A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B.

The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy.

[Expression of the interleukin-2 receptor in T lymphocytes of the rheumatoid synovial membrane]. / Espressione del recettore per l'interleuchina-2 nei T-linfociti della membrana sinoviale reumatoide.

Indirect immunofluorescence was used to stain DR antigen and interleukin-2 receptor (Tac) of T-lymphocytes (Leu 4+). Tissue samples of synovial membrane were cut from arthroscopic biopsies of inflamed knees in four patients with active rheumatoid arthritis (RA). Consecutive cryostatic sections of rheumatoid sinovium were analysed using monoclonal antibodies. It was found that a high percentage of T-lymphocytes express DR antigen. In contrast the proportion of T cells expressing Tac was small. We conclude that T cell activation in synovial membrane is incomplete, and this disfunction may contribute to the chronic inflammation of RA.

Tissue antigen distribution in hepatocellular carcinoma.

An immunohistochemical study on 63 hepatocellular carcinomas (HCC) was performed for the demonstration of alpha 1-antitrypsin (AAT), alpha-fetoprotein (AFP) and hepatitis B virus (HBV) antigens. AAT and AFP were also investigated in 54 cases of cirrhosis not associated with HCC. AAT was frequently expressed both in HCC (82.5%) and in cirrhosis (53.7%), whereas AFP was present in 41.2% of HCC and never detected in cirrhosis used as controls. These findings suggest that AFP is the more specific antigen for use as a marker of malignant cellular transformation. The HBsAg-positivity in 31.7% of HCC supports the hypothesis of a close link between virus B infection and the tumor.

Membranous glomerulopathy and hepatitis B virus (HBV) infection in children.

Histological examination of renal biopsies in 64 Neapolitan children aged 13 months to 14 years who presented with nephrotic syndrome or persistent hematuria and/or proteinuria revealed membranous glomerulopathy (M.G.) in 14. Hepatitis B surface antigen (HBsAg) was found in the serum of 9/14 children with M.G. and in 1/14 children in an age and sex matched control group. The prevalence of HBsAg positivity in the M.G. children suggests a relationship between HBV infection and the disease. The high prevalence of males in HBsAg positive M.G. children suggests that males have an increased risk of contracting M.G. The absence of chronic liver disease in 8/9 HBsAg positive M.G. patients, and the lack of correlation between the clinical manifestations of kidney disease and the rate of HBV replication indicate that different mechanisms underlie the hepatic and renal pathologies.

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.

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.

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.

An improved method for HBcAg demonstration in paraffin-embedded liver tissue.

Factors influencing the preservation of HBcAg in formalin-fixed, paraffin-embedded liver tissue have been analysed. Fixation time, choice of the embedding medium, deparaffinization and selection of anti-HBc proved to be critical variables. For optimal results, fixation in 4% buffered formalin for no longer than 24-48 h, the use of wax with a low melting point, a heating step prior to deparaffinization, and a search for anti-HBc specifically reactive for paraffinated HBcAg are recommended.

Histochemistry of gamma-glutamyl transpeptidase in human liver biopsies.

The histochemical activity of gamma-glutamyl transpeptidase is examined in human liver biopsy specimens in normal and pathological conditions. Different histochemical patterns can be recognized. In histologically normal liver a faint sinusoidal membrane staining is observed. In pathological liver tissue invariably a pronounced canalicular gamma-GT activity is detected in addition to the faint sinusoidal membrane activity. The canalicular staining pattern is variable in extent and staining intensity, without clear correlation with specific disease entities. Cases with severe degrees of cholestasis, however, show a "washed-out" appearance of the tissue, apparently parallel to the degree of cholestasis. This phenomenon may be explained by the detergent action of bile salts accumulating in cholestatic tissue.

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.

Ultrastructural changes in the liver of patients with chronic non-A, non-B hepatitis.

Electron microscopy examination of liver biopsies from 8 patients with chronic non-A, non-B hepatitis revealed ultrastructural changes similar to those previously described in chimpanzees with experimentally induced acute non-A, non-B hepatitis. These changes consisted of intranuclear clusters of electron-dense, 15-27-nm particles that were detected in five out of the eight patients and of circular cytoplasmic structures that were present in seven cases. Other cytoplasmic abnormalities found in our patients related to the presence of curved membranes apparently developing from apposition of two cisternae of endoplasmic reticulum. In contrast with what has been reported in infected chimpanzees, the nuclear and cytoplasmic changes were not mutually exclusive in our patients, but coexisted in four of them.

Changes in the small biliary passages in the hepatic localization of Hodgkin's disease.

The authors have investigated the behaviour of the small biliary passages in the liver biopsies of six patients suffering from untreated Hodgkin's disease with hepatic localization. No obstruction of the major bile ducts was demonstrated in any patient. Three of the patients were anicteric, while the three others presented with jaundice. In the first three cases typical Hodgkin's granulation tissue appears to be limited to portal tracts and collagen reaction is virtually absent. The three cases with cholestasis showed granulomatous tissue associated with heavy connective tissue rearrangement invading and dissociating the lobular structure. They also show a conspicuous bile-duct proliferation, which is not observed in the three anicteric patients. In these latter cases, however, the small bile ducts running within or near the granulomatous tissue present various morphologic changes, including basal membrane thickening, dilation or constriction of the lumen and alterations of the biliary epithelial lining. Complete disappearance of the bile duct may occur.