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Biomedical subjects

A Pagani

Publications and source records attributed to A Pagani.

At least 19 recordsLinked to original sources
PubMed2005

Relationships between human serum resistin, inflammatory markers and insulin resistance.

OBJECTIVE: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). SUBJECTS: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. RESULTS: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). CONCLUSIONS: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.

Biomarkers↗
PubMed2005

[A useful technical device to improve the sampling of uterine cervical conization].

Standardized procedures regarding the sampling of cervical conization are extensively described in the Literature. The cervical cone dimension depends on the surgical technical approach and on the extension of the dysplasic/neoplastic lesion. Current sampling procedures frequently turn out to be of problematic correct realization, with special regard to small size cervical cones and to fixed material with subsequent artefactual tissue coarctation. Here we describe a simple device, which makes the cone sampling procedure easier and more accurate, allowing better oriented and better recomposed samples. Perpendicular sections to the cervical lumen allow in fact an accurate evaluation of the lesion's depth and of the status of the resection surgical borders. After conization, preventive agreements with the surgeon provide that, before fixation, a 2-3 mm in diameter smooth plastic probe is inserted into the cervical channel, from the external cervical os to the conization apex (a fragment of the handle of an endocervical cytological brush can be used). The insertion of such a "specillum" must be performed with warning gently since superficial cervical epithelium, especially if dysplasic (overall in case of severe dysplasia), is particularly subjected to mechanical abrasions. The preventive insertion of the endocervical probe makes the cone sampling more manageable, in fact the cervical channel is slightly dilated and the subsequent fixation hardens the cone tissues. After the "specillum" extraction, the cervical lumen appears clearly visible; in such a situation, the endocervical cone apex will be exactly sampled, and the subsequent seriated clockwise sampling of the residual cone will be more smoothly performed, with following preparation of adequate histological sections 4. In our experience such a simple and easy-to-apply device, proves to be useful in making the uterine cone sampling more accurate and comfortable.

Cervix Uteri↗
PubMed2000

Human cytomegalovirus immediate-early mRNA detection by nucleic acid sequence-based amplification as a new parameter for preemptive therapy in bone marrow transplant recipients.

Human cytomegalovirus (HCMV) infection was monitored retrospectively by qualitative determination of immediate-early (IE) mRNA by nucleic acid sequence-based amplification (NASBA) in a series of 51 bone marrow transplant (BMT) recipients. The qualitative results for IE mRNA obtained by NASBA were compared with those obtained by prospective quantitation of HCMV viremia and antigenemia and retrospective quantitation of DNA in blood (DNAemia) by PCR as well as by qualitative determination of late pp67 mRNA by NASBA. On the whole, of the 39 HCMV-positive patients (all asymptomatic), HCMV was detected in 14 (35.9%) by quantitation of viremia, 15 (38.5%) by detection of pp67 mRNA by NASBA, 32 (82.1%) by quantitation of DNAemia, and 33 (84.6%) by quantitation of antigenemia, while HCMV was detected in 38 (97.4%) patients by detection of IE mRNA by NASBA. In the immunocompetent host, IE mRNA was not detected by NASBA in 100 blood donors or during reactivated infections in 30 breast-feeding mothers. Likewise, NASBA did not detect IE mRNA in 56 solid-organ transplant recipients in the first 21 days after transplantation. By using NASBA for detection of IE mRNA as the reference standard for detection of HCMV infection in blood samples, the diagnostic sensitivities were 67.7% for quantitation of DNAemia, 59.0% for quantitation of antigenemia, 18.3% for detection of pp67 mRNA by NASBA, and 16.0% for quantitation of viremia. Specificities and negative and positive predictive values were >90.0, >70.0, and >80.0%, respectively, for all four assays. The mean times to first HCMV detection after bone marrow transplantation were 37.7 +/- 15.4 days for detection of IE mRNA by NASBA, 39.6 +/- 15.6 days for quantitation of antigenemia, 40.9 +/- 15.2 days for quantitation of DNAemia, and 43.7 +/- 16.3 or 43.7 +/- 17.5 days for quantitation of viremia and detection of pp67 mRNA by NASBA, respectively. On the whole, 31 BMT recipients received preemptive therapy by using confirmed antigenemia positivity as a cutoff, while 35 patients could have been treated by using NASBA positivity as a cutoff and 31 could have been treated by using quantitation of DNAemia as a cutoff. In single patients, IE mRNA was detected in every episode of active HCMV infection, mostly preceding and sometimes accompanying antigenemia and DNAemia, whereas pp67 mRNA was detected only concomitantly with the highest peaks of infection. HCMV IE mRNA detection may represent a useful parameter for initiation of preemptive therapy in BMT recipients.

Adolescent↗
PubMed2000

Levels and molecular properties of secretoneurin-immunoreactivity in the serum and urine of control and neuroendocrine tumor patients.

We have determined the levels of secretoneurin (SN), a novel 33-amino acid neuropeptide belonging to the class of chromogranins, in the serum and urine of healthy subjects and patients suffering from various tumors. SN serum levels averaged 22.1+/-1.1 fmol/mL. They were 5-fold higher in younger children and then declined continuously. SN levels were positively correlated with serum creatinine, suggesting an influence of renal function on the clearance of SN from the serum. In the urine 80.0 fmol/mL SN was present. In patients with endocrine tumors like gut carcinoids, endocrine pancreatic tumors, oat cell lung carcinomas, and pheochromocytomas, SN serum levels were elevated up to 45-fold. Patients suffering from neuroblastomas, insulinomas, pituitary adenomas including acromegaly, and solid nonendocrine tumors had concentrations in the normal range. In human serum, SN-immunoreactivity was confined to the free peptide SN; neither larger intermediate-sized forms nor the precursor secretogranin II were detected. An efficient removal of the small molecule SN from the serum by the kidney explains why SN serum levels are lower when compared to chromogranin A, which is present as large molecule in serum.

Adolescent↗
PubMed1999

Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients.

BACKGROUND: Immunotherapy (IT) is the only causal treatment for allergic subjects recognized to be effective and to offer long-lasting efficacy. The noninjective routes, aimed at improving the safety of the treatment, have been validated as effective in adults, but documentation of their safety in children is still poor. The aim of the present survey study was to assess the safety of sublingual immunotherapy in pediatric patients, by evaluating a large population. METHODS: A total of 268 children (aged 2-15 years), receiving sublingual IT for respiratory allergy, were followed-up over a period ranging from 3 months to 7 years (mean 34 months). The side-effects possibly due to the treatment were recorded on a proper diary card; self-assessment of the clinical outcome was also evaluated. RESULTS: About 96000 doses of extract were globally administered. Local side-effects were of no clinical relevance. Eight side-effects were reported (3% of patients; 0.083 per 1000 doses). Seven systemic side-effects (abdominal pain, conjunctival itching, and rhinitis) were mild and required no treatment. One case of urticaria was well controlled with oral antihistamines. No life-threatening event occurred. The clinical outcome was judged excellent or good by 80% of the patients. CONCLUSIONS: The sublingual IT herein investigated appeared to be well tolerated and safe in pediatric patients. The risk/benefit ratio was therefore favorable.

Administration, Sublingual↗
PubMed1999

Stem cell factor is not essential for cell survival and proliferation of soft tissue sarcoma of neuroectodermal origin.

BACKGROUND AND OBJECTIVE: Stem cell factor (SCF), and its receptor (c-kit) play key roles in the expansion and differentiation of hematopoietic progenitor cells, in melanoblasts and primordial germ cells, making it possible that SCF and c-kit are involved in neoplastic processes deriving from these cells. C-kit has been described to be expressed at different levels in neuroblastoma and in soft tissue sarcoma of neuroectodermal origin, and seems to be required for survival processes. In this study we investigate how c-kit expression is regulated and whether a SCF autocrine loop is essential for survival of sarcoma cell lines. DESIGN AND METHODS: C-kit modulation and internalization was evaluated incubating cells with rhSCF. Cell differentiation and proliferation experiments were performed to test whether c-kit expression is related to cell cycle progression or to differentiation processes. Cell cultures were treated with neutralizing antibody and antisense oligonucleotides in order to assess the possible significance of the SCF autocrine loop. RESULTS: In vitro SCF stimulation induces c-kit down-regulation; this phenomenon could be connected with receptor internalization, and new protein synthesis is necessary for its re-expression. The cell proliferation arrest in G0/G1 does not modify c-kit expression while down-regulation of c-kit was demonstrated after cells had been treated with differentiating agents. SCF neutralization does not influence either the S phase or apoptosis in sarcoma cell lines. INTERPRETATION AND CONCLUSIONS: In sarcoma cell lines, c-kit is regulated by differentiation processes; moreover our results suggest that c-kit activity, but probably not the SCF autocrine loop, is essential for survival of these cell lines.

Antibodies, Monoclonal↗
PubMed1998

Neuroendocrine differentiation in Ewing's sarcomas and primitive neuroectodermal tumors revealed by reverse transcriptase-polymerase chain reaction of chromogranin mRNA.

Ewing's sarcomas (ESs), primitive neuroectodermal tumors (PNETs), and neuroblastomas (NBs) are closely related neoplasms supposedly derived from the neural crest and belonging to the family of the small blue round cell tumors of infancy and childhood. We investigated the expression of the neuroendocrine and neuroectodermal markers chromogranin A (CgA) and secretogranin II (SgII) in ESs, PNETs, and NBs, both in primitive tumors (five, nine, and four cases, respectively) and in established cell lines (three ES and two PNET cell lines). Different technical approaches, namely immunohistochemistry, Northern blot analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used in parallel. Chromogranin A and secretogranin II production was constantly detectable in NBs by all procedures. CgA mRNA was detectable in most ESs and PNETs only by RT-PCR, whereas SgII mRNA was detectable in some ESs and PNETs by Northern blot analysis and in all tumors by RT-PCR. CgA and SgII proteins were never detectable by immunohistochemistry in ESs and PNETs. We conclude that neuroendocrine differentiation is shared by all three tumor entities, being more overt in NBs and rudimentary in ESs and PNETs; traces of chromogranin mRNA are detectable only by a highly sensitive RT-PCR procedure.

Adolescent↗
PubMed1997

A case of hemolytic disease of the newborn due to anti-Kpa.

A patient with hemolytic disease of the newborn (HDN) due to maternal anti-Kpa alloimmunization is described. Although there are few reports in the literature, it appears that HDN due to anti-Kpa is often mild and transfusion therapy is rarely required. However, in this case, the baby's hemoglobin progressively decreased and on day 18 a blood transfusion was administered, but jaundice was not severe enough for exchange transfusion.

Journal Article↗
PubMed1996

Multiple endocrine neoplasia (MEN IIB) with Cushing's syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone.

We describe a case of Cushing's syndrome caused by a medullary thyroid carcinoma (MCT) secreting corticotropin-releasing-hormone (CRH) in a young woman presenting mucosal neuromas located on the top of the tongue and eyelid areas. Laboratory studies showed, basally and after dexamethasone suppression test, serum cortisol and plasma pituitary corticotrophin (ACTH) levels agreed with an ectopic Cushing's syndrome. Immunohistochemical studies of the MCT tissue revealed a production of CRH and scattered cells containing vasopressin but not ACTH peptides. This is the first demonstrated case of a CRH-secreting tumor in multiple endocrine neoplasia (MEN IIB) syndrome.

Adult↗
PubMed1996

Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction.

We previously reported the presence of somatostatin (SS-14)-binding sites in a wide panel of human neuroblastoma (NB) tumor cell lines. Given that the adrenal gland and its relative embryonal and adult tumors express an abundance of mRNA for somatostatin receptor type 2 (sst2) mRNA, we studied the quantitative expression of sst2 in 6 NB cell lines and 15 primary tumors using competitive reverse transcription (RT)-PCR. This method uses an insertion mutant of the target gene as a competitor for the RT-PCR reaction, thus allowing exact quantitation of sst2 mRNA abundance. We found expression of specific transcripts for sst2 in all of the NB cell lines and tumors investigated (range, 9 x 10(5)-4 x 10(9) molecules/microg RNA). In NB cells, the expression of sst2 was highly correlated with SS-14-binding sites (R = 0.93). In primary tumors, sst2 was positively related to the expression of the neuroendocrine marker secretogranin II (P < 0.05) and negatively related to N-myc amplification (a poor prognostic factor, P < 0.005) and metastatic dissemination (P < 0.05). In addition, Kaplan-Meier curves indicate that sst2 expression is positively related to survival (P = 0.01). In a patient with stage IVs disease (a spontaneously regressing form), we found the highest sst2 expression (4 x 10(9) molecules/microgram RNA), a value relatively similar to that of normal adrenal. In conclusion, these data indicate that quantitation of sst2, as assessed with competitive RT-PCR, could represent a new prognostic tool in the neuroendocrine tumor NB. Since sst2 recognizes octreotide with high affinity, these findings could also have both diagnostic and therapeutic value.

Adult↗
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↗
PubMed1995

Chromogranin gene expressions in colorectal adenocarcinomas.

Presence of neuroendocrine (NE) cells identified by argyrophilia and presence of NE markers, such as the chromogranins) is a common event (15 to 51% of the cases) in colorectal adenocarcinomas. The nature and significance of these cells, scattered in variable number within the neoplastic population, is unclear. Twenty-five cases of colorectal adenocarcinomas were investigated in parallel by immunocytochemical and hybridization (Northern blot) procedures to detect presence of three members of the chromogranin family, i.e., Chromogranin A, Chromogranin B, and Secretogranin II/secretoneurin and their synthetic machinery. The results indicate discrepancies between presence of immunoreactive cells and expression of the related specific mRNA molecules. Interestingly, such discrepancies were more remarkable for Chromogranin A than for Chromogranin B and Secretogranin II. Taking into account all three types of chromogranins, only a few cases provided the same results at the mRNA and protein levels investigated respectively by Northern blot and immunohistochemistry. The spectrum of observed events is therefore wider and more complex than hitherto believed. Our interpretation is that transient activation of NE differentiation genes can be a common and extensive event in neoplastic stem cells. In a few postmitotic cells, expression of NE genes would lead to cytoplasmic accumulation of NE markers and regulatory peptides, retained even after the switching off of the genes. This hypothesis might be valid for various mixed exocrine-endocrine patterns observed in carcinomas of different organs (gastrointestinal tract, pancreas, prostate, breast, lung).

Adenocarcinoma↗
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↗