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Biomedical subjects

V Rossi

Publications and source records attributed to V Rossi.

At least 19 recordsLinked to original sources
PubMed2006

Natural and synthetic retinoids in prostate cancer.

Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied class of chemopreventive drugs for PCa. Retinoids play a key role in several vital functions as vision and development, and also exert anti-proliferative actions. Anti-proliferative effects of retinoids rely on the regulation of many biological processes, including differentiation, cell proliferation, and apoptosis. Retinoid actions are mediated by two classes of nuclear proteins called retinoic acid (RARalpha,beta and gamma and retinoic alpha,beta and gamma receptors, which are ligand-regulated transcription factors. Effects of both all-trans-retinoic acid (RA), the natural active derivative of vitamin A, and its synthetic derivatives, on prostate gland or prostate cell lines implicate retinoids in the regulation of prostate growth and suppression of PCa development. Deficient retinoid availability and action at the cellular level because of either decreased content or altered metabolism in PCa cells can play a key role in abnormal cellular differentiation pathways, and the loss of anti-proliferative effects. Here we review the in vitro and in vivo effects of retinoids in PCa.

Animals↗
PubMed2005

Interpretive criteria for disk diffusion susceptibility testing of ulifloxacin, the active metabolite of prulifloxacin.

Prulifloxacin, a new fluoroquinolone, is a prodrug whose active compound, ulifloxacin, is derived from its transformation after oral administration and intestinal absorption. Based on early pharmacokinetic and pharmacodynamic data, the following MIC breakpoints have tentatively been proposed: < or = 1 microg/ml, susceptible; 2 microg/ml, intermediate; and > or = 4 microg/ml, resistant. In this report, ulifloxacin MIC vs. zone diameter scattergrams and discrepancy rates were analyzed in 461 freshly isolated clinical strains (237 Enterobacteriaceae, 101 nonfermenters, and 123 Gram-positive bacteria). In agreement with the guidelines of the National Committee for Clinical Laboratory Standards, a modification of the error rate-bounded method was used to select disk diffusion test breakpoints. The following zone diameter breakpoints were chosen and are proposed herein for the interpretation of ulifloxacin disk (5 microg) test results: < or = 15 and > or = 19 mm for Enterobacteriaceae, < or = 16 and > or = 20 mm for nonfermenters, and < or = 14 and > or = 18 mm for Gram-positive bacteria. By applying these breakpoint values, no very major errors were detected, while major and minor errors were largely below the accepted discrepancy rates.

Colony Count, Microbial↗
PubMed2005

Hemodiafiltration with post-dilution reinfusion of the regenerated ultrafiltrate: a new on-line technique.

AIMS: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. METHODS: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. RESULTS: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly after PDHFR treatment. CONCLUSIONS: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and beta2-m, and the filter. Finally, it's notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.

Adult↗
PubMed2004

Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to assess the compatibility between acetaminophen (Ac) and some excipients (polyvinylpyrrolidone (P), magnesium stearate (M), citric acid (C), aspartame (As), mannitol (Mn), cellulose (Cll) and starch (S)) in several of the more commercially available pharmaceutical formulations and in solid binary mixtures. The present study compared thermodynamic data on acetaminophen melting and vaporization processes of pure acetaminophen with those found for several solid mixtures and in some commercially available acetaminophen-based dosage forms. Appreciable modifications occur only for solid mixtures with high content of excipient. Acetaminophen-based dosage forms and its solid binary mixtures usually show "additivity" of calorimetric peaks number of pure components in their calorimetric curve profiles, thus revealing a good thermoanalytical compatibility between acetaminophen and the excipients examined, except for samples containing appreciable content of mannitol.

Acetaminophen↗
PubMed2004

Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H.

Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry or polymerase chain reaction after sequential treatment with fludarabine and Campath-1H. Concern has been raised regarding the ability to mobilize sufficient peripheral blood progenitor cells (PBPCs) for autografting after purine analogues, and there are few data about PBPC collection after Campath-1H. In all, 16 CLL patients responding to sequential chemo-immunotherapy entered the study. In 10, mobilization regimen consisted of granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/die. Patients failing mobilization or not achieving the target of 2.5 x 10(6) CD34+ cells/kg underwent a second attempt using intermediate-dose (ID) Ara-C, 800 mg/m(2) every 12 h for six doses+G-CSF. PBPC collection after G-CSF alone was successful in two out of 10 patients. An adequate number of CD34+ cells were collected after ID Ara-C+G-CSF in eight patients failing the mobilization with G-CSF alone and in five out of six who did not receive G-CSF before. Greater yields of PBPCs were collected with Ara-C+G-CSF compared with G-CSF alone (13.8 vs 3.3). The extrahematologic toxicity was manageable. In conclusion, PBPC collection is feasible in CLL patients treated with sequential therapy including fludarabine and Campath-1H. Excellent yields were obtained in 92.8% of patients primed with ID Ara-C+G-CSF.

Adult↗
PubMed2004

Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein.

Acute lymphoblastic leukemia (ALLs) expressing MLL-AF4, the fusion product of t(4;11)(q21;q23), show marked leucocytosis and extramedullary disease in multiple organs, respond poorly to chemotherapy and have poor prognosis. In vitro, leukemic cells with the t(4;11) show resistance to serum deprivation-induced or interferon gamma-regulated CD95-mediated apoptosis. In addition, t(4;11) cells have prolonged doubling time and lower percentage of cells in cycle compared to non-t(4;11) B lineage cell lines. In this study, we examine the time- and level-dependent effects of MLL-AF4 conditional expression on cell cycle and differentiation of myelomonocytic leukemia cell line U937. By varying the concentration of tetracycline in growth media, we found that increasing levels of MLL-AF4 expression result in a progressive decrease in growth rate and fraction of S phase cells, paralleled by an increase in percentage of cells expressing CD11b. Our results demonstrate a dosage-dependent effect of MLL-AF4 fusion oncoprotein on cell cycle progression, with increasing expression levels resulting in the accumulation in G1, prolonged doubling time, both findings that might be responsible for the increased resistance to etoposide-mediated cytotoxicity. We propose the cell cycle control exerted by MLL-AF4 may be responsible of resistance to cell-death promoting stimuli in leukemia carrying the t(4;11) translocation.

Cell Differentiation↗
PubMed2003

Prevalence of osteoporosis and fractures in a migrant population from southern to northern Italy: a cross-sectional, comparative study.

The purpose of this study was to assess whether a migrant population from southern regions of Italy showed differences in osteoporosis (OP) and fracture prevalence in comparison to a population born and living in Milan, a city in northern Italy. The study group consisted of 1764 postmenopausal women born in southern Italy who migrated after age 20 to Milan, where they had lived for at least 15 years. This group was compared with a sample of 4018 postmenopausal women born, raised and living in Milan. Bone mineral density (BMD) was measured at lumbar spine by dual-energy X-ray absorptiometry. Univariate analysis showed a significantly higher BMI, a greater parity, a lower postmenopausal estrogen (HRT) usage and a lower calcium intake in the Southern group (SG). Densitometric values showed a mean lumbar BMD significantly lower in SG ( P<0.001), resulting in a greater prevalence of OP (30.5% versus 24.9%; P<0.001). Consistent with this result, the number of women reporting low energy fractures after menopause was higher in SG (4.8% versus 3.6%; P=0.01). Multiple logistic regression analyses showed that OP was predicted by well-recognized variables, such as age, age at menopause, BMI, HRT, calcium intake together to belonging to SG, which independently increased the risk for OP by 42%. Age, age at menopause, BMI and belonging to SG significantly influenced the fracture risk, but the last variable was no longer associated with an increased fracture risk when BMD was entered in the model. Despite the results of previous epidemiological studies and protective anthropometric measures, a higher OP and fracture prevalence was found in the migrant group from southern Italy to Milan in comparison with the native sample. These differences are not solely explained by lifestyle variables. Our data suggest that changing environmental exposures can influence bone mass and fracture risk.

Adult↗
PubMed2003

Prenatal nicotine exposure and behavior.

Prenatal exposure to nicotine has been associated with changes in behavioral indices in offspring. Flank marking, a scent-marking behavior in golden hamsters, appears to be controlled by arginine vasopressin (AVP) neurons in the hypothalamus. The present study examines the effects of prenatal exposure to nicotine on the vasopressinergic system associated with flank marking behavior.

Animals↗
PubMed2002

Structural biology of C1.

The classical complement pathway is a major element of innate immunity against infection, and is also involved in immune tolerance, graft rejection and various pathologies. This pathway is triggered by C1, a multimolecular protease formed from the association of a recognition protein, C1q, and a catalytic subunit, the calcium-dependent tetramer C1s-C1r-C1r-C1s, which comprises two copies of each of the modular proteases C1r and C1s. All activators of the pathway are recognized by the C1q moiety of C1, a process that generates a conformational signal that triggers self-activation of C1r, which in turn activates C1s, the enzyme that mediates specific cleavage of C4 and C2, the C1 substrates. Early work based on biochemical and electron microscopy studies has allowed characterization of the domain structure of the C1 subcomponents and led to a low-resolution model of the complex in which the elongated C1s-C1r-C1r-C1s tetramer folds into a compact, figure-of-8-shaped conformation upon interaction with C1q. The strategy used over the past decade was based on a dissection of the C1 proteins into modular segments to characterize their function and solve their three-dimensional structure by X-ray crystallography or NMR spectroscopy. This approach allows deep insights into the structure-function relationships of C1, particularly with respect to the assembly of the C1 complex and the mechanisms underlying its activation and proteolytic activity.

Animals↗
PubMed2001

Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2.

Mannan-binding lectin (MBL)-associated serine proteases-1 and 2 (MASP-1 and MASP-2) are homologous modular proteases that each interact with MBL, an oligomeric serum lectin involved in innate immunity. To precisely determine their substrate specificity, human MASP-1 and MASP-2, and fragments from their catalytic regions were expressed using a baculovirus/insect cells system. Recombinant MASP-2 displayed a rather wide, C1s-like esterolytic activity, and specifically cleaved complement proteins C2 and C4, with relative efficiencies 3- and 23-fold higher, respectively, than human C1s. MASP-2 also showed very weak C3 cleaving activity. Recombinant MASP-1 had a lower and more restricted esterolytic activity. It showed marginal activity toward C2 and C3, and no activity on C4. The enzymic activity of both MASP-1 and MASP-2 was specifically titrated by C1 inhibitor, and abolished at a 1:1 C1 inhibitor:protease ratio. Taken together with previous findings, these and other data strongly support the hypothesis that MASP-2 is the protease that, in association with MBL, triggers complement activation via the MBL pathway, through combined self-activation and proteolytic properties devoted to C1r and C1s in the C1 complex. In view of the very low activity of MASP-1 on C3 and C2, our data raise questions about the implication of this protease in complement activation.

Base Sequence↗
PubMed2001

Interaction properties of human mannan-binding lectin (MBL)-associated serine proteases-1 and -2, MBL-associated protein 19, and MBL.

The mannan-binding lectin (MBL) activation pathway of complement plays an important role in the innate immune defense against pathogenic microorganisms. In human serum, two MBL-associated serine proteases (MASP-1, MASP-2) and MBL-associated protein 19 (MAp19) were found to be associated with MBL. With a view to investigate the interaction properties of these proteins, human MASP-1, MASP-2, MAp19, as well as the N-terminal complement subcomponents C1r/C1s, Uegf, and bone morphogenetic protein-1-epidermal growth factor (CUB-EGF) segments of MASP-1 and MASP-2, were expressed in insect or human kidney cells, and MBL was isolated from human serum. Sedimentation velocity analysis indicated that the MASP-1 and MASP-2 CUB-EGF segments and the homologous protein MAp19 all behaved as homodimers (2.8-3.2 S) in the presence of Ca(2+). Although the latter two dimers were not dissociated by EDTA, their physical properties were affected. In contrast, the MASP-1 CUB-EGF homodimer was not sensitive to EDTA. The three proteins and full-length MASP-1 and MASP-2 showed no interaction with each other as judged by gel filtration and surface plasmon resonance spectroscopy. Using the latter technique, MASP-1, MASP-2, their CUB-EGF segments, and MAp19 were each shown to bind to immobilized MBL, with K:(D) values of 0.8 nM (MASP-2), 1.4 nM (MASP-1), 13.0 nM (MAp19 and MASP-2 CUB-EGF), and 25.7 nM (MASP-1 CUB-EGF). The binding was Ca(2+)-dependent and fully sensitive to EDTA in all cases. These data indicate that MASP-1, MASP-2, and MAp19 each associate as homodimers, and individually form Ca(2+)-dependent complexes with MBL through the CUB-EGF pair of each protein. This suggests that distinct MBL/MASP complexes may be involved in the activation or regulation of the MBL pathway.

Amino Acid Motifs↗
PubMed2001

Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females.

Rett syndrome is an X-linked dominant neurological disorder, which appears to be the commonest genetic cause of profound combined intellectual and physical disability in Caucasian females. Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed. We review the literature on MECP2 mutations in Rett syndrome. This analysis has permitted us to produce a map of the recurrent mutations identified in this and previous studies. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, which is conserved among brain-specific regulatory factors.

Adolescent↗
PubMed2001

The maize WD-repeat gene ZmRbAp1 encodes a member of the MSI/RbAp sub-family and is differentially expressed during endosperm development.

Members of the MSI/RbAp sub-family of WD-repeat proteins are widespread in eukaryotic organisms and form part of multiprotein complexes that are involved in various biological pathways, including chromatin assembly, regulation of gene transcription, and cell division. In this study we report the isolation and characterization of a cDNA sequence from Zea mays, which encodes an RbAp-like protein (ZmRbAp1) that binds acetylated histones H3 and H4 and suppresses mutations that have a negative effect on the Ras/cAMP pathway in yeast. The ZmRbAp genes form a gene family and are expressed in different tissues of Z. mays L. plants. Determination of its expression pattern during maize seed development revealed that ZmRbAp transcripts are abundant during the initial stages of endosperm formation. In addition, the transcripts are specifically localized in shoot apical meristem and leaf primordia of the embryo. A possible role for the ZmRbAp genes in early endosperm differentiation and plant development is discussed.

Acetylation↗
PubMed2001

MECP2 gene mutation analysis in the British and Italian Rett Syndrome patients: hot spot map of the most recurrent mutations and bioinformatic analysis of a new MECP2 conserved region.

Rett syndrome (RTT) is an X-linked dominant neurological disorder, which appears to be the most common genetic cause of profound combined intellectual and physical disability in Caucasian females. This syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of unknown target genes. We report a detailed mutational analysis of a large cohort of RTT patients from the UK and Italy. This study has permitted us to produce a hot spot map of the mutations identified. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, conserved among brain-specific regulatory factors.

Adolescent↗
PubMed2001

Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain.

This article describes the discovery of a novel SNARE domain that might be involved in the regulation of membrane fusion. This domain is shared by a novel family of VAMPs called long VAMPs or longins. Members of this family are more conserved among eukaryotes than are classical VAMPs, possibly because of their underlying basic SNARE function.

Amino Acid Sequence↗
PubMed2001

Structural biology of C1: dissection of a complex molecular machinery.

The classical pathway of complement is initiated by the C1 complex, a multimolecular protease comprising a recognition subunit (C1q) and two modular serine proteases (C1r and C1s) associated as a Ca2+-dependent tetramer (C1s-C1r-C1r-C1s). Early studies have allowed identification of specialized functional domains in these proteins and have led to low-resolution models of the C1 complex. The objective of current studies is to gain deeper insights into the structure of C1, and the strategy used for this purpose mainly consists of dissecting the C1 components into modular fragments, in order to solve their three-dimensional structure and establish the structural correlates of their function. The aim of this article is to provide an overview of the structural and functional information generated by this approach, with particular emphasis on the domains involved in the assembly, the recognition function, and the highly specific proteolytic properties of C1.

Animals↗