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For the purpose of future visualization of the flow field in superfluid helium-4, clusters of the triplet state excimer 4He2 * are generated along the micro-scale recoil tracks of the neutron-absorption reaction n + 3He â 3T + p. This reaction is induced by neutron irradiation of the 3He fraction contained in natural isotopic abundance liquid helium with neutron beams either from the Japan Proton Accelerator Research Complex, Materials and Life Science Experimental Facility (JPARC)/Materials and Life Science Experimental Facility or from the Kyoto University Institute for Integrated Radiation and Nuclear Science. These 4He2 * clusters are expected to be ideal tracers of the normal-fluid component in superfluid helium with several advantageous properties. Evidence of the excimer generation is inferred by detection of laser induced fluorescence emitted from the 4He2 * clusters excited by a purpose-built short pulse gain-switched titanium:sapphire (Ti:sa) laser operating at a wavelength of 905 nm. The setup and performance characteristics of the laser system including the Ti:sa and two continuous wave re-pumping lasers are described. Detection at the fluorescence wavelength of 640 nm is performed by using optical bandpass filtered photomultiplier tubes (PMT). Electrical noise in the PMT acquisition traces could successfully be suppressed by post-processing with a simple algorithm. Despite other laser-related backgrounds, the excimer was clearly identified by its fluorescence decay characteristics. Production of the excimer was found to be proportional to the neutron flux, adjusted via insertion of different collimators into the neutron beam. These observations suggest that the apparatus we constructed does function in the expected manner and, therefore, has the potential for groundbreaking turbulence research with superfluid helium.
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BACKGROUND: Oesophageal squamous cell carcinoma is an aggressive disease owing to early and widespread lymph node metastases. Multimodal therapy and radical surgery may improve prognosis. Few studies have investigated the efficacy of radical lymph node and thoracic duct resection. METHODS: Patients with oesophageal squamous cell carcinoma who underwent transthoracic minimally invasive oesophagectomy (TMIE) for cancer at Keio University Hospital between January 2004 and December 2016 were selected. Between 2004 and 2008, TMIE was performed in the lateral decubitus position without thoracic duct resection (standard TMIE). From 2009 onwards, TMIE with extended lymph node and thoracic duct resection was introduced (extended TMIE). Demographics, co-morbidity, number of retrieved lymph nodes, pathology, postoperative complications and recurrence-free survival (RFS) were compared between groups. RESULTS: Forty-four patients underwent standard TMIE and 191 extended TMIE. There were no significant differences in clinical and pathological tumour stage or postoperative complications. The extended-TMIE group had more lymph nodes removed at nodal stations 106recL and 112. Among patients with cT1 N0 disease, RFS was better in the extended-TMIE group (P < 0·001), whereas there was no difference in RFS between groups in patients with advanced disease. CONCLUSION: Extended TMIE including thoracic duct resection increased the number of lymph nodes retrieved and was associated with improved survival in patients with cT1 N0 oesophageal squamous cell carcinoma.
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Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ducto Torácico/cirurgia , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Ducto Torácico/patologia , Resultado do TratamentoRESUMO
OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.
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Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Infecções por HIV/complicações , Sobreviventes de Longo Prazo ao HIV/estatística & dados numéricos , Adulto , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Contagem de Linfócito CD4 , Cálcio/metabolismo , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/imunologia , Espessura Intima-Media Carotídea , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Receptores de Superfície Celular/sangue , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Nivolumab, an anti-PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (t1dm), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant t1dm. We report the case of a 68-year-old woman who developed pancreatic islet-related autoantibody-negative t1dm, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event.
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Melanoma/induzido quimicamente , Nivolumabe/efeitos adversos , Idoso , Diabetes Mellitus Tipo 1/induzido quimicamente , Feminino , HumanosRESUMO
BACKGROUND: Oesophagectomy has a high risk of postoperative morbidity. The impact of postoperative complications on overall survival of oesophageal cancer remains unclear. This meta-analysis addressed the impact of complications on long-term survival following oesophagectomy. METHODS: A search of PubMed and Cochrane Library databases was undertaken for systematic review of papers published between January 1995 and August 2016 that analysed the relation between postoperative complications and long-term survival. In the meta-analysis, data were pooled. The main outcome was overall survival (OS). Secondary endpoints included disease-free (DFS) and cancer-specific (CSS) survival. RESULTS: A total of 357 citations was reviewed; 21 studies comprising 11 368 patients were included in the analyses. Overall, postoperative complications were associated with significantly decreased 5-year OS (hazard ratio (HR) 1·16, 95 per cent c.i. 1·06 to 1·26; P = 0·001) and 5-year CSS (HR 1·27, 1·09 to 1·47; P = 0·002). Pulmonary complications were associated with decreased 5-year OS (HR 1·37, 1·16 to 1·62; P < 0·001), CSS (HR 1·60, 1·35 to 1·89; P < 0·001) and 5-year DFS (HR 1·16, 1·00 to 1·33; P = 0·05). Patients with anastomotic leakage had significantly decreased 5-year OS (HR 1·20, 1·10 to 1·30; P < 0·001), 5-year CSS (HR 1·81, 1·11 to 2·95; P = 0·02) and 5-year DFS (HR 1·13, 1·02 to 1·25; P = 0·01). CONCLUSION: Postoperative complications after oesophagectomy, including pulmonary complications and anastomotic leakage, decreased long-term survival.
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Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien-Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN.
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Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Nervo Laríngeo Recorrente/patologia , Paralisia das Pregas Vocais/etiologia , Idoso , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Superconductivity is ubiquitous as evidenced by the observation in many crystals including carrier-doped oxides and diamond. Amorphous solids are no exception. However, it remains to be discovered in quasicrystals, in which atoms are ordered over long distances but not in a periodically repeating arrangement. Here we report electrical resistivity, magnetization, and specific-heat measurements of Al-Zn-Mg quasicrystal, presenting convincing evidence for the emergence of bulk superconductivity at a very low transition temperature of [Formula: see text] K. We also find superconductivity in its approximant crystals, structures that are periodic, but that are very similar to quasicrystals. These observations demonstrate that the effective interaction between electrons remains attractive under variation of the atomic arrangement from periodic to quasiperiodic one. The discovery of the superconducting quasicrystal, in which the fractal geometry interplays with superconductivity, opens the door to a new type of superconductivity, fractal superconductivity.
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INTRODUCTION: Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants. METHODS: HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. RESULTS: Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01). CONCLUSIONS: Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.
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Biomarcadores/sangue , Infecções por HIV/imunologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Fibrose , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Ácido Hialurônico/metabolismo , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Fator Plaquetário 4/sangueRESUMO
Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Neoplasias Esofágicas/terapia , Fluoruracila/administração & dosagem , Quimioterapia de Indução/métodos , Taxoides/administração & dosagem , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Docetaxel , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esofagoscopia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Human periodontal ligament cells (HPDLCs) express transforming growth factor-ß1 (TGF-ß1) that regulates differentiation and proliferation, and plays key roles in homeostasis of PDL tissue. Transgelin is a cytoskeleton-associated protein with an Smad-binding element in its gene promoter region. In this study, we examined the localization and potential function of transgelin in PDL tissue and cells. MATERIAL AND METHODS: Microarray analysis of HPDLC lines (2-14, 2-23 and 2-52) was performed. Expression of transgelin in HPDLCs was examined by quantitative reverse transcription-polymerase chain reaction, immunofluorescence staining and western blot analysis. Effects of TGF-ß1 and its signaling inhibitor, SB431542, on transgelin expression in HPDLCs were examined by western blot analysis. The effects of transgelin knockdown by small interfering RNA (siRNA) on HPDLC proliferation stimulated by TGF-ß1 were assessed by WST-1 assay. RESULTS: In microarray and quantitative reverse transcription-polymerase chain reaction analyses, the expression levels of transgelin (TAGLN) in 2-14 and 2-23 cells, which highly expressed PDL markers such as periostin (POSTN), tissue non-specific alkaline phosphatase (ALPL), α-smooth muscle actin (ACTA2) and type I collagen A1 (COL1A1), was significantly higher than those in 2-52 cells that expressed PDL markers weakly. Immunohistochemical and immunofluorescence staining revealed expression of transgelin in rat PDL tissue and HPDLCs. In HPDLCs, TGF-ß1 treatment upregulated transgelin expression, whereas inhibition of the type 1 TGF-ß1 receptor by SB431542 suppressed this upregulation. Furthermore, TAGLN siRNA transfection did not promote the proliferation of HPDLCs treated with TGF-ß1. The expression levels of CCNA2 and CCNE1, which regulate DNA synthesis and mitosis through the cell cycle, were also not upregulated in HPDLCs transfected with TAGLN siRNA. CONCLUSION: Transgelin is expressed in PDL tissue and might have a role in HPDLC proliferation induced by TGF-ß1 stimulation.
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Proteínas dos Microfilamentos/farmacologia , Proteínas Musculares/farmacologia , Ligamento Periodontal/efeitos dos fármacos , Fator de Crescimento Transformador beta/antagonistas & inibidores , Adulto , Benzamidas/farmacologia , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dioxóis/farmacologia , Feminino , Imunofluorescência , Humanos , Masculino , Proteínas dos Microfilamentos/fisiologia , Proteínas Musculares/fisiologia , Ligamento Periodontal/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Fator de Crescimento Transformador beta/farmacologia , Adulto JovemRESUMO
Hyperkalemia is an important complication of adrenalectomy for patients with primary aldosteronism (PA). The frequency of hyperkalemia after medication using mineralocorticoid receptor antagonists (MRAs) for PA is unclear. The aim of this study is to investigate the frequency and the risk factors of hyperkalemia after surgery and medication for PA. The data of 376 patients with PA registered in a multicentre-collaborative study in Japan, including surgically treated patients (group A; n=142) and medically treated patients with MRAs (group B; n=234) were studied. The prevalence of hyperkalemic patients (serum potassium >5.0 mEq l-1) after treatment was higher in group A than group B (9.9 vs 3.8%, P<0.01). At diagnosis, the hyperkalemic patients were older and had a poorer renal function than the non-hyperkalemic patients in both groups (P<0.05). The hyperkalemic patients had severer PA in group A and milder PA in group B. The independent risk factor by a logistic regression analysis was only age in both groups. After treatment, the percentages of patients withdrawing antihypertensive drugs and the normalization of aldosterone renin ratio were not different between hyperkalemic and non-hyperkalemic patients in group A. The type and dose of MRAs and the combination of other antihypertensive drugs were not different between hyperkalemic and non-hyperkalemic patients in group B. In conclusion, the potential occurrence of hyperkalemia should be considered after medical as well as surgical treatment for PA, especially in patients with older age (>60 years) and impaired renal function (estimated glomerular filtration rate <70 ml min-1 per 1.73 m2) at diagnosis.
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Adrenalectomia/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Hiperaldosteronismo/terapia , Hiperpotassemia/induzido quimicamente , Hipertensão/terapia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Potássio/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Distribuição de Qui-Quadrado , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatologia , Hiperpotassemia/sangue , Hiperpotassemia/epidemiologia , Hiperpotassemia/fisiopatologia , Hipertensão/fisiopatologia , Japão/epidemiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Regulação para CimaRESUMO
Although laterality assessed by computed tomography (CT) in primary aldosteronism (PA) is not always concordant with that assessed by adrenal vein sampling (AVS), it is unclear whether all patients diagnosed with PA should undergo AVS for subtype classification. The aim of the current study was to investigate the accuracy of CT in subtype classification and to develop a prediction score for bilateral subtype in patients without adrenal tumour. As part of the WAVES-J study, 393 patients with PA were analysed. Subtyping using CT was concordant with that using AVS in 68% (269/393) of patients in the total sample, and in 38% (68/156) of patients with unilateral tumours, 56% (5/9) of patients with bilateral tumours and 89% (204/228) of patients without tumour. In patients without tumour, female gender, plasma aldosterone concentration (pg ml-1) to plasma renin activity ratio ⩽550 and serum potassium ⩾3.8 mEq l-1 were shown to be independent predictors for bilateral subtype. A prediction score based on these three variables was constructed with one point attributed to each variable. A score of three points had 29% sensitivity and 96% specificity in a receiver operating characteristic curve analysis. The results suggest that although CT is not sufficiently accurate for subtype classification in patients with adrenal tumours, it is sufficient to determine bilateral subtype in patients without tumour. Moreover, using our clinical prediction score in patients without tumour could be useful in determining the necessity of AVS for subtype classification.
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Glândulas Suprarrenais/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Hiperaldosteronismo/classificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
In cases of pulp exposure due to deep dental caries or severe traumatic injuries, existing pulp-capping materials have a limited ability to reconstruct dentin-pulp complexes and can result in pulpectomy because of their low potentials to accelerate dental pulp cell activities, such as migration, proliferation, and differentiation. Therefore, the development of more effective therapeutic agents has been anticipated for direct pulp capping. Dental pulp tissues are enriched with dental pulp stem cells (DPSCs). Here, the authors investigated the effects of semaphorin 3A (Sema3A) on various functions of human DPSCs in vitro and reparative dentin formation in vivo in a rat dental pulp exposure model. Immunofluorescence staining revealed expression of Sema3A and its receptor Nrp1 (neuropilin 1) in rat dental pulp tissue and human DPSC clones. Sema3A induced cell migration, chemotaxis, proliferation, and odontoblastic differentiation of DPSC clones. In addition, Sema3A treatment of DPSC clones increased ß-catenin nuclear accumulation, upregulated expression of the FARP2 gene (FERM, RhoGEF, and pleckstrin domain protein 2), and activated Rac1 in DPSC clones. Furthermore, in the rat dental pulp exposure model, Sema3A promoted reparative dentin formation with dentin tubules and a well-aligned odontoblast-like cell layer at the dental pulp exposure site and with novel reparative dentin almost completely covering pulp tissue at 4 wk after direct pulp capping. These findings suggest that Sema3A could play an important role in dentin regeneration via canonical Wnt/ß-catenin signaling. Sema3A might be an alternative agent for direct pulp capping, which requires further study.
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Polpa Dentária/citologia , Odontoblastos/citologia , Semaforina-3A/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/fisiologia , Dentina/crescimento & desenvolvimento , Feminino , Imunofluorescência , Humanos , Odontoblastos/efeitos dos fármacos , Odontoblastos/fisiologia , Ratos , Ratos Wistar , Semaforina-3A/fisiologia , Adulto Jovem , beta Catenina/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Cigarette smoking has detrimental effects on periodontal tissue, and is known to be a risk factor for periodontal disease, including the loss of alveolar bone and ligament tissue. However, the direct effects of cigarette smoking on periodontal tissue remain unclear. Recently, we demonstrated that benzo[a]pyrene (BaP), which is a prototypic member of polycyclic aryl hydrocarbons and forms part of the content of cigarettes, attenuated the expression of extracellular matrix remodeling-related genes in human periodontal ligament (PDL) cells (HPDLCs). Thus, we aimed to examine the effects of BaP on the osteoblastic differentiation and collagen synthesis of HPDLCs. MATERIAL AND METHODS: HPDLCs were obtained from healthy molars of three patients, and quantitative reverse transcription-polymerase chain reaction were performed for gene expression analyses of cytochrome P450 1A1 and 1B1, alkaline phosphatase, bone sialoprotein and aryl hydrocarbon receptor (AhR), a receptor for polycyclic aryl hydrocarbons. We have also analyzed the role of the AhR, using 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), which is an AhR antagonist. RESULTS: The treatment of HPDLCs with BaP reduced mRNA expression of osteogenic genes, alkaline phosphatase activity, mineralization and collagen synthesis. The treatment with CH-223191 subsequently restored the observed suppressive effects of BaP on HPDLCs. CONCLUSIONS: The present results suggest that BaP exerts inhibitory effects on the maintenance of homeostasis in HPDL tissue, such as osteoblastic differentiation and collagen synthesis of HPDLCs, and that this signaling pathway could be suppressed by preventing the transactivity of AhR. Future studies may unveil a role for the inhibition of AhR as a promising therapeutic agent for periodontal disease caused by cigarette smoking.
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Colágeno/biossíntese , Osteoblastos/metabolismo , Ligamento Periodontal/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/fisiologia , Benzo(a)pireno/farmacologia , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/fisiologia , Receptores de Hidrocarboneto Arílico/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , TranscriptomaRESUMO
We report on the transmission experiment of seven 12.5-GHz spaced all optical-orthogonal frequency division multiplexed (AO-OFDM) subcarriers over a 35-km fiber link, using differential quadrature phase shift keying (DQPSK) modulation and direct detection. The system does not require chromatic dispersion compensation, optical time gating at the receiver (RX) or cyclic prefix (CP), achieving the maximum spectral efficiency. We use a wavelength selective switch (WSS) at the transmitter (TX) to allow subcarrier assignment flexibility and optimal filter shaping; an arrayed waveguide grating (AWG) AO-OFDM demultiplexer is used at the RX, to reduce the system cost and complexity.
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INTRODUCTION: During the past decade, neoadjuvant chemotherapy (NAC) has been increasingly used in patients to reduce large tumors to a size eligible for breast-conserving therapy (BCT). However, the association between NAC and Ki-67 has not yet been fully elucidated. The aim of this study was to evaluate the prognostic significance of Ki-67, specifically after NAC followed by BCT, particularly in terms of locoregional recurrence (LRR). METHODS: A total 217 patients who received BCT after NAC were retrospectively analyzed. In these patients, immunohistochemistry analyses defined four tumor subtypes, Luminal A, Luminal B, Triple negative, and HER2 type. Ki-67 was examined by immunohistochemistry in both pretreatment core needle samples and post-treatment surgical excision specimens. High Ki-67 expression was defined as >20%. The prognostic factors LRR, locoregional relapse-free survival (LRRFS), and overall survival (OS) were analyzed. RESULTS: In total, LRR developed in 14 patients, and the 5 year-LRRFS was 94.2%. Post-treatment high Ki-67 expression, triple negative, the presence of lymphovascular invasion, and histological grade 3 were significantly high in LRR for prognostic factors (P < 0.05). There were significant differences in Kaplan-Meier method for LRRFS curves according to these three factors for patients receiving BCT following NAC (P < 0.05). There was a significant difference in the 5 year-OS for patients with and without LRR (41.7% vs. 93.9%, P < 0.001). CONCLUSION: Post-treatment high Ki-67 expression could be one of the important prognostic factors of LRR, and require careful follow-up on LRR at the time of surveillance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Antígeno Ki-67/metabolismo , Mastectomia Segmentar , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Antraciclinas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/terapia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/administração & dosagem , TrastuzumabAssuntos
Hemangioma/embriologia , Linfangioma/embriologia , Velocidade do Fluxo Sanguíneo , Feminino , Coração Fetal/fisiopatologia , Feto/irrigação sanguínea , Hemangioma/diagnóstico por imagem , Hemangioma/fisiopatologia , Humanos , Linfangioma/diagnóstico por imagem , Linfangioma/fisiopatologia , Gravidez , Ultrassonografia Pré-Natal/métodos , Adulto JovemRESUMO
Hydroxyapatite (HAp) [Ca5(PO4)3OH] is an extremely popular biomaterial. Moreover, HAp durability is well-known to be enhanced by fluoridation. We prepared fluoridated HAp (F-HAp; Ca5(PO4)3(OH)1-xFx) ceramics by substituting F- ions for OH- ions of HAp. F-substitution dependence of dielectric properties in F-HAp was measured to detect the configuration change of OH- ion chains. Dielectric relaxation of two kinds was observed. Each kind had a different relaxation time. Faster relaxation, which is associated with the reorientation motion of OH- ions, was only observed at the low F-substitution range (0 ≤x < 0.35). The relaxation strength decreased as the F-substitution increased. It became zero at x = 0.35, suggesting that F-substitution induces hydrogen bonds. One F- ion substituted for an OH- ion forms two hydrogen bonds with the two neighboring OH- ions and inhibits the motion of OH- ions, which results in some kind of ordered configuration in F-HAp. The configuration might be an origin that enhances the durability of the F-HAp.
RESUMO
BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is continually exposed to mechanical loading caused by mastication or occlusion. Physiological loading is thus considered a key regulator of PDL tissue homeostasis; however, it remains unclear how this occurs. We recently reported that an appropriate magnitude of mechanical stretch can maintain PDL tissue homeostasis via the renin-angiotensin system. In the present study, we investigated the expression of interleukin-11 (IL-11) in human primary PDL cells (HPDLCs) exposed to stretch loading, the contribution of angiotensin II (Ang II) to this event and the effects of IL-11 on osteoblastic/cementoblastic differentiation of human PDL progenitor cells (cell line 1-17). MATERIAL AND METHODS: Human primary PDL cells, derived from human tissues, with or without antagonists against the Ang II receptors AT1 or AT2, were subjected to cyclical stretch loading with 8% elongation for 1 h. Expression of IL-11 was measured by ELISA in these cultures and by immunohistochemistry in the sectioned maxillae of rats. The osteoblastic/cementoblastic potential of cell line 1-17 was determined using cell proliferation, gene expression and Alizarin Red staining. RESULTS: Positive staining for IL-11 was observed in the PDL of rat maxillae and in cultures of HPDLCs. In HPDLCs exposed to stretch, expression of the IL11 gene and the IL-11 protein were up-regulated, concomitant with an increase in Ang II and via AT2. Recombinant human IL-11 (rhIL-11) stimulated an increase in expression of mRNA for the cementoblast-specific marker, CP-23, and for the osteoblastic markers, osteopontin and bone sialoprotein, and promoted proliferation in cell line 1-17. In addition, rhIL-11 also increased the degree of mineralized nodule formation in cell line 1-17 cultures treated with CaCl2 . CONCLUSION: Mechanical loading appears to control proliferation and osteoblastic/cementoblastic differentiation of human PDL stem/progenitor cells through the regulation of Ang II and AT2 by IL-11.