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F Torricelli

Publications and source records attributed to F Torricelli.

At least 19 recordsLinked to original sources
PubMed2005

Pharmacogenomics education: International Society of Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education.

Pharmacogenomics would be instrumental for the realization of personalized medicine in coming decades. Efforts are evident to clarify the potential bioethical, societal, and legal implications of key pharmacogenomics-based technologies projected to be soon introduced into the core practice of medicine. In sharp contrast, a lack of sufficient attention to educational aspects of pharmacogenomics, both for professionals and for society at large, is evident. In order to contribute to this discussion, a 'Pharmacogenomics Education Forum' was held on October 2, 2004 during the 3rd Annual Meeting of the International Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members of the ISP Pharmacogenomics Education Forum, after deliberate discussions, proposed a document of 'Background Statement' and 'Recommendations and Call for Action' addressed to Deans of Education at Medical, Pharmaceutical, and Health Schools globally. This document has been considered by the education committee of the International Society of Pharmacogenomics and the result is presented here. We hope that this call would be listened to, and soon followed by beneficial action, ultimately leading to enhanced implementation of personalized medicine into core medical education and practice.

Curriculum↗
PubMed2004

Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B.

BACKGROUND: Balanced X;autosome translocations interrupting the 'critical region' of the long arm of the human X chromosome are often associated with premature ovarian failure (POF). However, the mechanisms leading to X-linked ovarian dysfunction are largely unknown, as the majority of the X chromosome breakpoints have been mapped to gene-free genomic regions. A few genes have been found to be interrupted, but their role has never been clarified. METHODS AND RESULTS: By fine mapping of the X chromosome breakpoint of an X;autosome balanced translocation, we identified a new interrupted gene, POF1B. We performed a mutation analysis of POF1B and of another gene previously identified, DACH2, localized approximately 700 kb distal in Xq21, in a cohort of >200 Italian POF patients. Rare mutations were found in patients in both genes. CONCLUSIONS: Our findings could not demonstrate any involvement of POF1B, but suggest that rare mutations in the DACH2 gene may have a role in the POF phenotype.

Adolescent↗
PubMed2002

Anderson-Fabry disease with cerebrovascular complications in two Italian families.

We describe four patients with cerebrovascular complications from two unrelated Italian families with Anderson-Fabry disease. Clinical examination, neuroimaging (MRI), biochemical and genetic analyses were carried out in all the patients. Alpha-galactosidase A activity was detected by fluorimetric assay and genetic analysis was performed by DNA sequencing. Family 1. A male patient presented recurrent strokes when he was 34 years old, albuminuria and subsequently progressive renal failure to renal transplantation. Family 2. A male patient, aged 32 years, had diplopia for a few days and then recurrent strokes with left spastic hemiparesis and internuclear ophthalmoplegia. A female patient, aged 48 years, presented L-dopa-responsive parkinsonism, and her sister had stroke when she was 55 years old. MRI was abnormal in all the patients and showed lacunar infarctions in the periventricular white matter, basal ganglia and pons. Lesions were detected by MRI even before stroke in a female patients. In patients with Anderson-Fabry disease, stroke is a frequent complication, and may be the first threatening clinical manifestation. In young people with undefined stroke, even without signs of renal involvement, it is important to consider the diagnosis of Anderson-Fabry disease and so to perform clinical examination and biochemical analyses. The pre-clinical stage of cerebrovascular involvement may be evaluable by MRI.

Adult↗
PubMed2001

Possible case of Pitt-Hopkins syndrome in sibs.

In this article, we describe two sibs, a brother and sister, with severe mental retardation and multiple congenital anomalies including "coarse" facial features, short stature, seizures, hypertrichosis, short great toes, and overbreathing. Comparison of these patients with previous reports suggests that they could represent the first familial cases of the Pitt-Hopkins syndrome. The recurrence in sibs within the same family supports autosomal recessive inheritance for the condition. Variable expression of the respiratory symptoms, which has not been reported earlier, is underlined.

Abnormalities, Multiple↗
PubMed2001

Use of primed in situ labeling (PRINS) for the detection of telomeric deletions associated with mental retardation.

Rearrangements involving the telomeric regions of human chromosomes are often associated with mental retardation. These rearrangements, however, are difficult to detect using conventional cytogenetic techniques. We propose the use of primed in situ (PRINS) labeling as an alternative to fluorescence in situ hybridization because it is very fast, reproducible, and simple to perform. Sixty-five children with unexplained mental retardation were studied using PRINS technology; two of them were shown to have a telomeric deletion.

Base Sequence↗
PubMed2001

Isolation of fetal cells from the maternal circulation: prospects for the non-invasive prenatal diagnosis.

The research into non-invasive and invasive prenatal diagnostic techniques developed almost in parallel. On the one hand the need was arising to ensure the birth of normal progeny in all cases, while on the other, it was not possible to eliminate the abortion risks connected with the invasiveness of amniocentesis (risk of abortion 1/200), chorion villi sampling, (risk of abortion 2%) and funicolocentesis (risk of abortion 3-4%). One of the first researchers in the non-invasive field was Adinolfi who published the earliest data in 1974 on the possibility of detecting three types of fetal cells in the maternal circulation using flow cytometry. Adinolfi suggested the possibility of using fetal cells present in the maternal circulation for prenatal diagnosis of chromosome or biochemical anomalies. Our review takes into consideration the latest methodological and technical progress in relation to the study of fetal cells in maternal circulation, without considering cells present in the endocervical canal where from the 8th week of pregnancy it is only possible to obtain trophoblast cells. This technique has since been abandoned due to the scarcity of cellular material available, the greater risk of contamination by cells of maternal origin, and also because the recovery of the cells is unpredictable, despite their potential use for the early non-invasive diagnosis of sex. The following issues are addressed in this review: the characterization of the fetal cell types present in the maternal circulation, the methods of their separation and enrichment, and the methods of genetic diagnostics applied.

Cell Separation↗
PubMed1998

Hearing loss due to the mitochondrial A1555G mutation in Italian families.

Six Italian families with familial nonsyndromic hearing loss consistent with a maternal pattern of inheritance were analyzed for mitochondrial mutations. The three known mitochondrial mutations associated with nonsyndromic hearing loss were investigated by polymerase chain reaction amplification, followed by restriction fragment length analysis or DNA sequencing. The A7445G mutation and C7472 insertion were not present in either of the families, but the A1555G mutation in the 12S rRNA gene was identified in homoplasmic form in two of the families. In one of the families the onset of hearing loss is congenital, while in the other it starts later in life. The families are from different regions of Italy, and mitochondrial haplotype analysis showed that the mutation arose independently in these two families. This suggests that the A1555G mutation may not be an uncommon cause of hearing loss in Italians, and is clinically important because maternal hearing relatives of patients with the A1555G mutation are at risk for aminoglycoside induced deafness. We discuss potential reasons for the normal phenotype in some relatives with the mutation, and the different onset of hearing loss in the two families.

Adolescent↗
PubMed1998

Differential inhibitory effects on human endometrial carcinoma cell growth of luteinizing hormone-releasing hormone analogues.

In addition to its function as a key hormone in the regulation of the pituitary-gonadal axis, luteinizing hormone-releasing hormone (LHRH) probably also affects various extrapituitary tissues. LHRH binding sites and in vitro antiproliferative effects of LHRH analogues have been reported in human endometrial cancer. The effects of the LHRH agonist leuproreline and LHRH antagonist antide were studied on the cell growth, DNA synthesis, and cell cycle distribution of the human endometrial cancer cell lines HEC-1A and HEC-1B by the sulforhodamine B (SRB) method, [3H]thymidine assay incorporation, and propidium iodide DNA staining, respectively. In the presence of 1.0-100 microM leuproreline the proliferation of HEC-1A cells was significantly reduced as early as 3 days after drug exposure, with a minimum growth value of 69.9 +/- 3.6% (mean +/- SE) at the highest concentration tested (100 microM). Similar antiproliferative effects were obtained following a 6-day treatment with the LHRH antagonist antide. Also, inhibitory effects on [3H]thymidine incorporation into the DNA of the HEC-1A cell line were noted after a 6-day exposure to both LHRH analogues, in the above-mentioned concentration range. Cell cycle analysis of HEC-1A cells cultured in the presence of 10 microM leuproreline and antide showed a slight accumulation of cells in the G0/G1 phase, while the proportions of cells in the S and G2/M phases concomitantly decreased. No significant effects on proliferation, DNA synthesis, and cell cycle distribution were observed in HEC-1B cells with either leuproreline or antide (up to 100 and 10 microM, respectively) after a 6-day exposure. Both Northern blot analysis and reverse transcription polymerase chain reaction failed to detect expression of mRNA for the LHRH receptor in both HEC-1A and HEC-1B cell lines. In addition, the LHRH analogues did not affect the intracellular free calcium concentration, indicating that the classic signal transduction for LHRH is absent or impaired in HEC-1A cells. The observed direct inhibitory actions on HEC-1A cells support the concept that the two LHRH analogues may exert biological effects via cellular effectors distinct from the "classic" LHRH receptor. Although the mechanism by which these direct actions are produced is still obscure, these results might help to establish the basis for new approaches to the therapy of endometrial cancer.

Antineoplastic Agents, Hormonal↗
PubMed1996

Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy.

First-trimester chorion villosum plays the key role in the development of human placenta and secretes a large number of hormones and hormone-related substances. To test whether progesterone and estrogen could have regulatory effects on first-trimester chorion villosum functions, we investigated the presence of progesterone receptor (PR) and estrogen receptor (ER) in 47 chorion villosum samples from patients who underwent abortion during the first trimester of pregnancy. The study was carried out using immunohistochemical methods. No ER and PR positivity was evidenced in the 47 chorion villosum samples examined. The possibility that progesterone and estrogen play a role in the regulation of chorion villosum functions should therefore be excluded.

Antibodies, Monoclonal↗
PubMed1995

Maternal serum CA 125 levels in first trimester abortion.

OBJECTIVE: To assess the source of maternal serum CA 125 during the first trimester of pregnancy. STUDY DESIGN: CA 125 was measured in stored samples from nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome analysis of the products of conception demonstrated a normal caryotype were included. CA 125 levels were expressed in multiples of the median (MoM) for normal pregnancies of the same gestational age. RESULTS: Median MoM values of CA 125 were significantly higher in women with vaginal bleeding (1.81 MoM) as compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found between non-bleeding women and controls. CONCLUSIONS: The present study indicates that in non-viable pregnancies with euploid fetuses an increase in maternal serum CA 125 levels was found only in presence of decidual disruption associated to vaginal bleeding. These findings are compatible with a prevalent decidual source of this antigen.

Abortion, Spontaneous↗
PubMed1995

Amniotic fluid levels of CA 19.9 and CA 15.3 in normal and Down's syndrome pregnancies.

CA 125, CA 19.9 and CA 15.3 are antigenic determinants on glycoproteins commonly used as serum markers in gynecologic oncology. CA 125 was also investigated in the amniotic compartment of Down's syndrome pregnancies. The objective of this study was to evaluate the concentration of CA 19.9 and CA 15.3 in the amniotic fluid of normal and Down pregnancies. The concentration of these antigens was measured in stored amniotic fluid samples from 15-19 weeks pregnancies with and without Down's syndrome fetuses and expressed in multiples of the median for normal pregnancies of the same gestational age. The study group included 20 samples selected from single Down's syndrome pregnancies. Each of these samples were matched with three control samples from unaffected pregnancies, matched for maternal age, gestational age and duration of storage of the sample. The median MoM values of CA 19.9 and CA 15.3 in Down's syndrome pregnancies were respectively 1.11 MoM and 1.16 MoM, not significantly different from those of unaffected pregnancies (CA 19.9: 1.02 MoM; CA 15.3: 0.99 MoM). In the present study we have not found significantly different levels of CA 19.9 and CA 15.3 in the amniotic fluid of fetuses affected by Down's syndrome and in the controls.

Amniotic Fluid↗
PubMed1994

Decidual progesterone and estrogen receptors in the first trimester of pregnancy.

Receptor content of human decidua in early pregnancy (weeks 6-12) was investigated. Fifty-three tissue samples were obtained from voluntary patients undergoing abortion and whose gestational age range from 6 to 12 weeks. Blood samples were drawn at the time of operation in order to measure circulating estradiol (E) and progesterone (P) concentrations. Tissue samples underwent first histological confirmation and then were analyzed for receptor content by immunohistochemistry (IH) and by the conventional ligand binding technique (LBA). Estrogen receptors (ER) appeared to be always undetectable by IH (53 samples). LBA measured a significant amount of ER (> 10 fmol/mg) in two samples, borderline values (3-10 fmol/mg) in 6 and no binding in the other three. No relation was apparent between PR levels and either gestational age or blood P concentration. ER were possibly downregulated by the high E levels, and their synthesis inhibited by the high P levels.

Adult↗
PubMed1994

The predictive value of cytogenetic diagnosis after CVS based on 4860 cases with both direct and culture methods.

Cytogenetic analysis was performed in 4860 chorionic villus samples by means of both direct preparation and long-term culture. The results of the analysis were compared with a classification including all theoretical types of combinations between the chromosomal constitution of the cytotrophoblast, extraembryonal mesoderm, and fetus, with the aim of evaluating the cytogenetic variability along the trophoblast-embryo axis. Eighteen of 29 possible combinations were found demonstrating a considerable heterogeneity. A mosaic conceptus was found in 1.5 per cent of cases, with generalized mosaicisms and confined mosaicisms in 0.2 and 1.3 per cent, respectively. Cytogenetic variability along the trophoblast-embryo axis was found in 1.42 per cent of cases. Results possibly leading to diagnostic errors (false-positive and false-negative results) were found in only 1.38 per cent. False-positive results of direct preparation were the most commonly observed discrepancy (0.8 per cent), while the incidence of false-positive results of the culture method and of both methods was 0.31 and 0.16 per cent respectively. The incidence of false-negative results was 0.1 per cent, with false-negative results of direct preparation 0.08 per cent and false-negative results of both methods 0.02 per cent. False-negative results of the culture method were not found. Our data confirm the high diagnostic accuracy of chorionic villus sampling and the utility of the combined use of the two methods in minimizing diagnostic errors and in reducing the need for follow-up amniocentesis.

Chorionic Villi Sampling↗
PubMed1994

Cytogenetic effects on human lymphocytes of a mixture of fifteen pesticides commonly used in Italy.

Lymphocytes obtained from 5 healthy donors were incubated with a mixture of 15 pesticides commonly found in foods of central Italy (dithiocarbamates (20.7%), benomyl (19.6%), thiabendazole (14.9%), diphenylamine (14.4%), chlorthalonil (13.1%), procymidone (8.0%), methidathion (2.3%), chlorpyrifos-ethyl (2%), fenarimol (1.9%), parathion-methyl (1%), chlorpropham, parathion, vinchlozolin, chlorfenvinphos and pirimiphos-ethyl (< 1%)). The percent of each pesticide in the mixture was proportional to its average concentration in foods. Incubated with the lymphocytes at a concentration of 1-20 micrograms/ml the pesticide mixture did not induce significant variations in the number of hypodiploid, hyperdiploid and polyploid cells or in the number of chromosome and chromatid aberrations. On the contrary, we observed a dose-dependent increase in the number of nonsynchronous centromeric separations which reached the level of 37.9% at 20 micrograms/ml of pesticide mixture in the incubation medium. This effect was not observed when benomyl was excluded from the mixture. These data show that the removal of benomyl could decrease the toxicity of pesticide residues present in human food.

Adult↗
PubMed1993

Abnormal amniotic fluid levels of CA 125 in second-trimester Down syndrome pregnancies.

The aim of this study was to evaluate the concentration of CA 125 in second trimester amniotic fluid from Down syndrome pregnancies. CA 125 was measured in stored amniotic fluid samples from pregnancies of 14-19 weeks' gestation with and without Down syndrome fetuses. CA 125 levels were expressed in multiples of the median (MOM) for normal pregnancies of the same gestational age. Twenty-one pregnancies with Down syndrome fetuses and 63 unaffected controls matched for maternal age, gestational age, and duration of storage were studied. The median MOM values of the affected pregnancies were significantly higher than those of the controls (1.41 MOM versus 0.99 MOM). These findings show that there is an increased concentration of CA 125 in second-trimester amniotic fluid from Down syndrome pregnancies.

Amniotic Fluid↗