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1.
eNeuro ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31540999

RESUMO

Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patients with contributive copy number variations (CNVs): two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15- or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders.Significance Statement Useful in vitro models of psychiatric disorders such as schizophrenia and bipolar disorder are urgently required for pathological analysis and drug discovery. In this study, mature excitatory and inhibitory neurons were induced from patient-derived induced pluripotent stem cells. The patients-derived induced neurons exhibited abnormalities in dendrite and synapse formation in vitro, which are similar to the previously reported findings observed in the postmortem brains. Our in vitro model may reflect general phenotypes of psychiatric disorders and can be used to further examine therapeutic targets.

2.
J Med Case Rep ; 13(1): 298, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31540583

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney. CASE PRESENTATION: We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly. CONCLUSION: The patient's urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.

3.
Bioorg Med Chem ; 27(18): 4200-4210, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401009

RESUMO

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4ß2-nAChR agonist, we prepared A85380 derivatives labeled with 99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a 99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4ß2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 ±â€¯0.04 nM). Further, 99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that 99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.

4.
Sci Rep ; 9(1): 11352, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388057

RESUMO

Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke's Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.

5.
Stem Cell Reports ; 13(3): 530-544, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31402337

RESUMO

A simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that chondrocytes are robustly induced from human PSCs by simple combination of two compounds, CHIR99021, a glycogen synthase kinase 3 inhibitor, and TTNPB, a retinoic acid receptor (RAR) agonist, under serum- and feeder-free conditions within 5-9 days. An excellent differentiation efficiency and potential to form hyaline cartilaginous tissues in vivo were demonstrated. Comprehensive gene expression and open chromatin analyses at each protocol stage revealed step-by-step differentiation toward chondrocytes. Genome-wide analysis of RAR and ß-catenin association with DNA showed that retinoic acid and Wnt/ß-catenin signaling collaboratively regulated the key marker genes at each differentiation stage. This method provides a promising cell source for regenerative medicine and, as an in vitro model, may facilitate elucidation of the molecular mechanisms underlying chondrocyte differentiation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31216562

RESUMO

3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders.

7.
Chem Commun (Camb) ; 55(52): 7454-7457, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31184356

RESUMO

This study investigates oxygen electrocatalytic activities of perovskite-related compounds using a rotating disk electrode technique in an aqueous solution containing lithium chloride and lithium hydroxide. A hydrated oxyhydroxide Ruddelesden-Popper phase, Sr3Co2O5(OH)2·2H2O, exhibits excellent performance especially in the oxygen evolution reaction.

8.
Brain ; 142(7): 2127-2136, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096266

RESUMO

Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder's core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n = 18, crossover within-subjects design) and multisite confirmatory (n = 106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, -0.57; 95% CI, -1.27 to 0.13; P = 0.023) and confirmatory trials (-0.41; -0.62 to -0.20; P < 0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P < 0.001). Post hoc analyses revealed maximum efficacy at 2 weeks (P < 0.001, Cohen's d = -0.78; 95% CI, -1.21 to -0.35) and deterioration of efficacy at 4 weeks (P = 0.042, Cohen's d = -0.46; 95% CI, -0.90 to -0.01) and 6 weeks (P = 0.10, Cohen's d = -0.35; 95% CI, -0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P < 0.001, Cohen's d = -1.24; 95% CI, -1.71 to -0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals' facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.

9.
Transl Psychiatry ; 9(1): 146, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053702

RESUMO

The original Article required a few updates; one co-author name, which was given as Hiroki Kiumura, has been updated to Hiroki Kimura. Furthermore, supplementary information has been updated, and grant numbers have been added. These updates have been made to both the PDF and HTML versions of this Article.

10.
Transl Psychiatry ; 9(1): 126, 2019 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-31011151

RESUMO

Although a number of studies have identified several convincing candidate genes or molecules, the pathophysiology of schizophrenia (SCZ) has not been completely elucidated. Therapeutic optimization based on pathophysiology should be performed as early as possible to improve functional outcomes and prognosis; to detect useful biomarkers for SCZ, which reflect pathophysiology and can be utilized for timely diagnosis and effective therapy. To explore biomarkers for SCZ, we employed fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) of lymphoblastoid cell lines (LCLs) (1st sample set: 30 SCZ and 30 CON). Differentially expressed proteins were sequenced by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and identified proteins were confirmed by western blotting (WB) (1st and 2nd sample set: 60 SCZ and 60 CON). Multivariate logistic regression analysis was performed to identify an optimal combination of biomarkers to create a prediction model for SCZ. Twenty protein spots were differentially expressed between SCZ and CON in 2D-DIGE analysis and 22 unique proteins were identified by LC-MS/MS. Differential expression of eight of 22 proteins was confirmed by WB. Among the eight candidate proteins (HSPA4L, MX1, GLRX3, UROD, MAPRE1, TBCB, IGHM, and GART), we successfully constructed logistic regression models comprised of 4- and 6-markers with good discriminative ability between SCZ and CON. In both WB and gene expression analysis of LCL, MX1 showed reproducibly significant associations. Moreover, Mx1 and its related proinflamatory genes (Mx2, Il1b, and Tnf) were also up-regulated in poly I:C-treated mice. Differentially expressed proteins might be associated with molecular pathophysiology of SCZ, including dysregulation of immunological reactions and potentially provide diagnostic and prognostic biomarkers.

11.
Nat Commun ; 10(1): 1442, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926814

RESUMO

Exposure of articular cartilage to excessive mechanical loading is deeply involved in the pathogenesis of osteoarthritis. Here, we identify gremlin-1 as a mechanical loading-inducible factor in chondrocytes, detected at high levels in middle and deep layers of cartilage after cyclic strain or hydrostatic pressure loading. Gremlin-1 activates nuclear factor-κB signalling, leading to subsequent induction of catabolic enzymes. In mice intra-articular administration of gremlin-1 antibody or chondrocyte-specific deletion of Gremlin-1 decelerates osteoarthritis development, while intra-articular administration of recombinant gremlin-1 exacerbates this process. Furthermore, ras-related C3 botulinum toxin substrate 1 activation induced by mechanical loading enhances reactive oxygen species (ROS) production. Amongst ROS-activating transcription factors, RelA/p65 induces Gremlin-1 transcription, which antagonizes induction of anabolic genes such as Sox9, Col2a1, and Acan by bone morphogenetic proteins. Thus, gremlin-1 plays essential roles in cartilage degeneration by excessive mechanical loading.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Transdução de Sinais , Anabolizantes/farmacologia , Animais , Proteínas Morfogenéticas Ósseas/farmacologia , Condrócitos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Estresse Mecânico , Suporte de Carga , Proteínas rac1 de Ligação ao GTP/metabolismo
12.
J Shoulder Elbow Surg ; 28(7): 1363-1370, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30827834

RESUMO

BACKGROUND: The purpose of the study was to evaluate the bone healing potential of fascia lata autograft (FLA) by magnetic resonance imaging (MRI) and histologic analysis. METHODS: The study included 69 patients assessed by MRI after an FLA patch procedure. Three of the 69 patients underwent a revision procedure after the primary FLA procedure; 1 underwent a second-look arthroscopy and 2 underwent reverse shoulder arthroplasties (RSAs). In the 2 RSA patients, we histologically evaluated greater tuberosities with the repaired graft. Moreover, as a control, we harvested the greater tuberosity with the cuff tendon at the time of RSA for failed open reduction-internal fixation of 4-part proximal humeral fracture. Based on MRI, retear cases were divided into type 1 (the graft did not remain on the greater tuberosity) and type 2 (the graft remained on the greater tuberosity). Histologic sections were evaluated to examine fascia-bone or rotator cuff-bone interfaces. RESULTS: There were 35 intact repairs: 7 type 1 and 27 type 2 shoulders (type 1 vs. type 2, P < .001). Second-look arthroscopic findings confirmed that the graft was securely attached to the greater tuberosity. Histologic analysis of greater tuberosities in RSA patients showed solid continuity of the graft to the bone, with cells with nuclei in the collagen matrix oriented in parallel. The FLA to bone junction consisted of the FLA, fibrocartilage, and bone, which is similar to the normal cuff tendon to bone junction. CONCLUSIONS: These results indicate that a fresh cellular FLA has good to excellent bone healing potential.

13.
Cardiovasc Diabetol ; 18(1): 39, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902059

RESUMO

BACKGROUND: The efficacy of cell transplantation in heart failure is reportedly modest, but adjuvant drugs combined with cell therapy may improve this efficacy. Peroxisome proliferator-activated receptor (PPAR)γ, one of the hypoglycemic medicine for diabetes mellitus, reportedly enhances cytokine production in adipose tissue-derived regenerative cells (ADRCs). We hypothesized that combined administration of PPARγ agonists and ADRCs may enhance the paracrine effects of adiponectin (APN), leading to functional recovery in a chronic myocardial infarction (MI) model. METHODS: ADRCs were isolated from adipose tissues of adult rats by gradient centrifugation and embedded in bio-compatible fibrin-glue to produce ADRCs grafts. In the in vitro study, the ADRCs grafts released APN, which was significantly enhanced by the PPARγ agonist (PGZ, pioglitazone). Transplantation of ADRCs grafts (group A), ADRCs mixed with PGZ (group AP), APN knockdown-ADRCs (group Si) or PGZ (group P) onto the epicardium or a sham operation (group C) was performed (n = 10-20 per group). RESULTS: The AP group showed significant improvement in ejection fraction compared to that in the other groups. In the AP group, a significantly larger number of M2-polarized macrophages was detected and existed for a significantly longer duration in the infarct area. Furthermore, comparing Si group and P group, western blotting of T-cadherin revealed that exogenous APN and local expression of T-cadherin were essential to this histological change and recovery of cardiac function. CONCLUSIONS: Combined administration of PPARγ agonist and ADRSCs activated M2-polarized macrophages with enhancement of APN paracrine effects and lead to better cardiac function in a rat infarction model.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/transplante , Cardiomiopatias/terapia , Transplante de Células/métodos , Macrófagos/efeitos dos fármacos , Infarto do Miocárdio/terapia , PPAR gama/agonistas , Pioglitazona/farmacologia , Regeneração/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Caderinas/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , PPAR gama/metabolismo , Comunicação Parácrina/efeitos dos fármacos , Fenótipo , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
14.
J Foot Ankle Surg ; 58(3): 489-491, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30765251

RESUMO

Despite a high incidence of proximal diaphyseal stress fractures of the fifth metatarsal (zone 3) in soccer (football) players, studies that examine risk factors of the fractures in professional soccer players are scarce; in particular, ankle structures have not yet been investigated. This study was designed to investigate ankle structures of professional soccer players with proximal diaphyseal stress fractures of the fifth metatarsal. We reviewed the ankle radiographs of 100 professional soccer players (stress fractures n = 15; controls n = 85) and measured the medial malleolar slip angle (MMSA), the ratio of the medial malleolar length to the width of the talar dome (MML:TD ratio), the ratio of the lateral malleolar length to the width of the TD (LML:TD ratio), and the ratio of the MML to the LML (MML:LML ratio). The MMSA (p < .01: 28.7° ± 5.8° versus 23.0° ± 4.9°) in the stress fractures was significantly wider and the MML:TD ratio (p = .08: 0.49 ± 0.08 versus 0.52 ± 0.07) had a trend to be smaller compared with the values of the controls. Logistic regression analysis revealed that a wider malleolar slip angle became a factor associated with stress fractures in professional soccer players (p < .01: odds ratio 1.27, 95% confidence interval 1.110 to 1.463). Receiver operating characteristic curve with MMSA for the stress fractures was depicted with an area under the curve of 0.778, and the suitable cut-off point was set at MMSA >27° with a positive likelihood ratio of 3.67 (95% confidence interval 2.173 to 6.188). Our study results show that a wide MMSA was associated with proximal diaphyseal stress fractures of the fifth metatarsal in professional soccer players.

15.
Sci Rep ; 9(1): 2236, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783186

RESUMO

CD133 is a transmembranous protein that mainly localises to the plasma membrane in haematopoietic and neural stem cells as well as cancer stem cells. Although CD133 also localises to the cytoplasm, the mechanism of action and function of cytoplasmic CD133 currently remain unknown. We herein demonstrated that when Src family kinase activity is weak, CD133 interacts with HDAC6 and is transported to the pericentrosomal region after internalization and endosome formation via the dynein-based traffic system. Pericentrosomal CD133 is then recycled to the plasma membrane via recycling endosomes. At the pericentrosomal region, endosomal CD133 captures GABARAP, an initiator of autophagy, and inhibits GABARAP-mediated ULK1 activation and the subsequent initiation of autophagy. Furthermore, pericentrosomal CD133 suppresses cell differentiation, such as primary cilium formation and neurite outgrowth, by inhibiting autophagy. Thus, the present results provide evidence to suggest that pericentrosomal CD133 has the unique property of maintaining the undifferentiated status of cells by inhibiting autophagy.

16.
Am J Kidney Dis ; 73(6): 880-885, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30554801

RESUMO

Autoantibodies against thrombospondin type 1 domain-containing 7A (THSD7A) cause membranous nephropathy (MN); however, the mechanisms involved in THSD7A expression and immunization are uncertain. We present 2 cases of THSD7A-associated MN accompanied by angiolymphoid hyperplasia with eosinophilia (ALHE), a benign tumor characterized by proliferation of plump endothelial cells. Prednisolone therapy, but not surgical resection of ALHE tumors, successfully suppressed eosinophilia and proteinuria in both cases. Because ALHE is characterized by the proliferation of plump endothelial cells, we focused on the roles of vascular endothelial growth factor A (VEGF-A) in MN pathogenesis. We found that plump endothelial cells in ALHE modestly expressed THSD7A in both cases. We also found that eosinophils in ALHE expressed VEGF-A, which upregulated THSD7A expression, especially under T-helper type 2-prone conditions in cultured endothelial cells. Furthermore, double-positive cells for THSD7A and CD83 surrounded the proliferated small vessels. Our results suggest that VEGF-A-induced THSD7A expression outside the kidney may be important for MN pathogenesis.

17.
J Cutan Pathol ; 46(4): 267-270, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30582193

RESUMO

Pilomatrical carcinosarcoma is a very rare entity, with only six cases reported until now. This report describes the case of a 100-year-old woman with a mass on the left temple that had existed for several decades but had recently grown in size. Histology showed an asymmetric lesion composed of basaloid cells, spindle cells, and "shadow" or "ghost" cells. Cells had atypical hyperchromatic nuclei with prominent nucleoli, high mitotic activity, and atypical mitosis. In the central area, an epidermal cyst-like structure was seen. The diagnosis of pilomatrical carcinosarcoma was rendered. This case appeared to have arisen from malignant transformation of a pilomatricoma because of the long clinical history and existence of a benign epidermal cyst-like structure. In addition, the observation that the basaloid cells and spindle cells showed a gradual transition from one to the other and that both types were positive for ß-catenin would seem to support a common clonal origin for the carcinomatous and sarcomatous components.


Assuntos
Carcinossarcoma/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/patologia , Face , Feminino , Humanos , Pilomatrixoma/patologia
18.
Inorg Chem ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30507117

RESUMO

A polar LiNbO3 (LN)-type oxide LiSbO3 was synthesized by a high-temperature heat treatment under a pressure of 7.7 GPa and found to exhibit ferroelectricity. The crystal structural refinement using the data of synchrotron powder X-ray diffraction and neutron diffraction and the electronic structure calculation of LN-type LiSbO3 suggest a covalent-bonding character between Sb and O. When comparing the distortion of BO6 in LN-type ABO3, the distortions of SbO6 in LiSbO3 and SnO6 in ZnSnO3, which included a B cation with a d10 electronic configuration, were smaller than those of BO6 in LN-type oxides having the second-order Jahn-Teller active B cation, e.g., LiNbO3 and ZnTiO3. The temperature dependence of the lattice parameters, second harmonic generation, dielectric permittivity, and differential scanning calorimetry made it clear that a second-order ferroelectric-paraelectric phase transition occurs at a Curie temperature of Tc = 605 ± 10 K in LN-type LiSbO3. Further, first-principles density functional theory calculation suggested that perovskite-type LiSbO3 is less stable than LN-type LiSbO3 under even high pressure, and the ambient phase of LiSbO3 directly transforms to LN-type LiSbO3 under high pressure. The phase stability of LN-type LiSbO3 and the polar and ferroelectric properties are rationalized by the covalent bonding of Sb-O and the relatively weak Coulomb repulsion between Li+ and Sb5+.

19.
Biol Pharm Bull ; 41(12): 1745-1747, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30504676

RESUMO

Infliximab shows drastic efficacy for controlling inflammation in rheumatoid arthritis (RA), though the ideal dose of infliximab to keep suppressing inflammation has not yet been identified. Recently, it has been evidenced that the minimum trough serum infliximab levels required for suppressing inflammation are greater than 1 µg/mL. This cross-sectional study was designed to identify the minimum dosage of infliximab for maintaining serum infliximab levels greater than 1 µg/mL. Thirty seven RA patients were enrolled in this study and they were divided into two groups (high-infliximab vs. low-infliximab) in reference to Remi-check Q®, a kit for examining serum infliximab levels above/below 1 µg/mL by LC. Infliximab dosage (p=0.06) and dosage interval (p=0.05) had trends to have differences between groups. A formula calculated by infliximab dosage divided by dosage interval and body weight (mg/weeks/kg) was shown to have significantly higher levels among high-infliximab group (p=0.04). Based on whether serum infliximab levels above/below 1 µg/mL and values led by the equation, infliximab dosage/infliximab interval/body weight (mg/weeks/kg), a receiver operating characteristic curve (ROC) was depicted with area under the ROC curve 0.750 and the cut-off point for the serum infliximab levels greater than 1 µg/mL was identified as infliximab dosage/infliximab interval/body weight ≧0.750 with the sensitivity 0.393 and the specificity 1.000. In conclusion, we identified that the minimum infliximab dosage to maintain serum infliximab levels greater than 1 µg/mL was infliximab dose/dosage interval/body weight (mg/weeks/kg)≥0.750.

20.
J Plant Res ; 2018 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-30417276

RESUMO

Iron (Fe) is a micronutrient that is essential for plant development and growth. Basic helix-loop-helix (bHLH) transcription factors are a superfamily of transcription factors that are important regulatory components in transcriptional networks in plants. bHLH transcription factors have been divided into subclasses based on their amino acid sequences and domain structures. Among the members of clade IVb (PYE, bHLH121, and bHLH11), the functions of bHLH11 remain unclear. In the present study, we characterized bHLH11 as a negative regulator of Fe homeostasis. bHLH11 expression levels were high in the roots and up-regulated after plants were transferred to Fe sufficient conditions. Although T-DNA knockout mutants of bHLH11 were lethal, dominant negative (DN-) and overexpression (OX-) of bHLH11 plants exhibited sensitivity to Fe deficiency. Furthermore, the expression of FIT, a master regulator of Fe deficiency responses, was suppressed in the transgenic plants. These results suggest that the transcriptional repressor bHLH11 functions as a negative regulator of FIT-dependent Fe uptake and modulates Fe levels in Arabidopsis plants. Salicylic acid (SA) modulates the expression of genes involved in Fe-deficient responses. We found that SA levels were elevated in DN- and OX-bHLH11 plants. The T-DNA insertion mutant sid2-1, which was defective for the production of SA, did not exhibit sensitivity to Fe deficiency; however, the crossed plants of OX-bHLH11 and sid2-1 relieved sensitivity to the Fe deficiency observed in OX-bHLH11 plants. These results suggest that the accumulation of SA is closely related to iron homeostasis.

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