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Biomedical subjects

A Ledda

Publications and source records attributed to A Ledda.

28 records · Page 2Linked to original sources
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↗
PubMedDate not supplied

Unrelated bone marrow transplantation in a Wiskott-Aldrich syndrome patient sharing two HLA-extended haplotypes with the donor.

We report a case of BMT from an unrelated donor (MUD) in a patient affected by Wiskott- Aldrich syndrome (WAS). The donor-recipient pair was completely identical for two HLA-extended haplotypes. The conditioning regimen consisted of Bu 14 mg/kg followed by CY 200 mg/kg. GVHD prophylaxis was carried out with CsA plus short-term MTX. Allogeneic engraftment was obtained without any signs of acute or chronic GVHD. At fifteen months from the transplant the patient was in an excellent clinical condition. This case confirms the role of BMT from MUD in WAS, and suggests that complete donor-recipient identity for two entire HLA-extended haplotypes is a particularly favorable immunogenetical condition in this type of transplant.

Adult↗