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G Fabbretti

Publications and source records attributed to G Fabbretti.

At least 19 recordsLinked to original sources
PubMed2001

Genetic and immunological characterization of fibrinogen inclusion bodies in patients with hepatic fibrinogen storage and liver disease.

Fibrinogen storage in liver cells can occur under three different morphological inclusions. Type I contain all three fibrinogen chains (A alpha, B beta, and gamma) as well as D and E fragments, whereas type II and III lack B beta as well as D and E fragments. Patients with type I inclusions carry a point mutation (gamma 284 Gly-Arg). The mutation is not present in patients with type II and III inclusions. These results appear to suggest that the three various phenotypic expressions (i.e., morphological variants) reflect different genetical abnormalities of fibrinogen.

Fibrinogen↗
PubMed1994

Protracted high-dose interferon gamma therapy for chronic experimental nephropathy.

This study focused on the utility of interferon gamma (IFN gamma) as an anti-fibrotic drug in renal experimental fibrosis; the nephropathy was induced by two doses of Adriamycin (ADR) in 20 Sprague Dawley rats, 10 of which were randomly assigned to receive IFN gamma (45,000 UI) on alternate day for 16 weeks. At the end of the follow up, ADR rats treated with IFN gamma developed massive proteinuria, slight renal insufficiency, and presented diffuse glomerulosclerosis, tubulo interstitial infiltration and fibrosis. No difference was found in the composition of tubulo-interstitial infiltrates, mainly consisting in CD4+T lymphocytes with a minor component of CD8+T cells, in comparison with rats treated with ADR alone. These observations demonstrate the inefficacy of a protracted high-dose treatment with IFN gamma in chronic experimental nephropathy with interstitial fibrosis.

Animals↗
PubMed1994

Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro.

Chronic Adriamycin (ADR) nephropathy is invariably associated with glomerulosclerosis and tubulointerstitial fibrosis. To investigate the hypothesis that severe albuminuria plays a role in the pathogenesis of both processes, we purified the protein from conditioned media of rats with advanced ADR nephropathy and tested the fibrogenic effect on renal fibroblasts and mesangial cells in vitro. Albumin was purified by pseudoligand chromatography and was identified on the basis of the NH2 amino terminus. Furthermore, it was differentiated from the urinary homologue, being more anionic and more fatted while maintaining a conserved peptide composition. The exposure of renal cells to renal albumin induced a dose-dependent reduction in collagen synthesis with a half-maximal decrease with 0.2 microgram/ml of albumin. With renal albumin levels of 0.4 microgram/ml the collagen incorporation of 3H-proline by mesangial cells and renal fibroblasts (primary cultures and cell lines) was reduced by 76, 81 and 45% respectively. A qualitative analysis by SDS-polyacrylamide electrophoresis and immunoprecipitation of radiolabelled collagens demonstrated a drastic and unselective decrease in all major collagens synthesized by mesangial cells and fibroblasts, including type I, III and V. Previous immunoprecipitation of the protein with anti-rat albumin antibodies completely reversed this phenomenon. Finally, albumin purified from urines of rats with ADR nephropathy downregulated the synthesis by renal cells of the same collagens but this effect was less evident compared to renal albumin. These findings demonstrate that renal albumin drastically reduces the synthesis of collagens by mesangial cells and renal fibroblasts, this effect being most evident on those components which constitute the extracellular matrix in glomerulosclerosis and interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Immunohistochemical and genetic characterization of the M Cagliari alpha-1-antitrypsin molecule (M-like alpha-1-antitrypsin deficiency).

BACKGROUND: Genetic alpha-1-antitrypsin (AAT) deficiency may be due to defective secretion, intracellular degradation, or lack of synthesis. Defective secretion results in hepatocytic storage and liver disease. These two events occur only with the common deficiency variant, Z AAT, and with a few rare deficiency variants, called M-like. Hepatocytic storage of AAT (either Z or M-like) can be demonstrated in tissue sections by specific immunostaining with a polyclonal anti-AAT antibody, that recognizes all variants of AAT. A monoclonal antibody capable of selectively and exclusively reacting with Z AAT has been generated and successfully used in both serum and tissue studies. EXPERIMENTAL DESIGN: To determine whether a new M-like variant, M Cagliari, carries a mutation different from Z AAT, we have compared antigenic properties and DNA sequences of the two variants. Liver tissue sections from PiZ and PiM Cagliari patients were stained with both polyclonal anti-AAT and monoclonal anti-Z AAT antibodies. DNAs were polymerase chain reaction-amplified with AAT-specific primers and sequenced. RESULTS: Liver tissue sections from PiZ livers were positively stained with either the polyclonal or the monoclonal antibody. The PiM Cagliari liver sections reacted with the polyclonal antibody, but not with the monoclonal anti-Z AAT, thus indicating a difference in antigenicity from Z AAT. Accordingly, DNA analysis ruled out a Z mutation and revealed a microdeletion in exon II, identical with M Malton. CONCLUSIONS: A simple immunohistochemical assay based upon the application of both polyclonal and monoclonal antibodies represents a reliable test to distinguish Z and nonZ AAT deficiencies, thus assisting in the selection of cases worthy of more time-consuming analyses such as DNA sequencing. The same approach may be used for the characterization of as yet undefined PiM cases with AAT liver storage.

Adult↗
PubMed1993

Precancerous lesions of the biliary tree.

Malignant tumors may arise from any portion of the biliary tree. The term cholangiocarcinoma (CC) applies to both intra- and extrahepatic tumors. More than 95% of these tumors are adenocarcinomas. Differentiation between CC and metastatic adenocarcinoma represents a difficult task for the pathologist. The presence of an intratumoral mini-ductal plate, and in situ carcinoma in bile ducts near the tumor and modulation from the bile duct towards parenchymal liver cells represent the major criteria in assessing the identity of an adenocarcinoma as a primary CC. Primary sclerosing cholangitis and congenital bile duct cysts both put patients at risk of developing CC. Lithiasis, recurrent pyogenic cholangitis, and typhoid infection are suspected but not proven predisposing conditions. Fluke infestations (Clonorchis sinensis and Opisthorchis viverrini) play a role in Far Eastern countries. Bile duct adenoma and multiple biliary papillomatosis may carry a malignant transformation potential. Pseudopyloric metaplasia may be a precursor lesion of CC.

Adenoma, Bile Duct↗
PubMed1993

Hepatic tumor and tumor-like lesions in childhood.

Tumors of the liver are rare in infancy and childhood. Some are peculiar to the pediatric age, e.g., hepatoblastoma, infantile hemangioendothelioma, mesenchymal hamartoma, embryonal rhabdomyosarcoma. This review is based upon personal experience with a series of 32 cases. On the basis of the histological features it is proposed that focal modular hyperplasia (FNH) and mesenchymal hamartoma be considered as tumor-like lesions rather than true neoplasms. A few benign epithelial lesions (FNH, adenoma) were associated with inborn error of metabolism. In half of the patients, hepatocellular carcinoma (HCC) developed in perinatally hepatitis B virus (HBV)-infected children. HCC developed in a noncirrhotic liver in a single patient, in whom HBV-DNA integration had occurred.

Carcinoma, Hepatocellular↗
PubMed1993

N-myc gene amplification/expression in localized stroma-rich neuroblastoma (ganglioneuroblastoma).

Using nucleic acid analysis and in situ hybridization we have demonstrated N-myc amplification and expression in two children with a localized (stages I and II) stroma-rich neuroblastoma (NB) (ganglioneuroblastoma). The phenomenon was observed in both undifferentiated and mature ganglion-like cells. The two children are alive and disease-free without any treatment after 16 and 17 months. These observations suggest that morphologic differentiation in NB in vivo is not necessarily followed by a decrease in N-myc expression. Moreover, N-myc amplification does not represent an adverse prognostic factor. In contrast with what happens in undifferentiated NB, N-myc amplification does not have an adverse effect on prognosis when occurring in localized (stages I and II), stroma-rich NB with a favorable histology.

Child, Preschool↗
PubMed1993

Progression of chronic adriamycin nephropathy in leukopenic rats.

In this study, we examined the progression of chronic Adriamycin (ADR) nephropathy in mild leukopenic rats and tried to define the possible relationship between tubulointerstitial lesions and proteinuria in this model. Chronic ADR nephropathy was induced by 2 doses of ADR (2 mg/kg) in 32 Sprague-Dawley rats. Eight of these were randomly assigned to cyclophosphamide treatment (50 mg/kg), given intravenously every week, to keep the blood leukocyte count constantly lower than 5,000/mm3. Serial parameters were followed for 16 weeks including clearance studies with iothalamate and p-aminohippurate and the analysis of urinary protein composition by: (a) an enzymatic assay for beta-glucosidase; (b) specific ELISA using antibodies against rat albumin and RBP, and finally (c) two-dimensional electrophoresis. ADR-treated rats rapidly (within 2 weeks) developed massive proteinuria which was in constant increment throughout the disease evolution in each single component (i.e., high and low molecular weight proteinuria, enzymuria) and developed renal insufficiency. At week 8, in ADR rats, glomerulosclerosis was mild whereas tubulointerstitial infiltrates predominated, characterized mainly by CD4+ T lymphocytes while CD8+ T lymphocytes were inconspicuous, and macrophages were only occasionally present. All such alterations had worsened after 16 weeks when the tubulointerstitial infiltration was associated with marked interstitial fibrosis and tubular atrophy. Leukopenia induced by cyclophosphamide was in all cases associated with a net amelioration of renal histopathology reducing tubulointerstitial infiltrates (by 40%) and glomerulosclerosis (33 +/- 5 vs. 52.2 +/- 7.5% sclerotic glomeruli) and also ameliorated glomerular filtration indexes (Cl 780 +/- 40 vs. 447 +/- 66 microliters/min/kg-1). In spite of these differences, albuminuria and urinary-retinol-binding protein were comparable at weeks 4, 8 and 16 in this group, while urinary beta-glucosidase was decreased at week 16 (p < 0.001) in cyclophosphamide-treated rats. No other qualitative changes in urinary proteins were detectable by 2-dimensional electrophoresis during the disease development. We concluded that chronic leukopenia prevents interstitial cellular infiltration by lymphocytes, interstitial fibrosis and slows down the decline of renal function typical of chronic ADR nephropathy. Glomerulosclerosis is also reduced in leukopenic rats without any appreciable changes in the urinary excretion of high molecular weight proteins deriving from the glomerulus. Finally, the improvement in tubulointerstitial alteration is associated with the reduction in urinary lysosomal enzymes. Tubulointerstitial alterations are implicated with a prominent role in the progression towards renal failure in chronic ADR glomerulopathy.

Animals↗
PubMed1992

Expression of histone H3 cell cycle-related gene, vimentin and MYC genes in pediatric brain tumors. A preliminary analysis showing the different malignant cell growth potential.

Eleven pediatric brain tumors were studied for the histone H3, Vimentin and MYC gene expression. H3, an S phase cell cycle-related gene (ccr), was found prevalently expressed in tumors with a high mitotic index (MI). Vimentin gene, which contributes to maintaining the cell structure but is also demonstrated to be an early responder gene to growth stimulation was found variously expressed. The different expression of Vimentin gene in the examined samples suggests the active proliferation of the tumor cells. Analysis of MYC gene expression was found increased only in a mesenchymal chondrosarcoma while in other samples MYC mRNA was undetectable. Medulloblastoma, chondrosarcoma, and choroid plexus carcinoma have high S phase H3 gene expression associated with a high MI. Differently an astrocytoma shows a low MI associated with high H3 gene expression. This first preliminary report of H3, Vimentin and MYC gene expression in brain tumors demonstrates that malignant cells are characterized by a different gene expression and different growth potentials.

Adolescent↗
PubMed1992

Hepatic endoplasmic reticulum storage diseases.

Endoplasmic Reticulum Storage Diseases (ERSD) represent a novel group of inborn errors of metabolism affecting secretory proteins and resulting in hepatocytic storage and plasma deficiency of the corresponding protein. The hepatocellular storage is due to a molecular abnormality hindering the translocation of the abnormal protein from the rough (RER) to the smooth endoplasmic reticulum (SER). The molecular abnormality is genetically determined; hence it is hereditary, congenital, familial and permanent. The storage is selective and exclusive for the mutant protein and predisposes to the development of chronic cryptogenic liver disease. ERSD include alpha-1-antitrypsin deficiency, fibrinogen storage and alpha-1-antichymotrypsin deficiency. Basically, the diagnosis of ERSD is a morphological one: immunohistochemistry and electron microscopy are essential tools for their identification.

Afibrinogenemia↗
PubMed1992

From immunohistochemistry to in situ hybridization.

The revolutionary evolution in science and technology has made it possible to face adequately three main challenges in modern medicine: old diseases changing, new diseases appearing, diseases remaining unknown. In this paper we review the road travelled by the pathologist in search of a method which is based upon the application to routine work of instruments and techniques which once were available for research only. Application to tissue studies of immunological and molecular biology techniques allows a dynamic interpretation of biological phenomena with special regard to gene regulation and expression. The method implies stepwise investigations, including immunohistochemistry, EM and in situ hybridization, in order to progress from the suggestive features detectable in routinely stained preparations to more characteristic, specific and, finally, pathognomonic features. HE-stained preparations and appropriate immunohistochemical stains enable recognition of phenotypic changes which may reflect genotypic alterations. Thus there is a logical and methodological link between the simple HE and the most powerful techniques so far introduced in pathology: immunohistochemistry and in situ hybridization.

History, 20th Century↗
PubMed1992

Genetic variants of alpha-1-antitrypsin (AAT).

This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.

Base Sequence↗
PubMed1992

Metanephric adenoma.

In a recent survey of more than one hundred childhood renal tumors in our Laboratory files, we identified a unique case characterized by an unusual degree of differentiation and cell maturity. Histologically this case was notable for an orderly array of small and uniformly-packed tubules with a rosette-like configuration. The nuclei were oval, smooth and of a bland appearance. Mitoses were absent. Many glomerular figures were intermingled. This renal tumor picture is somewhat different from that known as tubular Wilms' tumor because of the well-differentiated adenomatous pattern and the absence of any blastema. The term metanephric adenoma is suggested for this tumor, which may represent the benign counterpart of Wilms' tumor.

Adenoma↗
PubMed1992

Histological diagnosis of hepatocellular carcinoma.

The classical morphological criteria in the diagnosis of hepatocellular carcinoma (HCC) include: a) the similarity of tumour cells to hepatic cord cells; b) the trabecular nature of the growth with capillary and canaliculi formation; and c) the intravascular growth of trabecular carcinoma. These criteria apply to the most common variants of HCC but they do not define all cases of HCC. That makes additional criteria and certain refinements necessary. A promising approach to the diagnosis of HCC is that based upon the consideration by the pathologist of some relevant aspects of the natural history of this tumour. A panel of tests exploring the various functions and properties of liver cells should be developed. This study provides a guideline to a dynamic approach in the diagnosis of HCC. The rationale is based on 5 points; among them, bile production, fibrinogen synthesis, Mallory body, fibrinogen G-G selection and HBV antigen expression can be considered at present as confident markers for the morphological diagnosis of HCC.

Bile↗
PubMed1991

Cirrhosis of the liver. A regenerative process.

The ancient story of Prometheus, chained to a rock for defying Zeus by stealing fire from Mount Olympus and subjected to daily tearing at his liver by an eagle, attests to the early recognition of the extraordinary regenerative capacity of the human liver. This process had remained an intriguing mystery over the millennia. In the last 20 years, following the pioneering work of Bucher (1) and Moolten et al (2), there has been an explosion of research that has clarified some of the mechanisms underlying the process of hepatic regeneration. Regeneration implies proliferation and regeneration. After the fetal and postnatal growth of the liver is completed, hepatocytes no longer proliferate actively, but they can proliferate in response to cell death or loss (3). Hepatocyte growth responses are of particular research interest because they occur in vivo and involve cells that are normally quiescent. Hepatic regeneration constitutes a highly regulated process that is best shown by the arrest of liver growth following a partial hepatectomy precisely at the moment the hepatic mass reaches the mass of the original intact liver (3). This suggests that hepatic regeneration after a partial hepatectomy is a strictly regulated nonautonomous growth process that is controlled by the same factors that are responsible for the determination and maintenance of hepatic mass in a normal individual. In response to a partial hepatectomy, hepatocytes enter the cell cycle and progress to DNA synthesis and replication but only in numbers sufficient to restore the hepatic mass. The regeneration response is both synchronized and universal in that it affects all intrahepatic cell lines, including nonparenchymal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗