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Biomedical subjects

M Pignatelli

Publications and source records attributed to M Pignatelli.

134 records · Page 8Linked to original sources
PubMedDate not supplied

HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection.

In a chimpanzee model of acute type B hepatitis, at the time of onset of hepatitis B virus replication and before the development of immunity to hepatitis B virus, interferon is present in the plasma. This is followed by an increase in the display of HLA class I, but not class II proteins, on the hepatocyte membrane. In chronic hepatitis B virus infection, there is a low density of HLA class I protein display on the infected hepatocyte. Administration of alpha-interferon enhances HLA display and in many cases is followed by a transaminase elevation, seroconversion of HBe antigen to antibody and disappearance of hepatitis B virus DNA from serum, changes implying clearance of infected hepatocytes. Successful response to interferon therapy may be predicted by a rapidly rising serum beta 2-microglobulin, a component of the HLA class I molecule, during the first 2 weeks of therapy, before the rise in transaminases.

Acute Disease↗
PubMedDate not supplied

Methods for quantitating HLA gene product expression in the liver during hepatitis B virus infection.

HLA antigens play an important role in the immunological responses to transplanted organs and in tumor surveillance and antiviral immunity. In several liver diseases qualitative and quantitative changes in the HLA gene product expression can be found on hepatocytes, bile duct epithelium and sinusoidal lining cells and these changes may affect the efficacy of the immune system in recognizing an exogenous antigen. In this paper we describe methods for quantitating the changes in HLA antigen expression occurring in the liver during various phases of hepatitis B virus infection and the way in which we have attempted to identify possible mechanisms leading to chronicity.

Animals↗
PubMedDate not supplied

Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples High Excitability rats.

Several evidences suggest that endocannabinoids exert a neurotrophic effect on developing mesencephalic dopamine neurons. Since an altered mesocorticolimbic system seems to underlie hyperactivity and attention deficit in clinical and animal studies of attention deficit hyperactivity disorder (ADHD), prenatal elevation of anandamide has been induced in Naples high excitability (NHE) rats by inhibition of its reuptake. To this aim, pregnant NHE and random-bred females received a subcutaneous injection of AM-404 (1 mg/kg) or vehicle daily from E11 until E20. Young adult male offsprings were exposed to a spatial novelty (Làt-maze) for 30 min and the behavior was videotaped and analysed for indices of activity (travelled distance, rearing frequency) and attention (rearing duration). Moreover, morphological analysis of the brains was carried out that pertained to cytochrome oxydase as marker of metabolic activity and thyrosine hydroxylase as marker of the dopamine systems. The results indicate that prenatal AM-404 treatment significantly reduces activity by about 20% during the entire testing period and modifies the distribution of scanning times towards short duration episodes in the first part of the test only in NHE-treated rats. In addition, image analysis revealed a significant increase in relative optical density of TH+terminals in the dorsal striatum and substantia nigra of AM-404 treated NHE rats and minor changes in the dorsal cortex of AM-404 treated NRB rats. The data suggest a corrected unbalance between the two dopamine systems that apparently leads to reduced hyperactivity and modified scanning times in this animal model of ADHD. This, in turn, might open new strategies in the treatment of a subset of ADHD cases.

Animals↗
PubMedDate not supplied

Expression patterns of the novel catenin p120cas in gastrointestinal cancers.

p120cas is involved in signal transduction upon src or growth factor stimulation as well as in E-cadherin mediated cell adhesion and may play an important role in carcinogenesis. In this study, we evaluated immunohistochemically the expression and cellular localization of p120cas in 40 gastric, 43 colorectal and 20 pancreatic carcinomas, and examined the relationship between p120cas expression and pathological features. Altered p120cas expression was observed in 70%, 65% and 60% of gastric, colorectal and pancreatic cancers, respectively. The most common abnormality was of cytoplasmic expression associated with loss of membranous distribution found in 37% of gastric, in 25% of colorectal and in 25% of pancreatic cancers. Heterogeneous staining was noted in 15%, 19% and 20%, and complete loss of expression in 18%, 21% and 15% of gastric, colorectal and pancreatic cancers, respectively. There was no correlation between p120cas staining pattern and tumour grade or stage. Aberrant expression of p120cas which may reflect changes in signal transduction pathways occurs frequently in human malignancies.

Catenins↗
PubMedDate not supplied

Biochemical analysis and subcellular distribution of E-cadherin-catenin in adenocarcinomas of the gastro-oesophageal junction.

BACKGROUND: Disturbances in the expression or structure of E-cadherin-catenin, a cell-cell adhesion complex, perturb its cell adhesive function. MATERIALS AND METHODS: We studied the expression and distribution of the E-cadherin-catenin complex in 24 adenocarcinomas of the gastro-oesophageal junction (GOJ) by immunohistochemistry and Western blotting of the Triton X-100-soluble (membrane bound) and insoluble fractions (cytoskeleton bound). RESULTS: Immunohistochemistry demonstrated redistribution of E-cadherin, alpha-, beta- and gamma-catenin from the membrane to the cytoplasm in 13/24 (54%), 18/24 (75%), 16/24 (67%) and 15/24 (63%) tumours, respectively. Five tumours showed nuclear localisation of beta-catenin. Western blotting showed redistribution between the TX-100 soluble and insoluble fraction of E-cadherin and the catenins in 5/11 (45%), 4/10 (40%), 5/11 (45%) and 5/11 (45%) tumours, respectively. CONCLUSION: Loss of membrane bound E-cadherin-catenin is frequently observed in adenocarcinomas of the GOJ and this may reflect loss of function of the E-cadherin-catenin complex in these cancers.

Adenocarcinoma↗
PubMedDate not supplied

Modulation of cell adhesion during epithelial restitution in the gastrointestinal tract.

Epithelial migration, which is a fundamental component of the ulcer healing process, is characterized by complex alterations in adhesion between cells and the extracellular matrix. Growth and motility factors involved in mucosal repair of the gastrointestinal tract seem to modulate these interactions in a coordinated fashion in order to reestablish functional and structural integrity of the mucosa. These findings may have important clinical implications for the treatment of ulcerative conditions of the gastrointestinal tract and lead to the development of specific drugs that promote mucosal healing by exploiting natural mechanisms of cell migration.

Animals↗