Biomedical subjects

R Mancini

Publications and source records attributed to R Mancini.

At least 37 records · Page 2Linked to original sources

PubMed2000

Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix.

To analyze relevant factors and their effects on neoplastic progression in cervical carcinoma, a panel of genetic markers was studied. Paraffin-embedded tissue sections were obtained from 37 patients with carcinoma of the uterine cervix, 14 noninvasive squamous cell carcinomas (NISCCs), and 23 invasive squamous cell carcinomas (ISCCs). Immunoreactivity of Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Positive staining of Msh2 was detected in 13 of 14 (92.9%) NISCCs and in 13 of 23 (56.5%) ISCCs (P < 0.02). Mlh1 immunoreactivity was observed in 10 of 14 (71.4%) NISCCs and in 8 of 23 (34.8%) ISCCs (P < 0.04). Overexpression of p53 protein was found in 4 of 14 (28.6%) NISCCs and in 16 of 23 (69.6%) ISCCs (P < 0.02). Bcl-2 overexpression was detected in 2 of 14 (14.3%) NISCCs and in 15 of 23 (65.2%) ISCCs (P < 0.003). No significant difference in the two types of lesion was found for Bax and Fhit expression. The relationship between Mlh1, Msh2, and p53 protein expression was significant (P < 0.001 and P < 0.001, respectively), as was that between Fhit and Bax immunoreactivity (P < 0.02). In conclusion, we consider that altered expression of Msh2, Mlh1, p53, and Bcl-2 may be a critical event during cervical cancer progression, whereas Fhit may be a component of a proapoptotic pathway.

Acid Anhydride Hydrolases↗

PubMed1999

CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid.

Membrane fission is essential in intracellular transport. Acyl-coenzyme As (acyl-CoAs) are important in lipid remodelling and are required for fission of COPI-coated vesicles. Here we show that CtBP/BARS, a protein that functions in the dynamics of Golgi tubules, is an essential component of the fission machinery operating at Golgi tubular networks, including Golgi compartments involved in protein transport and sorting. CtBP/BARS-induced fission was preceded by the formation of constricted sites in Golgi tubules, whose extreme curvature is likely to involve local changes in the membrane lipid composition. We find that CtBP/BARS uses acyl-CoA to selectively catalyse the acylation of lysophosphatidic acid to phosphatidic acid both in pure lipidic systems and in Golgi membranes, and that this reaction is essential for fission. Our results indicate a key role for lipid metabolic pathways in membrane fission.

Acyl Coenzyme A↗

PubMed1999

Complementation of the fol2 deletion in Saccharomyces cerevisiae by human and Escherichia coli genes encoding GTP cyclohydrolase I.

Saccharomyces cerevisiae is so far the only organism where a knock-out mutant in the gene encoding GTP cyclohydrolase I (FOL2) has been obtained. GTP cyclohydrolase I controls the de novo biosynthetic pathway of tetrahydrobiopterin and folic acid. Since deletion of yeast FOL2 leads to a recessive auxotrophy for folinic acid, we used a yeast fol2Delta mutant for an in vivo functional assay of heterologous GTP cyclohydrolases I. We show that the GTP cyclohydrolase I, encoded either by the E. coli folE gene or by the human cDNA, complements the yeast fol2Delta mutation by restoring folate prototrophy. Furthermore the folE-3x allele of the E. coli gene, carrying three base substitutions, failed to complement the yeast fol2Delta defect. This allele behaved as a negative semidominant to the wild type folE and, when overexpressed, completely abolished complementation of fol2Delta by folE. Thus, the yeast fol2 null mutant is a suitable system to characterize mutations in genes encoding GTP cyclohydrolase I.

Alleles↗

PubMed1999

Polycyclic aromatic hydrocarbon-DNA adducts in cervical smears of smokers and nonsmokers.

OBJECTIVES: The aim of this study was to detect polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in single cervical cells collected during a routine Papanicolaou smear and to relate this carcinogen exposure dose marker to smoking habit. METHODS: An immunohistochemical assay, using a polyclonal antiserum raised against benzo[a]pyrene diol epoxide-DNA adducts, was performed to evaluate PAH-DNA adducts in cervical cells collected from 16 volunteers who smoked at least 20 cigarettes/day and 16 nonsmokers. RESULTS: The mean adduct level, determined as relative staining intensity by an optical density image analyzer, was significantly higher in smokers compared to nonsmokers (AOD x 1000 +/- SD = 98 +/- 32 and 73 +/- 25, respectively) (P = 0.04). CONCLUSIONS: These results demonstrate that this immunohistochemical assay, much simpler than other methodologies used to evaluate PAH-DNA adducts in cervical tissue, is sufficiently sensitive for quantitative adduct evaluation in single epithelial cervical cells, as already verified for other exfoliated material. This work thus confirms that tobacco smoke is a risk factor for genotoxic damage generation in cervical cells and indicates a procedure likely adaptable to a large population screening.

Adult↗

PubMed1999

Multifocal neural conduction impairment in forestry workers exposed and not exposed to vibration.

OBJECTIVE: The aim of the study was to assess peripheral neural involvement induced by exposure to hand-arm vibration. METHODS: Twenty lumberjacks, working regularly with chain-saws and exposed to hand-arm vibration (group E) and 20 forestry workers performing heavy manual work and not exposed to vibration (group NE) were matched with a control group of 20 healthy non-manual workers (group C). The subjects of groups E and NE, all symptomatic, and of group C underwent extensive bilateral neurophysiological examination consisting of: sensory conduction (velocity and amplitude) of radial, median and ulnar nerves in digit-wrist segments; sensory conduction (velocity) of median nerve in wrist-elbow segment; mixed conduction (velocity and amplitude) of median and ulnar nerves in palm-wrist segments; motor conduction velocity, including distal motor latencies, and amplitude of median (elbow-wrist) and ulnar (elbow-wrist and across the elbow) nerves. RESULTS: Electrophysiological abnormalities were found in 85% of group E's limbs, versus 62.5% of group NE's limbs. The most frequent pathological pattern in group E was a 'multifocal' impairment (multiple sites of several nerve segments), with a prevalent involvement of sensory rather than motor fibres in the hand, seldom extending to the forearm. Multivariate analysis showed that the neurographic parameters which better characterized workers exposed to hand-arm vibration had a pattern different from that usually found in idiopathic carpal tunnel syndrome (CTS). CONCLUSION: These results suggest that vibration-induced neural involvement can be considered neither pure digital neuropathy, nor definite CTS, as previously described.

Action Potentials↗

PubMed1999

Staurosporine-induced activation of caspase-3 is potentiated by presenilin 1 familial Alzheimer's disease mutations in human neuroglioma cells.

Familial Alzheimer's disease (FAD) mutant forms of presenilin 1 (PS1) and 2 have been shown to sensitize cells to apoptotic cell death. Here we explore the effects of FAD mutant forms of PS1 on caspase activation during apoptosis. We show that caspase activation leads to increased generation of alternative C-terminal fragments (CTFs) from mutant as compared to wild-type (wt) PS1. For this purpose, very low expression levels of wt, A246E, L286V, and deltaE10 FAD mutant PS1 proteins in stably transfected human H4 neuroglioma cells were used to avoid artifactual induction of spontaneous apoptosis due to overexpression of PS1. Staurosporine treatment of these cells resulted in increased cell death and up to a 10-fold increase in caspase-3 activation in mutant versus wt PS1-expressing cell lines. Correspondingly, relative levels of caspase-cleaved PS1 CTFs were increased by five- to sixfold in the FAD mutant versus wt PS1 cells. Elevated caspase activation and caspase cleavage of FAD mutant PS1 suggest the possibility of either a direct proapoptotic effect of mutant PS1 or interference of mutant PS1 with antiapoptotic effects of wt PS1.

Alzheimer Disease↗

PubMed1999

[Determination of interleukin-6 messenger RNA as malignant progression index in monoclonal gammapathy of undetermined significance].

The monoclonal gammopathy of undetermined significance (MGUS) could be considered a preneoplastic condition since no clinical and laboratory features are able to identify in advance the patients at high risk of disease progression. In this study we analysed IL-6mRNA expression on both bone marrow mononuclear cells and peripheral blood mononuclear cells sample of multiple myeloma (MM) and MGUS patients for evaluation if IL-6mRNA expression could be considered diagnostic or prognostic aspect of progression disease risk to MM. We concluded that expression of IL-6mRNA hasn't prognostic significance for the progression disease risk to multiple myeloma but could have a discriminant significance the MM and MGUS pathologies when combined with gene rearrangements and immunochemicals analysis.

Blotting, Northern↗

PubMed1998

Leber's Hereditary Optic Neuropathy (LHON) with 14484/ND6 mutation in a North African patient.

We report the clinical and genetic study of a Leber's Hereditary Optic Neuropathy (LHON) patient of North African origin harboring the 14484/ND6 mutation of mtDNA. For over a year we followed the ophthalmological course of this 24-year-old male with LHON treated with idebenone and vitamin B12. Serum lactate after effort was evaluated before, during and after therapy. Muscle biopsy was obtained for morphological study. Homo/heteroplasmy of 14484/ND6 mutation was studied in different tissues. Recovery of visual acuity was documented 6 months after onset and 3 months after therapy was established. Baseline serum lactate was elevated but normalized after 3.5 months of therapy. Muscle biopsy demonstrated only a few fibers with a slightly increased subsarcolemmal SDH activity. Genetic analysis showed homoplasmic 14484/ND6 mutation in all tissues investigated. The clinical phenotype of LHON/14484 in this patient closely resembles that commonly found in European patients. Even if LHON/14484 patients are reported to have a better prognosis for visual recovery, it is possible that the evolution of visual recovery in this patient could have been influenced by therapy as suggested by changes in serum lactate levels. Bioenergetic impairment of skeletal muscle was documented by lactate levels and muscle morphology. The 14484/ND6 mutation behaves as a primary mutation regardless of mtDNA population-specific backgrounds.

Adult↗

PubMed1998

Environmental and biological monitoring of exposure to mancozeb, ethylenethiourea, and dimethoate during industrial formulation.

The results of environmental (11 subjects) and biological (57 subjects) monitoring of exposure to mancozeb, ethylenethiourea (ETU), and dimethoate are reported for employees of a firm producing commercial formulations containing these active ingredients. Urinary excretion [GM(GSD)] of ETU (microg/g creatinine) and alkylphosphates [dimethylphosphate (DMP) + dimethylthiophosphate (DMTP) + dimethyldithiophosphate (DMDTP)] (nmol/g creatinine) was 65.3(4.8) and 419.2(2.1), respectively, for employees engaged in the formulation of a product containing 80% mancozeb (n = 9), 36.6(1.9) and 296.4(2.4) for those formulating a product containing 35% mancozeb (n = 9), 9.5(6.1) and 1022.4(3.0) for those engaged in plant maintenance and internal transport of materials (n = 6), 10.3(4.2) and 322.8(3.3) for those engaged in packaging the mancozeb formulations (n = 16), 4.4(3.3) and 2545.4(3.9) for those formulating a product containing 40% dimethoate (n = 11), and 3.0(2.7) and 871.7(3.3) for those bottling the same dimethoate formulation (n = 10). Air concentrations (microg/m3) ranged from 25.3 to 194.4 for dimethoate, from 0.2 to 1.3 for ETU, and from 139.9 to 949.0 for mancozeb. Urinary excretion of ETU and alkylphosphates showed a significant correlation with mancozeb (r2 = .971), and ETU (r2 = .858), and dimethoate (r2 = .955) contamination of the hands. Potential dose estimates showed that the potential respiratory doses of mancozeb and dimethoate accounted, on the average, for 38% of the total potential dose. The potential respiratory dose of ETU was 7% of the total potential dose. Total estimated absorption did not exceed the accepted daily dose (ADI) for ETU and mancozeb, but the ADI for dimethoate was exceeded. Serum and erythrocyte cholinesterase activities in workers formulating dimethoate products were not significantly different before and after exposure.

Adult↗

PubMed1998

The relationship between serum-soluble interleukin-2 receptor and radiological evolution in psoriatic arthritis patients treated with cyclosporin-A.

Aims of the study to evaluate the radiologically detected progression of joint damage in patients with psoriatic arthritis (PA) treated with cyclosporin-A (CsA) and to look for clinical and/or immunological parameters that might predict outcome. Twenty-four out-patients suffering from active PA entered a 2-year open prospective study on low-dose CsA (starting dose 3 mg/kg/day). Fifteen patients completed the study. Plain radiographs of hands and feet at study entry and at the end of follow-up were compared for the number of eroded joints. Serum-soluble IL-2 receptor (sIL-2R) levels were available in 13/15 patients before CsA therapy, after 6 months and after 2 years. The mean number of eroded joints per patient increased significantly during the study period (P = 0.017). Nine patients had less than two new eroded joints (responders) while the remaining six patients had five or more new eroded joints (non-responders). Serum sIL-2R levels were in the normal range after 6 months and 2 years of CsA treatment in all the responder patients and were above the 95th percentile of the control population in the six non-responders. We did not find any other demographical, clinical, radiological or laboratory parameter predictive of outcome in conclusion. (1) CsA seems to be able to control the 2-year progression of the radiologically measured damage in peripheral joints in 60% of PA patients. (2) A normal serum sIL-2R level after 6 months of therapy seems to have a prognostic value for a good outcome in PA patients treated with CsA.

Administration, Oral↗

PubMed1998

A prospective study of the cold response of digital vessels in forestry workers exposed to saw vibration.

OBJECTIVES: To investigate the occurrence of vibration-induced white finger (VWF) and the cold response of digital vessels in a group of 68 forestry workers who underwent a first clinical examination in 1990 and were then reexamined in 1995. METHODS: The forestry workers were divided into three groups: group A (n = 27), active workers who did not have VWF in 1990 and continued to use chain saws; group B (n = 29), workers who did not have VWF in 1990 and retired before 1995; and group C (n = 12), active or retired workers who had VWF in 1990. The subjects underwent a medical interview, a complete physical examination, and a cold provocation test, which were performed by the same physicians at both surveys. The cold test consisted of measurement of the finger systolic blood pressure (FSBP) after local cooling to 10 degrees C, expressed as a percentage of the pressure recorded at 30 degrees C (FSBP%10 degrees). RESULTS: Three new cases of VWF occurred during the follow-up period among workers who had used only antivibration (AV) chain saws. The vasoconstrictor response to cold was unchanged in group A and improved in group B (P < 0.001). A significant decrease in VWF symptoms and abnormal response to cold was observed in group C (P < 0.05). As a result of preventive measures curtailing saw usage time in the VWF workers, the daily vibration exposure in group C was lower in 1995 than in 1990 (P = 0.02). In the retired workers, FSBP%10 degrees was positively related to the time since the cessation of work with chain saws (P < 0.01). CONCLUSIONS: The findings of this follow-up study indicate that a reduction in or cessation of exposure to vibration has a beneficial effect on finger-blanching symptoms and the cold response of digital vessels. The occurrence of new cases of VWF in subjects whose work experience was limited to AV chain saws argues for the maintenance of health surveillance in these workers.

Adult↗

PubMed1998

[Clinical use of leuprolide acetate depot in a group of gynecologic patients in the preoperative period].

BACKGROUND: The authors examined 33 patients with symptomatic uterine leiomyomas due to undergo total hysterectomy in order to evaluate the effects of treatment with GnRH analogues on leiomyoma and estrogen and progesterone receptors. METHODS: The patients were divided into two groups: one group was treated with leuprolide acetate (Group A) and the other did not receive treatment (Group B). RESULTS: A significant reduction in the volume of leiomyomas and estrogen and progesterone receptors was noted in patients in Group A. CONCLUSIONS: Treatment with GnRH analogues therefore represents a valid aid for patients with uterine leiomyomas and sideropenic anemia awaiting surgery.

Adult↗

PubMed1997

T-helper 2 type cytokine and soluble interleukin-2 receptor levels in seminal plasma of infertile men.

PROBLEM: The role of cell-mediated immunity (CMI) in unexplained male infertility and impaired sperm function has been explored. METHOD OF STUDY: The presence of cytokines, namely, interleukin-4 (IL-4), interleukin-6 (IL-6), and the soluble interleukin-2 receptor (SIL-2R), was investigated in seminal plasma of 18 fertile and 20 infertile subjects, using specific enzyme-linked immunoadsorbent assays. RESULTS: IL-4 was not detected. SIL-2R was detected, but the concentration difference between the fertile and infertile group was not significant. IL-6 was detected with significantly higher levels in the infertile group compared to the fertile group. IL-6 levels in seminal plasma correlated positively with leukocyte count and negatively with sperm count, motility, and morphology. CONCLUSIONS: These findings show: a) a lack of IL-4 in seminal plasma; b) similar SIL-2R levels in fertile and infertile seminal plasma; c) increased IL-6 secretion in seminal plasma of infertile subjects; and d) specific correlations of IL-6 with the main semen parameters.

Adult↗

PubMed1997

Impaired lymphocyte proliferation in human acute pancreatitis.

PURPOSE: We evaluated the proliferative response of lymphocytes to phytohemagglutinin P (PHA P), concanavalin A (Con A), and pokeweed mitogen (PWM) during the course of acute pancreatitis. PATIENTS AND METHODS: Sixty consecutive patients with acute pancreatitis were studied within 48 h of the onset of pain, and 16 of them were also studied 1 month after complete recovery. According to the Atlanta criteria, 21 patients had severe disease and 39 had mild disease. Fifteen healthy subjects and 11 patients with nonpancreatic acute abdomen were studied as controls. In 12 patients with acute pancreatitis the lymphocyte proliferation after stimulation with the three mitogens was also assessed in autologous and heterologous plasma. RESULTS: The lymphocyte proliferative response to optimal doses of PHA P, Con A, and PWM was significantly lower (p < 0.001) in acute pancreatitis patients (mean +/- SD; PHA P 74,310 +/- 22,960 cpm; Con A 64,669 +/- 20,188 cpm; PWM 26,714 +/- 6,436 cpm) than in healthy subjects (PHA P 111,316 +/- 12,044 cpm; Con A 96,276 +/- 12,327 cpm; PWM 33,957 +/- 3,601 cpm). Patients with nonpancreatic acute abdomen had a significantly higher lymphocyte proliferative response to PHA P and Con A than acute pancreatitis patients (PHA P p < 0.002; Con A p < 0.01; PHA P 91,116 +/- 22,995 cpm; Con A 77,879 +/- 19,083 cpm). In patients with acute pancreatitis, lymphocyte proliferation stimulated with PHA P and Con A was significantly lower (PHA P p < 0.005; Con A p < 0.001) in those with severe disease (PHA P 63,190 +/- 15,157 cpm; Con A 52,813 +/- 13,324 cpm) than in those with mild disease (PHA P 80,298 +/- 24,340 cpm; Con A 71,052 +/- 20,490 cpm). In the group of 16 patients studied during the initial phase of acute pancreatitis and 1 month after recovery, lymphocyte proliferation significantly improved after remission of the disease but remained impaired compared with that of healthy subjects. No difference was found in the lymphocyte proliferation of the 12 patients with acute pancreatitis assayed in autologous and heterologous plasma. CONCLUSIONS: The peripheral lymphocyte proliferative response to mitogen stimulation in patients with acute pancreatitis was decreased during the early phases of the disease.

Abdomen, Acute↗

PubMed1997

Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1 mutations and correlation with the mitochondrial genotype.

To clarify the bioenergetic relevance of mtDNA mutations in Leber's hereditary optic neuropathy (LHON), we investigated affected individuals and healthy carriers from six Italian LHON families harboring the 11778/ND4 and the 3460/ND1 mtDNA mutations. The enzymatic activities of mitochondrial complex I and its sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied in mitochondrial particles from platelets, in correlation with mtDNA analysis of platelets and leukocytes. In platelets homoplasmic for mutant mtDNA, both 11778/ND4 and 3460/ND1 mutations induced resistance to rotenone and the 3460/ND1 mutation also provoked a marked decrease in the specific activity of complex I. Individuals heteroplasmic in platelets for either mutation showed normal biochemical features, indicating functional complementation of wild-type mtDNA. There was no correlation between the clinical status and mtDNA homo/heteroplasmy in platelets, but the biochemical features correlated with the mitochondrial genotype of platelets. In some cases, the degree of mtDNA heteroplasmy differed in platelets and leukocytes from the same individual with a prevalence of wild-type mtDNA in the platelets. These results imply that biochemical studies on mitochondrial diseases should always be integrated with mtDNA analysis of the same tissue investigated and also suggest that the mtDNA analysis on the leukocyte fraction, as usually performed in LHON, does not necessarily reflect the mutant genotype level of other tissues. The differential tissue heteroplasmy may be more relevant than previously thought in determining disease penetrance.

Antineoplastic Agents, Phytogenic↗

PubMed1997

[Isolated cardiac amyloidosis. Presentation of a clinical case].

A 48-year old patient affected by congestive heart failure came to our observation for cardiac arrest due to ventricular fibrillation. After cardiopulmonary resuscitation and defibrillation he underwent complete evaluation. Echo Doppler findings were consistent with restrictive cardiomyopathy. Laboratory findings revealed monoclonal gammopathy and plasma cells dyscrasia. Diagnosis of amyloidosis was then suspected and biopsies of different organs and tissues were performed. Presence of amyloid deposits was found only in myocardial specimens from the right ventricle. Medical treatment with drugs of various classes, administered during hemodynamic invasive monitoring, was uneffective in improving the hemodynamic and clinical status of the patient and he entered in a heart transplantation list. He died six months later, while awaiting for transplantation. Although isolated cardiac amyloidosis is quite rare, we believe that this condition has ever to be kept in mind during differential diagnosis of restrictive cardiomyopathies and we remark that endomyocardial biopsy was mandatory and necessary for certain diagnosis in this case; in addition, the unefficacy of drugs nowadays available for treatment of congestive heart failure in amyloid cardiomyopathy is confirmed.

Amyloidosis↗

PubMed1996

Thermal resistance of pantetheine hydrolase.

Pantetheine hydrolase from pig kidney shows a very high resistance to denaturation with chemical denaturants, being unfolded at concentrations of guanidinium chloride higher than 6.5 M. On the contrary, chemical inactivation, followed by recording catalytic activity, occurs before conformational changes can be detected by fluorimetric or spectroscopic measurements. The enzyme resists temperatures as high as 80 degrees C, as monitored by second derivative spectroscopy and circular dichroism. Activity increases with temperature to an optimum of about 70 degrees C recording the initial velocity. The enzyme behaves very differently against chemical denaturants or against temperature denaturation. These results are unusual for a mesophilic protein.

Amidohydrolases↗

PubMed1996

Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis.

Interferon gamma (IFN-gamma) inhibits in vitro the activation of hepatic stellate cells (HSC), the primary extracellular matrix-producing cells in liver fibrosis. This study was undertaken to determine in vivo the effect of IFN-gamma in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an early response to cell injury. Rats were killed after 1 or 3 weeks of treatment with DMN, IFN-gamma, DMN + IFN-gamma, or saline. Immunohistochemistry was used to identify proliferating (desmin-positive/bromodeoxyuridine (BrdU)-positive cells) and activated (alpha-smooth-muscle actin [alpha-SMA]-positive cells) HSCs. Collagen deposition was determined colorimetrically and by morphometry. The parenchymal extension of desmin- and actin-positive cells and of fibrotic tissue was measured by point-counting technique and expressed as a percentage of area. Western blot was used to determine laminin and fibronectin accumulation. The levels of messenger RNA (mRNA) for procollagen type I, fibronectin, and laminin were evaluated by Northern blot. No differences were observed in rats treated with either saline or IFN-gamma alone. IFN-gamma reduced HSC activation induced by liver injury, as shown by the decreased number of proliferating HSC and the reduction of parenchymal area occupied by alpha-SMA-positive cells observed in DMN + IFN-gamma-treated animals compared with the DMN group. This was associated with reduced collagen, laminin, and fibronectin accumulation and lower levels of mRNA for procollagen type I, fibronectin, and laminin in the DMN + IFN-gamma group. Thus, this study indicates that IFN-gamma reduces extracellular matrix deposition in vivo by inhibition of HSC activation.

Actins↗