Biomedical subjects

A Pagani

Publications and source records attributed to A Pagani.

At least 19 recordsLinked to original sources

PubMed1995

Neural and mesenchymal differentiations in Ewing's sarcoma cell lines. Morphological, immunophenotypic, molecular biological and cytogenetic evidence.

Three established Ewing's sarcoma (ES) cell lines (TC106, 6647, A4573), grown both in vitro and as xenograft tumors, were analyzed. In all 3 lines and tumors, the ES characteristic reciprocal translocation (11;22), as well as the presence of the ES-associated p30/32MIC2 antigen, were documented. However, these cell lines showed discrepancies in their neural and mesenchymal differentiation. The TC106 line was characterized by expression of the neuroendocrine marker secretogranin II (SgII) which was detectable by Northern blot and by radioimmunological detection (RIA) in the culture medium of secretoneurin, a proteolytic product of SgII. In contrast, TC106 cells were immunohistochemically and radioimmunologically secretoneurin-negative. Rapid cellular secretion of the peptide is probably the explanation of such a discrepancy. The 6647 and A4573 cell lines were SgII/secretoneurin-negative and the former presented morphological and immunocytochemical evidence of mesenchymal differentiation. In fact, the 6647 xenograft tumor showed osteosarcomatous-type morphological features and the neoplastic cells were immunocytochemically positive for osteonectin and osteocalcin antigens. Expression of the CgA gene, which is typical of neuroblastomas, was absent in the Ewing's sarcoma cell lines investigated. Our findings provide experimental evidence that Ewing's sarcoma is a heterogeneous tumor which may show either neuroectodermal or mesenchymal differentiation. SgII/secretoneurin analysis by hybridization and RIA procedures is a reliable approach to the identification of ES with neuroendocrine differentiation.

Animals↗

PubMed1995

Diagnostic problems in medullary carcinoma of the thyroid.

Medullary carcinoma of the thyroid (MCT), the tumor entity related to parafollicular C cells of the thyroid gland, is characterized by peculiar morphological, functional and behavioral features. Apart from the constant finding of calcitonin production by MCT, heterogeneous patterns of growth as well as different associations with other lesions in the setting of MEN II syndrome have been observed. This review addresses these points, as were discussed at the 1992 European School of Pathology courses. Heterogeneity of histological patterns of MCT suggests caution in the interpretation of any thyroid tumor. Immunohistochemical demonstration of calcitonin is apparently the only valid criterion for a differential diagnosis. A correct identification of MCT is important for the individual patient (to plan proper therapy) but also for patient's relatives to screen other familiar cases in the setting of MEN II syndromes.

Carcinoma, Medullary↗

PubMed1994

PIP/GCDFP-15 gene expression and apocrine differentiation in carcinomas of the breast.

The frequency and the significance of apocrine differentiation in carcinomas of the breast are uncertain, because of the lack of reliable and reproducible criteria for morphological diagnosis. The 15 kDa glycoprotein of cystic breast disease (GCDFP-15) is regarded as a specific functional marker of apocrine cells. Expression of the prolactin-inducible protein (PIP)/GCDFP-15 gene was investigated by Northern blot analysis and in situ hybridization in breast cancer cell lines and in an unselected series (33 cases) of primary carcinomas of the breast. On the same cases, histological assessment of apocrine differentiation and immunocytochemical detection of GCDFP-15 were also performed and correlated with follow-up data. The presence of PIP/GCDFP-15 mRNA was a feature of a relatively high number of cases, but was incompletely correlated with histological and immunocytochemical evidences of apocrine differentiation. Expression of the PIP/GCDFP-15 gene was significantly associated with relapse-free survival, and may represent a novel variable of functional and prognostic relevance.

Adult↗

PubMed1994

[The procollagen-III peptide in the clinical surveillance of alcoholic hepatopathy and other chronic hepatopathies].

Liver fibrosis determines the course and prognosis of alcoholic liver disease. Evaluation of serum concentration of procollagen-III peptides (sPIIIP) is considered a biochemical test useful for evaluating a fibrotic process. We have investigated 30 healthy subjects and 53 patients with alcoholic liver disease, histologically diagnosed by percutaneous liver biopsy in four clusters: steatosis (11), fibrosteatosis (11), chronic active hepatitis (11) and cirrhosis (20). SPIIIP levels were increased in patients with cirrhosis and chronic active hepatitis; while they were regular in patients with steatosis and fibrosteatosis. Evaluation of serum concentration of sPIIIP by radioimmunoassay seems to be an useful test for identifying patients with alcoholic liver disease with a good prognosis and patients in progress to cirrhosis and it is an useful test for control the course and evolution of chronic liver disease.

Adult↗

PubMed1994

[Hepatitis C and chronic alcoholic hepatopathy].

We evaluated hepatitis C virus prevalence in 105 patients with chronic alcoholic liver disease by research of antibodies to hepatitis C virus (anti-HCV) by second generation recombinant based enzyme immunosorbent to assay and immunoblot to assay. 46 patients of 105 (43.7%) were anti-HCV positive: 2 in steatosis group (9.5%), 3 in steatofibrosis (23%), 10 in chronic active hepatitis (66.6%), 22 in cirrhosis (59.4%) and 9 in hepatocellular carcinoma (47.3%). These patients had higher levels of serum gammaglobulin and transaminases than seronegative patients. We think that there is a correlation between high prevalence of antibodies anti-HCV and the evolution of damage in chronic alcoholic liver disease.

Adult↗

PubMed1994

[The use of myoglobin for the early diagnosis of reperfusion in acute myocardial infarct].

Myoglobin (Mb) is an intracardiac protein known to be rapidly released after onset of reperfusion. The new automated latex-enhanced nephelometric immunoassay is an interesting fast alternative to the other methods. Therefore we sought to assess the accuracy of rapid rise of Mb concentration to predict the success of reperfusion. Thirty consecutive patients, admitted to the coronary care unit for first acute Q-wave myocardial infarction, were prospectively studied. They underwent thrombolysis 126 +/- 45 min (range 30-180) after onset of symptoms. Mb determinations were obtained before starting therapy and, thereafter, hourly for 5 hours, and after 8 and 12 hours. The usual non invasive markers of reperfusion were considered, and coronary arteriography was performed in all patients at 5.5 +/- 0.9 days (range 1-6). In 23 patients (77%) patent infarct-related artery (IRA) (TIMI II-III) and in 7 (23%) occluded IRA (TIMI 0-I) was observed at coronary arteriography. We modified the judgment in 3 cases (10%) with occluded IRA. All reperfused patients (Group A) showed a rapid rise of Mb concentration with a mean time to peak occurring 133 +/- 80 min (range 60-180) after therapy. Mean value of unreperfused patients (Group B) was 330 +/- 173 min (range 180-420). We retrospectively stated a time to peak of Mb concentration within 180 min as diagnostic threshold for reperfusion. Sensitivity was 100%, specificity 50%, positive predictive value 93%, negative predictive value 100%. The results of this study confirm that Mb release kinetics may play an interesting role in the early prediction of patency of IRA in acute myocardial infarction after thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Nonspecific in situ hybridization reaction in neuroendocrine cells and tumors of the gastrointestinal tract using oligonucleotide probes.

Oligonucleotides used in in situ hybridization (ISH), regardless of their sequence specificity, bind to neuroendocrine (NE) cells in normal gastrointestinal mucosa and tumors. This nonspecific binding, presumably related to the presence in NE cells of hidden NH2 groups of obscure origin, can be prevented by acetic anhydride treatment of the sections. This is a routine step in several ISH protocols but not in all. This study emphasizes the need to establish safe protocols and controls to check the specificity of ISH procedures.

Base Sequence↗

PubMed1992

Differential diagnostic patterns of lung neuroendocrine tumours. A clinico-pathological and immunohistochemical study of 122 cases.

A series of 3 tumourlets (TLs), 81 typical carcinoids (TCs), 14 atypical carcinoids (ACs) (well-differentiated neuroendocrine carcinomas, WDNCs) and 24 small cell-intermediate cell carcinomas (SCC-ICCs) of the lung were studied. Histopathological features were correlated with amine and peptide hormone immunoreactivity and with clinical data. All types of tumours expressed general neuroendocrine (NE) markers: Grimelius positivity and chromogranins were detected more frequently in well-differentiated (TLs, TCs) than in less well differentiated tumours [ACs (WDNCs) and SCC-ICCs] whereas neuron specific enolase (NSE) was prominent in the latter tumours. TLs and peripheral TCs were benign, often showing a paraganglioid pattern and frequently expressing gastrin-releasing peptide (GRP), which is present in the peripheral airways of normal lung. Central TCs were associated with lymph node metastases in 8.5% of the cases, frequently had a trabecular architecture, often associated with human milk fat globule 2 (HMFG2)-positive acinar and rosette-like structures, and were mainly immunostained for the alpha-subunit of human chorionic gonadotrophin (alpha-hCG) and serotonin. ACs (WDNCs) were associated with intrathoracic and/or extrathoracic metastases in 57.1% of the cases with a mortality rate of 35.7%. Their histological and cytological features were intermediate between those of TCs and SCC-ICCs. ACs (WDNCs) expressed serotonin and alpha-hCG less frequently than TCs. All SCC-ICCs were surgically treated and displayed a mortality rate of 91.6% with a mean survival of 10.2 months after operation. These tumours were characterized by high expression of HMFG2 and NSE, while the expression of both orthotopic (serotonin, GRP) and ectopic (ACTH) specific NE substances was very low. Since all TCs (either central or peripheral) had a favourable outcome, while about 36% of ACs (WDNCs) were fatal, the latter seem more appropriately designated "well-differentiated NE carcinomas". The differential diagnosis between different NE tumours of the lung is important and is mainly based on morphology. Both panendocrine and specific immunohistochemical markers are helpful in distinguishing the less aggressive, mostly benign varieties from the more malignant varieties.

Adult↗

PubMed1992

Primary oat cell (neuroendocrine) carcinoma of the breast. Report of four cases.

Four cases of oat cell (neuroendocrine) carcinoma of the breast are reported. Three patients died within 15 months of the diagnosis and the fourth patient is alive after 44 months. Histochemical, ultrastructural and mRNA markers of endocrine differentiation were present in three cases. These tumours show histological similarities to breast metastases of bronchial oat cell carcinoma, but a distinguishing feature is the presence of in situ ductal lesions. It appears that the breast is a further site which has to be added to the long list of extrapulmonary oat cell carcinomas.

Adult↗

PubMed1992

Expression of members of the chromogranin family in primary neuroblastomas.

Expression of the members of the chromogranin family [i.e., chromogranin A (CgA), chromogranin B, and secretogranin II (SgII)], the acidic proteins of the matrix of the chromaffin granules presently regarded as specific neuroendocrine markers, was investigated at gene and protein levels in a series of 14 cases of primary untreated neuroblastomas. Oligonucleotides and cRNA probes were employed for hybridization analysis of specific mRNAs (both by Northern blots and nonradioactive in situ hybridization); proteins were localized by immunocytochemistry. Expression of different amounts of each type of chromogranin was determined in all tumors. Cases found immunocytochemically negative were all positive by Northern blot and in situ hybridization. A better prognosis was associated with a higher relative expression of SgII; on the contrary, a worse outcome was observed in cases with a higher expression of CgA. These findings are consistent with the hypothesis that SgII is preferentially expressed in neuroblastomas undergoing neuronal differentiation. In cases of neuroblastomas, determination of expression levels of the different chromogranins in the tissues (and in the serum) can provide parameters of high diagnostic and prognostic value.

Adolescent↗

PubMed1992

Secretogranin II expression in Ewing's sarcomas and primitive neuroectodermal tumors.

Production of chromogranins, the acidic components of the chromaffin granules regarded as specific neuroendocrine markers, was analyzed by immunocytochemistry and hybridization (Northern blotting and in situ hybridization) in primary lesions and cell lines of Ewing's sarcomas, primitive neuroectodermal tumors (PNETs), and neuroblastomas. Antibodies and probes specific for chromogranin A (CgA), chromogranin B (CgB), and secretogranin II (SgII) were used. Ewing's sarcomas and PNETs, unlike neuroblastomas, were negative for CgA and CgB. Two primary Ewing's sarcomas, one primary PNET (an Askin tumor), and one PNET cell line (TC32) were found to strongly express the SgII gene, as shown by the presence of specific mRNA. This result supports the hypothesis that some Ewing's sarcomas represent a most primitive form of neuroectodermal tumor; in addition, it indicates a diagnostic role of SgII in cases of Ewing's sarcomas and PNETs.

Adolescent↗

PubMed1992

Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications.

The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies.

Antibodies, Monoclonal↗

PubMed1992

[Determination of serum procollagen-III peptide in chronic liver diseases. Clinical usefulness].

Liver fibrosis determines the course and prognosis of chronic liver disease. Histological examination of liver biopsy is essential for diagnosing hepatic disease. Evaluation of serum concentration procollagen III peptides (sPIIIP) by radioimmunoassay (RIA) is a biochemical test useful for evaluating a fibrotic process. We have investigated 20 healthy subjects and 50 patients with chronic liver disease, histologically diagnosed by percutaneous liver biopsy: steatosis (8), fibrosteatosis (7), chronic persistent hepatitis (10), chronic active hepatitis (7), cirrhosis (18). SPIIIP levels were increased in patients with cirrhosis and chronic active hepatitis and in these groups of patients such levels were well correlated with histological activity of hepatic disease. Evaluation of serum concentration of PIIIP by RIA seems to be a useful test for evaluating a fibrotic process in chronic liver diseases evolving towards cirrhosis.

Adult↗

PubMed1991

Expression of the gastrin-releasing peptide gene in carcinomas of the breast.

Expression of gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian bombesin, has been investigated at gene and protein level in a series of 28 primary breast carcinomas, in 6 mammary cancer cell lines and in one transplantable rat mammary carcinoma. Moderate to strong expression of GRP mRNA was detected in 5 breast carcinomas by Northern blot analysis with a pre-pro-GRP probe; 4 other cases were weakly reactive. Two of these cases also gave a specific immunocytochemical reaction for GRP, controlled with absorption experiments. Correlation with NE differentiation [as shown by chromogranins (Cg) and/or NSE and/or Grimelius positivity] was low, since only one case of breast carcinoma co-expressed GRP and Cg mRNAs. Breast cancer cell lines and a rat carcinoma gave negative results. GRP production in breast cancer did not appear to bear prognostic implications, but longer follow-up periods are needed to confirm these data. As shown in small-cell lung cancer, GRP might be involved in autocrine growth control mechanisms of a group of breast carcinomas.

Animals↗

PubMed1991

Significance of the smooth muscle cell component in Peutz-Jeghers and juvenile polyps.

We have previously reported the presence of smooth muscle cells (SMCs) in the lamina propria of both tubular and villous adenomatous polyps. In the current study, we investigated the presence and distribution of SMCs with immunohistochemical techniques using anti-alpha smooth muscle actin and anti-desmin antibodies on a series of hamartomatous polyps. In five Peutz-Jeghers polyps, large tree-like branches of SMCs were observed, while in 13 juvenile polyps, rare elongated SMCs were found in the lamina propria, partially surrounding cystically dilated glands. Apart from the quantitative differences, the SMC distribution was similar in the two types of hamartomatous polyps and not dissimilar from the pattern described in neoplastic polyps. These findings make the category "juvenile polyp" less clear and its differentiation from other histologic types of polyp less sharp. Thus, the presence or absence of SMCs cannot form the basis of the differential diagnosis between adenomatous and hamartomatous polyps.

Adolescent↗

PubMed1990

Chromogranin A and B gene expression in carcinomas of the breast. Correlation of immunocytochemical, immunoblot, and hybridization analyses.

Chromogranins (Cg) are regarded as specific neuroendocrine (NE) markers in cells and tumors. Expression of CgA and CgB genes has been demonstrated by correlative immunocytochemical, immunoblotting, in situ hybridization, and Northern blot procedures in seven argyrophilic breast carcinomas, while eight control cases of ductal carcinomas, not otherwise specified, were negative. A high degree of correlation was observed between the various techniques revealing CgA and/or CgB gene expression at different levels; minor discrepancies might be related to tumor heterogeneity or to technical factors. The present study, confirming previous investigations, establishes NE differentiation in a group of human breast cancers. The identification of this type of tumors, especially by testing chromogranin(s) production, appears to be of both biologic and clinical interest.

Biomarkers, Tumor↗

PubMed1989

Compressed spectral arrays for the analysis of 24-hr heart rate variability signal: enhancement of parameters and data reduction.

Heart rate variability signal in the form of an R-R interval tachogram is detected in Holter type 24-hr ECG recordings. Spectral analysis is carried out over consecutive nonoverlapping records, and the information is displayed in the form of a compressed spectral array through parametric techniques. The trends of spectral parameters such as low-frequency (LF) and high-frequency (HF) powers and central frequencies are also plotted, together with the classical mean R-R value and variance relative to each single spectrum. These parameters quantify the effect of sympatho-vagal balance on heart rate control during the 24-hr period and provide important elements for the diagnostic evaluation of various pathologies, like hypertension. A spectral compression algorithm which checks the position of the poles relative to LF and HF bands inside the unitary circle in the complex zeta-plane is also developed. Applications of this procedure are foreseen in the clinical evaluation of ambulant patients as well as in the study of physical and psychological stress.

Algorithms↗

PubMed1988

An unusual case of chronic myelocytic leukemia characterized by a conspicuous tissue infiltration treated with leukapheresis.

An unusual case of chronic myelocytic leukemia (CML) is described that presented leukocytosis at onset (720 X 10(9)/l), symptoms of stasis, organomegaly, and a conspicuous infiltration of leukemic cells from the pelvis to the right popliteal cavity. As initial therapy and in addition to chemotherapy, six therapeutic leukapheresis treatments (TL) were performed and the patient showed dramatic symptomatic improvement with reduction in leukocytosis (97 X 10(9)/l), organomegaly, and tissue infiltration.

Adult↗