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INTRODUCTION/AIMS: Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS. METHODS: Patients with ALS and age-matched healthy controls were enrolled. We used a proximal reference (pref) in addition to the conventional distal reference (dref). Routine CMAP was recorded from the belly-dref lead and FFP-CMAP from the dref-pref lead for the ulnar and tibial nerves. Multiple point stimulation motor unit number estimation (MUNE) was also examined in the ulnar nerve. Inter-rater reproducibility was evaluated by two examiners, and some patients were followed up every 3 mo for 1 y. RESULTS: We tested 17 patients with ALS and 10 controls. The amplitudes of routine CMAP and FFP-CMAP in the ulnar and tibial nerves, and hypothenar MUNE value in the ulnar nerve were significantly decreased in ALS compared to controls. Ulnar FFP-CMAP achieved the highest inter-rater intraclass correlation coefficient (ICC) value (0.942) when compared with routine CMAP (0.880) and MUNE (0.839). The tibial FFP-CMAP had a higher ICC value (0.986) than the routine CMAP (0.697). In this way, the FFP-CMAP showed high inter-rater reproducibility because its shape was not much influenced by the electrode position. During 1-y follow-up, decline of CMAP, FFP, and MUNE showed significant correlations with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). DISCUSSION: The FFP-CMAP shows promise as a reliable marker for ALS.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Neurônios Motores/fisiologia , Potenciais de Ação/fisiologia , Músculo Esquelético/fisiologia , Reprodutibilidade dos TestesRESUMO
INTRODUCTION/AIMS: In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. METHODS: This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. RESULTS: Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. DISCUSSION: Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.
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Miosite de Corpos de Inclusão , Miosite , Humanos , Miosite/diagnóstico por imagem , Miosite/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/diagnóstico por imagem , Miosite de Corpos de Inclusão/patologia , Ultrassonografia , Força MuscularRESUMO
Published studies describing outcomes for cats with nasal lymphoma (NLSA) receiving first-line palliative radiation (PRT) versus PRT after chemotherapy failure are currently lacking. The aims of this retrospective observational study were to compare outcomes for cats with NLSA that were treated with these two methods. A total of 48 cats were included in analyses; 32 receiving PRT alone and 16 receiving PRT after chemotherapy failure. The treatment response, progression-free survival (PFS), disease-specific survival (DSS), overall survival (OS), and incidence rate of systemic disease were compared between the two groups. The overall response rate (ORR) was calculated from the same target lesions between pre-RT (within a week before starting PRT) and post-RT (on date of PRT completion) by computed tomography (CT) imaging. The ORR was 94% in cats that received PRT alone, 13 had a complete response (CR) and 17 had a partial response (PR). The ORR was 88% in cats that received PRT after chemotherapy failure, with five having CR and nine with PR. There were no significant differences in the ORR between the two groups. The PFS, DSS, and OS significantly increased in the cats that received PRT alone compared to the cats that received PRT after chemotherapy failure (median PFS: 336 vs 228 days, P = 0.0012, median DSS: 360 vs 242 days, P = 0.0025, median OS: 346 vs 242 days, P = 0.0036, respectively). The incidence rate of systemic disease significantly increased in 75% (12/16) of cats receiving PRT after chemotherapy failure compared to 41% (13/32) of cats receiving PRT alone. The results suggested that clinical outcomes may improve in cats with NLSA with first-line PRT compared to PRT after chemotherapy failure.
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Doenças do Gato , Linfoma , Neoplasias Nasais , Animais , Doenças do Gato/tratamento farmacológico , Doenças do Gato/radioterapia , Gatos , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Linfoma/veterinária , Nariz , Neoplasias Nasais/diagnóstico por imagem , Neoplasias Nasais/tratamento farmacológico , Neoplasias Nasais/radioterapia , Neoplasias Nasais/veterinária , Estudos RetrospectivosRESUMO
Age-related sarcopenia is associated with a variety of changes in skeletal muscle. These changes are interrelated with each other and associated with systemic metabolism, the details of which, however, are largely unknown. Eicosapentaenoic acid (EPA) is a promising nutrient against sarcopenia and has multifaceted effects on systemic metabolism. In this study, we hypothesized that the aging process in skeletal muscle can be intervened by the administration of EPA. Seventy-five-week-old male mice were assigned to groups fed an EPA-deprived diet (EPA-) or an EPA-enriched diet with 1 wt% EPA (EPA+) for 12 wk. Twenty-four-week-old male mice fed with normal chow were also analyzed. At baseline, the grip strength of the aging mice was lower than that of the young mice. After 12 wk, EPA+ showed similar muscle mass but increased grip strength compared with EPA-. EPA+ displayed higher insulin sensitivity than EPA-. Immunohistochemistry and gene expression analysis of myosin heavy chains (MyHCs) revealed fast-to-slow fiber type transition in aging muscle, which was partially inhibited by EPA. RNA sequencing (RNA-Seq) analysis suggested that EPA supplementation exerts pathway-specific effects in skeletal muscle including the signatures of slow-to-fast fiber type transition. In conclusion, we revealed that aging skeletal muscle in male mice shows lower grip strength and fiber type changes, both of which can be inhibited by EPA supplementation irrespective of muscle mass alteration.NEW & NOTEWORTHY This study demonstrated that the early phenotype of skeletal muscle in aging male mice is characterized by muscle weakness with fast-to-slow fiber type transition, which could be ameliorated by feeding with EPA-enriched diet. EPA induced metabolic changes such as an increase in systemic insulin sensitivity and altered muscle transcriptome in the aging mice. These changes may be related to the fiber type transition and influence muscle quality.
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Envelhecimento , Ácido Eicosapentaenoico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Proteínas Musculares/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Proteínas Musculares/genéticaRESUMO
Skeletal muscle functions as a locomotory system and maintains whole-body metabolism. Sex differences in such skeletal muscle morphology and function have been documented; however, their underlying mechanisms remain elusive. Glucocorticoids are adrenocortical hormones maintaining homeostasis, including regulating whole-body energy metabolism in addition to stress response. In skeletal muscle, glucocorticoids can reduce the synthesis of muscle proteins and simultaneously accelerate the breakdown of proteins to regulate skeletal muscle mass and energy metabolism via a transcription factor glucocorticoid receptor (GR). We herein evaluated the related contributions of the GR to sex differences of gene expression profiles in skeletal muscle using GR-floxed (GRf/f) and skeletal muscle-specific GR knockout (GRmKO) mice. There were no differences in GR mRNA and protein expression levels in gastrocnemius muscle between males and females. A DNA microarray analysis using gastrocnemius muscle from GRf/f and GRmKO mice revealed that, although most gene expression levels were identical in both sexes, genes related to cholesterol and apolipoprotein synthesis and fatty acid biosynthesis and the immunological system were predominantly expressed in males and females, respectively, in GRf/f but not in GRmKO mice. Moreover, many genes were up-regulated in response to starvation in GRf/f but not in GRmKO mice, many of which were sex-independent and functioned to maintain homeostasis, while genes that showed sex dominance related to a variety of functions. Although the genes expressed in skeletal muscle may be predominantly sex-independent, sex-dominant genes may relate to sex differences in energy metabolism and the immune system and could be controlled by the GR.
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Metabolismo Energético/genética , Músculo Esquelético/metabolismo , Receptores de Glucocorticoides/metabolismo , Caracteres Sexuais , Transcriptoma , Animais , Feminino , Expressão Gênica/genética , Masculino , Camundongos , Camundongos Knockout , Análise em MicrossériesRESUMO
Glucocorticoids play a critical role in the regulation of homeostasis, including metabolism. In patients with Cushing's syndrome, chronic glucocorticoid excess disrupts physiological internal milieu, resulting in central obesity, muscle atrophy, fatty liver, and insulin resistance. However, the relationship among various metabolic effects of glucocorticoids remains unknown. In the present study, we studied a male mouse model of Cushing's syndrome and indicated that glucocorticoid excess alters metabolic phenotype and body composition involving possible communication among skeletal muscle, liver, and adipose tissue.
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Tecido Adiposo/metabolismo , Composição Corporal , Síndrome de Cushing/metabolismo , Fígado/metabolismo , Músculos Paraespinais/metabolismo , Adipócitos Brancos/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/patologia , Corticosteroides/toxicidade , Alanina/metabolismo , Alanina Transaminase/metabolismo , Animais , Glicemia/metabolismo , Corticosterona/toxicidade , Síndrome de Cushing/patologia , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Glucocorticoides/metabolismo , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Camundongos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Triglicerídeos/metabolismo , Microtomografia por Raio-XRESUMO
In humans, contrast-enhanced CT (CECT) has been used to indirectly assess the antiangiogenic effects demonstrated by a number of tyrosine kinase inhibitors. This retrospective, cross-sectional study aimed to quantitatively evaluate changes in tumor contrast-enhancement (CE) using CECT in solid tumor-bearing dogs treated with toceranib phosphate (TOC). The changes in tumor size and CE were measured using the Hounsfield unit (HU) scale in CECT images before TOC treatment and between 30 and 90 days after initiating the treatment. Among the 36 dogs treated with TOC, eight (22.2%) showed a partial response, 22 (61.1%) showed stable disease, and six (16.7%) showed progressive disease. Thirty (83.3%) of 36 dogs showed a decrease in tumor CE (median: -20%, range: -1% to -48%) after initiating the treatment. The results indicated that tumor CE and size changes were observed in tumor-bearing dogs that were treated with TOC; however, tumor CE was not significantly correlated with tumor regression. We suggest that these results could serve as pilot data to evaluate the antiangiogenic effects associated with TOC.
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Doenças do Cão/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias/veterinária , Pirróis/uso terapêutico , Tomografia Computadorizada por Raios X/veterinária , Animais , Antineoplásicos/uso terapêutico , Meios de Contraste/farmacologia , Estudos Transversais , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Humanos , Masculino , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
INTRODUCTION: The diagnostic importance of audio signal characteristics in needle electromyography (EMG) is well established. Given the recent advent of audio-sound identification by artificial intelligence, we hypothesized that the extraction of characteristic resting EMG signals and application of machine learning algorithms could help classify various EMG discharges. METHODS: Data files of 6 classes of resting EMG signals were divided into 2-s segments. Extraction of characteristic features (384 and 4,367 features each) was used to classify the 6 types of discharges using machine learning algorithms. RESULTS: Across 841 audio files, the best overall accuracy of 90.4% was observed for the smaller feature set. Among the feature classes, mel-frequency cepstral coefficients (MFCC)-related features were useful in correct classification. CONCLUSIONS: We showed that needle EMG resting signals were satisfactorily classifiable by the combination of feature extraction and machine learning, and this can be applied to clinical settings. Muscle Nerve 59:224-228, 2019.
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Eletromiografia/métodos , Potencial Evocado Motor/fisiologia , Aprendizado de Máquina , Músculo Esquelético/fisiologia , Doenças Musculares/fisiopatologia , Descanso/fisiologia , Feminino , Análise de Fourier , Humanos , Modelos Lineares , Masculino , Doenças Musculares/diagnóstico , Agulhas , Processamento de Sinais Assistido por ComputadorRESUMO
An 81-year-old woman who presented with chest and back pain was diagnosed as aortopulmonary fistula caused by rupture of an aortic arch aneurysm and was transferred to our hospital for surgical treatment. Additionally, she was diagnosed with aortic dissection( Stanford type B). Total arch replacement with open stent-grafting and direct closure of aortopulmonary fistula were performed because of her exacerbation of congestive heart failure. Manual compression of fistula during cardiopulmonary bypass was effective to control massive shunt. The patient recovered uneventfully and was transferred to other hospital for rehabilitation on postoperative day 24.
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Ruptura Aórtica , Fístula Artério-Arterial/etiologia , Artéria Pulmonar/anormalidades , Idoso de 80 Anos ou mais , Ruptura Aórtica/complicações , Feminino , HumanosRESUMO
Glial fibrillary acidic protein (GFAP) is expressed in peri-islet Schwann cells, as well as in glia cells, and has been reported to be an autoantigen candidate for type 1 diabetes mellitus (T1DM). We confirmed that the production of the autoantibodies GFAP and glutamic acid decarboxylase 65 (GAD65) was increased and inversely correlated with the concentration of secreted C peptide in female nonobese diabetic mice (T1DM model). Importantly, the development of T1DM in female nonobese diabetic mice at 30 wk of age was predicted by the positive GFAP autoantibody titer at 17 wk. The production of GFAP and GAD65 autoantibodies was also increased in KK-Ay mice [type 2 diabetes mellitus (T2DM) model]. In patients with diabetes mellitus, GFAP autoantibody levels were increased in patients with either T1DM or T2DM, and were significantly associated with GAD65 autoantibodies but not zinc transporter 8 autoantibodies. Furthermore, we identified a B-cell epitope of GFAP corresponding to the GFAP autoantibody in both mice and patients with diabetes. Thus, these results indicate that autoantibodies against GFAP could serve as a predictive marker for the development of overt autoimmune diabetes.-Pang, Z., Kushiyama, A., Sun, J., Kikuchi, T., Yamazaki, H., Iwamoto, Y., Koriyama, H., Yoshida, S., Shimamura, M., Higuchi, M., Kawano, T., Takami, Y., Rakugi, H., Morishita, R., Nakagumi, H. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes.
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Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Proteína Glial Fibrilar Ácida/metabolismo , Animais , Biomarcadores , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NODRESUMO
Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome.
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Adipócitos/citologia , Adipócitos/metabolismo , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Síndrome Metabólica/metabolismo , Globulina de Ligação a Hormônio Sexual/farmacologia , Células 3T3-L1 , Animais , Estradiol/metabolismo , Humanos , Interleucina-6/metabolismo , Metabolismo dos Lipídeos , Lipólise , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Fosforilação , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Purpose To assess the multiple texture features of skeletal muscles in neurogenic and myogenic diseases by using ultrasonography (US). Materials and Methods After institutional review board approval, muscle US studies of the medial head of the gastrocnemius were performed prospectively in patients with neurogenic diseases (n = 25 [18 men]; mean age, 66.0 years ± 12.3 [standard deviation]), in patients with myogenic diseases (n = 21 [12 men]; mean age, 68.3 years ± 11.5), and in healthy control subjects (n = 21 [11 men]; mean age, 70.5 years ± 8.4) between January 2013 and May 2016. Written informed consent was obtained. Muscle texture parameters were obtained, and five algorithms were used to classify the groups. Results The neurogenic and myogenic disease groups showed higher echo intensities than the control subjects. The histogram-derived texture parameters had overlaps between the neurogenic and myogenic groups and thus had a low discrimination rate. With assessment of more classes of texture parameters, three groups were correctly classified (100% correct, according to four of five classification algorithms). Tenfold cross validation showed 93.5%-95.7% correct classification between the neurogenic and myogenic groups. The run-length matrix, autoregressive model, and co-occurrence matrix were particularly useful in distinguishing the neurogenic and myogenic groups. Conclusion Texture analysis of muscle US data can enable differentiation between neurogenic and myogenic diseases and is useful in noninvasively assessing underlying disease mechanisms. © RSNA, 2017 Online supplemental material is available for this article.
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Interpretação de Imagem Assistida por Computador/métodos , Músculo Esquelético/diagnóstico por imagem , Doenças Musculares/diagnóstico por imagem , Doenças Neuromusculares/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Algoritmos , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.
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Esclerose Lateral Amiotrófica/patologia , Fibras Nervosas Mielinizadas/patologia , Tratos Piramidais/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Idoso , Anisotropia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Tratos Piramidais/diagnóstico por imagem , Curva ROC , Córtex Sensório-Motor/diagnóstico por imagem , Índice de Gravidade de DoençaRESUMO
Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl4) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα) stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity.
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Proteínas de Transporte/metabolismo , Cirrose Hepática/metabolismo , Complexos Multiproteicos/metabolismo , Acetaminofen/efeitos adversos , Animais , Apoptose/genética , Tetracloreto de Carbono/efeitos adversos , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepatócitos/metabolismo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intracelular , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Camundongos , Ligação Proteica , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Increased serum cortisol (COR) concentrations may induce glucocorticoid resistance by down-regulation of glucocorticoid receptor (GCR), resulting in decreased chemotherapy efficacy in dogs with lymphoma. HYPOTHESIS: Investigate the relationship between serum COR concentrations and chemotherapy outcomes in dogs with lymphoma. ANIMALS: Thirty client-owned dogs with lymphoma, with serum COR concentration measured using serum samples collected at diagnosis. METHODS: Retrospective study. Dogs were divided into 2 groups based on serum COR concentrations: a normal group (n = 16) with COR concentrations <6 µg/dL and a high group (14) with COR concentrations ≥6 µg/dL. We compared signalment, clinical signs, stage, type of lymphoma, adrenal gland size, alkaline phosphatase (ALP) activity, response to chemotherapy, progression-free survival (PFS), overall survival (OS), and rate of P-glycoprotein (P-gp)- and GCR-positive cells between the 2 groups. RESULTS: No significant differences were found in the demographic characteristics between the 2 groups. However, the high COR group exhibited a significantly lower response to chemotherapy, PFS, and OS compared with the normal COR group. Serum ALP activity was significantly higher in the high COR group than in the normal COR group. Adrenal gland size was also significantly larger in the high COR group. Although no significant differences were found in the rate of P-gp-positive cells between the 2 groups, the rate of GCR-positive cells was significantly lower in the high COR group. CONCLUSIONS AND CLINICAL IMPORTANCE: Our data suggests that measurement of serum COR concentrations may serve as a potential prognostic factor and evaluation index.
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Doenças do Cão , Hidrocortisona , Linfoma , Animais , Cães , Doenças do Cão/tratamento farmacológico , Doenças do Cão/sangue , Estudos Retrospectivos , Linfoma/veterinária , Linfoma/tratamento farmacológico , Linfoma/sangue , Feminino , Masculino , Hidrocortisona/sangue , Resultado do Tratamento , Antineoplásicos/uso terapêuticoRESUMO
Background: Constipation has been recently recognized as a complication associated with motor and autonomic dysfunction in patients with motor neuron disease (MND), typified by amyotrophic lateral sclerosis (ALS). However, the long-term characteristics of constipation remain unclear in patients with MND. We longitudinally investigated the prevalence and risk factors of constipation in a consecutive cohort of patients with MND. Methods: Data from Japanese patients with MND enrolled in a single-center registry from June 2017 to December 2021 were retrospectively investigated. The diagnosis of ALS was based on the updated Awaji criteria, and other MND subtypes were also included. The presence or absence of constipation symptoms was determined by referring to the Rome III criteria. The clinical backgrounds and symptoms of patients with and without constipation were compared. Results: Among 155 consecutive patients (female, 63; age, 66.5 ± 12.4 years), 30.3% had constipation at diagnosis and 52.9% after a median follow-up of 18 months. Univariate analysis showed that female sex, use of tracheostomy and invasive ventilation, and delivery of enteral nutrition were more frequent in the constipation group. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was significantly lower in the constipation group, especially for the sub-items related to physical motor function. Multivariate analysis showed that the use of enteral nutrition was an independent risk of constipation, with an odds ratio of 3.69 (95% CI, 1.49-9.17; p = 0.005). Conclusion: Constipation had a high prevalence in patients with MND with impaired motor function. Controlling defecation is important in patients with MND, especially during enteral nutrition.
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The structural aspects of ambient-temperature densification via pressurization at 25 GPa were studied by solid-state NMR for two case studies: An alkaline earth boroaluminosilicate glass with the composition 6CaO-3SrO-1BaO-10Al2O3-10B2O3-70SiO2 (labeled SAB) and a sodium magnesium borosilicate glass with the composition 10Na2O-10MgO-20B2O3-60SiO2 (labeled MNBS). For SAB glass, cold pressurization results in significant increases in the average coordination numbers of both boron and aluminum, in line with previous results found in hot-compressed alkali aluminoborosilicate glasses. In addition, 27Al/11B dipolar recoupling experiments reveal a significant decrease in the 11B/27Al dipolar interaction strength upon pressurization, suggesting that the higher-coordinated boron and aluminum species experience weaker magnetic interactions. While this is an expected consequence of the longer internuclear distances involving higher coordination states, the magnitude of the effect also is consistent with a decrease of average B-O-Al internuclear connectivity. By conjecture, a decreased B-O-Al connectivity may present a mechanism of plastic flow inhibiting crack initiation in aluminoborosilicate glasses. In the case of the MNBS glass, no change in the average boron coordination number was observed within experimental error; however, densification increases the extent of B-O-Si connectivity at the expense of small ring structures with dominant B-O-B connectivity. With regard to boron coordination, the data obtained for both case studies differ from those previously found in a series of alkali borosilicate glasses, which had shown an unexpected decrease in N4 upon increased pressure. The results of the present study highlight the importance of changes of medium-range order regarding densification.
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ApoA-I amyloidosis is an extremely rare form of systemic amyloidosis that commonly involves the heart, kidneys, and liver. ApoA-I amyloidosis is caused by amyloidogenic variants of APOA1 that are inherited in an autosomal dominant manner. Here, we report a 69-year-old man with sporadic cardiac amyloidosis who was born to consanguineous parents and carried a homozygous variant of p.Leu202Arg in APOA1.
RESUMO
Mutations in the Trk-fused gene (TFG) cause hereditary motor and sensory neuropathy with proximal dominant involvement, which reportedly has high co-incidences with diabetes and dyslipidemia, suggesting critical roles of the TFG in metabolism as well. We found that TFG expression levels in white adipose tissues (WATs) were elevated in both genetically and diet-induced obese mice and that TFG deletion in preadipocytes from the stromal vascular fraction (SVF) markedly inhibited adipogenesis. To investigate its role in vivo, we generated tamoxifen-inducible adipocyte-specific TFG knockout (AiTFG KO) mice. While a marked down-regulation of the peroxisome proliferator-activated receptor gamma target, de novo lipogenesis (DNL), and mitochondria-related gene expressions were observed in subcutaneous WAT (scWAT) from AiTFG KO mice, these effects were blunted in SVF-derived adipocytes when the TFG was deleted after differentiation into adipocytes, implying cell nonautonomous effects. Intriguingly, expressions of thyroid hormone receptors, as well as carbohydrate responsive element-binding protein ß, which mediates the metabolic actions of thyroid hormone, were drastically down-regulated in scWAT from AiTFG KO mice. Reduced DNL and thermogenic gene expressions in AiTFG KO mice might be attributable to impaired thyroid hormone action in vivo. Finally, when adipocyte TFG was deleted in either the early or the late phase of high-fat diet feeding, the former brought about an impaired expansion of epididymal WAT, whereas the latter caused prominent adipocyte cell death. TFG deletion in adipocytes markedly exacerbated hepatic steatosis in both experimental settings. Collectively, these observations indicate that the TFG plays essential roles in maintaining normal adipocyte functions, including an enlargement of adipose tissue, thyroid hormone function, and thermogenic gene expressions, and in preserving hypertrophic adipocytes.
RESUMO
Purpose: Non-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. Methods: Based on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. Results: In 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). Conclusion: Normal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.