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Biomedical subjects

G Ballardini

Publications and source records attributed to G Ballardini.

At least 73 records · Page 4Linked to original sources
PubMed1989

Dimethylnitrosamine-induced cirrhosis. Evidence for an immunological mechanism.

The present study is concerned with the early events associated with the development of cirrhosis induced by dimethylnitrosamine (DMN). The antigenic expression of MHC class II components (Ia) and of some intermediate filament proteins (vimentin and desmin) have been studied by immunohistochemistry and the findings correlated with ultrastructural data. Micronodular cirrhosis developed after 3 weeks of treatment with DMN but enhanced expression of Ia antigen on macrophages and on infiltrating lymphocytes was observed after 1 week, before the formation of septa, suggesting that immune-mediated mechanisms are involved in the response to DMN-induced liver injury. The expression of vimentin and of desmin also increased at an early stage and at 3 weeks the septa were outlined by cellular elements showing positivity for both intermediate filament proteins. In keeping with these observations, ultrastructural data showed active division of macrophages in situ, infiltration of the parenchyma by T and B lymphocytes, activation of lipocytes (Ito cells) showing evidence of mitosis, and the presence of transitional elements between lipocytes, myofibroblasts and fibroblasts. This experimental model may be helpful in understanding the relationship between immune-mediated response to liver injury and development of hepatic fibrosis.

Animals↗
PubMed1989

Liver fibrosis and extracellular matrix.

Liver fibrosis and extracellular matrix play a central role in liver function impairment. Little information is available on the dynamic aspects and the natural history of fibroplasia, even if there is growing evidence that extracellular matrix accumulation (collagen I, III, IV, fibronectin, laminin, proteoglycans, etc.) is not to be considered only a passive structural support for damaged hepatic tissue, but may actively modulate liver cell behaviour. Clinicians need to date liver fibrosis and to monitor connective tissue synthesis and degradation, but attempts to develop reliable serological markers for collagen metabolism are hampered by the absence of a well defined golden standard to validate them. Nevertheless, serum type III aminoterminal procollagen peptide, at the moment, seems to be the most acceptable parameter of fibrogenesis. The data concerning the mechanisms of collagen production-degradation are becoming so precise and numerous that even if they have not, to date, led to 'routine' advantages for patients, they will end up becoming important tools in the clinical practice and management of liver fibrosis.

Absorption↗
PubMed1989

Antigen presenting cells in liver biopsies from patients with primary biliary cirrhosis.

Although Langerhans, interdigitating and follicular dendritic cells have been occasionally identified in pathological human liver by ultrastructural morphology, no data are available on their phenotypical their phenotypical identification using monoclonal antibodies. Frozen normal liver samples and biopsies from patients with primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis were studied using a panel of 12 monoclonal antibodies (including anti class II antigens, follicular dendritic, macrophage and Langerhans cells). In normal liver, class II positive cells were represented by Kupffer and portal tract histiocytes with a macrophage phenotype. In pathological portal tracts non lymphocytic class II positive cells were represented by macrophages, clusters of follicular dendritic cells (which were detected in close association with B cell aggregates), and by sparse Langerhans cells (localized in areas of piecemeal necrosis and in a periductal position or infiltrating class II positive bile ducts). The present data suggest that both classical antigen presenting cells and class II positive bile duct cells may play some role in the induction of autoimmune reactions.

Antigen-Presenting Cells↗
PubMed1988

Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis.

It has been reported that myofibroblasts contain actin and that Ito cells are positive for desmin. The distribution of desmin and actin detected by immunofluorescence, of vitamin A autofluorescence and of Sudan III staining of lipid droplets has been evaluated in sequential stages of experimental liver fibrosis induced in rats by intraperitoneal injections of swine serum. In the normal rat liver Ito cells were positive for desmin and weakly positive for actin. Prior to the development of hepatic fibrosis a clearcut increase in number and desmin staining of lobular Ito cells was observed in treated rats, but the overall actin pattern was unchanged. In the fibrotic rat livers, highly cellular septa contained large numbers of strongly desmin-positive, actin-weakly positive Ito cells and strongly desmin- and actin-positive myofibroblasts. These observations indicate that both Ito cells and myofibroblasts are positive for desmin, but only myofibroblasts contain large amounts of actin. Visualization of actin and desmin using relatively simple techniques, allows the monitoring of Ito cells proliferation, the accumulation of these cells in fibrous septa and their evolution into myofibroblasts as characterized by their increased desmin and actin content; it also allows an indirect evaluation of the process of fibrogenesis.

Actin Cytoskeleton↗
PubMed1988

Cytoskeleton and extracellular matrix of cutaneous vessels in inflammatory processes: immunomorphological study.

In pathological conditions, vascular modifications occur in various stages involving both vessel structure and adjacent extracellular matrix. The relationships between vascular cells and surrounding microenvironmental stroma are mediated by cytoskeleton. Our investigation showed a high number of vimentin- and actin-positive cells in the vascular cutaneous bed, mainly related to reactive vascularization phenomena, whereas vessel cells with a desmin-positive reaction were barely detectable. Furthermore, in newly formed vessels ultrastructure showed that basement membrane synthesis strictly depends on close contact between the endothelium and extracellular matrix. Our data give structural evidence of the close morphofunctional interactions existing between vascular cells and extracellular matrix.

Actin Cytoskeleton↗
PubMed1987

HLA-A,B,C, HLA-D/DR and HLA-D/DQ expression on unfixed liver biopsy sections from patients with chronic liver disease.

The distribution of HLA-A,B,C, HLA-D/DR and HLA-D/DQ molecules was studied by indirect immunofluorescence with an avidin-biotin technique and monoclonal antibodies, in unfixed cryostat sections of liver biopsies from 76 patients with chronic liver diseases of various aetiologies and five normal liver biopsy specimens. In pathological liver, strong cytoplasmic or membrane-like positivity for HLA-A,B,C of hepatocytes was observed in piecemeal necrosis areas in all groups. Cytoplasmic staining was mainly seen in lobular areas in autoimmune, cryptogenic and HBV-related cases with viral replication, while membrane-like positivity was more frequently observed in primary biliary cirrhosis, alcoholic and HBV-related cases without viral replication. A weak cytoplasmic staining for HLA-D/DR was observed in piecemeal necrosis and lobular areas mainly in HBV-related cases with viral replication. While bile duct cells were positive for both HLA-D/DR and HLA-D/DQ, hepatocytes were consistently HLA-D/DQ negative. The increased HLA-A,B,C expression on hepatocytes should allow T cytotoxic cell aggression. Hepatocellular HLA-D/DR expression is definite but weak and probably does not allow direct autoantigen presentation and induction of autoimmunity. Negativity for HLA-D/DQ further supports this hypothesis. Since cytoplasmic staining for Class I and II molecules is greatly lowered by fixing cryostat liver sections, prestaining conditions should be taken into account when comparing different studies.

Bile Ducts↗
PubMed1985

Sequential behaviour of extracellular matrix glycoproteins in an experimental model of hepatic fibrosis.

The behaviour of extracellular matrix glycoproteins (fibronectin, laminin, basement membrane heparan-sulphate proteoglycan, type III, IV and V collagens) has been investigated in a sequential model of experimental hepatic fibrosis, using an immunofluorescence technique. The presence of some basement membrane macromolecules (such as type IV and V collagens, laminin and basement membrane heparan-sulphate proteoglycan) is detectable only in the early stages of septa formation, while type III collagen and fibronectin persist in late septa. These data suggest that hepatic fibroplasia proceeds through different steps in which stromal glycoproteins are preferentially engaged, as happens during organogenesis.

Animals↗
PubMed1985

Patterns of lacrimal dysfunction in primary biliary cirrhosis.

The lacrimal function has been evaluated in 23 patients suffering from primary biliary cirrhosis by rose bengal test, the Schirmer test 1, and the tear breakup time. Ocular dryness was present in 78% of cases studied. No difference was found with respect to the length or severity of the hepatic involvement between patients with and without lacrimal dysfunction, but in patients with signs of hypolacrimation the changes in the lacrimal tests increased with the duration and histological progression of liver disease.

Adult↗
PubMed1984

Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis.

Direct immunofluorescence with an avidinbiotin system was used to investigate the expression of MHC molecules HLA-DR and HLA-A,B,C on bileducts in cryostat sections from 10 primary biliary cirrhosis (PBC) patients. Needle biopsy specimens from 55 patients with various chronic liver disorders, surgical biopsy specimens from 2 patients with recurrent secondary cholangitis, and 4 normal livers were used as controls. Normal bileducts did not express DR whereas in 8/10 PBC biopsy specimens there were varying degrees of cytoplasmic DR staining in septal or interlobular bileduct epithelium. In the early histological stages of PBC the aberrant DR expression was multifocal, but in late-stage specimens whatever ducts remained were all positive. This pattern resembles that in focal thyroiditis and suggests that DR expression is an early manifestation of autoimmune cholangitis. In 6/61 control biopsies only weak staining was detected in occasional small interlobular ducts. The class I HLA-A,B,C expression normally seen on biliary epithelium was increased in 8/10 PBC cases and in 19/61 non-PBC biopsies. Perhaps the aberrant expression of HLA-DR antigens on bileduct epithelium in PBC enables these cells to present "self antigens" to sensitised T-lymphocytes and to promote autorecognition, possibly in response to several environmental triggers; the increased HLA-A,B,C, expression may be a means of amplifying T-cell cytotoxic responses.

Adult↗
PubMed1984

Steroid treatment lowers hepatic fibroplasia, as explored by serum aminoterminal procollagen III peptide, in chronic liver disease.

Serum aminoterminal type III procollagen peptide (sPIIIP) has been proposed as an index of hepatic fibroplasia. sPIIIP was retrospectively evaluated in 34 treated and five untreated patients affected by chronic active hepatitis with or without cirrhosis by an RIA test. Serum samples taken before and after 6 months of treatment were tested in all cases. In 15 of the treated and all untreated patients, 6-20 (median 13) sera, corresponding to a median follow-up of 43 months were studied. Before treatment, the sPIIIP median value was 18.6 ng/ml; after 6 months of treatment, it decreased to 13.6 ng/ml (p less than 0.005). Follow-up sPIIIP levels were significantly lower in treated than in untreated patients (p less than 0.05), at each interval considered, except for the last control (39 months). In seven patients, treatment was discontinued: sPIIIP rose rapidly in six; four of them were retreated and this was followed by a new decrease. In four patients, sPIIIP was tested weekly from the onset of the treatment: it reverted to normal values within the first week in all cases, while GOT decreased later. sPIIIP is significantly and rapidly reduced by steroids. Steroid withdrawal is generally followed by a rebound, with a new decrease when treatment is restarted. Since sPIIIP is more rapidly lowered than GOT levels, the above data support the hypothesis that steroids can directly affect collagen metabolism.

Adolescent↗
PubMed1983

Relationship between connective tissue cells and fibronectin in a sequential model of experimental hepatic fibrosis.

The cellular and non-cellular components of fibrous septa formed at early and late stages in a sequential model of experimental hepatic fibrosis have been investigated using ultrastructural and immunocytochemical techniques. In the early septa, cells with intermediate features between lobular Ito cells and active fibroblasts were formed. These cells frequently displayed subplasmalemmal microfilaments (myofibroblast-like cells). Macrophages were also present. Scanty typical fibroblasts were present in the late septa. This cellular recruitment might be related to an extracellular glycoprotein-fibronectin-which is at present under investigation as a chemotactic factor for fibroblasts. Strong positivity for fibronectin in early septa and its sharp decrease in late septa seems to support this view. Fibroblasts and/or macrophages are the likely source of fibronectin synthesis.

Animals↗
PubMed1983

Correlation between Ito cells and fibrogenesis in an experimental model of hepatic fibrosis. A sequential stereological study.

The relationship between Ito cells and hepatic fibrogenesis has been investigated in an experimental model: intraperitoneal injection of heterologous serum in rats leads to the appearance of fibrous septa within 5 weeks. Groups of rats were sacrificed at various intervals (from 2.5 to 20 weeks), saline-injected rats being used as controls. Liver fragments were prepared for light and electron microscopy and determination of hydroxyproline. Ito cells were identified by defined morphological criteria on 1 micron sections. The volume density (VD) of Ito cells and fibrous septa, and the Ito cell index were determined. Ito cells represent a very relevant component of early septa. In later stages, the VD of cells with morphological features of Ito cells falls to very low values. This might be related to modulation of Ito cells to fibroblasts. The increase of tissue hydroxyproline is delayed with respect to the peak VD of septal Ito cells, actually corresponding to the fall in the VD of septal Ito cells. The striking increase in the VD of total Ito cells cannot be related to a theoretically possible increase in the volume of single Ito cells, as VD always parallels the Ito cell index. These data suggest a hyperplastic reaction, possibly associated with a cellular migration from the lobules to early septa.

Animals↗
PubMed1983

A post-embedding method: demonstration of fibronectin on human liver by PAP technique.

Fibronectin, one of the most relevant components of extracellular matrix, seems to mediate cell to cell and cell to substrate interactions by means of selective links with collagen fibrils and glycosaminoglycans. Post-embedding technique using PAP method has allowed us a precise localization of fibronectin on semi-thin sections and on adjacent thin sections, improving the knowledge of fibronectin-collagen relationships.

Fibronectins↗
PubMed1981

HBsAg-induced hypertrophic smooth endoplasmic reticulum as a target for liver-kidney microsomal (LKM) antibodies.

To test the hypothesis that LKM antibodies are directed against antigen(s) of the smooth endoplasmic reticulum, liver biopsies from patients with HBsAg chronic hepatitis, rich in liver cells with HBsAg-induced hypertrophic SER, were used. A close correspondence was seen between cells with HBsAg-positive cytoplasm by immunoperoxidase and cells with a stronger and more homogeneous fluorescence by indirect immunofluorescence with LKM-positive sera. These results point to antigenic components of SER as reacting with LKM antibodies. The relevance of antigens present in the ribosomes and membranes of rough endoplasmic reticulum needs further evaluation.

Antibodies↗