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1.
Lupus ; 28(9): 1120-1127, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31299881

RESUMEN

Sensing self-nucleic acids through toll-like receptors in plasmacytoid dendritic cells (pDCs), and the dysregulated type I IFN production, represent pathogenic events in the development of the autoimmune responses in systemic lupus erythematosus (SLE). Production of high-mobility group box-1 protein (HMGB1) promotes type I IFN response in pDCs. To better understand the active pathogenic mechanism of SLE, we measured serum levels of HMGB1, thrombomodulin, and cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, IFNα, IFNγ, TNFα) in 35 patients with SLE. Serum HMGB1 and IFNα were significantly higher in patients with active SLE (SLE Disease Activity Index (SLEDAI) score ≥ 6) compared with healthy donors or patients with inactive SLE. Furthermore, the HMGB1 levels were significantly correlated with IFNα levels. By qualitative analysis, the detection of serum IFNα or HMGB1 suggests active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels are biomarkers reflecting disease activity, and qualitative analysis of IFNα or HMGB1 is a useful screening test to estimate SLE severity and manifestations. Our results suggest the clinical significance of type I IFNs and HMGB1 as key molecules promoting the autoimmune process in SLE.


Asunto(s)
Citocinas/sangre , Proteína HMGB1/sangre , Lupus Eritematoso Sistémico/fisiopatología , Trombomodulina/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Interferón-alfa/sangre , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
2.
J Periodontal Res ; 53(3): 353-361, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29159877

RESUMEN

BACKGROUND AND OBJECTIVE: Dental calculus is a mineralized deposit attached to the tooth surface. We have shown that cellular uptake of dental calculus triggers nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, leading to the processing of the interleukin-1ß precursor into its mature form in mouse and human phagocytes. The activation of the NLRP3 inflammasome also induced a lytic form of programmed cell death, pyroptosis, in these cells. However, the effects of dental calculus on other cell types in periodontal tissue have not been investigated. The aim of this study was to determine whether dental calculus can induce cell death in oral epithelial cells. MATERIAL AND METHODS: HSC-2 human oral squamous carcinoma cells, HOMK107 human primary oral epithelial cells and immortalized mouse macrophages were exposed to dental calculus or 1 of its components, hydroxyapatite crystals. For inhibition assays, the cells were exposed to dental calculus in the presence or absence of cytochalasin D (endocytosis inhibitor), z-YVAD-fmk (caspase-1 inhibitor) or glyburide (NLRP3 inflammasome inhibitor). Cytotoxicity was determined by measuring lactate dehydrogenase (LDH) release and staining with propidium iodide. Tumor necrosis factor-α production was quantified by enzyme-linked immunosorbent assay. Oral epithelial barrier function was examined by permeability assay. RESULTS: Dental calculus induced cell death in HSC-2 cells, as judged by LDH release and propidium iodide staining. Dental calculus also induced LDH release from HOMK107 cells. Following heat treatment, dental calculus lost its capacity to induce tumor necrosis factor-α in mouse macrophages, but could induce LDH release in HSC-2 cells, indicating a major role of inorganic components in cell death. Hydroxyapatite crystals also induced cell death in both HSC-2 and HOMK107 cells, as judged by LDH release, indicating the capacity of crystal particles to induce cell death. Cell death induced by dental calculus was significantly inhibited by cytochalasin D, z-YVAD-fmk and glyburide, indicating NLRP3 inflammasome involvement. In permeability assays, dental calculus attenuated the barrier function of HSC-2 cell monolayers. CONCLUSION: Dental calculus induces pyroptotic cell death in human oral epithelial cells and the crystalline structure plays a major role in this process. Oral epithelial cell death induced by dental calculus might be important for the etiology of periodontitis.


Asunto(s)
Muerte Celular/efectos de los fármacos , Cálculos Dentales/química , Células Epiteliales/efectos de los fármacos , Inflamasomas/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas , Caspasa 1/metabolismo , Línea Celular Tumoral , Permeabilidad de la Membrana Celular/efectos de los fármacos , Citocalasina D/farmacología , Humanos , Interleucina-1beta/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismo
3.
Phys Chem Chem Phys ; 19(47): 31842-31855, 2017 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-29171610

RESUMEN

Cupric oxide leaf-like nanostructures (CuONSs) (average dimensions: 80-180 nm in width and 400-750 nm in length) were synthesized via anodic electrochemical dissolution of copper in an ethanol solution containing LiCl electrolyte and water. Ultraviolet-visible (UV-Vis), Fourier-transform infrared (FT-IR), and Raman spectroscopies as well as scanning electron microscope (SEM), high-resolution transmission electron microscopy with energy dispersive X-ray (HD-TEM-EDS), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRD) were used to explore the metal surface plasmon, size, rheology, and structure of CuONSs. Then, pyridine α-aminophosphinic acid isomers (α-, ß-, and γ-NHPy) were synthesized and assembled on the CuONS/air and CuONS/aqueous solution interfaces at the pH level of solution = 7. Differences in adsorption and thus in the spectral response resulting from positional isomerism were examined by surface-enhanced Raman scattering (SERS) with an excitation wavelength of 785 nm. The manner of interaction of the investigated isomers with CuONSs in an aqueous solution was discussed in detail and compared with that at the CuONS/air interface. For γ-NHPy, at the CuONS/water interface, the time-dependent changes in the spectral profile were observed and analyzed. For ß-NHPy at the CuONS/air interface, tip-enhanced Raman scattering (TERS) measurements were performed. These measurements allowed observing single molecule behavior and avoiding interference from the molecule's surrounding environment.

4.
Neoplasma ; 64(1): 140-147, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27881016

RESUMEN

An increased platelet count is often observed in lung cancer patients. Whether and how the platelets affect cancer progression have yet to be established. The aim of the study was to investigate the involvement of the platelet count and mean platelet volume (MPV) in the prognosis and progression of lung cancer patients. This retrospective study included 146 patients with newly diagnosed primary lung cancer. The platelet count and MPV were measured before invasive diagnostic procedures and treatment. These platelet indices, overall survival of the patients, and tumor metastases for each organ were analyzed. On Kaplan-Meier survival analysis, the overall survivals of patients with platelet counts ≤ 244.0 × 109/L or MPV > 9.7 fL were longer than those of patients with platelet counts > 244.0 × 109/L or MPV ≤ 9.7 fL. Cox regression analysis showed that poor performance status, increased platelet count, and increased C-reactive protein were independent prognostic factors. The platelet indices were associated with metastases to bone, soft tissue, and lymph node, in addition to malignant pleural effusion. Increased platelet count and decreased MPV were unfavorable prognostic factors for patients with lung cancer, and they were involved in bone, soft tissue, and lymph node metastases and malignant pleural effusion.


Asunto(s)
Neoplasias Pulmonares/patología , Volúmen Plaquetario Medio , Recuento de Plaquetas , Derrame Pleural Maligno/diagnóstico , Neoplasias Óseas/secundario , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Pronóstico , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/secundario , Análisis de Supervivencia
5.
Lupus ; 24(14): 1505-19, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26162683

RESUMEN

OBJECTIVE: The objective of this paper is to determine which kinds of assays for antiphospholipid antibodies (aPL) should be tested for clinical practice for patients with recurrent pregnancy loss (RPL). MATERIALS AND METHODS: We studied 560 patients with a history of RPL prospectively. We determined the obstetric significance of 11 commercially available tested assays for lupus anticoagulant (LA)-aPTT StaClot, phosphatidylserine-dependent antiprothrombin (aPS/PT) IgG, IgM, classical cardiolipin (CL) IgG, IgM, CL IgG, IgM, IgA, and ß2glycoprotein I (ß2GPI) IgG, IgM, IgA Phadia. Obstetric significance was defined as the potential for anticoagulant therapy to improve the subsequent live birth rate, or a difference in the live birth rate between positive and negative untreated cases. RESULTS: The LA-aPTT StaClot assay and aPS/PT IgG assay, but not CL IgG, were found to have obstetric significance. Our conventional tests covered positive cases with the aPS/PT IgM and classical CL IgG assays. The results of the LA-aPTT StaClot, LA-aPTT and LA-RVVT assays showed different distributions, although strong or moderate correlation was observed. CONCLUSION: LA-aPTT StaClot and aPS/PT IgG might be suitable for use in routine practice for patients with RPL. Each test for aPL should be ascertained for obstetric significance, because similar assays may have different outcomes.


Asunto(s)
Aborto Habitual/inmunología , Anticuerpos Antifosfolípidos/análisis , Síndrome Antifosfolípido/inmunología , Obstetricia , Complicaciones del Embarazo/inmunología , Juego de Reactivos para Diagnóstico , Adulto , Anticuerpos Anticardiolipina/sangre , Femenino , Humanos , Obstetricia/métodos , Embarazo , Índice de Embarazo
6.
Arterioscler Thromb Vasc Biol ; 34(11): 2363-71, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25304324

RESUMEN

BACKGROUND: Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. OBJECTIVE: To review the literature on the global burden of disease caused by VTE. APPROACH AND RESULTS: We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. CONCLUSIONS: VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.


Asunto(s)
Costo de Enfermedad , Salud Global/estadística & datos numéricos , Trombosis de la Vena/epidemiología , Factores de Edad , Humanos , Incidencia , Grupos Raciales , Clase Social , Trombosis de la Vena/mortalidad
7.
Phys Chem Chem Phys ; 17(26): 17140-9, 2015 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-26068400

RESUMEN

In this paper, surface- (SERS) and tip-enhanced Raman scattering (TERS) techniques were used to determine the adsorption mode of bradykinin (BK), a small peptide implicated in, for example, carcinoma growth, onto colloidal suspended Ag surfaces under various environmental conditions, including: peptide concentrations (10(-5)-10(-7) M), excitation wavelengths (514.5 and 785.0 nm), and pH of aqueous sol solutions (from pH = 3 to pH = 11). The metal surface plasmon and rheology of the colloidal suspended Ag surface were explored by ultraviolet-visible (UV-Vis) spectroscopy and atomic force/scanning electron microscopy (AFM/SEM). The SERS results indicated that the peptide concentration of 10(-5) M was the optimal peptide concentration for monolayer colloidal coverage. The Phe(5/8) and Arg(9) residues of BK generally participated in the interactions with colloidal suspended Ag surfaces. The amide group appeared to be arranged in the same manner to the Ag surface in the pH range of 3 to 11. At acidic pH of the solution (pH = 3 to 5), the BK -COO(-) terminal group binds to the Ag surface as a bidentate (at pH = 3) or monodentate (at pH = 5) chelating ligand. At pH = 11, the imino group of Arg(9), probably due to its -C[double bond, length as m-dash]N(⊕)H2 protonation state, was not involved in the interaction with Ag. The reduction in the solution alkalinity (pH = 9) produced the deprotonation of the -C=N(⊕)H2 group followed by group rearrangement in a way favoring the interaction between the lone electron pair on N and Ag. The TERS studies confirmed the proposed, on the basis of SERS, behavior of BK onto the colloidal suspended Ag at pH = 7 and showed that in different points of the colloidal suspended Ag surface the same peptide fragments approximately having the same orientations with respect to this surface interact with it.


Asunto(s)
Bradiquinina/química , Plata/química , Espectrometría Raman , Adsorción , Coloides/química , Concentración de Iones de Hidrógeno , Propiedades de Superficie
8.
Phys Chem Chem Phys ; 17(35): 22882-92, 2015 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-26264526

RESUMEN

The tip-enhanced Raman scattering (TERS) spectra of bradykinin (BK) and its potent B2 BK receptor antagonists, [d-Arg(0),Hyp(3),Thi(5,8),l-Pip(7)]BK and [d-Arg(0),Hyp(3),Thi(5),d-Phe(7),l-Pip(8)]BK, approximately with a size of about 40 nm, adsorbed onto colloidal suspended Ag nanowires with diameter in the range of 350-500 nm and length of 2-50 µm were recorded. The metal surface plasmon resonance and morphology of the Ag nanowires were studied by ultraviolet-visible (UV-Vis) spectroscopy and scanning electron microscopy (SEM). Briefly, it was shown that two C-terminal amino acids of BK and [d-Arg(0),Hyp(3),Thi(5,8),l-Pip(7)]BK are involved in the interaction with the colloidal suspended Ag nanowire surface, whereas three last amino acids of the [d-Arg(0),Hyp(3),Thi(5),d-Phe(7),l-Pip(8)]BK sequence attached the Ag surface. Thus, BK adsorbs on the colloidal suspended Ag nanowires mainly through the Phe(5/8) ring (tilted orientation) and the one oxygen atom of the carboxylate group and the H2N-C-NH-CH2- fragment of Arg(9). In the case of [d-Arg(0),Hyp(3),Thi(5,8),l-Pip(7)]BK, the Thi(8) ring (through the lone electron pair on the sulfur atom) and the both oxygen atoms of the carboxylate group and the amine group of Arg(9) mainly participated in the interaction with the Ag nanowire surface. For [d-Arg(0),Hyp(3),Thi(5),d-Phe(7),l-Pip(8)]BK, the d-Phe(7) ring, the Pip(8) ring, and the Arg(9) side-chain assisted in the peptide interaction with the Ag surface. The obtained results emphasize the importance of the C-terminal part of these peptides in the adsorption process onto the colloidal suspended Ag nanowires.

9.
Tissue Antigens ; 83(1): 10-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24355003

RESUMEN

Super high-resolution single molecule sequence-based typing (SS-SBT) is a human leukocyte antigen (HLA) DNA typing method to the field 4 level of allelic resolution (formerly known as eight-digit typing) to efficiently detect new and null alleles without phase ambiguity by combination of long ranged polymerase chain reaction (PCR) amplification and next-generation sequencing (NGS) technologies. We previously reported the development and application of the SS-SBT method for the eight classical HLA loci, A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1. In this article, we describe the development of the SS-SBT method for three DRB1 linked loci, DRB3, DRB4 and DRB5 (DRB3/4/5) and characterization of DRB1-DRB3/4/5 haplotype structures to the field 4 level. Locus specific PCR primers for DRB3/4/5 were designed to amplify the gene regions from intron 1 to exon 6 [3' untranslated region (3'UTR)]. In total 20 DRB1 and 13 DRB3/4/5 allele sequences were determined by the SS-SBT to the field 4 level without phase ambiguity using 19 DR51, DR52 and DR53 positive genomic DNA samples obtained from Japanese. Moreover, 18 DRB1-DRB3/4/5 haplotypes were estimated to the field 4 level by the SS-SBT method in contrast to 10 haplotypes estimated by conventional methods to the field 1 level (formerly known as two digit typing). Therefore, DRB1-DRB3/4/5 haplotyping by SS-SBT is expected to provide informative data for improved HLA matching in medical research, transplantation procedures, HLA-related disease studies and human population diversity studies.


Asunto(s)
Cadenas HLA-DRB1/genética , Cadenas HLA-DRB3/genética , Cadenas HLA-DRB4/genética , Cadenas HLA-DRB5/genética , Prueba de Histocompatibilidad/métodos , Alelos , Cartilla de ADN/genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad/tendencias , Humanos , Reacción en Cadena de la Polimerasa , Inmunología del Trasplante
10.
Nutr Metab Cardiovasc Dis ; 24(3): 309-14, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24418379

RESUMEN

BACKGROUND AND AIMS: It remains unclear whether glycemic fluctuation can affect plaque rupture in acute myocardial infarction (AMI). Here we investigate the impact of glucose fluctuation on plaque rupture, as observed by optical coherence tomography (OCT), and monocyte subsets in patients with AMI. METHODS AND RESULTS: We studied 37 consecutive patients with AMI. All patients underwent OCT examination, which revealed 24 patients with plaque rupture and 13 patients without plaque rupture at the culprit site. Peripheral blood sampling was performed on admission. Three monocyte subsets (CD14(+)CD16(-), CD14(bright)CD16(+), and CD14(dim)CD16(+)) were assessed by flow cytometry. Glycemic variability, expressed as the mean amplitude of glycemic excursion (MAGE), was determined by a continuous glucose monitoring system 7 days after the onset of AMI. MAGE was significantly higher in the rupture patients than in the non-rupture patients (P=0.036). Levels of CD14(bright)CD16(+) monocytes from the rupture patients were significantly higher than those from the non-rupture patients (P=0.042). Of interest, levels of CD14(bright)CD16(+) monocytes correlated positively and significantly with MAGE (r=0.39, P=0.02). CONCLUSION: Dynamic glucose fluctuation may be associated with coronary plaque rupture, possibly through the preferential increase in CD14(bright)CD16(+) monocyte levels.


Asunto(s)
Glucemia/metabolismo , Monocitos/citología , Placa Aterosclerótica/sangre , Anciano , Angiografía Coronaria , Electrocardiografía , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/patología , Placa Aterosclerótica/patología , Estudios Prospectivos , Tomografía de Coherencia Óptica
11.
Scand J Rheumatol ; 42(4): 325-30, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23496326

RESUMEN

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


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Hipotiroidismo/diagnóstico , Hipotiroidismo/inmunología , Inmunoglobulina G/inmunología , Enfermedad de Mikulicz/diagnóstico , Pancreatitis/diagnóstico , Tiroiditis Autoinmune/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Enfermedades Autoinmunes/complicaciones , Colangitis/complicaciones , Colangitis/diagnóstico , Colangitis/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Hipotiroidismo/complicaciones , Masculino , Persona de Mediana Edad , Enfermedad de Mikulicz/complicaciones , Enfermedad de Mikulicz/inmunología , Pancreatitis/complicaciones , Pancreatitis/inmunología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Estadísticas no Paramétricas , Pruebas de Función de la Tiroides , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/inmunología
13.
J Obstet Gynaecol ; 33(2): 171-4, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23445142

RESUMEN

We conducted a prospective study to determine whether systematic examinations and provision of explanation regarding the successful birth rates might improve mood or anxiety disorders among childless women with recurrent miscarriages. A total of 305 first-visit patients with a history of 2-12 miscarriages completed a first questionnaire battery, including: 'K6', a new screening instrument for mood and anxiety disorders, the 'Symptom Checklist-90 Revised' (SCL-90-R) and the 'Emotional Impact' questionnaire. Of these, 170 patients who underwent routine examinations and received an explanation about successful live birth rates responded to the second questionnaire. A total of 15.4% of the patients were estimated to suffer from diagnosable depression or anxiety disorders. Patients with high scores on K6 also showed elevated scores on all the subscales of SCL-90-R, including depression and anxiety. The K6 of patients with translocation was significantly higher than that of patients with antiphospholipid antibodies. The K6 and depression scores in the 2nd questionnaire survey were significantly lower than those in the 1st survey in the 170 patients. Improvement in depression was found in patients who underwent routine examination and received an explanation.


Asunto(s)
Aborto Habitual/psicología , Depresión/terapia , Trastornos del Humor/terapia , Aborto Habitual/diagnóstico , Adulto , Depresión/diagnóstico , Depresión/etiología , Femenino , Humanos , Trastornos del Humor/diagnóstico , Trastornos del Humor/etiología , Embarazo , Estudios Prospectivos , Encuestas y Cuestionarios
14.
Breast Cancer ; 30(4): 657-665, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37217763

RESUMEN

INTRODUCTION: This study described, in routine clinical practice in Japan, the patient characteristics, treatment patterns, and outcomes of female patients with HR + /HER2- metastatic breast cancer (MBC) who started abemaciclib treatment. METHODS: Clinical charts were reviewed for patients starting abemaciclib in 12/2018-08/2021 with a minimum of 3 months follow-up data post-abemaciclib initiation regardless of abemaciclib discontinuation. Patient characteristics, treatment patterns, and tumor response were descriptively summarized. Kaplan-Meier curves estimated progression-free survival (PFS). RESULTS: 200 patients from 14 institutions were included. At abemaciclib initiation, median age was 59 years, and the Eastern Cooperative Oncology Group performance status score was 0/1/2 for 102/68/5 patients (58.3/38.9/2.9%), respectively. Most had an abemaciclib starting dose of 150 mg (92.5%). The percentage of patients receiving abemaciclib as 1st, 2nd, or 3rd line treatment was 31.5%, 25.8%, and 25.2%, respectively. The most frequent endocrine therapy drugs used with abemaciclib were fulvestrant (59%) and aromatase inhibitors (40%). Evaluation of tumor response was available for 171 patients, 30.4% of whom had complete/partial response. Median PFS was 13.0 months (95% CI 10.1-15.8 months). CONCLUSIONS: In a routine clinical practice setting in Japan, patients with HR + , HER2- MBC appear to benefit from abemaciclib treatment in terms of treatment response and median PFS, with the results broadly reflecting the evidence demonstrated in clinical trials.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/patología , Japón , Aminopiridinas/efectos adversos , Fulvestrant/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2
15.
Tissue Antigens ; 80(4): 305-16, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22861646

RESUMEN

Current human leukocyte antigen (HLA) DNA typing methods such as the sequence-based typing (SBT) and sequence-specific oligonucleotide (SSO) methods generally yield ambiguous typing results because of oligonucleotide probe design limitations or phase ambiguity for HLA allele assignment. Here we describe the development and application of the super high-resolution single-molecule sequence-based typing (SS-SBT) of HLA loci at the 8-digit level using next generation sequencing (NGS). NGS which can determine an HLA allele sequence derived from a single DNA molecule is expected to solve the phase ambiguity problem. Eight classical HLA loci-specific polymerase chain reaction (PCR) primers were designed to amplify the entire gene sequences from the enhancer-promoter region to the 3' untranslated region. Phase ambiguities of HLA-A, -B, -C, -DRB1 and -DQB1 were completely resolved and unequivocally assigned without ambiguity to single HLA alleles. Therefore, the SS-SBT method described here is a superior and effective HLA DNA typing method to efficiently detect new HLA alleles and null alleles without ambiguity.


Asunto(s)
Sitios Genéticos , Antígenos HLA/análisis , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Tipificación de Secuencias Multilocus/métodos , Regiones no Traducidas 3' , Alelos , Cartilla de ADN , Antígenos HLA/genética , Secuenciación de Nucleótidos de Alto Rendimiento/instrumentación , Humanos , Tipificación de Secuencias Multilocus/instrumentación , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN
16.
Clin Exp Immunol ; 159(3): 315-26, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20015272

RESUMEN

We have demonstrated previously that, in primary Sjögren's syndrome (SS), immature myeloid dendritic cells (DCs) are decreased in blood and mature myeloid DCs are accumulated in salivary glands, suggesting recruitment of the myeloid DCs from blood to salivary glands. To verify whether this finding is universal in patients of not only primary SS but also secondary SS, in this study we analysed the blood DCs of secondary SS patients. We examined 24 secondary SS and 29 primary SS patients. A direct correlation between the decreased number of myeloid DCs and the duration of Sicca syndrome in primary and secondary SS was observed; namely, the reduction of myeloid DCs in blood was restored spontaneously with duration time of Sicca syndrome. We also examined the immunohistochemical staining of salivary glands of SS patients with monoclonal antibodies against fascin, CD11c and human leucocyte antigen DR (HLA-DR). Fascin(+) or CD11c(+)/HLA-DR(+) mononuclear cells were present in the salivary glands of secondary SS patients, as in primary SS. However, fascin(+) mononuclear cells were barely detected in the salivary glands of a chronic phase of SS patients. We also found a negative correlation between the frequency of blood myeloid DCs and salivary gland-infiltrating DCs in secondary SS patients, as well as primary SS. Our results suggest that the reduction of blood myeloid DCs and preferential trafficking of myeloid DCs into salivary glands is a common event in the early stage of SS. Myeloid DCs may play essential roles in the pathogenesis of Sicca syndrome of SS by initiating T helper cell immune responses.


Asunto(s)
Células Dendríticas/inmunología , Células Mieloides/inmunología , Síndrome de Sjögren/inmunología , Adulto , Antígeno CD11c/inmunología , Antígeno CD11c/metabolismo , Proteínas Portadoras/inmunología , Proteínas Portadoras/metabolismo , Movimiento Celular/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Femenino , Antígenos HLA-DR/inmunología , Antígenos HLA-DR/metabolismo , Humanos , Inmunohistoquímica , Masculino , Proteínas de Microfilamentos/inmunología , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Células Mieloides/metabolismo , Células Mieloides/patología , Glándulas Salivales/inmunología , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/patología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patología
17.
Reproduction ; 139(1): 71-83, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19770224

RESUMEN

In order to study the regulation of the growth differentiation factor-9 (gdf9) gene in a primitive teleost with semelparous life history, we cloned a cDNA encoding shortfinned eel Gdf9, expressed a partial peptide in Escherichia coli, and raised an antiserum to evaluate changes in Gdf9 expression during its pituitary homogenate-induced reproductive cycle. The effects of in vivo and in vitro exposure to the androgen 11-ketotestosterone (11-KT), known to affect previtellogenic (PV) oocyte growth, were also determined. Furthermore, we investigated whether Gdf9 expression was metabolically gated by treating PV fish with recombinant GH in vivo. Immunoreactive proteins of ca. 52 and 55 kDa were identified by western blot analysis. Gdf9 message and protein were most abundant in PV oocytes, and peaked slightly earlier for mRNA than for protein. Captivity resulted in reduced gdf9 mRNA levels, which were restored following pituitary homogenate treatment. As oocytes progressed through induced oogenesis, Gdf9 expression decreased. Neither 11-KT nor GH treatment affected gdf9 mRNA levels in PV fish, although GH could partially restore handling- or captivity-induced decreases in gdf9 mRNA levels. Semelparous eels thus show an expression pattern of Gdf9 during oogenesis that is similar to that seen in other vertebrates, that appears responsive to handling or captivity stress, and whose control remains to be elucidated.


Asunto(s)
Andrógenos/farmacología , Anguilla/fisiología , Factor 9 de Diferenciación de Crecimiento/metabolismo , Hormona del Crecimiento/farmacología , Ovario/metabolismo , Reproducción , Testosterona/análogos & derivados , Anguilla/crecimiento & desarrollo , Anguilla/metabolismo , Animales , Femenino , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Factor 9 de Diferenciación de Crecimiento/química , Factor 9 de Diferenciación de Crecimiento/genética , Factor 9 de Diferenciación de Crecimiento/aislamiento & purificación , Hormona del Crecimiento/análogos & derivados , Inmunohistoquímica , Hibridación in Situ , Factor I del Crecimiento Similar a la Insulina/metabolismo , Técnicas de Amplificación de Ácido Nucleico , Oogénesis , Especificidad de Órganos , Ovario/citología , Ovario/efectos de los fármacos , Ovario/crecimiento & desarrollo , Filogenia , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN , Estrés Fisiológico , Testosterona/farmacología
19.
J Dairy Sci ; 93(7): 2887-95, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20630206

RESUMEN

The effects of whipping temperature (5 to 15 degrees C) on the whipping (whipping time and overrun) and rheological properties of whipped cream were studied. Fat globule aggregation (aggregation ratio of fat globules and serum viscosity) and air bubble factors (overrun, diameter, and surface area) were measured to investigate the mechanism of whipping. Whipping time, overrun, and bubble diameters decreased with increasing temperature, with the exception of bubble size at 15 degrees C. The aggregation ratio of fat globules tended to increase with increasing temperature. Changes in hardness and bubble size during storage were relatively small at higher temperatures (12.5 and 15 degrees C). Changes in overrun during storage were relatively small in the middle temperature range (7.5 to 12.5 degrees C). From the results, the temperature range of 7.5 to 12.5 degrees C is recommended for making whipped creams with a good texture, and a specific temperature should be decided when taking into account the preferred overrun. The correlation between the whipped cream strain hardness and serum viscosity was high (R(2)=0.906) and persisted throughout the temperature range tested (5 to 15 degrees C). A similar result was obtained at a different whipping speed (140 rpm). The multiple regression analysis in the range of 5 to 12.5 degrees C indicated a high correlation (R(2)=0.946) in which a dependent variable was the storage modulus of whipped cream and independent variables were bubble surface area and serum viscosity. Therefore, fat aggregation and air bubble properties are important factors in the development of cream hardness. The results of this study suggest that whipping temperature influences fat globule aggregation and the properties of air bubbles in whipped cream, which alters its rheological properties.


Asunto(s)
Productos Lácteos , Manipulación de Alimentos/métodos , Temperatura , Productos Lácteos/análisis , Reología , Factores de Tiempo , Viscosidad
20.
J Phys Chem B ; 113(11): 3385-94, 2009 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-19231883

RESUMEN

The surface melting and lamella rearrangement process that happen in commercially available linear low-density polyethylene (LLDPE) were studied with special emphasis on conformational and crystal structural changes during the process. The thermal melting behavior of the specimens was examined by using differential scanning calorimetry and the occurrence of the surface melting was strongly suggested in low-crystallinity LLDPE (LLDPE-L) in the temperature range of 90-120 degrees C at the heating rate of 2 degrees C/min. The structural and conformational disordering process during heating was studied by IR spectroscopy combined with two-dimensional spectral correlation analysis. The formation of conformational defects has been determined to proceed prior to the overall disordering of orthorhombic crystalline structure in all the PE specimens except for LLDPE-L. During the heating process, conformational defects are preferably developed in side chains that are excluded from tightly packed orthorhombic crystal in PEs other than in LLDPE-L. The temperature dependency in the thickness of lamella layers of LLDPE-L examined by small-angle X-ray scattering indicates the occurrence of the lamella thickening in the temperature range where surface melting has been observed. In this way, the formation of new orthorhombic cells due to the lamella rearrangement dominates over the formation of conformational defects in LLDPE-L while other specimens indicate opposite. Wide-angle X-ray scattering shows significantly suppressed dilation of the unit cell in LLDPE-L, especially toward orthorhombic unit cell parameter a in the temperature range where lamella thickening process undergoes. It is implied that the lamella thickening happens not only by rearranging the chains originally exist in the interfacial region but also it incorporates those originally existing in the orthorhombic crystal phase in LLDPE-L. The heat-induced morphological changes are explored by means of polarized light microscope with liquid crystal universal compensator and circular polarizer (LC-PolScope). Unlike other PE specimen, high-crystallinity LLDPE (LLDPE-H) shows the retardance histogram with multiple peaks, indicating the presence of several types of higher order structure, such as aggregation within the specimen.

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