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Biomedical subjects

L Larizza

Publications and source records attributed to L Larizza.

At least 109 records · Page 6Linked to original sources

Relationships between genes on human chromosome 11 encoding cell-surface antigens.

Genes encoding seven monoclonal antibody-defined cell-surface antigens have been regionally mapped on human chromosome 11, and compared to those of the AL complex defined by polyclonal antibodies using mutational analysis. MIC1, encoding W6/34 antigen, is probably identical to S1, previously mapped to 11pter-p13. MDU1 and MIC8, encoding 4F2 and TRA-1.10 antigens, respectively, are probably identical to S2(a4) and map to 11q13-q22. MIC9, which governs expression of 4D12 and 2E2 antigens, and maps to 11q22-qter, is not related to any of the five AL genes. MIC4 and MIC11, both mapping to 11pter-p13, may have some relationship to S3 and S1, respectively, but identity has not been proven.

Antibodies, Monoclonal↗

Inheritance of immunogenicity and metastatic potential in murine cell hybrids from the T-lymphoma ESb08 and normal spleen lymphocytes.

T-lymphoma cells were fused with normal lymphoid cells to examine the segregation of tumorigenicity and metastatic capacity in the hybrids. In independent fusions the immunogenic ESb08 T-lymphoma line fused successfully with normal syngeneic spleen cells (from DBA/2 and CD1 mice) enriched either with T-cells or B-cells. Ten times fewer hybrids were obtained with B-cells compared to the number obtained with T-cells, and marker assays showed that both types of fusions preferentially generated T-T hybridomas. Some of the hybrids resembled their tumor parent in their ability to form primary and secondary tumors only in irradiated DBA/2 mice, whereas other hybrids lost the high ESb08 immunogenicity, were equally tumorigenic, and in some cases metastatic, in nonirradiated mice. DNA distributions of the original hybrid lines ranged from a hexaploid DNA content (expected for complete hybrids derived from a tetraploid line and normal diploid cells) to a tetraploid DNA content, confirming the reported chromosome instability of T-T hybrids. No correlation was noted between the initial DNA content and tumorigenicity, but in the case of complete hybrids, reduction in the ploidy levels always was observed in the cells of primary and metastatic lesions. One chromosomally stable and highly malignant hybrid (C2), which was analyzed for segregation of chromosomes and for drug-resistance markers, showed preferential loss of chromosomes from the normal T-cell fusion partner. The decreased immunogenicity of this hybrid could not be related to any detectable loss of chromosomes from the ESb08 tumor parent.

Animals↗

Metastatic clones selected from an RSV-induced mouse sarcoma share a common marker chromosome.

Previous work has shown that the metastatic potential of RSV-transformed fibroblasts is correlated with the ability to form colonies in 0.6% ("hard") agar. Metastatic subclones were selected by this property from the non-metastasizing fibrosarcoma B77-313 line. A marker chromosome was found at high frequency (90% of cells) in all the subclones studied. This marker was detectable in only 0.5% of the parental B77-3T3 cells, demonstrating that metastatic clone precursors pre-existed, as a small minority, in the parental line. The genotypic marker appeared to be steadily associated with the metastatic phenotype since, after prolonged in vitro propagation, the subclones retained both the marker chromosome and the high metastatic potential. Although the marker chromosome was constantly present, chromosomal numerical and structural aberrations were also found in 20% of the long-term-propagated subclone cells, supporting the suggestion that metastatic properties are associated with cytogenetic instability.

Animals↗

Human fibroblasts X mouse cell hybrids, containing a human 11/X translocation, do not express human fibronectin.

Using a monoclonal antibody specific for human fibronectin (FN), we screened hybrid clones derived from the fusion of FN+ human fibroblasts, carrying a 11/X translocation, and FN-, HPRT- mouse cells for the production of this glycoprotein. Since no hybrid clone retaining the human der 11 chromosome was found to produce any human fibronectin, the segment of chromosome 11 included in the rearranged chromosome (11qter leads to 11p13) probably does not carry the structural locus for fibronectin.

Animals↗

Expression of transformation markers and suppression of tumorigenicity in human cell hybrids.

Somatic human cell hybrids produced by fusion of HeLa cells and diploid fibroblasts were analysed in a study designed to test the coordinate expression of transformation markers and tumorigenicity. The great majority of these hybrids displayed a finite lifespan in culture, but some of them inherited from the HeLa parent the capability to grow as permanent cell lines. Hybrids from both groups all had a plasminogen activator activity 20 to 100-fold higher and a cloning efficiency in semisolid medium 2 to 10-fold lower than the HeLa parent. Cell surface fibronectin was expressed at variable levels, albeit in a disorganized form. No correlation between the level of plasminogen activator or fibronectin content and cloning efficiency in agar was observed. Two hybrid lines, assayed for tumorigenicity in nude mice, did not produce tumors, even at inocula 20-fold greater than those at which the HeLa cells formed tumors.

Animals↗

Chromosome lesions in amniotic fluid cell cultures.

The frequencies of chromosome lesions were determined on 3537 mitoses in samples of varying sizes from cultures of 25 amniotic fluid specimens taken from patients at cytogenetic risk. The average percentage values of aberrant cells, including and excluding gaps, were 12.5 and 4.9, respectively. The corresponding values for fibroblasts and peripheral blood lymphocytes from normal adult donors, calculated under the same laboratory conditions, were 5.0 (including gaps) and 2.4 (excluding gaps) and 2.4 (including gaps) and 1.0 (excluding gaps), respectively. The hypothesis of a correlation between the increased incidence of chromosome lesions and the occurrence of abnormal karyotypes in amniotic fluid cell cultures is discussed.

Amniotic Fluid↗

Expression of thymidine kinase activity in hybrids between human leukemic cells and a TK-mouse cell line.

A series of actively proliferating clones have been isolated after PEG-induced fusion of a thymidine kinase deficient murine line and white blood cells from two leukemic patients. Their hybrid nature was proved both cytologically and biochemically. All the hybrids tested showed levels of TK activity significantly higher than the TK- mouse parental cell line and comparable to those exhibited by replicating TK+ cells.

Animals↗

Detection of aneuploid cells in fibroblast cultures from the father of two trisomy 21 patients.

Karyotype analysis was performed on successive cultures of fibroblasts from the parents of two trisomic 21 patients. Starting from the 7th passage in the father cultures an aneuploid clone showing an extra E-like chromosome was found, which eventually overgrew the cell population. The significance of this cytogenetic finding is discussed in relation to the recurrence of the trisomy in the family.

Aneuploidy↗

A family with three sibs carrying trisomy 21.

A family with three sibs, including a pair of dizygotic twins, all affected by Down's syndrome with regular trisomy 21, is described. The chromosome counts carried out on prolonged fibroblasts cultures of the mother, revealed the presence of the trisomy 21 in 6 out of 688 scored mitoses. The cytological findings give support to the hypothesis of a chromosome mosaicism in one of the normal parents, as a cause of the recurrence of the trisomy 21.

Age Factors↗

Identification of chromosomal rearrangements in the human myeloid leukemia cell line GF-D8 by dual-colour fluorescence in situ hybridization.

Fluorescence In Situ Hybridization (FISH) studies with chromosome-specific libraries and repetitive probes were performed on the human acute myeloid leukemia cell line GF-D8 in order to define the complex chromosomal rearrangements observed by conventional cytogenetic analysis. Two-colour FISH with whole chromosome painting probes 8 and 11 showed that the add(8) chromosome had an 11-derived region inserted at q24, whereas the add(11) chromosome had an 8-derived region translocated onto q23. It also demonstrated that no normal chromosome 11 is present in GF-D8 cells, since a translocation involving chromosomes 11 and 17q was detected in addition to the add(11). The der(7) chromosome with extra material in its long arm, identified by QFQ and GTG banding, turned out to have a chromosome 15-derived segment translocated to q22. The deletion of 7q was proved to be interstitial, as the 7q-specific telomere as well as a tiny 7-specific band were observed on an unknown chromosome. Fine mapping of the breakpoints involved in the multiple chromosomal rearrangements of the GF-D8 cell line might provide insights into the mechanisms of myeloid leukaemogenesis.

Chromosome Aberrations↗

High incidence of chromosomal lesions involving C-heterochromatin in four human melanoma lines.

Cytogenetic analysis of early in vitro cultures derived from human melanomas, two primary tumors (Me 10538, Me 1402) and two metastatic lesions in the same patient (Me 665/1, Me 665/2) showed non-random involvement of C-heterochromatin in clonal chromosome rearrangements. Marker chromosomes with C- and DA-Dapi-positive bands were identified in one of the metastases, Me 665/1 (m1) and in the two primary tumors, Me 10538 (m2) and Me 1402 (m3). C-positive fragments predominated in the other metastasis, Me 665/2, which lacked C-regions intercalated in rearranged chromosomes, and were also detected with appreciable frequency in the Me 665/1 and Me 1402 cells. The frequencies of marker chromosomes and their mean number per cell allowed m2 and m1 to be considered as early markers of tumor formation and m3 as a marker of tumor progression. Dissection of chromosome structure, including the origin of the intercalated C-band, has so far been achieved only with the m2 chromosome of the primary tumor Me10538. This was the only cell line which displayed few C-fragments and a narrow chromosomal distribution with a well defined mode. A gradient of malignancy could be detected in the four cell lines, by local and disseminated tumor growth in xenotransplanted mice, with the two primary melanomas 10538 and the 1402 cells at the lowest and upper extremes. This gradient closely parallels the increase in cytogenetic heterogeneity and C-heterochromatin lesions from the 10538 to the 1402 cells.

Chromosome Aberrations↗

Beneficial effect of fluoxetine in a case of sporadic hyperekplexia.

We studied a 67-year-old woman with a sporadic form of hyperekplexia, who experienced 8-10 excessive startle responses to unexpected stimuli per month. Therapy with fluoxetine had a definite beneficial effect. This finding supports the hypothesis that serotonergic mechanisms play a role in this disorder.

Aged↗