PubMed Health⌕ Search

Biomedical subjects

M Fanelli

Publications and source records attributed to M Fanelli.

At least 55 records · Page 3Linked to original sources
PubMed1998

Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO.

Nuclear receptor corepressor (CoR)-histone deacetylase (HDAC) complex recruitment is indispensable for the biological activities of the retinoic acid receptor fusion proteins of acute promyelocytic leukemias. We report here that ETO (eight-twenty-one or MTG8), which is fused to the acute myelogenous leukemia 1 (AML1) transcription factor in t(8;21) AML, interacts via its zinc finger region with a conserved domain of the corepressors N-CoR and SMRT and recruits HDAC in vivo. The fusion protein AML1-ETO retains the ability of ETO to form stable complexes with N-CoR/SMRT and HDAC. Deletion of the ETO C terminus abolishes CoR binding and HDAC recruitment and severely impairs the ability of AML1-ETO to inhibit differentiation of hematopoietic precursors. These data indicate that formation of a stable complex with CoR-HDAC is crucial to the activation of the leukemogenic potential of AML1 by ETO and suggest that aberrant recruitment of corepressor complexes is a general mechanism of leukemogenesis.

Cell Differentiation↗
PubMed1998

Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients.

To validate the prognostic value of the determination of p53 expression, intratumoral microvessel density (IMD) (a measure of angiogenesis), and the conventional features, we studied 531 patients operated of breast cancer (271 node-positive and 260 node-negative), with a median follow-up exceeding 6 years. IMD was assessed by using the anti-CD31 antibody to identify the microvessels. p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68, respectively. The prognostic value of the markers was analyzed by univariate and multivariate statistical analyses. In the overall series p53 expression, IMD, nodal status, ER and PgR were statistically significant prognostic indicators for both relapse-free survival (RFS) and overall survival (OS) in the final multivariate model. Likewise, tumor size and menopausal status were significant prognostic indicators for RFS and OS, respectively. In the subgroup of node-negative patients who did not receive adjuvant therapy only p53, IMD, and tumor size were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant chemotherapy, IMD, the number of involved nodes and PgR were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD and ER (and the number of involved nodes, only for OS) were statistically significant for both RFS and OS in the final multivariate model. Different markers played a diverse prognostic role in the diverse subgroups studied. Angiogenesis was the sole marker which retained prognostic value in all the sub-groups analyzed. p53 retained significance only in the subgroup of node-negative patients, whilst ER and PgR were statistically significant in the subgroups of node-positive patients treated with adjuvant hormone therapy or chemotherapy, respectively.

Adult↗
PubMed1997

Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis.

The BCR/ABL fusion protein transforms myeloid stem cells. Both chronic myelogenous leukemias (CML) and a subset of acute lymphoblastic leukemias (ALL) are associated with the expression of BCR/ABL proteins. This knowledge has not yet been translated into any specific tool to control ABL driven neoplastic cells growth. CGP57148B is an ATP-competitive inhibitor of the ABL protein kinase; it has been shown to inhibit the kinase activity of ABL both in vitro and in vivo and to inhibit the growth of v-abl and bcr/abl transfectants, as well as the in vitro formation of bone marrow (BM)-derived colonies in the presence of growth factors in some CML patients. These studies were performed to investigate the activity of CGP57148B on the spontaneous proliferation of both fresh and cultured, leukemic and normal, BCR/ABL positive and negative cells, and to study its mechanism of action. Six cell lines derived from BCR/ABL+ leukemias (K562, BV173, KCL22, KU812, MC3, LAMA84), thirteen BCR/ABL negative lines, both neoplastic (KG1, SU-DHL-1, U937, Daudi, NB4, NB4.306) and derived from normal cells (PHA blasts, LAK, fibroblasts, LCL, renal epithelial cells, endothelial cells, CD34(+) cells), and 14 fresh leukemic samples were tested using a tritiated thymidine uptake assay. The in vivo phosphorylation of the BCR/ABL protein was evaluated by western blot, while apoptosis was detected by the annexin V/propidium binding test. The induction of differentiation was assayed by immunofluorescence using multiple antibodies. All six BCR/ABL+ lines showed a dose dependent inhibition of their spontaneous proliferative rate, which was not accompanied by differentiation. The treatment caused, within minutes, dephosphorylation of the BCR/ABL protein, followed in 16-24 hours by a decrease in cycling cells and induction of apoptosis. No significant inhibition of DNA synthesis was observed in any BCR/ABL negative normal or neoplastic line at concentrations </=3 microM, with the exception of fibroblasts and CD34 cells. Proliferation inhibition was observed also when using fresh samples obtained from two Ph+ ALL and 12 consecutive CML patients. Induction of apoptosis was observed in these samples too. The activity of CGP57148B can be monitored in ex vivo isolated or cultured cells using a simple and reproducible assay, without the need for exogenously added growth factors. This molecule possibly exerts its effects through the inhibition of the kinase activity of BCR/ABL and the subsequent initiation of apoptosis, without inducing cell differentiation. Some normal cells are also affected. These data support the use of CGP57148B in initial clinical studies; possible toxic effects on BM and fibroblast-derived cells will have to be closely monitored. The in vivo monitoring of patients will have to be focused on the induction of apoptosis in leukemic cells.

Apoptosis↗
PubMed1997

["Odontogenic" anxiety. A study of a population of 1500 students from the public schools in the Bari area].

The authors have carried out a survey regarding 1500 students whose age ranged from 9 to 18 years. They belonged to some public schools of Gioia del Colle, a small town near the city of Bari. The aim of the study was to evaluate the dentist fear, the levels of anxiety and the main reasons or situations which can cause it. A questionnaire has been used for this purpose: the Dental Subscale Test. Results have shown that the 38.7% of the people questioned, has asserted to be afraid of the dentist and that this fear is much more felt in women than in men. Moreover has been demonstrated that this fear overcomes amongst those who have never undergone a dental treatment and that the degree of anxiety decreases from childhood to adulthood. In addition statistics analysis have proved that the sensation of choking, the sight and the sound of surgical instruments such as the drill and the fear of injections, are amongst those items which can be referred as the most frequent sources of anxiety for both males and females.

Adolescent↗
PubMed1996

Three-minute high-performance liquid chromatographic assay for NMN adenylyltransferase using a 20-mm-long reversed-phase column.

NMN adenylyltransferase (NAD pyrophosphorylase; NMNAT) reversibly catalyzes the synthesis of NAD from ATP and NMN. In this paper, we describe a rapid and sensitive high-performance liquid chromatographic assay for NMNAT, which uses a 20-mm-long C18 reversed-phase (RP) column. The activity was measured by separating in less than 3 min the substrates (NMN and ATP) from the product (NAD) with 0.1 M potassium phosphate, pH 6.0, at a 2 ml/min flow-rate and 22 degrees C. NAD was directly quantitated from its ultraviolet absorbance. Amounts of NAD as small as 25 pmol could be measured. The activity value closely agreed with that determined by the spectrophotometric assay. This method was successfully applied to the determination of NMNAT activity in human placental and bull testis extracts, as well as in rat pheochromocytoma (PC12) cells.

Adult↗
PubMed1996

Expression of tenascin is related to histologic malignancy and angiogenesis in b-cell non-Hodgkin's lymphomas.

The topography of and the area covered by tenascin, laminin and type IV collagen (all components of the subendothelial basement membrane), and the microvessel area (an index of angiogenesis), as evaluated with factor VIII, were investigated immunohistochemically in 61 B-cell non-Hodgkin's lymphomas (B-NHL) and 30 benign lymphadenopathies as controls. The three components were located in the microvessels and in a microvessel-bound stromal reticular network, the expression of tenascin being always more extended and finer than the other components. Of the lymphadenopathies, reactive and atypical lymphoid hyperplasias showed vessels and stromal network in the interfollicular zone only, whereas in Castleman's and angioimmunoblastic forms these structures were widely scattered in the tissue, and the area of the three components and that of the microvessels were significantly larger. Of the low-grade B-NHL, follicular subtypes had vessels and stromal network confined to the interfollicular inflammatory zone, but not in tumor follicles, whereas these structures were irregularly distributed throughout the small lymphocytic subtype. The levels of areas in low-grade B-NHL overlapped those of Castleman's and angioimmunoblastic lymphadenopathies. Among the intermediate-grade tumors, the follicular subtype resembled the follicular tumors, and the diffuse subtypes displayed vessels and stromal network throughout the tissue in close association with the neoplastic cells, and with significant increments of both the tenascin and the microvessel areas, but with a significant reduction of both the laminin and the type IV collagen areas. Distribution was similar in high-grade B-NHL, but tenascin and microvessel area variations, on the one hand, and those of laminin and type IV collagen areas were still more apparent than in the intermediate-grade. A high correlation was demonstrated in all groups of tissues between tenascin and microvessel area. In addition, in the diffuse intermediate-grade and high-grade B-NHL highly immature vessels were frequently detected by ultramicroscopy. The results show that tenascin expression and angiogenesis are closely related, and that both increase in function of tumor malignancy. Unlike laminin and type IV collagen, tenascin is associated with highly immature vessels in B-NHL. We suggest that tenascin expression and angiogenesis are governed by the B-NHL-associated inflammatory infiltrate, as well as by the B-NHL cells, particularly in more malignant tumors.

Endothelium, Vascular↗
PubMed1996

[Pregnancy in women over 35 years of age. What risk?].

A retrospective study of women who are delivered at the Dept. of Obstetrics and Gynecology at the University of Bari, in the period 1991-1994, was performed to evaluate if over 20 week pregnancies in women aged 35 years and over were at higher risk for maternal and neonatal complications than pregnancy in women aged 20 to 29 years. The results of these 4 years show that pregnancy in women aged 35 and over is burdened with a greater incidence of maternal complications and cesarean sections, but age is not a risk for neonatal outcomes. Moreover, most working women were obliged to delay the first birth child, but work does not increase the number of complications.

Adult↗
PubMed1995

Alexithymia in essential hypertensive and psychiatric outpatients: a comparative study.

The purported association between alexithymia and essential hypertension was investigated in a sample of 114 hypertensive patients using the well-validated twenty-item Toronto Alexithymia Scale. Alexithymia was also assessed in a group of 113 general psychiatric outpatients and in a group of 130 normal adults. A rate of 55.3% of alexithymia was found in the hypertensive group compared with significantly lower rates of 32.7% in the psychiatric group and 16.3% in the normal controls. The results support the view that a high prevalence of alexithymia may be found among patients with disorders that were categorized in the past as "classical" psychosomatic diseases. It is hypothesized that a deficit in the cognitive processing and modulation of emotions may leave alexithymic individuals prone to states of heightened sympathetic arousal that are conducive to the development of essential hypertension.

Adult↗
PubMed1995

Drug resistant bacteria in non carbonated mineral waters.

The presence of antibiotic resistant bacteria was revealed among bacteria isolated from non carbonated mineral waters bottled in plastic (PVC) and in glass containers. Heterotrophic plate count values ranged between < 10 and 4.3 x 10(3) and between < 10 and 1.2 x 10(4) colony forming units/ml for the waters bottled in PVC and glass, respectively. The greatest resistance to a single antibiotic, 39.1% of 320 isolates from mineral waters, was found for nalidixic acid. Resistance to the other antibiotics was as follows: ampicillin (26.2%), bacitracin (19.7%), cotrimoxazole (18.7%), streptomycin (15.0%), tetracycline (14.4%), gentamycin (11.6%), chloramphenicol and rifampin (9.7%). The strains resistant to two or more antibiotics (multiple antibiotic resistant, MAR) provided 51% of the total isolates. Identification of 127 MAR strains showed that in the mineral waters gram-positive cocci dominated. The second, third and fourth group of identified MAR phenotypes were, in order to importance, gram-negative non-fermentative rods, gram-positive rods and gram-negative fermentative rods. The importance of the antibiotic resistant bacteria in mineral water is discussed.

Anti-Bacterial Agents↗
PubMed1994

Myelin degrading activity in the CSF of HIV-1-infected patients with neurological diseases.

Degradation of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination.

AIDS Dementia Complex↗
PubMed1994

Serum beta 2-microglobulin in intravenous drug users and its correlation with human immunodeficiency virus infection.

High levels of serum beta 2-microglobulin have been associated with human immunodeficiency virus infection and beta 2-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of beta 2-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum beta 2-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4+ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum beta 2-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of beta 2-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of beta 2-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Brain amines in glucocorticoid-induced hypertension in the rat.

A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3-acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension.

Animals↗
PubMed1992

Gallbladder volume in adults, and relationship to age, sex, body mass index, and gallstones: a sonographic population study.

The influence of gender, age, body size, cholelithiasis, and obesity on fasting gallbladder volume (GBV) was investigated by real-time ultrasonography in a general population cohort of subjects whose ages were between 30 and 69 yr, living in Bari, a Southeastern Italian city. Of the 2076 subjects analyzed, 1246 (60%) were males and 830 (40%) were females (mean age 50 yr). Among them, 1703 subjects were healthy, 108 had gallstones, and 265 were obese. Fasting GBV in healthy individuals was larger in males (M) than in females (F) [M, 18.7 +/- 0.3 (SEM) ml vs. F, 17.0 +/- 0.3 ml; p less than 0.001] and obese (M, 23.4 +/- 1.5 ml vs. 19.7 +/- 0.9 ml; p less than 0.05). The trend was similar in gallstone patients, but it was not statistically significant (M, 23.0 +/- 2.0 ml vs. F, 18.8 +/- 1.5 ml; t = 1.64). Gallbladder size correlated positively with body size in the lean healthy population (p less than 0.01), increased with age in healthy nonobese males (p less than 0.01), and was smaller in healthy males than in males with gallstones (0.01 less than p less than 0.02) and obese, in both sexes (p less than 0.01). We conclude that fasting GBV 1) is larger in lean healthy and obese males than females, 2) increases with age in lean males and with body size in healthy lean females, and 3) is greater in patients with gallstones and in obese subjects, and this might partially account for the defective gallbladder motor function reported in these patients.

Adult↗
PubMed1991

Glucocorticoid-induced hypertension in rats: role of the central muscarinic cholinergic system.

Betamethasone was administered on alternate days to rats, and the role of the central cholinergic system in the development of hypertension assessed. After 15 days of treatment the systolic blood pressure of treated rats was significantly higher than that of control rats. Peripheral administration of atropine but not of methyl atropine reduced systolic pressure in glucocorticoid-treated rats and had no effect in controls. Therefore, [3H]quinuclidinyl benzylate binding, sodium-dependent high-affinity choline uptake and choline acetyltransferase studies were performed in the septal area, anteroventrolateral medulla (AVLM), anterior hypothalamic preoptic area (AH/PO) and hypothalamus. The density of muscarinic receptors was increased in the hypothalamus and AVLM of treated rats without significant changes in affinity. Choline acetyltransferase activity significantly decreased in the AVLM and increased in the AH/PO. In addition, a decrease in the hypothalamus and an increase in the AH/PO of sodium-dependent high-affinity choline uptake was observed in glucocorticoid-treated rats. These results suggest the presence of an enhanced muscarinic cholinergic activity in several brain nuclei in rats with glucocorticoid-induced hypertension. This activation could be due to pre- and post-synaptic hypersensitivity.

Animals↗
PubMed1983

[Methodological survey of erythrocyte filtration time].

We measured the whole blood filtration time of 30 healthy subjects. The influence of hematocrit, fibrinogen, leucocyte and platelet count on filtration time was also evaluated. Multiple regression analysis did not demonstrate any effect of the above-mentioned parameters when they were separately considered. We have subsequently taken from the entire population a group of 14 subjects in which were simultaneously found values of hematocrit greater than or equal to 41%, fibrinogen greater than or equal to 210 mg/100 ml and platelet count greater than or equal to 250,000/mm3. The filtration time was significantly higher in this group (69 +/- 4 sec) than in the remaining 16 normal subjects (56 +/- 4 sec), p less than 0.05. These data suggest that the simultaneous variation of several parameters could modify the whole blood filtration time, while these parameters have no effect when taken separately.

Adult↗