Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.922
Filtrar
1.
Nat Commun ; 15(1): 2871, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605019

RESUMEN

The development of van der Waals heterostructures has introduced unconventional phenomena that emerge at atomically precise interfaces. For example, interlayer excitons in two-dimensional transition metal dichalcogenides show intriguing optical properties at low temperatures. Here we report on room-temperature observation of interface excitons in mixed-dimensional heterostructures consisting of two-dimensional tungsten diselenide and one-dimensional carbon nanotubes. Bright emission peaks originating from the interface are identified, spanning a broad energy range within the telecommunication wavelengths. The effect of band alignment is investigated by systematically varying the nanotube bandgap, and we assign the new peaks to interface excitons as they only appear in type-II heterostructures. Room-temperature localization of low-energy interface excitons is indicated by extended lifetimes as well as small excitation saturation powers, and photon correlation measurements confirm antibunching. With mixed-dimensional van der Waals heterostructures where band alignment can be engineered, new opportunities for quantum photonics are envisioned.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38591550

RESUMEN

INTRODUCTION: The purpose of this study was to investigate the influence of undercut depths on abutment teeth regarding the retentive force of clasps fabricated through selective laser melting (SLM), and to compare them with conventional cast clasps. METHODS: Akers clasps made of cobalt chromium alloy were fabricated using the SLM method (SLM), and the retentive forces were compared with clasps made with the conventional cast method (Cast). Three undercut amounts (0.25 mm, 0.15 mm, and 0 mm) were applied on the abutment tooth. The specimens were subjected to 10,000 repetitive insertion/removal cycles. RESULTS: SLM-0.15 showed slightly lower initial retentive force than the Cast specimens, it remained within an acceptable range. During insertion/removal test, the SLM-0.15 specimen showed a significant difference between the initial retentive force and the retentive force after 5,000 cycles, indicating that SLM-0.15 was the least likely to change in retentive force within the parameters established in this study. The inner clasp surface on the SLM groups had higher surface roughness before testing compared to the Cast specimen. CONCLUSIONS: Akers clasps fabricated by SLM demonstrated optimal initial retentive forces with smaller undercuts than conventional Cast clasps, and the retentive forces changed less with repetitive insertion/removal.

3.
Eur J Clin Microbiol Infect Dis ; 43(3): 459-467, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38172403

RESUMEN

PURPOSE: During the last decade, the incidence of anaerobic bacteremia (AB) has been increasing. Patients with AB may develop complex underlying diseases, which can occasionally be accompanied by fatal or fulminant outcomes. However, the risk factors for AB-related mortality remain unclear. Herein, we sought to elucidate the risk factors for AB-related mortality. METHODS: In this multicenter, retrospective, observational study, we enrolled patients with culture-proven AB from six tertiary hospitals in Japan, between January 2012 and December 2021. Data on patient and infection characteristics, laboratory findings, treatment, and outcome were collected, and their associations with mortality were analyzed. RESULTS: A total of 520 participants were included. The 30-day mortality in the study cohort was 14.0% (73 patients), and malignant tumors were frequently observed comorbidities in 48% of the entire cohort. Multivariable logistic regression analysis showed a Charlson comorbidity score of > 6, serum creatinine level of > 1.17 mg/dL, and hypotension to be independent risk factors for 30-day mortality in AB (odds ratios [ORs] 2.12, 2.25, and 5.12, respectively; p < 0.05), whereas drainage significantly reduced this risk (OR, 0.28; p < 0.0001). Twelve patients (2.3% of the whole cohort and 16.4% of the deceased patients) presented with extremely rapid progression leading to fatal outcome, consistent with "fulminant AB." CONCLUSIONS: This study identified acute circulatory dysfunction and performance of drainage as independent predictive factors for 30-day AB-related mortality and revealed the existence of a fulminant AB sub-phenotype. Our findings could serve as a practical guide to predict the clinical outcomes of AB.


Asunto(s)
Bacteriemia , Humanos , Estudios Retrospectivos , Anaerobiosis , Estudios de Cohortes , Factores de Riesgo , Bacteriemia/microbiología , Antibacterianos/uso terapéutico
4.
Nat Commun ; 14(1): 8152, 2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071345

RESUMEN

Nanomaterials exhibit unique optical phenomena, in particular excitonic quantum processes occurring at room temperature. The low dimensionality, however, imposes strict requirements for conventional optical excitation, and an approach for bypassing such restrictions is desirable. Here we report on exciton transfer in carbon-nanotube/tungsten-diselenide heterostructures, where band alignment can be systematically varied. The mixed-dimensional heterostructures display a pronounced exciton reservoir effect where the longer-lifetime excitons within the two-dimensional semiconductor are funneled into carbon nanotubes through diffusion. This new excitation pathway presents several advantages, including larger absorption areas, broadband spectral response, and polarization-independent efficiency. When band alignment is resonant, we observe substantially more efficient excitation via tungsten diselenide compared to direct excitation of the nanotube. We further demonstrate simultaneous bright emission from an array of carbon nanotubes with varied chiralities and orientations. Our findings show the potential of mixed-dimensional heterostructures and band alignment engineering for energy harvesting and quantum applications through exciton manipulation.

5.
Plant Biol (Stuttg) ; 25(4): 563-570, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36790102

RESUMEN

C4 plants supply concentrated CO2 to bundle sheath (BS) cells, improving photosynthetic efficiency by suppressing photorespiration. Mesophyll chloroplasts in C4 plants are redistributed toward the sides of the BS cells (aggregative movement) in response to environmental stresses under light. Although this chloroplast movement is common in C4 plants, the significance and mechanisms underlying the aggregative movement remain unknown. Under environmental stresses, such as drought and salt, CO2 uptake from the atmosphere is suppressed by closing stomata to prevent water loss. We hypothesized that CO2 limitation may induce the chloroplast aggregative movement. In this study, the mesophyll chloroplast arrangement in a leaf of finger millet, an NAD-malic enzyme type C4 plant, was examined under different CO2 concentrations and light conditions. CO2 limitation around the leaves promoted the aggregative movement, but the aggregative movement was not suppressed, even at the higher CO2 concentration than in the atmosphere, under high intensity blue light. In addition, mesophyll chloroplasts did not change their arrangement under darkness or red light. From these results, it can be concluded that CO2 limitation is not a direct inducer of the aggregative movement but would be a promoting factor of the movement under high intensity blue light.


Asunto(s)
Dióxido de Carbono , Cloroplastos , Dióxido de Carbono/metabolismo , Cloroplastos/metabolismo , Fotosíntesis , Luz , Hojas de la Planta/fisiología , Plantas , Células del Mesófilo
6.
JAR Life ; 12: 100-104, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38186668

RESUMEN

Background: Frailty increases the risk of falling, hospitalization, and premature death, necessitating practical early-detection tools. Objectives: To examine the discriminative ability of KinectTM-based stepping parameters for identifying frailty phenotype. Design: Population-based cross-sectional study. Setting: Eighteen neighborhoods near Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo, Japan. Participants: In total, 563 community-dwelling older adults aged ≥75 years without mobility limitations, neurological disease, or dementia were included. Measurements: Step number (SN) and knee total movement distance (KMD) during a 20-s stepping test were evaluated using the KinectTM infrared depth sensor. Results: The number (%) of participants with frailty were 51 (9.1). The area under the receiver operating characteristic curves (95% confidence interval) of a parameter consisting of SN and KMD for frailty was 0.72 (0.64, 0.79). Conclusions: Stepping parameters evaluated using KinectTM provided acceptable ability in identifying frailty phenotype, making it a practical screening tool in primary care and home settings.

8.
J Frailty Aging ; 11(1): 26-32, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35122087

RESUMEN

BACKGROUND: Frailty is a dynamic process, with frequent transitions between frailty, prefrailty, and robust statuses over time. The effect of dietary intake on frailty transitions is unknown. OBJECTIVE: To examine the association between dietary intake and frailty transitions. DESIGN: Survey-based retrospective analysis of the National Institute for Longevity Sciences-Longitudinal Study of Aging data. SETTING: Areas neighboring the National Center for Geriatrics and Gerontology in Aichi Prefecture, Japan. PARTICIPANTS: We included 469 prefrail community dwellers aged 60-87 years who participated both in the baseline (2008-2010) and 2-year follow-up (2010-2012) surveys of the National Institute for Longevity Sciences-Longitudinal Study of Aging. MEASUREMENTS: Transitions of frailty were categorized by changes in status from baseline to follow-up: "deterioration (prefrail to frail)," "persistence (persistent prefrail)," and "reversal (prefrail to robust)." Estimated dietary (nutrients and food) intakes assessed by 3-day dietary records in each frailty transition were analyzed with a multivariate-adjusted general linear model after adjusting for sex, age, education, family income, smoking, and chronic disease. RESULTS: At the 2-year follow-up, 28%, 7%, and 65% of participants had robust, frail, and pre-frail status, respectively. Among 13 food groups, only milk and dairy product intake was positively associated with frailty reversal even after adjusting for all frailty criteria at baseline. Despite insignificant differences in the estimated mean intakes, the baseline intake of saturated fatty acids, potassium, and vitamin B1 tended to be the highest in the reversal group. The estimated mean (standard error) for milk and dairy product intake (g/day) was 79.1 (28.6), 129.3 (19.9), and 161.7 (21.7) for the deterioration, persistence, and reversal groups, respectively (P=0.0036, P-trend=0.0019). CONCLUSIONS: Daily consumption of dairy products may contribute to frailty reversal and frailty prevention among older community dwellers who consume small amounts of dairy products. Other food groups showed no association with frailty status transitions.


Asunto(s)
Fragilidad , Anciano , Anciano de 80 o más Años , Ingestión de Alimentos , Anciano Frágil , Fragilidad/epidemiología , Evaluación Geriátrica , Humanos , Vida Independiente , Estudios Longitudinales , Estudios Retrospectivos
9.
Osteoporos Int ; 33(6): 1265-1273, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35059774

RESUMEN

The effect of romosozumab is affected by previous osteoporosis treatment. Here we showed that the duration of the previous treatment just before romosozumab affects the therapeutic effect of romosozumab. Using denosumab and oral bisphosphonates for more than 1 year attenuates the effect of romosozumab. INTRODUCTION: As an anti-sclerostin antibody, romosozumab suppresses bone resorption and stimulates bone formation. We investigated whether the effectiveness of 12 months of romosozumab treatment depended on the duration of previous treatment with teriparatide, denosumab, or oral bisphosphonates. METHODS: In total, 259 osteoporosis patients received subcutaneous injections of romosozumab (210 mg) every 4 weeks during 2019 and 2020. This study was designed as a pre-post comparison. The end points were the percent changes of bone mineral density (BMD) after 12 months of romosozumab treatment. The patients were divided into seven groups depending on the type and duration of previous treatment before starting romosozumab as follows: non-previous treatment group, change from teriparatide used for 1 year or less/more than 1 year, change from denosumab used for 1 year or less/more than 1 year, and change from oral bisphosphonates used for 1 year or less/more than 1 year. RESULTS: The effects of previous treatment with teriparatide on the effectiveness of 12-month romosozumab did not clearly depend on the duration of treatment (p > 0.05). In contrast, the effects of previous treatments with denosumab or oral bisphosphonates on the effectiveness of 12-month romosozumab depended on the previous treatment duration, which was reflected by the differences in percent change of the spine BMD (both p < 0.05), however, there were no significant differences in the percent change of the total hip BMD (both p > 0.05). CONCLUSION: The duration of the previous treatment affected the effectiveness of romosozumab. Using denosumab and oral bisphosphonate for more than 1 year attenuated the effect of romosozumab.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Anticuerpos Monoclonales , Densidad Ósea , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/farmacología , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Femenino , Humanos , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Osteoporosis Posmenopáusica/inducido químicamente , Osteoporosis Posmenopáusica/tratamiento farmacológico , Teriparatido/farmacología , Teriparatido/uso terapéutico
10.
Infect Prev Pract ; 3(3): 100151, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34647007

RESUMEN

BACKGROUND: Periodic point prevalence surveys (PPSs) provide a method for assessing changes in healthcare-associated infections (HAIs) and antimicrobial use over time. Following the introduction of an antimicrobial stewardship programme at Nagoya University Hospital (Aichi, Japan) a five-year PPS study was performed to highlight any epidemiological changes. METHODS: One-day PPSs were performed annually in July at Nagoya University Hospital. Data on patient characteristics, medical devices, active HAIs and antimicrobial use were collected using a standard data-collection form. RESULTS: A total of 4339 patients were included. Over the five-year study period the median patient age was 62 years, median duration of hospital admission was nine days, 9% of patients had an HAI and 35.2% received at least one antimicrobial. Overall there were 406 HAIs (95% confidence interval, 369-447) with surgical site infection, pneumonia and febrile neutropenia occurring most frequently. Enterobacterales were the most common pathogens (N = 78, 28.6%) and 32.1% were third-generation cephalosporin-resistant. Meropenem was the most frequently prescribed antimicrobial for HAIs. Surgical antimicrobial prophylaxis changed drastically, with shorter durations and a marked reduction in oral cephalosporin use. However, antimicrobials for medical prophylaxis gradually increased. CONCLUSIONS: This five-year PPS study shows consistent data for patient background, HAIs and causative pathogens and highlights changes in antimicrobial use during the era of the National Action Plan on Antimicrobial Resistance. To describe the epidemiology of Japanese hospitals by PPS, multicentre PPSs including in community hospitals should be performed annually.

11.
Phys Rev Lett ; 127(6): 069902, 2021 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-34420355

RESUMEN

This corrects the article DOI: 10.1103/PhysRevLett.116.217201.

12.
ESMO Open ; 6(4): 100191, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34153652

RESUMEN

BACKGROUND: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. PATIENTS AND METHODS: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m2 each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. RESULTS: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade ≥3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade ≥3 or treatment-related death did not occur. CONCLUSIONS: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Quimioradioterapia/efectos adversos , Receptores ErbB/genética , Femenino , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Mutación , Estudios Prospectivos
13.
Osteoporos Int ; 32(10): 1999-2009, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33770201

RESUMEN

Romosozumab is an effective treatment for spine osteoporosis because it reduces the incidence of new fractures and significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications. INTRODUCTION: Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody, which increases bone formation and suppresses bone resorption. The aim of our study was to elucidate the clinical effects, safety, and predictors of the effects of one-year romosozumab treatment. METHODS: This study was an observational study designed as a pre-post study in 262 patients. Romosozumab (210 mg) was administered subcutaneously once every 4 weeks during 12 months. We focused on incidence of new fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. RESULTS: There were five cases of new fractures during one-year romosozumab treatment. There were no fatal adverse events. Percent changes from baseline in the spine and total hip BMD after 12 months of romosozumab treatment were 10.67% and 2.04%, respectively. Romosozumab had better effects in cases of severe osteoporosis with low spine BMD, high TRACP-5b, and high iP1NP at the start of romosozumab treatment. The percent change in the spine BMD at 12 months was significantly lower in the group transitioning from bisphosphonates than in the group not previously treated with other anti-osteoporosis medications. CONCLUSION: Romosozumab is an effective treatment for spine osteoporosis because it significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Anticuerpos Monoclonales/efectos adversos , Densidad Ósea , Conservadores de la Densidad Ósea/efectos adversos , Femenino , Humanos , Osteoporosis/tratamiento farmacológico
14.
Osteoporos Int ; 32(4): 653-661, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32979066

RESUMEN

Our 6-month study showed the usefulness of romosozumab for preventing fractures and its safety. It was effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP. Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with that from baseline of BMD after four to 6-month treatment. INTRODUCTION: Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody which increases bone formation and suppresses bone resorption. In this study, we analyzed the actual clinical effects, adverse effects, and the optimal way to evaluate the treatment. METHODS: Romosozumab was administered as subcutaneous injection of 210 mg once every 4 weeks. We conducted pre-post study in 185 patients treated for 6 months. We focused on the incidence of new vertebral fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. We evaluated BMD before romosozumab treatment and after 4 to 6 months and performed the serum analysis before romosozumab treatment, after 1, 3, and 6 months. RESULTS: There was no new fracture during treatment, and there was no fatal adverse event including cardiovascular disease. Since percent changes from baseline of the spine and total hip BMD were 6.34% and 1.53% after 4- to 6-month treatment, the treatment was effective for spine osteoporosis. Tartrate-resistant acid phosphatase 5b (TRACP-5b) and intact type I procollagen N-terminal propeptide (iP1NP) had significant changes during romosozumab treatment (p < 0.05). Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with percent change from baseline of BMD after 4 to 6 months of treatment. CONCLUSION: Romosozumab is effective in preventing fractures and useful for increasing the spine BMD. Also, romosozumab is relatively safe to use. It is especially effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Anticuerpos Monoclonales/efectos adversos , Biomarcadores , Densidad Ósea , Conservadores de la Densidad Ósea/efectos adversos , Humanos , Japón , Osteoporosis/tratamiento farmacológico
15.
Chin Neurosurg J ; 6: 19, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922948

RESUMEN

Globally, the discipline of neurosurgery has evolved remarkably fast. Despite being one of the latest medical specialties, which appeared only around hundred years ago, it has witnessed innovations in the aspects of diagnostics methods, macro and micro surgical techniques, and treatment modalities. Unfortunately, this development is not evenly distributed between developed and developing countries. The same is the case with neurosurgical education and training, which developed from only traditional apprentice programs in the past to more structured, competence-based programs with various teaching methods being utilized, in recent times. A similar gap can be observed between developed and developing counties when it comes to neurosurgical education. Fortunately, most of the scholars working in this field do understand the coherent relationship between neurosurgical education and neurosurgical practice. In context to this understanding, a symposium was organized during the World Federation of Neurological Surgeons (WFNS) Special World Congress Beijing 2019. This symposium was the brain child of Prof. Yoko Kato-one of the eminent leaders in neurosurgery and an inspiration for female neurosurgeons. Invited speakers from different continents presented the stages of development of neurosurgical education in their respective countries. This paper summarizes the outcome of these presentations, with particular emphasis on and the challenges faced by developing countries in terms of neurosurgical education and strategies to cope with these challenges.

17.
Nat Commun ; 11(1): 4619, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32934234

RESUMEN

The Weyl semimetal (WSM), which hosts pairs of Weyl points and accompanying Berry curvature in momentum space near Fermi level, is expected to exhibit novel electromagnetic phenomena. Although the large optical/electronic responses such as nonlinear optical effects and intrinsic anomalous Hall effect (AHE) have recently been demonstrated indeed, the conclusive evidence for their topological origins has remained elusive. Here, we report the gigantic magneto-optical (MO) response arising from the topological electronic structure with intense Berry curvature in magnetic WSM Co3Sn2S2. The low-energy MO spectroscopy and the first-principles calculation reveal that the interband transitions on the nodal rings connected to the Weyl points show the resonance of the optical Hall conductivity and give rise to the giant intrinsic AHE in dc limit. The terahertz Faraday and infrared Kerr rotations are found to be remarkably enhanced by these resonances with topological electronic structures, demonstrating the novel low-energy optical response inherent to the magnetic WSM.

18.
Sci Adv ; 6(22): eaba6712, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32524002

RESUMEN

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.


Asunto(s)
Microfluídica , Saccharomyces cerevisiae , Electrodos , Microfluídica/métodos
19.
J Endocrinol Invest ; 43(8): 1061-1071, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32016916

RESUMEN

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Pronóstico
20.
Immunol Lett ; 218: 22-29, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31866401

RESUMEN

OBJECTIVE: Pulmonary arterial hypertension (PAH) is an intractable complication in connective tissue diseases, but the pathological mechanisms responsible for progression remain obscure. This study aims to test whether patient IgG possesses biological activity promoting the migration of pulmonary artery smooth muscle cells (PASMCs). METHODS: Cell migration was estimated by lamellipodia formation and by utilizing a Boyden chamber method. The specificity of autoantibodies was established by western blotting, ELISA, and immunocytochemistry. The target antigen was investigated by mass spectrometry. RESULTS: IgG obtained from a patient with systemic lupus erythematosus (SLE) accompanied by PAH was found to promote lamellipodia formation and migration of PASMCs. The IgG bound to a ∼50 kDa protein expressed on the cell membrane, and in the cytoplasm and nucleus. This molecule was identified as enolase 1. Removal of enolase 1-binding antibodies from the IgG fraction, or treatment of the cells with an enolase inhibitor, significantly suppressed the migration of PASMCs. CONCLUSION: Patients with SLE may possess autoantibodies to enolase 1 which stimulate the migration of PASMCs and are likely to play a role in the progression of PAH.


Asunto(s)
Autoanticuerpos/inmunología , Biomarcadores de Tumor/inmunología , Proteínas de Unión al ADN/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Miocitos del Músculo Liso/metabolismo , Fosfopiruvato Hidratasa/inmunología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/metabolismo , Proteínas Supresoras de Tumor/inmunología , Secuencia de Aminoácidos , Autoanticuerpos/sangre , Autoantígenos/inmunología , Biomarcadores de Tumor/química , Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Células Cultivadas , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Ligandos , Miocitos del Músculo Liso/inmunología , Fosfopiruvato Hidratasa/química , Fosfopiruvato Hidratasa/metabolismo , Unión Proteica , Hipertensión Arterial Pulmonar/diagnóstico , Arteria Pulmonar/citología , Arteria Pulmonar/inmunología , Arteria Pulmonar/metabolismo , Transducción de Señal , Proteínas Supresoras de Tumor/química , Proteínas Supresoras de Tumor/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...