Role of Broviac catheters in infections in children with cancer.

In a 3-year period 157 single lumen Broviac catheters were inserted in 145 children with various neoplastic diseases. The overall duration of the catheter courses was 30,533 days (median, 171; range, 2 to 647). Sixty-five percent of the catheter courses (102 of 157) were complicated by at least 1 febrile episode, for a total of 157 episodes.

Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.

DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT transitions in codon 12 and one CAA----AAA transversion in codon 61. One case exhibited homozygosity for the mutation.

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.

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.

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.

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.

[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.

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).

Activation of N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia.

Human tumour cell lines of various histological origin contain genes that can transform NIH 3T3 cells in culture. Most frequently the gene is an activated K-ras gene, more rarely an activated H-ras gene, and sometimes the recently discovered N-ras. Other transforming genes, distinct from ras, have been found in B- and T-cell leukaemias.

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.

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.

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.

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.

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.

Antibody directed against Friend leukemia virus stimulates DNA synthesis in a subpopulation of mouse B lymphocytes.

Goat and rat antisera directed against Friend leukemia virus (anti-FLV) were found to be B-lymphocyte mitogens stimulating DNA synthesis in these cells but not in T lymphocytes. Membrane fluorescence microscopy showed that anti-FLV reacts with a subset of B lymphocytes of which the majority express immunoglobulin mu chains. The mitogenic effect was found with all mouse strains tested including 129 and AKR.

Foetal calf serum acts as an inducer of endogenous C-type virus in mouse lymphoid cells.

Several B-lymphocyte mitogens have been previously characterized as efficient inducers of endogenous C-type viruses in mouse spleen cell cultures. We now report that foetal calf serum is also capable of inducing C-type virus release in such cultures. While virus induction by B-cell mitogens was found to be serum independent, the combined effects of serum and mitogens were found to be additive and, with some serum batches, synergistic.