was the most frequent cause in teenagers (43.2%). CONCLUSIONS: This nationwide survey in Japan showed that estimated incidence of TSCI, rate of cervical cord injury, and incomplete injury by falls appear to be increasing with the aging of the population.


Assuntos
Traumatismos da Medula Espinal , Acidentes por Quedas , Adolescente , Idoso , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Traumatismos da Medula Espinal/epidemiologia
16.
BMC Ophthalmol ; 20(1): 426, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097012

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a hereditary disease that causes neurofibromas generally, but it has been reported to sometimes be associated with various forms of blood vessel stenosis, occlusion and vascular abnormalities of unknown mechanism. However, a symptomatic case with simultaneous ophthalmic artery stenosis and internal carotid artery stenosis is an extremely rare pathogenesis in a child with NF1. In this report, we performed the diagnosis and observation using various imaging modalities for this rare pediatric case. CASE PRESENTATION: A 6-year-old girl diagnosed with NF1 presented with gradual visual loss in the right eye. Best corrected visual acuity (BCVA) was 20/40 OD and the intraocular pressure (IOP) was normal in both eyes. Retinal vascular abnormalities with tortuous vessels and optic disc pallor were observed in the right fundus. Widefield fluorescein angiography revealed multiple sites of neovascularization and a large non-perfusion area in the peripheral retina. Optical coherence tomography angiography showed retinal vascular abnormalities in the right eye and revealed differences in inner retinal thickness and blood flow signal between the left and right eyes. Laser speckle flowgraphy showed that chorioretinal blood flow was significantly decreased in the right eye. Cerebral angiography revealed the right ophthalmic artery was significantly narrowed throughout. In addition, Magnetic resonance angiography revealed that the right internal carotid artery was significantly narrowed in the ophthalmic segment. We diagnosed ophthalmic artery and internal carotid artery stenosis with retinal vascular abnormalities and ocular ischemic syndrome in NF1. Because IOP increased to 35 mmHg, due to neovascular glaucoma in addition to mild vitreous hemorrhage occurred, panretinal photocoagulation was performed after intravitreal bevacizumab injection. After treatments, IOP normalized, but BCVA decreased to 20/100 OD. Arterial spin labeling showed normal cerebral blood flow. The patient is currently being carefully monitored. CONCLUSIONS: We have described the diagnosis and treatment of ocular ischemic syndrome due to multiple arteries stenosis in a child with NF 1. Utilization of various imaging modalities was helpful in diagnosing the complicated pathogenesis. However, since direct intervention by neurosurgery is not possible in this case, it is expected that treatment will be extremely difficult in the future.


Assuntos
Estenose das Carótidas , Neurofibromatose 1 , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Criança , Feminino , Angiofluoresceinografia , Humanos , Isquemia , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Retina
17.
Spinal Cord ; 58(1): 53-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31462759

RESUMO

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To elucidate serial changes in dysphagia and elucidate the critical period for dysphagia following acute traumatic cervical spinal cord injury (CSCI). SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: We prospectively examined individuals with acute traumatic CSCI admitted within 2 weeks after injury. Severity of dysphagia was evaluated using both the dysphagia severity scale (DSS) and functional oral intake scale (FOIS) at 2 weeks, 1 month, 2 months, and 3 months after injury. Condition of oral intake before injury was assessed by history taking. American Spinal Injury Association (ASIA) impairment scale grade and motor scores were also assessed at the same timepoints, and the correlation between dysphagia and paresis was analyzed. RESULTS: Sixty-five individuals with CSCI were assessed consecutively for 3 months after injury. Swallowing function, evaluated using both the DSS and FOIS, was significantly decreased at 2 weeks after injury, but significantly improved thereafter. Significant correlations between severity of dysphagia (DSS and FOIS scores) and motor scores were found at 2 weeks after injury (rs = 0.66 and 0.61; p < 0.001 and p < 0.001, respectively), indicating that individuals with lower motor scores had more severe swallowing dysfunction. CONCLUSIONS: Dysphagia occurred immediately after injury, but gradually improved over time. Individuals with more severe paralysis had significantly more severe dysphagia. Special attention for dysphagia should be paid to individuals with severe paralysis in acute phase.


Assuntos
Medula Cervical/lesões , Transtornos de Deglutição/fisiopatologia , Progressão da Doença , Paralisia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Idoso , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paralisia/etiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/complicações
18.
Spinal Cord ; 58(11): 1158-1165, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32444638

RESUMO

STUDY DESIGN: Retrospective statistical analysis of database. OBJECTIVES: Prediction of the Spinal Cord Independence Measure version III Total Score (SCIM-TS) at 6 months after injury based on physical findings at 1 month after injury is an important index for rehabilitation approach in the recovery phase. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: The study participants were selected from patients with traumatic spinal cord injuries who were registered in the Japan Single Center Study for Spinal Cord Injury Data Base (JSSCI-DB) of the Japan Spinal Injuries Center specializing in spine and spinal cord injuries. Of the 534 participants registered with the JSSCI-DB between January 2012 and October 2018, we retrospectively extracted 137 participants for 6 months after injury, and these participants were included in this study. RESULTS: According to multiple regression analysis, SCIM-TS at 6 months after injury could be predicted based on only six variables, i.e., age at injury, three key muscles (C6 wrist extensors, C8 finger flexors, and L3 knee extensors), and two mobility assessments (WISCI and SCIM-item13) (Adjusted R-Squared: 0.83). These six independent variables were significant factors reflecting SCIM-TS at 6 months. CONCLUSIONS: In rehabilitation after traumatic spinal cord injuries, a simple and reliable prognostic model can help accurately predict the achievable activity of daily living competency to set a goal. In addition, if the procedure is simple, evaluation can be completed in a short period of time, and the physical burden on both treating staff and patients can be reduced.


Assuntos
Traumatismos da Medula Espinal , Atividades Cotidianas , Avaliação da Deficiência , Humanos , Japão , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos
19.
Spinal Cord ; 58(3): 284-289, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31619753

RESUMO

STUDY DESIGN: Retrospective chart audits. OBJECTIVE: To investigate the optimal timing at which permanent complete cervical spinal cord injury (CSCI) can be confirmed when evaluating paralysis caused by traumatic CSCI. SETTING: Department of Orthopedic Surgery, Spinal Injuries Center, Japan. METHODS: Two-hundred and three patients with CSCI that was classified with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A (AIS A) within 72 h of the initial diagnosis of traumatic CSCI were included in the present study. Neurological data from the time of the initial diagnosis to 1 year after the injury were extracted. The number of those with recovery from AIS A and changes of AIS in the recovery were examined. RESULTS: Thirty-five of 203 (17%) patients whose injuries were initially classified with an AIS A showed recovery from AIS A. Thirty-four of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. CONCLUSION: If CSCI patients with AIS A have not recovered by 8 weeks, the likelihood that they will recover from AIS A is marginal. However, this conversely means that we must consider the possibility that a patient with a traumatic CSCI classified with an AIS A may still show recovery from AIS A within the first 8 weeks after injury.


Assuntos
Medula Cervical/lesões , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
20.
Shokuhin Eiseigaku Zasshi ; 61(1): 41-46, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32336718

RESUMO

DNA from hair that has undergone retort pouch sterilization shows considerably more fragmentation. Assessing the extent of DNA fragmentation using a PCR assay could therefore be applied to infer the sterilization history of a contaminated food sample. Such assessments could make it possible to determine whether a food sample had been contaminated by hair during the production process. To determine the extent of retort pouch sterilization, primers specific for the detection of human DNA were designed to give an amplification product of approx 500 bp. Hair was subjected to retort sterilization as a model of contamination, and PCR was performed using the extracted DNA as a template and the primer set for determining retort pouch sterilization. The results showed that no DNA amplification occurred in retort pouch samples, whereas amplification was observed in samples that were unheated, heated in hot water, or heated in a microwave oven. The present method was thus able to specifically detect thermal decomposition of DNA from hair that had undergone retort sterilization, and will be useful for determining whether hair discovered in a retort pouch was responsible for contamination.


Assuntos
Contaminação de Alimentos/análise , Manipulação de Alimentos , Embalagem de Alimentos , Cabelo , Temperatura Alta , Humanos , Reação em Cadeia da Polimerase
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