RESUMEN
Photoemission orbital tomography (POT) from photoelectron momentum maps (PMMs) is a powerful technique that visualizes the shape of the molecular orbitals (MOs) of molecular films. For further utilization of POT, a simple and low-cost method of POT is highly required. Here, we propose a new POT method based on the PhaseLift algorithm (PhaseLift POT). This method utilizes a lifting procedure to convert the PMM, which is a second-order polynomial of MO coefficients, into a first-order polynomial of the lifted MO coefficients and further relaxes the equality constraint for a given PMM. We also established a method to improve the accuracy of phase retrieval from the noisy PMM data by using sparsity for MO coefficients (sparse PhaseLift POT). These methods make it possible to reconstruct the three-dimensional MOs, including phases of the wave function, directly from a single experimental PMM. This method can also precisely determine the adsorption-induced molecular deformations with an accuracy of 0.05 [Å]. Furthermore, the robust sparse PhaseLift POT is robust against unavoidable noise in the experimental PMMs due to the relaxation of the matching condition for a given PMM. Therefore, this will be an innovative tool for POT, especially for analyzing the dynamics of the molecules during the chemical reaction and excitation processes.
RESUMEN
Basal cell carcinoma (BCC) is the most common human malignancy. The biological behavior of this entity is remarkably indolent. Claudin plays an important role in tight junctions, regulating paracellular passage of variable substance including growth factors and maintaining the polarity of epithelia. Up- or downregulated claudin expression has been reported in many cancers. Nevertheless, claudin expression in BCC of the skin remains unclear. We therefore examined the status of claudin 1 and 4 expressions in BCC and adjacent normal skin by immunohistochemistry (IHC). Our IHC results demonstrated high claudin 1 expression and low claudin 4 expression in 33 of 34 lower-grade BCCs. In lower-grade BCC, claudin 1 was increased and claudin 4 was decreased compared with the normal skin. Claudin 1 was inclined to be highly expressed in the membrane and cytoplasm of tumour cells in the periphery of tumour nest. Conversely, almost all lower-grade BCCs (33/34) and one of two higher-grade BCC lacked or showed focal positivity for claudin 4. These results imply that the expression pattern is characteristics of lower-risk BCC. Interestingly, one of the two higher-grade BCCs demonstrated the converse expression patterns of claudins, with decreased claudin 1 and increased claudin 4. The combination of immunohistochemical claudin 1 and 4 expression may offer a useful ancillary tool for the pathological diagnosis of BCC. Furthermore, membranous and intracellular claudins may present future therapeutic targets for uncontrollable BCC.
RESUMEN
BACKGROUND/AIM: This study aimed to assess the effects of telmisartan (TEL), a potential antitumor agent, and its mechanism of action in the regulation of apoptosis, autophagy, and cell cycle in scirrhous gastric cancer (SGC). MATERIALS AND METHODS: The effect of TEL on the viability and chromatin condensation of OCUM-2M and OCUM-12 cells was assessed. Protein expression and the cell cycle were analysed using western blotting and flow cytometry, respectively. RESULTS: TEL inhibited cell proliferation in a dose-dependent manner and increased chromatin condensation and autophagy marker LC3-II levels in OCUM-12 cells. TEL also increased the proportion of cells in the G0/G1 phase transition. CONCLUSION: Apoptosis and autophagy are partially involved in the inhibitory effect of TEL on cell proliferation. Additionally, TEL caused G0/G1 cell cycle arrest. Therefore, TEL could be a promising treatment for SGC.
Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Fase G1/efectos de los fármacos , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Telmisartán/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Humanos , Proteínas Asociadas a Microtúbulos/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaAsunto(s)
Interleucina-8 , Enfermedades de la Piel , Vasculitis Leucocitoclástica Cutánea , Eritema , Humanos , PielRESUMEN
AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.
Asunto(s)
Carcinoma Adenoide Quístico , Neoplasias de Cabeza y Cuello , Radioterapia de Iones Pesados , Reirradiación , Neoplasias de las Glándulas Salivales , Carcinoma Adenoide Quístico/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recurrencia Local de Neoplasia/radioterapia , Dosificación Radioterapéutica , Neoplasias de las Glándulas Salivales/radioterapiaRESUMEN
Tritium dating requires a good understanding of the tritium and water inputs into hydrologic systems, including their main trends due to latitudinal, seasonal and altitudinal effects. Although tritium reached ambient levels at the end of the 20th century, tritium released from nuclear facilities and bomb tests since then has the potential to confound use of tritium for age dating. We therefore collected precipitation and snowpack samples for tritium analysis to confirm that tritium levels in Japanese precipitation had not exceeded ambient levels following the North Korean nuclear tests in January 6th 2016 and September 3rd 2017. As the result, the highest tritium concentration was 5.52(±0.27)TU at samples collected from January 8 to 11th at one Honshu and four Hokkaido locations and samples collected at six Honshu locations had 8.01(±1.5)TU from September 6 to 19th 2017. Confirming ambient tritium concentrations after both events we investigated the latitude tritium effect at selected coastal stations in Asia, indicating a break of latitude trend around Tokyo area, and established the latitude scaling factors to the north and south of the Tokyo area data. The seasonal trend was investigated during the winter-spring 2016 in precipitation samples confirming the higher spring tritium compared with winter continental tritium values. The altitude effect on tritium and stable (18O and 2H) isotopes was observed in Hokkaido snowpack, which had tritium concentrations ranging between 4.08 and 5.93 TU during March-April, and demonstrated two trends for western and central Hokkaido mountain ranges. Using established latitude and altitude scaling factors with the long-term continuous time-series of monthly Tokyo area tritium we estimated the annual weighted tritium at 110 meteorological stations in Japan with monthly precipitation demonstrating the applicability of this approach for future tritium-tracer studies across Asia.
RESUMEN
The Fukushima accident was a compounding disaster following the strong earthquake and huge tsunami. The direct health effects of radiation were relatively well controlled considering the severity of the accident, not only among emergency workers but also residents. Other serious health issues include deaths during evacuation, collapse of the radiation emergency medical system, increased mortality among displaced elderly people and public healthcare issues in Fukushima residents. The Fukushima mental health and lifestyle survey disclosed that the Fukushima accident caused severe psychological distress in the residents from evacuation zones. In addition to psychiatric and mental health problems, there are lifestyle-related problems such as an increase proportion of those overweight, an increased prevalence of hypertension, diabetes mellitus and dyslipidaemia and changes in health-related behaviours among evacuees; all of which may lead to an increased cardiovascular disease risk in the future. The effects of a major nuclear accident on societies are diverse and enduring. The countermeasures should include disaster management, long-term general public health services, mental and psychological care, behavioural and societal support, in addition to efforts to mitigate the health effects attributable to radiation.
Asunto(s)
Desastres , Terremotos , Accidente Nuclear de Fukushima , Trabajo de Rescate , Tsunamis , Planificación en Desastres , Tratamiento de Urgencia , Estado de Salud , Humanos , Japón , Estilo de Vida , Salud Mental , Plantas de Energía Nuclear , Efectos de la RadiaciónRESUMEN
STUDY DESIGN: A cross-sectional study. OBJECTIVES: Neuropathic pain (NP) after spinal cord injury (SCI) tends to be hard to treat, and its heterogeneous properties make it difficult to identify and characterize. This study was conducted to assess the characteristics of SCI-related NP in detail. SETTING: A single hospital for SCI rehabilitation. METHODS: This study included 72 patients who were seen at our hospital in 2012 and 2013 and who had sustained SCI at least 3 months before enrollment. The patients completed the Neuropathic Pain Symptom Inventory (NPSI) and the Short Form (SF)-36 Health Inventory. The NPSI score was analyzed for correlations with clinical presentations of SCI and SF-36 subitems. RESULTS: Paresthesia/dysesthesia was the most common subtype of NP after SCI. With regard to location, below-level superficial NP was significantly more intense than at-level pain. Patients who underwent surgery showed significantly less evoked pain compared with patients with non-surgery. Patients reported significantly more severe pain if >1 year had elapsed after the SCI. Patients with an American Spinal Injury Association Impairment Scale grade of B for completeness of injury reported more intense NP than those with other grades. Among the SF-36 subitems, NP correlated significantly with bodily pain, general health and mental health. CONCLUSION: NP in SCI patients was significantly associated with the location of pain, the time period since the injury, surgery and quality-of-life factors. A more detailed understanding of the characteristics of NP may contribute to better strategies for relieving the pain associated with SCI.
Asunto(s)
Neuralgia/etiología , Calidad de Vida/psicología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Traumatismos de la Médula Espinal/cirugía , Estadística como Asunto , Estadísticas no ParamétricasRESUMEN
A novel process by using chemical leaching followed by bacterial reductive precipitation was proposed for selenium recovery from kiln powder as a byproduct of cement manufacturing. The kiln powder at a slurry concentration of 10 w/v% with 0.25 M Na2CO3 at 28°C produced wastewater containing about 30 mg-Se/L selenium. The wastewater was diluted four-fold and adjusted to pH 8.0 as preconditioning for bioreduction. A bacterial strain Pseudomonas stutzeri NT-I, capable of reducing selenate and selenite into insoluble elemental selenium, could recover about 90% selenium from the preconditioned wastewater containing selenium of 5 mg-Se/L when supplemented with lactate or glycerol. The selenium concentrations in the treated wastewater were low around the regulated effluent concentration of 0.1 mg-Se/L in Japan.
Asunto(s)
Pseudomonas stutzeri/metabolismo , Ácido Selénico/metabolismo , Selenio/aislamiento & purificación , Precipitación Química , Residuos Industriales , Japón , Oxidación-Reducción , Selenio/metabolismo , Compuestos de Selenio , Aguas ResidualesRESUMEN
The life expectancies and causes of death were evaluated in 299,555 dogs insured in Japan between 1 April 2010 and 31 March 2011, of which 4169 dogs died during this period. The overall life expectancy of dogs was 13.7 years. The probability of death was high in the first year of life, lowest in the second and third years, and increased exponentially after 3 years of age. The life expectancy was 13.8 years in the <5 kg body weight group, 14.2 years in the 5-10 kg body weight group, 13.6 years in the 10-20 kg body weight group, 12.5 years in the 20-40 kg body weight group and 10.6 years in the ≥40 kg body weight group. As body weight increases, life expectancy tended to decrease except in the <5 kg body weight group. The probability of death increased as dogs got older for most potential causes of death. Neoplasia resulted in the highest probability of death, especially in the large and giant breed groups. Cardiovascular system disorders were the second major cause of death and the toy group had a probability of death significantly higher than the other breed groups at age 12+.
Asunto(s)
Causas de Muerte , Enfermedades de los Perros/mortalidad , Tablas de Vida , Animales , Enfermedades de los Perros/etiología , Perros , Femenino , Seguro/estadística & datos numéricos , Japón/epidemiología , MasculinoRESUMEN
We calculated the annual prevalence of diseases of 18 diagnostic categories in the insured dog population in Japan, using data from 299,555 dogs insured between April 2010 and March 2011. The prevalence was highest for dermatological disorders (22.6% for females and 23.3% for males), followed by otic diseases (16.4% for females and 17.2% for males) and digestive system disorders (15.7% for females and 16.4% for males). The prevalence of cardiovascular, urinary, neoplasia and endocrine disorders, increased with age; infectious diseases and injuries showed a high prevalence at young ages, and the prevalence of musculoskeletal and respiratory disorders showed a bimodal peak at young and old ages. A large variation in prevalence was observed between breeds for dermatological, otic, digestive, ophthalmological and cardiovascular disorders.
Asunto(s)
Enfermedades de los Perros/epidemiología , Distribución por Edad , Animales , Enfermedades de los Perros/etiología , Enfermedades de los Perros/genética , Perros , Femenino , Japón/epidemiología , Masculino , Prevalencia , Especificidad de la EspecieAsunto(s)
Regulación de la Expresión Génica , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , FN-kappa B/metabolismo , ARN sin Sentido/metabolismo , ARN Viral/metabolismo , eIF-2 Quinasa/metabolismo , Adulto , Secuencia de Bases , Western Blotting , Citometría de Flujo , Genoma Viral , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Datos de Secuencia Molecular , FN-kappa B/genética , ARN sin Sentido/genética , ARN Mensajero/genética , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Células Tumorales Cultivadas , eIF-2 Quinasa/genéticaRESUMEN
OBJECTIVE: Aging is a major risk factor for osteoarthritis (OA). Forkhead-box class O (FoxO) transcription factors regulate mechanisms of cellular aging, including protein quality control, autophagy and defenses against oxidative stress. The objective of this study was to analyze FoxO transcription factors in normal, aging and OA cartilage. DESIGN: Knee joints from humans ages 23-90 and from mice at the age of 4-24 months and following surgically induced OA were analyzed for expression of FoxO proteins. Regulation of FoxO protein expression and activation was analyzed in cultured chondrocytes. RESULTS: Human cartilage expressed FOXO1 and FOXO3 but not FOXO4 proteins. FOXO1 and FOXO3 were more strongly expressed the superficial and mid zone as compared to the deep zone and were mainly localized in nuclei. During human joint aging, expression of FOXO1 and FOXO3 was markedly reduced in the superficial zone of cartilage regions exposed to maximal weight bearing. In OA cartilage, chondrocyte clusters showed strong FOXO phosphorylation and cytoplasmic localization. Similar patterns of FOXO expression in normal joints and changes in aging and OA were observed in mouse models. In cultured chondrocytes, IL-1ß and TNF-α suppressed FOXO1, while TGF-ß and PDGF increased FOXO1 and FOXO3 expression. FOXO1 and FOXO3 phosphorylation was increased by IL-1ß, PDGF, bFGF, IGF-1, and the oxidant t-BHP. CONCLUSIONS: Normal articular cartilage has a tissue specific signature of FoxO expression and activation and this is profoundly altered in aging and OA in humans and mice. Changes in FoxO expression and activation may be involved in cartilage aging and OA.
Asunto(s)
Envejecimiento/metabolismo , Cartílago Articular/metabolismo , Factores de Transcripción Forkhead/metabolismo , Osteoartritis de la Rodilla/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Animales , Artritis Experimental/metabolismo , Artritis Experimental/patología , Cartílago Articular/patología , Proteínas de Ciclo Celular , Células Cultivadas , Condrocitos/metabolismo , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Humanos , Articulación de la Rodilla/metabolismo , Ratones , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Fosforilación , Factores de Transcripción/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Apoptosis appears to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM). We have previously reported 3 HCM patients carrying the E334K MYBPC3, and that heterologous expression of E334K cMyBPC in cultured cells induced apoptosis. The purpose of this study was to identify pharmacological agents that would inhibit apoptosis in HL-1 cardiomyocytes expressing E334K cMyBPC. METHODS AND RESULTS: E334K cMyBPC expression in cells increased levels of pro-apoptosis (p53, Bax and cytochrome c) and decreased levels of anti-apoptosis (Bcl-2 and Bcl-XL). While the beta blocker carvedilol (1 µM) normalized the level of p53 and Bcl-2 and the calcium channel blocker (CCB) bepridil (0.5 µM) normalized that of Bcl-2, both the CCB azelnidipine (1 µM) and the angiotensin receptor blocker (ARB) olmesartan (10 µM) normalized those of p53, Bax, cytochrome c, and Bcl-XL. Among those proteins, cytochrome c was the one which showed the highest degree of change. Both azelnidipine (0.1 µM) and olmesartan (1 µM) reduced the level of cytochrome c by 40.2 ± 4.3% and 31.3 ± 5.1%, respectively. The CCB amlodipine and the ARB valsartan reduced it only by 19.1 ± 2.1% and 20.1 ± 5.2%, respectively. Flow cytometric analysis and annexin V staining showed that treatment of cells with azelnidipine (0.1 µM) plus olmesartan (0.3 µM) or that with amlodipine (0.1 µM) plus valsartan (0.3 µM) reduced the number of apoptotic cells by 35.8 ± 10.5% and 18.4 ± 3.2%, respectively. CONCLUSION: Azelnidipine plus olmesartan or amlodipine plus valsartan inhibited apoptosis of HL-1 cells expressing E334K cMyBPC, and the former combination was more effective than the latter.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Apoptosis/efectos de los fármacos , Ácido Azetidinocarboxílico/análogos & derivados , Bloqueadores de los Canales de Calcio/farmacología , Proteínas Portadoras/fisiología , Dihidropiridinas/farmacología , Imidazoles/farmacología , Miocitos Cardíacos/efectos de los fármacos , Tetrazoles/farmacología , Animales , Ácido Azetidinocarboxílico/farmacología , Células Cultivadas , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteína bcl-X/análisisRESUMEN
We examined the efficacy and safety of 4-drug combination therapy using high-dose mizoribine (MZR) (8 mg/kg/d), cyclosporine (CsA), basiliximab (BXM), and steroid (STR) in 39 renal transplant recipients. Acute rejection episodes (ARE), which occurred in 9 (23.1%) patients, correlated with lower blood levels of MZR (trough levels ≥ 2 µg/mL). In addition, lower MZR concentrations tended to be associated with a higher incidence of rejection episodes in children aged ≤ 10 years than in those aged ≥ 11 years. The area under the received operating characteristics (ROC) curve of MZR trough level to pred ARE was 0.825 (95% confidence interval, 0.690-0.962; P = .002). Based on the ROC analysis, are MZR cut-off of 1.6 µg/mL showed a sensitivity of 81.8% and a specificity of 75.0%. Adverse events were observed in 23 patients, including infections in 11 (7 patients positive for cytomegalovirus [CMV] antigen and 4 treated with anti-CMV drugs). The MZR trough levels seemed to be higher among patients with adverse events than in those free of them, but it was no significant. All patients experienced successful engraftment except 1 who died of unknown cause with a functioning graft. In conclusion, our study showed that low MZR trough levels correlated with the incidence of ARE. No serious adverse effects were encountered with this therapy.