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R Barrio

Publications and source records attributed to R Barrio.

At least 19 recordsLinked to original sources
PubMed2006

Wave-front dynamics in systems with directional anomalous diffusion.

In this paper we study the solutions of a generalized reaction-diffusion system with a bistable reaction term, and considering directional anomalous diffusion. We use the well-known properties of fractional derivatives to model asymmetric anomalous diffusion, and obtain traveling wave solutions that propagate in a direction that depends on the metastability of the front, the fractional exponent and the asymmetry of the diffusion.

Journal Article↗
PubMed2006

Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis.

BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general population requires that misinterpretations of apparently severe mutations in alleles carrying duplicated genes be avoided. Prenatal treatment prevents virilization in female fetuses and genetic counseling may be offered to couples in which one partner is either a patient or a carrier. This paper proposes a semiquantitative PCR method involving primer extension that distinguishes the severe point mutation Q318X in single gene copy alleles from the normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD carriers or patients, and one fetal sample (as well as the DNA of his family) were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific oligonucleotides hybridization for common mutations, Southern analysis, complementary direct sequencing and microsatellite typing. Primer extension analysis of the Q318X variants using fluorescent dideoxynucleotides was performed on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients, potential carriers and prenatal samples. RESULTS: Different fluorescence patterns were seen for the severe mutation (single gene copy) and the nondeficient (gene-duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M) ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method discriminated between the severe Q318X mutation and the normal Q318X variant in gene duplication, and could be a useful complementary tool in prenatal diagnosis and carrier detection.

Adrenal Hyperplasia, Congenital↗
PubMed2005

Therapy with insulin glargine (Lantus) in toddlers, children and adolescents with type 1 diabetes.

OBJECTIVE: To determine the efficacy and safety of insulin glargine (IG) in children and adolescents with type 1 diabetes. In a prospective, 6-month study, 80 patients, aged 2-19 years, received IG once daily plus insulin regular or rapid analogue before meals. The data of body mass index, frequency of severe hypoglycaemia, daily mean blood glucose, fasting blood glucose, haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected. RESULTS: After 6 months, the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70% (p<0.001). Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl (p<0.05) in the total group. Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy. The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day (p<0.05). Body mass index (BMI) remained unchanged. In the 14 preschooler children, the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57% (p<0.05). CONCLUSIONS: Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes. It also improved the metabolic control in preschool-age children, without increasing the number of hypoglycaemic events.

Adolescent↗
PubMed2005

[Type 2 diabetes mellitus in the pediatric age group].

In the past two decades, type 2 diabetes mellitus has increased in children and adolescents, especially within certain ethnic groups. This increase has been parallel to the rising prevalence of obesity. Because of the overlap between some clinical characteristics, the differential diagnosis between type 1 and 2 diabetes is difficult. Of 300 diabetic patients in our diabetes section, only three (1 %) had type 2 diabetes. Two patients were obese adolescents with a positive family history of type 2 diabetes mellitus; the third patient was a prepubertal, overweight girl with no family history of this disorder. The diagnosis was incidental in two patients and one patient presented with ketoacidosis. The differences between the three patients reveal the great clinical variability of this disorder and suggest that various underlying factors are involved in the pathophysiology of type 2 diabetes.

Adolescent↗
PubMed2002

Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families.

The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. Mutations in MODY genes were identified in 64% of the families. GCK/MODY2 mutations were the most frequently found, in 41%: seven novel (R369P, S411F, M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a previously unreported change (R271G). One family (4%) carried a novel mutation in the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1 pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal mutation when the mutation was of paternal origin. The MODY1 patient was diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite good metabolic control, and severe late-onset complications were common within her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.

Adolescent↗
PubMed2002

Treatment with the insulin analogue lispro in children and adolescents with type 1 diabetes mellitus: evaluation over a 3-year period.

The aim of the present study was to evaluate the degree of metabolic control obtained with the use of the insulin analogue lispro compared to the previous regimen with classical regular insulin in children and adolescents with Type 1 diabetes mellitus. HbA1c, lipid metabolism, body mass index (BMI), frequency of severe hypoglycaemia, carbohydrate intake, total daily insulin requirements and its distribution during the day were analysed in 44 diabetics patients (57% males and 43% females) throughout a 3-yr period. The mean age of the patients at the beginning of the study was 15.6 +/- 2.7 yr with a mean duration of the disease of 8.01 +/- 3.4 yr. All data were evaluated for the year before the change of treatment, and 1 yr (44 patients), 2 yr (19 patients) and 3 yr (13 patients) after the change. HbA1c levels did not significantly change (6.6 +/- 1.1% with regular insulin, 6.32 +/- 1.05% in the 1st year with lispro, 6.6 +/- 1.1% in the 2nd yr with lispro, 6.33 +/- 0.9% in the 3rd yr with lispro). However, significant differences (p = 0.03) were found after 3 yr of treatment in those patients who changed to insulin lispro therapy due to a bad glycaemic control. The total daily insulin dose (U/kg/d) remained unchanged. The total short-acting/intermediate-acting insulin ratio significantly decreased (45.9 +/- 0.1% regular insulin; 37.2 +/- 0.1% 1st yr lispro (p < 0.001); 33.6 +/- 0.1% 2nd yr lispro (p < 0.05); 35.5 +/- 0.1% 3rd yr lispro (p < 0.05). BMI and lipid profile remained unchanged. The self-reported daily carbohydrate in take significantly decreased due to a reduction of snacks. Total number of episodes of severe hypoglycaemia did not change significantly. In conclusion insulin lispro treatment did not modify the daily insulin dose, but reduced the short-acting/intermediate acting insulin ratio. The metabolic control remained unchanged. The number of patients reporting severe hypoglycaemia was similar despite the treatment schedule. After this 3-yr duration trial all patients decided to continue the treatment with lispro insulin.

Adolescent↗
PubMed2001

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes.

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

Animals↗
PubMed2000

Function of the spalt/spalt-related gene complex in positioning the veins in the Drosophila wing.

Spalt and Spalt-related encode conserved Zn-finger proteins that mediate the function of the TGF-beta molecule Decapentaplegic during the positioning of veins in the Drosophila wing. Here we show that Spalt and Spalt-related regulate the vein-specific expression of the transcription factors of the knirps and iroquois gene complexes, delimiting their domains of expression in the wing pouch. The effects of spalt/spalt-related mutations on knirps and iroquois expression are cell-autonomous, suggesting that they could be direct. The regulation of iroquois involves transcriptional repression by Spalt and Spalt-related, whereas the regulation of knirps involves a combination of transcriptional activation and repression mediated by the same genes. We suggest that the regulation of the iroquois and knirps gene complexes by Spalt and Spalt-related translates the Decapentaplegic morphogenetic gradient into precisely spaced pattern elements.

Animals↗
PubMed2000

High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus.

The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism.

Adult↗
PubMed1999

Identification of regulatory regions driving the expression of the Drosophila spalt complex at different developmental stages.

The zinc finger transcription factors Spalt and Spalt-related have been implicated in multiple developmental processes. In the wing they are regulated by the secreted protein Decapentaplegic and participate in the positioning of the wing veins. The function of Spalt has been also analyzed during tracheal development and embryonic segmentation. Here, we present the isolation and characterization of novel spalt/spalt-related alleles, which analysis indicates that these genes cannot substitute for each other in the developmental processes studied. The mutants present embryonic or pupal lethality, with phenotypes consistent with the loss of spalt function. We also present a detailed functional analysis of the DNA regions implicated in the regulation of these genes. This regulation is complex, integrating the information from both negative and positive regulators, and it is modular, with discrete fragments of DNA directing expression to discrete regions in embryonic and larval tissues.

Alleles↗
PubMed1999

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

OBJECTIVE: To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. DESIGN: Prospective clinical study. SETTING: Clinical pediatric department providing tertiary care. PATIENT(S): Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. INTERVENTION(S): Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. MAIN OUTCOME MEASURE(S): Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. RESULT(S): All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. CONCLUSION(S): Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

Adolescent↗
PubMed1999

Regulation of the spalt/spalt-related gene complex and its function during sensory organ development in the Drosophila thorax.

The nuclear proteins Spalt and Spalt-related belong to a conserved family of transcriptional regulators characterised by the presence of double zinc-finger domains. In the wing, they are regulated by the secreted protein Decapentaplegic and participate in the positioning of the wing veins. Here, we identify regulatory regions in the spalt/spalt-related gene complex that direct expression in the wing disc. The regulatory sequences are organised in independent modules, each of them responsible for expression in particular domains of the wing imaginal disc. In the thorax, spalt and spalt-related are expressed in a restricted domain that includes most proneural clusters of the developing sensory organs in the notum, and are regulated by the signalling molecules Wingless, Decapentaplegic and Hedgehog. We find that spalt/spalt-related participate in the development of sensory organs in the thorax, mainly in the positioning of specific proneural clusters. Later, the expression of at least spalt is eliminated from the sensory organ precursor cells and this is a requisite for the differentiation of these cells. We postulate that spalt and spalt-related belong to a category of transcriptional regulators that subdivide the thorax into expression domains (prepattern) required for the localised activation of proneural genes.

Animals↗
PubMed1999

Thyroid autoimmunity in children and adolescents with Type 1 diabetes mellitus.

Type 1 diabetic children and adolescents often present with autoimmune thyroid disorders. Two hundred and four diabetic patients, less than 20 years old, were studied in order to diagnose these diseases. The prevalence of thyroid autoimmune disorders was 17.6% and, of those, chronic autoimmune thyroiditis was the most frequent. Microsomal autoantibodies correlated more accurately with the presence of chronic autoimmune thyroiditis than thyroglobulin autoantibodies. The thyroid status of most of the patients with positive markers was euthyroidism (77%), but subclinical hypothyroidism (11%), overt hypothyroidism (3%), subclinical hyperthyroidism (3%) and overt hyperthyroidism (6%) were also present. Autoimmune thyroid disorders were the most prevalent immunological processes affecting diabetic patients. No significant associations of thyroid autoimmunity and other autoimmunological disorders, such as celiac disease or presence of other autoimmune antibodies, were found.

Adolescent↗
PubMed1997

Nocturnal hypoglycaemia in IDDM patients younger than 18 years.

The present multicentre study was undertaken to assess the prevalence of nocturnal hypoglycaemia and its determining factors in 117 diabetic children and adolescents, aged 2-18 years and diabetes duration > 1 year in Spain. Each child made 3 measurements of blood glucose (BG) at home at night (between 0000 h and 0600 h) on nine separate nights. A hypoglycaemic event occurred in 12-14% of children in any one night. This is lower than rates for nocturnal hypoglycaemia reported in literature, perhaps because of relatively late mealtimes and different meal content, in Spanish children. Children aged < 7 years were at higher risk of nocturnal hypoglycaemia than older children (p < 0.05). Mean HbA1c from the year before the study and mean HbA1c measured during the closest time to the study were significantly lower in those with nocturnal hypoglycaemia (p < 0.0001). Blood glucose concentrations 2 h before hypoglycaemia did not predict nocturnal hypoglycaemia. The occurrence of low or very low blood glucose concentrations before breakfast was related to a higher risk for nocturnal hypoglycaemia (chi 2 22.97; p < 0.001). No previous symptoms were detectable in 89% of cases.

Adolescent↗
PubMed1996

A gene complex acting downstream of dpp in Drosophila wing morphogenesis.

Localized expression of the transforming growth factor-beta (TGF-beta) homologue decapentaplegic (dpp) is crucial for Drosophila wing development. Here we show that spalt and spalt-related (sal and salr), two closely related genes that encode transcription factors, are expressed in response to dpp in a central territory of the wing imaginal disc, where they are required for the patterning of the wing. They are among the first identified elements that act downstream of dpp in wing development. The phenotypic consequences of misexpression of sal and salr suggest that an important outcome of dpp activity is the subdivision of the wing disc into territories smaller than lineage compartments, through the regulation of transcription-factor-encoding genes such as sal and salr.

Animals↗