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1.
Artículo en Inglés | MEDLINE | ID: mdl-39181954

RESUMEN

Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively. The 180-day cumulative incidence of aGVHD was 21% (95% confidence interval [CI] 17-25%) for grade II-IV and 11% (95% CI 8-14%) grade III-IV aGVHD. The use of haploidentical donors was associated with an increased risk of severe aGVHD. Among 75 patients receiving first-line systemic corticosteroids, 49% achieved a sustained complete response, while 23% and 24% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.4% (95% CI, 3.3-8.1). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of myeldysplastic neoplasms, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.

2.
Climacteric ; 25(6): 603-608, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35866470

RESUMEN

OBJECTIVE: This study aimed to analyze the association between rs3480 and rs16835198 of FNDC5/Irisin and their haplotypes with variations in bone mineral density (BMD) and osteopenia/osteoporosis in postmenopausal Mayan-Mestizo women. METHODS: We studied 547 postmenopausal women of Maya-Mestizo origin. BMD was measured in the lumbar spine and total hip by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time PCR allelic discrimination. Differences between the means of BMD according to genotype were analyzed with covariance. Allele frequency differences were assessed by χ2 and logistic regression was used to test for associations. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. RESULTS: Under a recessive model, we observed a significant association of rs3480 with the presence of osteopenia at the total hip and femoral neck (p = 0.008 and p = 0.003, respectively). For rs16835198, we found an association with osteopenia at the total hip and femoral neck in a dominant model (p = 0.043 and p = 0.009, respectively). CONCLUSIONS: We found an association of rs3480 with risk to present osteopenia at the total hip and femoral neck, while rs16835198 was associated as a protector for presence of osteopenia only at the femoral neck.


Asunto(s)
Enfermedades Óseas Metabólicas , Osteoporosis Posmenopáusica , Femenino , Humanos , Fibronectinas , Posmenopausia/genética , Polimorfismo de Nucleótido Simple , Enfermedades Óseas Metabólicas/genética , Densidad Ósea/genética , Absorciometría de Fotón , Osteoporosis Posmenopáusica/genética
3.
Nutr Metab Cardiovasc Dis ; 28(11): 1188-1195, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30143409

RESUMEN

BACKGROUND AND AIMS: Several studies propose that (-)-epicatechin, a flavonol present in high concentration in the cocoa, has cardioprotective effects. This study aimed to evaluate the impact of (-)-epicatechin on the development of dilated cardiomyopathy in a δ sarcoglycan null mouse model. METHODS AND RESULTS: δ Sarcoglycan null mice were treated for 15 days with (-)-epicatechin. Histological and morphometric analysis of the hearts treated mutant mice showed significant reduction of the vasoconstrictions in the coronary arteries as well as fewer areas with fibrosis and a reduction in the loss of the ventricular wall. On the contrary, it was observed a thickening of this region. By Western blot analysis, it was shown, and increment in the phosphorylation level of eNOS and PI3K/AKT/mTOR/p70S6K proteins in the heart of the (-)-epicatechin treated animals. On the other hand, we observed a significantly decreased level of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) heart failure markers. CONCLUSION: All the results indicate that (-)-epicatechin has the potential to prevent the development of dilated cardiomyopathy of genetic origin and encourages the use of this flavonol as a pharmacological therapy for dilated cardiomyopathy and heart failure diseases.


Asunto(s)
Cardiomiopatía Dilatada/prevención & control , Catequina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Sarcoglicanos/deficiencia , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Factor Natriurético Atrial/metabolismo , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/enzimología , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Fibrosis , Masculino , Ratones Noqueados , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Péptido Natriurético Encefálico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Sarcoglicanos/genética , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Vasoconstricción/efectos de los fármacos
4.
Dev Biol ; 434(2): 292-303, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29253505

RESUMEN

The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor ß (TGFß) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGFß signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGFß pathway is preferentially balanced with a prominent role of Alk1/TgfßR2/Smad1 and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acvrl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGFß through the Alk1/TgfßR2 receptor axis is acting on endothelial cells to produce hematopoiesis.


Asunto(s)
Aorta/embriología , Proteínas Aviares/metabolismo , Endotelio Vascular/embriología , Hematopoyesis Extramedular/fisiología , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Aorta/citología , Embrión de Pollo , Pollos , Endotelio Vascular/citología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo
5.
Nanotechnology ; 26(47): 475201, 2015 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-26526708

RESUMEN

In this work Au nanoparticles (AuNPs) are incorporated into poly(methyl methacrylate) (PMMA) waveguides to develop optical couplers that are compatible with planar organic polymer photonics. A method for growing AuNPs (of 10 to 100 nm in size) inside the commercially available Novolak resist is proposed with the intention of tuning the plasmon resonance and the absorption/scattering efficiencies inside the patterned structures. The refractive index of the MNP-Novolak nanocomposite (MNPs: noble metal nanoparticles) is carefully analysed both experimentally and numerically in order to find the appropriate fabrication conditions (filling factor and growth time) to optimize the scattering cross section at a desired wavelength. Then the nanocomposite is patterned inside a PMMA waveguide to exploit its scattering properties to couple and guide a normal incident laser light beam along the polymer. In this way, light coupling is experimentally demonstrated in a broad wavelength range (404-780 nm). Due to the elliptical shape of the MNPs the nanocomposite demonstrates a birefringence, which enhances the coupling to the TE mode up to efficiencies of around 1%.

6.
Folia Neuropathol ; 53(1): 24-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25909872

RESUMEN

The MTHFR gene has been reported as a susceptibility locus for sporadic Parkinson's disease (sPD). The functional variant rs1801133 has been linked to hyperhomocysteinemia and dopaminergic cell death. Among different populations, Mexican-Mestizos (most present-day Mexicans) have the highest frequency of this variant. Therefore, we sought to determine a possible association of rs1801133 with SPD. In total, 356 individuals were included: 140 patients with PD, diagnosed according to the Queen Square Brain Bank criteria, and 216 neurologically healthy controls. Genotyping was performed using TaqMan probes for rs1801133 and real-time PCR. Logistic regression analysis with adjustment for smoking and gender was used to test for an association between genotype and SPD. The CC genotype was associated with SPD; exp() = 2.06; 95% CI: 1.101-3.873, p = 0.024. No association with age at onset, cognitive impairment or gender was found in our study group. Our data suggest an important role of MTHFR gene variants in SPD.


Asunto(s)
Estudios de Asociación Genética/métodos , Variación Genética/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Polimorfismo de Nucleótido Simple/genética
7.
Opt Lett ; 39(16): 4962-5, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25121919

RESUMEN

In this Letter, we study a new kind of organic polymer waveguide numerically and experimentally by combining an ultrathin (10-50 nm) layer of compactly packed CdSe/ZnS core/shell colloidal quantum dots (QDs) sandwiched between two cladding poly(methyl methacrylate) (PMMA) layers. When a pumping laser beam is coupled into the waveguide edge, light is mostly confined around the QD layer, improving the efficiency of excitation. Moreover, the absence of losses in the claddings allows the propagation of the pumping laser beam along the entire waveguide length; hence, a high-intensity photoluminescence (PL) is produced. Furthermore, a novel fabrication technology is developed to pattern the PMMA into ridge structures by UV lithography in order to provide additional light confinement. The sandwich-type waveguide is analyzed in comparison to a similar one formed by a PMMA film homogeneously doped by the same QDs. A 100-fold enhancement in the waveguided PL is found for the sandwich-type case due to the higher concentration of QDs inside the waveguide.

8.
Genet Couns ; 25(2): 129-41, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25059011

RESUMEN

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.


Asunto(s)
Diagnóstico Tardío/estadística & datos numéricos , Manejo de la Enfermedad , Asesoramiento Genético/estadística & datos numéricos , Distrofia Muscular de Duchenne/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Países en Desarrollo , Femenino , Humanos , Lactante , Masculino , México/epidemiología , Distrofia Muscular de Duchenne/epidemiología , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Estudios Retrospectivos , Adulto Joven
9.
Opt Express ; 19(8): 7664-72, 2011 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-21503075

RESUMEN

In this work, we demonstrate experimentally the use of an array of gold nanodisks on functionalized silicon for chemosensing purposes. The metallic nanostructures are designed to display a very strong plasmonic resonance in the infrared regime, which results in highly sensitive sensing. Unlike usual experiments which are based on the functionalization of the metal surface, we functionalized here the silicon substrate. This silicon surface was modified chemically by buildup of an organosilane self-assembled monolayer (SAM) containing isocyanate as functional group. These groups allow for an easy surface regeneration by simple heating, thanks to the thermally reversible interaction isocyanate-analyte, which allows the cyclic use of the sensor. The technique showed a high sensitivity to surface binding events in gas and allowed the surface regeneration by heating of the sensor at 150 °C. A relative wavelength shift ∆λ(max)λ(0)=0.027 was obtained when the saturation level was reached.


Asunto(s)
Nanopartículas del Metal/química , Nanotecnología/métodos , Silicio/química , Espectroscopía Infrarroja Corta/métodos , Diseño de Equipo , Gases , Oro/química , Calor , Isocianatos/química , Óptica y Fotónica , Propiedades de Superficie , Temperatura
10.
J Androl ; 30(1): 41-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18723471

RESUMEN

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. To date, 4 different genes have been identified as responsible for the presence of KS; however, in many cases no mutations have been found in any of these genes. Herein, we report the molecular findings regarding the analysis of fibroblast growth factor receptor 1 (FGFR1), prokineticin receptor 2 (PROKR2), and prokineticin (PROK2) in patients with KS. Twenty-four patients with KS were studied in whom mutations in KAL1 had been investigated previously. Polymerase chain reaction products from FGFR1, PROKR2, and PROK2 were sequenced and mutations were sought in the open reading frame of the 3 genes. Two patients presented a heterozygous T-to-G transversion in exon 2 (c.518T>G) of the PROKR2, which results in a leucine-to-arginine substitution at codon 173. Our results strengthen the hypothesis of possible digenic inheritance in some patients with KS. Likewise, our data extend previous reports demonstrating that PROKR2 plays a role in the etiology of this syndrome.


Asunto(s)
Proteínas de la Matriz Extracelular/genética , Hormonas Gastrointestinales/genética , Síndrome de Kallmann/genética , Proteínas del Tejido Nervioso/genética , Neuropéptidos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Adolescente , Adulto , Análisis Mutacional de ADN , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
11.
Mol Hum Reprod ; 14(6): 325-30, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18453550

RESUMEN

SRY directs testicular development. It has been suggested that the only high-mobility group (HMG) box of the SRY is important for the function of this protein; however, other studies have suggested that the N- and C-terminal regions are also involved in this process. Herein, we analysed and compared in vitro the DNA-binding activity of the full-length SRY and three mutants (HMG box alone, N-terminal less and C-terminal less SRY proteins). DNA-binding capability was analysed by mobility shift assays, optical density and dissociation constant by using pure non-fusion SRY proteins. The structure of the full-length SRY was carried out using a protein molecular model. The HMG box SRY alone and C-terminal less SRY proteins had a statistically diminished DNA binding in comparison with the full-length SRY. In contrast, the affinity for DNA of the N-terminal less SRY was relatively similar to the full-length SRY. Likewise, three-dimensional structure of the full-length SRY suggested that some residues of the C-terminal region of the SRY interact with DNA. We demonstrate the importance that full-length SRY has, particularly the C-terminal region of the protein, in DNA binding in vitro. Likewise, the affinity of the HMG box alone is clearly reduced when compared with the full-length SRY.


Asunto(s)
ADN/metabolismo , Proteína de la Región Y Determinante del Sexo/metabolismo , Proteína de la Región Y Determinante del Sexo/fisiología , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/fisiología , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Dominios HMG-Box/fisiología , Humanos , Técnicas In Vitro , Modelos Moleculares , Estructura Terciaria de Proteína/fisiología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteína de la Región Y Determinante del Sexo/química
12.
Nanotechnology ; 19(12): 125302, 2008 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-21817723

RESUMEN

Charging of common resist materials during electron beam (e-beam) writing leads to deflection of the electron beam path, which can result in significant pattern displacement. Here we report a new conducting polymer to eliminate charging. A common approach is to place the conducting layer underneath the e-beam resist layer. Conductivity equal or greater than 10(-4) S cm(-1) has been reported to prevent pattern displacement. Some other properties such as a flat surface layer, chemical inertness and insolubility in both the top resist solvent and the developer are also necessary. The way to achieve all these properties consisted in synthesizing a conducting polymer inside an insulating polymer to form an interpenetrating polymer network (IPN) which could combine their properties. Novolak was used as the host polymer and terthiophene (3T) as the monomer to polymerize. Cu(ClO(4))(2) initiates simultaneously the oxidative polymerization of the 3T and its subsequent doping inside Novolak during the bake step in a one-step reaction. Solvent-resistant and homogeneous conducting films with smooth surfaces were achieved. The conductivity was of the order of 10(-2) S cm(-1). Patterning of the top resist was carried out without disturbing its lithographic performance.

13.
Rev. chil. nutr ; 32(2): 118-125, ago. 2005. tab
Artículo en Español | LILACS | ID: lil-476882

RESUMEN

El propósito de este estudio fue aportar nuevos antecedentes acerca de la suficiencia y calidad de la alimentación de mujeres adultas chilenas. Se determinó en 54 mujeres el Índice de Masa Corporal (IMC) y la calidad de la alimentación mediante su adecuación a las recomendaciones de energía y nutrientes, porciones de alimentos recomendadas por las Guías de Alimentación Chilenas y al Índice de Alimentación Saludable (ISA) adaptado. Se observó un 55 por ciento de exceso de peso, una buena adecuación del consumo de vitamina C y ácido Fólico y baja de energía, hierro, calcio, fibra. Para verduras, frutas y lácteos el consumo promedio fue menos del 50 por ciento de las porciones recomendadas. El G por ciento fue de 32.6 por ciento con un aporte de grasas saturadas menor del 10 por ciento y de colesterol menor al máximo sugerido. Sólo el 20.4 por ciento consumía una alimentación saludable. No se encontró una asociación entre IMC y consumo de energía e ISA. Se concluye que una importante proporción del grupo de mujeres estudiadas presenta una alimentación poco saludable, con un inadecuado consumo de alimentos y desequilibrios en el aporte de nutrientes.


The purpose of this study was to provide new data on the quality and adequacy of the diet of Chilean women. Body mass index (BMI) and the quality of the diet in terms of adequacy of nutrient intakes, food portions as suggested to the Chilean nutrient pyramid, and an adaptation of the healthy food index (HFI) were evaluated in a group of 54 women. Fifty-five percent of subjects had excess body weight. Adequate intakes of vitamin C and folic acid but not energy, iron, calcium, fiber were observed. Mean intakes of vegetables, fruits and dairy products were less than 50 percent of the recommended portions. F percent was 32.6 percent. Saturated fat was less than 10 percent and cholesterol intake less than maximum suggested. Appropriate values of HFI were obtained in 20.4 percent of individuals. No associations were found among BMI and energy intake and HFI. It is concluded that a high proportion of women presents less-than-adequate diets.


Asunto(s)
Humanos , Femenino , Adulto , Ingestión de Alimentos , Evaluación Nutricional , Estado Nutricional , Antropometría , Composición Corporal , Chile , Dieta/estadística & datos numéricos , Necesidades Nutricionales
14.
Hum Reprod ; 20(4): 965-9, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15695318

RESUMEN

BACKGROUND: Etiology and inheritance pattern in polycystic ovary syndrome (PCOS) remain uncertain. Granulosa cells from follicles of women with PCOS have little, if any, aromatase (encoded by the CYP19 gene) activity; follicles contain low levels of estradiol, P450arom mRNA and aromatase stimulating bioactivity. Mice with targeted disruption of the CYP19 gene present cystic follicles. It has been proposed that chronic exposure to high levels of LH, because of aromatase deficiency, determines the development of ovarian cysts. Herein, we investigated if mutations in the CYP19 gene and/or its ovary promoter are causal in patients with PCOS. METHODS: Twenty-five patients with PCOS and 50 control women were studied. PCR analysis of genomic DNA and complete sequence of all exons of the aromatase gene and its ovary promoter were performed. RESULTS: No heterozygous or homozygous mutant alleles were present in any of the patients studied. CONCLUSIONS: In the population studied, mutations of the P450arom gene or its promoter are not the cause of PCOS. However, these findings do not preclude the possible importance of an aromatase disorder in PCOS etiology. Variations in aromatase complex function could play a role in PCOS etiology, but the determinants of such variations might be located in other genes.


Asunto(s)
Aromatasa/genética , Síndrome del Ovario Poliquístico/genética , Adolescente , Adulto , Femenino , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Mutación , Regiones Promotoras Genéticas
15.
Mol Hum Reprod ; 11(11): 833-6, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16390857

RESUMEN

Aetiology of mixed gonadal dysgenesis (MGD) has not been completely elucidated. Molecular analyses have failed to demonstrate the presence of mutations in sex-determining region on Y chromosome (SRY); it has been suggested that these individuals may bear mutations in other genes involved in the testis-determining pathway. Desert hedgehog's (DHH) importance regarding male sex differentiation has been demonstrated in various studies we describe here, for the first time, two cases of MGD in which a monoallelic single base deletion in DHH is associated with the disorder. Genomic DNA was isolated from paraffin-embedded gonad tissue from 10 unrelated patients with MGD and three controls; in addition to, DNA from peripheral blood leukocytes in 100 controls. Coding sequence abnormalities in DHH were assessed by exon-specific PCR, single-stranded conformation polymorphism (SSCP) and direct sequencing. In two patients, a heterozygous 1086delG in exon 3 was found. Comparing previously described mutations in DHH to the one observed in this study, we can affirm that the phenotypic spectrum of patients with gonadal dysgenesis due to mutations in DHH is variable. This study continues to demonstrate the importance that DHH has in mammalian male sexual differentiation, providing extended evidence that DHH constitutes a key gene in gonadal differentiation.


Asunto(s)
Disgenesia Gonadal/genética , Mutación , Transactivadores/genética , Adolescente , Adulto , Preescolar , Exones , Tamización de Portadores Genéticos , Proteínas Hedgehog , Humanos , Lactante , Cariotipificación , Masculino , Valores de Referencia
16.
J Clin Endocrinol Metab ; 89(9): 4480-3, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15356051

RESUMEN

Mutations of SRY are the cause of complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. We describe the first report in which three cases of 46,XY complete PGD are attributed to mutations of the Desert hedgehog (DHH) gene. DHH was sequenced using genomic DNA from paraffin-embedded gonadal tissue from six patients with complete 46,XY PGD. Mutations were found in three patients: a homozygous mutation in exon 2, responsible for a L162P, and a homozygous 1086delG in exon 3. Mutated individuals displayed 46,XY complete PGD, differentiating from the only previously described patient with a homozygous DHH mutation, who exhibited a partial form of PGD with polyneuropathy, suggesting that localization of mutations influence phenotypic expression. This constitutes the first report where mutations of DHH are associated with the presence of 46,XY complete PGD, demonstrating that the genetic origin of this entity is heterogeneous and that disorders in other genes, different from SRY, involved in the testis-determining pathway are implicated in abnormal testicular differentiation in humans. These data extend previous reports demonstrating DHH is a key gene in gonadal differentiation.


Asunto(s)
Disgenesia Gonadal 46 XY/genética , Mutación , Transactivadores/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Codón , Exones , Proteínas Hedgehog , Humanos , Datos de Secuencia Molecular
17.
J Clin Endocrinol Metab ; 87(6): 2589-92, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12050219

RESUMEN

Kallmann's syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. Genetic defects have been observed throughout the KAL1 gene, located on the Xp22.3 region, in less than 50% of the patients. We report the molecular study of the KAL1 gene in 12 males with KS. PCR of the 14 exons of the KAL1 gene was performed on genomic DNA. PCR products of all exons were purified and sequenced. Three novel genetic defects were found. One patient exhibited a complete deletion of exon 5. The second presented a duplication of nucleotides 158-168; this insertion causes a termination codon (TGA) within the same exon. The third presented a mutation in exon 6, in which codon 262 changes from arginine to a stop codon. In the remaining nine individuals, no mutations were found. Three previously reported polymorphic changes were also documented. The deletion of exon 5 occurs within the region encoding the first fibronectin type III-like repeat of the KAL1 protein, this being the first KS patient who exhibits a complete deletion of a single exon of the KAL1 gene. The duplication of nucleotides in exon 1 is located in the conserved cysteine-rich N-terminal region that corresponds to the whey acidic protein motif, affecting the KAL1 protein either by interrupting the normal transcription or stopping the translation at the stop codon. The last novel mutation, a stop codon in exon 6, is located within the region encoding the first fibronectin type III-like repeat of the KAL1 protein. The absence of mutations in the majority of patients suggests the possibility of the existence of other genes involved or that in certain individuals the presence of various polymorphisms within the KAL1 gene could predispose to disease, as has been demonstrated in other pathological entities.


Asunto(s)
Moléculas de Adhesión Celular/genética , Proteínas de la Matriz Extracelular , Síndrome de Kallmann/genética , Mutación , Proteínas del Tejido Nervioso , Adolescente , Adulto , Secuencia de Bases/genética , Humanos , Masculino , Datos de Secuencia Molecular , Mutación/genética , Polimorfismo Genético
18.
Contraception ; 63(3): 143-6, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11368986

RESUMEN

This study purported to determine the effect of pretreatment counseling upon discontinuation of 150 mg depot-medroxyprogesterone acetate (Depo-Provera) given for contraception. A total of 350 Mexican women participated: 175 received detailed structured pretreatment counseling about the hormonal effects of the injectable vs. routine counseling upon duration of use and efficacy of the method. Study termination rates were significantly lower in the structured counseling group than in the control group. Cumulative life table discontinuation rates were 17% (30/175) and 43.4% (76/175), respectively (p <0.05). The most common reasons for terminating DMPA were menstrual changes (8.6 and 32% for counseling and control group, respectively). The findings suggest that pretreatment counseling on expected side effects increases the continuation rates of DMPA users.


Asunto(s)
Anticonceptivos Femeninos/administración & dosificación , Consejo , Acetato de Medroxiprogesterona/administración & dosificación , Cooperación del Paciente , Adulto , Amenorrea/inducido químicamente , Anticonceptivos Femeninos/efectos adversos , Femenino , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Trastornos de la Menstruación/inducido químicamente , México , Pacientes Desistentes del Tratamiento , Educación del Paciente como Asunto
19.
Clin Endocrinol (Oxf) ; 54(4): 493-8, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11318785

RESUMEN

BACKGROUND AND OBJECTIVE: Mutations in the GnRH receptor (GnRH-R) gene cause hypogonadotrophic hypogonadism. Here, we present the molecular studies of the GnRH-R gene in three families with isolated hypogonadotrophic hypogonadism. PATIENTS: Three unrelated families, with at least two members diagnosed with isolated hypogonadotrophic hypogonadism were included. MEASUREMENTS: DNA sequencing was performed after polymerase chain reaction amplification of each of the three exons of the gene. RESULTS: A novel homozygous missense mutation, at nucleotide 268, turning glutamic acid into lysine, located at the second transmembrane domain of the GnRH-R gene was found in two patients pertaining to one of the families studied. Both parents and an unaffected brother were heterozygous carriers of one mutant allele, an unaffected sister was homozygote wild type. In the other two affected families no mutations were found in the GnRH-R gene. CONCLUSIONS: This constitutes the first description of an spontaneous mutation located at the second transmembrane domain (Glu90Lys) of the GnRH-R, indicating that the integrity of glutamic acid at this position is crucial for receptor function. Also this report, complementing others, demonstrates that mutations are distributed throughout the GnRH-R gene and that as in the only other homozygous mutation previously described, affected patients present a complete form of hypogonadotrophic hypogonadism. Due to the fact that apparently consanguinity was present in our affected family, we presume that the mutation derived from a common ancestor, by a founder gene effect.


Asunto(s)
Hipogonadismo/genética , Mutación Missense , Receptores LHRH/genética , Adolescente , Adulto , Consanguinidad , Femenino , Hormona Folículo Estimulante/sangre , Ácido Glutámico/genética , Homocigoto , Humanos , Hipogonadismo/sangre , Hormona Luteinizante/sangre , Lisina/genética , Masculino , Linaje
20.
J Gerontol B Psychol Sci Soc Sci ; 56(3): S140-50, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11316839

RESUMEN

UNLABELLED: Objectives. Our main purpose was to examine similarities and differences in patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for moderately impaired husbands with probable AD and 27 noncaregiving wives from comparable sociodemographic backgrounds were videotaped in their homes during both mealtime and a future event planning task. In addition, they completed self-report questionnaires to assess depression, stress, relationship mutuality, and perceived hope. Results. Compared with their counterparts, caregiving wives reported higher levels of depression and stress, but similar shared values and closeness. For the three factors developed from the Marital Interaction Coding System (MICS, version IV; Supportive Facilitative, and Rapport Building), a complex pattern of results was found in which disease status, type of task, and gender interacted significantly. Noncaregiving couples were more interactive overall and expressed more support to each other. Caregiving wives were found to be most facilitative during the planning task, whereas AD husbands were highest on interactions that built rapport (e.g., smiling) during that same task. Caregiving wives actually increased their facilitative behavior from the mealtime to planning task, probably reflecting the increased demand characteristics of the latter. DISCUSSION: This study is one of a small body of literature to describe the negative impact of AD on spousal communication as observed and coded in two videotaped interaction situations in the home. Suggestions are made for future research, including the inclusion of longitudinal designs and non-Caucasian couples.


Asunto(s)
Enfermedad de Alzheimer/psicología , Cuidadores/psicología , Relaciones Interpersonales , Matrimonio/psicología , Esposos/psicología , Adaptación Psicológica , Anciano , Actitud Frente a la Salud , Estudios de Casos y Controles , Depresión/diagnóstico , Depresión/psicología , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moral , Análisis Multivariante , Escalas de Valoración Psiquiátrica , Apoyo Social , Factores Socioeconómicos , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Grabación de Cinta de Video
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