Biomedical subjects

P Ghetti

Publications and source records attributed to P Ghetti.

At least 19 recordsLinked to original sources

PubMed1997

Chromosomal fragility in the cancer-prone disease xeroderma pigmentosum preferentially involves bands relevant for cutaneous carcinogenesis.

Spontaneous and folate-induced chromosomal fragility was analyzed in peripheral blood lymphocytes from 6 patients affected by the cancer-prone disease xeroderma pigmentosum (XP), from the parents of 4 of the patients, and from 12 normal subjects. All XP patients were defective in nucleotide-excision repair; 4 belonged to group C and 1 each to groups A and D. A tendency toward increased spontaneous chromosomal fragility was observed in the XP family members, and lesions indicating substantial chromosomal damage, which were not observed in any healthy donors, were frequently found. The spontaneous lesion sites in lymphocytes from homozygous and heterozygous carriers of XP defects appeared to be significantly associated with those observed in normal skin fibroblasts from the same subjects. These XP spontaneous fragility sites showed a statistically significant association with the rearrangement breakpoints reported in skin pre-tumoral and tumoral lesions from normal and unrelated XP donors. Under conditions of folate deprivation, the chromosomal fragility level, the pattern and the frequency of expression of fragile sites in XP patients and in their parents were similar to normal. However, XP patients generally showed a higher susceptibility to breakage at sites described as mutagen and carcinogen targets.

Adolescent↗

PubMed1997

Solid-state investigation of fluocinolone acetonide.

Three crystalline modifications of fluocinolone acetonide, A, B and C, were characterized by means of FTIR, DSC, TG-FTIR, MICRO-FTIR and X-ray diffractometry. They were easily differentiated by their IR absorption bands in the 3600-3400 cm-1 range. The thermal behavior was also elucidated using combined techniques; thermomicroscopy and thermogravimetry coupled with Fourier transform infrared spectroscopy were found to be very useful tools for a better understanding of thermal events. On heating, form A and C were fully converted into form B. Polymorph A was found to be enantiotropically related to B, while form C was monotropically related to B. The existence of three polymorphs was confirmed by means of their different X-ray diffraction patterns. Detailed methods of preparation of the three modifications are also described.

Administration, Topical↗

PubMed1994

Dyschromatosis symmetrica hereditaria associated with idiopathic torsion dystonia. A case report.

The authors report a case of a family in which a diagnosis of dyschromatosis symmetrica hereditaria was established by a clinical pattern of cutaneous lesions and by assessment of cellular DNA repair synthesis. The skin lesions were characterized by a mixture of hyperpigmented and hypopigmented macules and were localized on the back of the feet of three patients (two male brothers and one sister). All the patients also had small freckle-like pigmented macules on their face. The father presented large symmetrical hypopigmented vitiligo-like macules. In this patient, mottled pigmentation and depigmentation of the extremities had been present since childhood. In the four patients no cellular abnormalities in DNA repair ability were found. These data exclude a mild form of xeroderma pigmentosum. The daughter, a 9-year-old girl, had since the age of 7 also shown a neurological disorder diagnosed as idiopathic torsion dystonia. The authors emphasize the association of dyschromatosis symmetrica hereditaria, a rare cutaneous disease, with idiopathic torsion dystonia, a rare idiopathic neurological disease, in this young girl.

Adolescent↗

PubMed1994

Lack of major mitochondrial bioenergetic changes in cultured skin fibroblasts from aged individuals.

Human skin fibroblasts from young and old donors were cultured in vitro and compared in their mitochondrial morphology and function. A decreased numerical density of mitochondria in the fibroblasts from old individuals was balanced by the increased size of individual mitochondria. The mitochondrial membrane potential, estimated in the intact cells by the difference between the total accumulation ratio of the lipophilic cation tetraphenylphosphonium and the accumulation ratio in presence of uncoupler, was unchanged, as were some mitochondrial enzymatic activities tested in the homogenates. The results point out that the decreased proliferating capacity observed in the fibroblasts from the old subjects was accompanied by a likely decrease of mitochondrial duplication; the decreased energy utilization for cell division balances a possible energetic decline in such way that the steady-state energy status is unchanged.

Aging↗

PubMed1992

Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun-exposed portions of the skin and a reduced capacity to repair the u.v.-induced DNA damage. One of the XP mutations (XP-D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell-mediated immunity has been proposed as a co-factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN) alpha and beta on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN-alpha or IFN-beta, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN-alpha or IFN-beta. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients.

Abnormalities, Multiple↗

PubMed1992

Trisomy 21 mosaicism in two subjects from two generations.

In the course of a chromosome fragility investigation on the cancer prone hereditary disorder xeroderma pigmentosum, a low proportion of cells with a 47,XY,+21 karyotype was found in lymphocyte cultures of a patient not showing any Down syndrome symptom. The presence of trisomy 21 mosaicism was demonstrated also in peripheral blood of the healthy father and confirmed by "chromosome painting" that allowed a rapid detection of chromosomes 21 on metaphase cells and interphase nuclei. The trisomic cell line was not detected in fibroblast cultures. The analysis of chromosome 21 heteromorphism indicated that in both subjects the mosaic could result from either a diploid or an aneuploid zygote. Since in the trisomic cell line of the father and the son the extra chromosome 21 seems to be the same, a predisposition toward mitotic errors (non-disjunction or anaphase lagging) may be postulated, leading to the recurrent gain or loss of a specific chromosome 21. In order to test the hypothesis of an abnormal mitotic behaviour of the chromosome 21, we investigated the centromere separation index and the DNA restriction pattern in Southern blots probed with satellite DNA sequences specific for chromosome 21 centromere. Both the approaches did not reveal any peculiar feature that may account for the genetically determined proneness to mitotic error observed in the family.

Adult↗

PubMed1991

Chromosome rearrangements in normal fibroblasts from xeroderma pigmentosum homozygotes and heterozygotes.

Chromosome analysis was carried out in cultured fibroblasts from unaffected skin of five unrelated xeroderma pigmentosum (XP) patients and nine family members. Structural chromosome changes were observed in cultures from all examined individuals. Furthermore, in one XPD patient and in one XPC patient and his parents, cytogenetically abnormal clones were detected. Some of these clones were present starting from the primary explant. This cytogenetic pattern is similar to that observed in an XPC patient previously studied by us. The analysis of breakpoint distribution from clonal and non-clonal chromosome rearrangements showed that some breakpoints were more frequent and common to different families or to different family members although definite evidence of preferential involvement of chromosome bands was not obtained. This investigation indicates that there is a consistent tendency toward chromosome instability in XP mutation carriers. The instability could be related to the multiple chromosome anomalies characterizing skin tumors in XP subjects.

Adolescent↗

PubMed1989

[Thymopentin in the treatment of recurrent condylomata acuminata].

Twelve patients who had been suffering from genital and/or perianal recurrent condyloma acuminatum for a minimum of 5 to a maximum of 24 months, in spite of treatment, were studied from the immunological viewpoint and treated with 50 mg s.c. Thymopentin three times a week for 4 or 6 weeks. Six of the patients were cured at the end of treatment, five after 5 months, and one was not cured. Analysis of the clinico-laboratory data shows a significant agreement between the course of clinical signs and the immunological picture. The various cure stages are probably attributable to the basic immune arrangement which was more impaired in the 5 patients who were cured more slowly and in the non-cured case. In the latter too, however, Thymopentin permitted correcting the balance of the relationship between the various lymphocyte subpopulations.

Adjuvants, Immunologic↗

PubMed1988