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1.
Zhonghua Fu Chan Ke Za Zhi ; 59(5): 383-390, 2024 May 25.
Artículo en Zh | MEDLINE | ID: mdl-38797568

RESUMEN

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Epitelial de Ovario , Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Persona de Mediana Edad , Quimioterapia Adyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Pronóstico , Adulto , Resultado del Tratamiento , Anciano , Estudios Retrospectivos , Estadificación de Neoplasias
2.
Zhonghua Wai Ke Za Zhi ; 62(5): 370-378, 2024 May 01.
Artículo en Zh | MEDLINE | ID: mdl-38548604

RESUMEN

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.


Asunto(s)
Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Masculino , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Pronóstico , Tasa de Supervivencia , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales , Cuidados Paliativos , Estimación de Kaplan-Meier , Hepatectomía/métodos , Resultado del Tratamiento
3.
Zhonghua Yan Ke Za Zhi ; 60(6): 528-536, 2024 Jun 11.
Artículo en Zh | MEDLINE | ID: mdl-38825952

RESUMEN

Objective: To explore the changes in gray matter volume of the cerebral cortex in patients with intermittent exotropia (IXT) using the voxel-based analysis and to analyze the correlation between these changes and clinical manifestations. Methods: This was a cross-sectional study. A collection of 15 consecutive patients diagnosed with IXT at Tianjin Eye Hospital from March 2021 to May 2022 formed the exotropia group, which comprised 8 males and 7 females, with an average age of (23.5±5.2) years. Ten healthy individuals, 3 males and 7 females, with an average age of (27.0±7.5) years, were selected as the control group. All participants underwent assessments of exotropia severity and Titmus stereoacuity. Three-dimensional high-resolution brain images were obtained through MRI scans. Voxel-based morphometry was employed to preprocess the MRI data, and the SPM toolbox in MATLAB was utilized to analyze differences of images between the two groups. Regions of interest (ROI) with structural abnormalities in the gray matter volume analysis were selected, and the ratio of gray matter voxel values in the ROI to the mean gray matter voxel values of the whole brain for each participant was calculated using the MarsBaR software. The correlation between this ratio and exotropia severity as well as the common logarithm of Titmus stereoacuity was analyzed. Results: The differences in age, gender distribution, and refractive error between the two groups were not statistically significant (all P>0.05). However, there were statistically significant differences in the degree of strabismus and Titmus stereoacuity (both P<0.001). Compared to the control group, patients in the strabismus group exhibited decreased gray matter volume in several brain regions, including the wedges of the medial surface of the cerebral hemisphere (decreased by 89 voxels), the left lingual gyrus (decreased by 176 voxels), the left calcarine sulcus V3 area (decreased by 30 voxels), the central anterior gyrus of the right frontal lobe (decreased by 192 voxels), the gray matter of the left hippocampal gyrus (decreased by 20 voxels), and the bilateral lateral geniculate nuclei (decreased by 100 and 40 voxels on the left and right sides, respectively). These differences were all statistically significant (all P<0.001). Additionally, there was an increase in gray matter volume in several brain regions, including the bilateral caudate nuclei (increased by 60 and 76 voxels on the left and right sides, respectively) and the left precentral gyrus (increased by 36 voxels). These differences were also statistically significant (all P<0.001). A group-level analysis identified 10 brain regions with structural differences between the two groups, which were used as ROI. The gray matter volume ratio was negatively correlated with the degree of exotropia (all P<0.05) in the ROI of the left wedges (r=-0.670), left calcarine sulcus V3 area (r=-0.610), and left lingual gyrus (r=-0.684). The gray matter volume ratio was negatively correlated with lgTS (all P<0.05) in the ROI of the left wedges (r=-0.568) and the central anterior gyrus of the right frontal lobe (r=-0.563). Conclusions: Patients with IXT exhibit decreased gray matter volume in the horizontal connection areas between the primary visual cortices V1 and V2. The reduction in gray matter volume of the lingual gyrus and the dorsal visual pathway V3 area becomes more pronounced with increasing exotropia severity, while the gray matter volume of the precentral gyrus (BA6 area) decreases with worsening stereoacuity.


Asunto(s)
Corteza Cerebral , Exotropía , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Exotropía/diagnóstico por imagen , Estudios Transversales , Adulto Joven , Adulto , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Casos y Controles
4.
Opt Lett ; 46(15): 3504-3507, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34329210

RESUMEN

This Letter, to the best of our knowledge, reports mid-infrared fiber lasing beyond 5 µm at room temperature for the first time, Ce3+-doped, chalcogenide glass, step index fiber employed in-band pumping with a 4.15 µm quantum cascade laser. The lasing fiber is was 64 mm long, with a calculated numerical aperture of 0.48 at the lasing wavelengths. The core glass was Ge15As21Ga1Se63 atomic % (at. %), doped with 500 parts-per-million-by-weight Ce, with a 9 µm core diameter. The cladding glass was Ge21Sb10Se69 at. % with a 190 µm outer diameter. As pump power increases continuous wave lasing corresponding to the 2F7/2→2F5/2, transition in the Ce3+ ion occurs at 5.14 µm, 5.17 µm, and 5.28 µm.

5.
Lupus ; 27(5): 716-721, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29087262

RESUMEN

Objective The objective of this paper is to investigate the association of clinical manifestations and laboratory parameters between familial systemic lupus erythematosus (SLE) and sporadic SLE. Methods All relevant literature was retrieved from the PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) databases. The qualities of these studies were evaluated using a modified version of the Newcastle-Ottawa scale. The characteristics and clinical manifestations of involved individuals were extracted from each study. Pooled odds ratio (OR) was calculated using the random effects-method, and the heterogeneity between studies was quantified using the I2 statistic. Results Of 330 studies identified by the search strategy, six were included in this review. In total, 733 cases were familial SLE and 1405 were sporadic SLE. Analysis revealed that photosensitivity, nephritis and thrombocytopenia were negatively associated with familial SLE, with OR (95% CI) values of 0.73 (0.60-0.89), 0.72 (0.59-0.88) and 0.75 (0.57-0.98), respectively. Conclusions Photosensitivity, thrombocytopenia and renal involvement could be more common in non-familial SLE, which should be further confirmed by well-designed studies with large populations.


Asunto(s)
Herencia , Lupus Eritematoso Sistémico/genética , Linaje , Distribución de Chi-Cuadrado , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Nefritis Lúpica/epidemiología , Nefritis Lúpica/genética , Masculino , Oportunidad Relativa , Fenotipo , Trastornos por Fotosensibilidad/epidemiología , Trastornos por Fotosensibilidad/genética , Pronóstico , Factores de Riesgo , Trombocitopenia/epidemiología , Trombocitopenia/genética
7.
Genet Mol Res ; 15(4)2016 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-27886347

RESUMEN

We previously described a novel densovirus [Myzus persicae nicotianae densovirus (MpnDV)] infecting M. persicae nicotianae (Hemiptera: Aphididae) with 34% prevalence. This single-stranded DNA virus has a 5480-nucleotide ambisense genome and belongs to the Densovirinae subfamily within the family Parvoviridae. In the present study, we estimated the genetic diversity of MpnDV using partial nonstructural protein (NS) and capsid protein (VP) gene sequences from 10 locations in China. First, we identified MpnDV-positive samples by amplifying a 445-bp fragment with primers MpDVF/MpDVR. Subsequently, we amplified and sequenced COI genes with primers MpCOIF/ MpCOIR, and partial NS and VP sequences with primers MpnDVF1/MpnDVR1. The respective 655-, 1461-, and 423-bp COI, NS, and VP fragments were used to analyze the genetic diversity of MpnDV using MEGA 6.0 and DnaSP 5.0. The high level of identity shared by all COI sequences (>99%) suggested that the aphids sampled were of the same species, and indicated population homogeneity across the 10 locations investigated. The nucleotide diversity of MpnDV sequences (0.0020 ± 0.0025) was significantly higher than that of the COI genes (0.0002 ± 0.0005). The pairwise fixation index for MpnDV was 0.832, and the total gene flow was 0.05. Phylogenetic analysis revealed that the MpnDV haplotypes clustered according to geographical location, except for those from the Liaoning and Shanxi provinces. In conclusion, MpnDV demonstrated a low level of gene flow and high genetic diversity, suggesting that it is vertically transmitted, and implying that endosymbiotic viruses could be used as markers in studies of insect population genetics.


Asunto(s)
Áfidos/virología , Proteínas de la Cápside/genética , Densovirus/genética , Proteínas no Estructurales Virales/genética , Animales , Flujo Génico , Variación Genética , Haplotipos , Filogenia
8.
Genet Mol Res ; 11(2): 956-65, 2012 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-22576922

RESUMEN

Body weight and abdominal fat traits in meat-type chickens are complex and economically important factors. Our objective was to identify quantitative trait loci (QTL) responsible for body weight and abdominal fat traits in broiler chickens. The Northeast Agricultural University Resource Population (NEAURP) is a cross between broiler sires and Baier layer dams. We measured body weight and abdominal fat traits in the F(2) population. A total of 362 F(2) individuals derived from four F(1) families and their parents and F(0) birds were genotyped using 29 fluorescent microsatellite markers located on chromosomes 3, 5 and 7. Linkage maps for the three chromosomes were constructed and interval mapping was performed to identify putative QTLs. Nine QTL for body weight were identified at the 5% genome-wide level, while 15 QTL were identified at the 5% chromosome-wide level. Phenotypic variance explained by these QTL varied from 2.95 to 6.03%. In particular, a QTL region spanning 31 cM, associated with body weight at 1 to 12 weeks of age and carcass weight at 12 weeks of age, was first identified on chromosome 5. Three QTLs for the abdominal fat traits were identified at the 5% chromosome-wide level. These QTLs explained 3.42 to 3.59% of the phenotypic variance. This information will help direct prospective fine mapping studies and can facilitate the identification of underlying genes and causal mutations for body weight and abdominal fat traits.


Asunto(s)
Grasa Abdominal , Peso Corporal/genética , Pollos/genética , Mapeo Cromosómico , Sitios de Carácter Cuantitativo , Animales , Ligamiento Genético , Marcadores Genéticos , Repeticiones de Microsatélite/genética
9.
J Anim Breed Genet ; 128(5): 366-75, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21906182

RESUMEN

Previously, a quantitative trait locus (QTL) that affects body weight (BW) at 4-12 weeks of age and carcass weight at 12 weeks of age had been mapped on chicken chromosome 1. After including more markers and individuals, the confidence interval was narrowed down to approximately 5.5 Mbps and located this QTL near a microsatellite marker (ADL328). This QTL is the same as the QTL for 12 bone traits, including metatarsus length and metatarsus circumference at 4, 6, 8, 10 and 12 weeks of age and keel length and metatarsus claw weight at 12 weeks of age, that was identified using the same population. In the current study, 1010 individuals from the Northeast Agricultural University F(2) resource population were used and 14 single-nucleotide polymorphism (SNPs) around ADL328 were developed to construct haplotypes, and an association analysis was performed to fine-map the QTL. The haplotypes were constructed on the basis of a sliding 'window', with three SNP markers included in each 'window'. The association analysis results indicated that the haplotypes in 'windows' 6-12 were significantly associated with BW and bone traits and suggested that the QTL for BW and bone traits was located between SNP8 and SNP14 or was in linkage disequilibrium with this region. The interval from SNP8 to SNP14 was approximately 400 kbps. This region contained five RefSeq genes (RB1, P2RY5, FNDC3A, MLNR and CAB39L) on the University of California Santa Cruz website. The RB1 gene was selected as a candidate gene and five SNPs were identified in the gene. The association results indicated that the RB1 gene was a major gene for BW and bone traits. The SNPs g.39692 G>A and g.77260 A>G in RB1 gene might be two quantitative trait nucleotides for BW and bone traits.


Asunto(s)
Peso Corporal/genética , Huesos/anatomía & histología , Pollos/genética , Sitios de Carácter Cuantitativo , Proteína de Retinoblastoma/genética , Animales , Mapeo Cromosómico , Clonación Molecular
10.
J Anim Breed Genet ; 127(6): 462-8, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21077970

RESUMEN

In broiler chickens, bone problems are an important welfare issue that has been linked to genetic selection for rapid growth. The objectives of this study were to identify and fine map quantitative trait loci (QTL) associated with bone traits. The Northeast Agricultural University resource population (NEAURP) being an F(2) population was used in this study, and a total of 17 bone traits were measured. In primary genome scan, the linkage map was constructed with 23 microsatellite markers across the entire chicken chromosome 1. Seventeen QTLs for bone traits were identified and 12 of these were found between LEI0079 and ROS0025 (50.8 cM apart). To fine map the QTLs located between LEI0079 and ROS0025, more markers and more individuals were used and a new partial linkage map was constructed. The confidence intervals for QTLs were sharply narrowed down from 24.5∼52.6 to 2.7∼17.0 Mb. This study identified chromosome regions harbouring significant QTLs affecting bone traits and showed that the use of more markers and individuals could decrease the confidence interval of QTL effectively. The results provide a useful reference for further candidate gene research and MAS for bone traits.


Asunto(s)
Desarrollo Óseo/genética , Pollos/crecimiento & desarrollo , Pollos/genética , Mapeo Cromosómico/veterinaria , Sitios de Carácter Cuantitativo , Bienestar del Animal , Animales , Femenino , Hibridación Genética , Masculino , Repeticiones de Microsatélite , Fenotipo
11.
Artículo en Zh | MEDLINE | ID: mdl-32086906

RESUMEN

The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed skin, especially on the face, scalp, neck and back of hands, mainly in elderly subjects but commonly between the 4th and 9th decades of life. We report a case of giant trichilemmal carcinoma. A 65-year-old man presented with a 5-year history of a slowly developing mass arising from his right retroauricular region, with local destruction of the auricle. The lesion appeared as a 8.0 cm×6.5 cm×2.0 cm sized, with surface ulceration and erosion, subcutaneous nodule, and mild tenderness. Preoperative pathological biopsy showed: "retroauricular" trichilemmal carcinoma. The patient underwent right retroauricular tumor resection, partial auriculectomy, neck adjacent skin flap repair and auricle reconstruction. Postoperative pathological report: "retroauricular" trichilemmal carcinoma. The margin of incision was negative, and the lymph nodes in zone II were negative. Immunohistochemistry: Tumor cells were CK5/6(++), p63(++), p40(++), CD10(-), EMA(-), Ki-67(+, about 60%).


Asunto(s)
Carcinoma/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Carcinoma/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Ganglios Linfáticos , Masculino , Neoplasias Cutáneas/cirugía , Colgajos Quirúrgicos
12.
Nucleic Acids Res ; 35(Database issue): D794-9, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17151074

RESUMEN

Prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines. Knowledge of polymorphism-induced and other types of drug-response variations is needed for facilitating such studies. Although databases of pharmacogenetic knowledge, polymorphism and toxicogenomic information have appeared, some of the relevant data are provided in separate web-pages and in terms of relatively long descriptions quoted from literatures. To facilitate easy and quick assessment of the relevant information, it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web-page and in brief descriptions. We developed a database, Pharmacogenetic Effect Database (PharmGED), for providing sequence, function, polymorphism, affected drugs and pharmacogenetic effects. PharmGED can be accessed at http://bidd.cz3.nus.edu.sg/phg/ free of charge for academic use. It currently contains 1825 entries covering 108 disease conditions, 266 distinct proteins, 693 polymorphisms, 414 drugs/ligands cited from 856 references.


Asunto(s)
Bases de Datos Genéticas , Farmacogenética , Polimorfismo Genético , Animales , Internet , Proteínas/genética , Proteínas/metabolismo , Interfaz Usuario-Computador
13.
Mol Immunol ; 44(5): 866-77, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16806474

RESUMEN

Peptide binding to MHC is critical for antigen recognition by T-cells. To facilitate vaccine design, computational methods have been developed for predicting MHC-binding peptides, which achieve impressive prediction accuracies of 70-90% for binders and 40-80% for non-binders. These methods have been developed for peptides of fixed lengths, for a limited number of alleles, trained from small number of non-binders, and in some cases based straightforwardly on sequence. These limit prediction coverage and accuracy particularly for non-binders. It is desirable to explore methods that predict binders of flexible lengths from sequence-derived physicochemical properties and trained from diverse sets of non-binders. This work explores support vector machines (SVM) as such a method for developing prediction systems of 18 MHC class I and 12 class II alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are 96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies substantially improved against other results. Our method correctly predicts 73.3% of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251 recently-published HLA-A*0201 non-epitopes predicted as binders by other methods, 63 are predicted as binders by our method. Screening of HIV-1 genome shows that, compared to other methods, a comparable percentage (75-100%) of its known epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at .


Asunto(s)
Alelos , Antígenos HLA/inmunología , Oligopéptidos/inmunología , Secuencia de Aminoácidos , Aminoácidos/química , Biología Computacional/métodos , Epítopos de Linfocito T/inmunología , Predicción , Genes MHC Clase I , Genes MHC Clase II , VIH-1/genética , Antígenos HLA/genética , Modelos Moleculares , Datos de Secuencia Molecular , Oligopéptidos/química
14.
Neuroscience ; 146(2): 555-61, 2007 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-17367940

RESUMEN

Cerebral hypoxia may be the main component of cell damage caused by ischemia. Previous studies demonstrated a neuroprotective effect of early hyperbaric oxygen (HBO) treatment in various animal models of focal cerebral ischemia. Neuropathologic study showed that exposure of HBO may prevent cell death in ischemic cortex. In the present study, we aimed to assess cellular function of ischemic rat brain after HBO treatment by means of a high-resolution positron emission tomography scanner (microPET) used specifically for small animal imaging. The male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO), with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. One hour after ischemia, HBO therapy (3 atm absolute, 1 h) was initiated. Local cerebral glucose utilization in the ischemic area was measured before, 1 h and 3 h after ischemia, with 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. Neurological deficits and infarct volumes were assessed at 24 h after ischemia. Our study showed that early HBO therapy significantly reduced infarct volume of brain 24 h after ischemia. Moreover, glucose utilization in the ischemic area underwent a severe decrease during 1-3 h after MCAO, while the early HBO treatment significantly attenuated the decrease in cerebral metabolic rate of glucose in the ischemic core of the cortex compared with controls. We report for the first time the application of microPET to quantify the rates of glucose metabolism in the ischemic core of rats exposed to HBO. Our results suggest that the early exposure of HBO can partially reverse the downward trend for glucose utilization in the ischemic core, which might contribute to the reported beneficial effects of early HBO therapy on permanent cerebral ischemia.


Asunto(s)
Circulación Cerebrovascular/fisiología , Glucosa/metabolismo , Oxigenoterapia Hiperbárica/métodos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Tomografía de Emisión de Positrones , Animales , Infarto Encefálico/etiología , Infarto Encefálico/patología , Infarto Encefálico/terapia , Circulación Cerebrovascular/efectos de los fármacos , Modelos Animales de Enfermedad , Fluorodesoxiglucosa F18/farmacocinética , Infarto de la Arteria Cerebral Media/complicaciones , Masculino , Examen Neurológico/métodos , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
15.
Pharmazie ; 61(10): 869-73, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17069428

RESUMEN

Aim of this study was to investigate liver metabolism of with regard to para toluene-sulfonamide (PTS), CYP isoforms, P-glycoprotein (P-gp), and drug interactions. Known substrates, inducers and inhibitors of CYP and inhibitor of P-gp were employed and metabolites were determined with HPLC. Male Wistar rats were pretreated with ip phenobarbital (PB), ketoconazole (Ket), or verapamil (Ver) for 3 days and in situ liver perfusion of PTS was conducted in a recirculation system. Rats were also pretreated with ip PTS (33 mg x kg(-1) x d(-1) or PTS 99 mg x kg(-1) x d(-1)) for 4 days before liver perfusions with dextromethorphan (Dex) and phenacetin (Phe) preparations were conducted. Microsome incubation was used to investigate PTS effect on five CYP isoforms and PTS-drug interactions probability with phyllotoxin and 5-fluorouracil (5-FU) in vitro. PTS at 60 min perfusates had areas of 61.4% and 133.6% of the blank control in PB group and Ket group, respectively. The result that PTS metabolism was enhanced by PB and inhibited by Ket treatments suggested liver CYP was attributed to PTS metabolism. PTS 99 mg x kg(-1) x d(-1) pretreatment slowed down the metabolism of Dex and Phe while in vitro incubations did not show a PTS (0-160 micromol/L) effect on CYP activities. PTS metabolite formation when co-incubated with phyllotoxin was 50.7% of the negative control. The potent inhibitory ability of phyllotoxin to PTS requires further clinical investigation regarding in concomitant administration.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Sulfonamidas/metabolismo , Tolueno/análogos & derivados , Animales , Bloqueadores de los Canales de Calcio/farmacología , Calibración , Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Antagonistas de Aminoácidos Excitadores/farmacología , Técnicas In Vitro , Isoenzimas/metabolismo , Ketamina/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Pentobarbital/farmacología , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Tolueno/metabolismo , Verapamilo/farmacología
16.
Braz J Med Biol Res ; 49(3)2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26840704

RESUMEN

The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.


Asunto(s)
Factor Activador de Células B/metabolismo , Receptor del Factor Activador de Células B/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Adolescente , Adulto , Albuminuria/orina , Factor Activador de Células B/análisis , Factor Activador de Células B/genética , Receptor del Factor Activador de Células B/análisis , Receptor del Factor Activador de Células B/genética , Linfocitos B/metabolismo , Biomarcadores/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Adulto Joven
17.
Transplant Proc ; 35(8): 3024-5, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14697968

RESUMEN

To investigate the change of Th1, Th2, Th3 cytokines during early liver transplantation. IFN-r, IL-4, TGF-beta production by CD4+ T cells were determined by fluorescence activated cell sorter analysis. Comparing the acute rejection with the non-acute rejection groups on the 7th, 14th, and 28th day showed that high interferon-gamma production associated with acute rejection in the early posttransplant period. There was no evidence of significant changes in interleukin-4 and transforming growth factor beta (TGF-beta) levels between non-acute rejection groups with acute rejection groups. Th1 cytokine high production is significantly associated with acute rejection in liver transplant recipients.


Asunto(s)
Citocinas/sangre , Trasplante de Hígado/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Células TH1/inmunología , Células Th2/inmunología , Relación CD4-CD8 , Células Cultivadas , Femenino , Citometría de Flujo , Rechazo de Injerto/inmunología , Humanos , Interferón gamma/sangre , Interleucina-4/sangre , Activación de Linfocitos , Masculino , Factores de Tiempo , Factor de Crecimiento Transformador beta/sangre
18.
Transplant Proc ; 36(5): 1498-9, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15251369

RESUMEN

OBJECTIVE: The objectives of this study was to analyze the peripheral blood T-lymphocyte subsets of the Th1-related versus Th2-related cytokines of CD4+ cells, and the Tc1 versus Tc2 cytokines of CD8+ cells liver transplant recipients with versus without active cytomegalovirus (CMV) infection. METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated using PMA/Ionomycin/Monensin. Interleukin (IL)-4 and interferon gamma (IFN-gamma) production by CD4+ and CD8+T cells were determined using fluorescence-activated cell sorter (FACS) analysis. RESULTS: The ratios of CD4/CD8 were significantly lower among active CMV-infected patients. The levels of Th2 and Tc2 cytokines (IL-4) were similar between CMV-infected and uninfected patients. However, the levels of Th1-type and Tc1-type cytokines (IFN-r) were significantly lower among active CMV-infected patients. CONCLUSIONS: Low levels of Th1-type cytokines seem to correlate with active CMV infection in liver transplant recipients.


Asunto(s)
Infecciones por Citomegalovirus/inmunología , Trasplante de Hígado/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Antígenos CD/inmunología , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Monitorización Inmunológica/métodos , Complicaciones Posoperatorias/inmunología
19.
Braz. j. med. biol. res ; 49(3): e4853, Mar. 2016. tab, graf
Artículo en Inglés | LILACS | ID: lil-771933

RESUMEN

The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Factor Activador de Células B/metabolismo , Receptor del Factor Activador de Células B/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Albuminuria/orina , Factor Activador de Células B/análisis , Factor Activador de Células B/genética , Receptor del Factor Activador de Células B/análisis , Receptor del Factor Activador de Células B/genética , Linfocitos B/metabolismo , Biomarcadores/metabolismo , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo
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