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Biomedical subjects

C Moroni

Publications and source records attributed to C Moroni.

At least 73 records · Page 4Linked to original sources
PubMed1991

Serum concentrations and safety of single daily dosing of amikacin in children undergoing bone marrow transplantation.

The serum concentrations and safety of single daily dosing of amikacin were studied in 16 episodes of fever and granulocytopenia in children undergoing bone marrow transplantation. Amikacin (20 mg/kg) was administered as a 20 min iv infusion once daily for 7 to 19 days; all patients received concomitant therapy with ceftazidime. Peak amikacin concentrations measured immediately after infusion on day 1 and 4 of therapy averaged 72.29 +/- 11.6 mg/l and 74.02 +/- 19.29 mg/l respectively. A slight but statistically significant increase 30 minute post-infusion concentrations was observed in most patients during therapy. Serum amikacin were less than 3 mg/l in all trough samples and within 6 h post-infusion in most patients. A significant increase in serum creatinine was observed in one patient, who was also receiving cyclosporin A. Auditory function was evaluated in 10 patients and showed no changes. Although other drugs were added to cover Gram-positive or fungal pathogens, all patients survived. These data combined with the recent experience of single daily dose amikacin in adults supports further evaluation of novel dosage regimens of aminoglycosides in children.

Adolescent↗
PubMed1991

Virological events leading to spontaneous AKR thymomas.

The spontaneous leukemias of AKR mice are caused by mink cell focus-forming (MCF) viruses. These viruses are generated by recombination between several endogenous murine retroviruses. The virological events leading to the generation of the leukemogenic agent were investigated by using an oligonucleotide specific for the U3 region of the leukemogenic virus and env-reactive oligonucleotide probes specific for the different classes of endogenous murine leukemia virus. It was shown that (i) the leukemogenic MCF virus is formed by recombination between at least three different endogenous sequences; (ii) the U3 donor for the leukemogenic virus is the inducible xenotropic virus Bxv-1; (iii) all spontaneous tumors contain viruses with duplicated enhancer regions in their long terminal repeats; (iv) enhancer duplication is a somatic event, since Bxv-1 contains only one copy; (v) the first recombinant virus detectable in mass populations of thymocytes by Southern hybridization analysis contains all structural features of the ultimate leukemogenic virus; and (vi) the multiple novel viruses in a given tumor represent progeny of the same unique recombination events. On the basis of these results, an analysis of the virological events leading to AKR thymomas is presented.

Animals↗
PubMed1991

Ras oncogenes amplify lymphokine (interleukin 3, granulocyte-macrophage colony-stimulating factor) induction by calcium ionophore.

Interleukin 3 (IL-3) expression in PB-3c mastocytes is transiently induced in vitro by treatment with the drug A23187, a calcium ionophore, or constitutively following ras-dependent transformation in vivo. While the mechanism of oncogenically induced IL-3 expression is not clear, A23187-mediated lymphokine mRNA accumulation is primarily the result of calcium-dependent mRNA stabilization. We investigated whether the expression of various ras alleles influenced IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA induction by A23187. It was found that activated forms of ras potentiated ionophore-mediated lymphokine mRNA accumulation. This enhancement involves a post-transcriptional mechanism, as ionophore-induced lymphokine mRNAs are significantly more stable in ras oncogene-expressing lines than in the control line. We propose that one way by which ras genes exert their oncogenic potential is by extending the half-life of short-lived growth factor mRNAs.

Blotting, Northern↗
PubMed1990

Infection with Fusarium species in two children with neuroblastoma.

Two cases of Fusarium infection in children with neuroblastoma are reported. One of the patients had an overwhelming infection and the diagnosis was based on isolation of Fusarium moniliforme from blood and skin biopsy, and histological findings. The second patient developed chronic polyarthritis and Fusarium solani was cultured from synovial fluid samples taken from two different joints four months apart. No histological documentation of infection was obtained. The response to antifungal therapy was unfavourable. Both patients died, but in the second case the relationship between fungal infection and death was not established.

Amikacin↗
PubMed1990

Regulation of interleukin 3 mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions.

Interleukin 3 (IL-3) is transiently produced by murine bone marrow-derived mast cells in response to antigen stimulation of the high-affinity immunoglobulin E receptors. We have studied the postreceptor signaling pathways involved in regulating expression of the IL-3 gene in the murine mast cell line PB-3c. Large amounts of IL-3 mRNA accumulated after exposure of cells to calcium ionophore A23187, a reagent that increases intracellular Ca2+. Phorbol 12-myristate 13-acetate, which stimulates protein kinase C, did not induce IL-3 mRNA accumulation, although it did potentiate the effect of A23187. Nuclear run-on analysis showed that the IL-3 gene is constitutively transcribed in unstimulated cells and that treatment with A23187 and/or phorbol ester has no influence on its transcription rate. The effect of A23187 was found to be due to stabilization of the IL-3 mRNA. In cells maintained in the presence of A23187 the IL-3 mRNA was stable during 3 hr of incubation with actinomycin D, whereas removal of A23187 under the same conditions resulted in rapid degradation of the mRNA. These results indicate that control of expression of the IL-3 gene in mast cells is primarily at the posttranscriptional level and that the Ca2(+)-dependent signal-transduction pathway plays an important role in this process. Synthesis of granulocyte/macrophage colony-stimulating factor mRNA in response to A23187 and phorbol ester was found to be subject to both transcriptional and posttranscriptional regulation.

Animals↗
PubMed1990

[Echocardiokimography and scintigraphy with Tc-MIBI in left ventricular asynergy in chronic myocardial infarct. Comparison of these methods].

The study compared echocardiography, specially echocardiokimography, and myocardial scintigraphy in the evaluation of the extent of chronic myocardial infarction. Eighteen subjects were enrolled and the following examinations performed: ECG, M- and B-mode echocardiography, echocardiokimography and myocardial scintigraphy with Tc-MIBI, a new perfusion radionuclide agent. We concluded: 1) accordance between the two kinds of methods; 2) specificity of echocardiokimography; 3) advantage in using both methods, specially with MIBI scintigraphy.

Adult↗
PubMed1989

Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation.

Mast cells have a central role in allergic diseases mediated by specific immunoglobulin E antibody responses to allergens. The binding of IgE to the high-affinity receptor for IgE (Fc epsilon R) on mast cells and basophils enables these cells to react specifically to allergens. Such contact leads to the activation of mast cells and the release of histamine and other pharmacological mediators, causing an immediate hypersensitivity and acute inflammatory reactions, accompanied by the development of allergic symptoms. Here we show that Fc epsilon R-mediated activation of murine mast cells results in the production of the haemopoietic growth factors granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). IL-3 and GM-CSF, in addition to their role in bone marrow haemopoiesis, also influence inflammation as they have the capacity to recruit, prime and activate inflammatory cells such as neutrophils, macrophages and eosinophils. Secretion of these factors by mast cells in response to allergens may therefore have an important role in local tissue defense.

Animals↗
PubMed1989

Reversible abrogation of IL-3 dependence by an inducible H-ras oncogene.

Immortalized, interleukin-3 (IL-3)-dependent mouse mast cells (PB-3c) were transfected with a human activated c-H-ras gene under the transcriptional control of the mouse mammary tumor virus long terminal repeat. Addition of increasing amounts of dexamethasone resulted in a concentration-dependent increase in expression of the H-ras oncogene. The elevation of p21 ras protein concentrations was paralleled by progressive growth of the transfectants in the absence of exogenous IL-3, leading to complete abrogation of growth-factor requirement at high p21ras levels. The maintenance of the IL-3-independent state required the continuous expression of the H-ras oncogene, since dexamethasone removal was followed by rapid cell death. Expression of the H-ras oncogene induced PB-3c cells to produce IL-3 and granulocyte-macrophage colony-stimulating factor, suggesting that their IL-3-independent proliferation may be due to an autocrine mechanism.

Animals↗
PubMed1989

Tumor suppression involves down-regulation of interleukin 3 expression in hybrids between autocrine mastocytoma and interleukin 3-dependent parental mast cells.

Interleukin 3 (IL-3)-dependent PB-3c mouse mastocytes can be transformed by the v-Ha-ras oncogene to generate autocrine IL-3-producing mastocytomas. Hybrid cell lines were constructed by fusing an IL-3-producing mastocytoma cell line with its IL-3-dependent normal parental cell. Unlike the mastocytoma parent cell line, hybrid cell lines required growth factor for in vitro proliferation, indicating that the IL-3-dependent phenotype is dominant. IL-3 mRNA, expressed at high levels in the tumor cells, appeared down-regulated in the cell hybrids. In contrast, p21v-Ha-ras levels were not reduced in the hybrids. The hybrid lines generated tumors in vivo with drastically prolonged latency times when compared to the tumor parent (10 versus 2 weeks). We propose that down-regulation of IL-3 mRNA production after cell fusion is responsible for the loss of growth autonomy in the hybrids and is likely to play a role in the partial suppression of tumor formation in vivo. Our data are consistent with the hypothesis that a tumor suppressor, present in PB-3c cells, acts as a negative regulator of IL-3 expression.

Animals↗
PubMed1989

A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production.

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.

Animals↗
PubMed1989

Stimulation of pp60c-src kinase activity in FDC-P1 cells by polyoma middle-T antigen and hematopoietic growth factors.

Either of two hematopoietic growth factors, GM-CSF or IL-3, are required for the growth of the bone marrow-derived FDC-P1 cell line. These factors induce cellular tyrosine-specific protein kinases when added to resting cells. The receptors for these factors have not been unambiguously shown to contain a kinase domain. To determine whether src-related kinases, in particular pp60-c-src, are regulated by GM-CSF or IL-3, FDC-P1 cells were transfected with plasmids carrying polyoma middle-T antigen, a potent activator of pp60c-src. Middle-T-expressing cells showed a reduced requirement for GM-CSF and IL-3 and selected clones grew in the absence of these factors. Middle-T formed a complex with pp60c-src and stimulated its in vitro kinase activity 20-50 fold. pp60c-src kinase activity was further increased if middle-T-expressing, factor-independent cells were treated with GM-CSF or IL-3.

Animals↗
PubMed1988

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. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow-up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N-ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N-ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.

Acute Disease↗
PubMed1988

Relapse cell population differs from acute onset clone as shown by absence of the initially activated N-ras oncogene in a patient with acute myelomonocytic leukemia.

We have conducted a follow-up study of a patient with myelomonocytic leukemia exhibiting an N-ras mutation (Gln61----Lys61) using the polymerase chain reaction method and synthetic oligonucleotide hybridization probes. This method allowed us to detect as little as 3% of N-ras-mutated cells within a population. When the patient went into clinical remission, the mutation became undetectable. When a relapse occurred, the blasts did not carry the N-ras mutation. Analysis of M13 cloned amplified N-ras sequences from relapse DNA revealed exclusively the wild type allele of the N-ras gene. These findings suggest that the relapse cell population is derived from a different clone than the acute phase population. Furthermore, the data argue that N-ras mutation is not an initiating lesion in this case of acute myelomonocytic leukemia (AMML).

Cell Transformation, Neoplastic↗
PubMed1988

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. According to European Organization for Research on Treatment of Cancer criteria, 79 febrile episodes (50%) were classified as microbiologically documented infections, 57 (36%) with and 22 (14%) without septicemia; 31 (20%) as clinically documented infections; and 47 (30%) as possible infections. Of the 79 microbiologically documented infections 21 were catheter-related infections (CRI), 32 were catheter-unrelated infections and 26 were infections of unknown source. Only 48% of CRI occurred during neutropenia (less than 1000 neutrophils/mm3), compared with 88% of catheter-unrelated infections and 96% of infections of unknown origin (P = 0.00007). Gram-positive microorganisms (56% staphylococci) accounted for 78% of all isolates in CRI, 47% in catheter-unrelated infections and 43% in infections of unknown origins (P = 0.03). Fungi represented 12% of all isolates. Clinical and microbiologic resolution without removal of the catheter was achieved in 12 of 21 CRI (57%) and no patient died from a CRI. This study indicates that over 3 of 4 of CRI are caused by Gram-positive bacteria, occur in neutropenic and non-neutropenic patients (approximately 50%) and can be successfully treated without removing the catheter.

Adolescent↗