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1.
J Intellect Disabil Res ; 67(7): 655-667, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37016552

RESUMO

BACKGROUND: Analysis of the errors in the Raven's Coloured Progressive Matrices (RCPM) has been previously performed for children with intellectual disabilities but has not been investigated for those with cerebral palsy (CP). This study aimed to investigate whether the types and positions of errors made by individuals with CP differed from those made by typically developing (TD) controls. METHODS: Forty-five participants with CP aged 4-18 years and 30 TD children aged 3-9 years underwent RCPM testing. We first compared the RCPM performance and error characteristics between the groups and then examined the association between RCPM and the severity of CP and receptive vocabulary in the CP group. RESULTS: The results showed that while mean total scores in the two groups were comparable, the types and positions of errors made by individuals with CP differed from those of TD controls. The development of non-verbal intelligence in children with CP increased with age; when controlling for age, non-verbal intelligence was significantly correlated with all three functional levels of CP severity and receptive vocabulary. CONCLUSIONS: This study provides valuable insights into the problem-solving strategies employed by children with CP.


Assuntos
Paralisia Cerebral , Deficiência Intelectual , Humanos , Criança , Adolescente , Testes de Inteligência , Resolução de Problemas , Inteligência
2.
Public Health ; 216: 39-44, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36791649

RESUMO

OBJECTIVE: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition. STUDY DESIGN: This was a cross-sectional questionnaire-based survey. METHODS: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses. RESULTS: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (ß = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (ß = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (ß = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (ß = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (ß = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (ß = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (ß = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (ß = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (ß = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (ß = -0.51, 95% CI = -0.94 to -0.09). CONCLUSIONS: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , Síndrome de COVID-19 Pós-Aguda , Teste para COVID-19 , Estudos Transversais , Tosse
3.
J Infect Chemother ; 28(11): 1546-1551, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35963600

RESUMO

OBJECTIVES: To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains. STUDY DESIGN: A single-center cross-sectional study. METHODS: Patients who recovered from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients' characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching. RESULTS: We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively. CONCLUSIONS: The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Qualidade de Vida
4.
Epidemiol Infect ; 148: e250, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33046159

RESUMO

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , COVID-19 , Comércio , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Tóquio/epidemiologia
5.
Spinal Cord ; 54(7): 521-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26481711

RESUMO

STUDY DESIGN: Experimental training model of rats with spinal cord injury (SCI). SETTING: Osaka, JapanObjective:To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. METHODS: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. RESULTS: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6±0.8, 7.7±1.3 and 10.3±0.4. The paw dorsiflexion angles were 34.1±5.2, 16.4±2.4 and 23.6±3.0 degrees, respectively. The stride angles were 5.1±0.9, 13.7±4.9 and 17.8±4.0 degrees for the left paws. Cavity volumes were 10.3±2.1, 31.0±2.0 and 28.2±4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. CONCLUSIONS: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. Forced training by PP of the hind paws promoted the behavioral and histological improvement of rats with SCI.


Assuntos
Teste de Esforço/métodos , Terapia por Exercício/métodos , Locomoção/fisiologia , Extremidade Inferior/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/reabilitação , Animais , Axônios/metabolismo , Axônios/patologia , Modelos Animais de Doenças , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Desempenho Psicomotor , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia
6.
Lupus ; 23(7): 703-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22187162

RESUMO

We report on an 11-year-old girl who developed steroid-resistant nephrotic syndrome (NS) at the onset of systemic lupus erythematosus (SLE), and clinical and renal histological findings suggested that her NS would be associated with SLE-related podocytopathy. Although initial treatment with intravenous pulse methylprednisolone was ineffective, following treatment with cyclosporine and an angiotensin receptor blocker was effective for her nephrotic proteinuria. She had developed posterior reversible encephalopathy syndrome (PRES), and mycophenolate mofetil (MMF) was started instead of cyclosporine. At present, 45 months after the onset, she is in remission of both NS and SLE. This case indicates that NS associated with SLE-related podocytopathy should be included in the spectrum of glomerulopathy accompanying SLE, also in the pediatric population.


Assuntos
Glucocorticoides/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Metilprednisolona/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Criança , Ciclosporina , Resistência a Medicamentos , Feminino , Humanos
7.
Knee Surg Sports Traumatol Arthrosc ; 22(1): 192-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23263260

RESUMO

Snapping syndrome rarely occurs at the knee joint. This is the first report of snapping pes syndrome after total knee arthroplasty. Surgeons should be aware of the presence of such a case and pay attention to the fact that snapping symptoms could be caused by a residual bony prominence and a change in alignment after total knee arthroplasty.


Assuntos
Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Idoso , Feminino , Humanos , Artropatias , Masculino , Amplitude de Movimento Articular , Síndrome
8.
Rev Sci Instrum ; 94(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088778

RESUMO

Nanosecond-gated hybrid complementary metal-oxide semiconductor imaging sensors are a powerful tool for temporally gated and spatially resolved measurements in high energy density science, including inertial confinement fusion, and in laser diagnostics. However, a significant oscillating background excited by photocurrent has been observed in image sequences during testing and in experiments at the National Ignition Facility (NIF). Characterization measurements and simulation results are used to explain the oscillations as the convolution of the pixel-level sensor response with a sensor-wide RLC circuit ringing. Data correction techniques are discussed for NIF diagnostics, and for diagnostics where these techniques cannot be used, a proof-of-principle image correction algorithm is presented.

9.
Rev Sci Instrum ; 93(8): 083516, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050109

RESUMO

The hardened single line of sight camera has been recently characterized in preparation for its deployment on the National Ignition Facility. The latest creation based on the pulse-dilation technology leads to many new features and improvements over the previous-generation cameras to provide better quality measurements of inertial confinement fusion experiments, including during high neutron yield implosions. Here, we present the characterization data that illustrate the main performance features of this instrument, such as extended dynamic range and adjustable internal magnification, leading to improved spatial resolution.

10.
J Hosp Infect ; 104(3): 344-349, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31790746

RESUMO

BACKGROUND: Though nurses have frequent contact with patients, their personal protective equipment (PPE) compliance rate is low, which poses a significant challenge in infection control. AIM: To investigate the relative influence of specific factors on PPE compliance. METHODS: A sequential two-stage mixed-methods design was applied. In a qualitative study, semi-structured interviews were conducted from May to July 2018. In a quantitative study, a nationwide, cross-sectional survey was conducted from January to March 2019, in which a questionnaire was mailed to 735 nurses in 28 tertiary care hospitals in Japan. FINDINGS: In the quantitative study, 435 (59.2%) analysable responses were obtained. In the linear regression analysis, the lack of the knowledge that 'standard precaution was the fundamental infection countermeasure applied when patients had signs of infections, and these countermeasures could be terminated if there was no infection found' was significantly associated with decreased PPE adherence, whereas an antimicrobial-resistant bacteria outbreak or a ward shutdown due to an outbreak and the belief 'I must never be the cause of spreading infection' were significantly associated with increased PPE adherence. The ß of standard coefficients and t-values of the items were -0.344, -7.784, 0.090, 2.089, 0.088, 2.018, respectively. CONCLUSION: This survey systematically identified nursing-associated factors that contribute to PPE compliance. As a practical approach to ensure positive outcomes, we suggest educating nurses by providing adequate knowledge on appropriate PPE use and sharing outbreak or ward shutdown experiences.


Assuntos
Controle de Infecções/métodos , Enfermeiras e Enfermeiros , Equipamento de Proteção Individual , Adulto , Estudos Transversais , Feminino , Fidelidade a Diretrizes , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Adulto Jovem
11.
Appl Ergon ; 88: 103148, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32421636

RESUMO

This article presents the results of an academic research project connecting the discipline of ergonomics (and work-related issues) with the theme of sustainability. Despite the stated aim of creating value for stakeholders, including employees, companies face difficulties in introducing effective sustainability policies. The research question addressed in this article is the following: How can companies improve their decision-making processes to increase workers' wellbeing using policies integrating issues related to corporate sustainability and ergonomics? Currently, corporate sustainability is focused mainly on the triple bottom line (TBL) concept. In this context, the integration of ergonomics is fragmented and arguably separate from strategic human-resource functions (which have largely been the primary promoter of the internal-social component of corporate sustainability). This research argues that corporate sustainability requires a new step, improving the decision-making process, with the inclusion of more types of rationalities and the recognition of the centrality of workers in the process of creating sustainable action. When corporate sustainability policies focus on worker centrality, they open space for the integration of ergonomics as a pillar of an organization's corporate sustainability strategy. Based on a complex view of work systems, ergonomics can introduce values aligned with sustainability and promote cooperation in organizations. Different stakeholders working at companies can make use of different concepts proposed by ergonomics and other work sciences to support changes in their decision-making processes. In view of broader sustainability objectives, integrating different work-related considerations can help improve performance, including productivity, quality and health.


Assuntos
Tomada de Decisões , Ergonomia , Desenvolvimento Sustentável , Integração de Sistemas , Humanos , Valores Sociais , Participação dos Interessados , Local de Trabalho/organização & administração , Local de Trabalho/psicologia
13.
Hand Surg Rehabil ; 37(3): 167-170, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29580686

RESUMO

We investigated the relationship between pain and hesitation during movement initiation among 11 adult female patients who had undergone surgery for a distal radius fracture. Data on the patients' pain at rest, pain during movement and score on the Pain Catastrophizing Scale were analyzed. Movement characteristics were assessed by the administration of a finger tapping (FT) task using the thumb and index finger, with the movement repeated 10 times, recorded and analyzed to determine the patient's hesitation when opening or closing her thumb/forefinger during the task. Hesitation of movement initiation was significantly correlated with subjective factors such as pain at rest, pain during movement, and rumination. Pain was not significantly correlated with the physical range of motion. Our findings suggest that hesitation during movement initiation for the FT task may be a type of behavior that is affected by subjective pain. Movement hesitation is a novel clinical sign indicating the possible progression of acute pain into chronic pain. The kinematic evaluation described herein is a convenient clinical measurement that captures a subjective factor.


Assuntos
Movimento/fisiologia , Dor/psicologia , Fraturas do Rádio/psicologia , Idoso , Feminino , Fixação de Fratura , Humanos , Dor/fisiopatologia , Período Pós-Operatório , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/cirurgia , Escala Visual Analógica
15.
Eur J Pain ; 21(1): 140-147, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27378656

RESUMO

BACKGROUND AND OBJECTIVE: We developed a quantitative method to measure movement representations of a phantom upper limb using a bimanual circle-line coordination task (BCT). We investigated whether short-term neurorehabilitation with a virtual reality (VR) system would restore voluntary movement representations and alleviate phantom limb pain (PLP). METHODS: Eight PLP patients were enrolled. In the BCT, they repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb. Drawing circles mentally using the phantom limb led to the emergence of an oval transfiguration of the vertical lines ('bimanual-coupling' effect). We quantitatively measured the degree of this bimanual-coupling effect as movement representations of the phantom limb before and immediately after short-term VR neurorehabilitation. This was achieved using an 11-point numerical rating scale (NRS) for PLP intensity and the Short-Form McGill Pain Questionnaire (SF-MPQ). During VR neurorehabilitation, patients wore a head-mounted display that showed a mirror-reversed computer graphic image of an intact arm (the virtual phantom limb). By intending to move both limbs simultaneously and similarly, the patients perceived voluntary execution of movement in their phantom limb. RESULTS: Short-term VR neurorehabilitation promptly restored voluntary movement representations in the BCT and alleviated PLP (NRS: p = 0.015; 39.1 ± 28.4% relief, SF-MPQ: p = 0.015; 61.5 ± 48.5% relief). Restoration of phantom limb movement representations and reduced PLP intensity were linearly correlated (p < 0.05). CONCLUSIONS: VR rehabilitation may encourage patient's motivation and multimodal sensorimotor re-integration of a phantom limb and subsequently have a potent analgesic effect. SIGNIFICANCE: There was no objective evidence that restoring movement representation by neurorehabilitation with virtual reality alleviated phantom limb pain. This study revealed quantitatively that restoring movement representation with virtual reality rehabilitation using a bimanual coordination task correlated with alleviation of phantom limb pain.


Assuntos
Atividade Motora/fisiologia , Reabilitação Neurológica/métodos , Membro Fantasma/reabilitação , Extremidade Superior , Realidade Virtual , Adulto , Plexo Braquial/lesões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Medição da Dor , Membro Fantasma/etiologia , Membro Fantasma/fisiopatologia , Amplitude de Movimento Articular , Interface Usuário-Computador
16.
Cancer Res ; 46(3): 1418-26, 1986 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2417703

RESUMO

A clonal neoplastic epithelial duct cell (HSGc) of human salivary gland origin has a fine structure similar to the intercalated duct cell and the capacity to express secretory component and lactoferrin. HSGc cells tend to form an occasional glandular arrangement in vitro and in vivo, and transplantation of cells into nude mice resulted in production of adenocarcinoma. By repeated single cell cloning, different types of clones could be isolated from HSGc. Cuboidal clones resemble the parent cell, but fail to form the glandular arrangement or express lactoferrin, suggesting a less differentiated type. Elongated clones have a fine structure similar to myoepithelial cells and carry myoepithelial markers such as S100 protein, actin, and myosin which are not detected in the HSGc and its cuboidal clones. These myoepithelial-like clones are able to express secretory component, lactoferrin, and lysozyme and to produce glycosaminoglycans, suggesting that they are a functionally active form of the neoplastic cell but different from the normal myoepithelial cell. Judging from their growth properties in vitro and in vivo, the myoepithelial-like clones are less malignant than HSGc or its cuboidal clones. Of four elongated clones, two did not produce tumors in athymic mice, while all of the cuboidal clones were tumorigenic. These findings suggest a possible conversion of the neoplastic duct cell to myoepithelial-like variants with low malignancy.


Assuntos
Neoplasias das Glândulas Salivares/patologia , Actinas/análise , Adenocarcinoma/patologia , Antígenos/análise , Carcinoma/patologia , Ciclo Celular , Linhagem Celular , Separação Celular , Células Clonais , Epitélio/imunologia , Epitélio/patologia , Imunofluorescência , Humanos , Queratinas/análise , Lactoferrina/análise , Microscopia Eletrônica , Muramidase/análise , Miosinas/análise , Proteínas S100/análise , Neoplasias das Glândulas Salivares/imunologia , Componente Secretório/análise
17.
Cancer Res ; 48(10): 2819-24, 1988 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-3359442

RESUMO

The present study demonstrates that normal human fibroblasts (WI-38) exert a profound influence on the growth and differentiation of HSGc-C5, a clonal neoplastic epithelial cell line of human salivary gland origin. Coculture of HSGc-C5 with WI-38 resulted in a slowing of growth and an increase in glycosaminoglycan synthesis by an indirect effect involving a diffusible factor(s). Conditioned medium (CM) from WI-38 grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum affected HSGc-C5 as follows. The CM suppressed growth of monolayer cells; inhibited DNA synthesis; suppressed growth (decrease in size of colonies) in semisolid agar; stimulated glycosaminoglycan synthesis, induced expression of functional markers of the salivary gland, such as the secretory component, lactoferrin, and lysozyme; inhibited expression of alkaline phosphatase; and induced morphological alteration into elongated cells. These findings strongly suggest that WI-38 CM contains a factor(s) which inhibits growth and induces differentiation of HSGc-C5. The CM was also active on other human cancer cells as a growth inhibitor, but not on normal human fibroblasts. Partial purification and characterization of the factor(s) suggests that it may be a novel protein carrying both tumor inhibiting and differentiation inducing activities.


Assuntos
Adenocarcinoma/patologia , Fibroblastos/fisiologia , Neoplasias das Glândulas Salivares/patologia , Diferenciação Celular , Divisão Celular , Meios de Cultura , DNA/biossíntese , Fibroblastos/análise , Glicosaminoglicanos/biossíntese , Inibidores do Crescimento/análise , Humanos , Células Tumorais Cultivadas
18.
Cancer Res ; 50(13): 4139-45, 1990 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-2162254

RESUMO

Two cell lines (ACCS and ACCY) were isolated from two individuals with adenoid cystic carcinoma (AdCC) using tissue culture techniques. Both cell lines have similar morphology, i.e., elongated and flattened cells with slender cytoplasmic processes. The two cell lines tend to form pseudocysts, which are a specific architectural feature of AdCC. Coexpression of cytokeratin and vimentin was found in the two cell lines, which occasionally also contained S-100 protein and lactoferrin or lysozyme immunoreactivity. Moreover, ACCS and ACCY displayed potential for the production of a large amount of extracellular matrix including basal lamina components such as fibronectin, laminin, and type IV collagen and glycosaminoglycans which are also part of the basal lamina. These findings suggest that the tumor cells, probably basal or myoepithelial like cells, are responsible for the formation of the peculiar stroma of AdCC consisting of a large amount of collagen-like fibers, basal lamina components, and mucopolysaccharides.


Assuntos
Carcinoma Adenoide Cístico/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/análise , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/ultraestrutura , Colágeno/biossíntese , Feminino , Glicosaminoglicanos/biossíntese , Humanos , Microscopia Eletrônica , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/análise , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/ultraestrutura , Glândulas Salivares Menores , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologia , Células Tumorais Cultivadas/ultraestrutura
19.
Oncogene ; 35(29): 3829-38, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-26973245

RESUMO

Sterol-regulatory element-binding proteins (SREBPs) are key transcription factors regulating cholesterol and fatty acid biosynthesis. SREBP activity is tightly regulated to maintain lipid homeostasis, and is modulated upon extracellular stimuli such as growth factors. While the homeostatic SREBP regulation is well studied, stimuli-dependent regulatory mechanisms are still elusive. Here we demonstrate that SREBPs are regulated by a previously uncharacterized mechanism through transforming growth factor-ß activated kinase 1 (TAK1), a signaling molecule of inflammation. We found that TAK1 binds to and inhibits mature forms of SREBPs. In an in vivo setting, hepatocyte-specific Tak1 deletion upregulates liver lipid deposition and lipogenic enzymes in the mouse model. Furthermore, hepatic Tak1 deficiency causes steatosis pathologies including elevated blood triglyceride and cholesterol levels, which are established risk factors for the development of hepatocellular carcinoma (HCC) and are indeed correlated with Tak1-deficiency-induced HCC development. Pharmacological inhibition of SREBPs alleviated the steatosis and reduced the expression level of the HCC marker gene in the Tak1-deficient liver. Thus, TAK1 regulation of SREBP critically contributes to the maintenance of liver homeostasis to prevent steatosis, which is a potentially important mechanism to prevent HCC development.


Assuntos
Homeostase , Metabolismo dos Lipídeos , Fígado/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Células HEK293 , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Immunoblotting , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MAP Quinase Quinase Quinases/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ligação Proteica , Interferência de RNA , Fatores de Risco , Proteínas de Ligação a Elemento Regulador de Esterol/genética
20.
J Am Coll Cardiol ; 30(4): 935-41, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9316521

RESUMO

OBJECTIVES: This study sought to assess the differences in coronary flow reserve in patients with and without diabetic retinopathy. BACKGROUND: Microvascular abnormalities throughout the body and impairment of coronary flow reserve have been described in patients with diabetes mellitus. However, the relation between diabetic retinopathy and coronary microvascular disease has not been investigated. METHODS: The study included 29 patients with diabetes mellitus (18 with and 11 without diabetic retinopathy) and 15 control patients with chest pain and normal coronary arteries. Diabetic retinopathy was nonproliferative in all 18 patients with this disorder (8 had background, 10 preproliferative retinopathy). Five minutes after injection of 3 mg of isosorbide dinitrate, phasic flow velocities were recorded in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg body weight per min of adenosine infused intravenously) using a 0.014-in. 15-MHz Doppler guide wire. Coronary blood flow was calculated, and coronary flow reserve was obtained from the hyperemic/baseline flow ratio. RESULTS: Coronary blood flow was significantly lower during hyperemia ([mean +/- SD] 107 +/- 23 and 116 +/- 18 vs. 136 +/- 17 ml/min, respectively) and higher at baseline (58 +/- 16 and 45 +/- 12 vs. 37 +/- 10 ml/min, respectively) in diabetic patients with and without retinopathy than in control subjects (p < 0.05 for both diabetic groups). As a result, coronary flow reserve in both groups of diabetic patients was significantly lower than in control patients (1.9 +/- 0.4 and 2.8 +/- 0.3 vs. 3.3 +/- 0.4, respectively, p < 0.01 for both diabetic groups), and its reduction was greater in patients with than without retinopathy (p < 0.01). Furthermore, in patients with diabetic retinopathy, maximal hyperemic coronary flow (102 +/- 11 vs. 114 +/- 16 ml/min, p < 0.05) and flow reserve (1.6 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly lower in those with preproliferative than background retinopathy. CONCLUSIONS: Coronary flow reserve is significantly restricted in patients with diabetes mellitus, and its reduction is more marked in those with diabetic retinopathy, especially in advanced retinopathy. Thus, diabetic retinopathy should identify marked restriction of coronary flow reserve in patients with diabetes mellitus.


Assuntos
Circulação Coronária , Doença das Coronárias/etiologia , Doença das Coronárias/fisiopatologia , Complicações do Diabetes , Retinopatia Diabética/complicações , Adulto , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Cateterismo Cardíaco , Estudos de Casos e Controles , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Humanos , Dinitrato de Isossorbida/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Vasodilatadores/farmacologia
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