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L Castaño

Publications and source records attributed to L Castaño.

At least 37 records · Page 2Linked to original sources
PubMed1998

Association of insulin-dependent diabetes mellitus and celiac disease: a study based on serologic markers.

BACKGROUND: The association of celiac disease and insulin-dependent diabetes mellitus has been known for some time. In an attempt to clarify this association, the prevalence of celiac disease among diabetic children was determined, and the risk of insulin-dependent diabetes mellitus was defined in pediatric patients with celiac disease. METHODS: Ninety-three children with diabetes were analyzed for the presence of celiac disease-related markers (antigliadin and antiendomysial antibodies) and characteristic alterations in the intestinal mucosa. In another group, 93 children with celiac disease were screened for pancreatic autoantibodies and pancreatic beta-cell function. RESULTS: Among children with insulin-dependent diabetes mellitus, a 6.45% prevalence of celiac disease was observed, a value significantly higher than that found among healthy controls. In contrast, only three celiac disease patients showed potential autoimmunity toward the pancreatic beta cell, a proportion not significantly different from that in the general population. Additionally, no alteration of glucose metabolism was observed in the antibody-positive patients. CONCLUSION: The increased risk of celiac disease among patients with diabetes requires a long follow-up to determine the presence of celiac disease markers among patients with diabetes, to avoid potential malignant disease derived from untreated celiac disease. In contrast, there is no evidence to support an increased risk of insulin-dependent diabetes mellitus among children with celiac disease. In accordance with the accepted influence of diet in the development of autoimmune diabetes, a hypothetical mechanism of protection against insulin-dependent diabetes mellitus that is mediated by environmental factors related to restricted diet is suggested in this population.

Adolescent↗
PubMed1998

Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disease caused by deficiency in the antidiuretic hormone arginine vasopressin (AVP) encoded by the AVP-neurophysin II (AVP-NPII) gene on chromosome 20p13. In this study, we analyzed two families with FNDI using direct automated fluorescent, solid phase, single-stranded DNA sequencing of PCR-amplified AVP-NPII DNA. In one of the families, affected individuals presented a novel nonsense mutation in exon 3 of the gene, consisting in a G to T transition at nucleotide 2101, which produces a stop signal in codon 82 (Glu) of NPII. The premature termination eliminates part of the C-terminal domain of NPII, including a cysteine residue in position 85, which could be involved in the correct folding of the prohormone. In the second family, a G279A substitution at position -1 of the signal peptide was observed in all affected individuals. This missense mutation, which replaces Ala with Thr, is frequent among FNDI patients and is thought to reduce the efficiency of cleavage by signal peptidases.

Adolescent↗
PubMed1998

A novel missense (R80W) mutation in 17-beta-hydroxysteroid dehydrogenase type 3 gene associated with male pseudohermaphroditism.

OBJECTIVE: Deficit of the testosterone converting enzyme 17-beta-hydroxysteroid dehydrogenase (17beta-HSD) has been shown to be responsible for male pseudohermaphroditism (MPH). We analysed the gene encoding 17beta-HSD type 3 (17beta-HSD3) in a patient with MPH. METHODS: We studied a 46, XY new-born diagnosed as having MPH. The child also had other congenital disorders, including a giant omphalocele and Fallot's tetralogy, and died of post-surgical complications at age 4.5 months. Basal hormonal levels, and after human chorionic gonadotrophin stimulation, suggested a deficiency in 17beta-HSD as the biochemical defect underlying this MPH. PCR amplification and subsequent sequencing of all coding exons of the 17beta-HSD3 gene were performed on genomic DNA from the patient and both parents. Messenger RNA was extracted from the patient's testis and 17beta-HSD3 cDNA was synthesized, PCR amplified and sequenced. RESULTS: Sequencing revealed the presence of a homozygous missense mutation (R80W) in exon 3 of the 17beta-HSD3 gene, which was also present in single doses in both parents, in accordance with the recessive inheritance of the defect. No other mutation was found, and cDNA sequencing confirmed correct synthesis and processing of 17beta-HSD3 mRNA. CONCLUSIONS: Confirming the abnormal delta4-androstenedione/testosterone ratios that suggested 17beta-HSD deficiency, a homozygous missense mutation in the gene coding for this enzyme was identified in the patient with MPH. This study adds further genetic evidence to the role of 17beta-HSD3 in male sexual development. There is no evidence supporting the association of this mutation in 17beta-HSD3 with the congenital malformations other than MPH present in the child.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Anti-insulin activity in normal newborn cord-blood serum: absence of IgG-mediated insulin binding.

Insulin autoantibodies (IAAs) are present in approximately 60% of type I diabetes patients at onset and are used as predictors for the disease. Although the prevalence of IAAs in the general population has been reported to be <1%, preliminary data have pointed out a higher proportion of IAA positivity in newborn cord-blood serum, and some authors have suggested that they are immunoglobulin G antibodies, resulting from a hypothetical gestational insulitis. To characterize this insulin-binding activity, we analyzed cord-blood sera from 100 healthy newborns, as well as serum from 21 of their mothers at delivery, 179 new-onset type I diabetic patients, and 200 healthy control subjects. IAAs were present in 0.5% of the control subjects and 54% of new-onset type I diabetic patients. On the other hand, 96% of the newborn cord-blood sera showed anti-insulin activity, while it was detected in only 14% of their mothers. No significant differences were observed between cord sera and the general population for islet-cell or anti-GAD autoantibodies. Anti-insulin activity in cord serum was not bound by protein A or protein G, in contrast with type I diabetes-related IAA activity. We conclude that this insulin-binding activity, present in most newborn cord sera and specific to the child, is not IgG mediated. These data, together with the absence of other pancreatic autoimmunity markers in this population, suggest that it is an isolated phenomenon not related to type I diabetes or other pancreatic autoimmune processes and is due to the presence of a cross-reacting molecule in cord blood that has yet to be identified.

Adolescent↗
PubMed1996

A novel postzygotic nonsense mutation in SRY in familial XY gonadal dysgenesis.

The Y chromosome gene SRY plays an important role in normal male sexual development and is thought to be the testis-determining factor. We describe a familial nonsense mutation in SRY, shared by two XY sisters with complete gonadal dysgenesis and, in a mosaic manner, by their father. This mutation, consisting of a C to T transition in position 1 of codon 97 of SRY, results in a truncated peptide with an incomplete DNA-binding domain. The mutation is also present in the father of the two cases, but a portion of wild-type SRY also remains. Our data suggest that the father suffered a postzygotic mutation early in development, but that he retained a remnant of functional SRY protein that accounts for his normal development.

Adolescent↗
PubMed1994

[The "arrhythmic pattern": a new method with prognostic significance in myocardial infarct].

OBJECTIVES: To establish a score or arrhythmic pattern for the prediction of long-term cardiac deaths on patients who have survived to the first acute myocardial infarction. PATIENTS AND METHODS: We studied prospectively 200 patients that survived at a first myocardial infarction and in whom ambulatory ECG monitoring during 24 hours between days 7th and 18th (mean 12th) from the infarction was performed. The mean follow-up time was 51 +/- 18 months. The number and type of ventricular arrhythmias were analyzed and a score was measured, accordingly with Castellanos and Lown's classifications. An "arrhythmic pattern" or "total punctuation" was defined and compared among two groups: group 1 > 65 points and group 2 < 65 points. RESULTS: The differential characteristics of both groups were: age (60 +/- 9 versus 56 +/- 10 years old; p = 0.004); hypertension (63% versus 29%; p < 0.001); clinic stage II-III (23% versus 11%; p = 0.02); echocardiographic ejection fraction (45 +/- 11% versus 50 +/- 10%; p = 0.04); positive exercise testing (73% versus 56%; p = 0.01); arrhythmias on the exercise test (15% versus 25%; p = 0.006). The long-term cardiac mortality was 25% versus 6% (p = 0.01), with an incidence of sudden death of 11% versus 3% (p < 0.05). Specificity, sensibility, positive predictive value and negative predictive value (reference cut point of 100) were 94, 65, 71 and 91%, respectively. CONCLUSIONS: The use of a score of arrhythmic pattern may identify 2 groups of patients with different clinic profiles that probably justify a different long-term prognosis after a first acute myocardial infarction.

Cardiac Complexes, Premature↗
PubMed1993

Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen.

We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambda gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA1. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules, and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function.

Amino Acid Sequence↗
PubMed1993

Characterization of insulin autoantibodies in relatives of patients with type I diabetes.

We studied in detail the anti-insulin autoantibodies in 29 nondiabetic relatives of patients with type I diabetes. The affinity of the autoantibodies for [125I]human insulin was high (1.34 x 10(9)-20.71 x 10(9) L/mol), and the capacity was low (0.84 x 10(-12)-37.80 x 10(-12) M). The product of affinity x capacity of each relative's antibodies directly correlated (r = 0.99) with the level of antibodies determined in our standard radioassay. The autoantibodies from each of the subjects studied had the same rank order of affinities for insulin from different species. Guinea pig, fish insulin, and insulin containing Trp rather than Leu in position 13 of the A-chain inhibited minimally the human insulin binding. Human proinsulin, insulin containing Gln rather than Glu in position 17 of the A-chain, and desoctapeptide insulin (des B23-30) all inhibited binding effectively. Insulin autoantibodies in relatives of patients with type I diabetes share common epitope(s), which suggests a common pathogenic mechanism for production of such antibodies. The epitopes from this initial analysis appear to include amino acids B1-B3 and A8-A13. The region recognized can be distinguished from the insulin receptor binding domain.

Adolescent↗
PubMed1991

Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type I diabetes.

Using serum from a prediabetic patient as a probe, we screened 0.5 x 10(6) recombinants from a rat islet lambda gt11 expression library. One plaque-producing antigen reactive with this prediabetic serum was identified, subcloned, and sequenced. Analysis of the sequence reveals that the clone encodes a 136-amino acid fragment of carboxypeptidase-H (enkephalin convertase). Carboxypeptidase-H is a molecule expressed within islet secretory granules and neurendocrine cells. The patient whose antibodies recognize this recombinant molecule (termed DG-1) was negative for anti-DG-1 antibodies in 1984, developed the antibodies by 1986, and remained positive until the development of diabetes in 1988. To date, serum from 5 of 20 cytoplasmic islet cell antibody-positive relatives reacted with the expressed protein, while none of 14 control sera reacted. On Western blotting, the initial patient's serum used for the screening reacts with a 52-kDa antigen corresponding to the mol wt of the membrane form of carboxypeptidase-N. The current study has identified carboxypeptidase-H as an autoantigen recognized by serum of pretype I diabetes, and the methodology used should aid in identification of additional autoantigens associated with type I diabetes.

Antibodies↗