PubMed Health⌕ Search

Biomedical subjects

M Trucco

Publications and source records attributed to M Trucco.

At least 163 records · Page 9Linked to original sources
PubMed1992

Susceptibility to type 1 (insulin-dependent) diabetes mellitus in Spanish patients correlates quantitatively with expression of HLA-DQ alpha Arg 52 and HLA-DQ beta non-Asp 57 alleles.

HLA-DQ alpha and beta alleles were chosen as the most sensitive Type 1 (insulin-dependent) diabetes mellitus susceptibility markers for evaluating the disease associations and Type 1 diabetes risk in a population-based registry from Madrid. The absence of aspartic acid in position 57 of the DQ beta chain (non-Asp 57), and the presence of arginine in position 52 of the DQ alpha chain (Arg 52) were found to be reliable markers of Type 1 diabetes susceptibility among the Spanish population, with significantly higher frequencies among the cases of Type 1 diabetes compared to randomly selected non-diabetic control subjects from the general Madrid population. While non-Asp 57 homozygosity conferred an absolute risk of 32.3 per 100,000 per year and Arg 52 of 31.5 per 100,000 per year, the risk for double homozygotes for both non-Asp 57 and Arg 52 was estimated as 101.7 per 100,000 per year. Individuals homozygous for only one of these alleles, and heterozygous at the other locus, had a markedly lower Type 1 diabetes risk (12.8 per 100,000 per year), approximating the general population incidence for Madrid. Thus, susceptibility to Type 1 diabetes in Spanish patients is associated, quantitatively, with non-Asp 57 DQ beta and Arg 52 DQ alpha alleles.

Alleles↗
PubMed1992

Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine. Clinical, neuroradiological and neurophysiological study on 9 cases.

Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is considered to be uncommon in western countries, although widely known and studied in Japan. We report on 9 cases of OPLL cervical myelopathy investigated by x-ray films and cervical CT and by somatosensory evoked potentials. The patients reported spastic tetraparesis, sensory disorders of the limbs and, in one case, sphincter incontinence. Neuroradiological examinations showed that the posterior columns of the spinal cord were more affected than the roots. Our data suggest that OPLL is more frequent in the West than has so far been reported and that combined radiological and neurophysiological investigation ensures correct diagnosis and accurate assessment of the cord impairment.

Aged↗
PubMed1992

Hemicrania continua: a case responsive to piroxicam-beta-cyclodextrin.

The case of a 53-year-old woman is described, who since the age of 38 years had been suffering from a unilateral headache that was at first remitting, but then evolved into an unremitting course. The headache was burning in quality, located in the left forehead and face, and was accompanied by mild ipsilateral autonomic symptoms. The clinical picture, as well as the absolute response to indomethacin, suggested a diagnosis of hemicrania continua. The presence of mild gastric discomfort on continuous indomethacin administration made us transfer the patient to another NSAID (piroxicam-beta-cyclodextrin). With this drug, complete relief and good tolerability was obtained.

Chronic Disease↗
PubMed1992

[Workers exposed to styrene: application of a neuropsychological evaluation computer system].

The purpose of this study was to adapt and apply a battery of neuropsychological tests administered by computer. The study comprised three phases: 1) An existing system (NES-2) was revised and adapted (mainly in its Spanish version, since the structure and time intervals were the same). 2) A pilot group of 18 subjects was administered the five selected tests. 3) A comparative study of 36 exposed workers with 40 unexposed controls was undertaken. It was concluded that computer-administered tests are acceptable and economic. No significant differences were found between exposed. The possible reasons for the negative findings are discussed, as well as the types of future studies that need to be carried out.

Adolescent↗
PubMed1991

Prevalence of HLA-DQ beta chain non-Asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset.

Particular HLA-DQ beta chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogeneous German population, we studied HLA-DR specificities and HLA-DQ beta chain alleles in young-onset (less than 21 years of age; n = 185) and adult-onset (greater than 40 years of age; n = 48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQ beta chain was significantly associated with type I diabetes in both cohorts (etiologic fraction: 93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQ beta chain provides a molecular risk marker for type I diabetes of both and adult onset.

Adolescent↗
PubMed1991

Mouse NKR-P1. A family of genes selectively coexpressed in adherent lymphokine-activated killer cells.

NK cells are a subpopulation of large granular lymphocytes. They are able to recognize and lyse a wide variety of virally infected or neoplastic target cells without previous sensitization or MHC restriction. The molecules involved in target recognition and subsequent triggering of the killing process are still undefined. Recently, a 30-kDa protein highly expressed on rat NK cells and capable of mediating transmembrane signaling was identified and the gene coding for it cloned and sequenced. To better understand the role of this protein in NK cell-mediated cytotoxicity, we cloned its mouse homologue by cross-hybridization of the rat gene to a cDNA library generated from highly purified mouse lymphokine-activated NK cells. Three messages, differing in size and sequence and encoded by different genes, are specifically cotranscribed in mouse NK cells. The protein products of this gene family express the lectin-like motif characteristic of type II transmembrane molecules. Both the rat and mouse proteins have conserved tyrosine and serine residues in their cytoplasmatic portion that are potential phosphorylation sites. They also share a sequence that could be the binding site of the P56lck tyrosine kinase. These observations are consistent with the signaling function hypothesized for these proteins.

Amino Acid Sequence↗
PubMed1991

Aspartic acid at position 57 of the HLA-DQ beta chain is protective against future development of insulin-dependent (type 1) diabetes mellitus.

Insulin-dependent (Type I) diabetes mellitus is a chronic autoimmune disease. From studies in discordant twins and multiplex families a long prediabetic period has been reported. In a population-based program started in 1983, fifteen individuals at possible risk for future Type I diabetes were followed for up to 74 months. Two individuals (13%) developed Type I diabetes. These probands were characterized by the presence of high-level cytoplasmic islet cell antibodies (ICA), complement-fixing ICA, and an impaired first-phase insulin response after intravenous glucose load. Both were homozygous for a high-risk immunogenetic marker of Type I diabetes, i.e., non-Asp at codon 57 of the HLA-DQ beta chain. In all other subjects studied, the immunogenetic marker that confers "dominant resistance", aspartic acid at codon 57, was found. On the basis of our data we conclude that a combination of assays which determine ICA, first-phase insulin release, and HLA-DQB1 polymorphisms will identify individuals with a high probability of developing Type I diabetes at the population level. Conversely, HLA haplotypes positive for aspartic acid seem to confer resistance to the disease.

Adult↗
PubMed1991

A new HLA-DR2 extended haplotype is involved in insulin-dependent diabetes mellitus susceptibility.

To ascertain why HLA-DR2 seems to confer only a moderate resistance to insulin-dependent diabetes mellitus (IDDM) in the high-incidence population of Sardinia, Italy, 32 families having one individual affected with IDDM (the proband) and 31 families without IDDM history were randomly selected from the same geographical area and serologically and molecularly HLA typed. The 64 haplotypes of the probands were then compared with the 122 haplotypes determined in the parents from the control families. Two haplotypes were found to have the highest percentage in the general population (12.3% and 7.3%, respectively). The first is the already described "Sardinian" extended haplotype A30, Cw5, B18, 3F130, DR3, DRw52, DQw2 (39.0% in IDDM patients). The second is an extended haplotype that has not been identified before (A2, Cw7, B17, 3F31, DR2, DQw1), and, due to the DR2 allele, we expected it to be decreased in IDDM. However, a stratified analysis performed by removing the DR3 and DR4 haplotypes showed that the frequency of this haplotype is significantly increased in IDDM patients. A peculiar feature of this haplotype is its DQw1 allele, which is DQB1*0502 and has serine in position 57 of the DQ beta chain. The absence of an aspartic acid in this position seems to confer susceptibility to IDDM and not resistance. The fact that DQB1*0502 was present in 75% of the Sardinian DR2 haplotypes may explain why, in Sardinia, DR2 is not providing the commonly recognized resistance to IDDM.

Autoimmune Diseases↗
PubMed1991

Genetics of diabetes. Genes and environment.

Many other autoimmune and chronic diseases exhibit marked geographic variation in incidence, which has been attributed to environmental differences across populations (Hutt and Burkitt, 1986). The results of our international IDDM research have provided evidence for the importance of large genetic variations in the frequency of HLA susceptibility genes between racial groups and countries. One may speculate that differences in the prevalence of susceptibility genes for other chronic diseases exist and significantly contribute to the geographic patterns of incidence of these disorders. Other autoimmune diseases are known to have epidemiological features similar to those described for IDDM. Although they are also characterized by an underlying HLA-related susceptibility, environmental factors are known to play an important aetiological role (Tiwari and Terasaki, 1985). DNA polymorphisms of the DR, DQ and DP locus antigens are associated with various autoimmune diseases (Todd et al, 1988; Thorsby et al, 1989). These molecular variations are similar to those described for IDDM, in that they are typically related to the hypervariable regions of the molecule and, thus, affect the peptide binding ability of the antigen. Based on the evidence for IDDM, population differences in the frequency of other HLA susceptibility genes are likely to be major determinants of the geographic distribution of diseases such as rheumatoid arthritis and multiple sclerosis. The epidemiological approach outlined in this review is, thus, applicable to other autoimmune diseases and will significantly contribute to our knowledge of the aetiology of these disorders. The emerging field of molecular epidemiology represents a new research approach which will lead to a better understanding of the relationships between specific risk factors and the aetiology of chronic diseases within populations and across the world.

Diabetes Mellitus, Type 1↗
PubMed1991

The HLA-DQ beta non-Asp-57 allele: a predictor of future insulin-dependent diabetes mellitus in patients with autoimmune Addison's disease.

HLA-DR specificities in 72 Addison's (AD) patients and 808 local controls were compared. We confirmed earlier reports that the HLA-DR3 specificity is significantly increased in AD patients. In our study a relative risk of 3.4 chi 2 = 22.5; pc = 0.01) for the disease was calculated. Analysis of HLA-DQB1 alleles in DR4+ Addison's patients with diabetes mellitus (N = 6) and without IDDM (14 of 18 individuals tested) revealed that the HLA-DQw8 allele (DQB1*0302) was significantly increased in AD patients with IDDM (chi 2 = 13.5; p = 0.001); conversely, a clustering of the HLA-DQw7 allele was detected in DR4+ Addison's patients without IDDM. We thus conclude that particular polymorphic alleles corresponding to non-charged amino acids at position 57 of the HLA-DQ beta-chain [non-Asp-57 alleles] are associated with IDDM also in Addison's patients.

Addison Disease↗
PubMed1991

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Adolescent↗
PubMed1991

The interface between epidemiology and molecular biology in the search for the causes of insulin-dependent diabetes mellitus.

Epidemiological techniques have been utilized to accumulate new knowledge about insulin-dependent diabetes mellitus (IDDM), leading to important insights into the disease process and the alteration of these mechanisms when viewed from a geographic or population base. More recently, highly powerful and sophisticated techniques of molecular biology have been added to the research arsenal, extending the knowledge on the genetic basis for IDDM and the probable environmental factors involved. The development and growth of the new discipline of epidemiological genetics promises exciting new developments for the future of our field as well as that of other major medical problems having a genetic base, but significantly influenced by environmental factors. This review stresses the importance of carefully validated diabetes registries in the study of the epidemiology of IDDM. The Children's Hospital of Pittsburgh and the University of Pittsburgh Medical Center have spear-headed the development of such registries, worldwide. The first international meeting on IDDM epidemiology in 1983 gave as a result, i.e., the finding that there were truly remarkable differences in the risk of developing IDDM depending upon the geographic location of the individual. Later collaborative work via the Diabetes Epidemiology Research International (DERI) group has confirmed the previous finding and added the description of secular trends and epidemics of IDDM. It is remarkable that the incidence rate of IDDM in children below 15 years vary from 1/100,000/yr in the Orient to 35/100,000/yr in Finland. The epidemiological approach in the study of IDDM has also stimulated research into the various facets of the etiology of the disease, genetic factors, autoimmune mechanisms and environmental factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1991

High-resolution linkage mapping for susceptibility genes in human polygenic disease: insulin-dependent diabetes mellitus and chromosome 11q.

Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic inheritance. In addition to genes mapping to the major histocompatibility complex (MHC), several lines of evidence point to the existence of other genetic susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a set of polymorphic DNA markers from chromosome 11q to investigate this region for linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data were investigated by maximization of lod scores over genetic models and by multiple-locus affected-sib-pair analysis. We were able to exclude the presence of a susceptibility gene (location scores less than -2) throughout greater than 90% of the chromosome 11q homology region, under the assumption that the susceptibility factor would cause greater than 50% of affected sib pairs to share two alleles identical by descent. Theoretical estimates of the power to map susceptibility genes with a high-resolution map of linked markers in a candidate region were made, using HLA as a model locus. This result illustrates the feasibility that IDDM linkage studies using mapped sets of polymorphic DNA markers have, both for other areas of the genome in IDDM and for other polygenic diseases. The analytic approaches introduced here will be useful for affected-sib-pair studies of other complex phenotypes.

Chromosome Mapping↗