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S Battista

Publications and source records attributed to S Battista.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increase in AP-1 activity is a general event in thyroid cell transformation in vitro and in vivo.

We have recently reported that neoplastic transformation of two rat thyroid epithelial cell lines by retroviruses carrying the v-mos and v-ras Ki oncogenes is associated with a drastic increase of AP-1 activity. The most important effects were represented by the dramatic junB and fra-1 gene induction, which was abolished by the block of the transformation-induced HMGI-C protein synthesis. Here, we have further characterized the transformation-dependent AP-1 activity, by analysing the expression of different jun- and fos-related components, in rat thyroid cell lines transformed by several oncogenes, in human thyroid carcinoma cell lines, and in naturally occurring human thyroid tumours. A significant increase of Fra-1 and JunB protein levels was detected in all oncogene transformed rat thyroid cell lines. Fra-1 gene induction was demonstrated to occur also in human thyroid carcinoma cell lines and tissues. Conversely, c-Jun and JunD proteins, rather than JunB, accumulated in human thyroid carcinoma cell lines. An induction of AP-1 target genes was also detected both in rat and human thyroid transformed cell lines. Therefore, in vivo and in vitro thyroid cell transformation is associated with important compositional changes in the AP-1 complex and an increased transcriptional activity.

Animals↗
PubMed1998

Prediction by mathematical simulation of different pathophysiological effects on D-sorbitol bioavailability.

In this study a mathematical model was applied to predict how changes in hepatic extraction ratio (E), fractional portal inflow (P) and renal elimination ratio (R) may affect fractional D-sorbitol bioavailability in cirrhotic patients. D-sorbitol bioavailability was computed as the ratio between cumulative urinary outputs measured after infusion into the superior mesenteric (Uma) or the hepatic artery (Uha) and a systemic vein (Usv). The present work was aimed at explaining by mathematical simulation the very large difference observed in the regression lines when plotting Uma or Uha against Usv values. The study was performed by considering a pathophysiological model of the hepatic circulation and simulating independent variations of the above considered parameters or assuming particular pathophysiological conditions like hepatic arterialization and hepatofugal flow. Computational results account for the wide dispersion of experimental data obtained in previous studies and provide reasonable explanations of unexpected findings.

Biological Availability↗
PubMed1998

Arterial-venous shunting in liver cirrhosis.

Controversial data exist in the literature about the presence and clinical relevance of hepatic arterial-venous shunting. An interesting opportunity for reconsidering the problem has been provided by the use, in the study of liver function, of D-sorbitol, a substance whose first-pass hepatic extraction is very high in normal subjects, while being directly related to circulatory alterations in liver cirrhosis. Because of this property, the systemic bioavailability of D-sorbitol during hepatic arterial infusion can be assumed to reflect arterial-venous shunting. Thirteen biopsy-proven cirrhotic patients (ages 35-66 years), who required diagnostic arterial catheterization, entered the study. Patients were studied on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct low-rate infusion (15 mg/min for 20 min) into the hepatic artery and the systemic circulation, respectively. Urine samples were spontaneously collected for 8-hr periods before and during/after each infusion. The hepatic arterial bioavailability of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs of D-sorbitol after infusions into the hepatic artery and the systemic vein. Observed values confirm the existence and the large variability (0-88.7%) of hepatic arterial-venous shunting in cirrhotic patients.

Adult↗
PubMed1998

Ultrasound transmission speed and ultrasound bone profile score (UBPS) of the phalanges in normal women and women with osteoporosis.

The distal metaphysis of the first phalanx of the fingers II-V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone because of the simultaneous presence of compact and trabecular bone. With an ultrasound device (DBM sonic 1200, IGEA, Italy), we measured the adSOS (the amplitude dependent speed of sound) and the UBPS (ultrasound bone profile score), a score which is calculated from the graphic traces of the receiving probe with an expert system which uses fuzzy-logic at phalanges II-IV, as well as bone mineral density (BMD) at lumbar spine using dual X-ray absorptiometry (DXA). Precision of the measurements was as follows: adSOS: short-time-CV% = 0.576, long-time-CV% = 1.1, SCV% = 5.9, RMSSD% = 1.825. UBPS: short-time CV% = 5.95. There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.804 (p<0.00001). The validity of adSOS and UBPS was examined in 25 young and healthy women (mean age: 33.4 year), 15 postmenopausal healthy women (mean age: 58.5 years), 17 women with osteopenia, (mean age: 52.4 years), as defined by a t-score between -1 to -2.5 SD as lumbar BMD (DXA), and 20 women with osteoporosis and vertebral fractures (mean age: 61.4 years). We compared the healthy postmenopausal women and the women with osteoporotic vertebral fractures, the z-score of the adSOS was below minus 1.5 SD and UBPS was below 40, sensitivity was 0.7 for adSOS, and 0.85 for UBPS, with a specificity 0.97 for adSOS, and of 0.93 for UBPS; positive predictive value: adSOS: 0.93, UBPS: 0.85. AdSOS declined with age (r= 0.694, p=0.021); the UBPS was not age dependent (r=-0.15, p = n.s.). The ROC-curve shows a value of 0.96 for adSOS and 0.94 for UBPS. AdSOS and UBPS could discriminate well between the healthy controls and the women with osteopenia or vertebral fractures (p<0.00001). These results show that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using the UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than change in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.

Absorptiometry, Photon↗
PubMed1998

Short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on functional liver plasma flow in patients with advanced cirrhosis.

AIMS/BACKGROUND: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short-term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D-sorbitol (S-HCl). METHODS: Twenty-five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady-state, during constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S-HCI before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was directly measured at the level of the right (Er), where TIPS was applied, and of the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t-test for paired data. RESULTS: After application of TIPS, a substantial reduction was observed in PCG (12.1+/-4.2 vs 24.8+/-4.3 mmHg; p<0.001) and Er values (20.6+/-14.8 vs 57.5+/-22.3 %; p<0.001) but not El values (47.4+/-22.0 vs 53.4+/-21.4 %; p=0.178). S-HCl measured 120 min after TIPS opening was not statistically different from pre-TIPS values (389.2+/-212.1 vs 394.6+/-152.7 ml/min; p=0.892), although S-HCl variations in Child-Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). CONCLUSION: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.

Aged↗
PubMed1997

Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression.

We have investigated the role of the NFkappaB complex in the process of thyroid carcinogenesis by analysing thyroid carcinoma cell lines. A significant increase in p65 NFkappaB mRNA and protein expression, compared to normal thyroid cultures or tissue, was found in all of the cancer cell lines. Conversely, only a modest increase in the p50 NFkappaB mRNA and protein was found in most, but not all carcinoma cell lines. The block of p65 protein synthesis with specific antisense oligonucleotides greatly reduced the ability of two undifferentiated carcinoma cell lines to form colonies in agar and reduced their growth rate. On the other hand, no effect was observed in the same cell lines when treated with p50 specific antisense oligonucleotides. These inhibitory effects seem to be mediated by the suppression of c-myc gene expression, since treatment with antisense oligonucleotides for p65 gene interfered negatively with c-myc gene expression. Our results indicate that activation of the NFkappaB complex by overexpression of p65 plays a critical role in the process of thyroid cell transformation.

Down-Regulation↗
PubMed1997

Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.

The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.

Animals↗
PubMed1997

Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins.

BACKGROUND/AIMS: Peripheral vasodilation represents the main vascular dysfunction associated with the hyperdynamic circulation of liver cirrhosis. This study was intended to measure directly regional and systemic levels of nitric oxide, a potent vasorelaxing mediator, in order to assess its role in the development of hemodynamic changes of cirrhosis. METHODS: We compared nitric oxide levels in the splanchinic and systemic circulation of 25 patients with cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt and in the hepatic vein and peripheral blood of 10 patients without cirrhosis submitted to venous catheterization. Nitric oxide levels were measured through electron paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes. RESULTS: Significantly higher nitric oxide levels were calculated in patients with cirrhosis with respect to controls, both in the peripheral and hepatic veins. In patients with cirrhosis, nitric oxide levels in the portal vein (3.44 +/- 2.17, expressed in arbitrary units) were higher than in the systemic circulation (1.89 +/- 1.15), but lower than in the hepatic vein (4.75 +/- 2.53; p < 0.001 by variance analysis). CONCLUSIONS: These data suggest that nitric oxide synthetic pathway activity as well as nitric oxide release are enhanced at the level of splanchnic vasculature and, more important, in the hepatic tissue, confirming evidence of the predominant role of nitric oxide in the pathogenesis of hemodynamic changes in patients with cirrhosis with portal hypertension.

Aged↗
PubMed1996

High level expression of the HMGI (Y) gene during embryonic development.

The HMGI protein family includes three proteins, named HMG-I, HMG-Y and HMGI-C. The first two proteins are coded for by the same gene, HMGI (Y), through an alternative splicing mechanism. Their expression is elevated in neoplastic tissues and cells and this overexpression has a causal role in the process of cellular neoplastic transformation. We demonstrate that the HMGI (Y) gene is expressed at very low levels in normal adult tissues, whereas in embryonic tissues it is expressed at high levels comparable to those detected in neoplastic tissues. Specifically, a very high expression of the HMGI (Y) gene was detected in all embryonic tissues at 8.5 dpc. Then in the following days, even though the gene is expressed essentially in all tissues, an abundant gene expression was restricted to some tissues. These results indicate an important role of the HMGI (Y) gene in development.

Adult↗
PubMed1996

Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins.

A correlation has previously been demonstrated between the presence of the three HMGI proteins (HMGI, HMGY, and HMGI-C) and the expression of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells; this being subsequently extended to experimental thyroid, lung, prostate, mammary, and skin carcinomas. Recently, we have demonstrated that expression of HMGI and HMGY proteins, coded for by the HMGI(Y) gene, is associated with the malignant phenotype of human thyroid neoplasias. Here, we show that HMGI(Y) gene expression is present both at the RNA and protein level in human colorectal carcinoma cell lines and tissues examined in this study. Conversely, no HMGI(Y) proteins were detected in normal intestinal mucosa. Therefore, these results suggest an involvement of HMGI and HMGY proteins overexpression in colorectal tumorigenesis.

Amino Acid Sequence↗
PubMed1996

Determination of functional portal-systemic shunting in patients submitted to hepatic angiography.

Angiographic visualization of the hepatic vascular bed by selective angiography can be profitably complemented with the evaluation of functional portal-systemic shunting by D-sorbitol bioavailability. Seventeen patients requiring diagnostic arterial catheterization were studied: most of them had biopsy-proven liver cirrhosis. Patients were studied at rest and after overnight fasting on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct infusion (15 mg/min for 20 min) into the superior mesenteric artery and an antecubital vein, respectively. The fractional bioavailability (Fma) of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs obtained after infusion through the catheter into the superior mesenteric artery and the systemic vein, respectively. A good correlation was found between the estimated fractional portal-systemic shunting, which in the present study ranged between 1.4% and 96.7%, and a suitable index scoring the clinical evidence of collateral circulation. Since the hepatic removal of D-sorbitol is not affected by sinusoidal capillarization and its hepatic extraction ratio is quite high and only slightly modified by reduction in the number or functional activity of hepatocytes, the measured Fma can be assumed as a parameter reflecting the entity of portal-systemic shunting. The test is safe and inexpensive, and appears potentially useful in several situations in which portal-systemic shunting is pathophysiologically relevant.

Adult↗
PubMed1996

Computer-aided diagnosis in jaundice: comparison of knowledge-based and probabilistic approaches.

The study reported in this paper is aimed at evaluating the effectiveness of a knowledge-based expert system (ICTERUS) in diagnosing jaundiced patients, compared with a statistical system based on probabilistic concepts (TRIAL). The performances of both systems have been evaluated using the same set of data in the same number of patients. Both systems are spin-off products of the European project Euricterus, an EC-COMAC-BME Project designed to document the occurrence and diagnostic value of clinical findings in the clinical presentation of jaundice in Europe, and have been developed as decision-making tools for the identification of the cause of jaundice based only on clinical information and routine investigations. Two groups of jaundiced patients were studied, including 500 (retrospective sample) and 100 (prospective sample) subjects, respectively. All patients were independently submitted to both decision-support tools. The input of both systems was the data set agreed within the Euricterus Project. The performances of both systems were evaluated with respect to the reference diagnoses provided by experts on the basis of the full clinical documentation. Results indicate that both systems are clinically reliable, although the diagnostic prediction provided by the knowledge-based approach is slightly better.

Artificial Intelligence↗
PubMed1995

A mutated p53 gene alters thyroid cell differentiation.

p53 is the gene most frequently found mutated in human neoplasias. In the majority of tumors, p53 mutations contribute to the progression towards stages of increasing malignancy with the appearance of an undifferentiated phenotype. Also in thyroid cancerogenesis, p53 mutations correlate with the loss of the differentiated phenotype. The results presented here, suggest a direct involvement of p53 in the molecular mechanisms regulating cellular differentiation in thyroid since a mutated p53 gene markedly affects the growth potential and differentiated functions of the rat thyroid cell line PC Cl 3. Blockage in the expression of the PAX-8 transcription factor seems to be a key event in the loss of thyroid differentiated functions induced by the mutated p53 gene. Thyroid cells carrying a mutated p53 gene did not form colonies in soft agar or tumors in athymic mice, suggesting that a mutation of the p53 gene is not sufficient for the induction of the malignant phenotype and probably a cooperation with other oncogenes is necessary to accomplish full malignancy. No effect on either growth or differentiation of thyroid cells was exerted either by overexpression of the wild-type p53 gene, or by the vector alone.

Amino Acid Sequence↗
PubMed1995

The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias.

High Mobility Group I (HMGI) proteins are nuclear proteins involved in the regulation of chromatin structure and function. Elevated expression of the HMGI proteins (HMGI, HMGY and HMGI-C) has been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells, and in several experimental carcinomas. Here, we demonstrate that HMGI and HMGY proteins are expressed in human thyroid carcinomas and thyroid carcinoma cell lines, but not in adenomas, goiters, normal thyroid tissues and cells. These results indicate a correlation between HMGI and HMGY expression and the malignant phenotype of thyroid neoplasias, suggesting that these proteins may be used as markers in thyroid cancer.

Adenoma↗
PubMed1993

Left ventricular hypertrophy and mortality after aortic valve replacement for aortic stenosis. A high risk subgroup identified by preoperative relative wall thickness.

OBJECTIVES: We investigated the relation between the extent and pattern of left ventricular hypertrophy and surgical outcome in 54 patients undergoing aortic valve replacement for severe aortic stenosis. BACKGROUND: Previous work from our laboratory has demonstrated that a subgroup of patients, mostly elderly women with Doppler evidence of abnormal intracavitary flow acceleration, had an unexpectedly high in-hospital mortality rate after aortic valve replacement for aortic stenosis. We hypothesized that marked concentric hypertrophy, rather than the Doppler signal itself, was related to the poor outcome. METHODS: A retrospective analysis of the clinical, hemodynamic and echocardiographic data in patients who survived aortic valve replacement versus those who died in the hospital was performed. RESULTS: There were no differences between the 42 survivors and 12 nonsurvivors with regard to the clinical or hemodynamic variables. Of the echocardiographic variables analyzed, diastolic relative wall thickness was found to be significantly different between the two groups. Patients who died had significantly greater relative wall thickness (mean +/- SD) than those who survived (0.72 +/- 0.38 vs. 0.56 +/- 0.15, p = 0.04). Analysis by gender demonstrated that the relation between ventricular geometry and mortality held true only for women. CONCLUSIONS: We conclude that excessive ventricular hypertrophy, manifested as a markedly increased relative wall thickness, is associated with a significantly increased risk of postoperative mortality after aortic valve replacement for aortic stenosis.

Aged↗
PubMed1993

Laser facilitated angioplasty and thrombolysis in acute myocardial infarction complicated by prolonged or recurrent chest pain.

To date, application of laser angioplasty in acute myocardial infarction (MI) has not been reported. In nine patients with acute myocardial infarction complicated by continuous or recurrent severe ischemia and chest pain, a mid-infrared, solid-state, pulse-wave holmium/thulium:YAG coronary laser was applied. In six of these patients the laser was specifically utilized for the purpose of coronary thrombolysis. In each case a guidewire was placed across the stenosis and a multifiber laser catheter was utilized, emitting 250-600 mJ/pulse at 5 Hz, followed by adjunctive balloon angioplasty. Laser success (defined as ability to cross the lesion, reduction of > or = 20% in stenosis and thrombolysis when a thrombus is present) was achieved in all patients. Final angiograms revealed residual stenosis < or = 30%, adequate thrombolysis and no major complication (MI, perforation, emergency CABGS, CVA, death) in each patient. Clinically, all nine patients improved, survived the acute infarction and were discharged. This initial clinical experience demonstrates the feasibility and safety of holmium/thulium:YAG laser application in thrombolysis and plaque ablation in selected patients who experience acute myocardial infarction complicated by prolonged or recurrent ischemia and chest pain.

Adult↗
PubMed1993

Bacterial and mammalian cell mutagenicity of four optically active bay-region 10,11-diol-8,9-epoxides of the nitrogen heterocycle dibenz[a,h]acridine.

The mutagenic activities of the enantiomers of the diastereomeric pair of bay-region 10,11-diol-8,9-epoxides of dibenz[a,h]acridine (DB[a,h]ACR) were evaluated in histidine-dependent strains of Salmonella typhimurium and in cultured Chinese hamster V79 cells. In strains TA98 and TA100 of S.typhimurium, the (-)-[8S,9R,10R,11S] diol-epoxide was the most mutagenic compound, inducing 1200 and 6900 His+ revertants/nmol respectively. The mutagenic activity of each of the remaining three isomers was essentially independent of the bacterial strain used and had 14-72% of the activity of the [S,R,R,S] isomer. However, in Chinese hamster V79 cells, the (+)-[8R,9S,10S,11R] diol-epoxide was the most mutagenic compound (68 8-azaguanine resistant variants/nmol/10(5) cells), inducing from 2 to 11 times as many mutations as the other three isomers. These results are analogous to previous studies with the bay-region diol-epoxides of other polycyclic hydrocarbons in that the isomer with [R,S,S,R] absolute configuration has had variable activity in the bacterial assays, but has generally been the most active in the mammalian cells. Furthermore, this isomer has almost always been highly tumorigenic in the mouse.

Acridines↗