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1.
Chemotherapy ; 62(4): 239-245, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28472787

RESUMEN

We retrospectively evaluated clinical data from patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy agents prior to treatment, to determine a reliable method for predicting prognosis in such patients. We analyzed 100 patients who received third-generation agents (paclitaxel, docetaxel, gemcitabine, irinotecan, and vinorelbine) for the treatment of advanced NSCLC. Factors significantly related to prognosis were evaluated using the Cox regression model, and the prognostic index (PI) was determined by combining these factors. The mean follow-up duration was 12.6 months (0.2-67.0 months). Multivariate analysis identified pleural effusion, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as significant factors that independently contribute to prognosis in patients with advanced NSCLC treated with third-generation agents (p < 0.05). The PI was calculated using these 3 factors, according to the following formula: PI = 0.581 × pleural effusion + 0.125 × ANC + 0.105 × CRP. The death rate in the group with the highest PI scores was significantly higher than in the group with the lowest scores (p < 0.001). Pleural effusion, ANC, and CRP level were the most important factors that contributed to prognosis following chemotherapy with third-generation agents in patients with advanced NSCLC. The PI is suggested to be an appropriate index to predict the prognosis of patients with NSCLC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Femenino , Humanos , Leucocitos/citología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Taxoides/administración & dosificación , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina , Gemcitabina
2.
Int Arch Allergy Immunol ; 156(2): 148-58, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21576985

RESUMEN

BACKGROUND: CD4(+)CD25(+) regulatory T (T(reg)) cells can control the allergic response to allergen, airway eosinophilia and airway hypersensitivity. We speculated that chronic inflammation persisting in asthma airways is dependent on abnormalities of these T(reg) cells. There are differences in the pathology of asthma in adults and children, and the airways of pediatric asthma are considered to be more naive than those of adults. Therefore, we analyzed the functionality of T(reg) cells in pediatric asthma and the relationship between T(reg) function and asthma symptoms. METHODS: The anergic state, which is one of the defining properties of T(reg), was analyzed by measuring intracellular Ca(2+) influx following T cell receptor (TCR) stimulation. FOXP3-positive cells and FOXP3 mRNA expression were measured by flow analysis and real-time PCR with the SYBR method, respectively. RESULTS: CD45RO(+) cells make up approximately 99% of CD4(+)CD25(high) T cells and 89% of CD4(+)CD25(low) T cells in human adult blood. The proportion of CD45RO(+) cells in CD4(+)CD25(+) (high + low) T cells from pediatric asthma was much smaller (about 56%). Interestingly, our data indicated that CD45RO(+) T(reg) cells from pediatric asthma aberrantly increased intracellular Ca(2+) concentrations following TCR activation compared with pediatric nonasthma controls. CONCLUSION: These impaired CD45RO(+) T(reg) cell functions were correlated with asthma symptoms. The correlation was observed in the group with a highly expressed atopic phenotype and longer duration of asthma. We suggest that chronic inflammation in pediatric asthma airways may be the result of impaired regulatory functions of CD45RO(+) T(reg) cells.


Asunto(s)
Asma/inmunología , Calcio/inmunología , Factores de Transcripción Forkhead/inmunología , Antígenos Comunes de Leucocito/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Niño , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/genética , Humanos , Lactante , Masculino , Microscopía Fluorescente , ARN Mensajero/química , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
3.
Yakugaku Zasshi ; 130(12): 1643-6, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21139389

RESUMEN

The increase in the number of universities in Japan in spite of a decrease in the number of enrollees is causing a decline in the academic ability of undergraduates. The diversification of selection methods also contributes to the deterioration of the situation. Some students and teachers in high schools still hold the prejudice that only chemistry is important in the entrance examination for schools of pharmacy. To study pharmaceutical sciences, biology is as important as chemistry, and the number of students who have difficulty in obtaining biology course credits is increasing. Logical thinking based on the established knowledge in basic sciences is necessary for a successful clinical clerkship. However, students are inexperienced in logical thinking using the knowledge learned in their classes. This is why practice is needed during the basic pharmaceutical course. We made it compulsory for all second- and third-year students to take practical courses in physics, chemistry, and biology. In addition, a program in which a tutor conducted individual practice for students was carried out. A change in students' sense of purpose in learning was achieved by changing the method and environment of learning.


Asunto(s)
Aptitud , Curriculum/tendencias , Educación en Farmacia/tendencias , Aprendizaje , Motivación , Estudiantes de Farmacia/psicología , Docentes , Humanos , Japón , Autoevaluación (Psicología)
4.
Immunol Invest ; 39(8): 796-806, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20718663

RESUMEN

Catalase is reported to be one of the target antigens for autoantibodies in various pathologies. To understand the mechanism of autoantibody production, we compared the several properties of autoantigenic epitopes (AE)-1 and -2 of mouse catalase, which reported to react with antibodies from sera of Helicobacter hepaticus-infected mice; AE-3 and -4 of rat catalase, which we found to be susceptible to autoimmunity; and antigenic epitope (E)-1 of H. pylori catalase, which is recognized by monoclonal antibodies produced by immunized mice. Amino acid sequences of AE-1 and -2 were similar among both mammalian and pathogenic microorganism catalases, whereas that of E-1 differed. Amino acid sequences of AE-3 and -4 were similar among mammalian catalases but differed from pathogenic microorganism catalases. Based on local relative rates of evolution, these vertebrate catalases were divided into 5 segments. E-1 included a faster evolving region, whereas AE-1 and -2 included a slowly evolving region; AE-3 and -4 comprised a slowly evolving patch within a faster evolving region. In conclusion, although AE-1 and -2 of catalase have been reported to contribute to autoimmune responses in animals infected with catalase-producing pathogens, AE-3 and -4 appear to have a different mechanism for autoantibody production.


Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Catalasa/inmunología , Mapeo Epitopo/métodos , Epítopos/química , Secuencia de Aminoácidos , Animales , Antígenos Bacterianos , Autoanticuerpos/biosíntesis , Autoinmunidad , Catalasa/química , Bovinos , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter hepaticus/enzimología , Helicobacter hepaticus/inmunología , Helicobacter pylori/enzimología , Helicobacter pylori/inmunología , Humanos , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Ratas , Alineación de Secuencia
5.
Gan To Kagaku Ryoho ; 37(4): 659-64, 2010 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-20414022

RESUMEN

OBJECTIVE: To assess the cost-effectiveness of chemotherapy for patients with non-resectable pancreatic cancer, we compared two regimens containing either gemcitabine (GEM) or S-1. METHODS: We developed a decision tree that showed the clinical processes of non-resectable pancreatic cancer patients. We calculated the probabilities of endpoint and life months gained (LMG) based on previously reported articles. To estimate the costs, we analyzed medical records of 44 inpatients with non-resectable pancreatic cancer treated with GEM(n=34)or S-1(n=10). Sensitivity analysis was used to check the robustness of the results. RESULTS: In the GEM group and S-1 group, costs were 1,636,393 and 985,042 yen, and LMG was 6. 0 and 9. 0 months, respectively. Thus, the cost-effectiveness ratio(CER)was calculated to be 272,732 and 109,449 yen/LMG, respectively, and the incremental cost effectiveness ratio (ICER) was -217,117 yen/LMG. The sensitivity analysis showed that the result was definitely robust. CONCLUSION: Our findings suggest that the markedly cost-effective S-1 regimen could prolong LMG with less cost than the GEM regimen.


Asunto(s)
Antineoplásicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Desoxicitidina/análogos & derivados , Ácido Oxónico/economía , Neoplasias Pancreáticas/economía , Tegafur/economía , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Costo-Beneficio , Desoxicitidina/economía , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Tegafur/uso terapéutico , Gemcitabina
6.
J Lipid Res ; 51(1): 210-5, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19620694

RESUMEN

Human plasma contains three forms of adiponectin, a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We previously reported HMW adiponectin was a gelatin-binding protein of 28 kDa (GBP28), it having been purified due to its affinity to gelatin-Cellulofine (Nakano, Y., et al. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996. 120: 803-12). Although HMW adiponectin binds to gelatin-Cellulofine, it cannot bind to gelatin-Sepharose. Gelatin-Cellulofine was made of formyl-Cellulofine and gelatin, and we found that HMW adiponectin binds to reduced formyl-Cellulofine with similar affinity as to gelatin-Cellulofine. Through only two steps using reduced formyl-Cellulofine and DEAE-Sepharose, HMW adiponectin can be effectively purified from human plasma.


Asunto(s)
Cromatografía de Afinidad/métodos , Cromatografía DEAE-Celulosa/métodos , Gelatina/química , Adiponectina/sangre , Adiponectina/aislamiento & purificación , Adiponectina/farmacología , Animales , Línea Celular , Celulosa/análogos & derivados , Celulosa/química , Humanos , Ratones , Peso Molecular , Osteoclastos/efectos de los fármacos , Ligando RANK/farmacología
7.
Horm Res ; 70(5): 268-72, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18824864

RESUMEN

AIMS: High-molecular-weight adiponectin (HMW-ad) is an active form of adiponectin. No information is available with respect to HMW-ad in neonates. The aims of this study were to examine whether HMW-ad is present in cord blood, to define the association between the concentrations of cord blood HMW-ad and leptin, and their correlation with anthropometric measurements of term neonates at birth. METHODS: Venous cord blood samples were obtained from 135 term healthy neonates (birth weight 2,261-4,164 g) born at Showa University Hospital. Total adiponectin (T-ad), HMW-ad and leptin levels were measured by ELISA. RESULTS: HMW-ad levels were 14.9 +/- 5.8 microg/ml and the ratio of HMW-ad to T-ad was 0.49 +/- 0.15. In a multiple regression analysis, cord blood HMW-ad levels were a significant predictor of birth weight and birth length, and leptin level was a significant predictor of birth weight and birth weight to body length ratio. There was a significant relationship between concentrations of HMW-ad and leptin controlling for sex, gestational age and birth weight. CONCLUSION: These results show that HMW-ad exists as a half of T-ad in the cord blood. Leptin and HMW-ad may regulate synergistically fetal growth.


Asunto(s)
Adiponectina/sangre , Sangre Fetal/química , Leptina/sangre , Peso al Nacer , Estatura , Femenino , Desarrollo Fetal/fisiología , Edad Gestacional , Humanos , Recién Nacido , Masculino , Peso Molecular , Embarazo
8.
J Neurochem ; 106(6): 2375-84, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18643870

RESUMEN

Math2 (NEX-1/NeuroD6) is a member of the basic helix-loop-helix transcription factor family and is involved in neuronal differentiation and maturation. In this study, we identified the genes targeted by Math2 using DNA microarrays and cultured rat cortical cells transfected with Math2. Of the genes regulated by Math2, we focused on plasticity-related gene 1 (Prg1). Prg1 expression induced by Math2 was confirmed in cultured rat cortical cells and PC12 cells analyzed by real-time quantitative PCR. In the promoter region of rat Prg1, we identified four E-boxes [designated -E1 to -E4 (CANNTG)] recognized by the basic helix-loop-helix transcription factor. Using chromatin immunoprecipitation assays, we found that Math2 directly bound to at least one of these E-boxes. The Prg1 reporter assay showed that -E1 was critical for the regulation of Math2-mediated Prg1 expression. Investigation of the functional roles of Math2 and Prg1 in PC12 cells revealed that 72 h after transfection with either Math2 or Prg1, neurite length and number were significantly induced. Co-transfection with Prg1-siRNA completely inhibited Math2-mediated morphological changes. Our results suggest that Math2 directly regulates Prg1 expression and that the Math2-Prg1 cascade plays an important role in neurite outgrowth in PC12 cells.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Encéfalo/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Neuronas/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Encéfalo/citología , Encéfalo/embriología , Proteínas de Unión a Calmodulina , Diferenciación Celular/genética , Células Cultivadas , Elementos E-Box/genética , Secuencias Hélice-Asa-Hélice/genética , Neuritas/metabolismo , Neuritas/ultraestructura , Células PC12 , Monoéster Fosfórico Hidrolasas/genética , Regiones Promotoras Genéticas/genética , Unión Proteica/genética , Ratas , Elementos Reguladores de la Transcripción/genética , Factores de Transcripción/genética
9.
Biol Pharm Bull ; 31(6): 1250-3, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18520063

RESUMEN

The quality of microparticle enzyme immunoassay (MEIA) for blood tacrolimus is guaranteed in samples with hematocrit (Ht) values of 25 to 45%. Because MEIA provides inaccurate blood tacrolimus concentrations in samples with Ht out of this range (i.e. <25% or >45%), correction of the calibration is required for therapeutic drug monitoring. The authors demonstrated previously that overestimated MEIA tacrolimus concentration could be corrected by modified, calibrated MEIA (cMEIA) using the original calibrator. Here, an equation was established to more easily derive a corrected tacrolimus concentration by calculation (MEIAcalc) using the Ht of each sample. The tacrolimus concentrations of 99 whole-blood samples with low Ht (<25%) were then tested by the 3 assay methods: MEIA, cMEIA, and MEIAcalc. MEIA gave a significantly higher blood concentration of tacrolimus (median 12.9 ng/ml, range 3.6-26.4 ng/ml) than did cMEIA (median 10.0 ng/ml, range 0.2-21.1 ng/ml, p<0.05). This overestimation was eliminated by using MEIAcalc. There was no difference in blood tacrolimus concentration between cMEIA and MEIAcalc (median 10.0 ng/ml, range 1.7-21.4 ng/ml). MEIAcalc can be used to correct the tacrolimus concentration in samples obtained from patients with unstable Ht values.


Asunto(s)
Hematócrito , Inmunosupresores/sangre , Tacrolimus/sangre , Algoritmos , Trasplante de Médula Ósea/inmunología , Ensayo de Inmunoadsorción Enzimática , Humanos , Técnicas para Inmunoenzimas , Inmunosupresores/administración & dosificación , Trasplante de Riñón/inmunología , Trasplante de Hígado/inmunología , Nanopartículas , Tacrolimus/administración & dosificación
10.
Circulation ; 116(24): 2809-17, 2007 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-18040027

RESUMEN

BACKGROUND: Overeating and obesity are major health problems in developed countries. Caloric restriction (CR) can counteract the deleterious aspects of obesity-related diseases and prolong lifespan. We have demonstrated that short-term CR improves myocardial ischemic tolerance and increases adiponectin levels. Here, we investigated the specific role of adiponectin in CR-induced cardioprotection. METHODS AND RESULTS: Adiponectin antisense transgenic (Ad-AS) mice and wild-type (WT) mice were randomly assigned to a group fed ad libitum and a CR group (90% of caloric intake of ad libitum for 3 weeks, then 65% for 2 weeks). Isolated perfused mouse hearts were subjected to 25 minutes of ischemia, followed by 60 minutes of reperfusion. CR increased serum adiponectin levels by 84% in WT mice. Gel filtration analysis of the oligomeric complex distribution showed that CR produced a marked increase in the high-molecular-weight complex of adiponectin in WT mice; in contrast, CR did not change serum adiponectin levels or their oligomeric pattern in Ad-AS mice. CR improved the recovery of left ventricular function after ischemia/reperfusion and limited infarct size in WT mice; these effects were completely abrogated in Ad-AS mice. CR also increased the phosphorylated form of AMP-activated protein kinase and acetyl-CoA carboxylase in WT but not in Ad-AS mice. Recombinant adiponectin restored CR-induced cardioprotection in Ad-AS mice, and inhibition of AMP-activated protein kinase phosphorylation completely abrogated CR-induced cardioprotection in WT mice. CONCLUSIONS: The cardioprotective effects of short-term CR are mediated by increased production of adiponectin and the associated activation of AMP-activated protein kinase.


Asunto(s)
Adenilato Quinasa/metabolismo , Adiponectina/fisiología , Dieta Reductora , Isquemia Miocárdica/dietoterapia , Isquemia Miocárdica/fisiopatología , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Isquemia Miocárdica/enzimología , Obesidad/prevención & control
12.
Yakugaku Zasshi ; 127(5): 905-17, 2007 May.
Artículo en Japonés | MEDLINE | ID: mdl-17473534

RESUMEN

The aim of this study was to analyze students, achievement rate and contents of assessment judged by instructors in objective structured clinical examination (OSCE) attempted at the Faculty of Pharmaceutical Science, Showa University. The OSCE was carried out for fourth-year students in May 28, 2005. In this trial, there were two stations, i.e., counting/measurement dispensing and subsequent audit of dispensed drugs, and 218 students and 31 instructors (as evaluators) participated. We developed a checklist to test students attitudes and skills (two stages) and overall evaluation (five stages). Each student was evaluated by two instructors. Examination time was 8 minutes for drug dispensing, and 4 minutes for the audit of dispensed drug. After the OSCE trial, we analyzed validity of examination time, contents of assessment, and differences in scores between different evaluators. More than half of the students could not finish the examination within the limit of time for dispensing the liquid and cream and audit for dispensed powder. The number of items that 60% of the students achieved was 48 (82.8%). Moreover, 20% of the assessment items did not agree among the evaluators with a disagreement rate of 20% or more. Thus, we distinguished between the items based on the extent of disagreement rates. It was suggested that most of the students achieved such a level to actually perform clinical training in pharmacies. From these results, it is necessary to set up an assignment to finish the within the time limit to extent the time limit depending upon examination contents, to standardize the evaluation to increase the agreement rate among evaluators, and to more clearly identify assessment criteria.


Asunto(s)
Pruebas de Aptitud , Competencia Clínica/estadística & datos numéricos , Educación en Farmacia/métodos , Evaluación Educacional/métodos , Evaluación Educacional/estadística & datos numéricos , Escolaridad , Docentes , Facultades de Farmacia , Estudiantes de Farmacia , Adulto , Competencia Clínica/normas , Humanos
13.
J Autoimmun ; 28(4): 201-7, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17418529

RESUMEN

FOXP3 is a key gene in the development of regulatory T cells (Treg). FOXP3 expression commits naïve T cells to become Treg cells. Indeed, mutations in the FOXP3 gene cause severe systemic autoimmune diseases in humans and in mice. Therefore, we hypothesized that the FOXP3 gene may be associated with thyroid autoimmunity which is among the typical autoimmune diseases that develop in individuals with FOXP3 mutations. Moreover, the FOXP3 gene is located within an X-chromosome locus (Xp11.23) previously shown to be linked with autoimmune thyroid diseases (AITD). We tested the FOXP3 gene locus for association with AITD in two large cohorts of US Caucasians and Japanese AITD patients. We analyzed 269 Caucasian AITD patients (52 males and 217 females) and 357 Caucasian controls (159 males and 198 females), as well as 377 female Japanese AITD patients and 179 female Japanese controls. The FOXP3 gene locus was analyzed using four microsatellite polymorphisms [(GT)n; (TC)n; DXS573; DXS1208] flanking the FOXP3 gene locus. Interestingly, while no association was found between FOXP3 polymorphisms and AITD in the Japanese cohort there was a significant association in the Caucasian cohort. There was a significant association of the (TC)n polymorphism with AITD in the Caucasian male AITD patients (p=0.011; 5 degrees of freedom [df]). Similarly, there was an association between the DXS573 microsatellite and AITD in the Caucasian female AITD patients (p=0.00023; 4 df). These results suggest that polymorphisms of the FOXP3 gene may play a role in the genetic susceptibility to AITD in Caucasians, perhaps by altering FOXP3 function and/or expression.


Asunto(s)
Pueblo Asiatico , Factores de Transcripción Forkhead/genética , Predisposición Genética a la Enfermedad , Linfocitos T Reguladores , Tiroiditis Autoinmune/genética , Población Blanca , Animales , Cromosomas Humanos X/genética , Cromosomas Humanos X/inmunología , Estudios de Cohortes , Femenino , Factores de Transcripción Forkhead/inmunología , Humanos , Masculino , Ratones , Repeticiones de Microsatélite , Polimorfismo Genético/inmunología , Sitios de Carácter Cuantitativo/inmunología , Factores Sexuales , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Tiroiditis Autoinmune/etnología , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/patología
14.
Mol Genet Genomics ; 277(6): 663-72, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17318585

RESUMEN

The identification of candidate genes for significant traits is crucial. In this study, we developed and tested effective and systematic methods based on linkage disequilibrium (LD) for the identification of candidate regions for genes with Mendelian inheritance and those associated with complex traits. Our approach entailed the combination of primary screening using pooled DNA samples based on DeltaTAC, secondary screening using an individual typing method and tertiary screening using a permutation test based on the differences in the haplotype frequency between two neighbouring microsatellites. This series of methods was evaluated using horse coat colour traits (chestnut/non-chestnut) as a simple Mendelian inheritance model. In addition, the methods were evaluated using a complex trait model constructed by mixing samples from chestnut and non-chestnut horses. Using both models, the methods could detect the expected regions for the horse coat colour trait. The results revealed that LD extends up to several centimorgans in horses, indicating that whole-genome LD screening in horses could be performed systematically and efficiently by combining the above-mentioned methods. Since genetic maps based on microsatellites have been constructed for many other species, the approaches present here could have wide applicability.


Asunto(s)
Genoma , Caballos/genética , Desequilibrio de Ligamiento , Repeticiones de Microsatélite , Animales , Mapeo Cromosómico , Haplotipos , Fenotipo
15.
Gene ; 392(1-2): 181-6, 2007 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-17306472

RESUMEN

Genetic maps are extremely important tools for tracing the genes that govern economically significant traits, and microsatellites are a significant component of these. In this study, we isolated 2346 novel horse microsatellites as resources for the construction of high-density horse genetic maps. Of these 2346 markers, 339 (14.5%) horse sequences showed sequence homology to DNA sequences in the human genome, demonstrating that microsatellites as type II markers are valuable resources for developing linkage maps and that they have a potential equal to that of type I markers for developing comparative maps. Of the 339 markers, 206 (60.8%) were assigned to horse chromosomes using the Animal Health Trust (AHT) full-sib reference family, and 195 (94.6%) of these localized to the expected syntenic locations on the human genome. These results confirmed the high level of accuracy of in silico mapping. Thus, the 339 markers that exhibited homology to the human genome increased the density of markers on the horse-human comparative map. The resulting comparative map will facilitate the use of horse microsatellites as genetic markers for the identification of quantitative trait loci (QTL) that have been mapped on the human genome. In addition, although the in silico and linkage mapping data did not agree for the other 11 (5.4%) of the assigned 206 markers, these may represent new putative regions of horse-human synteny.


Asunto(s)
Mapeo Cromosómico , Marcadores Genéticos , Caballos/genética , Animales , Bases de Datos Genéticas , Humanos , Repeticiones de Microsatélite , Datos de Secuencia Molecular , Homología de Secuencia de Ácido Nucleico
16.
Atherosclerosis ; 195(1): 153-9, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17049533

RESUMEN

Serotonin (5-HT), a potent vasoconstrictor in the large cerebral arteries, is considered to play a key role in atherothrombosis and to be implicated in ischemic cerebrovascular events followed by delayed neuronal death. The present study aims at evaluating the relationship between plasma levels of 5-HT and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Carotid artery intima-media thickness (IMT), plaques, plasma 5-HT levels and atherosclerotic parameters were determined in 20 patients with VaD and 40 age-matched controls. Age, gender, body mass index, systolic and diastolic blood pressure, fasting plasma glucose levels and serum levels of insulin, triglycerides, high-density lipoprotein cholesterol, leptin, adiponectin and interleukin-6 and plasma levels of plasminogen activator inhibitor-1 were not significantly different between the two groups. Serum levels of insulin-like growth factor-1 (IGF-1) were significantly lower in VaD patients than in controls. Plasma 5-HT levels, serum levels of hepatocyte growth factor (HGF), low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hs-CRP), max IMT and plaque frequency were significantly greater in VaD patients than in controls. There was a significant positive correlation of max IMT with 5-HT or HGF levels. Multiple logistic regression analysis revealed that increased plasma levels of 5-HT and carotid plaque prevalence had significantly independent association with VaD as compared with serum levels of IGF-1, HGF, LDL cholesterol and hs-CRP. These results suggest that increased plasma levels of 5-HT and carotid atherosclerotic plaques may be involved in the pathogenesis and progression of VaD.


Asunto(s)
Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/complicaciones , Demencia Vascular/sangre , Demencia Vascular/complicaciones , Serotonina/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores , Glucemia/metabolismo , Presión Sanguínea , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/diagnóstico , LDL-Colesterol/metabolismo , Demencia Vascular/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Serotonina/metabolismo
17.
Pediatr Allergy Immunol ; 17(8): 583-90, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17121586

RESUMEN

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.


Asunto(s)
Citocinas/genética , Dermatitis Atópica/genética , Hipersensibilidad a los Alimentos/genética , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad , Adolescente , Contaminación del Aire Interior , Actitud , Niño , Preescolar , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Humanos , Inmunoglobulina E/biosíntesis , Interleucina-10/fisiología , Interleucina-4/genética , Hepatopatías/etiología , Receptores de IgE/genética , Receptores de Interleucina-4/genética , Estudios Retrospectivos , Factores de Riesgo , Factor de Transcripción STAT6/genética
18.
J Biol Chem ; 281(43): 32741-54, 2006 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-16931517

RESUMEN

The mechanisms by which secretory phospholipases A(2) (PLA(2)s) exert cellular effects are not fully understood. Group IIF PLA(2) (gIIFPLA(2)) is a structurally unique secretory PLA(2) with a long C-terminal extension. Homology modeling suggests that the membrane-binding surface of this acidic PLA(2) contains hydrophobic residues clustered near the C-terminal extension. Vesicle leakage and monolayer penetration measurements showed that gIIFPLA(2) had a unique ability to penetrate and disrupt compactly packed monolayers and bilayers whose lipid composition recapitulates that of the outer plasma membrane of mammalian cells. Fluorescence imaging showed that gIIFPLA(2) could also readily enter and deform plasma membrane-mimicking giant unilamellar vesicles. Mutation analysis indicates that hydrophobic residues (Tyr(115), Phe(116), Val(118), and Tyr(119)) near the C-terminal extension are responsible for these activities. When gIIFPLA(2) was exogenously added to HEK293 cells, it initially bound to the plasma membrane and then rapidly entered the cells in an endocytosis-independent manner, but the cell entry did not lead to a significant degree of phospholipid hydrolysis. GIIFPLA(2) mRNA was detected endogenously in human CD4(+) helper T cells after in vitro stimulation and exogenously added gIIFPLA(2) inhibited the proliferation of a T cell line, which was not seen with group IIA PLA(2). Collectively, these data suggest that unique membrane-binding properties of gIIFPLA(2) may confer special functionality on this secretory PLA(2) under certain physiological conditions.


Asunto(s)
Membrana Celular/metabolismo , Fosfolipasas A/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , División Celular/efectos de los fármacos , Línea Celular , Membrana Celular/química , Escherichia coli/genética , Fosfolipasas A2 Grupo II , Humanos , Hibridomas/efectos de los fármacos , Hidrólisis , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Masculino , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Fosfolipasas A/química , Fosfolipasas A/genética , Fosfolipasas A/farmacología , Fosfolipasas A2 , Fosfolípidos/química , Fosfolípidos/metabolismo , ARN Mensajero/metabolismo , Homología de Secuencia de Aminoácido , Electricidad Estática , Especificidad por Sustrato , Linfocitos T/efectos de los fármacos
19.
Biochim Biophys Acta ; 1761(7): 709-16, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16815093

RESUMEN

Adiponectin is an adipose tissue-specific secretory protein known to be an insulin-sensitizing protein. In this study, we generated adiponectin sense and antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in the regulation of energy homeostasis during the growth stage. Spontaneous motor activity of antisense Tg mice were markedly reduced during fasting, particularly in young female mice, compared with wild type (Wt) and sense Tg mice. Furthermore, both body weight and adipose tissue mass of the antisense female Tg mice drastically reduced during fasting. To examine the relationship between the collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we measured the expression of genes related to energy expenditure, such as uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly increased during fasting. These findings suggest that the serum adiponectin is important to maintaining energy homeostasis under energy shortage conditions, such as over female pubertal development.


Asunto(s)
Adiponectina/metabolismo , Metabolismo Energético , Adiponectina/genética , Tejido Adiposo/metabolismo , Envejecimiento/fisiología , Animales , Peso Corporal , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , ADN sin Sentido , Metabolismo Energético/genética , Ayuno , Femenino , Regulación del Desarrollo de la Expresión Génica , Canales Iónicos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Ratones , Ratones Transgénicos , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Especificidad de Órganos , Factores Sexuales , Proteína Desacopladora 1 , Proteína Desacopladora 2
20.
Diabetes ; 55(7): 1954-60, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16804063

RESUMEN

Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-to-total adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients.


Asunto(s)
Adiponectina/sangre , Enfermedad Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , Anciano , Glucemia/metabolismo , Angiopatías Diabéticas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Peso Molecular , Subunidades de Proteína
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