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Biomedical subjects

G Franchini

Publications and source records attributed to G Franchini.

167 records · Page 10Linked to original sources

Common site of integration of HTLV in cells of three patients with mature T-cell leukaemia-lymphoma.

Human T-cell leukaemia-lymphoma virus (HTLV) was first isolated in the United States from a patient with an aggressive form of cutaneous T-cell lymphoma (CTCL) and was later found associated with clusters of adult T-cell leukaemia-lymphomas (ATL) in various parts of the world, including Japan and the Caribbean. Leukaemic cells of the HTLV-positive patients seem to be clonal expansions of single infected cells since the provirus(es) are found at the same sites in a given patient. In avian leukosis virus-induced B-cell lymphomas, the provirus very frequently integrates at several discrete sites in a common domain near the cellular gene, c-myc, that it activates and it has been speculated that the same would hold true for other chronic leukaemia viruses. We report here that cultured cells from two US patients with CTCL and fresh leukaemia cells of a Japanese patient with ATL contained an HTLV provirus integrated at the same site. In addition, a cord blood T-lymphocyte cell line established by co-cultivation with one of the two HTLV-positive CTCL cell lines also contained HTLV provirus contiguous with the same flanking cellular sequences. Ten other HTLV-positive cell samples did not show integration of HTLV at this site, suggesting that there is more than one discrete site of HTLV integration in tumour cells.

Cell Transformation, Viral↗

Chromosomal sublocalization of human c-myb and c-fes cellular onc genes.

The transforming genes of acutely transforming retroviruses are derived from conserved cellular genes (c-onc genes) which are believed to be important in normal cell growth and differentiation. Recent studies indicate that altered expression of c-onc genes, for example, by insertion of viral genomes, gene amplification or chromosomal translocation, can lead to development of malignant diseases in man and animals. c-myb and c-fes are homologues of the transforming genes of avian myeloblastosis virus and feline sarcoma virus (Gardner and Snyder-Theilen strains), respectively. c-myb is transcribed preferentially in immature haematopoietic cells and probably codes for a protein important in differentiation of these cells. The viral fes gene, like several other viral onc genes, encodes a tyrosine-specific protein kinase. However, c-fes transcripts have not been detected in the types of human cells examined so far. c-myb and c-fes have been assigned to human chromosomes 6 and 15, respectively. Specific aberrations involving these chromosomes have been observed at high frequency in several human neoplasms. We have now sublocalized c-myb to 6q22-24 and c-fes to 15q25-26 by in situ hybridization of the human c-onc probes to human mitotic chromosome preparations. These chromosomal segments are indeed involved in nonrandom translocations in several human tumours. The results encourage further investigation into the role of onc genes in the pathogenesis of specific neoplasms.

Chromosome Aberrations↗

Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses.

The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus) from macaques (STLV-IIIMAC) induces symptoms similar to those of AIDS in infected macaques, but isolates from African green monkeys (STLV-IIIAGM) and mangabeys (STLV-IIMM) appear to be non-pathogenic in these animals. A human virus immunologically related to STLV-IIIAGM (HTLV-IV), reported to have been isolated from healthy humans, has been shown to be almost identical to STLV-IIIAGM, which has called into question the independent origin of these viruses. Here we report the complete DNA sequence of STLV-IIIAGM and analyse its relationship with the genomes of the HTLV-IIIB strain of HIV-1, HIV-2ROD (previously called LAV-2) and several ungulate lentiretroviruses. STLV-IIIAGM and HIV-2 are closely related, and more distantly related to HIV-1.

Acquired Immunodeficiency Syndrome↗

Proliferative characteristics of head and neck tumors. In vivo evaluation by bromodeoxyuridine incorporation and flow cytometry.

Cell proliferation of head and neck cancers was studied in 52 patients using in vivo bromodeoxyuridine (BUDR) incorporation. Patients received 250 mg BUDR intravenously several hours prior to biopsy of the tumor tissue. Bivariate flow cytometry was used and enabled us to rapidly obtain DNA ploidy, labelling index (LI), DNA synthesis time (TS) and tumor potential doubling time (Tpot). This method was found to be suitable to obtain complete cytokinetic data in 46/52 (88.5%) patients. The mean BUDR LI was 7.9% (range 2-18%); mean TS was 11.6 h (range 6-28.5 h); mean Tpot was 5.7 days (range 2-30 days). BUDR LI and TS were significantly correlated with histological differentiation grading: G3 tumors showed higher LI values and shorter TS values than G1/G2 tumors. A similar correlation was found between LI or TS and tumor dimensions. Tpot was also significantly lower in larger tumors, such as in those with a higher grading. No significant correlation was found between LI or TS and DNA ploidy (50% of the tumors in our series were DNA aneuploid), while Tpot was found to be 10 days in diploid tumors, compared to only 6.3 days for the aneuploid tumors (p < 0.05). All cases with documented lymph node involvement (N+) showed significantly higher LI, and shorter TS and Tpot values if related to nodal free ones (Tpot = 10 days in N+ patients and 6.3 days in N- patients; p < 0.05). The results of this study suggest that the method employed is clinically feasible and could be a useful aid in defining the prognosis of head and neck cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗