Molecular interactions in copper metabolism.
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Animals↗
Biomedical subjects
G Faa
Publications and source records attributed to G Faa.
Chromosome instability in elastofibroma.
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Chromosome Aberrations↗
Chromosomal changes in dysplastic nevi.
The dysplastic nevus is considered to be a precursor lesion of melanoma, representing one of the first steps in the progressive transformation from normal melanocyte to melanoma. Various risk degrees of developing cutaneous melanoma in patients with dysplastic nevi have been advanced, based on the presence of dysplastic nevi or melanoma or both in members of the patient's family. We report on the cytogenetic study of three nevi in a young patient with a family history of melanoma. Each nevus showed a simple clonal chromosome change. The t(6;15)(q13;q21) translocation found in one of them seems of particular significance in view of the fact that a similar one, with breakpoint at 6q13 was reported both in an acquired nevus from a patient with a family history of melanoma and in a case of cutaneous metastatic melanoma. These observations seem to support the hypothesis of the existence of a biological continuum between normal melanocyte and melanoma. Furthermore, the finding of chromosome changes similar to those associated with melanoma reinforces the need for a careful follow-up of patients with dysplastic nevi.
Adult↗
[Rhabdoid tumor of the kidney arising in a newborn infant: description of a case with ultrastructural observations].
INTRODUCTION: Rhabdoid tumour of the kidney is a new independent entity. Before it was considered a variant of Wilms tumor of the kidney. Now we have enough parametres to define the rhabdoid tumor: immunohistochemistry positive by the vimentin, special histological features and behaviour. CASE: We report a very aggressive case of rhabdoid tumor found in a two week old infant. RESULTS: We studied aspects of histology and histochemistry. We found a positivity for vimentin and many cells in apoptosis. DISCUSSION: The mild positivity for vimentin and the high number of cells in apoptosis suggest a relationship between apoptosis and behaviour.
Apoptosis↗
[Molecular interactions in the metabolism of copper and iron].
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Copper↗
[Transmission and scanning microscopy of elastofibroma ultrastructure].
Elastofibroma is a rare benign tumor of soft tissues that has the elective localization in peri- or interscapular region. It is characterized by the proliferation of fibroblast-like cells which appear enveloped by abundant elastic and collagen fibers. Here we present a case of elastofibroma, observed in a 63 year old woman in the interscapular region. The neoformation has been studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Our hypothesis is the possibility that elastofibroma is the consequence of active neoformation of fibers elastic normal in the quality that subsequently is meet to progressive degenerative phenomenons.
Female↗
Expression of cytokeratin 20 in developing rat liver and in experimental models of ductular and oval cell proliferation.
BACKGROUND/AIMS: Recently, a novel type of cytokeratin (CK) has been added to the classical catalog of CKs as CK20. The aim of the present study was to examine the immunoreactivity for CK20 in normal and developing rat liver and in experimental models of bile ductular and oval cell proliferation. METHODS: Eighty-five Fischer rats, subdivided into five groups, were utilized in this study: fetal rats, ranging from day 10 to day 21 of gestation; newborn-neonatal rats, from 2 h to 10 days of age; bile duct ligated (BDL) rats; alpha-naphthyl-isothiocyanate (ANIT)-treated rats; and rats fed a choline-deficient diet containing N-2 Fluorenylacetamide (CD-AAF rats). Frozen sections from each liver were stained with the CK20 specific monoclonal antibody IT-Ks20.10. RESULTS: The present study shows that CK20 is a "bile duct type" CK. In the fetal rat, CK20 appears late during intrahepatic bile duct development, at day 20 of gestation. A marked increase in CK20 expression occurs after birth, suggesting that intrahepatic bile duct maturation continues after birth and that CK20 may be considered as a "maturation" marker of the biliary tree. In BDL rats and in ANIT-treated animals, immunoreactivity of bile ductules for CK20 was strikingly heterogeneous. A variable number of proliferating biliary cells were weakly positive or negative for CK20 and their number increased with the duration of the obstruction or ANIT treatment. In CD-AAF-treated rats, we found a uniform staining of proliferating oval cells for CK20. This finding is in contrast with the observation in BDL and in ANIT groups, and suggests the existence of different mechanisms regulating the proliferation and differentiation of biliary cells under those conditions. CONCLUSIONS: In rat liver, CK20 may be added to the list of "bile duct type" cytokeratins. During development, CK20 expression may be related to the maturation stage of the biliary tree. Typical ductular proliferation induced by BDL or ANIT feeding clearly differs from the oval cell proliferation in the CD-AAF model in terms of immunoreactivity for CK20.
1-Naphthylisothiocyanate↗
Alpha-1-antichymotrypsin immunoreactivity in papillary carcinoma of the thyroid gland.
AIM: Papillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid gland. The immunohistochemical profile of PTC is characterized by immunoreactivity of tumour cells for cytokeratins, thyroglobulin, vimentin, EMA and S100 protein. Recently, the presence of a serum protease inhibitor, alpha-1-antitrypsin (A1AT), has been demonstrated in tumour cells of PTC. The aim of our study was to test immunoreactivity of PTC for another inhibitor of proteases, alpha-1-antichymotrypsin (A1ACT). METHODS AND RESULTS: Serial paraffin sections of nine consecutive cases of PTC were tested with anti-A1AT and anti-A1ACT antibodies. No immunoreactivity for A1AT and A1ACT was found in the normal thyroid tissue surrounding each tumour. In seven out of nine cases, tumour cells of PTC showed cytoplasmic immunoreactivity for A1ACT. In two cases, A1ACT was detected even in the nuclei. Immunoreactivity for A1AT was found only in three cases. Two cases of PTC showed no staining for both A1ACT and A1AT. No significant correlation of A1ACT staining was found with various prognostic indices (age of patients, histological pattern, tumour size, presence of regional lymph node metastases). The two cases showing a lack of staining for both A1ACT and A1AT showed a more aggressive clinical behaviour. CONCLUSIONS: Our preliminary study shows that A1ACT is expressed by tumour cells in a large proportion of papillary carcinomas of the thyroid gland. Its significance remains, to the best of our knowledge, still unknown. The observation of a more aggressive behaviour in the two cases characterized by the absence of immunoreactivity for both A1ACT and A1AT suggests that the presence or absence of protease inhibitors could play a role in controlling tumour progression in PTC.
Adolescent↗
Value of histochemical stains for copper in the diagnosis of Wilson's disease.
AIMS: The histochemical demonstration of hepatic copper is important in the diagnosis of Wilson's disease (WD). Conflicting results have been published with regard to the ability of different histochemical methods to demonstrate copper storage in the liver. Therefore, we evaluated the diagnostic value of three available histochemical methods in a large series of patients affected by WD. METHODS AND RESULTS: Seventy-nine consecutive liver needle biopsies, from 74 patients, 39 males and 35 females, aged 4-60 years (mean age 28.5 years) were stained with orcein, rhodanine and using Timm's method. On the basis of the histological picture, liver biopsies were subdivided into three groups: group A, steatosis; group B, interface hepatitis; group C, chronic hepatitis with bridging fibrosis and/or cirrhosis. In group A, 30.4% of the cases were positive using Timm's method, vs 13.2% using the rhodanine and 17.5% using the orcein method. In group B, Timm's method was positive in 40.1% while rhodanine and orcein showed positivity in 26.7%. In group C, the Timm's method stained 58.6%, rhodanine 36.6% and orcein 29.3% positively. CONCLUSIONS: Our data show that: (1) Timm's silver stain is the most sensitive method for the demonstration of copper in all cases of WD; (2) rhodanine and orcein have minor value in the diagnosis of WD, especially in the early stages of the disease; (3) to increase the diagnostic value of histochemistry for copper multiple histochemical stains in serial sections are required; and (4) although hepatic copper concentration is highest in the early stages of WD, the histochemical demonstration fails in a large number of cases.
Adolescent↗
[Multiple histochemical methods in the diagnosis of Wilson's disease. (Presentation of 74 cases and review of the literature)].
Conflicting results have been reported on the usefulness of histochemistry for copper in the diagnosis of Wilson's Disease (W.D.). In spite of the high number of methods proposed in the literature, no-one has shown to have the characteristics typical of a good histochemical method: high sensitivity associated with high specificity. On this basis, it seemed of interest to evaluate, in a large series of patients with W.D., the diagnostic value of the most commonly used histochemical methods for copper (rhodanine, orcein and Timm's method). To this end, 74 liver needle biopsies from patients affected by W.D., 39 males and 35 females, aged 4-60 years (mean age 28.5 years), were stained with rhodanine (R), orcein (O) and Timm's (T) methods. On the basis of the histological picture, liver biopsies were subdivided in four evolutive stages: stage I = steatosis; stage II = interface hepatitis; stage III = bridging fibrosis; stage IV = cirrhosis. In stage I, histochemistry for copper was positive in 11 out of 21 cases: 6 cases were T+; 1 case R+ and 2 cases O+; 2 cases were T+, R+, O+. In stage II, 11 out of 14 cases were positive for copper staining: 4 T+, 2 R+ and 2 O+; 3 cases were contemporary positives for T, R, O. In stage III, 22 out of 25 cases resulted positive: 8 T+, 3 R+ and 1 O+; 10 cases were positives, in the mean time, for more of one method. In stage IV, 12 of 14 cases were positives: 5 T+, 2 R+, 2 O+ and 3 cases were contemporaneously positives for multiple methods. Our data show that: 1) the percentage of positivity obtained using three histochemical methods for copper is higher than using only one method. From a practical point of view, it is mandatory to utilize, in clinical practice, multiple histochemical stains in order to increase the diagnostic utility of histochemistry for copper; 2) the Timm's method appears to be the most sensitive method for the demonstration of copper in all stages of W.D.; 3) even though hepatic copper already abounds in the early stages of W.D., this pool of intrahepatic copper is not yet demonstrable with any of the three histochemical techniques utilized.
Adolescent↗
[Morphological diagnosis of chronic hepatitis. Minimal requirements for histopathological referral].
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Autoimmune Diseases↗
Polymorphous low-grade adenocarcinoma of the parotid gland.
Polymorphous low-grade adenocarcinoma of the salivary glands is a well-defined clinico-pathological entity which occurs almost exclusively in the oral cavity. Only few reports have documented it in the parotid gland. The authors report an additional case of de novo polymorphous low-grade adenocarcinoma of the parotid and describe the histological and immunocytochemical features of the neoplasm. The current literature is also reviewed.
Adenocarcinoma↗
Cellular fibrous histiocytoma of the skin: evidence of a clonal process with different karyotype from dermatofibrosarcoma.
Recently, a distinct variant of cutaneous fibrous histiocytoma (FH) has been histologically characterized as a "cellular" subtype. This variant is often mistaken for sarcoma, including dermatofibrosarcoma protuberans. We report a case of cellular FH of the skin in which the cytogenetic analysis demonstrated a novel chromosome pattern, possibly allowing distinction from its histologic simulants.
Adult↗
A 3D study of intra and extracellular structures of liver in beta-thalassemia intermedia: an OsO4 maceration analysis.
A scanning electron microscopy study of liver changes has been carried out in three patients affected by beta-thalassemia intermedia (BTI). Applying a new osmium maceration method, recently developed in our laboratory, we had the opportunity to obtain, at SEM, tridimensional images of intra and extracellular structures. Other than the previously reported lesions in BTI, we observed the following pathological findings: disarrangement of the cell structure by a high number of hemosiderin loaded lysosomes; alterations in shape and in diameter of the nuclear pores; presence of apoptotic bodies scattered among the parenchymal cells; deposition of collagen fibers in the space of Disse to form a perihepatocytic dam; enlargement of the sinusoidal endothelial cell fenestrae of the sieve plate. By complete digestion of liver cells, we evidenced a diffuse pericellular fibrosis, made up of interlacing fibrils. Our study evidences some not yet reported morphological lesions in BT. Since patients affected by BTI do not need blood transfusions, these lesions could be considered intrinsic of the disease.
Adult↗
Qualitative and quantitative analysis of AgNOR proteins in chemically induced rat liver carcinogenesis.
A qualitative and quantitative analysis of silver-stained nuclear organizer regions (AgNOR) proteins was performed during hepatocarcinogenesis induced in rats initiated by diethylnitrosamine (DENA) using the resistant-hepatocyte model. Nuclear proteins from control hepatocytes, hyperplastic nodules, and hepatocellular carcinomas (HCC) separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were transferred to nitrocellulose membranes and specifically silver-stained for AgNOR proteins. No difference was observed in the distribution pattern of the silver-stained bands among control, hyperplastic, or cancer cells. The same was true if human cirrhosis and HCC were compared. The evaluation of individual AgNOR protein amounts by computerized densitometric analysis showed that 1) the integrated optical density value of the total AgNOR proteins was greatest in cancer cells, lesser in hyperplastic hepatocytes, and lowest in control hepatocytes, and 2) the amount of the two major silver-stained proteins, nucleolin (105 kd) and protein B23 (39 kd), was always a constant percentage of total AgNOR proteins. An experiment using bromodeoxyuridine incorporation showed that, during hepatocarcinogenesis, AgNOR protein quantity progressively increased and was significantly related to the increased hepatocyte labeling index. These results show that AgNOR protein distribution changes during hepatocarcinogenesis are caused neither by the synthesis of new AgNOR proteins nor by an unbalanced synthesis of individual AgNOR proteins, but to an increased synthesis of nucleolin and protein B23, which is associated with a progressive increased hepatocyte proliferation rate.
Animals↗
Chromosome changes in nonneoplastic tissue. Numerical and structural abnormalities in nasal polyps with atypical stromal cells.
Cytogenetic investigation on short-term cultures of 13 nasal polyps disclosed the presence of chromosome aberrations in three cases: one (a recurrence) showed numerical changes; the other two had structural abnormalities, an inv(12)(q15q22) in one case, a der(6)t(6;12)(q22;q15) in the other. The three cases were characterized histologically by the presence of frequent atypical stromal cells, and were positive for vimentin and smooth muscle actin. Of the remaining 10 cases, three were not analyzable, and seven had normal karyotypes, although random structural changes were seen in two of them.
Adult↗
Zinc content and distribution in the newborn liver.
The newborn liver is a proven model for the study of liver storage of copper and iron. We analyzed zinc concentration and distribution in the livers of newborns and infants using a systematic tissue-sampling technique. We studied 14 newborns of 26-41 weeks of gestation (WG). One stillborn, and three infants (52-90 days old). At autopsy, a longitudinal liver slice extending from the right to the left lobe was subdivided into 10 samples that were analyzed for zinc concentration by atomic absorption spectroscopy. The mean zinc concentration in the newborn liver was 639 micrograms/g of dry tissue (dt). A striking interindividual variability in zinc liver stores was observed; the hepatic concentration of the metal ranged from 300 to 1,400 micrograms/g dt. We found a correlation between zinc liver content and gestational age. In newborns of 27-32 WG, the hepatic zinc concentration was significantly higher (p < 0.01) than in newborns of 34-41 WG. Zinc stores decreased in the postnatal period; in the infant group, the mean liver zinc concentration was 148 micrograms/g dt. The analysis of zinc concentration in 10 blocks from each liver revealed a regular distribution of the metal, without significant differences between liver lobes. Our data show that the newborn liver can be considered an interesting model for the study of zinc storage, which appears to correlate inversely with gestational age. From a practical point of view, the observed regular distribution of zinc implies that, at least in this model, zinc content determined in a small liver sample is representative of zinc content in the whole liver.
Female↗
[The role of the pathologist in the diagnosis and monitoring of Wilson's disease].
Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by copper accumulation in different organs. The clinical presentation of WD is variable: juvenile cirrhosis, with or without neurological symptoms, fulminant hepatitis, acute intravascular hemolysis or late onset with neurological or psychiatric symptoms. The histological picture, the histochemical stains and the ultrastructural findings of the liver are variable in WD. The recent cloning of the WD gene and the report of several mutations (at least 25) of the WD gene suggest the hypothesis that the clinical and pathological variability of this disease is related to a genetic polymorphism. These data may explain why the diagnosis of WD is often extremely difficult for the pathologist, since histochemical stains for copper may be highly variable or negative, despite increased levels of tissue copper concentrations. The most important pathological data are: 1) the evaluation of liver architecture, relevant in the staging of liver disease in three stages; 2) histochemistry for copper, which is variable and needs the use of multiple methods: Timm's method is probably the most useful one, since it shows copper deposits even in the first stage of WD, when liver changes are often reversible; 3) the determination of copper concentration may be crucial in WD diagnosis; copper levels exceeding 250 ug/g of dry tissue are considered diagnostic for the disease; 4) transmission electron microscopy shows, mainly in youngsters, mitochondrial changes considered typical of WD; the ultrastructural picture may be diagnostic for WD in cases with not specific histology and negative histochemical stains; 5) scanning electron microscopy after osmic maceration may be a new useful tool in the study of this liver disease: this technique may give both panoramic and high-power enlargements and allows the localization in the acinar zones of the intracellular hepatocytic changes. Finally, only the optimal approach to liver biopsy, obtaining the highest number of histological, histochemical, quantitative and ultrastructural data, may allow the pathologist to an early diagnosis of WD.
Biopsy, Needle↗