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Biomedical subjects

D Conte

Publications and source records attributed to D Conte.

At least 73 records · Page 4Linked to original sources
PubMed1999

Preferential activation of iron regulatory protein-2 in cell lines as a result of higher sensitivity to iron.

Iron regulatory proteins (IRP)-1 and 2 are cytoplasmic mRNA-binding proteins that control intracellular iron homeostasis by regulating the translation of ferritin mRNA and stability of transferrin receptor mRNA in an iron-dependent fashion. Although structurally and functionally similar, the two IRP are different in their mode of regulation, pattern of tissue expression and modulation by multiple factors, such as bioradicals. In the present study RNA bandshift assays demonstrated that IRP-2, but not IRP-1, activity was higher in cultured cells than in tissues. Increased expression of IRP-2 in cell lines was not related to immortalization and differentiation but seemed associated to cell proliferation, although not closely dependent on cell growth rate. As a growing cell consumes more iron than its quiescent counterpart, we assessed the iron status of cell lines and found that ferritin content was lower than in tissues. Analysis of IRP activity in cell lines supplemented with heme or non-heme iron and in livers of iron-loaded and iron-deficient rats indicated that IRP-2 responds more promptly than IRP-1 to modulations of iron content. We propose that enhanced IRP-2 activity in cultured cells could be due to a proliferation-dependent, relative iron deficiency that is sensed first by IRP-2.

Animals↗
PubMed1999

Mesenteric lymph node cavitation: a rare hallmark of celiac disease.

The cavitation of mesenteric lymph nodes represents a rare complication of celiac disease (only 30 reported cases) whose pathogenesis remains to be clarified. We here report the case of a 67-year-old woman referred to us because of a malabsorption syndrome lasting for 2 years; massive lymph node enlargement and cavitation were detected by means of ultrasonography and a computed tomography scan. Celiac disease was definitely diagnosed by means of duodenal histology, and a laparotomy was performed to exclude an underlying T-cell lymphoma. The adoption of a gluten-free diet led to a rapid and dramatic improvement in the clinical and histologic picture and normalization of the size of the lymph nodes. Celiac disease should be considered in the differential diagnosis of all patients with mesenteric lymph node cavitation.

Aged↗
PubMed1999

Effectiveness of IFN-gamma for liver abscesses in chronic granulomatous disease.

In chronic granulomatous disease, interferon-gamma (IFN-gamma) significantly reduces the incidence and severity of recurrent infections, but its effectiveness administered ex novo during acute infection has been reported in only one case. In this report, we describe two adult brothers with chronic granulomatous disease treated successfully with IFN-gamma for acute liver abscesses. Two brothers with severe recurrent infections of unknown origin were hospitalized for septic fever, malnutrition, and ultrasonographic evidence of liver abscess. Autosomal recessive chronic granulomatous disease was diagnosed based on lack of superoxide anion production by phagocytes and absence of p47-phox protein. An antibiotic regimen specifically directed against Staphylococcus aureus was ineffective, whereas treatment with 50 microg/m2 IFN-gamma s.c. thrice weekly induced complete healing with scarring within 3 months. No septic recurrence was observed during a 4-year follow-up period. In chronic granulomatous disease, IFN-gamma is effective not only in preventing but also in healing life-threatening acute infections.

Adolescent↗
PubMed1999

Gallbladder emptying and somatostatin and cholecystokinin plasma levels in celiac disease.

OBJECTIVE: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls. METHODS: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis. RESULTS: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings. CONCLUSIONS: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.

Adult↗
PubMed1999

Aspirin inhibits androgen response to chorionic gonadotropin in humans.

Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

Administration, Oral↗
PubMed1999

Mistaken diagnosis of eosinophilic colitis.

A 69-year-old male chronic alcohol abuser suffering from diarrhoea and with a number of discrete pruriginous and erythematous lesions of the trunk was referred to our Unit with a diagnosis of idiopathic eosinophilic colitis in order that we might determine corticosteroid treatment. Diagnosis was based on the presence of marked peripheral eosinophilia and massive eosinophilic infiltration at colonic biopsy, and the exclusion of parasitic infection by means of two different microscopic stool examinations of five samples. However, repeated stool examinations of ten samples collected on separate days and evidence of impaired cell-mediated immunity allowed a definite diagnosis of Strongyloides stercoralis autoinfection or hyperinfection. Due to the poor sensitivity of stool examination in the diagnosis of Strongyloides stercoralis infection, a careful search for this parasite should be made in all patients with comparable clinical findings before formulating a diagnosis of idiopathic eosinophilic colitis, because consequent steroid treatment may have a fatal outcome by inducing widespread dissemination of the parasite.

Aged↗
PubMed1999

Severe hypopharyngeal dysphagia in a patient on chronic steroid treatment.

A 44-year-old Caucasian male who had been on long-term steroid treatment for an unspecified collagen disease was referred to our Unit because of fever, severe hypopharyngeal dysphagia, night sweats and evidence of marked superior vena cava compression. Extrapulmonary disseminated tuberculosis also involving bone and liver was eventually diagnosed and proven by means of specific polymerase chain reaction assay. Antimycobacterial treatment, which led to a dramatic improvement within two months, was protracted for 18 months until the complete return to normal of both clinical and laboratory findings.

Adult↗
PubMed1998

Response of monocyte iron regulatory protein activity to inflammation: abnormal behavior in genetic hemochromatosis.

In genetic hemochromatosis (GH), iron overload affects mainly parenchymal cells, whereas little iron is found in reticuloendothelial (RE) cells. We previously found that RE cells from GH patients had an inappropriately high activity of iron regulatory protein (IRP), the key regulator of intracellular iron homeostasis. Elevated IRP should reflect a reduction of the iron pool, possibly because of a failure to retain iron. A defect in iron handling by RE cells that results in a lack of feedback regulation of intestinal absorption might be the basic abnormality in GH. To further investigate the capacity of iron retention in RE cells of GH patients, we used inflammation as a model system as it is characterized by a block of iron release from macrophages. We analyzed the iron status of RE cells by assaying IRP activity and ferritin content after 4, 8, and 24 hours of incubation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). RNA-bandshift assays showed that in monocytes and macrophages from 16 control subjects, IRP activity was transiently elevated 4 hours after treatment with LPS and IFN-gamma but remarkably downregulated thereafter. Treatment with NO donors produced the same effects whereas an inducible Nitric Oxide Synthase (iNOS) inhibitor prevented them, which suggests that the NO pathway was involved. Decreased IRP activity was also found in monocytes from eight patients with inflammation. Interestingly, no late decrease of IRP activity was detected in cytokine-treated RE cells from 12 GH patients. Ferritin content was increased 24 hours after treatment in monocytes from normal subjects but not in monocytes from GH patients. The lack of downregulation of IRP activity under inflammatory conditions seems to confirm that the control of iron release from RE cells is defective in GH.

Adult↗
PubMed1998

Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus.

BACKGROUND: Few data exist on the prevalence of genetic hemochromatosis among diabetic patients. OBJECTIVE: To compare the prevalence of genetic hemochromatosis in diabetic patients and a matched control group and to evaluate the accuracy of iron-related indexes in detecting hemochromatosis. DESIGN: Cross-sectional study. SETTING: Diabetes clinics of four hospitals in northern Italy. PATIENTS: 894 diabetic patients (117 with type 1 diabetes and 777 with type 2 diabetes) and 467 matched controls. MEASUREMENTS: Transferrin saturation and serum ferritin levels were measured in all study participants. After secondary iron overload was excluded as the cause of persistently elevated transferrin saturation and serum ferritin levels, liver biopsy was performed and siderosis was estimated semiquantitatively and quantitatively. A hepatic iron index greater than 1.9 was considered diagnostic for hemochromatosis. RESULTS: Hemochromatosis was diagnosed in 12 patients with type 2 diabetes (prevalence, 1.34% [95% CI, 0.7% to 2.3%]) and 1 control (prevalence, 0.2% [CI, 0.1% to 1.4%]; P = 0.032). The odds ratio of hemochromatosis in association with diabetes was 6.3 (CI, 1.1 to 37.7). Measurement of transferrin saturation was the most sensitive test for hemochromatosis. CONCLUSIONS: Genetic hemochromatosis is frequently not diagnosed in patients with diabetes, although it is a hallmark of the disease. Screening for hemochromatosis could be beneficial for patients with diabetes.

Adolescent↗
PubMed1998

Nitric oxide-mediated induction of ferritin synthesis in J774 macrophages by inflammatory cytokines: role of selective iron regulatory protein-2 downregulation.

Cytokine-treated macrophages represent a useful model to unravel the molecular basis of reticuloendothelial (RE) iron retention in inflammatory conditions. In the present study, we showed that stimulation of murine macrophage J774 cells with interferon (IFN)-gamma/lipopolysaccharide (LPS) resulted in a nitric oxide-dependent modulation of the activity of iron regulatory proteins (IRP)-1 and 2, cytoplasmic proteins which, binding to RNA motifs called iron responsive elements (IRE), control ferritin translation. Stimulation with cytokines caused a small increase of IRP-1 activity and a strong reduction of IRP-2 activity accompanied by increased ferritin synthesis and accumulation. Cytokines induced only a minor increase of H chain ferritin mRNA, thus indicating that IRP-2-mediated posttranscriptional regulation plays a major role in the control of ferritin expression. This was confirmed by direct demonstration that the translational repression function of IRP was impaired in stimulated cells. In fact, translation in cell-free extracts of a reporter transcript under the control of an IRE sequence was repressed less efficiently by IRP-containing lysates from cytokine-treated cells than by lysates from control cells. Our findings throw light on the role of IRP-2 showing that: (1) this protein responds to a stimulus in opposite fashion to IRP-1; (2) when abundantly expressed, as in J774 cells, IRP-2 is sufficient to regulate intracellular iron metabolism in living cells; and (3) by allowing increased ferritin synthesis, IRP-2 may play a role in the regulation of iron homeostasis in RE cells during inflammation.

Animals↗
PubMed1998

Hepatic artery resistance in alcoholic liver disease.

Patency and direction of flow in portal veins and their branches are generally assessed by duplex Doppler ultrasonography (DDUS), whereas few data are available on hepatic arterial hemodynamics. In this study, resistive (RI) and pulsatility indexes (PI) were calculated at DDUS in 21 controls, 22 chronic alcoholic patients without evidence of liver damage, 19 patients with acute alcoholic hepatitis (AAH), 30 patients with chronic viral hepatitis (CVH), 23 patients with alcoholic cirrhosis, and 22 patients with viral-related cirrhosis. Diagnosis was based on clinical and histological findings. Mean +/- SD RI was similar in controls and CVH patients (0.64 +/- 0. 02 and 0.66 +/- 0.04, respectively), significantly decreased in alcoholic patients without liver damage and AAH patients (0.61 +/- 0. 07 and 0.60 +/- 0.07) (P < .05), and significantly increased in patients with alcoholic (0.72 +/- 0.04) and viral-related cirrhosis (0.74 +/- 0.04) (P < .05). It was <0.60 in 9 of the 19 AAH patients (47%) and 11 of the 22 alcoholic patients without liver damage (50%), and >0.70 in 39 of the 45 cirrhotic patients (87%) and 12 of the 71 noncirrhotic patients pooled together (17%). A significant correlation was observed between RI and PI (r = .83; P < .05). The coefficients of variation for intraobserver variability were 6.3% +/- 5.1% for RI and 10.1% +/- 6.2% for PI, and the corresponding figures for interobserver variability were 5.2% +/- 3.5% and 9.3% +/- 4.6%. These findings support the existence of ethanol-related hepatic arterial vasodilation in AAH and alcoholic patients without liver damage. Progression of liver damage from AAH to cirrhosis profoundly impairs the hepatic responsiveness as a consequence of fibrosis with vascular distortion.

Adult↗
PubMed1998

Heterogeneity of hemochromatosis in Italy.

BACKGROUND & AIMS: Patients with hemochromatosis show variable phenotype expression. We evaluated the frequency of hemochromatosis gene (HFE) mutations and the contribution of HFE genotype, ancestral haplotype, ethnic background, and additional factors (alcohol intake, hepatitis viruses, and beta-thalassemia trait) to the severity of iron overload in a large series of Italian patients with a hemochromatosis phenotype. METHODS: HFE genotype was studied in 188 patients. Phenotype evaluation was available in 153 men and 20 women and was based mainly on iron removed. HFE genotype was determined by a polymerase chain reaction restriction assay and ancestral haplotype through D6S265 and D6S105 microsatellite analysis. RESULTS: The frequency of C282Y homozygotes was 64%, with a decreasing gradient from north to south. C282Y homozygotes showed more severe iron overload than the other HFE genotypes. In the same group, ancestral haplotype was associated with a more severe phenotype. Additional factors may favor the development of a relatively mild hemochromatosis phenotype in patients nonhomozygous for the C282Y mutation. CONCLUSIONS: Hemochromatosis in Italy is a nonhomogenous disorder in which genetic and acquired factors are involved. In patients with a single or no HFE mutation, further studies will enable a differentiation between true genetic disorders and interactions between genetic and acquired factors.

Adult↗
PubMed1998

Galanin stimulates steroidogenesis in rat Leydig cells.

The present study was designed to evaluate whether galanin could play a role in the regulation of testicular steroidogenesis. To this purpose, using purified rat Leydig cells, we examined the effects of galanin on basal and hCG- or LHRH-induced testosterone production and the interference of a specific galanin receptor antagonist, galantide, on galanin activity. Moreover, since it has been shown that galanin-induced stimulation of LHRH secretion appears to involve the release of prostaglandin E2 (PGE2) as intracellular mediator, we evaluated also the effect of galanin on Leydig cells PGE2 output and the interference of indomethacin, a cycloxygenase blocker, on its activity. Furthermore, the effect of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was also examined. Data obtained indicate that galanin amplified testosterone response to hCG or LHRH whilst galantide prevented its potentiating activity. Moreover, galanin stimulated PGE2 output though this fatty acid is not involved in galanin activity on Leydig cells as indomethacin failed to affect its amplification of testosterone production. The possible involvement of leukotrienes should also be excluded as NDGA did not modify galanin action. In summary, the present study indicates that galanin potentiates acute gonadotropin or LHRH steroidogenic action on Leydig cells and that this activity is specific and receptor-mediated as it is prevented by a specific receptor antagonist.

Animals↗
PubMed1998

Physical state of meal affects gastric emptying, cholecystokinin release and satiety.

To verify the influence of food consistency on satiety mechanisms we evaluated the effects of the same meal in solid-liquid (SM) and homogenized (HM) form on satiety sensation, gastric emptying rate and plasma cholecystokinin (CCK) concentration. Eight healthy men, aged 21-28 (mean 24.5) years were given two meals (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, total energy 2573 kJ, with water 300 ml) differing only in physical state: SM and HM. The subjects consumed the meals in randomized order on non-consecutive days. The sensations of fullness, satiety and desire to eat were evaluated by means of a questionnaire, gastric emptying was assessed by ultrasonographic measurement of antral area, and plasma CCK concentration was measured by radioimmunoassay. The vegetable-rich meal was significantly more satiating (P < 0.05) when in the HM form than when eaten in a SM state. Furthermore, the overall gastric emptying time was significantly slowed (255 (SEM 11) min after HM v. 214 (SEM 12) min after SM; P < 0.05) and CCK peak occurred later (94 (SEM 12) min after HM v. 62 (SEM 11) min after SM; NS) when the food was consumed in the HM form. Independently of the type of meal, antral area was significantly related to fullness sensations (r2 0.46, P = 0.004). These results demonstrate that meal consistency is an important physical food characteristic which influences both gastric emptying rate and satiety sensation. Moreover, the relationship observed between antral area and fullness sensation confirms that antral distension plays a part in the regulation of eating behaviour.

Adult↗
PubMed1998

Late-onset idiopathic hypoparathyroidism as a cause of diarrhoea.

A 62-year-old man presented with a 20-month history of intermittent watery diarrhoea and hypocalcaemia. At age 43 he had undergone partial gastrectomy with Billroth II anastomosis for perforated peptic ulcer and at age 57 developed megaloblastic anaemia with low serum cobalamin and folate levels. Exhaustive gastrointestinal studies performed to ascertain the cause of the diarrhoea were all negative. Plasma parathyroid hormone levels were undetectable and late-onset idiopathic hypoparathyroidism was diagnosed. Normalization of hypocalcaemia promptly corrected the bowel habit. Idiopathic hypoparathyroidism is an unusual cause of diarrhoea that should, however, be considered in patients with hypocalcaemia and associated diarrhoea without evidence of primary intestinal disease.

Diarrhea↗
PubMed1998

Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3.

Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of transpositional dormancy. We isolated a mutation, rtt100-1, that increases the transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase. In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic processing were not altered relative to those in FUS3 strains but steady-state levels of TyA, integrase, and reverse transcriptase proteins and Ty1 cDNA were all increased. These findings suggest that Fus3 suppresses Ty1 transposition by destabilizing viruslike particle-associated proteins. The Fus3 kinase is activated through the mating-pheromone response pathway by phosphorylation at basal levels in naive cells and at enhanced levels in pheromone-treated cells. We demonstrate that suppression of Ty1 transposition in naive cells requires basal levels of Fus3 activation. Substitution of conserved amino acids required for activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses revealed that components of the pheromone response pathway that act upstream of Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1 transposition by Fus3 provides a haploid-specific mechanism through which environmental signals can modulate the levels of retrotransposition.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Primary liver adenomatosis. Report of two cases and literature review.

BACKGROUND/AIMS: Liver adenomatosis is an uncommon condition and so far only 13 cases fulfilling the requirements for its diagnosis have been reported in the literature. Optimal treatment of the disease and follow-up criteria are still the subject of debate. METHODS: We report on 2 cases of liver adenomatosis. In both cases definite diagnosis was obtained only intraoperatively on biopsy. RESULTS: In neither case was liver transplantation done, due either to patient refusal or foreseeable poor compliance. Prolonged strict follow-up failed to demonstrate malignant changes. CONCLUSIONS: Removal of the huge masses often responsible for abdominal pain is the only real indication for resective surgery. Orthotopic liver transplantation should be reserved for those cases in which malignant changes are suspected due to elevation of the alpha-fetoprotein concentration or gross modifications in the shape of the hepatic lesions.

Adenoma↗