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1.
ESMO Open ; 8(6): 102030, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37852033

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients. PATIENTS AND METHODS: This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk. RESULTS: Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86). CONCLUSIONS: An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonía , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Retrospectivos , Neumonía/inducido químicamente , Neumonía/epidemiología
2.
J Hosp Infect ; 129: 75-81, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35987317

RESUMEN

BACKGROUND: Staphylococcus aureus - both meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) - is a major cause of neonatal infections. Infection control measures have not lowered the incidence of MSSA infections to the same degree as that of MRSA infections. AIM: To investigate the transmission pathway of MSSA in neonatal intensive care unit (NICU) using genetic analysis. METHODS: Neonatal patients, their parents, and healthcare workers were swab-tested in the NICU at our hospital at the time of hospitalization and then every month thereafter from October 1st, 2018 to March 31st, 2019. Whole-genome sequencing was performed to test for MSSA strains. Multi-locus sequence typing and single nucleotide polymorphism analysis were used to identify strains and understand their relatedness. FINDINGS: There were 16 MSSA-positive patients. Four MSSA-positive patients shared strains from the same phylogenetic groups as those of healthcare workers. One presented the same strain as the parent. MSSA-positive twin neonates shared the same strain. Ten had sporadic strains; 32 of the 97 tested healthcare workers were MSSA positive. CONCLUSION: The findings of this study suggest that the route of transmission of MSSA in NICU may be through MSSA in the hospital environment in addition to horizontal transmission via healthcare workers. Along with hand hygiene with alcohol, thorough environmental maintenance and parental education are important for infection control in NICUs targeting MSSA.


Asunto(s)
Infección Hospitalaria , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Recién Nacido , Humanos , Staphylococcus aureus/genética , Unidades de Cuidado Intensivo Neonatal , Epidemiología Molecular , Staphylococcus aureus Resistente a Meticilina/genética , Meticilina , Tipificación de Secuencias Multilocus , Filogenia , Infecciones Estafilocócicas/prevención & control , Infección Hospitalaria/prevención & control
3.
Clin. transl. oncol. (Print) ; 24(3): 568-577, marzo 2022.
Artículo en Inglés | IBECS | ID: ibc-203551

RESUMEN

ObjectivesRecently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20–30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab.Patients and methodsA total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed.ResultsPatients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%).ConclusionPD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.


Asunto(s)
Humanos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Antígeno B7-H1/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/metabolismo , Carcinoma , Estudios Retrospectivos
4.
Clin Transl Oncol ; 24(3): 568-577, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34687441

RESUMEN

OBJECTIVES: Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20-30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab. PATIENTS AND METHODS: A total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed. RESULTS: Patients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%). CONCLUSION: PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/biosíntesis , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/metabolismo , Moléculas de Adhesión Celular/biosíntesis , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Acta Endocrinol (Buchar) ; 17(2): 226-233, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34925572

RESUMEN

CONTEXT: Physical activity is important for the management of metabolic functions; however, little is known whether performing home-based moderate-intensity exercise (MIE) obtains further improvement on metabolic functions in adults with non-communicable diseases (NCDs) who already perform regular gym-based MIE. OBJECTIVE: The purpose of this study was to examine the effect of adding home-based MIE on metabolic functions in older adults with NCDs who have regularly performed gym-based MIE. DESIGN: This was a single-center randomized controlled study. The observation period was set for 24 weeks. SUBJECTS AND METHODS: Twenty-one older adults (age, 60-79 years) with uncomplicated NCDs, who have performed 30-40 min MIE, 2-3 days/week at a hospital gym for over 1 year, were randomly divided into two groups: performing home-based MIE, comprising aerobic and resistance exercises, at least 20 min/day, 3 days/week (HOME, n = 11), or not performing home-based MIE (CON, n = 10). All participants completed the study and continued their gym-based MIE as usual. RESULTS: After 24 weeks, there were no significant differences in the values of any outcomes. Conversely, the decrease in waist circumference (WC) was larger in the HOME group (-2.17 [-3.98, -0.36] cm) than in the CON group (0.57 [-1.42, 2.56] cm) (p < 0.05), although not in other outcomes. CONCLUSIONS: Although further studies are needed, we found that adding home-based MIE had a positive effect on WC, but little effect on other metabolic functions in older adults with NCDs who have continued regular gym-based MIE.

6.
Phys Rev Lett ; 123(13): 137203, 2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31697552

RESUMEN

The organizing of magnetic skyrmions shows several forms similar to atomic arrays of solid states. Using Lorentz transmission electron microscopy, we report the first direct observation of a stable liquid-crystalline structure of skyrmions in chiral magnet Co_{8.5}Zn_{7.5}Mn_{4}(110) thin film, caused by magnetic anisotropy and chiral surface twist. Elongated skyrmions are oriented and periodically arranged only in the ⟨110⟩ directions, whereas they exhibit short-range order along the ⟨001⟩ directions, indicating a smectic skyrmion state. In addition, skyrmions possess anisotropic interaction with an opposite sign depending on the crystal orientation, in contrast to existing isotropic interaction.

7.
Science ; 364(6437): 272-275, 2019 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-30890589

RESUMEN

The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu's surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.

8.
Osteoporos Int ; 30(3): 621-628, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30460382

RESUMEN

In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ. INTRODUCTION: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ. METHODS: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction. RESULTS: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036). CONCLUSIONS: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years.


Asunto(s)
Osteoporosis/fisiopatología , Extracción Dental , Cicatrización de Heridas/fisiología , Anciano , Anciano de 80 o más Años , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/farmacología , Femenino , Humanos , Cifosis/fisiopatología , Masculino , Persona de Mediana Edad , Osteoporosis/tratamiento farmacológico , Fracturas Osteoporóticas/fisiopatología , Periodo Posoperatorio , Factores de Riesgo , Fracturas de la Columna Vertebral/fisiopatología , Factores de Tiempo , Listas de Espera , Cicatrización de Heridas/efectos de los fármacos
9.
Physiol Res ; 67(1): 117-126, 2018 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-29137485

RESUMEN

This study aimed to investigate whether heat stress (HS) prevents a decrease in succinate dehydrogenase (SDH) activity and heat shock protein 60 (HSP60) and superoxide dismutase 2 (SOD2) contents in the extensor digitorum longus of streptozotocin (STZ)-induced diabetic rats. Twelve-week-old male Wistar rats were assigned to one of the four groups (n=6/group): control (Con), HS, diabetes mellitus (DM), and diabetes mellitus and heat stress (DM+HS). Diabetes was induced by the administration of STZ (50 mg/kg). HS was initiated 7 days after STZ treatment and performed at 42 °C for 30 min 5 times a week for 3 weeks. SDH activity was decreased in the DM and DM+HS groups. However, SDH activity was greater in the DM+HS group than in the DM group. Although HSP60 content was lower in the DM group than in the Con group, it was maintained in the DM+HS groups and was higher than that in the DM group. SOD2 content was decreased only in the DM group. These findings suggest that HS prevents the decrease in SDH activity in the skeletal muscle induced by DM. According to this mechanism, the maintenance of SOD2 and HSP60 by HS may suppress the increase in oxidative stress.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Respuesta al Choque Térmico/fisiología , Músculo Esquelético/enzimología , Succinato Deshidrogenasa/metabolismo , Animales , Glucemia/metabolismo , Chaperonina 60/metabolismo , Activación Enzimática/fisiología , Masculino , Proteínas Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Ratas , Ratas Wistar , Estreptozocina , Superóxido Dismutasa/metabolismo
11.
Cell Death Dis ; 6: e1880, 2015 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-26355343

RESUMEN

Epithelial-to-mesenchymal transition (EMT) and the reverse process mesenchymal-to-epithelial transition (MET) are events involved in development, wound healing and stem cell behaviour and contribute pathologically to cancer progression. The identification of the molecular mechanisms underlying these phenotypic conversions in hepatocytes are fundamental to design specific therapeutic strategies aimed at optimising liver repair. The role of autophagy in EMT/MET processes of hepatocytes was investigated in liver-specific autophagy-deficient mice (Alb-Cre;ATG7(fl/fl)) and using the nontumorigenic immortalised hepatocytes cell line MMH. Autophagy deficiency in vivo reduces epithelial markers' expression and increases the levels of mesenchymal markers. These alterations are associated with an increased protein level of the EMT master regulator Snail, without transcriptional induction. Interestingly, we found that autophagy degrades Snail in a p62/SQSTM1 (Sequestosome-1)-dependent manner. Moreover, accordingly to a pro-epithelial function, we observed that autophagy stimulation strongly affects EMT progression, whereas it is necessary for MET. Finally, we found that the EMT induced by TGFß affects the autophagy flux, indicating that these processes regulate each other. Overall, we found that autophagy regulates the phenotype plasticity of hepatocytes promoting their epithelial identity through the inhibition of the mesenchymal programme.


Asunto(s)
Autofagia/genética , Transición Epitelial-Mesenquimal/genética , Animales , Línea Celular Tumoral , Ratones , Factores de Transcripción/metabolismo
12.
Bone Joint J ; 97-B(7): 957-62, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26130352

RESUMEN

There is no consensus on the benefit of arthroscopically assisted reduction of the articular surface combined with fixation using a volar locking plate for the treatment of intra-articular distal radial fractures. In this study we compared the functional and radiographic outcomes of fluoroscopically and arthroscopically guided reduction of these fractures. Between February 2009 and May 2013, 74 patients with unilateral unstable intra-articular distal radial fractures were randomised equally into the two groups for treatment. The mean age of these 74 patients was 64 years (24 to 92). We compared functional outcomes including active range of movement of the wrist, grip strength and Disabilities of the Arm, Shoulder, and Hand scores at six and 48 weeks; and radiographic outcomes that included gap, step, radial inclination, volar angulation and ulnar variance. There were no significant differences between the techniques with regard to functional outcomes or radiographic parameters. The mean gap and step in the fluoroscopic and arthroscopic groups were comparable at 0.9 mm (standard deviation (SD) 0.7) and 0.7 mm (SD 0.7) and 0.6 mm (SD 0.6) and 0.4 mm (SD 0.5), respectively; p = 0.18 and p = 0.35). Arthroscopic reduction conferred no advantage over conventional fluoroscopic guidance in achieving anatomical reduction of intra-articular distal radial fractures when using a volar locking plate.


Asunto(s)
Artroscopía , Placas Óseas , Fijación Interna de Fracturas/métodos , Fracturas del Radio/cirugía , Traumatismos de la Muñeca/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/fisiopatología , Recuperación de la Función , Resultado del Tratamiento , Traumatismos de la Muñeca/diagnóstico por imagen , Traumatismos de la Muñeca/fisiopatología , Adulto Joven
13.
Spinal Cord ; 53(4): 306-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25644389

RESUMEN

STUDY DESIGN: Prospective cross-sectional study. OBJECTIVES: To investigate the timing of deep vein thrombosis (DVT) onset secondary to spinal cord injury without anticoagulant therapies. SETTING: Spinal Cord Injury Center in Hokkaido, Japan. METHODS: Between November 2012 and June 2013, patients with spinal cord injury who were admitted to our hospital within 1 day after the injury and treated surgically within 24 h underwent a neurological examination, leg vein ultrasonography and D-dimer test 1, 3, 7, 14 and 28 days after surgery. All patients received treatment with intermittent pneumatic compression and elastic stockings, but without any anticoagulant. RESULTS: DVT developed in 12 patients (11 men and 1 women), with a mean age of 62.2 years (range, 41-80 years; mean age of total sample, 63.2 years (range, 25-78 years)), all distal to the popliteal vein. DVT occurred more often with a more severe paralysis (66.3%, AIS A and B). The median (± standard error) length of time from the operation to DVT detection was 7.5±2.2 days. The mean D-dimer level upon DVT detection was 14.6±11.8 µg ml(-1), with no significant differences between those who developed DVT and those who did not at any of the time points. CONCLUSION: These results suggest that DVT can develop at the very-acute stage of spinal cord injury and the incidence increases with a more severe paralysis. DVT detection was more reliable with ultrasonography, which should be used with DVT-preventive measures, beginning immediately after the injury, for the management of patients with spinal cord injury.


Asunto(s)
Traumatismos de la Médula Espinal/complicaciones , Trombosis de la Vena/complicaciones , Enfermedad Aguda , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Parálisis/complicaciones , Parálisis/diagnóstico por imagen , Parálisis/epidemiología , Estudios Prospectivos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/cirugía , Factores de Tiempo , Ultrasonografía , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología
14.
Tissue Antigens ; 83(1): 45-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24355007

RESUMEN

A genetic polymorphism of the newly discovered interferon-λ 4 (IFNL4) gene was associated with hepatitis C virus (HCV) clearance in individuals of African ancestry. To assess whether a dinucleotide variant of IFNL4 (ss469415590) also affected treatment outcome of antiviral therapy in Japan, we genotyped 213 patients with chronic genotype 1 HCV infection and 176 healthy subjects. The ΔG allele was associated with treatment failure [odds ratio (OR) 4.73, P = 0.019], as was the IFL3 rs8099917 single nucleotide polymorphism (SNP) (OR 5.06, P = 0.068). The correlation between ss469415590 and rs8099917 was high (r(2) = 0.92, D' = 0.98). Multivariate analysis revealed that the rs8099917 SNP was independently associated with treatment failure (OR 5.28, P = 0.009). Therefore, ss469415590 may be another predictive marker of antiviral therapy outcome in the Japanese population.


Asunto(s)
Hepatitis C Crónica/genética , Hepatitis C Crónica/terapia , Interferón-alfa/uso terapéutico , Interleucinas/genética , Ribavirina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Hepatitis C Crónica/diagnóstico , Humanos , Japón , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Resultado del Tratamiento , Adulto Joven
15.
Scand J Rheumatol ; 42(4): 325-30, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23496326

RESUMEN

OBJECTIVES: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. METHOD: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland. RESULTS: Among the 22 patients (19%) in our cohort who were found to have hypothyroidism [thyroid stimulating hormone (TSH) > 4 mIU/L], 11 patients had clinical hypothyroidism [free thyroxine (FT4) < 1 ng/dL] and 11 patients had subclinical hypothyroidism (FT4 ≥ 1 ng/dL). Serum concentrations of IgG, IgG4, circulating immune complex (CIC), and ß2-microglobulin (ß2-MG) were significantly higher in the hypothyroidism group compared with the remaining 92 euthyroid patients, and serum C3 concentration was significantly lower. After prednisolone treatment, TSH values had decreased significantly (p = 0.005) in this group and FT4 values had increased significantly (p = 0.047). CT images showed that the thyroid glands of patients with clinical hypothyroidism had a significantly greater volume than those of the euthyroid and other groups. Pathological analysis of one resected thyroid gland disclosed a focused lesion with infiltration of lymphocytes and IgG4-bearing plasma cells and loss of thyroid follicles. CONCLUSIONS: Thyroid lesions associated with hypothyroidism can be considered as a new disease termed IgG4-related thyroiditis. Awareness of this condition should lead to appropriate corticosteroid treatment that may prevent progression to a fibrous state.


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Hipotiroidismo/diagnóstico , Hipotiroidismo/inmunología , Inmunoglobulina G/inmunología , Enfermedad de Mikulicz/diagnóstico , Pancreatitis/diagnóstico , Tiroiditis Autoinmune/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Enfermedades Autoinmunes/complicaciones , Colangitis/complicaciones , Colangitis/diagnóstico , Colangitis/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Hipotiroidismo/complicaciones , Masculino , Persona de Mediana Edad , Enfermedad de Mikulicz/complicaciones , Enfermedad de Mikulicz/inmunología , Pancreatitis/complicaciones , Pancreatitis/inmunología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Estadísticas no Paramétricas , Pruebas de Función de la Tiroides , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/inmunología
16.
Horm Metab Res ; 45(7): 501-6, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23508717

RESUMEN

Cytosolic 3,5,3'-triiodo-l-thyronine-binding protein plays pivotal roles in the regulation of intracellular 3,5,3'-triiodo-l-thyronine concentration in vivo. The expression of the protein, which is identical to µ-crystallin, is regulated by various factors. To elucidate the mechanisms of its expression, we evaluated the promoter transactivity and insulin signaling via the AP-1 site in the promoter. The isolated 600 bp human and 1976 bp mouse 5'-flanking regions were cloned in a luciferase reporter plasmid. The luciferase activity was estimated in GH3, dRLh-84, HEK293, and insulin receptor-overexpressing CHO-IR cells. The effects of 12-O-tetradecanoylphorbol 13-acetate and insulin on µ-crystallin mRNA expression were evaluated in various cells. The region between -200 and the transcriptional start site was crucial for constitutive expression in µ-crystallin-expressing dRLh-84 cells. This region contained an AP-1 site. 12-O-Tetradecanoylphorbol 13-acetate increased the level of µ-crystallin mRNA expression in HEK 293 cells. The compound also increased luciferase activity through the promoter. Mutation in the AP1 site diminished the response to the compound. The promoter was also activated by insulin treatment in CHO-IR cells. Insulin treatment increased µ-crystallin mRNA expression in Raw264.7 cells, but decreased in HEK293, P19, and dRLH-84 cells. The expression of µ-crystallin was regulated through the AP-1 site in the promoter. The signals related to AP-1 activation, such as insulin signaling may have diverse effects on µ-crystallin mRNA expression.


Asunto(s)
Cristalinas/química , Cristalinas/genética , Regiones Promotoras Genéticas , Triyodotironina/metabolismo , Regulación hacia Arriba , Animales , Sitios de Unión , Línea Celular , Cristalinas/metabolismo , Genes Reporteros , Humanos , Insulina/metabolismo , Ratones , Unión Proteica , Acetato de Tetradecanoilforbol/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Activación Transcripcional , Cristalinas mu
17.
Strahlenther Onkol ; 189(1): 26-32, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23161117

RESUMEN

BACKGROUND AND PURPOSE: Primary subglottic cancer is a rare malignancy. We investigated the efficacy and toxicity of radiotherapy for subglottic cancer. PATIENTS AND METHODS: Nineteen patients with primary squamous cell carcinoma of the subglottis received radiotherapy, 14 of whom also underwent chemotherapy. Of the 19 patients, 15 received definitive radiotherapy to the gross tumors with total doses of 70-70.2 Gy in 35-39 fractions, and 4 underwent preoperative radiotherapy with total doses of 37.8-55.8 Gy in 21-31 fractions, followed by total laryngectomy. RESULTS: Of the 19 patients, 5 developed local progression and 2 developed distant metastasis at the median follow-up period of 5 years. The 5-year local control and disease-free rates were 74 and 63%, respectively. Three patients died of tumor progression, and the 5-year overall and disease-free survival rates were 80 and 63%, respectively. Regarding acute toxicities, transient mucositis and dermatitis of grade 3 or lower were observed in all patients, but there were no late toxicities of grade 3 or higher. CONCLUSION: Radiotherapy is a safe and effective treatment for patients with primary squamous cell carcinoma of the subglottis. The use of chemotherapy together with radiotherapy may enhance treatment efficacy and contribute to larynx preservation through good local control.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/radioterapia , Laringe/efectos de la radiación , Traumatismos por Radiación/etiología , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Laríngeas/patología , Laringectomía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Dosificación Radioterapéutica , Resultado del Tratamiento
18.
Phys Rev Lett ; 109(18): 186804, 2012 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-23215312

RESUMEN

We performed systematic spin- and angle-resolved photoemission spectroscopy of TlBi(S(1-x)Se(x))(2) which undergoes a topological phase transition at x ~ 0.5. In TlBiSe(2) (x = 1.0), we revealed a helical spin texture of Dirac-cone surface states with an intrinsic in-plane spin polarization of ~0.8. The spin polarization still survives in the gapped surface states at x > 0.5, although it gradually weakens upon approaching x = 0.5 and vanishes in the nontopological phase. No evidence for the out-of-plane spin polarization was found, irrespective of x and momentum. The present results unambiguously indicate the topological origin of the gapped Dirac surface states, and also impose a constraint on models to explain the origin of mass acquisition of Dirac fermions.

19.
Exp Clin Endocrinol Diabetes ; 120(2): 96-100, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22231924

RESUMEN

AIMS: The present study was performed to develop a simple procedure for assessment of body temperature and to determine whether postprandial thermoregulation is related to metabolic regulation in diabetic patients. METHODS: We examined 101 male and female subjects with diabetes. Axillary temperature was measured prior to and after all meals (3 meals per day) and self-recorded for 1 week. The averages were calculated. Positive postprandial thermoregulation (PPT) was defined as a pattern in which each of 3 average postprandial temperatures was higher than the corresponding 3 preprandial temperatures. Negative postprandial thermoregulation (NPT) was defined as the pattern except for PPT. RESULTS: A significant increase in postprandial temperature was observed. With the exception of high-density lipoprotein (HDL)-cholesterol levels, there were no relationships between the categorized postprandial thermoregulation and other factors, including age, sex, body mass index, thyroid function, HbA1c, diabetic complications, lipid metabolism, and calorie intake. Logistic analysis indicated an independent positive relation between HDL-cholesterol and PPT. CONCLUSION: A simple method for measurement of body temperature indicated that HDL-cholesterol level was predominantly associated with thermic effects of food in diabetic patients, while other metabolic factors showed no such relations. HDL-cholesterol may affect the postprandial regulation of body temperature in diabetic patients.


Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Temperatura Corporal , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Autoevaluación Diagnóstica , Ingestión de Alimentos/fisiología , Periodo Posprandial/fisiología , Adulto , Anciano , Axila , Temperatura Corporal/fisiología , Diabetes Mellitus Tipo 2/sangre , Femenino , Fiebre/sangre , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Nat Commun ; 3: 636, 2012 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-22273674

RESUMEN

The three-dimensional topological insulator is a quantum state of matter characterized by an insulating bulk state and gapless Dirac cone surface states. Device applications of topological insulators require a highly insulating bulk and tunable Dirac carriers, which has so far been difficult to achieve. Here we demonstrate that Bi(2-x)Sb(x)Te(3-y)Se(y) is a system that simultaneously satisfies both of these requirements. For a series of compositions presenting bulk-insulating transport behaviour, angle-resolved photoemission spectroscopy reveals that the chemical potential is always located in the bulk band gap, whereas the Dirac cone dispersion changes systematically so that the Dirac point moves up in energy with increasing x, leading to a sign change of the Dirac carriers at x~0.9. Such a tunable Dirac cone opens a promising pathway to the development of novel devices based on topological insulators.

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