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A Francavilla

Publications and source records attributed to A Francavilla.

At least 19 recordsLinked to original sources
PubMed2002

Demonstration of a direct stimulatory effect of bile salts on rat colonic epithelial cell proliferation.

BACKGROUND: Despite the clear demonstration that an increase in faecal bile salt concentration can augment colonocyte proliferation, it is still controversial whether bile salts act on these cells as direct mitogens or by inducing a damage-related proliferative response. The goal of this study was to define the mechanism mediating the proliferative effect of bile salts on rat colonocytes. METHODS: Faecal bile salt concentration was increased by feeding rats on diets enriched with either bile salts or fats. Colonic mucosa proliferating cell nuclear antigen (PCNA) expression, histology and apoptosis, and faecal water cytolytic activity were evaluated to assess proliferation and direct or indirect signs of mucosal damage. RESULTS: Compared to standard diet, chenodeoxycholate-, deoxycholate- and fat-enriched diets produced a significant increase in both faecal water total bile salt concentration (46.0 versus 124.1, 145.9 and 498.5 micromol/L, respectively) and percentage of PCNA-positive nuclei (30.5, versus 37.7, 33.9 and 47.1, respectively) that appeared significantly correlated (r = 0.8; P < 0.001). Chenodeoxycholate and deoxycholate fed animals showed colonic mucosa histology and faecal water cytolytic activity similar to controls, with a significantly reduced apoptotic index. Rats fed on high fat diet, however, showed a mild inflammatory infiltrate associated with an increased apoptosis and faecal water cytolytic activity, all conditions not apparently determined by the increased faecal water total bile salt concentration. CONCLUSIONS: The results obtained in this study demonstrate that bile salts act as direct mitogens on colonic epithelial cells.

Animals↗
PubMed2001

Lamivudine and alpha-interferon in combination long term for precore mutant chronic hepatitis B.

BACKGROUND/AIMS: Alpha-interferon (alpha-IFN) and lamivudine are the two licensed drugs for patients with chronic hepatitis B, however, their efficacy in precore mutant chronic hepatitis B is limited. The aim of this study was to investigate the efficacy of 1 year alpha-IFN-lamivudine combination therapy for anti-HBe/hepatitis B virus- (HBV)-DNA positive patients. METHODS: Between 1997 and 1999, 29 consecutive anti-HBe/HBV-DNA positive patients entered this prospective pilot study. Patients received 100mg lamivudine orally daily and alpha-IFN 6 million units (MU) three times weekly for 52 weeks. All patients were followed-up for 12 months after stopping therapy. Primary end points were loss of serum HBV-DNA and alanine transaminase normalization at week 52. RESULTS: Overall, the end-treatment biochemical and virological response was 93% while the sustained response at week 104 was 14%. HBV-DNA negative patients did not experience a viral breakthrough during treatment; no tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase (YMDD) variant emerged. At week 52, 46% of patients with paired liver biopsies slides available, showed an histological improvement (histological activity index > or =2). CONCLUSIONS: Combination of lamivudine and interferon for 1 year is followed by high end-treatment virological and biochemical response rates, by improvement of liver histology and by the prevention of the emergence of YMDD mutation; however, the sustained response rate remains low.

Adult↗
PubMed2001

Mammalian augmenter of liver regeneration protein is a sulfhydryl oxidase.

BACKGROUND: Augmenter of Liver Regeneration is an important secondary hepatic growth factor. Augmenter of liver regeneration protein has been shown to control mitochondrial gene expression and the lytic activity of liver-resident Natural Killer cells through the levels of interferon-gamma, but the precise enzymatic function of this protein is unknown. AIMS: To define the enzymatic activity of augmenter of liver regeneration protein. The carboxy terminus of augmenter of liver regeneration protein contains a special CXXC motif characteristic for redox proteins and with faint homologies to the redox-active site of sulfhydryl oxidases. Tests were, therefore, carried out to establish whether isolated augmenter of liver regeneration protein can also function in the formation of sulfur bridges. METHODS: Purified augmenter of liver regeneration proteins from rat and human were tested in enzyme assays for the ability to introduce disulfide bonds into protein substrates. The isolated proteins were tested for the formation of dimers and the presence of bound FAD was investigated spectroscopically. The function of the conserved CXXC motif was investigated by in vitro mutagenesis experiments and subsequent enzyme assays. RESULTS: In this study, we demonstrate that rat and human augmenter of liver regeneration protein are flavin-linked sulfhydryl oxidases that catalyze the formation of disulfide bonds in reduced protein substrates. A flavin moiety is firmly but not covalently attached to the protein. In human cell cultures augmenter of liver regeneration protein is expressed in a long and short form that both exist as covalently linked dimers. The active site of the enzyme is associated with a conserved CXXC motif in the carboxy-terminal domain, that is present in the homologous proteins from yeast to humans and also in the human Q6 growth regulator protein. In vitro mutagenesis of one cysteine residue in the CXXC motif results in loss of enzymatic function and the mutated protein no longer binds FAD. CONCLUSIONS: For the first time, these data assign an enzymatic activity to the important hepatic growth factor augmenter of liver regeneration protein. The finding that augmenter of liver regeneration protein acts as a FAD-linked sulfhydryl oxidase is essential to identify the molecular targets inside liver cells and to elucidate the precise role of mammalian augmenter of liver regeneration protein in hepatic cell growth, liver disease and regeneration.

Animals↗
PubMed2001

Epithelial proliferation and ras p21 oncoprotein expression in rectal mucosa of patients with ulcerative colitis.

In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair and neoplastic evolution. Proliferative status is predominantly connoted in active disease, but not defined in remission. Histologically, remission is characterized by normalization of the picture or development of atrophy. Mutation of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work was to assess the proliferative pattern of rectal epithelium in UC during disease activity and in remission and correlate it with ras oncoprotein p21. The study was performed retrospectively in rectal biopsies from four groups each of 10 patients: active ulcerative colitis (AUC), remission with a normal histology (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C, control group). In all, immunohistostain was employed to evaluate the proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21. Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. PCNA LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells were predominant in the lower zone of crypts in RUC and C, while a significant expression of PCNA was also observed in the upper areas in AUC and ARUC. Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC patients, in all 10 ARUC patients and in none of RUC and C. The persistently increased epithelial proliferation associated with ras p21 expression in ARUC may be due to the action of an abnormal, mutated ras gene that could play a role in UC-related tumorigenesis.

Adult↗
PubMed2001

Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance.

AIM: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. METHODS: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. RESULTS: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. CONCLUSIONS: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials.

Administration, Oral↗
PubMed2001

Vertical transmission of hepatitis C virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective study.

BACKGROUND: Mother to infant transmission of hepatitis C virus (HCV) has been extensively studied in mothers with human immunodeficiency virus (HIV) infection, whereas fewer data are available on the vertical HCV transmission in HIV-negative women. METHODS: Between January 1995 and June 1997, 78 consecutive HCV-positive/HIV-negative women with their offspring entered this prospective study aimed to define the prevalence of and risk factors for HCV vertical transmission. Risk factors for HCV were carefully sought, and HCV viral load and genotype were determined in all positive mothers. The infants were tested for alanine aminotransferase (ALT) and HCV-RNA at birth and at 4, 8, 12, 18, and 24 months of age. RESULTS: Eight of 60 (13.3%) infants born to HCV-RNA positive mothers acquired HCV infection, but only 2 (3,3%) were still infected by the end of follow-up. Infants' genotypes matched that of the mothers. ALT levels were in the normal range in all study subjects throughout the follow-up. High maternal viral load (P < 0.05), possession of HCV risk factors (P < 0.004), and history of blood transfusion (P < 0.05) were associated with increased risk of HCV vertical transmission. CONCLUSIONS: This long-term prospective study shows that, although vertical transmission from HIV-negative mothers occurs in 13% of cases, there is a high rate of spontaneous viral clearance (75%). High maternal viral load and mothers belonging to HCV risk categories were the only variables predictive of the vertical transmission.

Adult↗
PubMed2001

Helicobacter heilmannii gastritis: a histological and immunohistochemical trait.

AIM: Biopsies of the gastric antrum were reviewed over a period of 10 years to determine the prevalence of Helicobacter heilmannii in symptomatic subjects from this geographical area and to relate its presence to distinctive histopathological and immunohistochemical features. METHODS: Biopsies from 7926 symptomatic patients were reviewed. Ten serial sections were stained with haematoxylin and eosin for conventional histology. Another 10 sections were stained with the Gram method for spiral bacteria. When H heilmannii was suspected, 10 additional serial sections were stained with methylene blue to obtain homogeneous colouring. An equal number of sections from patients affected by isolated H heilmannii or H pylori gastritis were analysed by immunohistochemistry to evaluate lymphoid aggregate/mucosal lymphocyte clonality (CD20 and CD3) and tumour necrosis factor alpha (TNF-alpha) in stromal cells. RESULTS: The prevalence of H heilmannii was 0.1% (eight of 7926), whereas H pylori was present in 60.7% of patients (4813 of 7926). In two of the eight H heilmannii positive patients both helicobacters were found. In all subjects infected by H heilmannii only, distinctive histology (lymphocyte exudation into gastric foveolae) was seen. Lymphoid aggregates, chronic mucosal inflammation with patchy activity, and the absence of epithelial mucus depletion were regular features of H heilmannii gastritis. Immunohistochemistry did not reveal different lymphocyte clonal patterns between H pylori and H heilmannii gastritis: CD20 positive cells were predominant in the centre of aggregates and mucosal infiltrates, whereas CD3 positive cells were prevalent at the periphery of follicles. Only H pylori gastritis showed a significant increase in TNF-alpha positive stromal cells. CONCLUSION: These data suggest that an unusual lymphocyte reaction, with the tendency to invade the foveolar lumen, is a distinctive histopathological aspect of H heilmannii chronic gastritis, although further studies in a larger series are necessary to confirm this fact. Nevertheless, lymphocyte clones do not differ qualitatively from those found in H pylori infection. Moreover, compared with H heilmannii, H pylori provokes a more intense release of TNF-alpha, suggesting that different inflammatory responses exist to these two organisms.

Adolescent↗
PubMed2000

Response

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Journal Article↗
PubMed2000

Molecular mechanisms of augmenter of liver regeneration as immunoregulator: its effect on interferon-gamma expression in rat liver.

BACKGROUND: We have shown that the administration of exogenous Augmenter of Liver Regeneration protein in intact rats i) regulates mitochondrial gene expression by inducing the transcription and translation of the nuclear-encoded mitochondrial transcription factor A, and ii) inhibits the lytic activity of liver-resident Natural Killer cells. AIMS: The present investigation was carried out to study the effect, in intact rats, of exogenous administration of Augmenter of Liver Regeneration protein on Interferon-gamma, a cytokine produced by activated Natural Killer cells and known to control the expression of mitochondrial transcription factor A, a nuclear gene responsible for mitochondrial metabolism. METHODS: Interferon-gamma was measured as messenger RNA in liver-derived mononuclear leukocytes and as protein in liver-derived Natural Killer cells after a single injection of Augmenter of Liver Regeneration protein. RESULTS: The data obtained demonstrate that: i) in intact rats, Augmenter of Liver Regeneration protein administration induces a reduction of Interferon-gamma in the liver-resident Natural Killer cells and ii) the administration of Interferon-gamma in 70% hepatectomized rats is followed by a significant reduction both of the mitochondrial transcription factor A expression and of liver regeneration. CONCLUSIONS: These data demonstrate the pivotal role of Augmenter of Liver Regeneration as Growth Factor and as immunoregulator by controlling, through Interferon-gamma levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident Natural Killer cells.

Animals↗
PubMed2000

Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum.

We describe the cases of two patients with Crohn's disease affected by severe perineal fistulae resistant to conventional therapies, successfully treated with FK 506, a new immunomodulatory drug. It is well absorbed from diseased bowel and preliminary experiences have indicated its short-term use in complicated Crohn's disease. The first patient was a 24-year-old male with perineal fistula and severe skin ulceration (8 cm of external opening diameter). He had undergone colectomy and ileostomy because of severe pancolitis refractory to medical treatment and had been treated with azathioprine and metronidazole. Two months after starting FK 506, a dramatic improvement made further surgical operation unnecessary. Local and general benefit was observed during the following 26 months, until FK 506 was withdrawn. The second patient was a 28-year-old male with a diagnosis of ulcerative pancolitis changed to Crohn's disease two months after the onset of a perineal fistula, recurring despite drainage procedures, steroid therapy, and total parenteral nutrition. FK 506 was administered for two months with a complete healing of fistula. Successively, it was stopped and corticosteroids (associated to enteral nutrition) were given because of recurrent rectal bleeding. Our experience encourages the use of oral FK 506 in complicated Crohn's disease and suggests the possibility of a long-term primary therapy other than the use as a "bridge" to other treatments.

Administration, Oral↗
PubMed1999

Recurrence of desmoid tumor in a multivisceral transplant patient with Gardner's syndrome.

BACKGROUND: Desmoid tumors are locally invasive fibromatous tumors, which, in patients with Gardner's syndrome, usually occur in the abdominal wall or intra-abdominally. After excision, they tend to recur, often leading to multiple bowel resections. METHODS: This is a report of the clinical course of a patient with Gardner's syndrome and desmoid tumor who had multiple enterectomies and gradually developed short-gut syndrome. He required prolonged parenteral nutrition, which damaged the liver. The patient underwent a multivisceral transplantation as a life-saving procedure. RESULTS: After the transplant, the desmoid tumor recurred in the thoracic wall twice and was successfully resected. It also recurred in the abdominal cavity, compressing the intestinal loops; the tumor was excised uneventfully, leaving the graft intact. The recurrent tumors were all of recipient origin. CONCLUSIONS: Intestinal and multivisceral transplantation could be considered in patients with short-gut syndrome caused by recurrent desmoid tumor. In the case of posttransplant tumor recurrence, resection is the only option recommended.

Adult↗
PubMed1999

The RXc graph in evaluating and monitoring fluid balance in patients with liver cirrhosis.

A recent study, using height-standardized resistance (R/H) and reactance (Xc/H) and assuming a bivariate distribution, has proposed the "RXc graph". We applied this new approach for patients with chronic liver disease in differentiating various degrees of fluid unbalance. Our data showed that a 95% confidence ellipse of patients with chronic hepatitis (CH) overlapped that of healthy control subjects (CONTR), while those of patients with liver cirrhosis (CIR), patients with cirrhosis and ascites (ACIR), and patients with cirrhosis, edemas, and ascites (AECIR) were clearly different for both genders. A progressively shorter mean impedance vector proportional to the stage of liver disease and to the degree of fluid unbalance was found. The lower half of the 50% tolerance ellipse for the healthy population proved to be a threshold for cirrhotics, while almost all the subjects with clinically detectable edema fell outside this limit. The RXc graph was shown to be useful in monitoring the treatment of fluid unbalance and for the immediate selection of patients in whom BIA can precisely assess body composition.

Adolescent↗