Biomedical subjects

Andrea Pasini

Publications and source records attributed to Andrea Pasini.

9 recordsLinked to original sources

PubMed2006

Utero-ovarian ultrasonographic and Doppler flow analyses in female childhood cancer survivors with regular menstruation and normal circulating follicle-stimulating hormone levels.

OBJECTIVE: To analyze the hormonal, ultrasonographic, and color Doppler parameters in a population-based follow-up study of female childhood cancer survivors with regular menstrual cycle and normal early follicular FSH values. DESIGN: Controlled, prospective clinical study. SETTING: University hospital. PATIENT(S): Twenty-eight female patients affected by a malignant tumor during childhood and 14 age-matched healthy controls. INTERVENTION(S): Hormonal, ultrasonographic, and color Doppler analyses. MAIN OUTCOME MEASURE(S): In the midluteal phase of the cycle, the patients underwent hormonal assay of gonadotropins, E2, and P; ultrasonographic evaluation of the uterine and ovarian volume, the endometrial thickness, and of the corpus luteum characteristics; color Doppler analysis of uterine, intraovarian, and periluteal arteries. RESULT(S): A greater uterine volume and a better utero-ovarian vascularization was observed in controls in comparison with cancer survivors. In patients who suffered from childhood malignancies the P values were lower than in controls. On the basis of circulating P (> or < 20 nmol/L) values, we divided the former group in ovulatory and nonovulatory patients. We observed that even if there were no differences between ovulatory cancer survivors and controls, the nonovulatory group showed a reduced uterine volume associated with elevated resistance at the level of uterine and intraovarian arteries. Among these two groups the time elapsed between the diagnosis of cancer and menarche was shorter in nonovulatory than in ovulatory women, and was directly correlated with both uterine volume (r = 0.660) and ovarian volume (r = 0.597). CONCLUSION(S): Ultrasonographic and Doppler analyses may noninvasively study the subtle utero-ovarian modification after anticancer therapies.

Arteries↗

PubMed2006

Formation of the ascidian epidermal sensory neurons: insights into the origin of the chordate peripheral nervous system.

The vertebrate peripheral nervous system (PNS) originates from neural crest and placodes. While its developmental origin is the object of intense studies, little is known concerning its evolutionary history. To address this question, we analyzed the formation of the larval tail PNS in the ascidian Ciona intestinalis. The tail PNS of Ciona is made of sensory neurons located within the epidermis midlines and extending processes in the overlying tunic median fin. We show that each midline corresponds to a single longitudinal row of epidermal cells and neurons sharing common progenitors. This simple organization is observed throughout the tail epidermis, which is made of only eight single-cell rows, each expressing a specific genetic program. We next demonstrate that the epidermal neurons are specified in two consecutive steps. During cleavage and gastrula stages, the dorsal and ventral midlines are independently induced by FGF9/16/20 and the BMP ligand ADMP, respectively. Subsequently, Delta/Notch-mediated lateral inhibition controls the number of neurons formed within these neurogenic regions. These results provide a comprehensive overview of PNS formation in ascidian and uncover surprising similarities between the fate maps and embryological mechanisms underlying formation of ascidian neurogenic epidermis midlines and the vertebrate median fin.

Animals↗

PubMed2005

Determinants of short term recurrence rate of endometriosis.

OBJECTIVE: To analyse the frequency and the determinants of recurrence rate of clinically detectable endometriosis. STUDY DESIGN: Prospective cohort multicenter study. Eligible for the study were all women observed for the first time during the period January-June 1998 at the participating centres with a laparoscopically confirmed first diagnosis of endometriosis. After diagnosis, patients were treated according to standard care of each centre and desire for pregnancy. The protocol required all women to be followed up at the centre each year for 2 years with a clinical examination, an ultrasound pelvic examination and a CA125 assay, unless pregnancy occurred. Second look laparoscopy was performed on a clinical basis. RESULTS: A total of 311 women (median age 36 years) entered the study. The two-year recurrence rate was 5.7% among cases stage I-II and 14.4% among stage III-IV (chi(1)2 adjusted for indication for surgery, p < 0.05). The recurrence rates tended to increase with age, being 4.6% among women aged 20-30 and 13.1% among women aged >30, but this finding was not statistically significant. CONCLUSION: The recurrence rate of clinically detectable endometriosis tends to be higher in older women with advanced stages of the disease and lower in women with infertility.

Adult↗

PubMed2005

Role of intratesticular ultrasonographic and Doppler flow analyses in evaluating gonadal status in male survivors of childhood malignancy.

Fifty-seven males, previously treated for malignancies in childhood, and who refused to masturbate for semen analysis, were submitted to hormonal, ultrasonographic, and Doppler evaluation to assess the effects of chemotherapy/radiotherapy on gonadal function. Nineteen normal healthy fertile males served as controls. In the studied population, FSH was inversely correlated with testicular volume and directly correlated with testicular vascularization, suggesting that ultrasonographic and color Doppler scanning of the testes may be used, if a sperm count is not available, to indirectly assess the gonadal function.

Adolescent↗

PubMed2005

Height as a risk factor for osteosarcoma.

Previous investigations have suggested that osteosarcoma may be associated with a taller stature, but the relationship between height and osteosarcoma remains controversial. Height at diagnosis was evaluated in a continuous series of 962 osteosarcoma subjects treated between 1981 and 2001. Patients diagnosed during growth (group 1) were separated from those diagnosed in adulthood (group 2). Height (H) and final height (FH) were expressed as standard deviation scores (SDS), calculated by national reference data. Group 1 subjects were above the 50th centile and their mean H-SDS values (0.31 +/- 1.1) were significantly higher than the mean FH-SDS values (P < 0.0001) of the group 2 subjects, both in males and females. In contrast, the mean FH-SDS (0.01 +/- 1.1) of group 2 did not differ from that of the reference population. The highest incidence of osteosarcoma was at 12.5 years in females, 14.5 years in males. These data confirm previous observations of an association between osteosarcoma development and height, at least in growing individuals. The higher incidence during the pubertal spurt, in the anatomic sites of greater growth and in taller individuals, suggests that growth factors play an important role in the pathogenesis of this bone cancer.

Adolescent↗

PubMed2005

JLK inhibitors: isocoumarin compounds as putative probes to selectively target the gamma-secretase pathway.

Alzheimer's disease is characterized by the extracellular deposition of the amyloid beta-peptide that derives from its precursor betaAPP by sequential actions of beta- and gamma- secretases, respectively. Recent studies aimed at identifying these enzymes have been reported as it is thougth that their inhibition should hopefully lead to reduce Abeta load in the AD brains. beta-secretase seems to be due to BACE1, a novel membrane-bound aspartyl protease. gamma-secretase identification is still a matter of controversy. Invalidation of presenilin genes was reported to impair both gamma-secretase-mediated Abeta production and Notch cleavage leading to NICD production. This observation together with another biochemical and pharmacological evidences led to suggest that presenilins could be the genuine long-searched gamma-secretase that would be responsible for both APP and Notch cleavages. We have designed novel non peptidic potential inhibitors of gamma-secretase (referred to as JLK inhibitors) and examined their ability to prevent Abeta40 and Abeta42 secretions as well as NICD production. Three out of a series of these agents drastically lower the recoveries of both Abeta40 and Abeta42 produced by betaAPP-expressing cell lines and concomitantly protect intracellular C99 and C83 recoveries. These inhibitors also prevent Abeta40/42 productions by C99-expressing cells. Interestingly, these inhibitors were totally unable to affect the DeltaENotch cleavage leading to NICD generation. Here, we also further characterize the pharmacological properties and specificity of these JLK inhibitors.

Amyloid Precursor Protein Secretases↗

PubMed2004

Two zebrafish Notch-dependent hairy/Enhancer-of-split-related genes, her6 and her4, are required to maintain the coordination of cyclic gene expression in the presomitic mesoderm.

Alterations of the Delta/Notch signalling pathway cause multiple morphogenetic abnormalities in somitogenesis, including defects in intersomitic boundary formation and failure in maintenance of somite regularity. Notch signalling has been implicated in establishing the anteroposterior polarity within maturing somites and in regulating the activity of a molecular segmentation clock operating in the presomitic mesoderm. The pleiotropy of Notch signalling obscures the roles of this pathway in different steps of somitogenesis. One possibility is that distinct Notch effectors mediate different aspects of Notch signalling. In this study, we focus on two zebrafish Notch-dependent hairy/Enhancer-of-split-related transcription factors, Her6 and Her4, which are expressed at the transition zone between presomitic mesoderm and the segmented somites. The results of overexpression/gain-of-function and of morpholino-mediated loss-of-function experiments show that Her6 and Her4 are Notch signalling effectors that feedback on the clock and take part in the maintenance of cyclic gene expression coordination among adjacent cells in the presomitic mesoderm.

Animals↗

PubMed2002

Stabilizing the regionalisation of the developing vertebrate central nervous system.

During embryonic development, a number of tissues are patterned by their subdivision into domains with distinct regional identity. An important question is how sharp interfaces are established and maintained between adjacent domains despite the potential for scrambling due to cell intermingling during tissue growth. Two mechanisms have been found to underlie the maintenance of sharp interfaces: the specific restriction of cell mixing across boundaries, or the switching of identity of cells that cross between domains. We review the evidence for these mechanisms at distinct boundaries in the developing vertebrate central nervous system, and discuss what is known about their molecular mediators.

Animals↗

PubMed2002

Low birth weight for gestational age and subsequent male gonadal function.

OBJECTIVE: To verify whether a reduced birth weight for gestational age was associated with a testicular dysfunction in postpubertal boys. STUDY DESIGN: Boys born small for gestational age (SGA) (n = 25) were compared to 24 born with an appropriate weight. All subjects were postpubertal (mean age 17.5 +/- 1.3 and 17.6 +/- 2.0 years, respectively). The following clinical and endocrinologic variables were evaluated: final height, target height, body mass index, testicular volume, follicle-stimulating hormone, luteinizing hormone, testosterone, and inhibin B. RESULTS: The SGA group had reduced testicular size (16.3 +/- 2.7 mL vs 22.8 +/- 3.2 mL; P <.0001) with a lower testosterone level (3.76 +/- 1.35 ng/mL vs 4.77 +/- 1.55 ng/mL; P <.05) and a higher LH value (4.41 +/- 1.61 IU/L vs 3.44 +/- 1.29 IU/L; P <.05). Among the SGA group, 54% had a mean testicular volume >2 SD below the control mean (ie, <16 mL) and in these subjects, the inhibin B level was low (143 +/- 46 pg/mL vs 229 +/- 76 pg/mL; P <.0001). SGA patients with smaller testes had lower final height relative to target height(P <.05 vs patients with larger testes) and for the SGA group, inhibin B correlated with testicular size (P <.0001). Positive correlations also were found between the reduction of final height relative to target height and testicular volume (P <.005) and inhibin B values (P <.05). CONCLUSIONS: SGA subjects have pituitary-gonadal axis function that tends toward hypogonadism. There is a disruption of the exocrine function in subjects with smaller testicular size who failed to show a complete height catch-up growth. This study supports a link between low birth weight and lower fertility in adult males.

Adolescent↗