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1.
Zhonghua Fu Chan Ke Za Zhi ; 58(3): 178-184, 2023 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-36935194

RESUMEN

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.


Asunto(s)
Microcefalia , Diagnóstico Prenatal , Femenino , Humanos , Embarazo , Variaciones en el Número de Copia de ADN , Feto , Cariotipo , Cariotipificación , Análisis por Micromatrices/métodos , Microcefalia/diagnóstico , Microcefalia/genética , Diagnóstico Prenatal/métodos , Recién Nacido
2.
Zhonghua Fu Chan Ke Za Zhi ; 57(9): 671-677, 2022 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-36177578

RESUMEN

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.


Asunto(s)
Cuerpo Calloso , Variaciones en el Número de Copia de ADN , Niño , Aberraciones Cromosómicas , Cuerpo Calloso/diagnóstico por imagen , Femenino , Feto , Humanos , Cariotipo , Análisis por Micromatrices/métodos , Embarazo , Diagnóstico Prenatal/métodos
3.
Eur Rev Med Pharmacol Sci ; 24(14): 7573, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32744678

RESUMEN

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K/AKT/mTOR signal pathway, by F. Wang, W.-H. Tan, W. Liu, Y.-X. Jin, D.-D. Dong, X.-J. Zhao, Q. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 1891-1898-DOI: 10.26355/eurrev_201804_14711-PMID: 29687840" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14711.

4.
Med J Malaysia ; 75(3): 286-291, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32467546

RESUMEN

AIM: This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet). MATERIALS AND METHODS: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods. RESULTS: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects. CONCLUSION: It can be concluded that the test preparation is bioequivalent to the reference preparation.


Asunto(s)
Gliburida/administración & dosificación , Gliburida/farmacocinética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Metformina/administración & dosificación , Metformina/farmacocinética , Equivalencia Terapéutica , Adolescente , Adulto , Estudios Cruzados , Quimioterapia Combinada , Humanos , Masculino , Adulto Joven
5.
J Intellect Disabil Res ; 64(3): 246-250, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31854050

RESUMEN

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar. METHODS: Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings. RESULTS: Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups. CONCLUSIONS: The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.


Asunto(s)
Síndrome de Angelman/diagnóstico , Síndrome de Angelman/fisiopatología , Orden de Nacimiento , Hermanos , Ubiquitina-Proteína Ligasas/genética , Factores de Edad , Síndrome de Angelman/genética , Niño , Preescolar , Diagnóstico Precoz , Femenino , Humanos , Lactante , Masculino
6.
Hernia ; 23(1): 29-35, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30370479

RESUMEN

PURPOSE: Transversus abdominis muscle release (TAR) combines retromuscular mesh placement with posterior component separation and muscle release. TAR is usually an open technique for abdominal wall reconstruction; however, several centers have performed this operation robotically and claim better clinical outcomes when compared to open surgery. We sought to compare robotic versus open TAR utilizing a porcine model. METHODS: Animals were randomized to open versus robotic TAR with mesh placement, survived for 4 weeks, then underwent diagnostic laparoscopy to assess adhesive burden and adhesion tenacity. T-peel testing was utilized to assess mesh ingrowth. The primary outcome was adhesive burden; secondary outcomes included mesh incorporation, contraction, and operative time. RESULTS: Nine robotic and eight open TARs were performed. Mean operative time was significantly shorter for the open cases compared to robotic cases (88.6 ± 12.9 min versus 228.3 ± 46.2, p < 0.01). Operative time in the robotic arm of the study decreased over time, from 300 to 165 min. No difference was seen in the mean adhesion area between the two groups. Adhesion tenacity and mesh flatness were similar. The work required to peel the mesh off surrounding tissue was significantly higher in the open TAR than in the robotic TAR group: 52.6 ± 15.5 and 32.9 ± 10.6 mJ/cm2, respectively (p < 0.01). CONCLUSIONS: There were no differences in adhesions between the robotic and open approaches, but greater mesh contraction and ingrowth was observed in the open TAR group. Though operative time was longer in the robotic group, time dropped by about 40% from the first case to the last.


Asunto(s)
Músculos Abdominales , Hernia Ventral , Herniorrafia , Procedimientos Quirúrgicos Robotizados , Mallas Quirúrgicas , Animales , Femenino , Músculos Abdominales/cirugía , Hernia Ventral/cirugía , Herniorrafia/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Porcinos , Distribución Aleatoria
8.
Eur Rev Med Pharmacol Sci ; 22(7): 1891-1898, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29687840

RESUMEN

OBJECTIVE: PI3K/AKT/mTOR pathway plays important roles in tumor pathogenesis. mTOR is up-regulated and miR-214 is down-regulated in cervical can-*cers. This study investigated whether miR-214 regulated mTOR expression and affected cervical cancer cell proliferation, apoptosis or invasion. PATIENTS AND METHODS: Cervical cancer tissues were collected in parallel with normal epithelium for measuring the expression of miR-214 and mTOR. Dual luciferase expression assay was performed to evaluate the targeted relationship between miR-214 and mTOR. In vitro cultured SiHa cells were treated with miR-214 mimic or si-mTOR followed by measuring mTOR, p-mTOR and Bcl-2 expression. Cell apoptosis, proliferation and invasion were measured by flow cytometry and transwell assay. RESULTS: Bioinformatics analysis showed targeted binding sites between miR-214 and 3'-UTR of mTOR mRNA. Dual luciferase reporter assay confirmed this regulatory relationship between miR-214 and mTOR mRNA. Compared to normal cervical epithelium, cancer tissues had lower expression of miR-214 and higher mTOR, both of which were correlated with TNM stage and tissue pathology grade. Compared to Ect1/E6E7 cells, SiHa cells had lower level of miR-214 and higher mTOR/p-mTOR and Bcl-2 expression. Transfection of miR-214 mimic or si-mTOR significantly decreased mTOR/p-mTOR or Bcl-2 expression, inhibited cell proliferation or invasion, and enhanced cell apoptosis. CONCLUSIONS: miR-214 down-regulation plays a role in elevating mTOR expression and in facilitating cervical cancer pathogenesis. Over-expression of miR-214 inhibits cervical cancer cell proliferation or invasion, and facilitates apoptosis via targeted inhibition of mTOR expression.


Asunto(s)
Apoptosis , MicroARNs/fisiología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Serina-Treonina Quinasas TOR/fisiología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/genética
9.
J Dent Res ; 96(6): 678-684, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28530472

RESUMEN

Nonmammalian vertebrates have the capacity of lifelong tooth replacement. In all vertebrates, tooth formation requires contact and interaction between the oral or pharyngeal epithelium and the underlying mesenchyme. To secure lifelong replacement, the presence of odontogenic stem cells has been postulated, particularly in the epithelial compartment. This study uses an advanced teleost fish species, the marine medaka Oryzias melastigma, a close relative to Oryzias latipes, to examine the expression and distribution of telomerase reverse transcriptase (Tert), the catalytic unit of telomerase, in developing pharyngeal teeth and to relate these data to the proliferative activity of the cells. The data are complemented by expression analysis of the pluripotency marker oct4 and bona fide stem cell marker lgr5. Tert distribution and tert expression in developing tooth germs show a dynamic spatiotemporal pattern. Tert is present first in the mesenchyme but is downregulated as the odontoblasts differentiate. In contrast, in the epithelial enamel organ, Tert is absent during early stages of tooth formation and upregulated first in ameloblasts. Later, Tert is expressed and immunolocalized throughout the entire inner enamel epithelium. The pattern of Tert distribution is largely mutually exclusive with that of proliferating cell nuclear antigen (PCNA) immunoreactivity: highly proliferative cells, as revealed by PCNA staining, are negative for Tert; conversely, PCNA-negative cells are Tert-positive. Only the early condensed mesenchyme is both Tert- and PCNA-positive. The absence of tert-positive cells in the epithelial compartment of early tooth germs is underscored by the absence of oct4- and lgr5-positive cells, suggesting ways other than stem cell involvement to secure continuous renewal.


Asunto(s)
Odontogénesis/fisiología , Oryzias , Faringe/enzimología , Telomerasa/metabolismo , Animales , Proteínas de Peces/metabolismo , Técnicas para Inmunoenzimas , Hibridación in Situ , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Faringe/anatomía & histología , Receptores Acoplados a Proteínas G/metabolismo
10.
J Med Syst ; 38(8): 80, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24957396

RESUMEN

In a computerized image analysis environment, the irregularity of a lesion border has been used to differentiate between malignant melanoma and other pigmented skin lesions. The accuracy of the automated lesion border detection is a significant step towards accurate classification at a later stage. In this paper, we propose the use of a combined Spline and B-spline in order to enhance the quality of dermoscopic images before segmentation. In this paper, morphological operations and median filter were used first to remove noise from the original image during pre-processing. Then we proceeded to adjust image RGB values to the optimal color channel (green channel). The combined Spline and B-spline method was subsequently adopted to enhance the image before segmentation. The lesion segmentation was completed based on threshold value empirically obtained using the optimal color channel. Finally, morphological operations were utilized to merge the smaller regions with the main lesion region. Improvement on the average segmentation accuracy was observed in the experimental results conducted on 70 dermoscopic images. The average accuracy of segmentation achieved in this paper was 97.21 % (where, the average sensitivity and specificity were 94 % and 98.05 % respectively).


Asunto(s)
Color , Dermoscopía/métodos , Interpretación de Imagen Asistida por Computador/métodos , Melanoma/diagnóstico , Algoritmos , Diagnóstico Diferencial , Humanos , Sensibilidad y Especificidad
11.
Mol Psychiatry ; 19(3): 368-79, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23587880

RESUMEN

Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions and the associated human psychopathology, 22 individuals with genomic disruption of MBD5 (translocation, point mutation and deletion) were identified through whole-genome sequencing or cytogenomic microarray at 11 molecular diagnostic centers. The genomic impact ranged from a single base pair to 5.4 Mb. Parents were available for 11 cases, all of which confirmed that the rearrangement arose de novo. Phenotypes were largely indistinguishable between patients with full-segment 2q23.1 deletions and those with intragenic MBD5 rearrangements, including alterations confined entirely to the 5'-untranslated region, confirming the critical impact of non-coding sequence at this locus. We identified heterogeneous, multisystem pathogenic effects of MBD5 disruption and characterized the associated spectrum of psychopathology, including the novel finding of anxiety and bipolar disorder in multiple patients. Importantly, one of the unique features of the oldest known patient was behavioral regression. Analyses also revealed phenotypes that distinguish MBD5 disruptions from seven well-established syndromes with significant diagnostic overlap. This study demonstrates that haploinsufficiency of MBD5 causes diverse phenotypes, yields insight into the spectrum of resulting neurodevelopmental and behavioral psychopathology and provides clinical context for interpretation of MBD5 structural variations. Empirical evidence also indicates that disruption of non-coding MBD5 regulatory regions is sufficient for clinical manifestation, highlighting the limitations of exon-focused assessments. These results suggest an ongoing perturbation of neurological function throughout the lifespan, including risks for neurobehavioral regression.


Asunto(s)
Ansiedad/genética , Trastorno Bipolar/genética , Proteínas de Unión al ADN/genética , Discapacidades del Desarrollo/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Mutación
12.
Artículo en Inglés | MEDLINE | ID: mdl-23077803

RESUMEN

This retrospective study was conducted among 59 HIV/AIDS patients with opportunistic infections admitted to the University Malaya Medical Centre between 2000 and 2009. Fifty-five point nine percent of cases were Chinese, 25.4% were Malays, 11.9% were Indians and 6.8% were of unknown ethnic origin. The male:female ratio was 2.9:1 (44 males and 15 females). The highest prevalence (38.9%) occurred in the 30-39 year old age group. Men comprised 47.7% and women 53.3%; the majority of both were married. The majority of cases were Malaysians (89.8%) and the rest (10.2%) were immigrants. Most of the patients (18.6%) were non-laborers, followed by laborers (11.9%), the unemployed (5.1%) and housewives (3.4%). The most common risk factor was unprotected sexual activity (20.3%). The two most common HIV/AIDS related opportunistic infections were Pneumocystis carinii (jirovecii) pneumonia (PCP) (62.7%) and toxoplasmosis (28.8%). Seventy-two point nine percent of patients had a CD4 count <200 cells/microl and 5.1% had a CD4 count >500 cells/microl. Eleven point nine percent of cases died during study period. A low CD4 count had a greater association with opportunistic infections. Most of the patients presented with fever (44.1%), cough (42.4%) and shortness of breath (28.8%). Detection of the etiologic pathogens aids clinicians in choosing appropriate management strategies.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Centros Médicos Académicos/estadística & datos numéricos , Infecciones por VIH/epidemiología , Neumonía por Pneumocystis/epidemiología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adulto , Distribución por Edad , Anciano , Recuento de Linfocito CD4 , Comorbilidad , Emigrantes e Inmigrantes/estadística & datos numéricos , Femenino , Conductas Relacionadas con la Salud , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Factores Socioeconómicos
14.
Knee Surg Sports Traumatol Arthrosc ; 18(4): 496-503, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19855958

RESUMEN

Injured articular cartilage has a poor capacity for spontaneous healing. So far, satisfactory solution to this subsistent problem has not been found, but transgenic therapy may be a promising way. This study aims to evaluate the effectiveness of a tissue-engineered cartilage that was transfected with morphogenetic protein 7 (BMP 7) in repairing the cartilaginous defects of rabbit knee joints. Chondrocytes were transfected with BMP-7 gene (5 x 10(6) cells/ml), inoculated into the collagen-fibrin gel scaffolds, and cultured for 14 days. Then, the scaffolds were implanted onto the created defects (5.0 mm in diameter) in rabbits' knee joints. After 12 weeks, the rabbits were sacrificed and histological sections were evaluated using modified O'Driscoll cartilage scores; In situ hybridization and immunohistochemistry were performed to detect the expression of BMP-7 mRNA and BMP-7 at the implanted site while the content of DNA and GAG was determined as well. A better quality of repairs was observed at the 12th week after implantation when compared to the control group using histological analyses. The content of DNA and specific secretion of GAG in the treatment group is statistically significant different compared with the control group. Gene therapy may be a promising treatment method, but the novel therapy approach needs further studies with respect to a longer follow-up period.


Asunto(s)
Proteína Morfogenética Ósea 7 , Cartílago Articular/lesiones , Cartílago Articular/cirugía , Condrocitos/trasplante , Traumatismos de la Rodilla/cirugía , Ingeniería de Tejidos/métodos , Animales , Proteína Morfogenética Ósea 7/genética , Proteína Morfogenética Ósea 7/uso terapéutico , Modelos Animales de Enfermedad , Estudios de Seguimiento , Glicosaminoglicanos/análisis , Conejos , Andamios del Tejido , Transfección/métodos , Resultado del Tratamiento
15.
Leukemia ; 23(2): 235-44, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19151784

RESUMEN

Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells depends on molecular probes against these proteins. To be used effectively for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA-RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-based SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers, which can recognize AML cells with dissociation constants (Kd's) in the nanomolar range. Interestingly, one aptamer (KH1C12) compared with two control cell lines (K562 and NB4) showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies show that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Aptámeros de Nucleótidos , Leucemia Mieloide Aguda/diagnóstico , Técnica SELEX de Producción de Aptámeros , Antígenos de Superficie/metabolismo , Aptámeros de Nucleótidos/farmacocinética , Línea Celular Tumoral , Humanos , Leucemia Mieloide Aguda/patología , Técnicas de Sonda Molecular , Unión Proteica , Sensibilidad y Especificidad
16.
J Med Genet ; 46(4): 242-8, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18805830

RESUMEN

BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.


Asunto(s)
Trastorno Autístico/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 15/genética , Discapacidad Intelectual/genética , Adolescente , Trastorno Autístico/patología , Niño , Preescolar , Deleción Cromosómica , Hibridación Genómica Comparativa , Femenino , Duplicación de Gen , Humanos , Lactante , Discapacidad Intelectual/patología , Masculino , Fenotipo , Adulto Joven
17.
Singapore Med J ; 47(2): 143-6, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16435057

RESUMEN

INTRODUCTION: The National Cancer Survivors Day Foundation defines a cancer "survivor" as anyone living with a history of cancer--from the moment of diagnosis through the remainder of life. Little is known about the size and make-up of this population or about the medical care experience of and social implications for patients who have had a diagnosis of cancer in Singapore. An opportunistic survey was undertaken to understand how members of the public believe about this population. METHODS: A sample of the general public was undertaken during the "CancerVive" event in 2004. Questionnaires regarding employment as well as attitudes towards cancer and cancer survivorship were distributed. RESULTS: Members of the public held certain misconceptions about cancer survivors. They also have certain negative attitudes toward cancer survivors. Beliefs and attitudes about cancer are similar for cancer survivors and the general public. Although members of the public had positive attitudes towards working with cancer survivors, the majority felt that cancer survivors should not be given equal opportunities at work, by not employing cancer survivors if they were in the position to hire. CONCLUSION: Further research with larger and more representative samples needs to be undertaken to extend the understanding into cancer survivorship issues.


Asunto(s)
Actitud , Empleo , Neoplasias/rehabilitación , Prejuicio , Sobrevivientes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Singapur
19.
Arch Dis Child Fetal Neonatal Ed ; 87(3): F214-6, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12390995

RESUMEN

AIM: To determine the safety, efficacy, and need to measure peak serum vancomycin concentrations in a neonatal population using a standard vancomycin dosage regimen. METHOD: A total of 101 infants who were admitted to a regional neonatal intensive care unit and received vancomycin (15 mg/kg every 12 or 18 hours depending on postnatal age) were studied retrospectively. Infants who had been started on vancomycin before they were transferred to the unit were excluded. The proportion of infants was measured whose serum vancomycin concentrations were within a conservative therapeutic range of trough 5-10 mg/l, peak 20-40 mg/l, and a less conservative, but still safe, range of trough 5-12 mg/l, peak 15-60 mg/l. RESULTS: Trough concentrations of 5-10 mg/l were achieved by 46.5% of infants, and 5-12 mg/l by 55.4%. Peak concentrations of 20-40 mg/l were found in 83.2% of infants, and 15-60 mg/l in 99.0%. Highest peak concentration was 47.2 mg/l. Some 89.4% of infants with trough concentrations of 5-10 mg/l had a peak concentration of 20-40 mg/l. CONCLUSIONS: The vancomycin dosage regimen used in this study produces acceptable therapeutic serum vancomycin concentrations. Peak serum vancomycin concentrations do not need to be measured in neonates using this dosage regimen.


Asunto(s)
Antibacterianos/administración & dosificación , Cuidado Intensivo Neonatal/organización & administración , Sepsis/tratamiento farmacológico , Vancomicina/administración & dosificación , Antibacterianos/sangre , Antibacterianos/farmacocinética , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Edad Gestacional , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Sepsis/sangre , Vancomicina/sangre , Vancomicina/farmacocinética
20.
Biol Trace Elem Res ; 73(2): 113-25, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11049204

RESUMEN

Keshan disease is a cardiomyopathy restricted to the endemic areas of China and seen in residents having an extremely low selenium (Se) status. Prophylactic administration of sodium selenite has been shown to decrease significantly the incidence of acute and subacute cases. The aim offthe study was to assess the relative bioavailability of selenite versus organic Se-yeast in a Se-deficient area in China with a randomized double-blind double-dummy design. Healthy children (n=30) between 14 and 16 yr of age were randomized into three equal groups receiving either 200 microg/d selenite Se or 200 microg/d Se-yeast or placebo for 12 wk. Blood was drawn at baseline, 4, 8, and 12 wk and 4 wk postsupplementation. The plasma Se concentration (mean +/- SD) was 0.16+/-0.03 micromol/L at baseline. Selenite and Se-yeast supplementation increased plasma Se to plateau values, 1.0+/-0.2 and 1.3+/-0.2 micromol/L, respectively. In red cells, Se-yeast increased the selenium level sixfold and selenite threefold compared to placebo. The relative bioavailability of Se-yeast versus selenite measured as glutathione peroxidase (GSHPx) activity was similar in plasma, red blood cells, and platelets. GSHPx activity reached maximal levels in plasma and platelets of 300% and 200%, respectively, after 8 wk compared to the placebo group, but continued to increase in red cells for 16 wk. Our study showed that although both forms of Se were equally effective in raising GSHPx activity, Se-yeast provided a longer lasting body pool of Se. Se-yeast may be a better alternative to selenite in the prophylaxis of Keshan disease with respect to building up of body stores.


Asunto(s)
Glutatión Peroxidasa/sangre , Selenio/deficiencia , Adolescente , Disponibilidad Biológica , Plaquetas/enzimología , China , Dieta , Suplementos Dietéticos , Método Doble Ciego , Eritrocitos/enzimología , Femenino , Humanos , Masculino , Selenio/sangre , Vitamina E/sangre
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