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M Capone

Publications and source records attributed to M Capone.

At least 37 records · Page 2Linked to original sources
PubMed1995

T cell development in TCR-alpha beta transgenic mice. Analysis using V(D)J recombination substrates.

The major pathway of intrathymic T cell differentiation leads CD4-8- (DN) T lineage-committed precursors to TCR-alpha beta+ CD4+8- or CD4-84+ (SP) T lymphocytes. The expression of functionally rearranged TCR-alpha beta transgenes (Tg-TCR) may influence thymocyte development by affecting the various selection events that control T cell differentiation. To gain insights into these processes, we have produced double transgenic animals carrying V(D)J recombination substrates in addition to the MHC class I (H-2Kb) allospecific KB5C20 Tg-TCR. We have analyzed substrate rearrangements in purified populations of Tg-TCR+ thymocytes in the situation of positive or negative selection. The profile of rearrangements found in SP thymocytes, positively selected for the Tg-TCR, suggests that expression of the KB5C20 Tg-TCR has only a minimal influence on substrate V(D)J recombination in cells differentiating along the major alpha beta T cell developmental pathway. In contrast, Tg-TCR+ DN thymocytes, in both positively and negatively selecting haplotypes, presented a profile that implies premature cessation of substrate rearrangements. This profile was maintained in peripheral Tg-TCR+ DN cells and was distinct from the one found in CD25+, alpha beta+, or gamma delta+ DN cells purified from mice transgenic for the recombination substrates only. These results are discussed with respect to the possible origin and differentiation pathway of Tg-TCR+ DN and SP cells.

Animals↗
PubMed1995

The V(D)J recombinational and transcriptional activities of the immunoglobulin heavy-chain intronic enhancer can be mediated through distinct protein-binding sites in a transgenic substrate.

Immunoglobulin and T-cell receptor gene transcriptional enhancers encompass sequences which stimulate V(D)J recombination of associated variable gene segments. To address the question of whether enhancer-mediated transcriptional activation and recombinational activation depend on the same cis-regulatory sequences, we have produced transgenic mice by using recombination substrates containing various mutations in the immunoglobulin heavy-chain intronic enhancer (E mu). Analysis of substrate rearrangements indicated that specific compound elements including E-box transcriptional motifs are crucial for the recombinational activity of E mu in the developing B and T lymphocytes. In most cases, a faithful correlation between the levels of substrate germ line transcription and recombination was observed. However, some of the E mu mutants which were able to activate transcription of the unrearranged substrate were inefficient in stimulating transgene recombination, implying that the latter function depends on molecular events other than the mere activation of transcription and that both activities can be mediated through distinct regulatory sequences. Together, these results support a model in which lymphoid gene enhancers, in addition to providing docking sites for factors that dictate transcriptional accessibility, must have some specific function(s) for activating V(D)J recombination.

Animals↗
PubMed1994

Sequences affecting the V(D)J recombinational activity of the IgH intronic enhancer in a transgenic substrate.

The immunoglobulin heavy chain intronic transcriptional enhancer (E mu) is part of a complex cis-regulatory DNA region which has notably been shown to modulate V(D)J rearrangements of associated variable gene segments. We have used recombination substrates comprised of the E mu enhancer together with various lengths of additional downstream mu sequences to assess the individual contribution of those sequences to the V(D)J recombinational regulatory activity. Surprisingly, in the absence of large amounts of mu sequences, substrate rearrangements were not detected in Southern blot analyses of the lymphoid tissues from independent transgenic mice, but were readily detectable following transfection into cultured pre-B cells. A short mu segment which includes matrix association regions (MARs) was not sufficient to restore high levels of rearrangements within the reporter transgenes. However, additional experiments demonstrated that the mu sequences are dispensable for V(D)J recombination in transgenic thymuses, implying a suppressive effect exerted by the vector sequences left in the transgenic insert, when they are attached near the E mu regulatory region. This suppression of V(D)J recombination, which correlates with an hypermethylation of the transgenes, is discussed in view of previously reported transgenic and gene targeting experiments.

Animals↗
PubMed1993

TCR beta and TCR alpha gene enhancers confer tissue- and stage-specificity on V(D)J recombination events.

We describe transgenic mice carrying germline variable gene segments associated with either the T cell receptor (TCR) beta or alpha gene enhancers (E beta or E alpha). Transgenic constructs underwent high rates of site-specific rearrangements predominantly in T cells from independent mice. Rearrangements of the E beta-containing transgenes began at different stages of T cell differentiation in embryonic and adult thymus than did the E alpha-containing ones, with a pattern superimposable upon the patterns of TCR beta or TCR alpha gene expression, respectively. We demonstrate that sequences within the TCR beta and TCR alpha gene enhancers confer tissue- and stage-specificity upon the V(D)J recombination events affecting adjacent gene segments. The patterns of transgene expression also gave information on developmental events and lineage relationships (gamma delta versus alpha beta) during T cell development.

Aging↗
PubMed1992

[Involvement of the urogenital system in HIV virus infection].

Despite the genitourinary system is prone to infections by the Human Virus of Immunodeficiency, so far poor interest has been focused on urological manifestations of AIDS. We thoroughly reviewed the Literature and examined the different patterns of HIV infections on the kidneys, the prostate and the testes. An extensive description is given.

HIV↗
PubMed1989

Treatment of reversible chronic airways obstruction with doxofylline compared with slow-release theophylline: a double-blind, randomized, multicentre trial.

A multicentre, double-blind, randomized trial was carried out in 11 Italian Pneumologic Clinics to investigate the therapeutic efficacy and tolerability of doxofylline compared with slow-release theophylline in 139 patients (86 males, 53 females) aged 17-77 years suffering from reversible chronic airways obstruction. The two groups of 69 patients on doxofylline and 70 patients on theophylline did not differ in their baseline clinical and functional parameters. After one week of wash-out, the two drugs were administered orally at a dose of 400 mg twice daily of doxofylline and 300 mg twice daily of theophylline. The treatment and follow-up lasted 28 days. Inhaled salbutamol on demand was allowed in the wash-out week and throughout the trial. The average serum levels at day 14 and 28 were: doxofylline 7.5 and 8.5 micrograms/ml; theophylline 10.4 and 7.95 micrograms/ml respectively. Both drugs significantly increased spirometric parameters (p less than 0.001 for all tests) and significantly reduced salbutamol consumption (p less than 0.001 for both drugs). Doxofylline was better tolerated than theophylline considering either the number of unwanted side-effects: (doxofylline 12; theophylline 37) or number of drop-outs due to side-effects (doxofylline 5; theophylline 10). From these results doxofylline seemed to be a good alternative to theophylline in the treatment of reversible chronic airway obstruction in view of its better safety profile.

Adolescent↗
PubMed1987

[Medium- and long-term clinical study on the use of the new non-steroidal anti-inflammatory drug flunoxaprofen in osteoarthrosis].

The efficacy and the tolerability of the new non-steroidal antiinflammatory agent flunoxaprofen was assessed in the long-lasting management of pain and joint motility impairment of 28 patients suffering from radiologically proven osteoarthritis localized on the large joints (hip and knee). The patients were treated with flunoxaprofen 200-400 mg/day per os for 2 months (18 patients) or for 4 months (10 patients) and the following variables were assessed: spontaneous diurnal and nocturnal pain, pain on passive motion, pain on active motion with or without load, quality of sleep, joint motion range, intercondylar and intermalleolar straddles and gluteus-heel straddle; patients' and physician' evaluation of flunoxaprofen efficacy. Moreover a number of clinical and laboratory controls were carried out to study the tolerability of the drug (arterial blood pressure, heart rate, hepatic and renal function tests, haematological examination). The assessments were made before the starting of the treatment and at 15-day intervals thereafter. The results show that all variables for pain intensity greatly and progressively improved during flunoxaprofen treatment; the quality of sleep as well as the joint motion range improvement went along the progressive decrease in pain intensity. None of the clinical and laboratory parameters studied showed any modification during flunoxaprofen treatment. No side-effects were observed in any patients, either after 4 months treatment or using 400 mg/die. It is concluded that flunoxaprofen may be considered an effective and safe non-steroidal antiinflammatory agent in the long-lasting management of pain and joint motility impairment of osteoarthritic patients.

Aged↗
PubMed1976

[Heredity of twinning in families of monozygotic twins (author's transl)].

Whereas the existence of some genetic factor underlying the phenomenon of twinning is almost generally accepted with respect to DZ twins, no such agreement exists with respect to MZ twins. The possible existence of genetic factors underlying MZ twinning has been verified through an analysis of segregation in the sibships of MZ twins and in those of their parents, carried out on a sample of 57 MZ twin pairs (30 M and 27 F). Haldane's a priori method has been applied, considering the sample as obtained through a complete and through an incomplete ascertainment. The results may lead to cautiously confirm the hypothesis of some genetic conditioning of MZ twinning.

Alleles↗