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N Del Grosso

Publications and source records attributed to N Del Grosso.

12 recordsLinked to original sources

The ATT strand of AAT.ATT trinucleotide repeats adopts stable hairpin structures induced by minor groove binding ligands.

AAT.ATT is the most abundant and also the most frequently polymorphic class of trinucleotide repeats in the human genome. To characterize its structural properties and conformational changes induced by minor groove ligands, (AAT)(6) and (ATT)(6) oligomers as well as their complexes with DAPI were investigated by electrophoretic mobility and UV thermal stability as well as fluorescence and NMR spectroscopy. The results show that individual (AAT)(6) and (ATT)(6) strands exist principally as monomeric non-hydrogen-bonded structures. Their individual interaction with DAPI induces the formation of base-paired structures with different thermal stabilities by quite spectroscopically distinct binding mechanisms. In the presence of DAPI, (ATT)(6) forms a monomeric hairpin structure stabilized by two ligands located in the minor groove with a strong apparent binding constant of 3.4 x 10(6) M(-)(1). The DAPI-induced (ATT)(6) hairpin is characterized by well-stacked A.T Watson-Crick and T.T wobble base pairs, a high electrophoretic mobility, and a melting temperature of 41 degrees C. Interaction of DAPI with the complementary (AAT)(6) strand favors less stable base-paired structures, and the results are consistent with electrostatic and hydrogen-bond interactions of the ligand with the phosphodiester backbone of (AAT)(6) by minor involvement of DNA bases.

Base Pairing↗

Italian family with cranial cervical dystonia: clinical and genetic study.

A white Italian family affected by primary torsion dystonia (PTD) is described. The family phenotype most commonly presented with adult onset, cranial cervical involvement, and focal or segmental distribution without progression to generalization. Thirty-nine family members and nine spouses were studied. Five subjects received a diagnosis of definite PTD, three of probable PTD. Age at onset was in adulthood for all. In four definitely affected subjects, dystonia started in the cranial or cervical districts; in one it presented as writer's cramp. Familial writer's cramp also occurred in the family of the unrelated parent of the latter patient. The mean age at time of examination was 61.8 years in the individuals with a definite diagnosis; 60 in those with a probable diagnosis. At the time of examination, in most of the affected subjects, dystonia was focal; in three cases (two definitely and one probably affected), it was segmental. DNA linkage analysis, although limited by the size of the family, suggested exclusion of linkage between the disease and known PTD loci (DYT6 and DYT7). The GAG deletion in the DYT1 gene was excluded in the proband and in the family member affected by writer's cramp.

Adult↗

Non-DYT1 dystonia in a large Italian family.

A large non-Jewish Italian family affected by idiopathic torsion dystonia with autosomal dominant transmission and almost complete penetrance is reported. The prevalent phenotype was characterised by early onset with cranial-cervical involvement and progression to a segmental distribution; progression to generalisation was also found. Among 45 people examined, 14 were considered definitely or probably affected by idiopathic torsion dystonia. Eight definitely affected members had mean age (SD) at onset of 15.6 (12.5); idiopathic torsion dystonia started in the cranial-cervical region in six of them, in the upper limbs in two; in four cases dystonia progressed to other body regions, in two cases a generalisation was seen. Linkage analysis with 9q34 markers excluded the region containing the DYT1 locus in this family; linkage to the dopa-responsive dystonia markers was also excluded. A comparison of the phenotype in the present family and other non-DYT1 families shows striking overlapping features differing from those of DYT1 idiopathic torsion dystonia.

Adult↗

Cell cycle analysis by the relative movement approach: effect of variability across S-phase of DNA synthesis rate.

Cell populations pulse-labelled with BrdUrd, and sampled at increasing times after the pulse, yield DNA-BrdUrd distributions from which the relative movement (RM) and the depletion function (DF) of labelled, undivided cells can be calculated. In this paper we present an extension of the equation for the time course of RM, given by White and Meistrich (Cytometry 1986, 7, 486-490), to the case in which the rate of DNA synthesis changes across S-phase. Some modalities of cell loss were also considered. Computer simulations showed that different patterns of DNA synthesis rate across S-phase can result in appreciably different RM curves. An analytical expression of the RM curve, in which the variability across S-phase of the rate of DNA synthesis is accounted for by only one parameter, was proposed. This expression was used for the simultaneous fitting of time sequences of RM and DF data of U937 cells, in order to estimate the phase transit times TS and TG2+M, and the potential doubling time Tpot. The use of the extended model gave better results than those obtained under the assumption of constant rate of DNA synthesis across S-phase.

Bromodeoxyuridine↗

1H NMR study of [d(GCGATCGC)]2 and its interaction with minor groove binding 4',6-diamidino-2-phenylindole.

Two-dimensional NMR spectroscopy has been applied to study the solution binding of 4',6-diamidino-2-phenylindole (DAPI) to synthetic DNA duplex [d(GCGATCGC)]2. The structure of the complex at a molar ratio of 1:1 drug:duplex has been investigated. NMR results indicate that DAPI binds selectively in the minor groove of the DNA region containing only two A:T base pairs. The results disagree with conclusions drawn from footprinting experiments and show that the presence of the G3NH2 group in the minor groove does not prevent the binding. A molecular model is proposed that closely resembles the crystal structure previously published for the interaction of DAPI with the dodecamer [d(CGCGAATTCGCG)]2, containing four A:T base pairs in the binding site. In this model, DAPI lies in the minor groove, nearly isohelical, with its aromatic rings adjacent to H4' protons of T5 and C6 deoxyribose and the NH indole group oriented toward the DNA axis. The binding does not perturb the B-type conformation of the duplex, and the DNA oligomer conserves its 2-fold symmetry, indicating that fast exchange dynamics exist between the two stereochemically equivalent binding sites of the palindromic sequence. The binding constant and the exchange rate between free and bound species were also measured by NMR spectroscopy.

Base Sequence↗

Neutralizing antibodies against 33 human adenoviruses in normal children in Rome.

There are few data about the distribution of neutralizing antibodies (NA) against adenovirus types in the Italian population, especially the high-numbered ones. We tested the sera from 453 children and 51 young adults to evaluate NA against adenovirus prototypes 1-33. Using the microneutralization test, 338 (74.6%) of the children's sera were positive for at least one adenovirus type. Antibody to type 2 was the most frequently detected followed, in descending order, by antibody to types 5, 1 and 3. All these types are known to be associated with disease but antibody to type 7, a type also associated with disease, was less frequent than that to other serotypes such as 18 and 31, the pathogenicity of which in man is not clearly established. The antibody positivity rate rose with age for the more frequent types while it did not vary for the less frequent ones. The number of sera with NA against more than one adenovirus type increased with age. With regard to types 1-8, we found that their frequencies in Italy were similar to those found in the U.S.A.

Adenoviruses, Human↗

Neurological and electroencephalographic abnormalities after febrile seizures. Possible association with cytomegalovirus.

In order to assess the possible association of cytomegalovirus (CMV) with cerebral damage, 65 children aged between 2 and 10 years were tested for CMV isolation and antibody status. All of them had previously presented one or more episodes of febrile convulsions. At the time of our study, they were grouped according to their clinical features and electroencephalogram (EEG). 21 had typical and/or atypical absence attacks with 3 c/s spike-wave EEG (primary generalized epilepsy), 21 presented febrile seizures and spontaneous fits with focal EEG abnormalities, 23 had no seizures and a normal EEG. We performed the same investigation in 41 healthy children. The study showed a similar isolation rate of CMV in healthy subjects and in patients without neurological and EEG alterations, while a significantly higher isolation rate was observed in the groups with neurological and EEG abnormalities. As for serology, no significant difference was observed between the four groups, although the positivity rate of the healthy children was lower than in the other three groups. The study suggests a possible association of CMV with neurological and EEG abnormalities after febrile seizures.

Antibodies, Viral↗

[Conditioning of active type avoidance in the rat : effect of the interval between conditioned stimulus and unconditioned stimulus].

Lengthening the time interval between the conditioned stimulus and the unconditioned stimulus increases the number of active avoidance conditioned responses in subjects that have been trained to a stable level of performance in many previous conditioning sessions. In the present research, rats chosen from a population specially selected for low rates of avoidance conditioning have been used. In addition to this characteristic, subjects were chosen for the exhibition of an apparent absence of retention from one day to another. The dependency of the number of conditioned responses on the time interval between conditioned stimulus and unconditioned stimulus may lead to wrong evaluation of the subjects' conditioning level. In fact, the level of conditioning may be attributed to either learning or memory processes when in many cases it is determined only by the latency time of the conditioned response. The conditioned response has no possibility of manifesting itself when its latency time exceeds in length the time interval between conditioned stimulus and unconditioned stimulus.

Animals↗

[Methods for grading the strength of passive conditioned avoidance reaction].

Three methods for obtaining passive avoidance conditioned responses of different strength are described. The first method consists of delayed reinforcement, constituted by a foot-shock, in the conditioning trial. The second method corresponds to the "detention" procedure, through which the animal is kept in one part of the apparatus for some time, after the conditioning trial. The third method consists of using foot-shocks of different strength in the conditioning trial. This method, however, is not advisable in most cases, since it produces strong differences in the subjects' level of arousal after conditioning and therefore a different reactivity to the various treatments.

Animals↗