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Biomedical subjects

D Conte

Publications and source records attributed to D Conte.

At least 37 records · Page 2Linked to original sources

Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease.

It has been suggested that excess iron may facilitate the occurrence of cancer. Patients with hereditary hemochromatosis (HH) are at high risk of developing liver cancer, and studies of limited series reported a high frequency of nonhepatic cancers. To verify whether patients with HH are at higher risk of liver cancer and other malignancies as compared with patients with non-iron-related chronic liver disease (CLD), we analyzed the occurrence of neoplasms in 230 patients with HH and 230 with non-iron-related CLD. The patients were matched by sex, age, duration of follow-up (+/-5 years), and severity of liver disease. On enrollment, the following variables were considered: hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol abuse, smoking, and a family history of cancer (first-degree relatives). The diagnosis of primary cancers was confirmed by histology. During the follow-up, hepatocellular carcinoma (HCC) developed in 49 and 29 patients (all cirrhotic patients) with HH and non-iron-related CLD, respectively, with a relative risk of 1.8 (95% confidence interval [CI] 1.1-2.9); nonhepatic cancers occurred in 20 and 11 patients, respectively, with a relative risk of 1.8 (95% CI 0.8-4). Four patients with HH and 1 with non-iron-related CLD developed 2 different primary cancers during follow-up. The risk of cancer after adjustment for alcohol abuse, smoking, and family history of cancer was 1.9 (95% CI 1.1-3.1) in the patients with HH. In conclusion, patients with HH are at high risk of both liver cancer and other malignancies, which should be carefully sought during follow-up.

Adult↗

Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans.

PURPOSE: Prostaglandins (PGs) modulate the activity of the hypothalamus-pituitary axis, and pituitary hormones are largely involved in the physiological responses to exercise. The purpose of this study was to analyze the effects of acetylsalicylic acid (ASA), an inhibitor of PGs synthesis, in the pituitary responses to physical stress in humans. METHODS: Adrenocorticotropin (ACTH), beta-endorphin, cortisol, growth hormone (GH), and prolactin (PRL) responses to exercise were evaluated after administration of either placebo or ASA. Blood samples for hormone evaluations before (-30, -15, and 0 pre) and after (0 post, +15, +30, +45, +60, and +90 min) a 30-min treadmill exercise (75% of .VO(2max)) were taken from 12 male athletes during two exercise trials. One tablet of ASA (800 mg), or placebo, was administered two times daily for 3 d before and on the morning of each exercise-test. RESULTS: The results clearly show that, compared with placebo, ASA ingestion significantly blunted the increased serum ACTH, beta-endorphin, cortisol, and GH levels before exercise (anticipatory response) and was associated with reduced cortisol concentrations after exercise. Furthermore, although no differences in the GH response to exercise were shown, a significantly reduced total PRL response to stress condition was observed after ASA. CONCLUSION: ASA influences ACTH, beta-endorphin, cortisol, GH, and PRL responses to exercise-related stress in humans (preexercise activation/exercise-linked response). Even though it is not possible to exclude direct action for ASA, our data indirectly confirm a role of PGs in these responses. We have to further evaluate the nature of the preexercise endocrine activation and, because of the large use of anti-inflammatory drugs in athletes, whether the interaction between ASA and hormones might positively or negatively influence health status, performance, and/or recovery.

Adrenocorticotropic Hormone↗

The Sgs1 helicase of Saccharomyces cerevisiae inhibits retrotransposition of Ty1 multimeric arrays.

Ty1 retrotransposons in the yeast Saccharomyces cerevisiae are maintained in a genetically competent but transpositionally dormant state. When located in the ribosomal DNA (rDNA) locus, Ty1 elements are transcriptionally silenced by the specialized heterochromatin that inhibits rDNA repeat recombination. In addition, transposition of all Ty1 elements is repressed at multiple posttranscriptional levels. Here, we demonstrate that Sgs1, a RecQ helicase required for genome stability, inhibits the mobility of Ty1 elements by a posttranslational mechanism. Using an assay for the mobility of Ty1 cDNA via integration or homologous recombination, we found that the mobility of both euchromatic and rDNA-Ty1 elements was increased 32- to 79-fold in sgs1Delta mutants. Increased Ty1 mobility was not due to derepression of silent rDNA-Ty1 elements, since deletion of SGS1 reduced the mitotic stability of rDNA-Ty1 elements but did not stimulate their transcription. Furthermore, deletion of SGS1 did not significantly increase the levels of total Ty1 RNA, protein, or cDNA and did not alter the level or specificity of Ty1 integration. Instead, Ty1 cDNA molecules recombined at a high frequency in sgs1Delta mutants, resulting in transposition of heterogeneous Ty1 multimers. Formation of Ty1 multimers required the homologous recombination protein Rad52 but did not involve recombination between Ty1 cDNA and genomic Ty1 elements. Therefore, Ty1 multimers that transpose at a high frequency in sgs1Delta mutants are formed by intermolecular recombination between extrachromosomal Ty1 cDNA molecules before or during integration. Our data provide the first evidence that the host cell promotes retrotransposition of monomeric Ty1 elements by repressing cDNA recombination.

DNA Helicases↗

Renovascular impedance and esophageal varices in patients with Child-Pugh class A cirrhosis.

PURPOSE: To evaluate the frequency of increased renovascular impedance and its relationship with the presence of esophageal varices in patients with Child-Pugh class A cirrhosis without ascites. MATERIALS AND METHODS: The intraparenchymal renal resistive index (RI) (reference value, <0.7) and portal congestive index (ie, the ratio between the portal cross-sectional area and mean flow velocity; reference value, <0.07) were measured by using duplex Doppler ultrasonography in 50 consecutive patients. The frequency of varices was assessed endoscopically. The data were analyzed with the Fisher exact test. RESULTS: The renal RI was consistent with increased impedance (ie, >0.7) in 18 (36%) patients and was normal in 32 (64%). The proportion of patients with varices was significantly higher in the former group: 14 (78%) versus 10 (31%) (P =.002). In detection of the presence of varices, the renal RI was uniformly better than the portal congestive index in terms of sensitivity (58% vs. 48%), specificity (84% vs 54%), and positive (3.60 vs 1.04) and negative (0.50 vs. 0.96) likelihood ratios. RI determination improved the ability to exclude the presence of varices from a basal pretest probability of 52% (26 of 50 patients) to a final one of 69% (22 of 32 patients) and that of predicting the presence of varices from 48% (24 of 50 patients) to 78% (14 of 18 patients). CONCLUSION: A substantial proportion of patients with Child-Pugh class A cirrhosis without ascites have increased renovascular impedance; this significantly correlates with the presence of varices.

Esophageal and Gastric Varices↗

[Role of HDL cholesterol in the prediction of exercise stress test abnormalities in asymptomatic high-risk patients].

The diagnosis of coronary artery disease in asymptomatic patients is useful in order to target therapeutic intervention in the patients at highest risk. Systematic testing of all asymptomatic adults with coronary risk factors is not feasible. The aim of this study, carried out in 950 healthy subjects, was to assess the predictive value of classical risk factors for positive exercise stress tests (EE). All subjects underwent stress testing using the Bruce protocol. Statistical analysis was performed by multiple logistic regression on half the samples, then by CART (Classification and Regression Trees) analysis on all subjects. Age, HDL-cholesterol and interaction between lipid lowering treatment and LDL-cholesterol were significantly correlated (p < 0.05) to a positive exercise stress test. In both groups, treated or untreated by lipid lowering drugs. CART identified HDL-cholesterol (< 0.40 g/l) as a predictive factor for positive stress testing. Subgroups of elderly patients (> or = 60 years) with probabilities of 20 to 28% for a positive stress test were identified. The authors conclude that the diagnosis of coronary artery disease by systematic exercise stress testing is potentially valuable in elderly patients with low HDL-cholesterol values.

Adult↗

Unusual peripheral T cell lymphoma presenting as acute liver failure and reappearing in the liver allograft.

A 25-year-old man presented with fulminant hepatic failure from an unusual peripheral T cell lymphoma involving the liver and spleen without lymphadenopathy. He underwent liver transplantation before establishing a definitive diagnosis and 21 days later, died from liver allograft failure because of recurrent lymphoma. In both the native liver and hepatic allograft, the lymphoma presented as a sparse cytologically atypical malignant infiltrate intermixed with numerous reactive macrophages, which showed marked angio- and epitheliotropism and irregular areas of coagulative necrosis. The malignant cells were CD3+/ granzyme B+/TIA1+/CD8-/CD56-/S100-- with variable staining for beta F1, CD5, and CD7. Multiplex polymerase chain reaction (PCR) showed rearrangement of the T cell receptor gamma chain gene in the native and transplanted liver and spleen. Even in the absence of a mass lesion or lymphadenopathy, peripheral T cell lymphoma should be included in the differential diagnosis of fulminant hepatic failure in young patients who show no evidence of viral or autoimmune diseases.

Adult↗

Redox properties of protein disulfide bond in oxidized thioredoxin and lysozyme: a pulse radiolysis study.

We have studied the one-electron reduction of oxidized Chlamydomonas reinhardtii thioredoxin and compared it to that of hen egg white lysozyme, using CO(2)(*) (-) free radicals as reductants. This comparison shows that the thioredoxin disulfide/thiol redox couple has different properties than that of lysozyme: the disulfide radical pK(a) is much lower (around 5 for small disulfides, 4.62 for lysozyme, <3 for thioredoxin). To get a better understanding of the modulation of the thioredoxin redox properties we have constructed the mutants W35A and D30A. Their reduction by pulse radiolysis indicates that W35 strongly controls both the disulfide radical acidity (the pK(a) in W35A is equal to ca. 4), and the thiol reactivity. Asp30 is also involved in the control of proton transfer to the disulfide free radical. In addition, its removal seems to increase the reduction potential of the thioredoxin thiyl/thiol couple. Overall, the reduction properties of thioredoxin confirm its nature as a unique reductant.

Alanine↗

Increased prevalence of celiac disease in patients with dyspepsia.

BACKGROUND: Although 30% to 40% of patients with celiac disease (CD) (which affects 1 in 200 individuals) have dyspeptic symptoms, there is a lack o data concerning the prevalence of CD in patients with dyspepsia. METHODS: In this prospective series, we enrolled all consecutive outpatients undergoing endoscopy of the upper gastrointestinal tract for dyspepsia at our centers between January and June 1998. The exclusion criteria were age younger than 12 years, workup or follow-up of an already known disease of the gastrointestinal tract, suspected CD, malabsorption, and/or iron-deficiency anemia. RESULTS: Of the 3019 patients who were evaluated, 517 (17%) were eligible for the study. Endoscopic findings suggested CD in 5 cases. Celiac disease was histologically diagnosed in 6 patients (5 women and 1 man; mean age, 31.3 years; age range, 20-46 years), 3 of whom had a normal endoscopic pattern and 3 of whom had an endoscopic pattern that was consistent with CD. In the patients with histologically diagnosed CD, antiendomysium antibody positivity supported the diagnosis. The relative risk for CD was 2.32 (95% confidence interval, 1.06-5.07) in comparison with the general population and higher among females (3.22; 95% confidence interval, 1.37-7.56). CONCLUSIONS: The present results indicate that the prevalence of CD in patients with dyspepsia is twice that of the general population. Thus, serological screening for CD should be considered in the early workup of these patients to allow diagnosis and treatment of an eminently treatable disease.

Adult↗

Iron overload and gene expression in HepG2 cells: analysis by differential display.

The aim of the present study was to evaluate the effect of iron overload on gene expression in HepG2 cells by differential display. Iron-treated cells showed a 50% decrease in apolipoprotein B100 (Apo B100) and a 2- and 3-fold increase in semaphorin cd100 and aldose reductase mRNA, respectively, with parallel variations in Apo B100 and aldose reductase proteins. These effects were time-dependent. Vitamin E prevented the increase in aldose reductase expression, but had no effect on Apo B100 and semaphorin cd100. Treatment with hydrogen peroxide and 4-hydroxy-2,3-nonenal increased only aldose reductase mRNA. These data suggest that iron can affect mRNA levels by lipid peroxidation-dependent and -independent pathways.

Aldehyde Reductase↗

Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.

The prevalence and natural course of chronic hepatitis C virus (HCV) infection was evaluated in 15,250 consecutive pregnant women. The rate of HCV vertical and perinatal transmission was also assessed. The presence of anti-HCV was tested by means of EIA III and confirmed by recombinant immunoblot assay III. Alanine transaminase (ALT), anti-human immunodeficiency virus (HIV), and HCV-RNA were tested during the first month and third trimester of pregnancy, and 6 months after delivery; the same tests were made in all of the newborns of anti-HCV-positive mothers at birth (on cord blood samples) and then at 4-month intervals. Anti-HCV positivity was found in 370 cases (2.4%), 72% of whom were also HCV-RNA-positive. The proportion of women with hypertransaminases decreased from 56.4% at the first examination during the first month of pregnancy to 7.4% in the last trimester, and then increased again after delivery (54. 5%), without any concomitant changes in the proportion of those with viremia. The proportion of anti-HCV- and HCV-RNA-positive newborns was 5.1% after 1 year (8 of 155), all of whom had the same genotype as their mother. The rate of HCV transmission was not affected by the type of delivery or feeding, or the HIV status of the mother. The results of this large-scale study confirm previous data in smaller series concerning the prevalence of HCV infection in pregnant women, and strongly support the hypothesis of a favorable (possibly immunomediated) effect of pregnancy on liver cell necrosis in anti-HCV-positive women.

Adult↗

Adult syncytial giant cell chronic hepatitis due to herbal remedy.

Syncytial giant cell hepatitis is an uncommon form of chronic hepatitis in adults, although it has been reported in association with viral infection (including HCV and HIV infection), drug reactions and autoimmune disorders. We here report a very unusual case of giant cell chronic hepatitis in a 26-old-woman, who had been taking a herbal remedy (ISABGOL) for chronic constipation. The presence of viral and metabolic diseases has been excluded; an autoimmune etiology was very unlikely as the autoimmunity test remained negative during the year of follow-up and the total disease score normalized (from 13 to 8) without corticosteroid treatment. The causative role of the herbal remedy was further supported by the spontaneous and dramatic clinical, biochemical and histologic improvement observed following its withdrawal, despite the absence of any treatment.

Adult↗

Recurrent cholestasis and hypereosinophilia in a young female.

A 22-year-old female presented, in December 1998, with asthenia, itching and hypereosinophilia. In January 1997, due to the same clinical picture, the patient had inappropriately been diagnosed elsewhere to have an "idiopathic eosinophilic syndrome" and complete remission was obtained after short-term steroid treatment. Upon admission, physical examination was negative and blood tests revealed absolute eosinophilia [42%, i.e., 3,800 of 9,600 white blood cells], aspartate aminotransferase 4 x upper limits of normal, alanine aminotransferase 5 x upper limits of normal and alkaline phosphatase 2 x upper limits of normal. Both liver biopsy and endoscopic retrograde cholangiopancreatography findings were totally consistent with primary sclerosing cholangitis, while all known causes of hypereosinophilia and alteration in liver function tests were carefully excluded. The clinical course was characterized by complete clinical and biochemical normalization in absence of any treatment and further follow-up was completely negative.

Adult↗

The physical state of a meal affects hormone release and postprandial thermogenesis.

There is evidence that food consistency may influence postprandial physiological responses. Recently we found that homogenization of a vegetable-rich meal significantly delayed the gastric emptying rate and was more satiating than the same meal in solid-liquid form. In this present study we investigated whether homogenization also influences endocrine and metabolic responses to the meal. Eight healthy men, aged 21-28 (mean 24.5) years, were given the meal (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, with water 300 ml; total energy 2.6 MJ) in both solid-liquid (SM) and homogenized (HM) form, in random order, at 1-week intervals. Variables assayed were plasma glucose, insulin and glucose-dependent insulinotropic peptide (GIP) levels for 2 h and diet-induced thermogenesis (DIT) for 5 h. Plasma glucose pattern was similar after both meals. However, HM induced significantly greater insulin, GIP and DIT responses than SM. Mean integrated areas under the curves (AUC) were 1.7 (SEM 0.38) v. 1.2 (SEM 0.33) U/l per 120 min (P = 0.005) for insulin, 19.9 (SEM 2.44) v. 16 (SEM 1.92) nmol/l per 120 min (P = 0.042) for GIP, and 237.7 (SEM 16.32) v. 126.4 (SEM 23.48) kJ/300 min (P = 0.0029) for DIT respectively. Differences between GIP-AUC after HM and SM correlated significantly with differences between insulin-AUC after HM and SM (r2 0.62, P = 0.021). These findings demonstrate that homogenization of a meal results in a coordinated series of changes of physiological gastroentero-pancreatic functions and confirm that the physical state of the meal plays an important role in modulating endocrine and metabolic responses to food.

Adult↗

Fus3 controls Ty1 transpositional dormancy through the invasive growth MAPK pathway.

Fus3, the mitogen-activated protein kinase (MAPK) of the mating pheromone response pathway, inhibits a post-translational step of Ty1 retrotransposition. Fus3 also inhibits haploid invasive growth by blocking cross-activation of invasive growth gene expression by the pheromone response signal cascade. Here, we show that Fus3 kinase activity and dosage co-ordinately regulate Ty1 transposition and invasive growth. A chromosomal copy of the kinase-defective fus3-K42R allele fails to inhibit either Ty1 transposition or invasive growth. When overexpressed, kinase-defective Fus3 weakly inhibits both Ty1 transposition and invasive growth, but is much less inhibitory than wild-type Fus3 expressed at the same level. Moreover, increasing the dosage of wild-type Fus3 intensifies the inhibition of both Ty1 transposition and invasive growth. To demonstrate that Fus3 regulates Ty1 transposition via its negative regulation of the invasive growth pathway, we show by epistatic analysis that the invasive growth pathway transcription factors Ste12 and Tec1 are both required for Fus3-mediated inhibition of Ty1 transposition. When haploid invasive growth is stimulated by high-copy expression of TEC1, by expression of the dominant hypermorphic allele STE11-4 or by deletion of HOG1, Ty1 transposition is concomitantly activated. In summary, these results demonstrate that the haploid invasive growth pathway activates Ty1 transposition at both transcriptional and post-transcriptional levels and that Fus3 inhibits Ty1 transposition by inhibiting the invasive growth pathway.

Blotting, Northern↗

Reevaluation of duodenal endoscopic markers in the diagnosis of celiac disease.

BACKGROUND: Loss or reduction of duodenal folds, scalloping of Kerkring folds and a micronodular or mosaic duodenal mucosal pattern have been described in celiac disease (CD), endoscopic findings that are considered reliable in the diagnosis of this disorder. However, most data have been obtained in patients with suspected or certain disease. We assessed the accuracy of the above markers in diagnosing CD in patients with nonulcer dyspepsia. METHODS: In this prospective study, in 705 consecutive dyspeptic patients (284 men, 421 women, mean age 51 +/- SD 15.8 years) duodenal biopsies were obtained only in the presence of typical endoscopic markers, whereas in another 517 (207 men, 310 women, mean age 49.9 +/- SD 16 years) duodenal biopsies were done irrespective of macroscopic findings. CD was diagnosed histologically and on the basis of positive antiendomysium antibody. RESULTS: Endoscopic markers were found in 4 patients of the first group but CD was ruled out. In the second group 5 patients had an endoscopic pattern that was consistent and CD was diagnosed in 3, whereas 3 others with normal endoscopic findings were eventually diagnosed as having CD. Endoscopic markers had a sensitivity of 50% and a specificity of 99.6% (95% CI [11.8, 88.2 and 98.6, 99.9], respectively) with positive and negative predictive values of 60% and 99.4%, respectively. CONCLUSION: The accuracy of endoscopic markers in the diagnosis of CD must be reevaluated in relation to the characteristics of the population studied.

Adolescent↗

Influence of caloric intake on gastric emptying of solids assessed by 13C-octanoic acid breath test.

BACKGROUND: The 13C-octanoic breath test (13C-OBT), a recently developed technique to evaluate gastric emptying of solids, has been validated in comparison to scintigraphy with low caloric meals (250 kcal). However, there is consensus that for clinical studies total caloric load should be in excess of 300 kcal, but studies comparing 13C-OBT results after low and medium caloric meals are lacking. METHODS: Ten healthy subjects were given a 250-kcal and a 550-kcal meal in randomized order. Gastric emptying was assessed simultaneously by ultrasonography and 13C-OBT. Breath samples were taken according to both classic (21 samples over 5 h) and simplified (11 samples) schedules. RESULTS: Increasing the meal energy content resulted in significantly longer half emptying time (T(1/2)) estimates by both ultrasonography (P < 0.01, Wilcoxon test) and 13C-OBT (P < 0.05). T(1/2) estimates by the two methods significantly correlated for both the 250 (r(s) = 0.733, P = 0.018) and the 550 (r(s) = 0.637, P = 0.035) kcal meal. However, differences between T(1/2) estimates by 13C-OBT and ultrasonography were greater after the 550- than the 250-kcal meal (median 172.5 versus 76.5 min, P < 0.05). Interindividual variability was also 2-fold greater for indexes estimated by 13C-OBT with the 550-kcal meal compared with the 250-kcal meal. For both meals 13C-OBT yielded similar results with the classic and simplified schedules. CONCLUSIONS: In healthy subjects caloric intake is a major determinant of gastric emptying rate. However, after a medium caloric meal 13C-OBT shows some inaccuracy, which raises questions about its routine clinical application. Nevertheless, when using 13C-OBT one must take into account that the simplified schedule is just as effective as the classic one, and is far lower in cost.

Adult↗

Gastric emptying and plasma neurotensin levels in untreated celiac patients.

BACKGROUND: Upper gastrointestinal motor abnormalities could account for some of the dyspeptic symptoms of celiac patients. However, the data on gastric emptying time are conflicting, and the pathophysiology of motor disturbances is still unclear. Neurotensin modulates upper gastrointestinal motor activity, and its postprandial increase is a reliable index of nutrient delivery to the ileum. We therefore assessed both plasma neurotensin levels and gastric emptying in untreated celiacs. METHODS: The gastric antral area of nine untreated celiac patients and nine controls was measured with ultrasound at base line and every 30 min after a fatty meal (227 kcal, 45% fat); the base-line and postprandial neurotensin plasma levels were determined by means of radioimmunoassay. The data are mean values +/- standard deviation and were analyzed by using non-parametric tests. RESULTS: The overall and half gastric emptying time were significantly longer in the patients (203+/-32 versus 133+/-15 min, P = 0.0117, and 137+/-32 versus 78+/-11 min, P = 0.0001). The pattern of the changes in antral area was similar in both groups during the observation period as a whole but differed significantly in the first 120 min (P = 0.0343). Base-line neurotensin levels were significantly higher in the patients (41.6+/-23.9 versus 18.2+/-5.5 pg/ml, P = 0.0214) and their net postprandial increase was lower than in controls (15.0+/-15.9 versus 29.8+/-13.0 pg/ml, P = 0.046). In both groups the base-line neurotensin levels were related to the half gastric emptying time (P = 0.023). CONCLUSIONS: In untreated celiac patients gastric emptying time is longer than in controls and is concomitant with an increase in base-line plasma neurotensin levels.

Adult↗