18 research outputs found
In-beam tests of the AMS RICH prototype with 20 A GeV/c secondary ions
Abstract A prototype of the AMS Cherenkov imager (RICH) has been tested by means of a low intensity 20 GeV /c per nucleon ion beam coming from the fragmentation of a primary beam of Pb ions. Data have been collected for charges
Genetic evidence of the association of DEAH-box helicase 37 defects with 46,XY gonadal dysgenesis spectrum
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes
Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (âŒ20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems
ALS deficiency caused by an exon 2 deletion and a novel missense variant in the gene encoding ALS
La metilacion del promoter de la enzima 11\u3b2HSD2 aumenta con la edad y representaria un nuoevo factor de riesgo para el desarrollo de hipertension arterial
Promoter methylation at HSD11B2 gene increases with age and is a novel marker of arterial hypertensio
Mutations in MAGEL2 and L1CAM are associated with congenital hypopituitarism and arthrogryposis
Context
Congenital hypopituitarism (CH) is rarely observed in combination with severe joint contractures (arthrogryposis). Schaaf-Yang syndrome (SHFYNG) phenotypically overlaps with Prader-Willi syndrome, with patients also manifesting arthrogryposis. L1 syndrome, a group of X-linked disorders that include hydrocephalus and lower limb spasticity, also rarely presents with arthrogryposis.
Objective
We investigated the molecular basis underlying the combination of CH and arthrogryposis in five patients.
Patients
The heterozygous p.Q666fs*47 mutation in the maternally imprinted MAGEL2 gene, previously described in multiple patients with SHFYNG, was identified in patients 1 to 4, all of whom manifested growth hormone deficiency and variable SHFYNG features, including dysmorphism, developmental delay, sleep apnea, and visual problems. Nonidentical twins (patients 2 and 3) had diabetes insipidus and macrocephaly, and patient 4 presented with ACTH insufficiency. The hemizygous L1CAM variant p.G452R, previously implicated in patients with L1 syndrome, was identified in patient 5, who presented with antenatal hydrocephalus.
Results
Human embryonic expression analysis revealed MAGEL2 transcripts in the developing hypothalamus and ventral diencephalon at Carnegie stages (CSs) 19, 20, and 23 and in the Rathke pouch at CS20 and CS23. L1CAM was expressed in the developing hypothalamus, ventral diencephalon, and hindbrain (CS19, CS20, CS23), but not in the Rathke pouch.
Conclusion
We report MAGEL2 and L1CAM mutations in four pedigrees with variable CH and arthrogryposis. Patients presenting early in life with this combined phenotype should be examined for features of SHFYNG and/or L1 syndrome. This study highlights the association of hypothalamo-pituitary disease with MAGEL2 and L1CAM mutations
Effect of imatinib on plasma glucose concentration in subjects with chronic myeloid leukemia and gastrointestinal stromal tumor
Abstract Background Type 2 diabetes mellitus has become one of the most important public health concerns worldwide. Due to its high prevalence and morbidity, there is an avid necessity to find new therapies that slow the progression and promote the regression of the disease. Imatinib mesylate is a tyrosine kinase inhibitor that binds to the Abelson tyrosine kinase and related proteins. It enhances ÎČ-cell survival in response to toxins and pro-inflammatory cytokine. The aim of this study is to evaluate the effect of imatinib on fasting plasma glucose in subjects with normal fasting glucose, subjects with impaired fasting glucose and in subjects with type 2 diabetes mellitus. Methods We identified 284 subjects diagnosed with chronic myeloid leukemia or gastrointestinal stromal tumors from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran database. 106/284 subjects were treated with imatinib. We compared the effect of imatinib on fasting plasma glucose after 1 and 6Â months of treatment. We used ANOVA test of repeated samples to determine statistical significance in fasting plasma glucose before imatinib treatment and the follow-up. Statistical analysis was performed with Statistical Package for the Social Sciences v22. Results We included a total of 106 subjects: 76 with fasting plasma glucose concentrations <â100Â mg/dL (normal FG), 19 subjects with fasting plasma glucose concentrations â„100Â mg/dL (impaired fasting glucose), and 11 subjects with â„126Â mg/dL (type 2 diabetes mellitus). We found a significant increase in fasting plasma glucose concentration in the normal fasting glucose group (pâ=â0.048), and a significant decrease in fasting plasma glucose concentration in the type 2 diabetes mellitus group (pâ=â0.042). In the impaired fasting glucose group, we also found a tendency towards a decrease in fasting plasma glucose (pâ=â0.076). We identified 11 subjects with type 2 diabetes mellitus, of whom, 7 (64%) had a reduction in their fasting plasma glucose concentrations after 6Â months. A significant glycosylated hemoglobin reduction (pâ=â0.04) was observed. Conclusion Subjects with chronic myeloid leukemia or gastrointestinal stromal tumor with type 2 diabetes mellitus had a significant reduction in fasting plasma glucose and glycosylated hemoglobin at 1 and 6Â months while using imatinib