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Biomedical subjects

C Nesti

Publications and source records attributed to C Nesti.

At least 19 recordsLinked to original sources
PubMed2004

Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia.

BACKGROUND: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by multiple organ involvement. The prevalence of thyroid disorders in MC has not yet been studied. AIM: To investigate the prevalence and clinical features of thyroid involvement in patients with HCV-associated MC (HCV + MC). DESIGN: Case-control study. METHODS: HCV + MC patients (n = 93, 17 men and 76 women, mean +/- SD age 63 +/- 10 years, mean disease duration 14 +/- 7 years) consecutively referred to the Rheumatology Unit were matched by sex and age (+/- 2 years) to (i) 93 patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV-negative) controls from the local population. Measurements included prevalence of hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid cancer. RESULTS: By McNemar's chi(2) test, the following thyroid abnormalities were significantly more frequent in HCV + MC patients than in HCV-negative controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p = 0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p = 0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035). DISCUSSION: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia. We suggest careful monitoring of thyroid function in these patients.

Aged↗
PubMed2003

Type 2 diabetes in hepatitis C-related mixed cryoglobulinaemia patients.

OBJECTIVES: Mixed cryoglobulinaemia (MC) is a systemic vasculitis frequently associated with hepatitis C virus (HCV) infection. A possible link between HCV infection and type 2 diabetes has been suggested. This study evaluated the prevalence and clinical phenotype of diabetes in MC-HCV+ patients. METHODS: Two hundred and twenty-nine consecutively recruited MC-HCV+ patients were compared with 217 sex- and age-matched controls without HCV infection. RESULTS: The prevalence of type 2 diabetes was significantly higher in MC-HCV+ patients than in controls (14.4 vs 6.9%, P < 0.01). Diabetic MC-HCV+ patients were leaner than diabetic patients without MC-HCV (P < 0.0001), and showed significantly lower total and low-density lipoprotein cholesterol levels (P < 0.001) and lower systolic (P = 0.01) and diastolic blood pressure (P = 0.005). MC-HCV+ diabetic patients had non-organ-specific autoantibodies more frequently (34 vs 18%, P = 0.032) than non-diabetic MC-HCV+ patients. CONCLUSIONS: The prevalence of type 2 diabetes is higher in patients with MC-HCV than in controls. Diabetic MC-HCV+ patients show an attenuated diabetic phenotype and are more likely to carry non-organ-specific autoantibodies.

Aged↗
PubMed2002

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes.

AIMS/HYPOTHESIS: Autoantibodies against CD 38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i). overlaps with anti-GAD autoimmunity, (ii). identifies an insulin-deficient phenotype, (iii). is under the influence of genetic factors. METHODS: We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). RESULTS: CD 38-autoantibodies were found in 8.4% of Type II diabetic patients ( p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD 38 ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti- CD 38 positive had DQB1*02 compared with 38% of anti-CD 38 negative ( p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired ( p=0.02) only in association with anti-GAD positivity (3.2+/-3.1 U/mol, mean +/- SD) but not in anti- CD 38 positive patients (5.6+/-2.9) as compared with patients free of autoimmunity (4.5+/-4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti- CD 38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD 38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. CONCLUSION: Anti-CD 38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.

ADP-ribosyl Cyclase↗
PubMed2001

Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease.

Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD(+) and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading > 3 s.d. higher than the mean value of control I, 10.4% of patients with thyroiditis and 7.7% of Graves' patients were anti-CD38 positive (P = 0.0009 versus 1.8% of control I). Similarly, 13.1% of patients with thyroiditis and 10.5% of Graves' patients had a standardized optical reading > 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0.002 versus 1.2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0.03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0.05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated.

ADP-ribosyl Cyclase↗
PubMed2000

Cytokinesis-block micronucleus assay in primary human liver fibroblasts exposed to griseofulvin and mitomycin C.

Primary liver fibroblasts were applied in a cytokinesis-block micronucleus assay in combination with fluorescence in situ hybridization (FISH) using two protocols. In protocol A (Prot. A), cytochalasin B (Cyt B) was added at the end of the treatment time directly to the medium containing the standard compounds, whereas in protocol B (Prot. B) the chemical-containing medium was removed and fresh medium with Cyt B was added. The study was performed using the aneugen griseofulvin (GF) and the clastogen mitomycin C (MMC) as standard compounds. With both protocols GF induced a significant increase in MN frequency over controls in a dose-related manner at the lower concentrations tested (7.5 and 15 microg/ml). At the highest dose (30 microg/ml) the aneugen effect was substantially reduced. MN induction obtained with Prot. A was significantly higher ( approximately 3-fold) than with Prot. B at the most effective concentration. The aneugen effect induced by GF did not change when different cell densities were used, but again with Prot. A we obtained the highest effect. MN induced by MMC showed a dose- and time-dependent increase in both protocols. In contrast to GF, the greater clastogenic response induced by MMC in human liver fibroblasts was obtained with Prot. B, approximately 3-fold higher than Prot. A at the most effective concentration and approximately 2-fold with 24 h treatment at 0.17 microg/ml MMC. With GF, the FISH data in human liver fibroblasts (80% C+MN) were fairly consistent with those obtained in the rodent cell lines. In human whole blood cultures, the same dose used in our experiment produced a relatively higher percentage of C+MN. FISH analysis showed that MMC induced mainly MN containing acentric fragments rather than whole chromosomes. In conclusion we have demostrated that chemically induced genetic effects are strongly dependent on the cell culture employed, treatment schedule and intra- and post-treatment experimental conditions.

Antifungal Agents↗
PubMed1999

Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts.

The capability of some metal compounds for inducing micronuclei (MN) in human lymphocytes was studied. In this investigation, Al (III), Cd (II), Hg (II), Sb (V), Te (VI), and Tl (I) salts were considered. The FISH (fluorescence in situ hybridization) technique with a centromeric probe was coupled with the MN assay in binucleated cells in order to detect both centromere-positive MN (C+ MN) due to malsegregation phenomena and centromere-negative MN (C- MN) due to chromosome breakage. The blood of two young nonsmoking male donors was employed for all experiments. In both donors, all the tested metal compounds, with the exception of Tl(2)SO(4), showed a statistically significant increase of MN compared to controls, at least at one dose. FISH analysis revealed an increase in the fraction of C+ MN for Al, Cd, and Hg compounds, and of C- MN for the Sb salt; however, this was not a statistically significant increase. A different efficiency was observed for the different metal compounds, in particular, KSbO(3) and CH(3)HgCl, which were highly genotoxic, whereas the others showed minimal effects.

Alum Compounds↗
PubMed1999

Expression of a novel human sialidase encoded by the NEU2 gene.

Sialidases (E.C.3.2.1.18) belong to a group of glycohydrolytic enzymes, widely distributed in nature, which remove sialic acid residues from glycoproteins and glycolipids. All of the sialidase so far characterized at the molecular level share an Asp block, repeated three to five times in the primary structure, and an F/YRIP sequence motif which is part of the active site. Using a sequence homology-based approach, we previously identified a human gene, named NEU2, mapping to chromosome 2q37. NEU2 encoded protein is a polypeptide of 380 amino acids with two Asp block consensuses and the YRIP sequence in the amino terminal part of the primary structure. Here we demonstrate that NEU2 encodes a functional sialidase. NEU2 was expressed in COS7 cells, giving rise to a dramatic increase in the sialidase activity measured in cell extracts with the artificial substrate 4-MU-NANA. Using a rabbit polyclonal antiserum, on Western blots a protein band with a molecular weight of about 42 kDa was detectable, and its cytosolic localization was demonstrated with cell fractionation experiments. These results were confirmed using immunohistochemical techniques. NEU2 expression in E.coli cells allowed purification of the recombinant protein. As already observed in the enzyme expressed in COS7 cells, NEU2 pH optimum corresponds to 5.6 and the polypeptide showed a K(m)for 4-MU-NANA of 0.07 mM. In addition, based on the detectable similarities between the NEU2 amino acid sequence and bacterial sialidases, a prediction of the three-dimensional structure of the enzyme was carried out using a protein homology modeling approach.

Amino Acid Sequence↗
PubMed1998

Isonymy and isolation by distance in Germany.

The isonymy structure of Germany was studied using the surname distributions of 5,150,310 private telephone users selected from 39,000,000 users registered in a 1996 commercial CD-ROM, which contains all telephone users in the country. The users were distributed in 106 towns selected on a geographic basis. Germany was subdivided into 50 adjacent rectangles, each 115 x 80 km, and at least the largest town in the rectangle was selected for study; the private telephone users in that district were downloaded from the CD-ROM and included in the analysis. The shortest distance between nearest neighbor towns was 10.7 km (Travemunde and Lübeck), and the largest distance was 69.8 km (Meppen and Osnabruck). The number of different surnames found in the whole analysis was 462,526. Lasker's distance, the negative value of the logarithm of isonymy between localities, was found to be linearly and significantly correlated with geographic distance (r = 0.51 +/- 0.010). A dendrogram was built with the matrix of isonymy distances, using UPGMA. This method separates the German towns into two main clusters, one in the southern half of the country and the other in the northern half. Within each cluster small subclusters with specific geographic distributions could be delimited. The two main clusters correspond fairly well to the north-south division of German sublanguages (Nieder- and Mitteldeutsch in the north vs. Frankisch-Alemannisch in the south). The other clusters are related to minor sublanguages. Comparisons with the results of a previous analysis of Switzerland's structure are given. From the present analysis isolation by distance emerges clearly, although it is less strong than in Switzerland and indicates that Germany has a fairly homogeneous isonymy structure. The random component of inbreeding estimated from isonymy indicates that eastern Germany is on average more inbred than western Germany.

CD-ROM↗
PubMed1998

Clinical validity of the elbow flexion test for the diagnosis of ulnar nerve compression at the cubital tunnel.

We evaluated the elbow flexion test in 216 elbows without compression of the ulnar nerve at the cubital tunnel and without other neuropathies. We used Rayan's four positions as our test. The percentage of positive tests was only 3.6% at one minute, whereas evaluating the responses at three minutes we saw positive results in 16.2%. Therefore we find that if the test is performed for one minute it may be useful to help in diagnosing ulnar nerve compression at the cubital tunnel.

Adult↗
PubMed1996

Correlation between age and DNA damage detected by FADU in human peripheral blood lymphocytes.

Fluorometric analysis of DNA unwinding (FADU) is a fast and reliable method for detecting single strand DNA breaks as an index of DNA damage induced by clastogenic agents. A study of damage detected by FADU was conducted on DNA extracted from peripheral blood lymphocytes of 128 healthy nonsmoking regular donors (ranging in age from 19 to 67 years) and from 5 umbilical cord blood samples. DNA damage was measured as percentage of unwound DNA after alkalinization. Statistical analyses, both parametric (Pearson r correlation coefficient, b regression coefficient, ANOVA) and nonparametric (Kruskal-Wallis H test, Spearman rs rank correlation coefficient), support a significant correlation between age of donors and amount of DNA damage. The same results are found when adult donors are divided in four age classes and the ANOVA test performed among the mean percentages of unwound DNA of each class. Furthermore, donors of the same age belonging to different blood groups (A, B, AB and O) do not show any difference in DNA damage detected by FADU.

Adult↗
PubMed1995

Phylogeny inferred from codon usage pattern in 31 organisms.

We employed the Codonusage database to analyze the codon usage pattern in 31 organisms from all the main biological taxa. We tested the similarity in codon usage pattern between each organism and all the others by the Pearson linear correlation coefficient. The 465 values obtained were located in a 31 x 31 triangular matrix from which a correlation distance matrix was calculated. An evolutionary dendrogram was then constructed from these distances. The results showed a fair correlation between codon usage patterns and phylogenetic relationships, at least for organisms which diverged in rather recent times (end of Jurassic--beginning of Cretaceous).

Animals↗
PubMed1994

Possible identity of transcription and translation signals in early vital systems.

The distribution of codons was analysed in three classes of eukaryote proteins having widely different evolutionary rates: 78 histones, 40 tubulins, and seven fibrinogens. In this set of genes, (i) it was confirmed that codons which are components of known transcription signals, like ATA, are used infrequently when a synonym is available, particularly in the more constrained proteins, and (ii) it was observed that the three codons which have an iso-accepting transfer with anticodon UAA, UAG or UGA are also suppressed. Then, the distribution of UAA, UAG and UGA trimers was studied in 498 tDNAs and 198 rDNAs. It was found that these trimers are weakly but significantly suppressed in tDNAs and to a lesser extent in rDNAs. It was advanced that the present suppression of ATA, which codes for Methionine in several mitochondria, and of the TAA, TAG and TGA trimers in tDNAs, might be an indication that at the very early stages of the evolution of translation and transcription the signals for initiation and termination were shared by the two processes.

Amino Acid Sequence↗
PubMed1994

Codon usage and evolutionary rates of proteins.

The 61 codons and the three terminators were counted in the coding sequences of 31 families of proteins of higher vertebrates. The protein families were ordered according to their evolutionary rate. In each family, the ratio between the Observed and Expected frequency of each codon was obtained (O/E ratio). A strong and significant positive correlation was observed between the O/E ratio of the eight codons AAC, TAT, ATA, GAA, ACA, AAT, ATG and CGA and the evolutionary rate of the protein. A negative and significant correlation was observed for codons AAG and GAG. It was advanced that the functional constraints of proteins can influence the usage of codons, particularly for those trimers which are components of signal sequences. It was also observed that the O/E ratios of the terminators are negatively correlated with the evolutionary rate of the protein they terminate, and the correlation is significant for TAA and TGA, which in vertebrates might be older than TAG.

Animals↗
PubMed1994

A set of Alu-free frequent decamers from mammalian genomes enriched in transcription factor signals.

We have recently reported that the statistical analysis of the frequency distribution of short oligonucleotides within mammalian and viral genomes allows the production of sets of DNA sequences enriched in signals for transcription factors. Such statistical approaches could facilitate the identification of new promoter regions playing a role in the transcriptional regulation of gene expression. In the case of mammalian oligonucleotides, we found that the published set of frequent decamers enriched in transcriptional motifs is not suitable for studies on genes of Homo sapiens and evolutionarily related genomes, because it contains decameric sequences belonging to genomic repeats. We report here that most of the decameric sequences of DNA repeats belong to Alu repeats. Accordingly, we produced a subset of Alu-free frequent decamers. In addition, we eliminated from the subset of Alu-free frequent decamers those that are frequently present within other common human repeats, including (GT)n, (AT)n, (CA)n, (ATT)n, (CAA)n and (GTT)n. The Alu-free (repeats-free) subset of frequent mammalian decamers is enriched in signals for transcription factors and allows the identification of putative signals in genes, such as those coding for plasminogen activator, adenosine deaminase and p53, that contain a large number of Alu-like repeats interspersed within our genomic sequences. The newly generated compilation of frequent decamers described here might be used to locate genomic regions playing functional roles in the expression of genes of Homo sapiens and related primates.

Animals↗
PubMedDate not supplied

Isonymy and the genetic structure of Switzerland. I. The distributions of surnames.

The surname distribution of the population of Switzerland was studied using a sample of 1,702,000 private users registered for the year 1994 in the Helvetic Telephone Directory. These users were distributed in four linguistic areas, in 26 Cantons and 271 Communes of the Confederation. Estimates of unbiased random isonymy, of Fisher's alpha, an indicator of abundance of surnames converging to the allele effective number in standard genetic polymorphisms, and of Karlin-McGregor's v, an indicator of immigration rates, were calculated for each Commune, each Canton, each linguistic area and for the whole Confederation. The Commune with the highest value of alpha was Geneva (alpha = 5312) followed by Versoix (3713) and by the Communes of Vaud on the north shore of Lake Leman, Chavannes (3381), Montreux (3200), Nyon (3114) and Lausanne (3109). The Italian-speaking Communes of the Ticino were next. The lowest value (alpha = 29) was observed in Poschiavo, south of the Berninapass; alpha = 39 was observed in Einsiedeln (Schwyz); then Mels and Widnau (62 and 67, Canton of St Gallen), Frutingen in Bern (72), and Appenzell (80). Accordingly, the highest consanguinity values were observed in the Grisons and in the nucleus of the founding Cantons, while the lowest were observed in the Cantons of Geneva and Vaud, preferential areas of immigration to Switzerland from abroad. The effect of subdivision on isonymy is large at the Commune level, and decreases in Cantons and linguistic groups. French and Italian languages indicate minor, German and Romanisch major inbreeding.

Data Collection↗
PubMedDate not supplied

Isonymy and the genetic structure of Switzerland. II. Isolation by distance.

Isolation by distance in Switzerland was detected comparing the surname distributions between Cantons. The decay of isonymy with geographic distance between Cantons was consistent with Malecot's exponential decay of kinship. Lasker's distance was defined as the negative value of the logarithm of isonymy between localities, and it was found that it is linearly and significantly correlated with the log of geographic distance, both within and between languages. The peculiar geographic and linguistic structure of the Confederation, where mountain barriers exist at short distances separating different languages, might explain the rapid changes in surname similarity. It was predicted that the frequency of markers linked to the Y chromosome would show a similar association with distance in Switzerland.

Genetics, Population↗