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L Cimino

Publications and source records attributed to L Cimino.

At least 19 recordsLinked to original sources
PubMed2004

Differential inflammatory involvement in retina and choroïd in birdshot chorioretinopathy.

BACKGROUND: Birdshot chorioretinopathy is characterised by dual unrelated inflammatory involvement of the retina and the choroid. Indocyanine green angiography made it possible to assess and follow choroidal disease with the same precision as retinal involvement was followed so far. The aim of this study was to analyse the severity, progression and response to therapy of both retinal involvement using fluorescein angiography and choroidal involvement using indocyanine green angiography. PATIENTS AND METHODS: Patients with birdshot retinochoroidopathy followed at La Source Eye Centre in Lausanne, Switzerland from January 1995 to December 2002 were subdivided into three subgroups according to the duration of evolution of the disease: untreated patients with no more than one year duration of the disease (group 1, n = 6); treated patients with disease duration of 1 - 7 years duration (group 2, n = 5) and patients with disease lasting for more than 7 years (group 3, n = 4). Fluorescein and indocyanine green angiographic signs (angiographic scores given by a masked observer) were analysed in the 3 groups and compared to the "cream-coloured" fundus lesions. RESULTS: Fifteen out of the 742 patients (2.0 %) seen at La Source Eye Centre during the time period considered presented BC and were included in the study. In the "early disease group" fluorescein and ICG angiography showed more severe choroidal than retinal involvement with respective scores of 3 +/- 0.79 (ICG) and 2 +/- 1.17 (FA) while there were few depigmented fundus lesions to be seen (score 1 +/- 0.27). The choroidal involvement responded well to systemic corticosteroids +/- immunosuppressive therapy (scores in groups 2 and 3 = 1.2 and 0.75), while retinal disease was stabilised at best (scores in groups 2 and 3 = 2.2. and 2.4) and depigmented fundus lesions increased (scores in groups 2 and 3 = 2.8 and 3). CONCLUSION: The evolution and response to therapy of retinal and choroidal disease in birdshot chorioretinopathy have a different course with choroidal disease responding well to therapy while retinal disease is more resistant, possibly explaining the slow deterioration of functional parameters despite therapy. The increase of "cream-coloured" fundus lesions despite good choroidal response to therapy could be explained by depigmentation left behind after resolution of choroidal stromal granulomas, a hypothesis recently confirmed by an autopsy case of birdshot chorioretinopathy.

Adrenal Cortex Hormones↗
PubMed2004

Shielding analysis of the Microtron MT-25 bunker using the MCNP-4C code and NCRP Report 51.

A cyclic electron accelerator Microtron MT-25 will be installed in Havana, Cuba. Electrons, neutrons and gamma radiation up to 25 MeV can be produced in the MT-25. A detailed shielding analysis for the bunker is carried out using two ways: the NCRP-51 Report and the Monte Carlo Method (MCNP-4C Code). The walls and ceiling thicknesses are estimated with dose constraints of 0.5 and 20 mSv y(-1), respectively, and an area occupancy factor of 1/16. Both results are compared and a preliminary bunker design is shown.

Electrons↗
PubMed2003

Natural history of chronic viral hepatitis in southern Italy: epidemiological changes since the introduction of the anti-HCV test.

We investigated whether there are differences between the natural history of B and C chronic hepatitis in a southern Italian population, and whether the chronic viral hepatitis population was modified by the introduction of the anti-HCV test in 1989. We examined clinical charts of 1120 patients consecutively admitted to our division from January 1979 to December 1998 with the histological diagnosis of chronic viral hepatitis (304 from 1979 to 1988; 816 from 1989 to 1998). We found significant differences only in age at diagnosis (higher in the second decade, P = 0.001), and in aetiology (HBV decreased in the second decade, P < 0.0001). We were able to follow up 449 patients for 2-20 years (311 with HCV and 138 with HBV infection), and found that chronic HCV evolved to cirrhosis more frequently than did chronic HBV; but in both types time to development of cirrhosis and the incidence of death were similar. Our data confirm that a higher onset age of HBV and of HCV is frequently observed in those subjects who have a faster disease progression.

Adult↗
PubMed2001

Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects.

BACKGROUND/AIMS: Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS: We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS: Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS: Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

Adolescent↗
PubMed2001

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Adolescent↗
PubMed2001

Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study.

The optimal therapy for patients with chronic hepatitis C who have not responded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-alpha2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN. Forty consecutive patients with chronic hepatitis C, genotype 1b, who had not responded to IFN-alpha, were randomized to receive: (i) IFN 4.5 MU daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plus amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at the same dosage and duration (group B). After 1 month of therapy, normal alanine aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in group A and in six (31.6%) in group B. At the end of treatment, six patients (28.6%) in group A and three (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was detectable in all of them at levels comparable to the basal values; an ALT relapse occurred within 3 months of stopping therapy. The combination of daily IFN plus amantadine was ineffective in this setting.

Amantadine↗
PubMed2000

p53 regulates myogenesis by triggering the differentiation activity of pRb.

The p53 oncosuppressor protein regulates cell cycle checkpoints and apoptosis, but increasing evidence also indicates its involvement in differentiation and development. We had previously demonstrated that in the presence of differentiation-promoting stimuli, p53-defective myoblasts exit from the cell cycle but do not differentiate into myocytes and myotubes. To identify the pathways through which p53 contributes to skeletal muscle differentiation, we have analyzed the expression of a series of genes regulated during myogenesis in parental and dominant-negative p53 (dnp53)-expressing C2C12 myoblasts. We found that in dnp53-expressing C2C12 cells, as well as in p53(-/-) primary myoblasts, pRb is hypophosphorylated and proliferation stops. However, these cells do not upregulate pRb and have reduced MyoD activity. The transduction of exogenous TP53 or Rb genes in p53-defective myoblasts rescues MyoD activity and differentiation potential. Additionally, in vivo studies on the Rb promoter demonstrate that p53 regulates the Rb gene expression at transcriptional level through a p53-binding site. Therefore, here we show that p53 regulates myoblast differentiation by means of pRb without affecting its cell cycle-related functions.

Animals↗
PubMed2000

Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies.

BACKGROUND: Inflammatory choriocapillaropathies (choriocapillaritis) correspond to the clinical spectrum of lesions of the fundus, including acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis (MC), and other rarer entities caused by inflammatory disturbances of choriocapillaris perfusion. The aim here was to study the sensitivity of indocyanine green (ICG) angiography in investigating and following inflammatory choriocapillaropathies. PATIENTS AND METHODS: Patients with inflammatory choriocapillaropthies were included who had had a dual fluorescein and ICG angiography as well as visual field testing (Goldman or computerized perimetry) at presentation and on follow-up visits. ICG angiography was performed according to a routine angiographic protocol used for inflammatory diseases and was correlated with fundus examination, fluorescein angiography, and visual field testing. RESULTS: Three patients with MEWDS, two with APMPPE, and two with MC were included. The visual field alterations in all seven patients were well correlated with the extent of the hypofluorescent areas seen on ICG angiography, whereas they were badly correlated with fluorescein angiographic signs and their evolution. The visual field in MEWDS was particularly well correlated with the importance of peripapillary hypofluorescence seen on ICG angiography. In MC, the evolution of new lesions was well demonstrated by ICG angiography and well correlated with visual symptoms and visual fields, but was barely detected on fundus examination and by fluorescein angiography. CONCLUSIONS: ICG angiographic signs were shown to be closely correlated with visual function (visual field testing). This was not the case for either fundus examination or fluorescein angiography. ICG angiography appears as a very sensitive follow-up parameter in inflammatory choriocapillaropathies, giving morphological information on the evolution of the disease and on the response to treatment when therapy is indicated.

Adult↗
PubMed1998

Regulation of E2F4 mitogenic activity during terminal differentiation by its heterodimerization partners for nuclear translocation.

E2F/DP heterodimers play a pivotal role in the regulation of cell growth and differentiation. A decrease in E2F/DP activity occurs during cell cycle arrest and differentiation. However, very little is known about the specific role of the various E2F/DP members along the transition from proliferation to terminal differentiation. We have previously shown that E2F4 accounts for the vast majority of the endogenous E2F in differentiating muscle cells. Here, we show that E2F4, which lacks a nuclear localization signal (nls), is distributed in both the nucleus and the cytoplasm, in either asynchronously growing myoblasts or differentiated myotubes. E2F4 nuclear accumulation is induced by the binding in the cytoplasm with specific partners p107, pRb2/p130, and DP3delta, an nls-containing spliced form of DP3, which provide the nls. Although overexpression of E2F4/DP3delta reactivates the cell cycle in quiescent cells, the E2F4 nuclear accumulation induced by pRb2/p130 and p107 correlates with cell growth arrest Moreover, E2F4/DP3delta-induced cell cycle reactivation is efficiently counteracted by either p107 or pRb2/p130 overexpression. Reinduction in quiescent cells of DNA synthesis by E2F1/DP1 overexpression is abrogated by coexpression of pRb and is hampered by MyoD overexpression. Both pRb2/p130 and pRb, as well as MyoD, are up-regulated in myotubes. Accordingly, multinucleated myotubes, which are induced to reenter the S-phase by oncoviral proteins, are refractory to cell cycle reactivation by forced expression of E2F4/DP3delta or E2F1/DP1. Thus, E2F/DP repression represents only one of multiple redundant circuits that control the postmitotic state in terminally differentiated cells and that are targeted by adenovirus E1A and SV40 large T antigen.

Animals↗
PubMed1998

Effect of N-acetyl-cysteine on lymphomonocyte glutathione and response to interferon treatment in C-virus chronic hepatitis.

BACKGROUND/AIM: Much controversy exists concerning effect of N-acetyl-cysteine, a precursor of glutathione, on the response to interferon treatment in patients with C-virus chronic hepatitis. The aim of this study was to evaluate the efficacy of interferon therapy with and without oral N-acetyl-cysteine. We also measured glutathione concentrations in lymphomonocytes of 25 patients with chronic C-virus hepatitis before and after interferon treatment and correlated the results with treatment response. METHODS: Glutathione was extracted from lymphomonocytes and measured with a modified high performance liquid chromatographic method in the 25 hepatitis patients and 12 healthy controls. RESULTS/CONCLUSIONS: 1) Hepatitis patients and controls had similar basal concentrations of lymphomonocytic glutathione; 2) neither interferon nor N-acetyl-cysteine significantly affected glutathione concentrations in patients; and 3) N-acetyl-cysteine did not affect response to interferon.

Acetylcysteine↗
PubMed1997

Uncoupling of p21 induction and MyoD activation results in the failure of irreversible cell cycle arrest in doxorubicin-treated myocytes.

Doxorubicin (Dox, Adriamicin), a potent broad spectrum anthracycline anticancer drug, selectively inhibits muscle specific gene expression in cardiac cells in vivo and prevents terminal differentiation of skeletal muscle cells in vitro. By inducing the expression of the helix-loop-helix (HLH) transcriptional inhibitor ld2, Dox represses the myogenic function of the MyoD family of muscle regulatory factors (MRFs). In many cell types, terminal differentiation is coupled to an irreversible exit from the cell cycle and MyoD plays a critical role in the permanent cell cycle arrest of differentiating myocytes by upregulating the cyclin dependent kinase inhibitor (cdki) p21. Here, we correlate Dox effects on cell cycle with changes of E2F/DP complexes and activity in differentiating C2C12 myocytes. In Dox-treated quiescent myoblasts, which fail to differentiate into myotubes under permissive culture conditions, serum re-stimulation induces cyclin/cdk re-association on the E2F/DP complexes and this correlates with an evident increase in E2F/DP driven transcription and re-entry of myoblasts into the cell cycle. Despite Dox ability to activate the DNA-damage dependent p53/p21 pathway, when induced in the absence of MyoD or other MRFs, p21 fails to maintain the postmitotic state in Dox-treated myocytes induced to differentiate. Thus, uncoupling p21 induction and MyoD activity results in a serum-reversible cell cycle arrest, indicating that MRF specific activation of cdki(s) is required for permanent cell cycle arrest in differentiating muscle cells.

Animals↗
PubMed1997

Beta 4 integrin subunit expression is downregulated in low metastatic carcinoma variants.

Organization and expression of the gene coding for beta 4 integrin subunit were investigated in murine carcinoma lines endowed with low and high metastatic potential maintained both in vivo and in vitro. Probes corresponding to either the extracellular or the cytoplasmic domains of the protein were generated and employed for Southern and Northern blot hybridization experiments. Southern blot analysis demonstrates a restriction fragment-length polymorphism between BALB/c and C57BI/6J DNAs. The different genomic organization of the beta 4 gene apparently does not generate variation in mRNA length. Northern blot analysis reveals a 7-kb transcript encoding full-length beta 4 protein and shorter transcripts that apparently correspond to nonfunctional mRNAs. In carcinoma cells endowed with low metastatic capacity, the 7-kb mRNA cannot be revealed in spite of the presence of shorter transcripts. In contrast, the 7-kb transcript is always present in tumor cells endowed with high metastatic capacity. Accordingly, the beta 4 protein is detectable, either by immunofluorescence or by Western blot analyses, only in highly metastatic carcinoma cells. In conclusion, the data presented show that in these murine carcinoma cell lines (i) the 7-kb mRNA is associated with a more invasive phenotype, and (ii) missing expression of the beta 4 integrin subunit in low metastatic carcinoma cells depends, at least in part, on mechanisms acting at a post-transcriptional level. The possibility that beta 4 subunit expression is a consequence of specific differentiation stages of lung carcinoma cells is discussed.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1996

The beta 4 integrin subunit is expressed in mouse fibroblasts and modulated by transforming growth factor-beta 1.

Integrin beta 4 subunit is present in association with alpha 6 chain on both normal and transformed epithelial cells. Recently alpha 6 beta 4 heterodimer was found on the endothelium of medium-sized blood vessels and on immature thymocytes. In this report we show, by Northern blotting, indirect immunofluorescence, immunoprecipitation, and Western blotting, that beta 4 subunit is expressed also on cells of mesenchymal origin such as fibroblasts, myoblasts, and myotubes. Increased expression of alpha 6 beta 4 has been related to the aggressive metastatic phenotype of human and murine carcinomas. The transforming growth factor beta 1 (TGF-beta 1) has been found to modulate the expression of several integrins and intracellular matrix proteins, as well as to stimulate cell invasion and metastatic potential. To evaluate whether alpha 6 beta 4 expression is modulated by TGF-beta 1, we transfected 3T3 fibroblasts with an expression vector carrying the human TGF-beta 1 cDNA driven by the SV40 early promoter. We observed by indirect immunofluorescence a modification in the subcellular distribution of beta 4 subunit, which acquires a perinuclear localization. This finding suggests this integrin subunit correlates with the cytoskeletal reorganization induced by TGF-beta 1.

3T3 Cells↗
PubMed1996

Interference with p53 protein inhibits hematopoietic and muscle differentiation.

The involvement of p53 protein in cell differentiation has been recently suggested by some observations made with tumor cells and the correlation found between differentiation and increased levels of p53. However, the effect of p53 on differentiation is in apparent contrast with the normal development of p53-null mice. To test directly whether p53 has a function in cell differentiation, we interfered with the endogenous wt-p53 protein of nontransformed cells of two different murine histotypes: 32D myeloid progenitors, and C2C12 myoblasts. A drastic inhibition of terminal differentiation into granulocytes or myotubes, respectively, was observed upon expression of dominant-negative p53 proteins. This inhibition did not alter the cell cycle withdrawal typical of terminal differentiation, nor p21(WAF1/CIP1) upregulation, indicating that interference with endogenous p53 directly affects cell differentiation, independently of the p53 activity on the cell cycle. We also found that the endogenous wt-p53 protein of C2C12 cells becomes transcriptionally active during myogenesis, and this activity is inhibited by p53 dominant-negative expression. Moreover, we found that p53 DNA-binding and transcriptional activities are both required to induce differentiation in p53-negative K562 cells. Taken together, these data strongly indicate that p53 is a regulator of cell differentiation and it exerts this role, at least in part, through its transcriptional activity.

Animals↗
PubMed1996

Differential diagnosis between hepatocellular carcinoma and cirrhosis through a discriminant function based on results for serum analytes.

We applied a multivariate analysis to a large series of serum biochemical tests in an attempt to identify a function that could efficiently discriminate cirrhosis from hepatocellular carcinoma (HC). We analyzed two successive temporal cohorts (1987-90; 1991-94) of HC and cirrhotic patients, all histologically classified (first cohort: 69 cirrhosis and 39 HC; second cohort: 66 cirrhosis and 38 HC). Using data from the first temporal cohort of patients, we obtained a discriminant function based on seven serum analytes: alpha-fetoprotein, the hepatic isoenzyme of alkaline phosphatase, lactate dehydrogenase isoenzyme 5, total gamma-glutamyltransferase (GGT), GGT isoforms complexed with low-density lipoprotein, aspartate aminotransferase, and copper. The same panel of analytes emerged when the second cohort was tested and also when both cohorts were tested together. In the two successive cohorts (total, 212 patients) with a prevalence of cirrhosis vs HC of approximately 2:1, the discriminant function correctly classified 93% of cases, the highest percentage of correct classification of the two diseases obtained so far by laboratory approaches. Validation with the jackknife reallocation statistical algorithm confirmed these results. In addition, of six patients with liver cirrhosis for whom we had the opportunity of following up and observing the evolution to HC, five were classified as HC at diagnosis by the multivariate discriminant analysis; i.e., discriminant analysis provided a diagnostic lead time of 6-12 months over histology. This discriminant function, based on easy-to-perform serum biochemical tests, may help solve a fundamental problem of differential diagnosis in the evolution of chronic liver diseases from cirrhosis to HC.

Alkaline Phosphatase↗
PubMed1996

Ascitic pseudouridine discriminates between hepatocarcinoma-derived ascites and cirrhotic ascites.

Various biochemical indexes discriminate neoplastic from nonneoplastic ascites. However, within the latter group, the distinction between cirrhotic ascites and ascites caused by hepatocarcinoma (HC) is usually based on liver biopsy or cytology. HC-derived ascites is included in the group of nonneoplastic ascites because it is not associated with peritoneal spreading of neoplastic cells. In 54 cases of cirrhotic ascites and 17 cases of HC ascites, all histologically diagnosed, ascitic pseudouridine concentrations discriminated cirrhotic from HC ascites. For example, using the cutoff value of 4.25 mumol/L (obtained by ROC curve analysis) resulted in a diagnostic sensitivity of 88.2% and a diagnostic specificity of 90.8%. Moreover, in cirrhosis, the ascitic concentrations of pseudouridine were lower than serum concentrations, and the two sets of values were correlated; in HC, however, ascitic pseudouridine concentrations were higher than serum concentrations, and the two were unrelated. These findings strongly suggest that in cirrhotic patients ascitic pseudouridine derives from serum by diffusion, whereas in HC patients the mechanism appears to be more complex.

Aged↗