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Biomedical subjects

A Ledda

Publications and source records attributed to A Ledda.

At least 37 records · Page 2Linked to original sources
PubMed1993

Association of the HLA-A2, CW2, B27, S31, DR2 haplotype with ankylosing spondylitis. A possible role of non-B27 factors in the disease.

With the aim of searching for HLA haplotypes and non-B27 allele frequency variations in Sardinian AS patients, HLA-A, B, Cw, DR, DQ and Bf, C4A and C4B typing and haplotype assignment was carried out in the families of 25 AS patients and in 44 healthy individuals, all B27 heterozygotes. In the AS patients a significant increase of the A2, Cw2, B27, DR2, DQ1 haplotype was found. This depends only partially on the linkage disequilibrium existing in the Sardinian population between B27 and the other alleles of this haplotype, and rather seems to be due to a primary association of Cw2 and DR2 alleles with AS. Preliminary data seem to show that this haplotype bears the S31 complotype and the DRB1*1601 allele both in the AS patients and in the healthy controls. The pathogenetic implications of these findings are discussed.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation combined with multiple anti-HIV-1 treatment in a case of AIDS.

A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow engraftment occurred after 18 days and tests for HIV-1 were negative after 30 days but the hematologic reconstitution of the patient was poor. A second BM infusion from the same donor was ineffective and treatment with GM-CSF only induced a transient increase of the blood cell count, suggesting iatrogenic damage to the BM microenvironment. The development of ARDS led to the death of the patient 10 months after transplantation. Post-mortem investigation did not reveal any active infections and PCR on autopsy tissues was negative for HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Study of HLA segregation in 479 thalassemic families.

479 families, each with a proband affected by homozygous beta-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between beta-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.

Alleles↗
PubMed1992

Role of family history in patients with myocardial infarction. An Italian case-control study. GISSI-EFRIM Investigators.

BACKGROUND: A family history of heart disease has been reported to increase the risk of coronary heart disease. We examined the relation between family history of myocardial infarction (MI) and risk of acute MI to establish the independency of this association, the degree of risk in relation to the number and age of relatives affected, and the possible interaction between family history and other major risk factors for MI. METHODS AND RESULTS: In a case-control study conducted in Italy within the framework of the GISSI-2 Trial, 916 cases of newly diagnosed MI and 1,106 hospital controls were identified. Using a structured questionnaire, data were collected on the history of MI in first-degree relatives and the age at which the event occurred. Compared with subjects without family history of MI in first-degree relatives, the relative risk (RR) of MI was 2.0 (95% confidence interval, CI, 1.6-2.5) in those with one and 3.0 (95% CI, 2.0-4.4) in those with two or more relatives affected (chi 2(1) test for trend, 54.1; p less than 0.001). Such an increase was not substantially affected by allowance for recognized risk factors. The risk related to family history involving at least two relatives was higher for early MI (less than 55 years) (RR, 20.0; 95% CI, 3.3-121.2) compared with later MI (less than or equal to 65 years) (RR, 3.5; 95% CI, 1.8-6.6). When known risk factors were considered for their interaction with family history, the effect on RR was approximately multiplicative for several variables, including smoking, serum cholesterol, hypertension, and hyperlipidemia but not for diabetes and body mass index. Thus, the presence of both family history and smoking and cholesterol levels greater than or equal to 226 mg/dl led to an RR of 14 (95% CI, 3.7-50.0) and 8.3 (95% CI, 1.8-38.7), respectively. CONCLUSIONS: This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI.

Case-Control Studies↗
PubMed1989

Absence of liver DNA fragmentation in rats treated with high oral doses of 32 benzodiazepine drugs.

Literature data on mutagenic-carcinogenic activity of benzodiazepines are scarce, restricted to few of them, and contradictory. Consequently, in order to provide additional information for the assessment of the genotoxic risk connected with the use of this family of drugs, 32 benzodiazepines of various chemical structure have been tested for their capability to induce DNA damage in vivo, which is considered a sensitive index of potential mutagenic-carcinogenic activity. The frequency of DNA single-strand breaks and/or alkali-labile sites was checked in the liver of rats given orally a single dose (1 mmol/kg) or 15 successive daily doses (0.2 mmol/kg) by the use of a new viscometric technique capable of detecting one DNA lesion per 10(10) Da. Statistically significant changes of viscometric parameters indicative of liver DNA fragmentation were absent with all 32 benzodiazepines, after both acute and subacute treatments. Since the doses tested in rats were from 100 to more than 5000 times higher than doses usually administered to humans, these negative results are in favor of the absence of mutagenic-carcinogenic effects in patients taking benzodiazepines.

Animals↗
PubMed1987

A computerized system for acquiring DNA solution viscosity data.

A new computerized system for monitoring time-dependent viscosity changes of DNA solutions is reported. It provides an extremely sensitive measure of DNA lesions induced by chemical carcinogens. The described apparatus consists of some precision mechanical modules, derived by an early manual version of the system, and of some new electronic parts as optical sensors, a microprocessor-based unit and a personal computer. The new system allows the analysis of more than one specimen at the same time. Compared with the early manual method of measuring, this computerized system, by removing subjectivity and a certain number of casual and systematic errors that might occur with the operator manual intervention, makes possible the evaluation of the resolving power of the viscometers themselves in detecting viscosity changes.

DNA↗
PubMed1987

Systolic anterior motion of the mitral valve in patients with hypertrophic cardiomyopathy. Disappearance after treatment with amiodarone.

We used amiodarone as the only drug in three consecutive patients with hypertrophic cardiomyopathy, marked systolic anterior motion of the mitral valve on M-mode echocardiogram, and paroxysmal atrial fibrillation. The effective control of atrial fibrillation was associated with good symptomatic relief and with reduction until disappearance of the systolic anterior motion of the mitral valve. These data were confirmed in a follow-up of 46, 30 and 30 months.

Adult↗
PubMed1986

Lack of DNA fragmentation in rats treated with high oral doses of drugs acting on the central nervous system.

Five drugs acting on the central nervous system-chlorpromazine, triflupromazine, thioridazine, chlordiazepoxide, and ethosuximide--which provided conflicting results in previous genotoxicity assays have been tested for their DNA-damaging activity in vivo. The capability of these drugs of inducing DNA fragmentation was investigated by the use of two different techniques: rate of DNA strand separation in alkali as measured by hydroxylapatite chromatography, and changes of DNA viscometric behavior as detected by a new highly sensitive method. DNA damage, as checked by the first technique, was absent in both liver and gastric mucosa of rats given a single p.o. administration of 1/2 LD50 of the drugs. These negative results were confirmed by the subsequent viscometric analysis of liver DNA from rats treated with the same doses.

Animals↗
PubMed1985

Viscometric detection of liver DNA fragmentation in rats treated with ten aromatic amines. Discrepancies with results provided by the alkaline elution technique.

A new viscometric technique, capable of detecting DNA strand breaks and alkali-labile sites by monitoring time-dependent changes of DNA reduced viscosity, has been used to evaluate DNA fragmentation in liver of rats treated with single i.p. doses of ten aromatic amines. Persistent and dose-dependent changes of DNA viscometric parameters, which are considered indicative of DNA fragmentation, were produced by six hepatocarcinogenic aromatic amines: 2-naphthylamine, benzidine, 2,4-diaminotoluene, auramine O, 4-aminoazobenzene, and 4-dimethylaminoazobenzene. In contrast, changes of liver DNA viscometric parameters were minimal and transient or practically absent in rats treated with aniline, 1-naphthylamine, 4,4'-oxydianiline and 2,4-diaminoanisole, all of which are devoid of hepatocarcinogenic activity. The comparison with data previously obtained with the alkaline elution technique demonstrates that the two methods can give different results, and that viscometrically-detected DNA damage is better correlated with carcinogenic activity than DNA damage detected by alkaline elution.

Amines↗
PubMed1984

Phase transitions in nuclei and chromatin. Is nuclear volume controlled by the chromatin or by the nuclear matrix?

Changes in the volume of rat liver nuclei have been monitored as a function of modifications in ionic environment (from 0 to 20 mM), temperature (from 4 to 37 degrees C), and pH (from 1 to 8). An abrupt reduction of nuclear volume occurred with increasing ion concentration, this contraction being more pronounced with bivalent (either Ca2+ or Mg2+) than with monovalent (either Na+ or K+) cations. The lowering of pH produced a similar effect. Parallel changes in chromatin structure took place at the same time as phase-like transitions. Atomic absorption spectroscopy allowed determination of free and nuclei-bound ions, pointing to the presence of a sizeable number of free binding sites for chromatin-DNA even within intact nuclei. DNA-phosphate sites appear to be neutralized by ions strictly according to the size of the electric charge and polyelectrolyte theory. Partial digestion (by micrococcal nuclease) or simple breaks (by chemical carcinogens) of the chromatin-DNA fiber caused respectively elimination or reduction of the abrupt volume changes in the intact nuclei. The apparent role of chromatin structure versus nuclear matrix in determining the shape and volume of intact nuclei is briefly discussed.

Animals↗
PubMed1983

Viscometric analysis of DNA damage in kidney and lung following exposure of rats to small doses of chemical carcinogens.

A new viscometric technique has been used to detect DNA damage in kidney and lung of rats treated with six chemical carcinogens. In alkaline conditions (pH 12.5) the reduced viscosity (eta red) of kidney and lung DNA from control rats increased slowly with time reaching a maximum, (eta red)max, after 9-12 h. Carcinogens, by inducing DNA strand breaks either chemically or indirectly by excision repair or during incubation in alkali, cause a reduction of DNA supercoiling which can be sensitively measured by monitoring changes in viscosity. Computerized analysis of time-viscosity curves showed that a statistically significant reduction of the time required for eta red to reach 95% of its maximum value (t-95) was induced by the following single i.p. doses: N-nitrosodimethylamine (DMN), kidney 0.07 mg/kg, lung 0.28 mg/kg; N-nitrosodiethylamine (DEN), kidney 3.2 mg/kg, lung 12.8 mg/kg; N-nitroso-N-methylurea, kidney and lung 0.5 mg/kg; 1,2-dimethylhydrazine (DMH), kidney 1 mg/kg, lung 16 mg/kg; 4-nitroquinoline-1-oxide (NQO), kidney 2.5 mg/kg, lung 0.63 mg/kg; 2-acetylaminofluorene, kidney and lung 12.5 mg/kg. The decrease of t-95 was constantly dose-related. The comparison with data previously obtained from liver demonstrates that DMN, DEN, DMH and NQO caused the greatest amount of DNA damage in the organ most susceptible to tumor induction. Viscosity changes elicited by DMN, DEN and DMH are quantitatively well correlated with the extent of DNA alkylation.

Animals↗
PubMed1983

Viscometric detection of liver DNA fragmentation in rats treated with minimal doses of chemical carcinogens.

A new technique, using an oscillating viscometer capable of measuring changes of DNA reduced viscosity (eta red), has been used to detect DNA damage in liver of rats treated with various chemical carcinogens. In denaturing conditions (pH 12.5), the eta red of liver DNA from control rats increased slowly with time, reaching a maximum, (eta red)max, after 10 to 13 hr. Single i.p. doses of N-nitrosodimethylamine (0.07 mg/kg), N-nitrosodiethylamine (0.2 mg/kg), N-nitroso-N-methylurea (0.5 mg/kg), 1,2-dimethylhydrazine (0.06 mg/kg), procarbazine (1 mg/kg), methyl methanesulfonate (8 mg/kg), and N-diazoacetylglycine amide (3.7 mg/kg) induced a statistically significant reduction of the time (t95) required for eta red to reach its maximal value. A dose-dependent decrease of t95 was observed for dosages markedly lower than those found to be effective in eliciting DNA fragmentation by the use of alkaline elution or alkaline sucrose gradient sedimentation. 2-Acetylaminofluorene (12.5 mg/kg) and 4-nitroquinoline 1-oxide (10 mg/kg) caused a clear-cut increase of (eta red)max. 7,12-Dimethylbenz(a)anthracene (10 mg/kg) markedly prolonged t95. This viscometric assay of in vivo DNA damage allows a reliable assessment of DNA lesions induced by doses of chemical carcinogens sufficiently small not to produce significant alterations in the pharmacokinetic behavior of these compounds.

Animals↗
PubMedDate not supplied

Serological and molecular studies of HLA in Sardinian patients with Graves' disease.

HLA Class I and Class II antigens were studied in 103 unrelated Sardinian patients with Graves' disease (GD), 71 of whom had ophthalmopathy, and in 220 healthy controls. Molecular typing of the DQB1 allelic variants was carried out on 34 GD patients and 35 healthy controls, selected for the HLA-DR2-DQw1 phenotype. The results of the serological typing showed a positive association with the DR2 and the DQw1 antigens and a negative association with DR3 and DQw2 antigens. These associations were stronger in the GD patients with ophthalmopathy. The DQB1 molecular analysis in patients with the HLA-DR2-DQw1 phenotype revealed the presence of the DQB1*0502 allele in 91.1 per cent of the patients and in 82.2 per cent of the controls. In the Sardinian population GD seems to present a different HLA association than that observed in other Caucasian populations (DR3-Dw24). The DR2 and DQw1 positive associations may be explained by the high frequency of the DQB1*0502 allelic variant (37.7 per cent) which is rare in the other Caucasian populations. The absence of an association between DR3 and GD in Sardinia can be attributed to the very low frequency of the HLA-B8-DR3 (Dw24) haplotype. In fact, in the Sardinian population, DR3 is associated with the allelic variant Dw25 carried by the HLA-B18-DR3 haplotype.

Adolescent↗