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1.
J Eur Acad Dermatol Venereol ; 35(10): 2059-2066, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34077574

RESUMEN

BACKGROUND: Although polypharmacy is known to cause side-effects due to drug-drug interactions, dermatological symptoms triggered by polypharmacy are not fully addressed. OBJECTIVE: To investigate whether polypharmacy is associated with the risk of pruritus. METHOD: A cohort study was performed to examine cross-sectional and longitudinal relationships between polypharmacy and pruritus in a general population. Data were collected from the Norm Study conducted in 2016 and 2017, which is a nationwide survey based on a self-administered questionnaire with Japanese representative participants aged 16-84 years. Presence of polypharmacy which was defined as concurrent use of ≥5 prescribed drugs. Primary outcomes were the presence of severe pruritus at baseline for the cross-sectional analysis and the development of severe pruritus after one year for the longitudinal analysis. Multivariable modified Poisson regression analyses were performed to estimate risk ratios (RRs) and 95% confidence intervals (95%CIs) with adjustment for potential confounders (age, gender, smoking habits, drinking habits, depressive symptoms, moderate activities based on IPAQ score and presence of 11 comorbid conditions including skin disease). RESULTS: The study included 3126 participants (mean age, 48.7 years); nearly half (49.8%) were male. In all, 332 participants (10.3%) had polypharmacy in the cross-sectional analysis. Participants with polypharmacy were more likely to present with severe pruritus at baseline than those who were not using drugs (adjusted RR = 1.52 [95%CI 1.15-2.01, P = 0.003]). The longitudinal analysis (n = 1803) was limited to those without severe pruritus at baseline; participants with polypharmacy at baseline were more likely to develop severe pruritus after a one-year follow-up period than those not using drugs (adjusted RR = 1.46 [95%CI 1.14-1.87, P = 0.002]). CONCLUSION: Polypharmacy was associated with the presence of pruritus at baseline and may predict the future risk of developing pruritus.


Asunto(s)
Polifarmacia , Prurito , Estudios de Cohortes , Estudios Transversales , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prurito/inducido químicamente , Prurito/epidemiología
2.
Clin Radiol ; 75(7): 507-519, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32067698

RESUMEN

AIM: To compare the goodness of fit and correlations between diffusion kurtosis imaging (DKI) and a mono-exponential (ME) model, to compare the corrected apparent diffusion coefficient (Dapp) and apparent kurtosis (Kapp) of the DKI model, and the apparent diffusion coefficient (ADC) of the ME model among the various orofacial lesions, and to evaluate the diagnostic performances between the two models. MATERIALS AND METHODS: A total of 100 orofacial lesions underwent echo-planar diffusion magnetic resonance imaging (MRI) with four b-values. The goodness of fit was evaluated using Akaike information criterion. The correlations of the diffusion-derived parameters were evaluated. The diagnostic performance was analysed by receiver operating characteristics (ROC). RESULTS: The DKI model showed a significantly better goodness of fit than the ME model (p<0.0001). The Kapp had a strongly negative correlation with the Dapp (ρ=-0.749) and ADC (ρ=-0.938). A strongly positive correlation existed between the Dapp and ADC (ρ=0.906). All parameters differed significantly between benign tumours and malignant tumours (p<0.05). In differentiating benign tumours from the malignant tumours, the AUC of Dapp (0.871) was larger than that of ADC (0.805); however, a significant difference was not found (p=0.102). CONCLUSION: The DKI model had better goodness of fit than the ME model. Furthermore, the Dapp and Kapp were also characteristic for each pathological category; however, the DKI model did not yield a significantly higher diagnostic performance than the ME model, which might be related to the high correlation among the diffusion-derived parameters and wide variation among categories.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias Faciales/diagnóstico por imagen , Neoplasias de la Boca/diagnóstico por imagen , Diagnóstico Diferencial , Neoplasias Faciales/diagnóstico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Neoplasias de la Boca/diagnóstico , Curva ROC , Estudios Retrospectivos
3.
Clin Radiol ; 70(11): 1289-98, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26272529

RESUMEN

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.


Asunto(s)
Neoplasias del Mediastino/patología , Adulto , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Linfoma/patología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Glandulares y Epiteliales/patología , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Curva ROC , Radiofármacos , Sensibilidad y Especificidad , Timoma/patología , Neoplasias del Timo/patología , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
4.
Clin Radiol ; 69(7): 758-64, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24824977

RESUMEN

AIM: To verify whether quantitative analysis of the extent of ground-glass opacity (GGO) on high-resolution computed tomography (HRCT) could show a stronger correlation with the therapeutic response of interstitial pneumonia (IP) associated with systemic sclerosis (SSc) compared with qualitative analysis. MATERIALS AND METHODS: Seventeen patients with IP associated with SSc received autologous peripheral blood stem cell transplantation (auto-PBSCT) and were followed up using HRCT and pulmonary function tests. Two thoracic radiologists assessed the extent of GGO on HRCT using a workstation. Therapeutic effect was assessed using the change of vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLco) before and 12 months after PBSCT. Interobserver agreement was assessed using Spearman's rank correlation coefficient and the Bland-Altman method. Correlation with the therapeutic response between quantitative and qualitative analysis was assessed with Pearson's correlation coefficients. RESULTS: Spearman's rank correlation coefficient showed good agreement, but Bland-Altman plots showed that proportional error could be suspected. Quantitative analysis showed stronger correlation than the qualitative analysis based on the relationships between the change in extent of GGO and VC, and change in extent of GGO and DLco. CONCLUSION: Quantitative analysis of the change in extent of GGO showed stronger correlation with the therapeutic response of IP with SSc after auto-PBSCT than with the qualitative analysis.


Asunto(s)
Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/terapia , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Pruebas de Función Respiratoria , Estudios Retrospectivos , Esclerodermia Sistémica/fisiopatología , Esclerodermia Sistémica/terapia , Tomografía Computarizada por Rayos X
5.
Br J Cancer ; 102(5): 873-82, 2010 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-20160729

RESUMEN

BACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells.


Asunto(s)
Apoptosis , Carcinoma de Células Renales/patología , Proliferación Celular , Interferón-alfa/farmacología , Neoplasias Renales/patología , Fase S , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Western Blotting , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Ciclina E/genética , Ciclina E/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética
6.
J Cell Biol ; 147(2): 221-34, 1999 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-10525530

RESUMEN

Nuclear domain 10 (ND10), also referred to as nuclear bodies, are discrete interchromosomal accumulations of several proteins including promyelocytic leukemia protein (PML) and Sp100. In this study, we investigated the mechanism of ND10 assembly by identifying proteins that are essential for this process using cells lines that lack individual ND10-associated proteins. We identified the adapter protein Daxx and BML, the RecQ helicase missing in Bloom syndrome, as new ND10-associated proteins. PML, but not BLM or Sp100, was found to be responsible for the proper localization of all other ND10-associated proteins since they are dispersed in PML-/- cells. Introducing PML into this cell line by transient expression or fusion with PML-producing cells recruited ND10-associated proteins into de novo formed ND10 attesting to PMLs essential nature in ND10 formation. In the absence of PML, Daxx is highly enriched in condensed chromatin. Its recruitment to ND10 from condensed chromatin requires a small ubiquitin-related modifier (SUMO-1) modification of PML and reflects the interaction between the COOH-terminal domain of Daxx and PML. The segregation of Daxx from condensed chromatin in the absence of PML to ND10 by increased accumulation of SUMO-1-modified PML suggests the presence of a variable equilibrium between these two nuclear sites. Our findings identify the basic requirements for ND10 formation and suggest a dynamic mechanism for protein recruitment to these nuclear domains controlled by the SUMO-1 modification state of PML.


Asunto(s)
Proteínas Portadoras/metabolismo , Núcleo Celular/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Línea Celular , Núcleo Celular/ultraestructura , Proteínas Co-Represoras , Eliminación de Gen , Humanos , Microscopía Confocal , Chaperonas Moleculares , Proteínas Nucleares/genética , Proteína de la Leucemia Promielocítica , Unión Proteica , Proteína SUMO-1 , Transfección , Proteínas Supresoras de Tumor
7.
J Nutr Health Aging ; 23(8): 732-738, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31560031

RESUMEN

OBJECTIVES: To validate the SARC-F questionnaire for sarcopenia screening in musculoskeletal disease setting, and to assess improvements in diagnostic accuracy by adding "EBM" (elderly and body mass index information) to the SARC-F. DESIGN: Diagnostic accuracy study. SETTING AND PARTICIPANTS: The center involved in this study was located in an urban area of Kobe City, Japan. People with musculoskeletal disease in the knee, hip, or spine who were scheduled for surgical treatment were included. MEASUREMENTS: Sarcopenia was evaluated using the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP2), which included bioimpedance, handgrip strength, and gait speed. Patients answered the SARC-F questionnaire and their body mass index was measured. SARC-F and "EBM" information were combined into an original score. The sensitivities, specificities, and areas under the receiver operating characteristic curve (AUC) were estimated and compared to identify sarcopenia. RESULTS: A total of 959 patients were included. Sarcopenia by AWGS criteria was identified in 36 (3.8%) patients. SARC-F had a sensitivity of 41.7% and specificity of 68.5%. SARC-F+EBM had a sensitivity of 77.8% and specificity of 69.6%, with substantial improvement in sensitivity (P<0.001). The AUCs for SARC-F and SARC-F+EBM were 0.557 (95% confidence interval [CI] 0.452-0.662) and 0.824 (95% CI 0.762-0.886), respectively (P<0.001). Similar results were obtained when EWGSOP2 criteria were used as the reference standard. CONCLUSION: The SARC-F alone is not adequate for finding cases in musculoskeletal disease settings. SARC-F+EBM significantly improved the sensitivity and overall diagnostic accuracy of the SARC-F for screening sarcopenia. SARC-F+EBM is potentially useful for screening sarcopenia in different ethnic and disease settings.


Asunto(s)
Programas de Detección Diagnóstica/normas , Enfermedades Musculoesqueléticas/fisiopatología , Sarcopenia/diagnóstico , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Tamizaje Masivo , Reproducibilidad de los Resultados , Sarcopenia/patología
8.
J Clin Invest ; 89(4): 1172-7, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1532587

RESUMEN

A T cell hybridoma mutant, which expressed a markedly reduced level of glycosylphosphatidylinositol (GPI)-anchored proteins on the cell surface, was characterized. The surface expression level of Thy-1 was approximately 17% of the wild-type level, whereas the surface expression of Ly-6A was approximately 2.4% of the wild-type level. We show here that these cells synthesized limiting amounts of the GPI core and that the underlying defect in these cells was an inability to synthesize dolichyl phosphate mannose (Dol-P-Man) at the normal level. The defect in Ly-6A expression could be partially corrected by tunicamycin, which blocked the biosynthesis of N-linked oligosaccharide precursors and shunted Dol-P-Man to the GPI pathway. Full restoration of Thy-1 and Ly-6A expression, however, required the stable transfection of a yeast Dol-P-Man synthase gene into the mutants. These results revealed that when the GPI core is limiting, there is a differential transfer of the available GPI core to proteins that contain GPI-anchor attachment sequences. Our findings also have implications for the elucidation of the defects in paroxysmal nocturnal hemoglobinuria.


Asunto(s)
Glucolípidos/metabolismo , Hemoglobinuria Paroxística/metabolismo , Hibridomas/metabolismo , Proteínas de la Membrana/análisis , Fosfatidilinositoles/metabolismo , Linfocitos T/metabolismo , Animales , Glicosilfosfatidilinositoles , Ratones , Mutación
9.
Biochim Biophys Acta ; 1489(2-3): 303-14, 1999 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-10673031

RESUMEN

In yeast, RAD52 has been shown to be essential for homologous recombination of DNA and to be involved in the repair of double-stranded DNA breaks. Recently, the human homologue of yeast RAD52, a 418-amino-acid protein, has been identified. In this study, we report three different isoforms of human RAD52 isolated from brain and testis cDNA libraries. cDNAs of these isoforms contain distinct insertions and encode truncated proteins due to translational frame-shifts. The three isoforms consist of 226-, 139-, and 118-amino-acid residues, and are designated as RAD52beta, gamma, and delta, respectively. The original RAD52 is termed as RAD52alpha in this paper. Messages of these isoforms have been detected in various human tissues. We found that the RAD52 isoforms were unable to interact with RAD52alpha because of partial defect of the self-interaction domain. Furthermore, like RAD52alpha, the isoforms have been shown to bind to both single-stranded and double-stranded DNA. These results suggest that RAD52beta, gamma, and delta might affect RAD52alpha function through their DNA-binding property and their inability to bind to RAD52alpha. Thus, these isoforms might act as dominant negative mutants or negative regulators of RAD52alpha.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Isoformas de Proteínas/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Cartilla de ADN , Humanos , Datos de Secuencia Molecular , Proteína Recombinante y Reparadora de ADN Rad52 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido
10.
Br J Radiol ; 88(1050): 20140814, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25906295

RESUMEN

OBJECTIVE: To probe the utility of dynamic contrast-enhanced MRI (DCE-MRI) parameters in assessing the clinical characteristics of oral squamous cell carcinoma. METHODS: A total of 85 tumours were included. We applied the Tofts and Kermode model for the DCE-MRI data and obtained three dependent parameters: the influx forward volume transfer constant into the extravascular extracellular space (EES) from the plasma (K(trans)), the fractional volume of EES per unit volume of tissue (ve) and the fractional volume of plasma (vp). We evaluated the correlations between these parameters and the clinical stages. RESULTS: The T stage showed a negative correlation with the K(trans) (r = -0.2272; p = 0.0365), but it did not show a significant correlation with the other parameters. The N stage showed a negative correlation with K(trans) (r = -0.1948; p = 0.0404), and there were significant differences between N1 and N2+3 (0.119 ± 0.027 vs 0.096 ± 0.023 min(-1); p = 0.0198) and between N0 and N2+3 (0.114 ± 0.29 vs 0.096 ± 0.023 min(-1); p = 0.0288). CONCLUSION: A decrease in the K(trans) at the primary site was found in advanced N stage cases, which might indicate that the hypoxic status cause a high possibility of the metastasis. ADVANCES IN KNOWLEDGE: A decrease in the K(trans) at the primary site suggested the high possibility of an advanced N stage.


Asunto(s)
Carcinoma de Células Escamosas/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de la Boca/patología , Anciano , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos
11.
Br J Radiol ; 88(1053): 20150159, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26153902

RESUMEN

OBJECTIVE: To evaluate the confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose screening CT with hybrid iterative reconstruction (IR). METHODS: Simulated lesions (emphysema, mediastinal masses and interstitial pneumonia) in a chest phantom were scanned by a 320-row area detector CT. The scans were performed by 64-row and 160-row helical scans at various dose levels and were reconstructed by filtered back projection (FBP) and IR. Emphysema, honeycombing and reticular opacity were visually scored on a four-point scale by six thoracic radiologists. The ground-glass opacity as a percentage of total lung volume (%GGO), CT value and contrast-to-noise ratio (CNR) of mediastinal masses were calculated. These scores and values were compared between FBP and IR. Wilcoxon's signed-rank test was used (p < 0.05). Interobserver agreements were evaluated by κ statistics. RESULTS: There were no significant differences in visual assessment. Interobserver agreement was almost perfect. CT values were almost equivalent between FBP and IR, whereas CNR with IR was significantly higher than that with FBP. %GGO significantly increased at low-dose levels with FBP; however, IR suppressed the elevation. CONCLUSION: The confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose CT screening were not degraded with hybrid IR compared with FBP. ADVANCES IN KNOWLEDGE: Hybrid IR did not degrade the confidence ratings of diagnoses on visual assessment and differential diagnoses based on CT value of mediastinal masses, and it showed the advantage of higher GGO conspicuity at low-dose level. Radiologists can analyse images of hybrid IR alone on low-dose CT screening for lung cancer.


Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Humanos , Fantasmas de Imagen , Radiografía Torácica/instrumentación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/instrumentación
12.
J Cereb Blood Flow Metab ; 5(4): 554-9, 1985 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-4055926

RESUMEN

To determine the possible role that leukotrienes (LTs) may play in the regulation of cerebral blood flow, the responses of cerebral arterioles to LTs and 12-hydroxyeicosatetraenoic acid (12-HETE) were studied in vivo in rabbits equipped with a cranial window for direct observation of the microcirculation. Topical application of LTC4, LTD4, or 12-HETE (1.6 X 10(-9)-3.1 X 10(-6) M) neither constricted nor dilated the pial arteries. LTB4 produced only a 5% vasoconstriction at 3.0 X 10(-6) M. However, bradykinin induced dose-dependent arteriolar vasodilation and histamine and 5-hydroxytryptamine induced dose-dependent arteriolar vasoconstriction. Although some LTs have potent vasoconstrictor activity in peripheral tissues and 5-lipoxygenase products have been hypothesized to be mediators of vasospasm after subarachnoid hemorrhage, LTB4, LTC4, LTD4, and 12-HETE apparently are unable to induce significant constriction of the cerebral arterioles in the anesthetized rabbit.


Asunto(s)
Bradiquinina/farmacología , Arterias Cerebrales/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Histamina/farmacología , Ácidos Hidroxieicosatetraenoicos/farmacología , SRS-A/farmacología , Serotonina/farmacología , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Animales , Arterias/efectos de los fármacos , Arterias Cerebrales/anatomía & histología , Masculino , Microcirculación/efectos de los fármacos , Piamadre/irrigación sanguínea , Conejos
13.
Gene ; 248(1-2): 1-14, 2000 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-10806345

RESUMEN

Ubiquitin is a small polypeptide that covalently modifies other cellular proteins and targets them to the proteasome for degradation. In recent years, ubiquitin-dependent proteolysis has been demonstrated to play a critical role in the regulation of many cellular processes, such as cell cycle progression, cell signaling, and immune recognition. The recent discovery of three new ubiquitin-like proteins, NEDD8, Sentrin/SUMO, and Apg12, has further broadened the horizon of this type of post-translational protein modification. This review will focus on the biology and biochemistry of the Sentrin/SUMO and NEDD8 modification pathways, which are clearly distinct from the ubiquitination pathway and have unique biological functions.


Asunto(s)
Péptido Hidrolasas , Ubiquitinas/metabolismo , Secuencia de Aminoácidos , Cisteína Endopeptidasas , Endopeptidasas/metabolismo , Humanos , Datos de Secuencia Molecular , Proteína NEDD8 , Procesamiento Proteico-Postraduccional , Proteína SUMO-1 , Homología de Secuencia de Aminoácido , Ubiquitinas/genética
14.
J Hypertens ; 8(11): 1003-6, 1990 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1963181

RESUMEN

We have investigated the growth characteristics of adult rat ventricular cells (ARVC) in culture from 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Protein synthesis in ARVC estimated from tritiated leucine uptake was augmented in both strains after exposure of cells to either norepinephrine or fetal bovine serum (FBS), but the response was significantly smaller in SHR than in WKY. A relative increase in the protein content of ARVC incubated with norepinephrine or FBS was also smaller in SHR than in WKY. These results demonstrate that SHR cardiac myocytes are not genetically growth-accelerated and show a decreased growth response to growth stimuli such as norepinephrine and serum during the adult period.


Asunto(s)
Envejecimiento/fisiología , Miocardio/patología , Animales , División Celular , Células Cultivadas/patología , Masculino , Norepinefrina/farmacología , Tamaño de los Órganos , Biosíntesis de Proteínas , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
15.
Immunol Lett ; 28(3): 219-25, 1991 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1679415

RESUMEN

Though the functional roles of human CD2 are well characterized, murine studies have been lacking until very recent years. Our previous work showed that a mAb against the T11(1)-like domain of CD2 clearly inhibited T cell proliferation induced by mitogenic and allo-antigenic stimuli, but the degree of inhibition was much smaller than had been demonstrated in the human system. In the present study, we observed functional aspects of murine CD2 on CD4+ T cell clones. It was shown that all T cell clones tested were CD2-positive, and that proliferation induced by APC + Ag was inhibited by anti-CD2 mAb. The maximum inhibition was also partial (40-60% inhibition) but CD2-mediated inhibition was observed even at concentrations as low as 0.2 microgram/ml. In contrast to the APC + Ag stimulation, the proliferation induced by lymphokines or immobilized anti-CD3 mAb was not inhibited at all. Taken together, these findings indicate that: (1) CD2 is also involved in the interaction between HTL and APC in murine system; but (2) perturbation of murine CD2 does not influence TCD/CD3- and lymphokine-mediated signal transduction.


Asunto(s)
Antígenos de Diferenciación de Linfocitos T/inmunología , Linfocitos T CD4-Positivos/inmunología , Activación de Linfocitos/inmunología , Receptores Inmunológicos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Células Presentadoras de Antígenos/inmunología , Antígenos CD2 , Línea Celular , Células Clonales , Citometría de Flujo , Interleucina-2/inmunología , Ratones , Ratones Endogámicos
16.
J Neurol ; 247(5): 356-63, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10896267

RESUMEN

To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied 8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral degeneration (SND), and 16 patients with idiopathic Parkinson's disease (PD) with a mean duration of illness shorter than 5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied. In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis of parkinsonian syndromes in addition to clinical criteria.


Asunto(s)
Encefalopatías/fisiopatología , Potenciales Evocados Visuales , Degeneración Nerviosa/fisiopatología , Enfermedad de Parkinson/fisiopatología , Degeneración Estriatonigral/fisiopatología , Parálisis Supranuclear Progresiva/fisiopatología , Anciano , Envejecimiento/fisiología , Enfermedades de los Ganglios Basales/fisiopatología , Corteza Cerebral , Personas con Discapacidad , Potenciales Relacionados con Evento P300 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Tiempo de Reacción , Valores de Referencia
17.
Eur J Pharmacol ; 100(2): 145-54, 1984 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-6329772

RESUMEN

The mechanism of nitroglycerin-induced vasodilation was examined in isolated arteries. Nitroglycerin relaxed the large coronary artery preferentially whereas nitroprusside and the so-called non-specific vasodilators showed the same activities on both the large and small coronary arteries. Nitroglycerin-induced vasodilation but not the vasodilation induced by the other agents was antagonized markedly by pretreatment with CuSO4. Other metal ions except Fe2+ had no antagonizing effect. The Cu2+-induced antagonism was restored by treatment with sulfhydryl reagents. Nitroglycerin formed inorganic nitrite by non-enzymatic reaction with the tissue sulfhydryl groups; the reaction was also inhibited by Cu2+ . Cu2+ suppressed the membrane stabilizing effect of Ca2+. It seems that nitroglycerin reacts with the sulfhydryl groups on the inner surface of the cell membrane, which may take part in the selectivity of this drug, and subsequently the intermediate(s) formed may activate guanylate cyclase.


Asunto(s)
Cobre/farmacología , Nitroglicerina/farmacología , Vasodilatación/efectos de los fármacos , Animales , Arterias/efectos de los fármacos , Perros , Ácido Etacrínico/farmacología , Femenino , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Nitritos/metabolismo , Nitroprusiato/farmacología , Papaverina/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Compuestos de Sulfhidrilo/farmacología , Verapamilo/farmacología
18.
Eur J Pharmacol ; 98(3-4): 357-66, 1984 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-6144557

RESUMEN

The mechanism of the hypotensive effect of 1-O-octadecyl-2-O-acetyl-glycero-3-phosphorylcholine (C18- AGPC ) was examined. Synthetic C18- AGPC caused dose-dependent hypotension in conscious rats. The activity was almost the same in DOCA and renal hypertensive rats. This suggests that it is not a renin inhibitor. Hypotension also appeared in pithed rats. This suggests that the effect is not due to a central mechanism. Hypotension did not result from platelet aggregation or bronchial constriction. Since C18- AGPC suppressed not only the pressor response to noradrenaline but also to angiotensin II and vasopressin, and furthermore, did not disturb the dose-response curve of noradrenaline in the isolated aorta, the possibility of the agent being an alpha-adrenergic antagonist is ruled out. In the PGF2 alpha-contracted rat aorta. C18- AGPC caused marked vasodilation, which disappeared after removal of the endothelium. Perfusion pressure decreased in the blood-perfused rat hindquarters but not in the Tyrode solution-perfused ones. C18- AGPC induced a positive inotropic effect in isolated rat atrium. The hypotensive effect of synthetic C18- AGPC seems to be mainly due to endothelium-dependent vasodilation.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Antihipertensivos/farmacología , Factor de Activación Plaquetaria/análogos & derivados , Vasodilatadores/farmacología , Animales , Aorta Torácica/fisiología , Función Atrial , Presión Sanguínea/efectos de los fármacos , Bronquios/efectos de los fármacos , Estado de Descerebración , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Contracción Miocárdica/efectos de los fármacos , Perfusión , Factor de Activación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Endogámicas , Vasodilatación/efectos de los fármacos
19.
Neurosci Lett ; 294(2): 89-92, 2000 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-11058794

RESUMEN

We studied scalp visual evoked potentials (VEPs) during a simple visual attention paradigm using a dot stimulus, which was presented every 1600 ms, at the center of a screen. The visual attention paradigm consisted of three tasks: task R, task L and task N. The subjects were instructed to press a button either with the right hand (task R) or with the left hand (task L) after seeing the dot. They were also instructed just to look at a dot, without pressing the button (task N). We defined N1 as a negative wave with a latency of 50-130 ms, P1 as a positive wave with a latency of 110-150 ms and N2 as a negative wave with a latency of 130-210 ms. During task R, P1-N2 amplitude at T6 was significantly greater than that at T5. The N1-P1 and N2 amplitudes at O2 were significantly greater than those at O1. During task L, the waveforms at T6 and O2 were more clearly detected than those at T5 and O1. We conclude that there is a functional dominance of the right cerebral hemisphere in our simple visual reaction tasks.


Asunto(s)
Encéfalo/fisiología , Dominancia Cerebral/fisiología , Potenciales Evocados Visuales/fisiología , Lateralidad Funcional/fisiología , Tiempo de Reacción/fisiología , Adulto , Atención/fisiología , Presentación de Datos , Electroencefalografía , Femenino , Humanos , Masculino , Estimulación Luminosa/métodos
20.
Neurosci Lett ; 282(3): 133-6, 2000 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-10717409

RESUMEN

P300 was evoked by a visual oddball and an S1-S2 task in 22 non-demented Parkinson's disease (PD) patients (13 in the early stage, nine in the late stage) and 18 normal controls. Reaction time was also measured. All patients undertook the (99)Tc-ECD SPECT examination. Quantitative regional cerebral blood flow (rCBF) was obtained by overlying SPECT image on the 3D-magnetic resonance image. In the PD patients in the late stage, P300 latency to S2-same and reaction time were significantly prolonged, while rCBF at bilateral frontal, temporal, and the right parietal lobes was decreased. P300 latency to S2-same was significantly correlated with the rCBF at bilateral temporal lobes. Reaction time was significantly correlated with the rCBF at the right frontal and parietal lobes, as well as the temporal and occipital lobes. The results suggest that P300 changes in non-demented PD in the late stage could be related to the temporal lobe dysfunction.


Asunto(s)
Circulación Cerebrovascular , Potenciales Relacionados con Evento P300 , Enfermedad de Parkinson/fisiopatología , Anciano , Electrooculografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Tiempo de Reacción , Tomografía Computarizada de Emisión de Fotón Único
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