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V Tassi

Publications and source records attributed to V Tassi.

34 records · Page 2Linked to original sources
PubMed1995

A thyroid hormone receptor beta gene polymorphism associated with Graves' disease.

Autoimmune thyroid diseases (AITDs) are clustered in families, but the nature of this clustering is still poorly understood. One possible approach to the identification of genetic factors interacting with the AITDs is the study of the association between polymorphic markers and AITDs themselves. In the present study we have shown an association between an allele of a HindIII restriction fragment length polymorphism (EA beta H) intragenic to c-erbA beta, which codes for the thyroid hormone beta receptor, and Graves' disease. This polymorphism can be detected by PCR followed by digestion with the restriction enzyme HindIII. The allelic frequencies were analysed in a panel of DNAs extracted from a population of individuals affected by thyroid disease and originating from southern Italy. A control group (n = 120) from the same area was also analysed. The distribution of EA beta H alleles was significantly different (P < 0.001) in Graves' disease (n = 94) but not in autoimmune thyroiditis (n = 60), as compared with controls. Also the distribution of the EA beta H genotypes was significantly different in Graves' patients (P = 0.003), as compared with controls, the homozygous state EA beta H+/EA beta H+ being more frequent in Graves' patients than in all the other groups. We did not find any association between EA beta H genotypes and clinical parameters in Graves' patients, including eye signs, thyroid volume and level of TSH-binding inhibiting immunoglobulins. Our data support the idea that Graves' disease is a genetically distinct group within the AITDs.

Adult↗
PubMed1994

Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) represents the most frequent adult leukemia in the Western world. The molecular pathogenesis of B-CLL is largely unknown. Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data. Among tumor suppressor genes, p53 mutations have been reported in a fraction of cases. In this study, we have attempted a conclusive definition of the involvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q-) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV). Rearrangements of Bcl-1 and Bcl-2 and deletions of 6q and 17p were analyzed by Southern blot using multiple probes. Mutational analysis (single strand conformation polymorphism and polymerase chain reaction direct sequencing) was used to assay p53 inactivation. No alterations of Bcl-1 or Bcl-2 were detected in the 100 cases tested. Mutations of p53 were found in 10/100 cases without any significant association with clinical stage. Deletions of 6q were present in 4/100 cases. Overall, our data indicate that: 1) contrary to previous reports, Bcl-1 and Bcl-2 rearrangements are not involved in CD5+ B-CLL pathogenesis and 2) p53 mutations are present in 10% of cases at all stages of the disease.

Blotting, Southern↗
PubMed1993

Opposite regulation of gene transcription and cell proliferation by c-Myc and Max.

c-Myc and Max are nuclear phosphoproteins capable of forming DNA-binding, homo- and heteropolymeric complexes in vitro and in vivo. Using a transient cotransfection assay involving c-Myc and Max expression vectors and a reporter gene plasmid containing the Myc/Max binding site, we find that Max represses transcription, whereas a significant stimulation is obtained when Max is coexpressed with c-Myc. Analysis of specific mutants indicates that transcriptional activation requires both the c-Myc and the Max dimerization and DNA-binding domains, as well as the c-Myc transactivation function; transcriptional repression by Max requires both DNA binding and dimerization. Analogously, in stably transfected human B-lymphoblastoid cell lines, overexpressed c-Myc and Max synergize to cause malignant transformation, whereas overexpression of Max alone leads to growth inhibition. These results indicate that the c-Myc and Max are transcriptional regulators with the ability to oppositely regulate target-gene expression and cell proliferation, most likely as the result of the opposite effects of heterodimeric c-Myc-Max (positive) versus homodimeric Max (negative) complexes.

Animals↗
PubMed1993

Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) develops in about 5% to 10% of acquired immunodeficiency syndrome (AIDS) patients. The vast majority of AIDS-NHL are clinically aggressive B-cell NHL that are histologically classified as small noncleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large noncleaved cell lymphoma (LNCCL). In an attempt to understand the molecular pathogenesis of these tumors, we have investigated the involvement of dominantly acting oncogenes (c-myc, N-, K-, H-Ras), tumor suppressor genes (p53, RB1), and Epstein-Barr virus (EBV) infection in 27 AIDS-NHL samples (16 SNCCL, 5 LC-IBP, and 6 LNCCL). The following lesions were detected in AIDS-NHL: EBV infection (10/24; 41.6%), c-myc rearrangement (19/24; 79.1%), Ras mutation (4/27; 14.8%), and p53 loss/mutation (10/27; 37.0%). These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation. These data show that AIDS-NHL are associated with multiple genetic lesions that involve both proto-oncogenes and tumor suppressor genes and may accumulate in the relatively short period of time (4 to 6 years) between human immunodeficiency virus infection and AIDS-NHL development. These genetic lesions differ in the various AIDS-NHL subtypes, suggesting the involvement of distinct molecular pathway.

Adult↗
PubMed1993

In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection.

Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.

Adult↗
PubMed1992

Molecular pathogenesis of HIV-associated lymphomas.

The data presented here indicate that the pathogenesis of AIDS-NHL is variably associated with multiple genetic alterations including monoclonal EBV infection, oncogene activation (c-myc, N-, Ki-ras) and tumor suppressor gene (p53) inactivation. Up to three (3 cases) or four (1 case) different lesions have been observed in the same tumor. The distribution of these lesions among the various histotypes is heterogeneous, although some preferential associations have been found either between lesion and histotype or between lesions. The most notable case involves p53 mutations/loss that is exclusively associated with the SNCC lymphoma subtype. Since alterations of the c-myc gene occur at very high frequency in this same histotype it is possible that both lesions may be required for the pathogenesis of the BL phenotype. The consistent negativity of p53 lesions in other NHLs associated or non associated with HIV infection (18) reinforces this hypothesis. Finally, we note that the frequency of p53 mutations is significantly higher in AIDS-BL than in non HIV-related BL (18), although the significancy of this difference remains to be assessed. This study confirms the relatively low frequency of EBV infection in systemic AIDS-NHL in general, but reinforces the notion that EBV may be required for the pathogenesis of AIDS-LC-IBP, as recently suggested by the high frequency of EBV positivity in primary CNS AIDS-NHL which are mostly represented by LC-IBP (2). Conversely, the low frequency of EBV sequences in the AIDS-SNCC lymphomas appears similar to that observed in sBL. Only in a small minority of cases were ras oncogene mutations found, mostly associated with the BL type.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes, myc↗
PubMed1991

Immunogenicity of anti-idiotypic antibodies and of their F(ab')2 fragments.

Within the idiotype/anti-idiotype network, immunoglobulins act alternatively as reactive molecules and as antigens. To investigate the antigenic properties of immunoglobulins, we evaluated the immunogenicity in rabbits of three murine monoclonal anti-idiotypic antibodies and of their F(ab')2 fragments. These antibodies, bearing the internal image of a human melanoma antigen, may be useful in view of a human therapeutic application. The effect was evaluated as specific anti-anti-idiotypic response, related to the immunogenicity of the idiotypic epitopes in the combining sites of the immunoglobulins, and as total anti-murine immunoglobulin response, which represents the recognition of all the immunological determinants of the molecule. The results showed that the administration of the F(ab')2 fragments results in either higher or similar degrees of anti-anti-idiotypic immunization, compared to those induced by the whole immunoglobulins. Nevertheless, when anti-anti-idiotypic immunogenicity was increased, the anti-murine response did not increase proportionally. This suggests that the use for in vivo administration of F(ab')2 fragments is more convenient than the use of their original molecules, since this results, at least, in a similar or eventually in an increased specific immunogenicity, while the possibility of aspecific recognition is reduced.

Animals↗
PubMed1987

Tobacco smoking, occupational exposure and bladder cancer in Argentina.

The highest rate for bladder cancer in Latin America has been reported from La Plata, Argentina. A case-control study was carried out to investigate the reasons for this high rate. A total of 117 cases, 117 hospital controls and 117 neighbourhood sex- and age-matched controls were interviewed regarding their smoking and drinking habits and occupational exposures. Cigarette smoking and coffee drinking were identified as the major risk factors, and a significant association was also found for truck and railway drivers and for oil refinery workers. The relative risks for male smokers who ever smoked cigarettes vs. non-smokers was 4.3 (95% Cl: 1.9-10.3). The risk associated with black tobacco cigarettes was 2-3 times higher than that of blond cigarettes. For male ex-smokers the risk after 5 years of no smoking is less than one third of that of current smokers. The RR for drinking coffee was 2.4 (95% Cl: 1.4-4.4) after adjusting for the effects of tobacco smoking, and the risk increased with the number of cups per day. No association was found with the use of saccharin.

Age Factors↗
PubMed1982

The segregation into microsomal vesicles and core-glycosylation in vitro of a 300-kDa rat thyroglobulin subunit.

Translation of rat thyroid mRNA in a cell-free protein synthesis system derived from rabbit reticulocytes results in synthesis of a 300-kDa thyroglobulin polypeptide [C.G. Alvino et al. (1982) FEBS Lett. 137, 307-313]. In the presence of dog pancreas microsomal membranes this polypeptide is segregated into the microsomal vesicles and core-glycosylated, as shown by increased protection against proteolytic treatment and binding to concanavalin-A-Sepharose. The segregation process appears to be strictly coupled to glycosylation, i.e. no detectable amounts of unglycosylated chains are found in the vesicles, and both processes only occur cotranslationally. The glycosylated protein exhibits lower electrophoretic mobility with respect to its non-glycosylated form and comigrates with a glycosylated 330-kDa polypeptide found in rat thyroid epithelial cells cultured in vitro [F.S. Ambesi-Impiombato et al. (1980) Proc. Natl Acad. Sci. USA, 77, 3455-3459]. Both glycosylated and non-glycosylated forms are immunoprecipitated by antibodies to 19-S rat thyroglobulin. Some features of the tyroglobulin polypeptide segregation and glycosylation have been studied by synchronized translation of rat thyroid mRNA: (a) the signal sequence seems to be located at the amino-terminal portion of the nascent polypeptide chain; (b) the distribution of the carbohydrate units is mostly clustered in the amino-terminal half of the protein as monitored by posttranslational analysis of the polypeptides synthesized in the presence of pancreatic membranes during competition experiments carried out with the detergent Nonidet P40.

Animals↗
PubMedDate not supplied

ACE, PAI-1, decorin and Werner helicase genes are not associated with the development of renal disease in European patients with type 1 diabetes.

BACKGROUND: Genetic factors are involved in the development of diabetic nephropathy in Type 1 diabetes. We have examined the association of four candidate genes, angiotensin converting enzyme (ACE): insertion/deletion (I/D) polymorphism, plasminogen activator inhibitor-1 (PAI-1): 4G/5G polymorphism, decorin: 179/183/185 polymorphism and Werner syndrome helicase: C/R polymorphism, with the presence of diabetic nephropathy in Type 1 diabetic patients. METHODS: 175 Type 1 diabetic patients with albuminuria (59 with microalbuminuria and 116 with macroalbuminuria) were compared with 136 Type 1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years (mean+/-SD: 25+/-8 years). 200 non-diabetic subjects were also studied as background population. RESULTS: We found no association in the polymorphism of the four genes examined between patients with and without diabetic nephropathy and the control subjects. CONCLUSIONS: The genes studied are unlikely to be involved in the susceptibility to nephropathy in Type 1 diabetic patients.

Adult↗
PubMedDate not supplied

High insulin levels do not influence PC-1 gene expression and protein content in human muscle tissue and hepatoma cells.

BACKGROUND: To verify whether insulin levels influence PC-1 tissue content, we studied PC-1 gene expression and protein content in skeletal muscle of patients with insulinoma, a model of primary hyperinsulinemia. Data were compared with those obtained in matched insulin sensitive or resistant healthy subjects. In addition, the effect of high insulin concentration on PC-1 protein content was studied in HepG2 cells. METHODS: The following measurements were performed: insulin sensitivity by euglycemic clamp; PC-1 protein content and insulin receptor autophosphorylation by specific ELISAs; PC-1 gene expression by competitive polymerase chain reaction (PCR); phosphatidyl-inositol-3 kinase by immunoprecipitation and thin layer chromatography; glycogen synthesis by (14)C-glucose incorporation. RESULTS: Muscle PC-1 content was similar in the insulinoma patients and in insulin sensitive controls but higher (p<0.01) in insulin resistant controls (21.9+/-4.6 ng/mg protein, 23.8+/-3.9, 48.0+/-8.7, respectively). PC-1 protein content was inversely correlated with insulin sensitivity (r=-0.5, p<0.015) but with neither plasma insulin nor glucose levels. PC-1 protein content was correlated with PC-1 gene expression (r=0.53, p<0.05, n=14). Exposure to high insulin (100 nmol/l for 16 h) caused a significant (p<0.05-0.01) impairment of insulin receptor autophosphorylation, phosphatidyl-inositol-3 kinase activity and glycogen synthesis, but not of PC-1 protein content (114+/-3 vs 102+/-14 ng/mg protein) in HepG2 cells. CONCLUSION: These findings suggest that chronic high insulin levels do not influence PC-1 expression.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Use of peripheral blood stem cells to accelerate hemopoietic recovery following autologous bone marrow transplantation.

Twenty-one patients with high risk non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Nine out of 21 patients received in addition to bone marrow (BM) cells also peripheral blood (PB) cells collected by leucapheresis performed in the recovery phase after high-doses of either cyclophosphamide or etoposide (7 patients), or after ara-C (2 patient). All patients receiving BM + PB cells had ABMT as salvage therapy following extensive relapse or progression of their disease. The addition of PB cells to BM cells allowed a significantly faster recovery after ABMT. Median time to reach WBC greater than 1,000/microL was 14 days versus 20.5 days for patients receiving BM only. Furthermore, a reduced requirement of supportive care and a shorter period of isolation was observed. These results confirm that PB cells combined with BM cells allow a prompt hematopoietic reconstitution after myeloablation. In addition, the data demonstrate the efficacy of PB cells collected after various cytotoxic drugs, even in patients previously exposed to cytoreductive regimens.

Adolescent↗
PubMedDate not supplied

Mobilization and collection of PBSC in healthy donors: a retrospective analysis of the Italian Bone Marrow Transplantation Group (GITMO).

BACKGROUND AND OBJECTIVE: The number of allogeneic transplants of peripheral blood stem cells (PBSC) is rapidly increasing. Collection of PBSC in healthy subjects currently implies the administration of G-CSF or GM-CSF and, of course, the use of apheretic devices. These procedures involve potential risks, in particular the risk of leukemia secondary to growth-factor treatment. To evaluate the current practice of PBSC mobilization and collection, and initially assess the short-term side effects and efficiency of procedures, the GITMO (Gruppo Italiano Trapianti di Midollo Osseo) promoted a retrospective cooperative study among the Italian centers. METHODS: Seventy-six healthy individuals donating to their HLA-identical or partially matched sibling recipients in seven Italian centers form the basis of the present analysis. The data were retrospectively collected by proper forms, pooled and analyzed by means of a commercially available statistical soft package. RESULTS: All donors received G-CSF as mobilizing agent with different schedules according to each single center policy. A median of 2.5 (range 1-4) aphereses per donor were run. The most frequent side effect was bone pain. In no case did the medium term follow-up reveal subjective complaints or laboratory modifications. After G-CSF mobilization, WBC and lymphocytes counts increased to a maximum of (mean +/- SD) 48.1 +/- 15.6 x 10(9)/L and 4.2 +/- 1.5 x 10(9)/L, respectively. The peak was reached on day 5 in both cases. Platelets decreased after the apheretic procedures, reaching a minimum of (mean +/- SD) 77 +/- 26 x 10(9)/L on day 8 and returning to normal values on day 11. Overall, the apheretic collection yielded (mean +/- SD) 18.6 +/- 19.2 x 10(8)/kg donor body weight MNC; 10.4 +/- 5.7 x 10(6)/kg CD34+ cells; 90.6 +/- 75.9 x 10(4)/kg CFU-GM and 4.3 +/- 1.8 x 10(8)/kg CD3+ cells. The target dose of 4 x 10(6)/kg CD34+ cells was harvested in 51.3% donors after a single apheresis, in 85.5% after the second, and in nearly 100% after a maximum of 3 aphereses. INTERPRETATION AND CONCLUSIONS: These data demonstrate that collection of adequate numbers of circulating progenitors is feasible and well tolerated in healthy donors. However, only careful monitoring of donors and international cooperation will help to definitively assess the long-term safety of G-CSF for mobilization of PBSC.

Adolescent↗