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1.
J Forensic Odontostomatol ; 42(1): 38-57, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38742571

RESUMEN

OBJECTIVES: This meta-analysis addresses the use of mandibular computed tomography (CT) scans for age and/or sex determination in forensic science. METHODS: Six databases were searched until June 2023, using the keyword "mandible" combined with keywords related to "multislice computed tomography" (MCT) or "cone-beam computed tomography" (CBCT) and keywords related to "skeletal age determination" or "sex determination analysis." MAIN RESULTS: Among the 23 studies included, 11 used MCT and 12 used CBCT to perform forensic assessments. Age determination was the aim of a single study, sex and agedeterminations were the objective of five studies, and the other studies investigated the determination of sex only. Metaanalysis could be performed only for sex determination. CONCLUSIONS: Mandible measurements are useful in sex determination, as the bicondylar and bigonial breadth are larger in males than in females. For the mandible angle, the meta-analysis results confirm sex dimorphism in CBCT scans but not in MCT scans. For age estimation, further studies are needed to prove that the mandible hole is a reliable parameter for age estimation. PROSPERO registration number: CRD42021260967.


Asunto(s)
Determinación de la Edad por el Esqueleto , Tomografía Computarizada de Haz Cónico , Mandíbula , Determinación del Sexo por el Esqueleto , Humanos , Mandíbula/diagnóstico por imagen , Mandíbula/anatomía & histología , Determinación del Sexo por el Esqueleto/métodos , Determinación de la Edad por el Esqueleto/métodos , Tomografía Computarizada Multidetector , Antropología Forense/métodos
2.
Musculoskelet Surg ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705948

RESUMEN

BACKGROUND: In end-stage arthritis indicated for total ankle arthroplasty (TAA), full-thickness cartilage damage, subchondral bone defect/shaving, and fluttering of the talar dome occur, shortening the distance between the tibial and talar insertions of ligaments and leading to laxity of ligaments surrounding the ankle joint. Under such conditions, medial ligaments (including the deltoid ligament) would not be expected to function properly. To stabilize the ankle joint during the stance phase, medial ligament function under tension is important. This study therefore examined whether TAA contributes to lengthening of the medial tibio-talar joint as evaluated radiographically, as a preferable method for achieving tensile effects on medial ligaments. MATERIALS AND METHODS: Twenty-four feet with end-stage varus deformity of the ankle joint that underwent TAA were retrospectively investigated, excluding cases with any malleolar osteotomy or fracture. Distance between proximal and distal insertions of medial ligaments, lateralization of the talus, and talar tilt angle under valgus/varus stress condition were evaluated pre- and postoperatively. RESULTS: Distance between proximal and distal insertions of medial ligaments was significantly elongated after TAA. At the same time, the talus showed significant lateralization. Furthermore, talar tilt under valgus/varus stress conditions was also significantly reduced after TAA. CONCLUSION: TAA affects distal translation and lateralization of the talus in cases of varus ankle deformity. These effects might contribute to re-providing tensile force on lax medial ligaments, improving ligament function.

3.
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.

4.
Knee Surg Relat Res ; 36(1): 12, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539272

RESUMEN

INTRODUCTION: Patient satisfaction is an important outcome of total knee arthroplasty (TKA). However, we cannot predict how and why patients are satisfied or dissatisfied with TKA. The hypothesis of this study was that patient-reported outcomes (PROs) correlate with in vivo kinematics after TKA. MATERIALS AND METHODS: One hundred knees were analyzed after TKA. The in vivo kinematics of deep knee bending motion were estimated from single-plane fluoroscopy using a two-to-three-dimensional registration technique. Active knee flexion, femoral rotation and rollback were evaluated. The PROs were obtained after surgery using the 2011 Knee Society Scoring System (KSS), and their relationship with in vivo kinematics was determined. RESULTS: The average minimum and maximum flexion were -2.4 ± 7.3° and 113.2 ± 13.6°, respectively. The average femoral rotation was 7.4 ± 3.4°, and the average medial and lateral rollback were 2.4 ± 4.8 mm and 7.2 ± 5.6 mm, respectively. The multiple regression analysis revealed that the maximum flexion angle significantly contributed to symptoms and satisfaction. In addition, lateral rollback was also a significant factor affecting patient satisfaction. Lateral rollback and lateral Anterior-Posterior (AP) position at maximum flexion were correlated with the maximum flexion angle, whereas femoral rotation did not correlate with flexion angles. CONCLUSIONS: Maximum flexion and lateral rollback are important for better patient satisfaction after TKA. To obtain the maximum flexion angle, it was necessary to perform the normal kinematic pattern with a large amount of lateral rollback.

5.
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.

6.
Plant Mol Biol ; 112(4-5): 279-291, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37326800

RESUMEN

A long-held goal of synthetic biology has been the transfer of a bacterial nitrogen-fixation pathway into plants to reduce the use of chemical fertiliser on crops such as rice, wheat and maize. There are three classes of bacterial nitrogenase, named after their metal requirements, containing either a MoFe-, VFe- or FeFe-cofactor, that converts N2 gas to ammonia. Relative to the Mo-nitrogenase the Fe-nitrogenase is not as efficient for catalysis but has less complex genetic and metallocluster requirements, features that may be preferable for engineering into crops. Here we report the successful targeting of bacterial Fe-nitrogenase proteins, AnfD, AnfK, AnfG and AnfH, to plant mitochondria. When expressed as a single protein AnfD was mostly insoluble in plant mitochondria, but coexpression of AnfD with AnfK improved its solubility. Using affinity-based purification of mitochondrially expressed AnfK or AnfG we were able to demonstrate a strong interaction of AnfD with AnfK and a weaker interaction of AnfG with AnfDK. This work establishes that the structural components of the Fe-nitrogenase can be engineered into plant mitochondria and form a complex, which will be a requirement for function. This report outlines the first use of Fe-nitrogenase proteins within a plant as a preliminary step towards engineering an alternative nitrogenase into crops.


Asunto(s)
Azotobacter vinelandii , Nitrogenasa , Nitrogenasa/genética , Nitrogenasa/metabolismo , Azotobacter vinelandii/genética , Azotobacter vinelandii/metabolismo , Hierro , Fijación del Nitrógeno , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
7.
Phys Rev Lett ; 130(17): 173001, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37172243

RESUMEN

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

8.
Rev Sci Instrum ; 93(10): 103520, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319387

RESUMEN

A visible light tomographic imaging system has been developed for the collisional merging experiment of field-reversed configurations (FRCs) on the FRC Amplification via Translation-Collisional Merging device at Nihon University. Two FRCs formed by field-reversed theta-pinch translate at super-Alfvénic velocity and collide with each other. The translation and collision processes are completed in 20-30 µs, and a single FRC is reformed in ∼70 µs. To study these translation and collisional merging processes, the tomographic system, including fast response tomographic cameras and a reconstruction method assuming a Rigid-Rotor (RR) model, is developed. The developed tomographic cameras simply consist of 16 channels of multi-anode photomultipliers, a band-pass filter, a slit, and a cylindrical lens, which expands the viewing angle. Because the viewing angle is limited by the size of the viewports of the metal chamber, the iterative method assuming the RR model has been applied to reconstruct tomographic images from a small number of projections. The developed tomographic imaging system can estimate the behavior of FRCs. Four cameras are installed in the two cross sections near the collision point. The radial shift of each translated FRC can be calculated by this system. Details of the developed tomographic camera system and RR reconstruction method are reported.

9.
Osteoporos Int ; 33(8): 1807-1813, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35362725

RESUMEN

In patients with postmenopausal osteoporosis, prior osteoporosis treatment affected the bone mineral density increase of following treatment with 12 months of romosozumab, although it did not affect that of following treatment with 12 months of denosumab after romosozumab. PURPOSE: To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, multicenter study, treatment-naïve patients (Naïve; n = 55) or patients previously treated with bisphosphonates (BP; n = 37), DMAb (DMAb; n = 45) or teriparatide (TPTD; n = 17) (mean age, 74.6 years; T-scores of the lumbar spine [LS] - 3.2 and total hip [TH] - 2.6) were switched to ROMO for 12 months, followed by DMAb for 12 months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24 months. RESULTS: A BMD increase was observed at 12 and 24 months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (P < 0.001 between the groups at both 12 and 24 months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (P < 0.01 between the groups at 12 months and P < 0.001 at 24 months) in TH, respectively. The BMD increase in LS from 12 to 24 months was negatively associated with the levels of bone resorption marker at 24 months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%). CONCLUSIONS: Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Anciano , Anticuerpos Monoclonales , Biomarcadores , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/farmacología , Denosumab/uso terapéutico , Difosfonatos/farmacología , Femenino , Humanos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Estudios Prospectivos , Teriparatido/farmacología , Teriparatido/uso terapéutico
10.
Phys Rev Lett ; 128(11): 112503, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35363014

RESUMEN

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

11.
Phys Rev Lett ; 127(5): 053001, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34397250

RESUMEN

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

12.
Acta Gastroenterol Belg ; 84(2): 317-320, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34217182

RESUMEN

BACKGROUND AND STUDY AIMS: Hypoxic hepatitis (HH) is an acute liver injury that develops in patients with underlying diseases, such as heart failure, respiratory failure, septic/toxic shock. However, some patients do not have underlying diseases or episodes which are known to result in HH. Here, we analyzed the clinical characteristics of this particular patient group (called 'unknown HH' hereafter) to understand its pathogenesis. PATIENTS AND METHODS: Between October 2010 and January 2016, 157 consecutive patients with acute liver injury were admitted to our hospital. Among these patients, 15 patients were categorized as unknown HH. Medical histories and blood test results of unknown HH were analyzed. RESULTS: Among 15 patients of unknown HH, 11 were habitual drinkers and all experienced one of digestive symptoms which might result in mild hypovolemia such as vomiting, diarrhea, appetite loss, and epigastralgia. All patients of unknown HH presented marked elevation of serum ferritin concentration paralleled with aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) concentrations. The serum levels of ferritin, ALT, LDH, and prothrombin time-international normalized ratio (PT-INR) were rapidly decreased during hospitalization and all 15 patients of unknown HH recovered without any complication. CONCLUSIONS: We found the particular group of HH with marked elevation of serum ferritin probably due to intrahepatic macrophage activation. Anti-inflammatory treatments might be effective for this group of hypoxic hepatitis.


Asunto(s)
Hepatitis , Alanina Transaminasa , Aspartato Aminotransferasas , Ferritinas , Humanos , Macrófagos
13.
World J Urol ; 39(1): 209-215, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32172330

RESUMEN

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.


Asunto(s)
Pelvis Renal , Ureteroscopios , Diseño de Equipo , Modelos Anatómicos
14.
Clin Exp Immunol ; 204(1): 1-13, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33289074

RESUMEN

Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti-neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs ) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting Tregs , activated Tregs and non-suppressive Tregs . The frequency of activated Tregs (CD4+ CD25+ FoxP3high CD45RA- T cells) as well as that of total Tregs (CD4+ CD25+ FoxP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vß repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vß families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vß family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR-Vß family was individually compared, different use was prominently observed in the TCR-Vß 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR-Vß repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.


Asunto(s)
Autoinmunidad/inmunología , Linfocitos T CD4-Positivos/inmunología , Neutropenia/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T CD4-Positivos/metabolismo , Niño , Preescolar , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/inmunología , Factores de Transcripción Forkhead/metabolismo , Humanos , Lactante , Subunidad alfa del Receptor de Interleucina-2/inmunología , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Masculino , Neutropenia/diagnóstico , Neutropenia/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/metabolismo
16.
J Frailty Aging ; 8(4): 186-191, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31637404

RESUMEN

BACKGROUND: With increasing interest in addressing quality of life of older individuals, tests such as the Functional Independence Measure (FIM) are widely used measures of infirmity and burden of care. However, these scales are largely qualitative and especially problematic when assessing movement-based tasks. While effective, reliable analysis of human movement is technically complicated and expensive; an infrared depth sensor is potentially a low-cost, portable devise which may provide a quantitative aspect to clinical testing. OBJECTIVE: to assess the utility of the KinectTM sensor in providing an objective evaluation of human movement using an oft measured ADL (chair stand). DESIGN: Cross-sectional study. SETTING: Community, geriatric day-care center in Japan. PARTICIPANTS: Men (n=136) and women (n=266) between 50 and 93 years of age, consisting of healthy (HE; n=312) and physically frail (FR; n= 90) individuals. MEASUREMENTS: Subjects completed two trials of the chair stand, conducted without assistance. Trials were timed and recorded with KinectTM v2. Coronal plane angle (CPA) was determined by a line transecting the shoulder-center and waist relative to the vertical axis and was used to assess quality of the chair stand movement pattern. RESULTS: Age, height, and body mass were not different between groups. CPA was significantly greater in FR (29.3 ± 8.3°) than HE (19.5 ± 6.5°). CPA and age were significantly related (r=0.148, p<0.01). An optimal threshold for CPA identifying frailty was determined by a receiver-operator characteristic curve with a CPA of 23.1° providing the greatest combination of sensitivity (79%) and specificity (73%). CONCLUSION: During the chair stand, frail older adults adopted a forward lean position (increased CPA) compared to healthy older adults. This compensatory posture appears to facilitate torso rotation while reducing lower-limb muscular effort during standing. As such, CPA serves as an indicator of reduced lower-body function in older, frail adults.


Asunto(s)
Evaluación Geriátrica/métodos , Rendimiento Físico Funcional , Equilibrio Postural , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Anciano Frágil , Humanos , Japón , Masculino , Persona de Mediana Edad
17.
BJS Open ; 3(4): 436-444, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31463422

RESUMEN

Background: The presence of extraintestinal manifestations may be associated with the development of pouchitis in patients with ulcerative colitis after ileal pouch-anal anastomosis. The aim of this study was to assess this correlation. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Library. Studies published in English up to 22 May 2017 investigating the association between extraintestinal manifestations and development of pouchitis in adults with ulcerative colitis were included. Case reports were excluded. The association of extraintestinal manifestations with the development of overall and chronic pouchitis was investigated using a random-effects model. Results: Of 1010 citations identified, 22 observational studies comprising 5128 patients were selected for analysis. The presence of extraintestinal manifestations was significantly associated with both chronic pouchitis (odds ratio 2·28, 95 per cent c.i. 1·57 to 3·32; P = 0·001) and overall pouchitis (odds ratio 1·96, 1·49 to 2·57; P < 0·001). Conclusion: The presence of extraintestinal manifestations is associated with development of pouchitis after ileal pouch-anal anastomosis.


Asunto(s)
Colitis Ulcerosa/cirugía , Complicaciones Posoperatorias , Reservoritis , Proctocolectomía Restauradora , Colangitis Esclerosante , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reservoritis/epidemiología , Reservoritis/etiología , Proctocolectomía Restauradora/efectos adversos , Proctocolectomía Restauradora/estadística & datos numéricos , Factores de Riesgo
18.
Scand J Rheumatol ; 48(6): 491-496, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31272272

RESUMEN

Objectives: Kawasaki disease (KD) is a systemic vasculitis of early childhood. Intravenous immunoglobulin (IVIG) is the standard treatment for KD. However, IVIG is not effective in approximately 15% of children with KD, and the mechanisms for this are unclear. We investigated changes in monocyte and T-cell activation from pre- to post-IVIG in IVIG-effective and IVIG-resistant KD.Method: We analysed peripheral CD14+CD16+ cells and human leucocyte antigen-DR (HLA-DR) expression on CD4+ and CD8+ cells in 46 children with KD who were admitted to Yamaguchi University Hospital between January 2011 and May 2016. We compared the kinetics in the absolute numbers of CD14+CD16+ cells, CD4+HLA-DR+ cells, and CD8+HLA-DR+ cells before and after IVIG treatment between IVIG-effective and IVIG-resistant groups.Results: Among the 46 subjects, 30 had IVIG-effective KD and 16 had IVIG-resistant KD. The absolute number of CD14+CD16+ cells in the IVIG-effective group decreased significantly after IVIG, while that in the IVIG-resistant group showed no change after IVIG. The absolute number of CD4+HLA-DR+ cells increased significantly after IVIG in both groups. The absolute number of CD8+HLA-DR+ cells before IVIG was low and significantly increased after IVIG in the IVIG-resistant group, while that in the IVIG-effective group showed no change after IVIG.Conclusions: Our results suggest that insufficient control of monocyte suppression and T-cell activation, especially in terms of the CD8-related immune system, are associated with IVIG resistance. The restoration of T-cell suppression may be important for KD recovery. These findings provide insight into the mechanism of IVIG resistance.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Activación de Linfocitos , Monocitos/inmunología , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Niño , Preescolar , Femenino , Antígenos HLA-DR/análisis , Humanos , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/inmunología
19.
Clin Exp Immunol ; 190(2): 268-279, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28677152

RESUMEN

Regulatory T cells (Tregs ) control immune responses by suppressing various inflammatory cells. Tregs in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of Tregs during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7-8 days after birth) and late (2-4 weeks after birth) neonatal periods. CD4+ forkhead box protein 3 (FoxP3+ ) T cells were classified into resting Tregs (CD45RA+ FoxP3low ), activated Tregs (CD45RA- FoxP3high ) and newly activated T cells (CD45RA- FoxP3low ). Compared with CB and PB during the late neonatal period, the percentage of Tregs and all Treg subpopulations in the CD4+ lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated Tregs were increased markedly compared with other Treg subpopulations, such as resting Tregs and newly activated T cells (non-Tregs ), in the early neonatal period. Increased Tregs concomitantly expressed the suppressive molecule cytotoxic T lymphocyte antigen-4 (CTLA-4). The up-regulated expression of chemokine receptor 4 (CCR4) and down-regulated expression of CCR7 were also observed in expanded Tregs . When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4+ CD45RA- FoxP3high cells were increased significantly during the culture. Thus, the presence of increased activated Tregs in early neonates may play an important role in immunological regulation by suppressing excessive T cell activation caused by the immediate exposure to ubiquitous antigens after birth.


Asunto(s)
Sangre Fetal/citología , Recién Nacido/inmunología , Activación de Linfocitos , Linfocitos T Reguladores/inmunología , Anticuerpos Monoclonales , Complejo CD3/análisis , Linfocitos T CD4-Positivos/inmunología , Antígeno CTLA-4 , Femenino , Sangre Fetal/efectos de los fármacos , Citometría de Flujo , Factores de Transcripción Forkhead/análisis , Humanos , Lactante , Antígenos Comunes de Leucocito/análisis , Recuento de Linfocitos , Masculino , Fenotipo , Receptores CCR4/análisis , Receptores CCR7/análisis , Linfocitos T Reguladores/fisiología
20.
Oncogene ; 36(37): 5252-5262, 2017 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-28481873

RESUMEN

Primary effusion lymphoma (PEL), which is an aggressive subgroup of B-cell lymphoma associated with Kaposi sarcoma-associated herpes virus/human herpes virus-8, is refractory to the standard treatment, and exhibits a poor survival. Although PU.1 is downregulated in PEL, the potential role of its reduction remains to be elucidated. In this investigation, we analyzed the DNA methylation of PU.1 cis-regulatory elements in PEL and the effect of restoring PU.1 on PEL cells. The mRNA level of PU.1 was downregulated in PEL cells. The methylated promoter and enhancer regions of the PU.1 gene were detected in PEL cells. Suppression of cell growth and apoptosis were caused by the restoration of PU.1 in PEL cells. A microarray analysis revealed that interferon-stimulated genes (ISGs) including pro-apoptotic ISGs were strongly increased in BCBL-1 cells after the induction of PU.1. Reporter assays showed that PU.1 transactivated pro-apoptotic ISG promoters, such as the XAF1, OAS1 and TRAIL promoters. Mutations at the PU.1 binding sequences suppressed its transactivation. We confirmed the binding of PU.1 to the XAF1, OAS1 and TRAIL promoters in a chromatin immunoprecipitation assay. PU.1 suppressed ORF57 activation by inducing IRF7. The reinduction of PU.1 reduced formation of ascites and lymphoma cell infiltration of distant organs in PEL xenograft model mice. Collectively, PU.1 has a role in tumor suppression in PEL and its down-regulation is associated with PEL development. Restoring PU.1 with demethylation agents may be a novel therapeutic approach for PEL.


Asunto(s)
Interferones/genética , Linfoma de Efusión Primaria/genética , Linfoma de Efusión Primaria/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Metilación de ADN , Xenoinjertos , Humanos , Factor 7 Regulador del Interferón/biosíntesis , Factor 7 Regulador del Interferón/genética , Interferones/farmacología , Linfoma de Efusión Primaria/patología , Masculino , Ratones , Ratones Endogámicos NOD , Análisis por Micromatrices , Regiones Promotoras Genéticas , Activación Transcripcional , Transfección
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