PubMed Health⌕ Search

Biomedical subjects

M Paolucci

Publications and source records attributed to M Paolucci.

At least 19 recordsLinked to original sources
PubMed2003

Analysis of reelin as a candidate gene for autism.

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.

Autistic Disorder↗
PubMed2001

Leptin presence in plasma, liver and fat bodies in the lizard Podarcis sicula: fluctuations throughout the reproductive cycle.

Leptin is a 16 kDa peptide produced by adipocytes in response to increasing fat stores and signals to the brain to stop eating and increase energy expenditure. Recent studies point out that the role of leptin is much broader and includes the regulation of reproduction. The lizard, Podarcis sicula, is an oviparous species characterized, at this latitude, by a seasonal reproductive cycle. Since in Podarcis sicula the recovery of the gonadal function coincides with the recovery of metabolic activity, we have hypothesized that leptin might be involved in the regulation of the reproductive function in this species. We have identified an immunoreactive band in the plasma of the female of Podarcis sicula, which comigrated with recombinant mouse leptin and cross reacted with polyclonal antibodies against mouse leptin. A RIA method developed by Linco (St. Louis, MO) was utilized to measure leptin concentration in plasma, liver and fat bodies of Podarcis sicula throughout the reproductive cycle. The antibody used in this kit (Linco's Multi-Species Leptin Radioimmunoassay kit) was produced in the guinea pig against human leptin but displays crossreactivity to leptin molecules of many species. The level of leptin in the plasma of Podarcis sicula was in the same range as that of mammals. Leptin levels in plasma, liver and fat bodies fluctuated during the reproductive cycle, in a way consistent with its possible role in reproduction.

Animals↗
PubMed2001

Sex steroid hormone fluctuations and morphological changes of the reproductive system of the female of Octopus vulgaris throughout the annual cycle.

Sex steroids (17beta-estradiol and progesterone) and morphological variations of the reproductive system of the female of Octopus vulgaris from the Bay of Naples were followed over a period of 2 years. The increase in the ovary weight was independent of body weight as demonstrated by the gonado-somatic index (GSI). Both 17beta-estradiol and progesterone have been detected in the ovary of O. vulgaris, and their concentrations changed in correlation with the ovarian development. No 17beta-estradiol or progesterone was found in the hemolymph. 3beta-Hydroxysteroid dehydrogenase activity has been detected in the ovary, indicating that in the female of O. vulgaris the reproductive system is a source of sex steroid hormones. According to the morphological changes of the ovary, the ovarian cycle can be divided into the following phases: previtellogenesis; early vitellogenesis, full vitellogenesis and late vitellogenesis. The morphological changes of the oviducts and oviducal glands throughout the reproductive cycle were in accordance with their role in the transport and secretion of gelatinous coat covering the eggs, as well as in sperm storage and sperm reactivation during fertilization. J. Exp. Zool. 289:33-47, 2001.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Seasonal variation in plasma lipids, lipoproteins, apolipoprotein A-I and vitellogenin in the freshwater turtle, Chrysemys picta.

An analysis of plasma lipids and lipoprotein fractions was performed over the course of the annual ovarian cycle of the female turtle, Chrysemys picta. Determinations of total plasma triglycerides, cholesterol, vitellogenin and apolipoprotein A-I (apoA-I) were made. The lipid and protein composition of the lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and very high density lipoprotein (VHDL)] were also observed over the same period. Plasma triglyceride and vitellogenin levels were significantly increased in the spring preovulatory period and fall recrudescent phase. Total plasma cholesterol levels were significantly elevated only at the onset of the fall recrudescent phase and apoA-I levels were highest during the postoviposition/ovarian arrest phase. The triglyceride content of VLDL was highest in preovulatory animals and there were apparent seasonal changes in the expression of apoA-I and apoE of HDL/VHDL. We conclude that the coordinate regulation of lipids and protein contributes to seasonal ovarian growth and clearance of lipids from plasma, both of which are most likely under hormonal control.

Animals↗
PubMed2001

Prevalence of and risk factors for Helicobacter pylori infection among healthcare workers at a teaching hospital in Rome: the Catholic University Epidemiological Study.

OBJECTIVES: To evaluate the prevalence of and the risk factors for Helicobacter pylori in a population of medical and non-medical workers at a teaching hospital in Rome, Italy. DESIGN: A cross-sectional study. METHODS: From January to October 1998, 655 subjects (65% of the total population) underwent a 13C-urea breath test to assess H. pylori infection. Subjects completed a questionnaire concerning sociodemographic characteristics, work departments and history of some gastrointestinal symptoms. Differences in means and proportions were evaluated and independent predictors of H. pylori infection status were assessed by multiple logistic regression analysis. RESULTS: Forty percent of the subjects were found to be H. pylori infected. The mean age of positive subjects was significantly higher than that of negative ones (38 +/- 14 versus 34 +/- 12 years; P < 0.01). No significant difference was found between males and females concerning the infection status (40.2% males versus 39.9% females). Lower years of father's education [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.9-5.1] and age older than 35 years (OR, 2.0; 95% CI, 1.3-3.1) were the only independent predictors of the likelihood of H. pylori positivity. Prevalence of gastrointestinal symptoms was similar in infected and uninfected subjects. Physicians were significantly less infected than nurses and auxiliary personnel (26% versus 47% versus 55%, respectively); however, a loss of association was observed after adjustment by multiple logistic regression (OR, 1.8; 95% CI, 0.9-3.7). In all groups, some specific departments appear to be associated with a higher infection status. CONCLUSIONS: Among healthcare workers, H. pylori infection was associated with specific sociodemographic characteristics, such as age and level of father's education. The prevalence of H. pylori infection was not associated with different professional categories. However, some specific departments seem to increase infection risk.

Adult↗
PubMed2001

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas.

BACKGROUND: Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". AIMS: To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS: Pancolonoscopy was performed in 15 patients with resected adenomas (> or =1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS: No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS: The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.

Adenoma↗
PubMed2000

Stage I nonsmall cell lung carcinoma: analysis of survival and implications for screening.

BACKGROUND: Skepticism about the radical curability of lung carcinoma, even when diagnosed in Stage I, has been long fostered by the epidemiologists' dogma against lung cancer screening, and by official recommendations not to screen for lung carcinoma. Follow-up of patients with asymptomatic screen-detected Stage I nonsmall cell lung carcinoma (NSCLC), however, shows that patients who underwent radical resection have long term survival rates, whereas patients nonsurgically treated or undergoing suboptimal operations have much poorer prognosis. The latter clinical outcome data strongly suggest the importance of detecting lung carcinoma when it is in Stage I and cast serious doubts on the recommendation not to screen for lung carcinoma. DATA: The scrutiny of the biology, epidemiology, and clinical features of Stage I NSCLC clarifies important aspects of the ongoing controversy concerning the value of screening for early diagnosis (Stage I) of lung carcinoma. The biologic characteristics of Stage I NSCLC (histologic types, doubling time, metastases) indicate its malignant potential. The asymptomatic screen-diagnosed Stage I carcinomas have longer doubling time than the more advanced cancers; nevertheless, they are not overdiagnosed tumors because they cause fatal outcome if they are not resected. Chest X-ray screening identifies approximately 50% of cancers in Stage I. Screening by helical low dose computed tomography scan detects greater than 80% of lung carcinomas in Stage I. The resectability, the surgical techniques (lobectomy vs. limited resections), and the influence of the extent of surgical resection of Stage I NSCLC on prognosis are reviewed. These data show that radical surgical treatment offers 5-year survival rate to 60-80% of patients with Stage I NSCLC. SYNTHESIS: Asymptomatic Stage I lung carcinomas, detected by screening or by incidental findings, are truly malignant, because they metastasize and cause fatal outcome if they are not radically resected. The possibility to cure lung carcinomas relies on radical resection (lobectomy or, less frequently, pneumonectomy) of early diagnosed (Stage I) disease, which is usually asymptomatic. The limited parenchymal resections (segment or wedge resections) do not fulfill the requirements of radicality because they are accompanied by higher incidence of local recurrences and shorter survival rates. CONCLUSIONS: The documented improvement of long term survival of NSCLC, which can be achieved by early diagnosis and radical resection, strongly indicates that the current dogma against lung cancer screening is untrue. Every effort should be made to detect the disease when it is in Stage I and radically operable, by implementing screening in at risk smokers and former smokers, with the most effective screening method that is locally available.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Lung cancer screening in cigarette smokers in the province of Varese, Italy.

BACKGROUND: For heavy cigarette smokers and recent former smokers who have accumulated a high risk of lung carcinoma, a primary objective is the early detection of that disease; this goal can be achieved by annual screening with one of the radiologic imaging methods available. While awaiting for the implementation of computed tomography or of other, more sensitive methods, it is quite reasonable to screen those who are at risk with annual chest X-ray (CXR), an examination that is readily available at low cost. Indeed, with the annual CXR screening of heavy smokers, it is possible to detect about 50% of lung carcinomas in TNM Stage I. The 5-year survival rate of patients with asymptomatic, screen-detected Stage I disease after radical surgery is significantly greater than the survival rate of patients with symptomatic disease. METHODS: At the Center for Thoracic Surgery of the University of Insubria Medical School in Varese we developed a project, called "PRE.DI.CA" (an acronym for "early diagnosis of cancer"), of annual CXR screening for the early diagnosis of asymptomatic lung carcinoma in the high risk population of heavy cigarette smokers and recent former smokers in the province of Varese, Italy. From June 1997 to August 1999, 2444 heavy smokers were enrolled in the PRE.DI.CA project. RESULTS: About 75% of participants complied with the annual screening protocol. Overall, 23 patients (all males) with asymptomatic lung carcinoma were detected by CXR screening; moreover, 1 patient developed symptoms of lung carcinoma 6 months after his initially negative CXR and was diagnosed with interval carcinoma (Stage IIIA). In the initial (prevalence) screening, the authors detected 16 patients with lung carcinoma in 2444 screened participants (0.65%). In the subsequent incidence screening, the authors detected 7 patients with lung carcinoma in 1361 screened participants (0.51%); it is noteworthy that 5 of 7 patients (71%) with lung carcinoma that was detected by incidence CXR screening had Stage I disease. CONCLUSIONS: In the province of Varese, Italy, it is possible to make an early diagnosis of lung carcinoma with CXR annual screening in asymptomatic, high risk smokers. Incidence screening in 1361 participants detected 7 patients with asymptomatic lung carcinoma; 5 of 7 patients (71%) with such screen-detected lung carcinoma had Stage I disease.

Aged↗
PubMed2000

Effect of testosterone and 17beta-estradiol treatment on sex steroid binding proteins in the male of the green frog Rana esculenta.

In this paper we report the effect of gonadectomy and/or long-term sex steroid (testosterone and estradiol-17beta) treatment and prolonged captivity (two months) on testosterone and estradiol-17beta binding proteins (TBP and EBP, respectively) in the plasma of the male of the green frog Rana esculenta. Experiments were carried out during different periods of the reproductive cycle. Gonadectomy and prolonged captivity were carried out in winter, when the spermatogenic activity slowed down and the concentration of circulating androgens was high. Both gonadectomy and prolonged captivity resulted in a significant decrease in TBP binding activity, which could not be restored by the hormonal treatment. On the contrary, when the hormonal treatment was carried out in the early summer, when the spermatogenesis was active but the concentration of circulating androgens was low, a significant increase in TBP binding activity was observed. Neither gonadectomy, nor the prolonged captivity, nor the hormonal treatment affected EBP levels. Our data indicate that TBP apparent changes in response to testosterone and estradiol-17beta treatment varied according to the period of the reproductive cycle, an indication that studies on sex steroid binding proteins regulation should take into consideration the internal endocrine condition before drawing any final conclusion especially in species with a seasonal mode of reproduction.

Animals↗
PubMed2000

Estrogen receptors and aromatase activity in the hypothalamus of the female frog, Rana esculenta. Fluctuations throughout the reproductive cycle.

It is well known that certain actions of androgen are mediated through in situ aromatization to estrogen in neural target tissues. This study was undertaken to investigate androgen utilization in the hypothalamus of the female frog, Rana esculenta, through a quantification of estrogen receptors and aromatase activity during the reproductive cycle. 3H-estradiol-binding molecules were present in both the cytosol and the nuclear extract of the hypothalamus. These molecules bound specifically 3H-estradiol with high affinity (Kd 10(-10) M) and low capacity (cytosol: 1.2+/-0.4 fmol/mg protein; nuclear extract: 7.9+/-0.6 fmol/mg protein). Aromatase activity was detected in the microsomal fraction of the hypothalamus using a sensitive in vitro radiometric assay. Both aromatase activity and nuclear estrogen receptor binding fluctuated in synchrony throughout the reproductive cycle. Western blot analysis of aromatase protein revealed one immunoreactive band with a molecular weight of approximately 56 kDa. In contrast to aromatase enzyme activity, the relative levels of aromatase protein changed little during the reproductive cycle suggesting that post-translational mechanisms may be involved in regulating estrogen synthesis in the frog brain. A possible role for estrogens in the modulation of the reproductive behavior in this species is suggested.

Animals↗
PubMed2000

Idarubicinol myelotoxicity: a comparison of in vitro data with clinical outcome in patients treated with high-dose idarubicin.

We evaluated in vitro the toxicity of idarubicin and its active metabolite idarubicinol on haematopoietic progenitors, using human umbilical cord blood and peripheral blood progenitors to obtain dose-response curves. We treated 16 patients with poor prognosis lymphoma in a phase I-II trial of high-dose idarubicin and melphalan and investigated if idarubicinol persisting in patients' plasma at the time of transplantation (day 0), on day +1 and +2 could result in an inhibition of infused progenitors. Colony inhibition was correlated with pharmacokinetic data and with the time of patients' engraftment. Plasma samples obtained before idarubicin treatment demonstrated a colony-stimulating effect, increasing the cloning efficiency by 72%. The inhibitory activity on colony forming unit granulocyte-macrophage (CFU-GM) of patients' plasma collected on the day of transplantation was lower than expected from dose-response curves (21% measured vs 70% expected). The time to patients' WBC and PLT recovery correlated with the amount of CD34+ cells reinfused and, to a lesser extent, with the colony-inhibiting effect of patients' plasma. The correlation between idarubicinol concentration and CFU-GM inhibition was not significant. These data suggest that plasma drug concentration on the day of stem cell reinfusion may overestimate the toxicity of residual anthracyclines to the transplanted cells.

Adult↗
PubMed1999

Evidence of a progesterone receptor in the liver of the green frog Rana esculenta and its down-regulation by 17 beta estradiol and progesterone.

Progesterone is a versatile hormone showing an ample variety of effects. One of the numerous functions attributed to progesterone is the modulation of vitellogenesis in oviparous vertebrates. As a prerequisite for the possible involvement of progesterone in vitellogenesis modulation, we investigated the presence of a progesterone receptor (PR) in the liver of the female green frog Rana esculenta. 3H-Progesterone (3H-P) binding activity was found in both cytosol and nuclear extract of the liver of Rana esculenta. The progesterone-binding moiety showed the typical characteristics of a true receptor, such as high affinity, low capacity, and specificity for progesterone. It also bound to DNA-cellulose and was eluted with a linear salt gradient at a concentration of 0.05 M of NaCl. The progesterone-binding moiety was down regulated by steroid hormones, in that ovariectomy resulted in a significant increase, in both cytosol and nuclear extract, of 3H-P binding activity with respect to intact females. On the contrary, 3H-P binding activity was almost undetectable after estradiol and/or progesterone treatment. The progesterone binding moiety of Rana esculenta was analyzed by Western blotting with the aid of a monoclonal antibody raised against the subunits A and B of the chicken PR. An immunoreactive band of about 67 kDa was observed in the liver of both intact and treated females. The 67 kDa band showed an increased intensity in ovariectomized animals, while it was faint following treatment with estradiol and/or progesterone. This is the first report on the presence of a progesterone receptor (PR) in the liver of an amphibian. PR of Rana esculenta is down regulated by estradiol and/or progesterone and shows peculiar immunological and biochemical characteristics, which make it rather different from the PR of other vertebrates.

Animals↗
PubMed1999

Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma.

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management.

Adult↗
PubMed1998

Progesterone receptor in the reproductive system of the female of Octopus vulgaris: characterization and immunolocalization.

In this study for the first time we have characterized a progesterone receptor in the reproductive system of the female of Octopus vulgaris. Scatchard analysis revealed that one binding component with high affinity and low capacity for the ligand was present only in the nuclear extract. Competition experiments showed that the progesterone receptor was strictly specific for progesterone. DNA-cellulose binding and DEAE-Sephacel both confirmed the presence of one 3H-progesterone binding component which eluted at a salt concentration of 0.14 +/- 0.05 M NaCl and 0.15 +/- 0.05 M NaCl respectively. By using monoclonal antibodies against chicken progesterone receptor (subunits A and B), we have localized on Western Blot one band of about 70 kDa. Immunoreactivity for progesterone binding molecules has been localized in the nuclei of the follicle cells of the ovary, of the proximal portion of the oviduct and of the outer region of the nidimental gland. These data, taken together, provide evidence that in Octopus vulgaris the progesterone receptor has biochemical and immunohistochemical characteristics resembling those of progesterone receptor in vertebrates.

Animals↗