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Biomedical subjects

C Moroni

Publications and source records attributed to C Moroni.

At least 91 records · Page 5Linked to original sources
PubMed1987

High-dose cisplatin and etoposide in advanced malignancies of childhood.

Thirty-two children with poor-prognosis solid tumors were treated with a combination of high-dose cisplatin (CDDP) (200 mg/m2 over 5 days) and VP16. In the 30 children evaluable for antitumor effect, there were 7 complete, 12 partial, and 3 minor tumor responses. Wilms' tumor and rhabdomyosarcoma responded best. There were no therapy-related deaths. Severe neutropenia (PMN less than 500/mmc) developed after 29 out of the 45 evaluable courses and lasted a median of 8 days; during periods of neutropenia 8 episodes of fever occurred, 1 of which was caused by streptococcal sepsis. Platelet levels were depressed to less than 50,000/mmc after 17/45 cycles and this thrombocytopenia lasted a median of 8 days. No neurological toxicity occurred. One case developed acute renal failure. A hearing deficit for high frequencies was documented in 14/22 patients evaluated after the first cycle and in all cases after the subsequent cycles; the deficits correlated with the total dose of CDDP administered. High-dose cisplatin and VP16 is an effective association in children with advanced cancer, but cumulative dosage is limited by ototoxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Glycine-cysteine substitution at codon 13 of the N-ras proto-oncogene in a human T cell non-Hodgkin's lymphoma.

Tumor-derived DNA from a non-Hodgkin's (T cell) lymphoma patient, assayed by NIH3T3 transfection followed by inoculation of cells into nude mice, was found to contain an activated N-ras proto-oncogene. The mode of activation was determined by hybridization with N-ras-specific oligonucleotide probes detecting mutations at codons 12, 13 and 61. A transversion in codon 13 (GGT----TGT) resulting in replacement of glycine13 by cysteine13 in ras p21 protein was found. The mutation was detected in DNA from mouse tumors induced by transfected NIH3T3 cells and in DNA from patient tumor lymphoblasts. The patient was heterozygous for this mutation. These data identify the first base of codon 13 as a novel mutation site in ras genes and indicate that cysteine at position 13 of the ras p21 is a transforming substitution.

Cell Transformation, Neoplastic↗
PubMed1985

Activation of an N-ras gene in acute myeloblastic leukemia through somatic mutation in the first exon.

A transforming N-ras gene has been cloned from acute myeloblastic leukemia bone marrow cells, in parallel with the N-ras gene derived from fibroblasts of the same patient. N-ras derived from fibroblasts lacked focus-forming activity in NIH/3T3 cells, indicating that gene activation in the leukemia cells must have occurred by a somatic event. Construction of chimeric molecules between the transforming and the normal N-ras genes and subsequent biological and sequence analysis of these constructs revealed that the transforming gene was altered by a point mutation changing amino acid 12 of the N-ras protein from glycine to aspartic acid.

Alleles↗
PubMed1985

Proliferation and differentiation requirements for the induction of two retroviral loci during B-cell activation.

Mitogen treatment of murine (BALB/c) B-cells induces two different endogenous retroviruses involving two unlinked, presumably proviral, loci Bxv-1 and Bdv-1. To determine the usefulness of these loci as genetic markers for B-cell differentiation their expression was studied under conditions that interfered with B-cell proliferation and differentiation into IgM-secreting plaque-forming cells (p.f.c.). Maximum production of both viruses followed peak DNA synthesis by an interval of about 18 h. Treatments that blocked DNA synthesis or killed proliferating cells inhibited virus production. Addition of BUdR to mitogen-stimulated cultures selectively induced Bxv-1 while inhibiting the generation of p.f.c. Both effects require BUdR incorporation into the DNA of proliferating cells. 5-Azacytidine induced Bxv-1-dependent virus production without inhibiting terminal B-cell differentiation. Pretreatment of mitogen-stimulated B-cells with anti-mouse IgM serum decreased both virus production and generation of p.f.c., but had little effect on DNA synthesis. Experiments using a mitogenic F(ab')2 preparation of anti-IgM in the presence and absence of lymphokines also suggested that the generation of p.f.c. and Bxv-1-dependent virus production are linked phenomena. The data imply that Bxv-1- and Bdv-1-dependent virus production require DNA synthesis and cell proliferation and, at least for Bxv-1, B-cell differentiation. It is proposed that the induction of these loci reflects the involvement of neighbouring DNA sequences in B-cell proliferation or differentiation.

Animals↗
PubMed1984

[Oncogene activation in the leukemias].

Retroviral oncogenes are derived in evolution from normal cellular genes termed proto-oncogenes. This discovery has prompted the question whether human tumor cells show alteration of proto-oncogenes. Alteration found in leukemias (gene amplification, translocation and point mutation) are briefly discussed. The genes termed myc, abl, ras are involved. A case of acute myeloblastic leukemia with a point mutation in the N-ras gene is briefly discussed.

Humans↗
PubMed1984

Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: analysis of xenotropic and defective endogenous mouse viruses.

In addition to the known induction of xenotropic endogenous virus in B-mitogen-stimulated murine lymphocyte cultures, distinguishable defective viruses were also induced in different mouse strains (NFS/N, 129, BALB/c). AKR cells produced xenotropic virus and also, in contrast to BALB/c, ecotropic virus. The drug bromodeoxyuridine appeared to have differential effects on virus expression, amplifying xenotropic virus induction but inhibiting the spontaneous production of the ecotropic virus in AKR cultures and of the defective virus in NFS/N cells. Infecting stimulated BALB/c or AKR cultures with Friend leukaemia virus resulted in the production of ecotropic-xenotropic pseudotype viruses, indicating that the infecting ecotropic virus replicates in the cells in which xenotropic virus is induced. No pseudotypes or recombinants were observed following infection of spleen cells releasing defective viruses. Friend leukaemia virus and xenotropic virus with an ecotropic envelope replicated equally well in stimulated lymphocytes from the different strains examined. Taken together, these findings indicate that the non-infectious viruses are encoded by defective proviruses, rather than resulting from faulty, host cell-controlled, virus maturation.

Animals↗
PubMed1984

Monoclonal antibodies recognizing structural components of murine retroviruses including an FMR antigen on protein p12.

Monoclonal antibodies were prepared from mice and rats immunized with Friend leukaemia virus and BALB/c xenotropic virus. By immunoprecipitation of 125I-labelled and [35S]methionine-labelled viruses and by protein blotting, ten antibodies were found to react with the viral components p12, p15, p30, gp70 and p15E/p12E. A dot-immunobinding assay was found to be a reliable method to type the antibody reactivity with different murine leukaemia viruses (MuLVs). When tested on a panel of ecotropic and xenotropic MuLVs the antibodies revealed the following antigenic specificities: ecotrop-specific on p15E/p12E; xenotrop-specific on p15E; group-specific on p30 and p15E; FM-specific on gp70; FR-specific on gp70 and p15. Of particular interest is a cytotoxic antibody recognizing an FMR determinant localized on p12.

Animals↗
PubMed1983

Endogenous retrovirus expression in stimulated murine lymphocytes. Identification of a new locus controlling mitogen induction of a defective virus.

Germ line DNA from all strains of mice contains numerous endogenous retroviruses. One of these viruses, a virus with xenotropic host range is induced from lymphocytes of most strains by treatment with B cell mitogens. Virus induction is amplified by 5-bromo-2'-deoxyuridine (BrdU) treatment. We report here studies of the genetic control of retrovirus induction from lymphocytes in crosses between BALB/cTif mice and noninducible 129/Rrj mice. We identify a novel locus, Bdv-1, which controls the expression of a reverse transcriptase-positive, defective retrovirus in BALB/cTif lymphocytes. In addition, we confirm previous reports that xenotropic virus is controlled by a locus, Bxv-1, mapping to chromosome 1. The two loci are nonlinked and respond differently to inducing stimuli. Bxv-1 is induced mainly by BrdU and only marginally by mitogen; in contrast, Bdv-1 is induced by mitogen and BrdU has little effect. The induction of these two loci is discussed with respect to B cell differentiation.

Animals↗
PubMed1981

Transcriptional control of endogenous virus genes in murine lymphocytes.

The expression of endogenous retrovirus in murine lymphocytes is under genetic control and also depends on the differentiation state of the lymphocytes. We have used a cDNA probe complementary to induced virus RNA to quantify transcription of virus sequences in lymphocytes from mitogen-stimulated lymphocytes of the AKR, 129/J and Balb/c mice. Balb/c lymphocytes show the clearest case for induction of new virus sequences in response to stimulation. All strains including 129/J show expression of virus sequences in unstimulated control lymphocytes. The data indicate that mitogen induction of endogenous retrovirus is regulated at the transcriptional level.

Animals↗
PubMed1981

Lipopolysaccharide induces retroviral antigen expression in 129/J mouse lymphocytes: evidence for assembly of a defective viral particle.

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles. We conclude that 129/J mice are inducible with lipopolysaccharide but that the virus produced is a defective particle deficient in reverse transcriptase activity.

Animals↗
PubMed1980

Two siblings with acute T-cell lymphocytic leukemia.

The only two children of clinically healthy parents both developed an acute lymphocytic leukemia of the T-cell type, one with a mediastinal mass, one without. Extensive laboratory studies revealed a combination of the following unusual circumstances. (1) The injection of leukemic bone marrow into BALB/c-nu/nu mice led to an explosive simultaneous development of disseminated lymphomatous tumors with murine karyotype. (2) HLA typing and MLC testing of all four family members revealed sharing of HLA-A,D and DRw determinants between the parents and pointed to the appearance of suppressor cell activity with the outbreak of the acute leukemia of one sibling. (3) Parental lymphocytes gave a low response to mitogen stimulation, suggesting a subclinical cellular immune defect. It is proposed that the siblings inherited from each parent a defective immune response factor, possibly related to HLA-D/DRw antigens, that predisposed to acute T-cell leukemia. The neoplastic process might have been triggered by a transferable agent.

Animals↗